 1 WARNING SIGNS THAT SHOULD SEND ADULTS TO THE DOCTOR
 2 Dengue Fever
 3 Diabetes
 4 DISEASES EXPLAINED
 5 Disease, Evolution & Origins
 6 Diseases, Tropical
 7 Diseases of Animals
 8 Epidemiology
 9 Ebola (Marburg virus)
 10 Flu Vaccine Effectiveness
 11 Foot-and-Mouth 8/01
 12 Future of diseases

\1 WARNING SIGNS THAT SHOULD SEND ADULTS TO THE DOCTOR

Significant abdominal pain with sudden onset, or pain that is less severe but not going away. Vomiting anything that looks like bloody material, or having dark black or bloody stools, with or without abdominal discomfort. It may be a bleeding ulcer or other bleeding in the intestinal tract. Weakness may accompany the bleeding. 

Severe or persistent vomiting or diarrhea. If urine output is diminishing, fluid intake is getting reduced. "Keeping track of urine output is your own barometer," Phillips said. "It's an easy clue that you are getting dehydrated." 

High fever. For chemotherapy patients, even a low-grade fever can be very serious. Others with fever should check in with their doctor. 

Head injuries that cause you to pass out, have a behavior change, become agitated, lethargic or have persistent vomiting. 

Falls. If elderly fall, especially if they are on medications such as blood thinners, they should be evaluated, Stegman said. There may be bleeding inside the head, and it can be hours before the symptoms show. Cuts. "If the edges are separated where stitches would bring those edges together, or if there is persistent bleeding, the wound should be checked," said Phillips. A loss of function or numbness beyond the cut may mean a tendon or nerve is cut. 

Blurred vision, double vision, a sensation of flashing lights, any sudden vision problem or sudden severe headache. "I used to think that women waited too long, but actually it's often the men who wait to come in," Phillips said. "Women tend to take better care of their health."

Emergency medicine for children brings a whole new set of problems, and the biggest problems are in the littlest kids, said pediatric emergency physician Karen Balzanto at Edward Hospital's Pediatric Emergency Room in Naperville.

"Children up to 3 months old should do four things: Eat, sleep, pee and poop. If they're not doing it, something's wrong," Balzanto said.

Rectal temperatures should be taken in newborns because they are more accurate, and parents should ask their pediatrician about fevers. But generally, a newborn with a rectal temperature over 100 degrees needs to be seen by a doctor, according to Balzanto. At this tender age, their bodies are unable to localize an infection, and it can spread through the bloodstream, Phillips said.

Parents should also monitor urine output in babies. Babies should have 6 to 8 wet diapers a day, no vomiting and no diarrhea. Projectile vomiting, especially yellow-green vomiting, is cause to worry about congenital bowel malformation. Go to the doctor.

Crying that won't quit - "In a small baby, persistent crying is always worth a call to the doctor. If there is nothing you can do to ease the child, the child needs to get seen right way. Don't wait until the next day," Balzanto said. "Too many people wait."

If a baby is breathing too fast, or not breathing as much as he should, check to see if his tongue and gums are healthy and pink. If they are not, or if the child stops breathing for as long as 10 to 15 seconds, see the doctor right away.

A baby who is sweating while feeding and does not have enough energy to finish feeding should be seen to make sure there is no congenital heart disease, Balzanto said.

Babies older than 3 months and toddlers under 3 or 4 should be seen by a doctor if they have two days of a persistent fever of 100 or 101 degrees with no other symptoms. Though better than babies at communication, toddlers still are not good at explaining what hurts.

Lethargic children who have no cold or flu symptoms but are just lying around and not wanting to play or eat should be looked at. "At ages 2 and 3, they are supposed to play, sleep and eat. If they aren't doing those things, they should be seen," Balzanto said.

Over the age of 3, health concerns become more clear cut, according to Balzanto.

Persistent belly pain that doesn't just come and go warrants a call. "Usually if you put them in a warm tub, they are going to do just fine," Balzanto said. "But if it doesn't go away, call the doctor."

Other warning signs for children include: Head injuries: "If they don't pass out and don't throw up, call your doctor to get information on what to watch for, and then watch them closely. If they throw up, call the doctor and wake them every two hours. Make sure the child knows where he is and who you are. "The bottom line is: If your kid had a head injury and doesn't seem himself, go to the doctor," Balzanto said. 

Eye injuries: See the doctor. They are hard to detect at home. 

Ear problems: Call the doctor. Ear pain will not be stopped immediately with antibiotics, but the doctor can suggest something to ease the pain. 

Allergic reactions: If your child gets stung or eats something and develops a rash but is not breathing oddly, has no swelling of the lips or tongue and no sore throat, give him a dose of Benadryl and watch closely. If the reaction involves trouble swallowing, swollen lips or tongue or a sudden sore throat, call 911. You do not know how long it will be before the airway swells, Balzanto said. Children of parents who experience severe allergic reactions can be tested for the same allergies. 

Headaches: Sudden headaches with no cold or flu symptoms can be significant. If the child faints or the headache makes him throw up, have him checked. 

Purple rashes: An all-over purple rash that does not temporarily disappear when you push your finger on it means a doctor should be seen immediately. This rash can be a sign of meninococcemia, a life-threatening infection that involves meningitis. A headache and a stiff neck, sore at the back of the neck, can be a sign of meningitis and requires immediate care. 

Appendicitis: Persistent pain in the right lower quadrant can be appendicitis. If the child's cramped in a ball with stomachache, have him seen. If your child falls with a bicycle and gets hit with the handlebars or gets kicked in the stomach, have him checked. There could be damage to the spleen or the intestines. 

Blood in the urine or stool: Call the doctor. Swelling in the feet or the face may be a sign of a kidney problem. 

Bloody noses: Most bloody noses are taken care of by squeezing the nose at the tip, not the bridge. Tilt the head down, not back. If you hold strong pressure for 10 minutes, it should stop, Balzanto said. If it doesn't, see the doctor. 

Dental injuries: If a permanent tooth gets knocked out, stuff it back in and get to an emergency dentist. If you're too squeamish to stuff it in, put it in milk and go to the dentist. 

Burns: If it is a large burn that blisters, or if the burn goes all the way around any body part, have it checked. 

Fevers: If a child age 6 or older has a fever of 103 or 104, the doctor should be called. "Many times parents will see that the fever is gone and think the child is better," Balzanto said. "Fever is a sign of an infection that has to be treated. The child needs to be seen." 


\2 Dengue Fever

Dandy fever, Dengue (breakbone, a viral (epidemic) infection transmitted by Aedes mosquito is found everywhere except in western countries. Disease is seldom fatal in adults. A red rash appears 3-5 days moving from torso to limbs followed by sudden high fever 5-8 days after exposure (stops and recurs) with chills, muscle pain, headache, and exustion. Medical test is necessary as symptoms are  similar to flu, hepititis, malaria, Jap B encephalitis.
 Severe joint/muscle pains before a sudden onset of fever that subsides in days, headaches and severe joint and muscle pains are the first signs before a rash develops on trunk spreading to limbs. Recovery may be prolonged. engue & dengue hemorrhagic fever (DHF) are caused by one of four closely related, but antigenically distinct, virus serotypes (DEN-1-4), of the genus Flavivirus. Infection with one of these serotypes does not provide cross protective immunity, so persons living in a dengue endemic area can have four dengue infections during their lifetimes.  Dengue is primarily a disease of the tropics, and the viruses that cause it are maintained in a cycle that involves humans and Aedes aegypti, a domestic, day biting mosquito that prefers to feed on humans. Infection with dengue viruses produces a spectrum of clinical illness ranging from a nonspecific viral syndrome to severe and fatal hemorrhagic disease. Important risk factors for DHF include the strain and serotype of the infecting virus,as well as the age, immune status, and genetic predisposi- tion of the patient.

History of Dengue: The first reported epidemics of dengue fever occurred in 1779-1780 in Asia, Africa, and N.Amer; the near simultaneous occurrence of outbreaks on three continents indicates that these viruses and their mosquito vector had a worldwide dist in the tropics for more hhan 200 yrs. During most of this time, dengue fever was considered a benign, nonfatal disease of visitors to the tropics with long intervals (10-40 yrs) between major epidemics, because the viruses and their vector could only be transported between pop ctrs by sailing vessels.

There is no preventative drug available for this mosquito borne viral illness which can be fatal in children. Treat fever with aspirin, plenty of liquids (IV if necessary) to avoid dehydration. Antibiotics are useless. No cure, vaccine, or other treatment available. Future Outlook. No dengue vaccine is avail. Recently, however, attenuated candidate vaccine viruses have been developed in Thailand. These vaccines are safe & immuno- genic when given in various formulations, including a quadrivalent vaccine for all four dengue virus serotypes.

Efficacy trials in human volunteers have yet to be initiated. Research is also being conducted to develop second-generation recombinant vaccine viruses; the Thailand attenuated viruses are used as a template. Therefore, an effective dengue vaccine for public use will not be avail for 5-10 yrs.    
A global pandemic of dengue began in SE Asia after WW II and has intensified during the last 15 years. Epidemics caused by multiple serotypes (hyperendemicity) are more frequent, the geographic distribution of dengue viruses and their mosquito vectors has expanded, and DHF has emerged in the Pacific region and the Americas. In SE Asia, epidemic DHF first appeared in the 1950s, but by 1975 it had become a leading cause of hospitalization and death among children in many countries in that region.

In the 1980s, DHF began a second expansion into Asia when Sri Lanka, India, and the Maldive Islands had their first major DHF epidemics; Pakistan first reported an epidemic of dengue fever in 1994. The recent epidemics in Sri Lanka and India were associated with multiple dengue virus serotypes, but DEN-3 was predominant and was genetically distinct from DEN-3 viruses previously isolated from infected persons in those countries.

After an absence of 35 years, epidemic dengue fever occurred in both Taiwan and the People's Rep of China in the 1980s. The PRC had a series of epidemics caused by all four serotypes, and its first major epidemic of DHF, caused by DEN-2, was reported on Hainan Island in 1985. Singapore also had a resurgence of dengue/DHF from 1990 to 1994 after a successful control program had prevented significant transmission for over 20 years. In other countries of Asia where DHF is endemic, the epidemics have become progressively larger in the last 15 years. 

In the Pacific, dengue viruses were reintroduced in the early 70s after an absence of more than 25 yrs. Epidemic activity caused by all four serotypes has intensified in recent yrs with major DHF epidemics on several islands. 

Despite poor surveillance for dengue in Africa, epidemic dengue fever caused by all four serotypes has increased dramatically since 1980. Most activity has occurred in East Africa, and major epidemics were reported for the first time in the Seychelles (1977), Kenya (1982, DEN-2), Mozambique (1985, DEN-3), Djibouti (1991-92, DEN-2), Somalia (1982, 1993, DEN-2), and Saudi Arabia (1994, DEN-2). Epidemic DHF has been reported in neither Africa nor the Middle East, but sporadic cases clinically compatible with DHF have been reported from Mozambique, Djibouti, and Saudi Arabia. 

The emergence of dengue/DHF as a major public health problem has been most dramatic in the American region. In an effort to prevent urban yellow fever, which is also transmitted by Ae. aegypti, the Pan American Health Organization organized a campaign that eradicated Ae. aegypti from most Central and South American countries in the 1950s and 1960s. As a result, epidemic dengue occurred only sporadically in some Caribbean islands during this period.

The Ae. aegypti eradication pgm, which was officially discontinued in the US in 1970, gradually eroded else- where, and this species began to reinfest countries from which it had been eradicated. In 1997, the geographic distribution of Ae. aegypti is wider than its distribu- tion before the eradication pgm. 

In 1970, only DEN-2 virus was present in the Americas, although DEN-3 may have had a focal distribution in Colombia and Puerto Rico. In 1977, DEN-1 was introduced and caused major epidemics throughout the region over a 16-year period. DEN-4 was introduced in 1981 and caused similar widespread epidemics. Also in 1981, a new strain of DEN-2 from SE Asia caused the first major DHF epidemic in the Americas (Cuba). 

This strain has spread rapidly throughout the region and has caused outbreaks of DHF in Venezuela, Colombia, Brazil, French Guiana, Suriname, and Puerto Rico. By 1997, 18 countries in the American region had reported confirmed DHF cases, and DHF is now endemic in many of these countries. 

DEN-3 virus recently reappeared in the Americas after an absence of 16 years. This serotype was first detected in association with a 1994 dengue/DHF epidemic in Nicaragua. Almost simultaneously, DEN-3 was confirmed in Panama and, in early 1995, in Costa Rica. In Nicaragua, considerable numbers of DHF cases were associated with the epidemic, which was apparently caused by DEN-3. In Panama and Costa Rica, the cases were classic dengue fever. 

Viral envelope gene sequence data from the DEN-3 strains isolated from Panama and Nicaragua have shown that this new American DEN-3 virus strain was likely a recent intro from Asia since it is genetically distinct from the DEN-3 strain found previously in the Americas, but is identical to the DEN-3 virus serotype that caused major DHF  epide- mics in Sri Lanka and India in the 1980s. As suggested by the finding of a new DEN-3 strain, and the susceptibility of the population in the American tropics to it DEN-3 spread rapidly throughout the region caused major epide- mics of dengue/DHF in Central America in 1995.

In 97, dengue is the most important mosquito-borne viral disease affecting humans; its global distribution is comparable to that of malaria, and an estimated 2.5 billion people live in areas at risk for epidemic transmission. Each year, tens of millions of cases of dengue fever occur and, depending on the year, up to hundreds of thousands of cases of DHF. The case-fatality rate of DHF in most countries is about 5%; most fatal cases are among children and young adults. 

There is a small, but significant, risk for dengue out- breaks in the continental US. Two competent mosquito vectors, Ae. aegypti and Aedes albopictus, are present and, under certain circumstances, each could transmit dengue viruses. This type of transmission has been detected three in the last 16 years in south Texas (80, 86, and 95) and has been assoc with dengue epidemics in northern Mexico. Moreover, numerous viruses are intro- duced annually by travelers returning from tropical areas where dengue viruses are endemic. From 77-94, 2248 sus- pected cases of imported dengue were rept in the US.

Although some specimens collected were not adequate for lab diags, 481 (21%) cases were confirmed as dengue. Many more cases probably go unreported each year because surveillance in the US is passive and relies on physici- ans to recognize the disease, inquire about the patient's travel history, obtain proper diag samples, and report the case. These data suggest that southern Texas and the SE US, where Ae. aegypti is found, are at risk for dengue transmission and sporadic outbreaks. 

The reasons for this dramatic global emergence of dengue /DHF as a major public health problem are complex and not well understood. However, several important factors can be identified. First, effective mosquito control is virtually nonexistent in most dengue-endemic countries. Considerable emphasis for the past 20 yrs has been placed on ultra-low-volume insecticide space sprays for adult mosquito control, a relatively ineffective approach for controlling Ae. aegypti. Second, major global demographic changes have occurred, the most important of which have been uncontrolled urbanization and concurrent pop growth.

These demographic changes have resulted in substandard housing and inadequate water, sewer, and waste mgmnt sys all of which increase Ae. aegypti pop densities and facilitate transmission of Ae. aegyptiborne disease. Third, increased travel by air provides the ideal mech- anism for transporting dengue viruses between pop ctrs of the tropics, resulting in a constant exchange of dengue viruses and other pathogens. Lastly, in most countries the public health infrastructure has deteriorated.

Limited financial and human resources and cmmpeting priorities have resulted in a "crisis mentality" with emphasis on implementing so-called emergency control methods in response to epidemics rather than on develop- ing programs to prevent epidemic transmission.

This approach has been particularly detrimental to dengue control because, in most countries, surveillance is (just as in the U.S.) very inadequate; the system to detect increased transmission normally relies on reports by local physicians who often do not consider dengue in their differential diagnoses. As a result, an epidemic has often reached or passed transmission before it is detected. 

Prospects for reversing the recent trend of increased epidemic activity and geographic expansion of dengue are not promising. New dengue virus strains and serotypes will likely continue to be introduced into many areas where the population densities of Ae. aegypti are at high levels. With no new mosquito control technology avail, in recent years public health authorities have emphasized disease prevention and mosquito control through community efforts to reduce larval breeding sources. 

Although this approach will probably be effective in the long run, it is unlikely to impact disease transmission in the near future. We must, therefore, develop improved, proactive, laboratory-based surveillance systems that can provide early warning of an impending dengue epidemic. At the very least, surveillance results can alert the public to take action and physicians to diagnose and properly treat dengue/DHF cases. 

Div of Vector-Borne Infectious Diseases  CDC Jun 97.

Dengue viruses are transmitted by mosquitoes, which are most active during the day. These vector mosquitoes are found near human habitations and are often present indoors. Epidemic transmission is usually seasonal, during and shortly after the rainy season.

Dengue fever is characterized by sudden onset, high fever, severe headaches, joint and muscle pain, nausea/vomiting, and rash. The rash may appear 3–4 days after the onset of fever. Infection is diagnosed by a blood test that detects the presence of the virus or antibodies. The illness may last up to 10 days, but complete recovery can take 2–4 weeks. Dengue is commonly confused with other infectious illnesses such as influenza, measles, malaria, typhoid, leptospirosis, and scarlet fever. 

The symptoms of dengue can be treated with bed rest, fluids, and medications to reduce fever, such as acetaminophen; aspirin should be avoided. Travelers should alert their physician of any fever illnesses occurring within 3 weeks after leaving an endemic area. There is no vaccine for dengue fever; therefore, the traveler should avoid mosquito bites by remaining in well screened or air-conditioned areas. Travelers to tropical areas are advised to use mosquito repellents on skin and clothing, to bring aerosol insecticides to use indoors, and use bednets.

The risk of dengue for each geographic area will have variations. The risk is generally higher in urban areas. There are no requirements precluding traveler entry to any country.

Africa Dengue fever occurs endemically in most of the region and as periodic epidemics. It is found in both rural and urban areas and poses a health hazard to travelers; the risk of infection is highest in urban centers. (Please check the information in the Destinations section on Central Africa, East Africa, North Africa, Southern Africa, and West Africa.)

SE Asia and China - Dengue fever occurs endemically in most of the region and as periodic epidemics. It is found in both rural and urban areas and poses a health hazard to travelers; the risk is highest in urban centers.

Indian Subcontinent - Dengue fever occurs endemically and as periodic epidemics. It is found in both rural and urban areas and poses a health hazard to travelers; the risk is highest in urban centers. (Please check the information in the Destinations section on the Indian Subcontinent.)

The Middle East - Dengue fever is endemic in some urban centers and occurs sporadically in epidemics; the risk of infection is small for most travelers except during periods of epidemic transmission. (Please check the information in the Destinations section on the Middle East.)

South America - Dengue fever occurs endemically in many urban centers and as periodic epidemics. It occurs in both rural and urban areas and poses a health hazard to travelers; the risk is highest in urban centers.

Central America - Dengue fever occurs endemically in most urban centers and as periodic epidemics. It occurs in both rural and urban areas and poses a health hazard to travelers; the risk is highest in urban centers.

Caribbean - Dengue fever occurs endemically in most Caribbean Islands and as periodic epidemics. It occurs in both rural and urban areas and poses a health hazard to travelers; the risk is highest in urban centers.

Australia and the South and Central Pacific - Dengue fever is endemic with periodic epidemics in parts of northern Queensland and the Torres Strait Islands of Australia as well as most of the South and Central Pacific Islands; there is a risk to the traveler in those specific areas. New Zealand is free of dengue fever.


\3 Diabetes

A group of diseases in which there are high levels of blood glucose (blood sugar) due to a lack of insulin or the body not being able to use the insulin that is produced by the pancreas.

Insulin is needed in order for the body to use blood glucose that comes from the digestion of the food we eat for energy. During digestion, starches and sugars are broken down into glucose (a sugar) and absorbed into the blood stream. Insulin, a hormone produced by the pancreas, helps the glucose enter the body’s cells. The cells use the glucose to make energy for the body. Normally, the pancreas produces the right amount of insulin to turn the food we eat into energy. 

In diabetes, insulin is either not produced or insulin is produced, but it does not work properly. As a result, glucose is unable to enter cells. Since the cells are unable to use the glucose, the glucose builds up in the blood stream. If cells do not get enough glucose, they begin burning fat for energy. Burning fat supplies energy but also releases a substance called ketones. Ketones are toxic to the body when allowed to build up in the blood. 

Diabetes is one of the top 10 causes of death and disabi- lity in the US. Diabetes places a person at risk for serious complications and other conditions such as: Blindness, Kidney failure, Amputation, Heart disease (heart attack), Stroke, or Nerve damage. It is a chronic disease for which there is no cure at this time. It can be managed with correct treatment. Correct treatment can greatly reduce or delay the chance of complications from diabetes.

There are two major types of diabetes, type 1 and type 2, however, diabetes also includes gestational diabetes (diabetes during pregnancy), and several other specific types.

Type 1 diabetes was known in the past as juvenile diabetes, insulin dependent diabetes (IDDM), and type I diabetes. It is a disease in which the pancreas makes no insulin. The cause of this type of diabetes is basically a destruction of the Beta cells of the pancreas because of an autoimmune response by the body. An autoimmune response happens when the body’s defense system turns on itself and causes damage to the body’s own organs. People with type 1 diabetes must inject themselves daily with insulin for life.

Type 1 diabetes appears most often in kids and young adults before the age 30. The symptoms usually come on quickly and are fairly severe. About 5-10% of diabetes cases are diagnosed as type 1. It is estimated that 123,000 kids and 1.4 million adults in the US have type 1 diabetes.

Risk factors for type 1 diabetes, besides an autoimmune response, are believed to include genetic (handed down from family members) and environmental (things around us) factors. Those at greatest risk of having type 1 diabetes are the brothers or sisters of people with type 1 or children of parents with type 1 diabetes. There is no known prevention at this time for type 1 diabetes.

Type 2 diabetes was known in the past as adult-onset diabetes, non-insulin dependent diabetes (NIDDM), and Type II diabetes. Some people with type 2 diabetes may still produce insulin, but their pancreas does not make enough. Others produce enough insulin, but their body cannot use it. This is known as insulin resistance. The cause of type 2 diabetes is not known at this time.

Type 2 diabetes is the more common type of diabetes. It usually occurs after age 45. There are approximately 16 million people in the United States with diabetes. About 90 - 95 % (14.9 million) diabetes cases are diagnosed as type 2. 

Most people who develop type 2 diabetes are overweight. Life style plays an important role in developing type 2 diabetes, and it seems to "run" in families. Risk factors for type 2 diabetes include: •Over age 45 •Family history of diabetes •Overweight •Lack of regular exercise (sedentary lifestyle) •Abnormal blood fats (low amounts of "good" cholesterol and high levels of triglycerides) •Race and ethnic group -- Blacks, Hispanics, Asians and Native Americans are at higher risk •History of gesta- tional diabetes (only when pregnant) •Birth of a baby weighing 9 or more pounds 

Two other risk factors for developing type 2 diabetes are Impaired Glucose Tolerance (IGT) and Impaired Fasting Glucose (IFG). Blood glucose (blood sugar) levels are higher than normal but not high enough for a diagnosis of diabetes.

IGT is a major risk factor for future development of type 2 diabetes. Blood glucose (blood sugar) results of a 2 hour glucose tolerance test greater than or equal to 140 but less than 200. This is considered abnormal but does not indicate diabetes. Persons with IGT may only have elevated blood sugar if given oral glucose as a part of the standard oral glucose tolerance test. Symptoms of diabetes are not present. IGT can get better, stay the same, or advance to the development of diabetes. IGT is not "borderline" diabetes. 

IFG is not diabetes. IFG is a new category to describe symptoms in which a person has fasting plasma glucose results of 110-125. The fasting glucose results in this category are above the upper limit of normal that has been set at 109, but lower than the new diagnostic level for diabetes that is 126 or greater. No symptoms of diabetes are present in IFG. IFG is not "border line diabetes". However, IFG is considered a risk factor for development of type 2 diabetes. 

Having a healthy lifestyle such as not being over weight and getting regular exercise can often reduce the risk of developing type 2 diabetes.

•25 years of age or older •Less than 2  years of age and obese (very overweight) •Family history of diabetes in a close relative •Member of an ethnic/racial group with a high rate of occurrence of diabetes 

Secondary diabetes is diabetes assoc with certain condi- tions or syndromes. This type diabetes could be the result of meds, reaction to chemicals, diseases of the pancreas, or genetic syndromes.

SIGNS AND SYMPTOMS Usually the symptoms of type 1 diabetes are clear as the symptoms usually begin suddenly and are fairly severe. The classic symptoms of diabetes are: 

•Increased thirst •Increased urination (frequent passing of urine) •Increased appetite (feeling very hungry) •Weight loss (unexplained weight loss) •Fatigue (feeling very tired) •Sores that do not heal •Blurred vision •Itchy skin •Pain in legs, hands, and feet 

Other symptoms for type 1 include irritability and nausea (feeling sick to the stomach) and vomiting (throwing up).

Symptoms of type 2 diabetes can come on very slowly or they may be absent causing many people with type 2 to be undiagnosed. Many people do not find out they have diabetes until they are treated for a complication such as heart disease, blood vessel disease (atherosclerosis), stroke, blindness, skin ulcers, kidney problems, nerve trouble, or impotence.

When symptoms are present in type 2 diabetes they can include the classic symptoms of diabetes, any of the other type 1 symptoms, and can also include unexplained weight gain; pain, cramping, tingling, or numbness in the feet; or frequent vaginal (yeast) or skin infections. Anyone who has symptoms of diabetes or risk factors for developing diabetes should see a doctor.

DETECTION AND DIAGNOSIS Early detection, diagnosis, and treatment of diabetes is important in order to prevent or slow down the beginning of complications from diabetes. Diagnosis of diabetes when you see your doctor should include a complete history and physical and blood tests. The American Diabetes Association recommends using a fasting blood glucose test for the diagnosis of diabetes.

This test can be done in the doc’s office or a lab. It requires that a person not have any thing to eat or drink for at least 8 hours. Usually this involves fasting overnight and having the blood drawn the next morning. Two other tests are also acceptable for use in diagnosing diabetes, a random/casual plasma glucose, or a glucose tolerance test can be done. Blood for the random/casual plasma glucose can be drawn at anytime, regardless of when food was last eaten. 

A glucose tolerance test, which checks the body’s ability to process glucose requires fasting over night. A fasting blood sugar is drawn first, and then a large dose of sugar solution is drunk. During this test, blood sugar levels in the blood and urine are done in 30 minutes and then hourly over a 3 hour period.

Diagnosis of diabetes is made using the following test results, which are repeated on another day for confir- mation (to be sure): •Fasting blood sugar of 126 or higher •Random/casual blood sugar of 200 or higher plus symptoms of diabetes •2 hour blood sugar level of 200 or higher during a glucose tolerance test 

TREATMENT - Type 1 diabetes is treated with insulin, diet, exercise, and careful self-monitoring (using a hand-held glucose meter) of blood sugar at home. All people with type 1 must take daily insulin injections in order to live. Insulin currently is only available in injectable form. It cannot be taken by mouth as a pill because the stomach destroys it. The doctor will pre- scribe the type of insulin, the amount, and the time it should be injected. Type 1 diabetes can not be treated with diabetes pills.

Type 2 diabetes is controlled in some people with diet, exercise, and careful self-monitoring of blood sugar at home. The addition of diabetes pills or insulin is sometimes needed by other people with type 2. Often, losing weight reduces the need for diabetes pills or insulin. Diet and exercise are often recommended as the beginning treatment for type 2 diabetes.

The American Diabetes Assoc recommends diabetes care should be managed using a team approach arranged by the person’s doctor. The idea of the team approach is that the person will benefit from the work of a group of specialists in diabetes care. That way, state-of-the-art treatmnt is avail. Team members focus on their specialty:

•The doctor diagnoses and prescribes •The diabetes teaching nurse helps people to learn about managing diabetes, •The dietitian develops and explains balanced healthy meal plans, •The counselor listens and helps people handle the emotions people feel about having diabetes. 

Certain standards that outline the minimum care that should be provided to every individual with diabetes have been established by The American Diabetes Assoc.

GLOSSARY OF MEDICAL TERMS

autoimmune process: A process where the body’s immune system attacks and destroys body tissue that it mistakes for foreign matter.

blood glucose: The main sugar that the body makes from the food we eat. Glucose is carried through the bloodstream to provide energy to all of the body’s living cells. The cells cannot use glucose without the help of insulin.

blood sugar: See Blood glucose.

cholesterol: A substance similar to fat that is found in the blood, muscles, liver, brain, and other body tissues. The body produces and needs some cholesterol. However, too much cholesterol can make fats stick to the walls of the arteries and cause a disease that decreases or stops circulation.

diabetes: The short name for the disease called diabetes mellitus. Diabetes results when the body cannot use blood glucose as energy because of having too little insulin or being unable to use insulin. See also Type 1 diabetes, Type 2 diabetes, and Gestational diabetes.

diabetes pills: Pills or capsules that are taken by mouth to lower the blood glucose level. These pills may work for people who are still taking insulin.

diabetic eye disease A disease of the small blood vessels of the retina of the eye in people with diabetes. In this disease, the vessels swell and leak liquid into the retina, blurring the vision and sometimes leading to blindness.

diabetic kidney disease: Damage to the cells or blood vessels of the kidney.

diabetic nerve damage: Damage to the nerves of a person with diabetes. Nerve damage may affect the feet and hands, as well as major organs.

gestational diabetes: A type of diabetes that can occur in pregnant women who have not been known to have diabetes before. Although it usually subsides after pregnancy, many women who have had gestational diabetes develop Type 2 diabetes later in life.

glucose: A sugar in our blood and a source of energy for our bodies.

heart attack: Damage to the heart muscle caused when the blood vessels supplying the muscle are blocked, such as when the blood vessels are clogged with fats (a cond called hardening of the arteries).

high blood glucose: A condition that occurs in people with diabetes when their blood glucose levels are too high. Symptoms include having to urinate often, being very thirsty, and losing weight.

hormone: A chemical that special cells in the body release to help other cells work. For example, insulin is a hormone made in the pancreas to help the body use glucose as energy.

impotence: A condition of being unable to keep an erect penis and ejaculate. Some men who have had diabetes a long time become impotent if their nerves have become damaged.

inject: To force a liquid into the body with a needle and syringe.

insulin: A hormone that helps the body use blood glucose for energy. The beta cells of the pancreas make insulin. When people with diabetes cannot make enough insulin, they may have to inject it from another source.

ketones: Chemical substances that the body makes when it does not have enough insulin in the blood. When ketones build up for a long time, serious illness or coma can result.

kidneys: Twin organs found in the lower part of the back. The kidneys purify the blood of all waste and harmful material. They also control the level of some helpful chemical substances in the blood.

meal plan: A guide to help people get the proper amount of calories, carbohydrates, proteins, fats, vitamins, minerals, and fiber in their diet. 

pancreas: An organ in the body that makes insulin so that the body can use glucose for energy. The pancreas also makes enzymes that help the body digest food.

risk factors: Traits that make it more likely that a person will get an illness. For example, a risk factor for getting Type 2 diabetes is having a family history of diabetes. 

self-monitoring blood glucose: A way for people with diabetes to find out how much glucose is in their blood. A drop of blood from the fingertip is placed on a special coated strip of paper that "reads" (often through an electronic meter) the amount of glucose in the blood.

stroke: Damage to part of the brain that happens when the blood vessels supplying that part are blocked, such as when the blood vessels are clogged with fats (sometimes called hardening of the arteries).

type 1 diabetes: A condition in which the pancreas makes so iittle insulin that the body cannot use blood glucose as energy. Type 1 diabetes most often occurs in people younger than age 30 and must be controlled with daily insulin injections.

type 2 diabetes: A condition in which the body either makes too little insulin or cannot use the insulin it makes to use blood glucose as energy. Type 2 diabetes most often occurs in people older than age 40 and can often be controlled through meal plans and physical activity plans. Some people with Type 2 diabetes have to take diabetes pills or insulin.

ulcer: A break or deep sore in the skin. Germs can enter an ulcer and may be hard to heal.

yeast infection: A vaginal infection that is usually caused by a fungus. Women who have this infection may feel itching, burning when urinating, and pain, and some women have a vaginal discharge.


\4 Diseases explained

How Your Doctor Diagnoses an Infectious Disease. Doctors who diagnose and treat infectious diseases are considered some of the best detectives of medicine, and with good reason: Infectious diseases can affect any body system, be acute (short-acting) or chronic (long-acting), occur with or without fever, strike any age group, and overlap each other.
 The patient history takes on major importance in these cases. Your doctor may begin by asking you to describe the symptoms you are experiencing fever, pain, rashes, stomach upset, and so on. He or she may also ask about personal factors, that may not seem at all related to your health, including the following:
 What have you been immunized against, and when? Do you have any pets? Do you work in a job in which you are frequently exposed to young children or sick people? Do you travel a great deal? If so, where? Have you used intravenous drugs? What is the nature of your sexual activity? These questions help in diagnosis because each disease has a description, called an epidemiology, that sums up all the factors that contribute to the likelihood of infection. These elements include how the disease is transmitted, where it is most prevalent, and what groups of people are most likely to be susceptible to it.
 Knowing about your home and work environments, habits, and lifestyle can help your doctor determine if you are at risk for a particular infectious disease. For example, toxoplasmosis is an infectious disease caused by the protozoan Toxoplasma gondii, and cats are the definitive host. When people handle a cat's litter box or garden in areas that might contain cat feces, it is possible for them to contract the disease. Your eating habits also provide clues.
If you regularly eat sushi or other raw or undercooked meat, you are at increased risk for several protozoal infections. Perhaps the most critical disclosure concerns your sexual activity. If you are not in a mutually monogamous relationship, you may be considered a candidate for sexually transmitted disease.
 Clues from your history may lead to more pointed ques- tions about your condition. The doctor may also have an idea of what to look for during a physical examination. For example, if you live in or recently visited the mid-Atlantic states, and you have fever and joint aches, one possibility your doctor might investigate is Rocky Mountain spotted fever, which is carried by ticks that are found in large numbers in that area. During the physical examination, he or she may come closer to this diagnosis by spotting its characteristic red rash.
 Your doctor will then analyze these factors—your history, your symptoms, and the epidemiology of diff infectious diseases—for any overlapping areas. In most cases, especially for commonly encountered infections, your doctor will use this information to make an educated guess about the infection and prescribe a standard treatment. However, there is great concern about the overuse of antibiotics; a number of drugs are now ineffective against today's more resistant infectious organisms. In addition, antibiotics are of little use if a virus or fungus is responsible for your infection.

For these reasons, many doctors are not so quick to pull out the prescription pad. If your doctor prefers to be conservative about prescribing antibiotics, he or she may suggest some diagnostic testing. The problem is that some infectious agents are difficult to detect or isolate, and test results may not be available for days or weeks. 

Meanwhile, the infection can grow and cause more diffi- culty. Thus, the doctor's conclusion takes all these factors into consideration. If your doctor prescribes a treatment that does not take care of the infection in a reasonable amount of time, he or she may then turn to one or more of the diagnostic tests listed on the following pages to determine a new course of treatment (see table 22.1), (the box on gen tests used to diag infectious diseases, and the specific tests described below).

Selected Infectious Diseases, Their Symptoms, and Appropriate Diagnostic Tests. Viral Infections Diag tests for viral infections gen involve the search for antibodies that are produced to fight a particular virus. Often no diagnostic tests are necessary because many viruses, such as measles or chicken pox, require no treatment in otherwise healthy children except to relieve symptoms. They run a limited course, and usually result in lifelong immunity. 

In certain situations, your doctor may run tests to see if you have an immunity to a particular virus. This is frequently the case when a woman decides to become pregnant. Her doctor may assess her immunity to viruses such as rubella, which causes an otherwise mild disease but could be dangerous to her developing fetus if the mother contracted it during pregnancy.

Disease Symptoms Diagnostic Tests AIDS (acquired immunodeficiency syndrome)Weakened immune system causes numerous symptoms such as fatigue, swollen glands, fever, and increased susceptibility to other infections.HIV antibody by ELISA, HIV, p24 antigen, and Western blot (a more specific antibody-detection test). (Also See chapter 21.)Chicken pox/shingles (Varicella zoster virus VZV)Painful skin blisters.Varicella zoster virus (VZV) culture, VZV titer, and VZV antigen from tissue samples.EncephalitisInflammation of the brain, high fever, headache, delirium, nausea, and vomiting.Titers for the different viruses that can cause encephalitis: California, Eastern equine, and Western equine viruses; and CSF culture.Flu (influenza)Fever, chills, sore throat, cough, aches and pains, and fatigue.Influenza A and B titer, influenza virus culture, and influenza virus direct antigen detection.HepatitisSwollen, painful liver, nausea/vomiting, and diarrhea.Hepatitis A, B, and C antigen and antibody tests.Herpes simplex (genital herpes)Painful, recurrent blisterlike sores in genital area.Herpes simplex virus 2 (HSV2) culture, HSV direct antigen detection, and HSV2 antibody.Herpes simplex (oral herpes)Painful blisterlike sores around the mouth and nose.Herpes simplex virus 1 (HSV1) culture, HSV direct antigen detection, and HSV1 antibody.Infectious mononucleosis (caused by Epstein-Barr virus)Constant fatigue, persistent fever, swollen glands, and sore throat.Epstein-Barr virus (EBV) antibody titer, and heterophil antibody (an antibody toward EBV) agglutination test.MeaslesFever followed by red spots inside cheeks followed by pink rash.Measles virus antibody titer.RabiesRange from fever and headache to severe brain inflammation and death.Rabies virus direct antibody detection, and rabies virus antigen detection in tissues.Rubella (German measles)High fever, skin rash, joint pain, and swollen lymph nodes.Rubella virus culture and rubella antibody test.Viral meningitisSevere headache, stiffness in neck and back, high fever, and skin rash.Titers for viruses that cause meningitis such as Coxsackie A or B virus, poliovirus, echoviruses, mumps virus, and antibody titers.

Bacterial Infections. In diagnosing bacterial infections, cultures are the most commonly used tools. Treatment may be concurrent or may precede any diagnostic tests. For example, the signs of an infection such as gonorrhea or pneumonia may be so obvious that your doctor may deem it unimportant to determine the specific bacterium responsible; prompt treatment with an antibiotic that kills a wide variety of organisms may be the best course. DiseasesSymptomsDiagnostic TestsBacterial gastroenteritisStomach pain, diarrhea, nausea/vomiting, and appetite loss.Cultures of bacteria that commonly cause gastroenteritis: salmonella, shigella, campylobacter, E. coli, and yersinia.Bacterial meningitisSevere headache, stiffness in neck and back, high fever, and skin rash.Cultures of CSF and blood for meningitis-causing bacteria, and test for bacterial antigens in CSF.GonorrheaPain and burning upon urination, itching, and genital pus discharge.Gonorrhea culture or smear.Legionnaires' disease (type of pneumonia)Flulike symptoms with coughing and diarrhea.Tests for Legionnaires' disease antibodies, and Legionella pneumophila culture.LeptospirosisFever, chills, muscular aches, headache, and jaundice.Leptospira urine, urinary legionella antigen, and CSF culture.Lyme diseaseJoint pain, fever, chills, and fatigue.Blood and/or CSF serology for antibody against Borrelia burgdorferi.Pertussis (whooping cough)A barking-type cough, fever, sneezing, and runny nose.Bordetella pertussis nasopharyngeal culture.PharyngitisSore throat and fever.Throat culture for Group A streptococcus and Corynebacterium diphtheriae.Pneumonia (bacterial)Severe cough producing thick, off-colored sputum, high fever, fatigue, and chills.Cultures of sputum for pneumonia-causing microorganisms including Streptococcus pneumoniae, Mycoplasma pneumoniae, Chlamydia pneumoniae, Klebsiella pseudomonas, and Staphylococcus aureus; and chest X-ray.SinusitisSwelling and/or blockage of sinus passages causing difficulty breathing and pressure headache.Culture of sinus samples.Staphylococcus aureus infectionVary according to disease produced.Staphylococcus aureus culture.Streptococcal (strep) infectionVary according to disease produced.Streptococcal culture.Syphilis (caused by a spirochete microorganism, Treponema pallidum)Sores called chancres, fever, joint pain, headache, and fatigue.Treponema pallidum dark-field examination, Venereal Disease Research Laboratory (VDRL) test (antibody test named for the laboratory that developed it), FTA-ABS (fluorescent treponemal antibody absorption test), and MHA-TP (microhemagglutination assay for Treponema pallidum).Tuberculosis (TB)Fever, cough, chest pain, and difficulty breathing; also weight loss and fatigue.Tuberculin skin test, chest X-ray, and sputum culture for TB. Chlamydial InfectionsChlamydia microorganisms can cause a variety of illnesses. For instance, chlamydial infection is the leading sexually transmitted disease in the United States. In the past, it has often been overlooked or misdiagnosed. If untreated in women, it can progress to pelvic inflammatory disease (PID), a leading cause of infertility. Because of this and the fact that it is difficult to culture, doctors usually begin treatment as soon as they suspect chlamydial infection. DiseaseSymptomsDiagnostic TestsChlamydia trachomatis infection (conjunctivitis or pink eye, and sexually transmitted chlamydia)For conjunctivitis: Redness and inflammation of tissue around eyes, excessive eye discharge, and tearing. For sexually transmitted chlamydia: Burning sensation during and frequency of urination.Chlamydia culture, Chlamydia trachomatis complement fixation test, and immunofluorescence tests for IgM.Chlamydia pneumoniae infection (pneumonia)Symptoms of pneumonia including fever and productive cough.Chlamydia culture and serology. Rickettsial InfectionsRickettsial diseases are spread through ticks, fleas, or lice. People become infected when they are bitten or come into contact with insect feces. Often these infections are spread by rodents carrying the ticks, fleas, or lice. Because of public health measures to limit rodent populations, many of these infections, such as typhus, are rare in the United States, and thus are not mentioned here. One exception is Rocky Mountain spotted fever, which is transmitted by the dog tick in the eastern United States and by the wood tick in the west. It is characterized by a red skin rash, fever, and joint pain and is tested for by Rickettsia rickettsii serology and Weil-Felix reaction (an agglutination test).Fungal InfectionsFungal infections often occur because of the use of antibiotic drugs for other conditions. In addition to killing the offending microorganisms, the antibiotic may also kill off the "good" bacteria that normally keep fungi at bay. For example, women who take tetracycline to control acne may develop a vaginal yeast infection. Fungal infections are also a major problem for people with weakened immune systems, such as AIDS patients.

DiseaseSymptomsDiagnostic TestsAspergillosisVary according to the syndrome produced, such as bronchial infection, skin infection, or sinusitis.Aspergillus serology (antigen and antibody), tissue biopsy, and sputum culture.Candidiasis (oral thrush, thrush nipples, and vaginitis)For oral thrush: White patches in mouth and mouth pain. For thrush nipples: Red spotted rash, peeling skin, and pain in nipples of breast-feeding women. For vaginitis: Thick, curdlike, vaginal discharge, and pelvic pain.Cultures for Candida albicans on samples from affected areas.CryptococcosisSymptoms of pneumonitis or meningitis.Cryptococcus antigen titer, cryptococcus culture, and stain of tissue biopsy.HistoplasmosisFlulike symptoms such as fever, cough, headache, chest pain, and loss of appetite.Fungal antibody screen, culture with stain of biopsy tissue, and urine antigen assay. Parasitic Infections or InfestationsThis category includes infections caused by protozoal microorganisms and worms (sometimes called helminthic infection). The latter set up shop in the intestines and can cause considerable gastrointestinal discomfort and diarrhea. Protozoal infections often occur during or after travel to a foreign country. A microorganism that the local people tolerate well may wreak havoc in a visitor's system. "Traveler's diarrhea" is a general term for this condition. The infections are highly contagious—the parasites can be ingested in food or water or passed by even casual contact—so usually the whole family must be diagnosed and treated. The same is true for parasitic worm infection. Diagnosis of parasitic infections relies on serology and stool examination for eggs (ova) or the microorganisms themselves. DiseaseSymptomsDiagnostic TestsAmebiasisDiarrhea, abdominal cramps, and loss of appetite.Entamoeba histolytica serologic tests, and ova and parasite exam of stool.Ascariasis (worms)Symptoms of lung infection including cough.Stool exam for ova and parasites.GiardiasisDiarrhea and abdominal cramps.Ova and parasite exam of stool.MalariaFever, chills, headache, nausea, and anemia.Malaria smear for plasmodium in blood.PinwormsItching in and around the anus, especially at night; most common in children.Stool exam for ova and parasites.TapewormsUsually none, sometimes nausea, diarrhea, and abdominal pain.Stool exam for ova and parasites.ToxoplasmosisFever, headache, swollen glands, stiff neck, and sore throat.Serology for Toxoplasma gondii antibodies (IgG and IgM), and biopsy of involved tissue.

PATIENT TIPS
 You can help control the proliferation of infectious organisms that are resistant to treatment if you do the following:
 •Do not insist that your doctor give you an antibiotic when there is no clear indication that you have a bacterial infection. The antibiotic won't help you if you hvve a viral or fungal infection; in fact, it may make it worse. At the same time, it may alter a type of bacteria living harmlessly in your body so that it becomes resistant to the antibiotic. This resistance can then be passed on to disease-causing bacteria. •Always finish your full prescription of antibiotics, even if your symptoms disappear before you have taken all your pills. If you don't, you may simply weaken, not kill, the bacteria, which may then become resistant to the drug and may cause repeat infection. •Never refill your prescription to use on another illness without checking with your doctor.
 General Tests Used in Diagnosing Infectious Diseases Most tests for infectious disease involve laboratory analysis of body fluids—blood, urine, cerebrospinal fluid, genital secretions, sputum, and others. Basic procedures in obtaining these specimens are described in chapter 4. How they apply to the diagnosis of infectious diseases is described below.
 Smears A small portion of the sample is looked at under a microscope for identification of the cells present. It is a quick way to see some microorganisms or detect abnormal cell activity such as white blood cell response to an invader.
 Cultures The best way to make a diagnosis involving an infectious agent is to isolate and identify the microorganism itself. A culture is often the best method of accomplishing this task. The culture can be performed using fluids such as blood, cerebrospinal fluid (CSF), or joint fluid to screen for a wide variety of bacteria. Or it can be used to look for specific organisms, such as salmonella or shigella (common causes of gastrointestinal infection), in stool samples. The sample is placed in an environment, or medium, that is designed to encourage specific organisms to reproduce. This medium is usually a jellylike substance that provides nutrients for the microorganisms. If the organism is present, it may multiply rapidly or it may take several weeks to grow.

Sometimes a culture is used to determine which drug will best treat your infection, a procedure called antibiotic susceptibility testing. The drug is added to the cultured sample directly to see if it kills the offending organism. This procedure may help determine further drug therapy when standard treatments fail or when a particularly unusual or virulent organism is responsible for illness.
 Antigen and Antibody Tests Tests to identify antibodies or antigens are usually performed on blood serum, the liquid product that is left when blood clots and the clot is then removed. Tests performed using blood serum are called serologic tests or serology. Some of these tests are designed simply to identify a particular substance in the serum. Others, called titers, measure the concentration of that substance.
 In antigen tests, a known antibody is used to test a blood specimen for antigens with which it might associate in response to different infections. This mimics the immune system's antigen-antibody reaction. In antibody tests, the process is done in reverse: a known antigen is used in an attempt to identify the antibodies that might be attracted to it. There are several techniques used for both kinds of tests. These include the following:
 •Observing for a precipitation reaction. A substance may separate or "precipitate out" of a mixture once the antigen-antibody reaction has taken place. This occurs because the substance cannot dissolve in its environment. Rain and snow are called precipitation because they result when the skies cannot "contain" any more moisture and some of it must precipitate out of the atmosphere. These conditions can be produced in a beaker in a laboratory. If some component of a human sample reacts with something added to it, then the product may be observed; it may separate and settle on the bottom of the beaker if the test is run in a solution that cannot dissolve or contain that product. •Observing for an agglutination reaction, a clumping of antigen or antibody cells that occurs when they come into contact with their corresponding antibody or antigen. This is the same thing that happens in the body when antibodies cause agglutination of antigens so the offending microorganisms can be eliminated more easily. •Initiating a complement fixation, or CF, in which an antigen binds with an antibody and this combination allows the complement (a unique set of proteins) to become fixed at the same location. This fixation reaction can be detected indirectly, thereby identifying the original antigen. •Tagging specific antibodies with special dye, so that the antigens they attract can be seen. They show up as green, glowing particles under a fluorescent microscope. This test is sometimes called the fluorescent antibody test, or immunofluorescence. •Enzyme-linked immunosorbent assay (ELISA) or radioimmunoassay (RIA) are two other techniques that rely on tagging and identification. In ELISA, the antibodies are tagged with certain enzymes, which are proteins the body uses to speed up a variety of bodily functions. In RIA, the antibodies are tagged with radioactive material.
 Other Tests Other tests described elsewhere in this book also help the doctor determine a diagnosis. In fact, the diagnosis of infectious disease often occurs when these tests are done for other reasons.
 •Imaging tests (see chapter 3) include X-rays, computed tomography (CT) scans, and bone and other radionuclide scans. These are often useful in diagnosing infection because of their ability to show inflammation of inner organs or fluid buildup that may not be obvious from simple observation. •Invasive tests are accomplished by introducing a fiber-optic scope or fine needle into the body to visualize internal structures or obtain a biopsy—a sample of tissues or fluid. Examples include bronchoscopy (for examining the bronchial tubes; See chapter 7 ), colonoscopy (for examining the large intestine; See chap 8 ), and thoracocentesis (for withdrawing fluid present in the chest cavity; See chapter 7.)


\5 Disease, Evolution & Origins

The principles of evolution by natural selection are finally beginning to inform medicine. Thoughtful contemplation of the human body elicits awe--in equal measure with perplexity. The eye, for instance, has long been an object of wonder, with the clear, living tissue of the cornea curving just the right amount, the iris adjusting to brightness and the lens to distance, so that the optimal quantity of light focuses exactly on the surface of the retina. Admiration of such apparent perfection soon gives way, however, to consternation. Contrary to any sensible design, blood vessels and nerves traverse the inside of the retina, creating a blind spot at their point of exit.
 The body is a bundle of such jarring contradictions. For each exquisite heart valve, we have a wisdom tooth. Strands of DNA direct the development of the 10 trillion cells that make up a human adult but then permit his or her steady deterioration and eventual death. Our immune system can identify and destroy a million kinds of foreign matter, yet many bacteria can still kill us. These contradictions make it appear as if the body was designed by a team of superb engineers with occasional interventions by Rube Goldberg.
 In fact, such seeming incongruities make sense but only when we investigate the origins of the body's vulnerabilities while keeping in mind the wise words of distinguished geneticist Theodosius Dobzhansky: "Nothing in biology makes sense except in the light of evolution." Evolutionary biology is, of course, the scientific foundation for all biology, and biology is the foundation for all medicine. To a surprising degree, however, evolutionary biology is just now being recognized as a basic medical science. The enterprise of studying medical problems in an evolutionary context has been termed Darwinian medicine. Most medical research tries to explain the causes of an individual's disease and seeks therapies to cure or relieve deleterious conditions. These efforts are traditionally based on consideration of proximate issues, the straightforward study of the body's anatomic and physiological mechanisms as they currently exist. In contrast, Darwinian medicine asks why the body is designed in a way that makes us all vulnerable to problems like cancer, atherosclerosis, depression and choking, thus offering a broader context in which to conduct research.
 DEFENSIVE RESPONSES: The evolutionary explanations for the body's flaws fall into surprisingly few categories. First, some discomforting conditions, such as pain, fever, cough, vomiting and anxiety, are actually neither diseases nor design defects but rather are evolved defenses. Second, conflicts with other organisms--Escherichia coli or crocodiles, for instance--are a fact of life. Third, some circumstances, such as the ready availability of dietary fats, are so recent that natural selection has not yet had a chance to deal with them. Fourth, the body may fall victim to trade-offs between a trait's benefits and its costs; a textbook example is the sickle cell gene, which also protects against malaria. Finally, the process of natural selection is constrained in ways that leave us with suboptimal design features, as in the case of the mammalian eye.
 Evolved Defenses. Perhaps the most obviously useful defense mechanism is coughing; people who cannot clear foreign matter from their lungs are likely to die from pneumonia. The capacity for pain is also certainly beneficial. The rare individuals who cannot feel pain fail even to experience discomfort from staying in the same position for long periods. Their unnatural stillness impairs the blood supply to their joints, which then deteriorate. Such pain-free people usually die by early adulthood from tissue damage and infections. Cough or pain is usually interpreted as disease or trauma but is actually part of the solution rather than the problem. These defensive capabilities, shaped by natural selection, are kept in reserve until needed.
 Less widely recognized as defenses are fever, nausea, vomiting, diarrhea, anxiety, fatigue, sneezing and inflammation. Even some physicians remain unaware of fever's utility. No mere increase in metabolic rate, fever is a carefully regulated rise in the set point of the body's thermostat. The higher body temperature facilitates the destruction of pathogens. Work by Matthew J. Kluger of the Lovelace Institute in Albuquerque, N.M., has shown that even cold-blooded lizards, when infected, move to warmer places until their bodies are several degrees above their usual temperature. If prevented from moving to the warm part of their cage, they are at increased risk of death from the infection. In a similar study by Evelyn Satinoff of the University of Delaware, elderly rats, who can no longer achieve the high fevers of their younger lab companions, also instinctively sought hotter environments when challenged by infection.

A reduced level of iron in the blood is another misunderstood defense mechanism. People suffering from chronic infection often have decreased levels of blood iron. Although such low iron is sometimes blamed for the illness, it actually is a protective response: during infection, iron is sequestered in the liver, which prevents invading bacteria from getting adequate supplies of this vital element.
 Morning sickness has long been considered an unfortunate side effect of pregnancy. The nausea, however, coincides with the period of rapid tissue differentiation of the fetus, when development is most vulnerable to interference by toxins. And nauseated women tend to restrict their intake of strong-tasting, potentially harmful substances. These observations led independent researcher Margie Profet to hypothesize that the nausea of pregnancy is an adaptation whereby the mother protects the fetus from exposure to toxins. Profet tested this idea by examining pregnancy outcomes. Sure enough, women with more nausea were less likely to suffer miscarriages. (This evidence supports the hypothesis but is hardly conclusive. If Profet is correct, further research should discover that pregnant females of many species show changes in food preferences. Her theory also predicts an increase in birth defects among offspring of women who have little or no morning sickness and thus eat a wider variety of foods during pregnancy.)
 Another common condition, anxiety, obviously originated as a defense in dangerous situations by promoting escape and avoidance. A 1992 study by Lee A. Dugatkin of the University of Louisville evaluated the benefits of fear in guppies. He grouped them as timid, ordinary or bold, depending on their reaction to the presence of smallmouth bass. The timid hid, the ordinary simply swam away, and the bold maintained their ground and eyed the bass. Each guppy group was then left alone in a tank with a bass. After 60 hours, 40 percent of the timid guppies had survived, as had only 15 percent of the ordinary fish. The entire complement of bold guppies, on the other hand, wound up aiding the transmission of bass genes rather than their own.
 Selection for genes promoting anxious behaviors implies that there should be people who experience too much anxiety, and indeed there are. There should also be hypophobic individuals who have insufficient anxiety, either because of genetic tendencies or antianxiety drugs. The exact nature and frequency of such a syndrome is an open question, as few people come to psychiatrists complaining of insufficient apprehension. But if sought, the pathologically nonanxious may be found in emergency rooms, jails and unemployment lines.
 The utility of common and unpleasant conditions such as diarrhea, fever and anxiety is not intuitive. If natural selection shapes the mechanisms that regulate defensive responses, how can people get away with using drugs to block these defenses without doing their bodies obvious harm? Part of the answer is that we do, in fact, sometimes do ourselves a disservice by disrupting defenses.
 Herbert L. DuPont of the University of Texas at Houston and Richard B. Hornick of Orlando Regional Medical Center studied the diarrhea caused by Shigella infection and found that people who took antidiarrhea drugs stayed sick longer and were more likely to have complications than those who took a placebo. In another example, Eugene D. Weinberg of Indiana University has documented that well-intentioned attempts to correct perceived iron deficiencies have led to increases in infectious disease, especially amebiasis, in parts of Africa. Although the iron in most oral supplements is unlikely to make much difference in otherwise healthy people with everyday infections, it can severely harm those who are infected and malnourished. Such people cannot make enough protein to bind the iron, leaving it free for use by infectious agents.
 On the morning-sickness front, an antinausea drug was recently blamed for birth defects. It appears that no consideration was given to the possibility that the drug itself might be harmless to the fetus but could still be associated with birth defects, by interfering with the mother's defensive nausea.
 Another obstacle to perceiving the benefits of defenses arises from the observation that many individuals regularly experience seemingly worthless reactions of anxiety, pain, fever, diarrhea or nausea. The explanation requires an analysis of the regulation of defensive responses in terms of signal-detection theory. A circulating toxin may come from something in the stomach. An organism can expel it by vomiting, but only at a price. The cost of a false alarm--vomiting when no toxin is truly present--is only a few calories. But the penalty for a single missed authentic alarm--failure to vomit when confronted with a toxin--may be death.
 Natural selection therefore tends to shape regulation mechanisms with hair triggers, following what we call the smoke-detector principle. A smoke alarm that will reliably wake a sleeping family in the event of any fire will necessarily give a false alarm every time the toast burns. The price of the human body's numerous "smoke alarms" is much suffering that is completely normal but in most instances unnecessary. This principle also explains why blocking defenses is so often free of tragic consequences. Because most defensive reactions occur in response to insignificant threats, interference is usually harmless; the vast majority of alarms that are stopped by removing the battery from the smoke alarm are false ones, so this strategy may seem reasonable. Until, that is, a real fire occurs.
 Conflicts with Other Organisms Natural selection is unable to provide us with perfect protection against all pathogens, because they tend to evolve much faster than humans do. E. coli, for example, with its rapid rates of reproduction, has as much opportunity for mutation and selection in one day as humanity gets in a millennium. And our defenses, whether natural or artificial, make for potent selection forces. Pathogens either quickly evolve a counterdefense or become extinct. Amherst College biologist Paul W. Ewald has suggested classifying phenomena associated with infection according to whether they benefit the host, the pathogen, both or neither. Consider the runny nose associated with a cold. Nasal mucous secretion could expel intruders, speed the pathogen's transmission to new hosts or both [see "The Evolution of Virulence," by Paul W. Ewald; Scientific American, April 1993]. Answers could come from studies examining whether blocking nasal secretions shortens or prolongs illness, but few such studies have been done.
 EVOLUTION OF VIRULENCE. Humanity won huge battles in the war against pathogens with the development of antibiotics and vaccines. Our victories were so rapid and seemingly complete that in 1969 U.S. Surgeon General William H. Stewart said that it was "time to close the book on infectious disease." But the enemy, and the power of natural selection, had been underestimated. The sober reality is that pathogens apparently can adapt to every chemical researchers develop. ("The war has been won," one scientist more recently quipped. "By the other side.")
 Antibiotic resistance is a classic demo of natural selection. Bacteria that happen to have genes that allow them to prosper despite the presence of an antibiotic reproduce faster than others, and so the genes that confer resistance spread quickly. As shown by Nobel laureate Joshua Lederberg of the Rockefeller Univ, they can even jump to diff species of bacteria, borne on bits of infectious DNA. Today some strains of TB in NYC are resistant to all three main antibiotic treatments; patients with those strains have no better chance of surviving than did TB patients a century ago. Stephen S. Morse of Columbia Univ notes that the multidrug-resistant strain that has spread throughout the East Coast may have originated in a homeless shelter across the street from Columbia Presbyterian Med Ctr. Such a phenomenon would indeed be predicted in an environment where fierce selection pressure quickly weeds out less hardy strains. The surviving bacilli have been bred for resistance.
 Many people, including some physicians and scientists, still believe the outdated theory that pathogens necessarily become benign after long association with hosts. Superficially, this makes sense. An organism that kills rapidly may never get to a new host, so natural selection would seem to favor lower virulence. Syphilis, for instance, was a highly virulent disease when it first arrived in Europe, but as the centuries passed it became steadily more mild. The virulence of a pathogen is, however, a life history trait that can increase as well as decrease, depending on which option is more advantageous to its genes.
 For agents of disease that are spread directly from person to person, low virulence tends to be beneficial, as it allows the host to remain active and in contact with other potential hosts. But some diseases, like malaria, are transmitted just as well--or better--by the incapacitated. For such pathogens, which usually rely on intermediate vectors like mosquitoes, high virulence can give a selective advantage. This principle has direct implications for infection control in hospitals, where health care workers' hands can be vectors that lead to selection for more virulent strains.
 In the case of cholera, public water supplies play the mosquitoes' role. When water for drinking and bathing is contaminated by waste from immobilized patients, selection tends to increase virulence, because more diarrhea enhances the spread of the organism even if individual hosts quickly die. But, as Ewald has shown, when sanitation improves, selection acts against classical Vibrio cholerae bacteria in favor of the more benign El Tor biotype. Under these conditions, a dead host is a dead end. But a less ill and more mobile host, able to infect many others over a much longer time, is an effective vehicle for a pathogen of lower virulence. In another example, better sanitation leads to displacement of the aggressive Shigella flexneri by the more benign S. sonnei.
 NEW ENVIRONMENTS, NEW THREATS Such considerations may be relevant for public policy. Evolutionary theory predicts that clean needles and the encouragement of safe sex will do more than save numerous individuals from HIV infection. If humanity's behavior itself slows HIV transmission rates, strains that do not soon kill their hosts have the long-term survival advantage over the more virulent viruses that then die with their hosts, denied the opportunity to spread. Our collective choices can change the very nature of HIV.
 Conflicts with other organisms are not limited to pathogens. In times past, humans were at great risk from predators looking for a meal. Except in a few places, large carnivores now pose no threat to humans. People are in more danger today from smaller organisms' defenses, such as the venoms of spiders and snakes. Ironically, our fears of small creatures, in the form of phobias, probably cause more harm than any interactions with those organisms do. Far more dangerous than predators or poisoners are other members of our own species. We attack each other not to get meat but to get mates, territory and other resources. Violent conflicts between individuals are overwhelmingly between young men in competition and give rise to organizations to advance these aims. Armies, again usually composed of young men, serve similar objectives, at huge cost.
 Even the most intimate human relationships give rise to conflicts having medical implications. The reproductive interests of a mother and her infant, for instance, may seem congruent at first but soon diverge. As noted by biologist Robert L. Trivers in a now classic 1974 paper, when her child is a few years old, the mother's genetic interests may be best served by becoming pregnant again, whereas her offspring benefits from continuing to nurse. Even in the womb there is contention. From the mother's vantage point, the optimal size of a fetus is a bit smaller than that which would best serve the fetus and the father. This discord, according to David Haig of Harvard University, gives rise to an arms race between fetus and mother over her levels of blood pressure and blood sugar, sometimes resulting in hypertension and diabetes during pregnancy.
 Coping with Novelty. Making rounds in any hosp provides sad testimony to the prevalence of diseases humanity has brought on itself. Heart attacks, for example, result mainly from atherosclerosis, a problem that became widespread only in this century and that remains rare among hunter-gatherers. Epidemiological research furnishes the information that should help us prevent heart attacks: limit fat intake, eat lots of vegetables, and exercise hard each day. But hamburger chains proliferate, diet foods languish on the shelves, and exercise machines serve as expensive clothing hangers throughout the land. The proportion of overweight Americans is one third and rising. We all know what is good for us. Why do so many of us continue to make unhealthy choices?
 Our poor decisions about diet and exercise are made by brains shaped to cope with an environment substantially different from the one our species now inhabits. On the African savanna, where the modern human design was fine-tuned, fat, salt and sugar were scarce and precious. Individuals who had a tendency to consume large amounts of fat when given the rare opportunity had a selective advantage. They were more likely to survive famines that killed their thinner companions. And we, their descendants, still carry those urges for foodstuffs that today are anything but scarce. These evolved desires-inflamed by advertisements from competing food corporations that themselves survive by selling us more of whatever we want to buy--easily defeat our intellect and willpower. How ironic that humanity worked for centuries to create environments that are almost literally flowing with milk and honey, only to see our success responsible for much modern disease and untimely death.
 Increasingly, people also have easy access to many kinds of drugs, especially alcohol and tobacco, that are responsible for a huge proportion of disease, health care costs and premature death. Although individuals have always used psychoactive substances, widespread problems materialized only following another environmental novelty: the ready availability of concentrated drugs and new, direct routes of administration, especially injection. Most of these substances, including nicotine, cocaine and opium, are products of natural selection that evolved to protect plants from insects. Because humans share a common evolutionary heritage with insects, many of these substances also affect our nervous system.
  This perspective suggests that it is not just defective individuals or disordered societies that are vulnerable to the dangers of psychoactive drugs; all of us are susceptible because drugs and our biochemistry have a long history of interaction. Understanding the details of that interaction, which is the focus of much current research from both a proximate and evolutionary perspective, may well lead to better treatments for addiction.
 The relatively recent and rapid increase in breast cancer must be the result in large part of changing environments and ways of life, with only a few cases resulting solely from genetic abnormalities. Boyd Eaton and his colleagues at Emory University reported that the rate of breast cancer in today's "nonmodern" societies is only a tiny fraction of that in the U.S. They hypothesize that the amount of time between menarche and first pregnancy is a crucial risk factor, as is the related issue of total lifetime number of menstrual cycles. In hunter-gatherers, menarche occurs at about age 15 or later, followed within a few years by pregnancy and two or three years of nursing, then by another pregnancy soon after. Only between the end of nursing and the next pregnancy will the woman menstruate and thus experience the high levels of hormones that may adversely affect breast cells.
 In modern societies, in contrast, menarche occurs at age 12 or 13--probably at least in part because of a fat intake sufficient to allow an extremely young woman to nourish a fetus--and the first pregnancy may be decades later or never. A female hunter-gatherer may have a total of 150 menstrual cycles, whereas the average woman in modern societies has 400 or more. Although few would suggest that women should become pregnant in their teens to prevent breast cancer later, early administration of a burst of hormones to simulate pregnancy may reduce the risk. Trials to test this idea are now under way at the UC at San Diego.
 Trade-offs and Constraints. Compromise is inherent in every adaptation. Arm bones three times their current thickness would almost never break, but Homo sapiens would be lumbering creatures on a never-ending quest for calcium. More sensitive ears might sometimes be useful, but we would be distracted by the noise of air molecules banging into our eardrums.
 Such trade-offs also exist at the genetic level. If a mutation offers a net reproductive advantage, it will tend to increase in frequency in a population even if it causes vulnerability to disease. People with two copies of the sickle cell gene, for example, suffer terrible pain and die young. People with two copies of the "normal" gene are at high risk of death from malaria. But individuals with one of each are protected from both malaria and sickle cell disease. Where malaria is prevalent, such people are fitter, in the Darwinian sense, than members of either other group. So even though the sickle cell gene causes disease, it is selected for where malaria persists. Which is the "healthy" allele in this environment? The question has no answer. There is no one normal human genome--there are only genes.
 SMALL APPENDIX: Many other genes that cause disease must also have offered benefits, at least in some environments or they would not be so common. Because cystic fibrosis (CF) kills one out of 2,500 Caucasians, the responsible genes would appear to be at great risk of being eliminated from the gene pool. And yet they endure. For years, researchers mused that the CF gene, like the sickle cell gene, probably conferred some advantage. Recently a study by Gerald B. Pier of Harvard Medical School and his colleagues gave substance to this informed speculation: having one copy of the CF gene appears to decrease the chances of the bearer acquiring a typhoid fever infection, which once had a 15 percent mortality.
 Aging may be the ultimate example of a genetic trade-off. In 1957 one of us (Williams) suggested that genes that cause aging and eventual death could nonetheless be selected for if they had other effects that gave an advantage in youth, when the force of selection is stronger. For instance, a hypothetical gene that governs calcium metabolism so that bones heal quickly but that also happens to cause the steady deposition of calcium in arterial walls might well be selected for even though it kills some older people. The influence of such pleiotropic genes (those having multiple effects) has been seen in fruit flies and flour beetles, but no specific example has yet been found in humans. Gout, however, is of particular interest, because it arises when a potent antioxidant, uric acid, forms crystals that precipitate out of fluid in joints. Antioxidants have antiaging effects, and plasma levels of uric acid in different species of primates are closely correlated with average adult life span. Perhaps high levels of uric acid benefit most humans by slowing tissue aging, while a few pay the price with gout.
 Other examples are more likely to contribute to more rapid aging. For instance, strong immune defenses protect us from infection but also inflict continuous, low-level tissue damage. It is also poss, that most genes that cause aging have no benefit at any age-they simply never decreased reproductive fitness enough in the natural environment to be selected against. Nevertheless, over the next decade research will surely ID specific genes that accelerate senescence, and researchers will gain the means to interfere with their actions or even change them. Before we tinker, however, we should determine whether these actions have benefits early in life.
 Because evolution can take place only in the direction of time's arrow, an organism's design is constrained by structures already in place. As noted, the vertebrate eye is arranged backward. The squid eye, in contrast, is free from this defect, with vessels and nerves running on the outside, penetrating where necessary and pinning down the retina so it cannot detach. The human eye's flaw results from simple bad luck; hundreds of millions of years ago, the layer of cells that happened to become sensitive to light in our ancestors was positioned differently from the corresponding layer in ancestors of squids. The two designs evolved along separate tracks, and there is no going back.
 Such path dependence also explains why the simple act of swallowing can be life-threatening. Our respiratory and food passages intersect because in an early lungfish ancestor the air opening for breathing at the surface was understandably located at the top of the snout and led into a common space shared by the food passageway. Because natural selection cannot start from scratch, humans are stuck with the possibility that food will clog the opening to our lungs.
 The path of natural selection can even lead to a potentially fatal cul-de-sac, as in the case of the appendix, that vestige of a cavity that our ancestors employed in digestion. Because it no longer performs that function, and as it can kill when infected, the expectation might be that natural selection would have eliminated it. The reality is more complex. Appendicitis results when inflammation causes swelling, which compresses the artery supplying blood to the appendix. Blood flow protects against bacterial growth, so any reduction aids infection, which creates more swelling. If the blood supply is cut off completely, bacteria have free rein until the appendix bursts. A slender appendix is especially susceptible to this chain of events, so appendicitis may, paradoxically, apply the selective pressure that maintains a large appendix. Far from arguing that everything in the body is perfect, an evolutionary analysis reveals that we live with some very unfortunate legacies and that some vulnerabilities may even be actively maintained by the force of natural selection.
 Evolution of Darwinian Medicine. Despite the power of the Darwinian paradigm, evolutionary biology is just now being recognized as a basic science essential for medicine. Most diseases decrease fitness, so it would seem that natural selection could explain only health, not disease. A Darwinian approach makes sense only when the object of explanation is changed from diseases to the traits that make us vulnerable to diseases. The assumption that natural selection maximizes health also is incorrect-selection maximizes the reproductive success of genes. Those genes that make bodies having superior reproductive success will become more common, even if they compromise the individual's health in the end.

Disease, Evolution & Origins R.M.Nesse and G.C.Williams 
 Finally, history and misunderstanding have presented obstacles to the acceptance of Darwinian medicine. An evolutionary approach to functional analysis can appear akin to naive teleology or vitalism, errors banished only recently, and with great effort, from medical thinking. And, of course, whenever evolution and medicine are mentioned together, the specter of eugenics arises. Discoveries made through a Darwinian view of how all human bodies are alike in their vulnerability to disease will offer great benefits for individuals, but such insights do not imply that we can or should make any attempt to improve the species. If anything, this approach cautions that apparent genetic defects may have unrecognized adaptive significance, that a single "normal" genome is nonexistent and that notions of "normality" tend to be simplistic.
 The systematic application of evolutionary biology to med is a new enterprise. Like biochemistry at the beginning of this century, Darwinian medicine very likely will need to develop in several incubators before it can prove its power and utility. If it must progress only from the work of scholars without funding to gather data to test their ideas, it will take decades for the field to mature. Depts of evolutionary bio in med schools would accelerate the process, but for the most part they do not yet exist. If funding agencies had review panels with evolutionary expertise, research would develop faster, but such panels remain to be created. We expect that they will.
 The evolutionary viewpoint provides a deep connection between the states of disease and normal functioning and can integrate disparate avenues of medical research as well as suggest fresh and important areas of inquiry. Its utility and power will ultimately lead to recognition of evolutionary biology as a basic medical science.


\6 Diseases, Tropical

Some of the organisms that cause tropical diseases are bacteria and viruses, terms that may be familiar to most people since these types of organisms cause illness common in the U.S. Less well known are those more complex organisms commonly referred to as parasites. All of these types of agents may be referred to generically as pathogens - meaning any organisms that cause disease.
 In the temperate climate zones, many familiar viral and bacterial diseases are spread directly from person to person, by airborne routes of transmission or by sexual contact. In the tropics, respiratory diseases (such as measles, respiratory syncytial virus, tuberculosis) and sexually transmitted diseases are also of great importance. In addition, many diseases are spread by contaminated water and food sources, since clean water and sanitary conditions are often a luxury in developing countries. Alternatively, some tropical disease agents are transmitted by an intermediate carrier or vector. The insect or other invertebrate vector picks up the pathogen from an infected person or animal and transmits it to others in the process of feeding. Often, tropical disease agents must undergo important developmental changes within the vector before they complete their life cycle and once again become infective for man.

Viruses - Viruses are minute infectious agents that generally consist only of genetic material covered by a protein shell. They only replicate within cells, which provide the synthetic machinery necessary to produce new virus particles. Arboviruses (ar'bow) The term "arboviruses" is short for "arthropod-borne viruses". Arthropods include many of the medically important bugs (mosquitoes, ticks, flies, etc.) that may transmit pathogens to humans. Arboviruses are of special relevance as tropical diseases. Dengue (deng'ee) fever, caused by a mosquito-borne flavivirus, is found in tropical and subtropical regions of the Americas, Africa, Asia and Australia. In its acute form, dengue is characterized by flu-like symptoms including severe pain in the head, eyes, muscles and joints. Some patients, particularly infants and children, develop "dengue hemorrhagic fever", a severe and sometimes fatal variation involving circulatory failure and shock. The incidence of both forms of dengue infection has recently been increasing, as expanding urbanization enlarges the regions inhabited by the Aedes mosquito vector. Mosquitoes capable of transmitting this disease are also found within the United States. Yellow fever is another arboviral disease, characterized by fever, hemorrhage, and often fatal liver complications. It is limited to tropical South America and Africa, where it is sometimes epidemic in spite of the existence of a safe and effective vaccine. The potential for increased incidence of yellow fever appears to be growing with the expanding distribution of the vector Aedes mosquitoes.
 Rotavirus (row'ta) Rotavirus causes watery diarrhea and vomiting, primarily in young children. These viruses are distributed worldwide and transmission is usually due to contact with infected individuals or fecally contaminated objects. The majority of infections are self-limiting, but infant mortality is higher in developing countries and is generally associated with severe dehydration. As with cholera, treatment consists of replacing lost fluids and electrolytes.

 AIDS The human immunodeficiency viruses (HIV) associated with the Acquired Immunodeficiency Syndrome (AIDS) have become widespread in developing nations. By 1996, over 13 million adults were living with HIV in sub-Saharan Africa, representing about 60% of the global number of infected individuals. The spread of HIV in this region has been exacerbated by recent crises, such as natural disasters and armed conflict, with resulting mass population movements. The number of infected individuals in Asia is also rapidly rising; it is currently estimated that over 5 million people are living with HIV/AIDS in South and Southeast Asia. The progressive erosion of the immune system suffered by HIV-infected individuals renders them more susceptible to other infections. Often these secondary (or "opportunistic") infections are atypical or more severe than they would appear in an immunocompetent person. Since different diseases are prominent in tropical regions, patterns of the HIV-associated infections may diverge significantly from those seen in the developed nations. Moreover, it is thought that being infected with one or more tropical diseases may affect the course of AIDS upon subsequent HIV infection.
 Ebola (ee-bow'lah) Ebola virus causes fever, severe headache, backache, vomiting, diarrhea, and severe hemorrhaging. The method by which Ebola is transmitted in nature, and what animal is its natural host, remains unclear. In recent outbreaks such as those that have occurred in Zaire, Sudan and Gabon, man's initial contact with the virus has clearly been accidental. When humans acquire the infection, however, it spreads rapidly to those in contact with body fluids from the patient and the mortality rate is very high.
 Marburg virus is related to Ebola, but usually has a somewhat lower mortality rate.
 Lassa fever (lah'sah) Lassa is another often fatal hemorrhagic fever virus. It is transmitted by rodents. Symptoms of Lassa fever include sharp backache and/or headache, sore throat, fever, rashes, dehydration, general swelling, skin hemorrhaging, irregular heart beat, and disorientation.
 Viruses causing several types of South American hemorrhagic fevers belong to the arenavirus family like Lassa, and are also carried by rodents.
 Bacteria - Bacteria (singular = bacterium) are more complex than viruses, containing genetic information and much of the equipment necessary to produce energy and replicate independently. Some bacteria, however, can only reproduce when growing inside a cell, from which they derive required nutrients
 Cholera (kol' er-ah) Cholera is a diarrheal disease caused by infection with Vibrio cholerae, a bacterium most often found in contaminated water and shellfish, which produces a toxin that upsets the biochemical balance of cells lining the intestine and makes them secrete copious amounts of water and electrolytes. Cholera is endemic in a number of tropical countries, and periodically major epidemics break out such as that affecting some 900,000 persons in South America between 1991 and 1993. Cholera is characterized by severe watery diarrhea which, if left untreated, can result in serious dehydration and death. Treatment consists of replacement of lost water, salts and sugar.
 Escherichia coli (esh-er-i'kee-a koh'lye) Escherichia coli bacteria, more widely known as E. coli, can produce toxins similar to those of the cholera bacteria, causing illness ranging from traveler's diarrhea to persistent diarrhea with associated malnutrition. An extremely pathogenic form of these bacteria causes bloody diarrhea and kidney complications, such as recently observed in outbreaks in the U.S., Japan, and Scotland, which can be lethal - particularly in children and the elderly. This form, sometimes known as 0157:H7 or EHEC (enterohemorrhagic E. coli) is often associated with ingestion of undercooked meat, but has also been found in other foods, including unpasteurized milk and fruit juices.
 Tuberculosis (tu-ber-ku-loh'sis) Caused primarily by the bacterium Mycobacterium tuberculosis (my-koh-bak-teer'ee-uhm), this is an infection that can last a lifetime, resulting in disease to virtually every organ in the body but primarily affecting the lungs. Tuberculosis occurs all over the world. Until recently, it was thought to be well controlled in the more developed countries; unfortunately, however, it is again on the increase due to its association as an opportunistic infection of AIDS and its prevalence in drug-abusers. Tuberculosis remains a major problem in the developing world, where conditions of poverty, poor nutrition and crowding contribute to its prevalence.

TREATING TROPICAL DISEASES

When adventurer Sandra Levy, 61, of Short Hills, N.J., visited Ecuador and the Galapagos Islands in December 1993, she tried to protect herself against tropical diseases and the insects that transmit them. Before leaving home, Levy got vaccinated against yellow fever and took medicine to ward off malaria. At the headwaters of the Amazon River, she took precautions. Whether trekking into the jungle or canoeing across the river to see leaf-eating ants on the opposite bank, she wore long-sleeved shirts and knee-high boots and used an insect repellent containing DEET. 

In her thatch hut at night, she slept under mosquito netting. After she returned home, however, Levy noticed a sore the size of a dime above her left ankle. "It didn't hurt or itch," she says, "but it didn't go away. I decided to see my dermatologist." By the end of March, despite antibiotics, her sore had grown to the size of a silver dollar, so she made another medical appointment. "The doctor took a biopsy. Knowing I'd been in Ecuador, he had the lab check for deep fungus and leishmaniasis." 

The diagnosis was indeed leishmaniasis, a tropical disease spread by infected female sandflies. Levy's doctor put her in touch with a tropical disease specialist for treatment. As Levy's experience shows, travelers' precautions against tropical diseases are not foolproof. "The American public shouldn't be complacent about these diseases," says Randolph Wykoff, M.D., associate commissioner for operations at the Food and Drug Administration.

 "Tropical diseases are absolutely devastating in other countries, killing hundreds of thousands of people. We are not immune." While most such infections are acquired during travel, Wykoff says, some people can also become infected from other travelers who bring home the disease. Still, tropical diseases are more prevalent in developing countries, where conditions all too commonly foster their spread. War refugees migrating to other areas carry infections with them. Economic and social crises stress health systems. And unsanitary conditions due to rapid urbanization and rapid population growth foster an environment in which insects and other animals can transmit disease-producing organisms.

 "King" Malaria Sometimes called the King of Diseases, malaria yearly strikes up to 500 million people, 90 percent of them in Africa, with up to 2.7 million deaths, mostly young children. Malaria is caused by four species of Plasmodium parasites, transmitted to humans by infected female Anopheles mosquitoes. Symptoms include a spiking fever, shaking chills, and flu-like symptoms. Anemia or liver problems may develop. If treatment is delayed, severe infection may lead to kidney failure, coma, and death. 

Malaria kills so many African children because they lack immunity, says tropical disease specialist LTC Alan Magill, M.D., of Walter Reed Army Institute of Research, Department of Defense. Americans in Africa--travelers or troops--also are at risk because their immunity to malaria is like a child's, he says. They have more severe malaria than Africans who have survived past age 5 and developed immunity. "At our study site in Kenya," he says, "if you drew blood from 100 seemingly normal Africans at the local market, you'd find malaria parasites in most of their bloodstreams. They're infected, and the transmission cycle goes on, but they don't have obvious ill effects." 

The national Centers for Disease Control and Prevention gets about 1,000 reports a year of malaria in the United States. Since 1957, nearly all these cases were acquired in areas of the world where malaria is known to occur. Domestic malaria, in fact, was declared eradicated in this country in the 1940s. But from 1957 through 1994, CDC got 76 reports of malaria cases that may have been transmitted locally, including some from suburban New Jersey in 1991 and New York City in 1993. A 1995 report from Michigan was the first that far north since 1972. "In most cases, evidence indicated that locally infected mosquitoes did transmit the disease," says CDC malaria expert Lawrence Barat, M.D. "Anopheles mosquitoes are present throughout the contiguous United States. But we've never found an infected mosquito in the United States. More recently, we've had outbreaks of Plasmodium falciparum malaria, the more severe form. We want to monitor this very closely." For several decades after the Second World War, the drug of choice for malaria treatment and prevention was chloroquine (Aralen and generics). "The drug was well-tolerated, fast-acting, and cost only 9 cents to cure a child," says Robert Gwadz, Ph.D., assistant chief, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases (NIAID). However, in the 1950s, he says, resistance to chloroquine in falciparum malaria appeared in South America and Southeast Asia and spread throughout both continents and eventually into Africa. "Chloroquine is now useless in most malarious areas." FDA has since approved numerous anti-malaria drugs. Many are not marketed here or are used here only for indications other than malaria. Chloroquine remains the treatment of choice for patients with malaria caused by species still susceptible to the drug. Resistance to chloroquine is becoming more common, however, and alternative drugs are necessary. In the United States, Barat says, oral quinine given together with either tetracycline or sulfadoxine-pyrimethamine (Fansidar) is the best regimen for treatment of mild to moderate falciparum malaria acquired in areas where resistance to chloroquine has been identified. For patients with complicated malaria who are too ill to take oral medicine, intravenous quinidine is used in the United States. Mefloquine (Lariam) and halofantrine (Halfan) are also used to treat chloroquine-resistant falciparum malaria. Halofantrine is not currently marketed here. Intravenous quinine is used in other countries. The incidence of malaria continues to increase, Gwadz says, "in part due to the spread of resistance to chloroquine and several of its substitutes, but also to reduced effectiveness and acceptability of mosquito-killing insecticides." In 1995, the World Health Organization established a system to monitor the drug resistance in Southeast Asia and the Western Pacific. The parasite can be difficult to treat because it can change form to escape the human immune system, says Neil Goldman, Ph.D., associate director for research at FDA's Center for Biologics Evaluation and Research. Goldman says scientists at the center's Laboratory of Parasitic Biology and Biochemistry conduct research "to learn how this process takes place and figure out how to interrupt it. If we make a break in the circle, maybe we can stop infection." Gwadz and colleagues are studying how to give mosquitoes a beneficial gene that prevents transmission of the parasite. To learn more about mosquito biology, they collaborate with scientists at West Africa's National School of Medicine and Pharmacy, in Mali. NIAID scientists also are conducting the first human trial of a vaccine to block transmission of malaria parasites from infected people. More from Mosquitoes: Dengue Fever, Yellow Fever Aedes mosquitoes, mainly A. aegypti, an urban-dwelling insect, can transmit four types of dengue viruses, causing about 20 million cases of disease in more than 100 countries each year. A. aegypti mosquitoes tend to bite in the daytime, especially just after dawn and just before dark. Dengue fever begins suddenly with high fever, severe frontal headache, joint and muscle pain, and sometimes vomiting and rash. Patients usually recover without complications. More serious, dengue hemorrhagic fever can lead to shock, bleeding and death. There is no specific treatment. Symptoms can be treated with bed rest, intravenous fluids, and drugs to reduce fever. In 1995, the worst dengue epidemic in 15 years hit Latin America and the Caribbean. Worldwide, the more than 600,000 cases of hemorrhagic fever caused 24,000 deaths. CDC in 1995 diagnosed dengue fever in 86 U.S. travelers, up from 46 during 1993-1994 and 17 in 1992. A. aegypti mosquitoes also spread the yellow fever virus. Peru in 1995 had the biggest yellow fever epidemic in the Americas since 1950. West Africa also experienced an epidemic that year. Mild yellow fever causes flu-like symptoms. Severe cases may involve bleeding and liver problems, sometimes leading to delirium, convulsions, coma, and death. Treatment is symptomatic. Prevention consists of vaccination and personal protection against mosquitoes. Yellow fever vaccine must be approved by WHO and given at approved vaccination centers. The Pan American Health Organization (PAHO) helped in the vaccination campaign that controlled the Peru epidemic. PAHO is the regional WHO office for the Americas. Elephantiasis and River Blindness Worms related to the heartworms that can hurt dogs, can give humans lymphatic filariasis, a disease affecting about 120 million people worldwide. Infected female Aedes, Anopheles, and various other mosquitoes deposit the worm larvae while biting. The adult worm can damage the lymph system, resulting in elephantiasis--disfiguring swelling in the legs, arms, and other areas. FDA has approved diethylcarbamazine (Hetrazan) for treatment. Surgery may be needed if certain areas, such as the scrotum, are affected. River blindness (onchocerciasis) is caused by pre-larval and adult stages of Onchocerca volvulus, a filarial parasite transmitted by female black flies. Living near rapidly flowing rivers and streams, black flies bite by day. Most of the 17.6 million people who have onchocerciasis are in Africa, though the disease is common in certain areas of Central America as well. Short-term travelers appear to be at low risk for infection, which is usually found in Americans only when they stay in these areas a long time in roles such as missionaries, field scientists, and Peace Corps volunteers. Symptoms include an extremely itchy rash, lumps under the skin, and eye inflammation that can lead to blindness. Ivermectin kills the parasite at the stage when it causes symptoms. Merck, Sharp & Dohme provides this drug free to countries where river blindness is common. It is available here from CDC under an agreement with FDA. According to John Becher, one of two pharmacists who oversee the drug service, "We provide certain drugs and biologics as a public health service. Most are for rare diseases." Ivermectin and other drugs for tropical diseases available through the service are not approved in the United States but are provided under investigational drug exemptions granted by FDA. NIAID's Laboratory of Parasitic Diseases conducts research toward vaccines for elephantiasis and river blindness. While nearly everyone exposed becomes infected, a few individuals are resistant, says Thomas Nutman, M.D., who heads one immunology section. "These resistant individuals have antibodies in their blood that are specific to certain important parasite proteins. We identify the proteins, clone them, manufacture enough so we can study them, and then test them." Testing is in test tubes instead of in animals, which don't take the infection as humans do. Flatworms, Snails and Schistosomiasis Flatworms cause schistosomiasis. First-stage larvae infect freshwater snails, then evolve into cercariae larvae, which exit the snails and swim along to find a human host. Penetrating the skin, male and female cercariae move in the bloodstream to the intestines or bladder and mate. Eggs excreted in human waste end up in the water supply, restarting the cycle. About 200 million people worldwide are infected. Severe disease leads to about 200,000 deaths each year.

Most symptoms are due not to the worms, but to eggs trapped in tissue. Short-term infection may be symptomless or cause such symptoms as fever, itchy rash, headache, joint and muscle pain, diarrhea, and nausea. Chronic infection can damage the liver, kidneys and bladder, or intestines. FDA has approved praziquantel (Biltricide) as treatment. Places where schistosomiasis is most prevalent include Brazil, Puerto Rico, and St. Lucia (an island in the East West Indies); Egypt and most of sub-Saharan Africa; and Southern China, the Philippines, and Southeast Asia, according to CDC. At greatest risk are people who wade, swim or bathe in fresh water in rural areas where sanitation is poor and snail hosts are present. Travelers to such areas should not swim in fresh water; salt water like the ocean and chlorinated pools are considered low risk. Bathing water should be heated to 50 degrees Celsius (122 degrees Fahrenheit) or treated with iodine or chlorine, as for drinking. Filtering water with paper coffee filters may remove the parasites. If these methods are impossible, CDC recommends that travelers let bathing water stand three days; cercariae rarely live longer than 48 hours. WHO-led researchers are planning to test a vaccine in humans. Trypanosoma Diseases: Sleeping Sickness, Chagas' Disease The parasites Trypanosoma brucei gambiense and T. brucei rhodesiense cause African sleeping sickness. About 20,000 cases worldwide are reported yearly. Infected tsetse flies, which bite during the day, transmit this extremely serious disease. East Africa's sleeping sickness, due to T. brucei rhodesiense infection, causes symptoms within days to weeks. West Africa's chronic gambiense variety may not cause the "sleeping" part of the illness until months to years after exposure. Symptoms include fever, headache, lethargy, and confusion, which may progress to convulsions, coma and death. Suramin, available from CDC, is for the early stages of both gambiense and rhodesiense sleeping sickness. Melarsoprol, an arsenic derivative, is also available from CDC to treat final stages of both varieties. If the patient is known to have gambiense, however, the drug eflornithine (Ornidyl), approved by FDA, is more effective and safe because melarsoprol can cause serious, even fatal, nervous system problems in some patients. Eflornithine is useful for both early and late stages of gambiense sleeping sickness; it is not effective for rhodesiense sickness. Trypanosoma cruzi causes Chagas' disease, which affects at least 16 million people in Central and South America. The parasite infects reduviid bugs. When the bugs defecate, they deposit the parasite, which can enter a human through a break in the skin or through a mucous membrane, such as that which lines the nose, mouth or eyes. The best prevention is to avoid potential reduviid habitats--mud, adobe and thatch buildings, especially those with cracks or crevices. If this isn't feasible, spraying infested areas and using bed nets can help prevent infection. In its short-term stage, Chagas' disease may cause no symptoms or may cause fever, swollen lymph nodes, and inflammation of the heart or, rarely, the brain. Deaths occur, mainly in children, but most patients survive, their symptoms usually disappearing after four to six weeks. Many years later, about a fourth of patients develop serious, sometimes fatal, heart infection or damaged digestive organs such as an enlarged esophagus or colon for the long term. Nifurtimox is available from CDC for the treatment of short-term Chagas' disease. There is no accepted anti-parasitic treatment for chronic illness. About 70 percent of cases occur in Argentina, Bolivia, Brazil, Chile, Paraguay, and Uruguay. In 1991, the health ministers of those six countries began a program to eliminate Chagas' disease by the end of this century. Since then, house infestation has declined 75 to 98 percent in some areas, PAHO reports. The Leishmaniases Sandra Levy is one of an estimated 12 million people worldwide with leishmaniasis. This group of diseases is spread through the bite of female sandflies infected with any of about 20 different species of Leishmania parasites. Levy had cutaneous leishmaniasis, which causes skin sores that may leave ugly scars. Mucocutaneous leishmania-sis can cause disfiguring destruction of membranes in the nose, mouth, or upper throat (pharynx). 

In visceral leishmaniasis, parasites invade internal organs, causing death if the symptoms are untreated. According to the Defense Department's Magill, "You have chronic fever, depression of bone marrow and blood cells, weight loss, and a huge spleen so full of parasites it comes down into the pelvis." Years may pass before symptoms appear. Recently, 32 Persian Gulf War veterans were identified as leishmaniasis victims, 12 with viscerotropic leishmaniasis, a chronic syndrome associated with the infection, Magill says. They had fever and vague flu-like symptoms, but few signs of overt disease, he says. "Some had lymph-node enlargement that tended to come and go. A couple had slightly enlarged spleens." A free clinical evaluation program has been set up to identify and treat all veterans infected with leishmaniasis. (See "Want More Information?") The only current way to confirm a leishmaniasis diagnosis is by finding parasites in a clinical specimen. FDA is evaluating a skin test developed by the Defense Department for mass screening of troops. Preventive measures are staying indoors from dusk to dawn and using bed nets with 18 or more holes per inch--sandflies are a third the size of mosquitoes. Treatment of choice is with injectable drugs containing pentavalent antimony, a potentially toxic metal. "Drugs in this class remain unapproved by FDA, and no manufacturer has applied for approval," says Andrea Meyerhoff, M.D., an infectious disease specialist with the agency. Levy took one such drug, sodium stibogluconate, available on a patient by patient basis from CDC. Through home care, Levy had an intravenous dose each day for 20 days. Although she had a reaction that she describes as "the worst scenario of flu symptoms," Levy urges those who get leishmaniasis, "Don't think, 'Oh, 1'11 knock it off.' Go on that medication if it's what your doctor ordered. It isn't worth taking a chance." In 1994, FDA designated aminosidine, an antibiotic that does not contain antimony, as an orphan drug for visceral leishmaniasis, and a sponsor is working to develop it. Goldman and colleagues are studying new ways to make a leishmaniasis vaccine. "We're trying to skew the immune response," he says, "so it gives a protective reaction to the infection." Richard Kenney, M.D., a colleague, says, "Past efforts clearly show the need for a better understanding of the immune response to the parasite." Toward this end, Kenney and Shyam Sundar, of the Institute of Medical Sciences, Banaras Hindu University, India, collaborate on studies of the immune response at various stages of infection and treatment. The Global Fight Continues WHO Director-General Hiroshi Nakajima, M.D., Ph.D., in his message in the WHO 1996 report, writes that many diseases, including Chagas' disease and river blindness, "sooner rather than later ... will join smallpox as diseases of the past." But he also writes that the world is "on the brink of a global crisis in infectious diseases;' requiring "a global response ... that goes beyond selfish interests and national boundaries." Responses by WHO include development of a network of laboratories to strengthen collaboration in detecting and controlling outbreaks. WHO teams can be on site within 24 hours with supplies and equipment to set up epidemic control measures. The Clinton administration last June established a Presidential Decision Directive on Emerging Infectious Diseases, including tropical disease, to improve U.S. and international disease surveillance and prevention and response measures. Meanwhile, international travelers can find health advice in CDC's annually updated handbook, Health Information for International Travel. As for Levy, her globetrotting has cooled. "My jungle trips are over," she says. Her latest trip, last August, was to Iceland. Prevention Tips Personal protection measures are the first line of defense against tropical diseases. The national Centers for Disease Control and Prevention advises that international travelers take these steps to avoid bites from bugs carrying infective organisms: o At least six weeks before departure, get current health information from CDC on regions you plan to visit. (See "Want More Information?") Other sources may be your health department, doctor, or travel agency. o Avoiding rural areas when possible may keep you away from some disease-causing vectors. o When outdoors, wear a hat, long-sleeved shirt tight at the wrists and tucked in at the waist, long pants tight at the ankles and tucked into socks, and shoes covering the whole foot. o On clothing, use a repellent containing permethrin. (Apply it before wearing the clothing, and let the clothing thoroughly dry before wearing, the Environmental Protection Agency advises.) o On skin, use a repellent containing DEET, no higher than 30 percent concentration. Follow instructions carefully. There have been associated rare cases of toxicity, including deaths. o When accommodations are inadequately screened or air-conditioned, use a bed net sprayed with permethrin repellent and tucked under the mattress.

If in an area where Leishmania-infected sandflies are likely present, use a bed net with 18 or more holes per inch. o Spray screens with permethrin. o Use aerosol insecticides to clear rooms of insects. Follow instructions carefully. --D.F. Want More Information? o For health information for international travel, contact CDC's Voice or Fax Information Service at (404) 332-4559; World Wide Web site at http://www.cdc.gov/; or File Transfer Protocol server at ftp.cdc.gov. o Doctors can apply for compassionate use of investigational drugs for tropical diseases through the CDC Drug Service by calling (404) 639-3670. o The World Health Report 1996 is available on the World Health Organization's World Wide Web site at http://www.who.ch/. o Veterans with health-care concerns for themselves, spouses or children can call the Department of Defense Persian Gulf Veterans Medical Hotline (1-800) 796-9699 or Department of Veterans Affairs at (1-800) 749-8387. More details are at VA's electronic bulletin board, (1-800) 871-8387; World Wide Web site, http://www.va.gov/health/environ/persgulfhtm; and File Transfer Protocol/Telnet server, vaonline.va.gov. DIAGRAM: The Malaria Parasite: A Quick-Change Artist A human gets malaria when the bite of an infected female Anopheles mosquito(1) sends Plasmodium parasite sporozoites(2) into the person's bloodstream. The sporozoites travel to the liver(3), where they turn into merozoites and re-enter the bloodstream(4). The merozoites invade red blood cells(5) and multiply. Some merozoites develop into the male and female gametocytes(6), which are passed on to the next mosquito that bites the infected person. In the newly infected mosquito, male and female gametocytes fuse and develop into fertilized eggs, or zygotes(7). The zygotes develop into oocysts, producing new sporozoites to continue the cycle. --D.F. PHOTO (BLACK & WHITE): An unwelcome souvenir from a trip to the tropics: a skin sore caused by leishmaniasis disease. PHOTO (BLACK & WHITE): These people working in a West African river are at risk for schistosomiasis, a tropical disease transmitted by parasites in the water. (Photo courtesy of Mark L. Wilson, Sc.D., of the University of Michigan) ~~~~~~~~ By Dixie Farley Dixie Farley is a staffwriter for FDA Consumer. Lenore Gelb, a press officer in the Office of Public Affairs, also contributed to this article. ****** Copyright of the publication is the property of the publisher and the text may not be copied without the express written permission of the publisher except for the inprint of the video screen content or via the print options of the software. Text is intended solely for the use of the individual user.


\7 Diseases of Animals

Diseases of Animals, disorders that influence an animal's health and ability to function. Animal diseases are of great concern to humans for several reasons. Diseases can reduce the productivity of animals used to produce food, such as hens and dairy cows. Animals that are raised as food, such as pigs and beef cattle, that become ill may affect the economic well-being of many industries. Some animal diseases can be transmitted to humans, and control of these types of diseases, known as zoonoses, is vital to public health. In the wild, animal populations reduced by disease can upset the ecological balance of an area. And, in the case of pets, prevention and treatment of animal diseases helps pets live long and healthy lives, enhancing the companionship shared by a pet and its human owner.

Animal diseases are characterized as infectious and noninfectious. Infectious diseases are caused by an agent, such as bacteria or a virus, that penetrates the body's natural defense mechanisms, while noninfectious diseases are caused by factors such as diet, environment, injury, and heredity. Sometimes the cause of a disease is unknown. An animal may also experience one disease or a combination of diseases at any one time.

To identify a disease, a veterinarian (a doctor who treats animals) first determines the animal's signalment—its species, breed, age, and sex. This information helps to identify a disease because some diseases are more prevalent in certain species, or a disease may preferentially affect one sex or age group. The veterinarian then gathers a complete history of the animal and its problem. This history includes the symptoms the animal is displaying and when they first appeared, as well as whether the animal has been exposed to something new in its surroundings or to other animals. The veterinarian gives the animal a thorough physical examination, which may include measuring its body temperature, listening to its heart, checking its pulse, and feeling its abdomen and lymph nodes. The veterinarian then creates a list of possible diseases that may be making the animal sick. The list may be narrowed by running diagnostic tests such as X rays, electrocardiograms, blood analyses, and bacterial or fungal cultures. Once the disease is identified, the doctor develops a treatment plan for the animal (see Veterinary Medicine).

II. Infectious Diseases
 Many microscopic organisms naturally and peacefully exist in enormous quantities within animal bodies. For example, the multichambered stomach of a cow contains bacteria that help the animal digest its food. But many other microscopic organisms, known as pathogens, cause diseases in animals. Pathogens include bacteria, viruses, fungi, prions—newly identified mutated proteins—and parasites. Pathogens are easily spread: an animal may consume food or drink something that has been contaminated with infected fecal material, for example. If the ground is contaminated by Salmonella bacteria, for instance, infection can travel from barn to barn on the soles of a farmer's boots. Or an animal may be exposed while walking across contaminated ground. Some diseases are transmitted by biting insects; others are spread by sexual contact.

In addition to reducing the productivity of livestock, some infectious diseases pose a danger to humans. More than 100 zoonoses are recognized. Most cases are transmitted from animals that have close contact with humans, such as pets, farm animals, or rats. Examples of zoonoses include toxocariasis, a disease caused by a parasitic worm transmitted by infective eggs within canine feces; psittacosis, a respiratory disease caused by the bacteria-like Chlamydia psittaci and transmitted from infected birds; hantavirus pulmonary syndrome, spread by contact with rodent feces and urine; and rabies, a viral infection transmitted in the saliva of infected animals, typically foxes, bats, and raccoons, that causes damage to the brain and spinal cord.

As the human population grows and expands into wilderness territories, humans are coming into closer contact with other animals that carry pathogens dangerous to humans. Some of these pathogens are carried by insects, as in the case of yellow fever, spread from monkeys to humans via mosquito bites. Some hemorrhagic fevers, such as that caused by the Ebola virus, are recognized as zoonoses, but the exact transmission route from animal to human is still unknown.

A. Bacterial Diseases
 Salmonellosis is any disease caused by the Salmonella bacteria, characterized by septicemia and severe diarrhea. In its many forms, it is one of the major diseases of wild and domestic mammals, birds, and reptiles, as well as humans. Salmonella bacteria usually enter the body through the mouth, most commonly along with food or water contaminated by infected feces. Transmission also may occur through direct contact with an infected animal. In addition, salmonella bacteria can be spread by contact with objects, such as bowls and cutting boards, that have been contaminated by infected animal products, such as eggs or meat.

Anthrax is one of the oldest and most destructive diseases recorded in history. Caused by the bacterium Bacillus anthracis, anthrax can affect virtually all warm-blooded animals and humans. The onset of anthrax may be sudden and death may occur before symptoms are observed. In other cases, typical symptoms include restlessness, lethargy, appetite loss, fever, rapid breathing, and unsteady gait. The disease is contracted from contaminated soil, feed, or water. It can also spread when the skin is penetrated by insect bites or by objects contaminated with anthrax spores.

Leptospirosis, caused by spiral Leptospira bacteria, affects cattle, dogs, pigs, sheep, goats, and humans. Ponds, lakes, and other bodies of water are common sources of leptospirosis, and rodents may carry the infection. This infection causes kidney disease and destruction of red blood cells with potential anemia; it may also cause abortion. Brucellosis also causes abortion, as well as swelling of the reproductive organs in males. Caused by the Brucella bacterium, it occurs primarily in cattle, pigs, sheep, dogs, and goats, and may be transmitted to humans (see Undulant Fever).

Tuberculosis (TB) is a chronic disease of animals and humans, caused by bacteria of the genus Mycobacterium and transmitted by inhalation of droplets from an infected animal's cough or sneeze, or by wound infection. TB infection causes lesions called tubercles to develop in certain tissues, such as the lung or liver. Symptoms include fever, emaciation, and progressive loss of strength.

Kennel cough is a respiratory disease of dogs that is caused by the bacterium Bordetella bronchiseptica, with or without the aid of various viruses. Symptoms include a harsh, dry cough, appetite loss, discharge from the nose or eyes, and lethargy. It typically spreads when dogs are grouped together, such as at dog shows or boarding kennels.

B. Viral Diseases
 Viruses are unable to grow and reproduce outside of the living cells from other hosts. Viruses attach and invade a cell and replicate, and then the newly created viruses destroy the host cell and seek out other cells to continue replication.

Feline leukemia is caused by the feline leukemia virus. Often fatal, it can seriously impair the immune system and, in some cases, cause the growth of life-threatening tumors. Spread from direct contact with an infected cat, symptoms of the disease include lethargy, weight loss, anemia, and fever. A cat may not appear ill until years after exposure.

Foot-and-mouth disease is caused by a virus found in the saliva of cattle, pigs, and other hoofed animals. Highly contagious, it is spread from direct contact with an infected animal. It may also spread in milk or in garbage that contains contaminated meat. Typical symptoms include blisters that appear on the mouth and feet; animals may become lame when their hooves degenerate.

Canine distemper is a highly contagious disease caused by the paramyxovirus, which is transmitted in discharges from the nose and eyes. Symptoms begin with fever, malaise, and nasal and ocular discharges and may progress to convulsions and other nervous system disorders. Parvoviruses affect dogs and in some cases cattle, pigs, and humans. Usually fatal if left untreated, canine parvovirus causes inflammation of the intestines, producing diarrhea, vomiting, fever, and loss of appetite.

C. Fungal Diseases
 A fungal infection typically develops slowly and recurs more frequently than a bacterial infection. Histoplasmosis, characterized by a chronic cough and diarrhea, is contracted by inhaling the Histoplasma capsulatum fungus, which grows in soil. In the Central United States histoplasmosis is the most widespread fungal disease diagnosed in dogs, although it also affects other animals. Ringworm, a common skin disease of many species, causes circular patches of hair loss and scaly, reddened skin. It readily spreads by direct contact with an infected animal.

Yeast, another type of fungus, grows in warm and moist places, such as the ear canals of dogs. It may cause otitis externa, an infection of the outer ear. The yeast Candida albicans is commonly found in the intestinal tract of birds and other animals. It may be the primary cause of disease, or it may be a secondary invader in an animal already sick with another infection.

D. Parasitic Infections
 Diseases caused by parasites are widespread in domestic animals and wildlife. Parasites may be internal or external. Internal parasites include Coccidia, a microscopic protozoal (single-celled) organism that causes diarrhea and extreme weight loss in many young animals.

Other internal parasites include the roundworm, tapeworm, and fluke. Larval roundworms can cause considerable damage to lungs and other organs in some animals. For instance, Capillaria worms may attack the lining of the digestive tract of chickens and turkeys; they parasitize the respiratory and urinary tracts of dogs. Adults of the heartworm Dirofilaria immitis, another roundworm, live in the heart of dogs and produce microscopic larval stages, which swim in the blood. Symptoms of heartworm disease include coughing, fatigue, and weight loss. If left untreated, an animal may experience heart failure. Tapeworms may have very damaging larval stages. In echinococcosis, the larval tapeworms may form large cysts in liver, lungs, and other organs of humans and animals.

Flukes may directly damage the liver, lungs, or intestines, or they may act as carriers of other disease agents, as in the case of salmon poisoning of dogs in which the fluke, encysted in the body of a salmon, carries a virulent rickettsial agent.

External parasites live or feed on the surface of the animal's body. This group includes bloodsucking insects, such as mosquitoes, gnats, some flies, fleas, and some lice. Some insects are bloodsuckers in larval stages, such as ear maggots of hawk nestlings. Others, including some larval flies and some lice, eat tissue. Great damage to the meat and hides of cattle is caused by larval flies such as the ox warble, which migrates through the tissues and, after boring breathing holes through the skin, leaves the body to reproduce. Bloodsucking flies can transmit parasitic blood protozoans and some viruses.

Lice are of two types, those with chewing mouthparts and those with sucking mouthparts. Lice cause irritation, carry disease agents, and may cause anemia. Fleas are all bloodsuckers, and may transmit larval tapeworms, roundworms, and other disease agents. The sticktight flea may kill young birds by excessive bloodsucking. Mites may be external bloodsuckers, such as the red mite of birds (it can also affect humans and other animals), or they may be internal parasites, such as the Sternostoma mites of the lungs and air passages of canaries and other birds. Ticks, larger than mites, feed on blood and can carry serious infectious agents such as the bacteria that cause Q Fever and Lyme disease, which can be transmitted to humans.

E. Prion Diseases
 Newly identified protein particles called prions have been found in the brains of animals that have died from diseases such as scrapie and bovine spongiform encephalopathy, more commonly known as mad cow disease. How prions act is unclear, but scientists theorize that prions attach to normal proteins in the brain. Once attached, the prions cause the normal proteins to change into an abnormal shape, leading to progressive destruction of brain cells and death. Prion diseases are thought to spread by means of feed supplements derived from infected animals. In recent years, public health officials have been concerned about the possibility that prion diseases may be transmitted to humans. This happens when humans eat contaminated beef or organs, causing them to contract such rare neurological diseases as Creutzfeldt-Jakob disease.

F. Prevention and Treatment
 Controlling the spread of infectious animal diseases begins with isolating, or quarantining, animals with threatening infections, such as salmonella, to prevent further transmission. Many bacterial diseases can be treated with various antibiotics, such as penicillin and streptomycin. But as with all disease, prevention is more important than treatment, and a major activity for veterinarians is immunization of animals. Immunization commonly involves an injection of a weakened or killed pathogen for a specific disease that encourages the immune system to fight off infection. Many infectious diseases, including rabies, canine distemper, feline leukemia, anthrax, and brucellosis, can be prevented by immunization. In the case of severe outbreaks of infectious disease, public health officials may work with animal owners to destroy large groups of animals. This was the case in the early 1990s, when an outbreak of bovine spongiform encephalopathy triggered the slaughter of many beef cattle in Britain.

Transmission of animal diseases to humans is a constant concern of public health officials. To protect people from disease, veterinarians inspect food animals for wholesomeness; quarantine and examine animals brought into the United States from other countries; test animals for the presence of disease; and actively work to prevent and eradicate diseases that threaten human health.

III. Noninfectious Diseases
 Even if it were possible, a world without pathogens would not be disease-free. Many animal diseases are caused by noninfectious factors such as an animal's environment, genetics, and nutrition. Heatstroke, for example, occurs when an animal is forced to endure high temperatures without access to water, adequate ventilation, or suitable shade. A common scenario involves an animal that has been locked inside a car without air-conditioning during hot weather. Conversely, extreme cold can lead to hypothermia or frostbite. Other environmental hazards include the vast array of products humans use to eliminate pests and weeds from homes, farms, and gardens. For example, rodenticide, poison used to kill rats and mice, can cause fatal internal hemorrhaging in any animal that ingests this toxic substance. Improper use of flea powders, sprays, dips, and collars can also cause illness. Automobile antifreeze is another well-known poison. Its sweet taste appeals to some animals, such as cats and dogs, but consuming only a small amount can result in death. Many plant species are also toxic to animals. Some, such as pokeweed and yew, commonly grow in pastures and yards.

Poor feeding practices can lead to diseases such as nutritional secondary hyperparathyroidism, a condition involving the muscles and bones of dogs that is associated with an all-meat diet. Large, rapidly growing puppies that consume too many calories and too much calcium can develop hypertrophic osteodystrophy, a disease resulting in lameness. Cats need sufficient amounts of an essential amino acid called taurine in their diets. Without it, they may develop eye problems. Not enough iodine intake can cause a goiter, or enlargement of the thyroid gland, in cows, horses, and other animals.

Trauma is a leading cause of injury and premature death in animals, especially pets that are allowed to roam free outdoors. Many animals are hit by cars or bitten by other animals. Farm animals may be attacked by predators, or they may harm themselves on sharp fencing or discarded nails. Untreated wounds can become infected and cause permanent damage.

Hip dysplasia, a painful and debilitating skeletal condition, is a noninfectious disease caused in part by heredity. Certain defects of the heart or palate, the roof of the mouth, may also be inherited. Some animals are genetically predisposed to diseases such as generalized demodectic mange, a skin disease caused by mites and characterized by hair loss and scaling around the eyelids, mouth, and front legs.

An animal's immune system is designed to detect and eliminate invading organisms. Occasionally, however, it behaves as though the animal's own body were the attacker, and it destroys healthy tissue. Diseases caused by this response, known as autoimmune diseases, include pemphigus foliaceous, a skin disease of dogs, cats, and horses; and rheumatoid arthritis, a severe type of arthritis that involves inflammation of the joints. In the autoimmune disease hemolytic anemia, the animal's own red blood cells are destroyed by its immune system.

Cancer exists in all animals. It is classified as either benign—that is, relatively noninvasive and unlikely to return after treatment; or as malignant—that is, aggressive and likely to spread. Any organ or system can be affected, either directly or through metastasis—when cancer cells from one part of the body spread to other areas of the body. Some forms of cancer are more widespread in animals of a particular breed, age, or sex, and even individuals of a specific color. For example, cancer of the mammary gland occurs more often in female animals, while melanoma, or skin cancer, is the most frequent tumor of elderly gray horses, and lymphosarcomas, tumors of the lymph nodes, are the most common type of specific tumor in cats. The study of cancer, known as oncology, is a growing field in veterinary medicine.

Elizabeth M. Bodner, B.A., Ph.D. Editor, American Kennel Club Complete Dog Book. Author of American Kennel Club Care in Training.


\8 Epidemiology

Epidemiology is the study of how often diseases occur in different groups of people and why. Epidemiological information is used to plan and evaluate strategies to prevent illness and as a guide to the management of patients in whom disease has already developed.

Like the clinical findings and pathology, the epidemiology of a disease is an integral part of its basic description. The subject has its special techniques of data collection and interpretation, and its necessary jargon for technical terms. This short book aims to provide an ABC of the epidemiological approach, its terminology, and its methods. Our only assumption will be that readers already believe that epidemiological questions are worth answering. This introduction will indicate some of the distinctive characteristics of the epidemiological approach.

All findings must relate to a defined population A key feature of epidemiology is the measurement of disease outcomes in relation to a population at risk. The population at risk is the group of people, healthy or sick, who would be counted as cases if they had the disease being studied. For example, if a general practitioner were measuring how often patients consult him about deafness, the population at risk would comprise those people on his list (and perhaps also of his partners) who might see him about a hearing problem if they had one. Patients who, though still on the list, had moved to another area would not consult that doctor. They would therefore not belong to the population at risk.

The importance of considering the population at risk is illustrated by two examples. In a study of accidents to patients in hospital it was noted that the largest number occurred among the elderly, and from this the authors concluded that "patients aged 60 and over are more prone to accidents." Another study, based on a survey of hang gliding accidents, recommended that flying should be banned between 11 am and 3 pm, because this was the time when 73% of the accidents occurred. Each of these studies based conclusions on the same logical error, namely, the floating numerator: the number of cases was not related to the appropriate "at risk" population. Had this been done, the conclusions might have been different. Differing numbers of accidents to patients and to hang gliders must reflect, at least in part, differing numbers at risk. Epidemiological conclusions (on risk) cannot be drawn from purely clinical data (on the number of sick people seen).

Implicit in any epidemiological investigation is the notion of a target populationabout which conclusions are to be drawn. Occasionally measurements can be made on the full target population. In a study to evaluate the effectiveness of dust control measures in British coal mines, information was available on all incident (new) cases of coal workers' pneumoconiosis throughout the country.

More often observations can only be made on a study sample, which is selected in some way from the target population. For example, a gastroenterologist wishing to draw general inferences about long term prognosis in patients with Crohn's disease might extrapolate from the experience of cases encountered in his own clinical practice. The confidence that can be placed in conclusions drawn from samples depends in part on sample size. Small samples can be unrepresentative just by chance, and the scope for chance errors can be quantified statistically. More problematic are the errors that arise from the method by which the sample is chosen. A gastroenterologist who has a special interest in Crohn's disease may be referred patients whose cases are unusual or difficult, the clinical course and complications of which are atypical of the disease more generally. Such systematic errors cannot usually be measured, and assessment therefore becomes a matter for subjective judgement.

Systematic sampling errors can be avoided by use of a random selection process in which each member of the target population has a known (non-zero) probability of being included in the study sample. However, this requires an enumeration or censusof all members of the target population, which may not be feasible.

Often the selection of a study sample is partially random. Within the target population an accessible subset, the study population, is defined. The study sample is then chosen at random from the study population. Thus the people examined are at two removes from the group with which the study is ultimately concerned:

Target population study population study sample This approach is appropriate where a suitable study population can be identified but is larger than the investigation requires. For example, in a survey of back pain and its possible causes, the target population was all potential back pain sufferers. The study population was defined as all people aged 20-59 from eight communities, and a sample of subjects was then randomly selected for investigation from within this study population. With this design, inference from the study sample to the study population is free from systematic sampling error, but further extrapolation to the target population remains a matter of judgement.

The definition of a study population begins with some characteristic which all its members have in common. This may be geographical("all UK residents in 1985" or "all residents in a specified health district"); occupational("all employees of a factory," "children attending a certain primary school", "all welders in England and Wales"); based on special care("patients on a GP's list", "residents in an old people's home"); or diagnostic ("all people in Southampton who first had an epileptic fit during 1990-91"). Within this broad definition appropriate restrictions may be specified - for example in age range or sex.

Oriented to groups rather than individuals Clinical observations determine decisions about individuals. Epidemiological observations may also guide decisions about individuals, but they relate primarily to groups of people. This fundamental difference in the purpose of measurements implies different demands on the quality of data. An inquiry into the validity of death certificates as an indicator of the frequency of oesophageal cancer produced the results shown in Table 1.1.

Inaccuracy was alarming at the level of individual patients. Nevertheless, the false positive results balanced the false negatives so the clinicians' total (53 + 21 = 74 cases) was about the same as the pathologists' total (53 + 22 = 75 cases). Hence, in this instance, mortality statistics in the population seemed to be about right, despite the unreliability of individual death certificates. Conversely, it may not be too serious clinically if Dr. X systematically records blood pressure 10 mm Hg higher than his colleagues, because his management policy is (one hopes) adjusted accordingly. But choosing Dr. X as an observer in a pop study of the frequency of hypertension would be unfortunate.

Conclusions are based on comparisons - Clues to aetiologycome from comparing disease rates in groups with differing levels of exposure - for example, the incidence of congenital defects before and after a rubella epidemic or the rate of mesothelioma in people with or without exposure to asbestos. Clues will be missed, or false clues created, if comparisons are biased by unequal ascertainment of cases or exposure levels. Of course, if everyone is equally exposed there will not be any clues - epidemiology thrives on heterogeneity. If everyone smoked 20 cigarettes a day the link with lung cancer would have been undetectable. Lung cancer might then have been considered a "genetic disease", because its distribution depended on susceptibility to the effects of smoking.

Identifying high riskand prioritygroups also rests on unbiased comparison of rates. The Decennial Occupational Supplement of the Registrar General of England and Wales(1970-2) suggested major differences between occupations in the proportion of men surviving to age 65:

Table 1.2 Men surviving to 65, by occupation  Farmers (self employed) 82%  Professionals 77%  Skilled manual workers 69%   Labourers 63%  Armed forces 42% 

These differences look important and challenging. However, one must consider how far the comparison may have been distorted either by inaccurate ascertainment of the deaths or the populations at risk or by selective influences on recruitment or retirement (especially important in the case of the armed forces).

Another task of epidemiology is monitoringor surveillanceof time trends to show which diseases are increasing or decreasing in incidence and which are changing in their distribution. This information is needed to identify emerging problems and also to assess the effectiveness of measures to control old problems. Unfortunately, standards of diagnosis and data recording may change, and conclusions from time trends call for particular wariness.

The data from which epidemiology seeks to draw conclusions are nearly always collected by more than one person, often from different countries. Rigorous standardisationand quality controlof investigative methods are essential in epidemiology; and if an apparent difference in disease rates has emerged, the first question is always "Might the comparison be biased?"


\9 Ebola (Marburg virus)

Highly contagious and lethal. May not be desirable as a biological agent because of uncertain stability outside of animal host. Symptoms, appearing two or three days after exposure, include high fever, delirium, severe joint pain, bleeding from body orifices, and convulsions, followed by death. No known treatment. A simple viral piece of RNA that lies dormant until it finds a live cell to enter and reproduce, doing so kills the cell. It then moves on to the next cell. Named for a river in Zaire near where first discovered in 1976 and is centered there. See HEMORRAGIC diseases.
Fever, chills, muscle aches 4-16 days after infection progressing to respirtory problems, severe bleeding, kidney problems, shock, and death. Incubation period of 3-12 days or less. Usually fatal.

Ebola: Emerging Horror- In 1976 fear and anxiety, spread through villages in Zaire, Africa with the appearance of the Ebola Virus, which annihilated 340 people. Families of victims watched helplessly as their loved ones had respiratory problems, loss of appetite, and severe hemorrhaging. As body systems shut down the victims went into shock and 90% of the victims died. 

Ebola disease, named after the Ebola River in Zaire, Africa where it was first discovered, is a highly contagious virus. Three of the strains of this virus (Zaire, Sudan & Tai Forest) are known to cause hemorrha- gic fever in humans. Another strain of the virus Reston, is believed to be airborne, does not have any effect on humans. Where as, strains affecting humans do not appear to be airborne. Other strains may still be unidentified. 

Ebola is part of the family Filoviridae, which are char- acterized by their thread like appearance. The viruses, are usually 800 to 1000 nanometers (nm) long (1nm is equal to one-billionth of a meter), but particles as long as 14,000 nm have been seen. Each virus consists of a coiled strand of ribonucleic acid (RNA) contained in an envelope derived from host cell membrane that is covered with spikes. The differences in gene sequences result in different properties for each strain. 

Since 1976 ,the history of Ebola exposure has been carefully monitored by centers for disease control, local or imported, and the WHO of the UN. Although there have been isolated incidences, no epidemics have been reported since the 1996 Gabon outbreak. 

History - The Ebola virus was first documented in Zimbabwe, South Africa and in Kenya in 1976. Two major outbreaks occurred almost simultaneously in Zaire and Sudan. Over 500 cases were reported, with a mortality rate of 88% in Zaire and 53% in Sudan. A single case was confirmed by virus isolation in Zaire in 1977 and 1979. Ebola hemorrhagic fever occurred again in Sudan at the same site as in 1976.

Besides these episodes, doc by virus isolation, two more fatal and two nonfatal cases have been reported. A th ird filovirus, serologically related to Ebola virus was isolated from cynomolgus monkeys (Macaca fascicularis ) which originated in the Philippines. A Bolivian Hemor- rhagic Fever outbreak in July, 1962 had a 50% Mortality rate. It is not yet proven if this was an Ebola strain or a seperate Hemorrhagic FeverIn 1980, David Heymann, discovered the presence of the Ebola antibodies in pygmies living in the deeper forests of Cameroon. 

This led the scientists to again feel that the vector or vectors may have orig inated in an animal or in more than one species such as bats or monkeys.The study was inconclusive as to origin of the virus. 

TRANMISSION OF EBOLA - Ebola virus is spread through close personal contact with a person who is very ill with Ebola. In previous outbreaks, person-to-person spread frequently occurred among hospital care workers or family members who were caring for an ill person infected with Ebola virus. Blood and body fluids contain large amounts of virus, thus transmission of the virus has also occurred as a result of hypodermic needles being reused in the treatment of patients.

Reusing needles is a common practice in developing countries, such as Zaire and Sudan, where the health care system is underfinanced. Medical facilities in the US do not reuse needles.
  Previous outbreaks of Ebola appear to have continued only as long as a steady supply of victims came in contact with body fluids from the infected. The epidemics were resolved by teaching the local pop about how to avoid spreading the disease and improving conditions at hosp in impacted areas (unsterilized needles and syringes were a major factor in the 1976 outbreak in Zaire). Ebola's virulence may also serve to limit its spread: it's victims die so quickly that they don't have a chance to spread infection very far. 

Symptoms of Ebola? That causes hemorragic fever, begins 4 to 10 days after the infection. It is characterized by such symptoms as fevers, chills, headaches, muscle aches, and loss of appetite. As the disease progresses, vomiting, diarrhea, abdomin al pain, sore throats, chest pain, and bleeding from body openings can occur. The blood fails to clot and patients may bleed from injection sites as well as into the gastrointestinal tract, skin, and internal organs.

Pregnant women had a high stillborn rate if they were infected with the virus.Patients exhibit mental con- fusion,agitation and delirium.Patients with primary exposure tended to have a substantially higher mortality rate than those exposed as secondary infections. Second- ary infections generally were due to poor hygienic techniques in dealing with patient's bodily fluids or from the use of unsterile hypodermic needles or other unhygienic practices at area hospitals. 

DIAGNOSIS OF EBOLA - A diagnosis of Ebola is made by the detection of Ebola antigens, antibodies, or by a culture of the virus from a patient? body fluids or other mater- ial from the patient. An example of a diagnosed case was confirmed by a Center for Disease Control and Prevention . A Swiss researcher , working in central Africa, became ill after dissecting one of the chimpanzees that he was studying. He not only had the symptoms of the disease but also had viral particles in his cells. 

The researcher was treated in Switzerland, in Nov 1996, and managed to survive the infection. Ebola infection is thought to have a 77% to 90% mortality rate. Based upon the studies of the Ebola epidemic since 1976, it would appear that the incubation period is anywhere from 2 to 21 days, although 7-14 days is the most common interval. The virus may be present in survivors in their genital secretions for a period of up to 7 weeks. 

TREATMENT OF EBOLA - To this day ,no specific antiviral therapy presently exists against the Ebola virus, nor does interferon have any effect. Past recommendations for isolation of the patient in a plastic isolator have given way to the more moderate recommendation of strict barrier isolation with body fluid precautions.

There is a possible treatment for the deadly virus. Scientists in the United States began experiments with steroids in 1996. There is some hope offered by recent reports of antisera development. However, at this time, the only treatment for this disease is supportive. Careful management of fluid and electrolyte balance is critical. Prior to advent of clinical shock, replacement of plasma albumin may be useful. 

CURE: There is no known cure for the infected people. At present, no vaccines are available, as any vaccines must be strain specific. This limits production of a universal vaccine. 

CONTROL: continued work on the unknown vector(s) or reservoirs is necessary. 

improving public sanitation, health care and health education.

medical personnel must use isolation and barrier techniques in the treatment of Ebola patients

(including gowns, masks , face shields, and eye protection).

Quarantining of infected,symptomatic people.

Proper disposal of patient’s wastes and corpses.

Improving communications for reporting and coordination of outbreaks.

Restricting or surveying of international travel.

Restricted sexual contact with infected or symptom free patients until no viral particles are present  in genital secretions.

Ebola's epidemiologic history. There have been only five known outbreaks among humans: Ebola Zaire (the initial one) in 1976, Ebola Sudan, also in 1976, another Sudan outbreak in 1979, and the Ebola Zaire outbreak in Kikwit in 1995, and the Ebola Zaire outbreak in Gabon. The Ebola Reston in 1989 and the Ebola Reston outbreak that happened in Texas affected only monkeys. 

The Swiss researcher who survived her Ebola Tai infection in Cote d'Ivoire (Ivory Coast) is the only known case of that strain so far.

Viral hemorrhagic fevers are a group of diseases caused by viruses from four distinct families of viruses: filo- viruses, arenaviruses, flaviviruses, and bunyaviruses. The usual hosts for most of these viruses are rodents or arthropods (such as ticks and mosquitoes). In some cases, such as Ebola virus, the natural host for the virus is unknown. 

All forms of viral hemorrhagic fever begin with fever and muscle aches. Depending on the particular virus, the disease can progress until the patient becomes very ill with respiratory problems, severe bleeding, kidney problems, and shock. The severity of viral hemorrhagic fever can range from a relatively mild illness to death. 

 Woman in Canada Ebola-Free; Unknown Virus Feared 

TORONTO (Reuters Health) Feb 08 2001 - A woman lying quarantined in a Canadian hosp after arr from central Africa has been found free of the Ebola virus, raising new fears that a more mysterious disease could have been brought to North America's shores. 

The woman, who flew to Toronto from the Rep of Congo via NY, was admitted to a hosp in Hamilton, Ontario. "Ebola has been ruled out from Health Canada's perspective," Dr. Douglas MacPherson, an infectious disease specialist at the federal health dept, said, "There are still other viral hemorrhagic tropical fevers under consideration," he added. 

The case, which is gaining wide media attention, had raised fears that the woman had brought the first case of Ebola infection to North America. But infection control specialists said that actually the best-case scenario would be an Ebola diags, because doctors would then know what they were dealing with and how to contain it. 

"The worst-case scenario is definitely not Ebola. Every- one wanders around saying Ebola is incredibly dangerous and it is not," Dr. Allison McGeer, director of infection control at Mt. Sinai Hospital in Toronto, told Reuters. "She could have some brand-new hemorrhagic fever that nobody has yet described...the biggest concern that most of us have is this is some other virus that is trans- mitted by an airborne rte, which is incredibly unlikely."

Dr McGeer doubts that a diagnosis will ever be made, and questioned why the woman would be thought to have the Ebola virus after coming from a country without a recent history of Ebola infection. 

While the condition of the woman in hosp remains serious, signs of late-stage Ebola infection, such as bleeding ears and eyes, have not been part of her symptoms, and she is showing some clinical improvement, said Mark Loeb, an infectious disease expert at Hamilton Health Sciences Corp. 

Health officials said they are still being "super cautious" when treating the woman and continue to monitor people who came in close contact with her, including two of her personal contacts and ten hospital workers 


\10 Flu Vaccine Effectiveness

Influenza Vaccine Effectiveness in Preventing Hosp and Deaths in Persons 65 Yrs or Older in Minnesota, NY, and Oregon: Data from 3 Health Plans 09/26/2001
  Influenza Vaccine Effectiveness in Preventing Hospitalizations and Deaths in Persons 65 Years or Older in Minnesota, New York, and Oregon: Data from 3 Health Plans [Nordin J et al. JID 2001:184:665]: The authors reviewed data for three large health plans including Kaiser Northwest, HealthPartners, and Oxford Health Plans for the influenza seasons of 1996-97 and 1997-98 for health plan members over 65 years of age. The results showed that the frequency of hospitalization for pneumonia or influenza was reduced by 20-24% and the frequency of deaths was reduced 39-60% in vaccinated persons.  Both differences are highly significant statistically.

Comment: This is an unusual study because of its size and potential importance in vaccine strategies. Data were pooled from three large health plans in differing geographic areas with a cumulative total of nearly 123,000 participants over age 65 in the 1996-97 influenza season and over 158,000 members for the 1997-98 season. The two seasons examined were of particular interest: in the 1996-97 season there was a good match between circulating virus and the vaccine strength. In contrast, the 1997-98 season was characterized by the first appearance of the Sydney strain and represents the worst match between circulating virus and vaccine strain in the past 12 years.  Despite this problem for the 1997-98 season, there was a 24% reduction in hospitalizations and a 39% reduction in deaths. 

Previous investigators have shown influenza vaccine is associated with a 58% reduction in influenza illness among the elderly (JAMA 1994:272:1661), reduction in mortality by 41% (Lancet 1995:346:591), and an average $117 reduction in medical care costs for elderly persons (NEJM 1994:331:778). Thus, the findings of this retrospective analysis are perhaps not surprising except for the data for the year of the poor match. Nevertheless, the study serves as an important reminder about the priority of this vaccine as we approach the next season in which there is an anticipated delay in supply with the need to prioritize; elderly patients are in the high priority group and should be according to this report as well as others.  By John G. Bartlett, M.D.,  9/26/2001

Antibiotic Treatment of Adults with Sore Throat by Community Primary Care Physicians: A National Survey, 1989-1999 [Linder JA and Stafford RS JAMA 2001:286:1181]: The authors reviewed the data available from the National Ambulatory Medical Care Survey for 1989 through 1999. The NAMCS was established in 1989 and collects information on patient visits to non-federally funded office-based physicians throughout the United States. This survey includes 2,244 visits to primary care physicians by adults with the chief complaint of a sore throat. Projection of these data indicates an estimated 6.7 million pharyngitis-related office visits in the U.S.

The results indicated that 73% of the surveyed visits resulted in an antibiotic prescription. The overall use of antibiotics indicated that 12% received penicillin and an additional 12% received erythromycin. "Nonrecommended antibiotics" were given to 49% including 23% given amoxicillin, 14% given oral cephalosporins, 4% given "extended macrolides" (azithromycin or clarithromycin), 3% received tetracyclines, and 2% received Augmentin. The authors expressed concern about the overuse of antibiotics in this population with a condition that is most frequently caused by viruses and also by the selection of drugs in which only 24% received the current recommended drugs for adult pharyngitis: penicillin or erythromycin.

Comment: This review is particularly timely in view of the recent recommendations for managing acute pharyngitis in adults from the CDC (Ann Intern Med 2001;134:509) and the American College of Physicians (Ann Intern Med 2001;134:506). Both documents note that the only important treatable bacterial pathogen for adults with pharyngitis is group A streptococcus, which is found in 5-15% of cases and is preferably treated with penicillin or, in the event of betalactam allergy, erythromycin. Both guidelines recommend the decision for treatment based on the Centor criteria (exudative pharyngitis, adenopathy, fever, and lack of cough) preferably accompanied by a positive antigen assay for group A strep.

Even these criteria are considered overly liberal by a noted authority in the field, Alan Bisno who feels there remains an important role for throat cultures as an alternative to antigen assays. Thus, some confirmation of the pathogen is his recommendation on behalf of the IDSA (CID 1997;25:574). The obvious concerns are antibiotic abuse and the cost of drugs that have no clear benefit. The data from this report suggests that the CDC, ACP/AISM, and the IDSA have a substantial challenge. Unfortunately, the present report provides no information about the frequency of either clinical or microbiological criteria to support the antibiotic decision.

Flu 1/99 Just weeks after federal health officials warned there would be a nationwide delay in the distribution of supplies of the flu vaccine, the shots are becoming avail at some Chicago-area locations. The US CDC said recently that the delay was due to flu strains failing to grow as rapidly as expected, causing manufacturing problems, and the decision of one manufacturer not to produce the vaccine this season. 

A total of about 75 mil doses of the vaccine are in the pipeline for distribution nationwide this year, based on vaccine manufacturers' reports. About 74 mil doses were used during last 2000 flu season, according to the CDC. Typically, vaccine doses are avail to providers by Oct, with virtually all the doses available before Dec. This year, however, as many as 18 million doses - about 24% of the total supply -- may not be distributed until Dec, according to the CDC. 

The Cook County Dept of Public Health will launch its flu clinics on Nov. 1, a few weeks later than usual, said spokeswoman Kitty Loewy. Starting today, Walgreens began offering flu shots under a pgm that will rotate through its area stores daily until Nov. 18, said company spokeswoman Carol Hively. Walgreen's shots cost $12. Call 800-FLU-9950 for sched. 

Walgreen's is passing along the CDC's request that only those in high-risk groups receive the vaccination now. But Hively said the chain has enough of the vaccine to satisfy even a large demand for shots. "We're a little bit earlier than some people, but we're still going by the recommendation of the CDC and encouraging that just people at-risk come for the early program," Hively said. 

People at high risk for influenza, flu, include the foll: Persons 65 and older. Nursing home residents. Persons with chronic metabolic disease, such as diabetes. Persons with chronic pulmonary or cardiovascular disorders, such as asthma. Women in their second or third trimester of a pregnancy. Youths receiving long-term aspirin therapy. 

Robert Snyder, public adviser to the CDC's National Immunization Pgm, said even those immunized run a risk of developing the flu because the vaccines have been optimized to fight three separate strains determined to be most likely to cause death or hospitalization. Altho those three strains potentially can affect up to 80% of flu sufferers, they're just a fraction of the as many as 60 strains each season, according to Snyder. "It's a scientific guess," Snyder said. "But it's a gamble." 

The trick, Snyder said, is predicting when the flu will hit hardest. In 11 of the last 15 years, he said, the flu was at its strongest from late Jan through early Mar. That suggests most low-risk people can still wait a few months before getting vaccinated, allowing the admin of shots now to those most at risk, he said. "As long as you get the flu vaccine before the flu hits, you should have no problem," Snyder said. 

Flu 2000 Early flu shots scarce, but avail by Jimmy Greenfield Tribune Staff Writer Oct 23, 2000 Tribune Staff Writer Sue Ellen Christian contributed to this rpt.

Influenza, commonly called the flu, is a major cause of illness and death in the U.S., according to the CDC, leading to an average of 20,000 deaths and at least 110,000 hospitalizations annually. Flu vaccines are 70% to 90% effective in preventing influenza among healthy adults and help prevent severe illness in high-risk patients that contract the virus.

Flu pandemics can envelop the globe in a lethal embrace. In 1918, the death toll neared 30 million. Where do deadly flus come from? Hong Kong's bout with bird flu offers a scary new answer. There was a moment at the peak of HKG's bird flu crisis, around Christmas 1997, that Kennedy Shortridge will never forget. Shortridge, an Australian virologist who has called HKG home for almost 27 yrs, was in the Cheung Sha Wan Wholesale Poultry Market with a team testing poultry for the avian influenza virus designated A (H5N1). 

The previous spring, the virus had killed thousands of chickens in farms bordering southern China before fizzling out. In May 97 it killed its first human victim, a three-year-old boy whose preschool had kept little chicks and ducklings. Now, with winter setting in, this fluky virus was breaking out in humans again--4 cases were confirmed in Nov, 13 in Dec. More alarming still, a third of the victims were dying. Shortridge knew that the birds would have to go. In all his years of influenza surveillance, Shortridge had never seen anything like this. A sick chicken isn't usually hard to spot, but this chicken was standing in its wooden cage, looking perfectly normal. And then, very gently, the bird just tipped over, and Shortridge saw blood trickling from its cloaca, the opening at its rear end. "Do we have a chicken Ebola on our hands?" he wondered, using Ebola as shorthand for the bird's unbelievably fast hemorrhagic death.

"In this one market, chickens were literally dying before our eyes. Were we on the verge of seeing a change in the virus? Were we going to see an explosion of virus across the markets of HKG?" One could take comfort in the know- ledge that as long as H5N1 remained an "unreconstructed" bird virus, its opportunities for infecting people--now and then, and one at a time--were limited. 

But what if H5N1 mutated into a form more at home in humans? Or what if it joined in unholy matrimony with a human flu virus and created viral offspring that spread easily--flying from person to person through coughs and sneezes? "This had never happened before in history," says Shortridge. "It was terrifying." Throughout that Christmas holiday, Shortridge and his increasingly worried--and exhausted--colleagues at Queen Mary Hosp continued the testing. About one-fifth of the chickens sampled were infected with H5N1. On Dec 29, even before the tests were completed, the govt grimly went ahead with the slaughter of all the chickens in the markets and farms, well over a million birds, and began the monumental cleanup of the shuttered stores. Chinese New Year came and went, celebrated without the traditional fresh poultry dishes.

No more human H5N1 cases. Months went by. The crisis in HKG began to seem--in some quarters at least--less like a close call than an overreaction. Robert Webster, a viro- logist at St Jude Children's Research Hosp in Memphis, completely disagrees. "If this virus had really adapted to humans," he says, "half the world's pop could be dead by now. We'd be looking at the next pandemic." Our world has been swept by three influenza pandemics in this century. The most devastating by far was the so- called Spanish flu in 1918: virtually every person on Earth was infected, and an estimated 30 mil died, many more than those killed in WW I. The Asian flu of 1957 killed about 70,000 Americans (figures for the rest of the world are not known), and the HKG flu of 1968 killed about 36,000.

As far as we know, these flu pandemics, and the epidemics that occur like aftershocks in between them, are caused by the influenza virus's changeable nature: epidemics result from genetic "drift"--tiny mutations just large enough to let the virus lip by many people's immune systems; pandemics, on the other hand, involve a seismic "shift"--gene substitutions so large they leave pretty much everyone defenseless. But a host of questions remain: Where do these pandemic viruses spring from? What makes them so fierce? Did we have a lucky escape in HKG?

Is it only a matter of time before we face a flu as deadly as the 1918 virus? Flu viruses belong to one of three families, designated influenza A, B, and C. Pandemics appear to be a specialty of type A viruses (a grp to which the HKG chicken flu belongs). Like all flu viruses, they use sgl-stranded RNA as their genetic material, and they make sloppy mistakes when they copy themselves, so bit by bit the viruses change--they drift from their original form. The changes that matter most are in the spiky surface proteins they use to infect cells in the human respiratory tract, proteins called hemagglutinin (H) and neuraminidase (N). But type A viruses are odd: their RNA genome comes in eight segments. If two different type A viruses infect the same cell at once, they can shuffle their gene seg- ments like cards in a deck. This reassortment can produce viral subtypes with combinations of genetic material unlike any our immune systems are used to, with genes that code for completely new H or N proteins, and maybe other proteins as well. By the late 1960s, flu researc- hers were beginning to understand that reassortment was behind the sudden shifts that underlie pandemics.

They were also beginning to accept that the donors of the new, dangerous genes were probably animals. But which animals? It had long been known that domestic pigs get the flu: every fall since 1918, pigs in the US have come down with classic swine flu, a gift of the virus H1N1, which is a relative of the 1918 human virus. (The flu classification system numbers flu strains by variations in their hemagglutinin and neuraminidase genes.) 

The HKG flu of 68, however, had a hemagglutinin related to one found not in pigs but in birds. In the wake of that pandemic, Webster became part of an intl surveill- ance team that would seek out the world's wild flu reser- voirs. By analyzing flu viruses in animals, researchers hoped to trace the source of the genes that mingled with human flu viruses to create such terrifyingly deadly strains.

During the 1970s and early 1980s, Webster and his colleagues at St. Jude amassed an impressive amount of evidence implicating birds--beginning in their own backyard. Right at home in Memphis, Webster found flu viruses in ducks returning from Canada in the fall. In Canada, he found "about 25 percent of newly hatched ducks had influenza viruses." More viruses turned up in geese and gulls and in the small shorebirds that travel each spring between South and North America. "In a nutshell," Webster says, you can find them "wherever you look in migrating waterfowl." While humans get the flu by breathing in viruses, waterbirds are infected by the fecal-oral route. They pour out huge quantities of virus in their feces.

Surprisingly, the viruses are passed from bird to bird but cause no disease at all. "Among them, these birds harbor all 15 of the known subtypes of influenza A," says Webster, "and none of them get sick." The diversity of viruses in these birds hints at a long, shared evolutionary history. Moreover, the genes of these bird viruses are at an apparent evolutionary standstill--so nicely adapted to their hosts that new mutations offer no advantages and thus are not perpetuated. "That alone suggests to me we've described the main reservoir of the virus," says Webster. "That and the fact that the viruses cause no illness." Viruses don't gain much by killing their hosts, and when a virus has a very long history in a species, it tends to reach a compromise with the animal's immune system and cause little disease.

The problems come when flu viruses get into domesticated birds like chickens and turkeys--species in which they are not so well adapted--and the evolutionary brakes are taken off. The viruses make their new hosts sick, the hosts' immune systems respond, and the viruses mutate to avoid the immune systems. They may even kill their hosts.

In the early 1990s, for example, a virulent outbreak in Mexican chickens was traced to a flu strain very much like the one found harmlessly infecting shorebirds. Flu outbreaks have also caused huge losses among poultry farms in the United States, many of which are clustered along the flight path of migrating waterfowl. The problem can spread to cities too. In December 1997, in fact, while Hong Kong was dealing with H5N1, New York was temporarily shutting down and cleaning up its bird markets in response to an outbreak of another avian virus, H7N2. H7 viruses, like H5 viruses, are notorious for mutating into frightful fowl plagues. New York officials are quick to point out that this H7 flu has never been a threat to humans. But of course, until the Hong Kong incident last year, the same was said about H5 viruses.

"I'm more concerned than I would have been pre-Hong Kong," says Edwin D. Kilbourne, a member of the NIH's Pandemic Planning Committee. "Now we've seen what an avian virus can do."

There had already been evidence that the 1957 and 1968 flu pandemics were caused by human viruses that had substituted avian genes--probably from waterfowl--for some of their own. Yet catching flu from pigs seemed more likely. While humans don't carry receptors for bird flu on their cells, pigs do. The going theory was that flu viruses might reassort more easily, and become more compatible with humans, if they mixed in an intermediate host like a pig. Pigs on farms in Asia (where both the 1957 and 1968 pandemics originated) are often kept close to ducks and chickens. And pigs have receptors in their snouts not just for their own swine virus but for bird and human viruses as well. So, potentially, a pig could snort up a bird virus in infected droppings or water, inhale a human virus spread by a coughing farmer, and become a mixing vessel for the two. The viral progeny might then infect humans nearby.

What the Hong Kong outbreak has now demonstrated is that a direct hop from birds to humans is absolutely possible. Maybe pigs aren't as crucial as was thought. On the other hand, the pig-as-mixing-vessel theory is seductive, and it too has been observed: in 1993 a human virus, H3N2, and a bird version of H1N1 mixed in European pigs and produced a virus that infected two children in the Netherlands. But according to Yoshihiro Kawaoka, a virologist at the University of Wisconsin in Madison, there's no direct proof that pigs were involved when bird genes appeared in the human influenzas of 1957 and 1968.

So who is giving what to whom? Bird viruses may have figured in the last two pandemics, but the closest relative to the 1918 Spanish flu has always looked like classic swine--the porcine H1N1 virus that also first appeared in 1918 and that still circulates in pigs today.

By some historical accounts, humans actually got sick first--implying that people gave the virus to pigs. That global killer of 80 years ago is obviously the flu we most want to understand. Unfortunately, it is also the hardest to get a handle on. No one even knew influenza was caused by viruses in 1918, so the cause was essentially lost from the start. By the 1930s, when researchers realized a virus was responsible, the original, deadly 1918 virus was long gone. Or at least we thought it was, until 1997, when researchers began resurrecting its genetic ghost.

Jeffery Taubenberger did not start out as a flu researcher. He's chief of the division of molecular pathology at the Armed Forces Institute of Pathology in Washington, D.C. He and his collaborators work on coaxing genetic information out of tissues fixed in formaldehyde and preserved in little paraffin blocks. The institute has a long history--it was founded by Abraham Lincoln, who realized that more soldiers died of infectious diseases than of gunshot wounds, and its tissue archives date back to the Civil War. Since formal cataloging began in 1917, more than 3 million cases have been doc, "showing a quasi-Victorian passion for collecting," as Taubenberger puts it.

"In an era of budget cutting," he adds, "we wanted to showcase the repository, so we looked for a good project." That's how he got into the 1918 flu business. The first step was to look for tissues of 1918 flu victims. Of the 70 initial samples studied, just two were positive for influenza RNA.

"The first case was a 21-year-old Army private from Fort Jackson, South Carolina," recalls Taubenberger. "Amazingly, he died on September 26, 1918, the very same day the second fellow died, at Camp Upton in New York. The second soldier had one of those very unusual 1918 pathologies. He died in three days of massive pulmonary edema--lungs completely filled with fluid."

The Spanish flu washed over the world in two waves. During the spring wave, it was very infectious but not very virulent. By September, the beginning of the fall wave, the virus was killing people in droves--specially young adults. Taubenberger had two questions: Where did the virus come from, and why did it suddenly become so ferocious?

His initial study, published in March 1997, focused on pieces of the hemagglutinin gene from RNA found in the first victim, which looked pretty. much like classic swine flu, H1N1. And it still looks like a mammalian gene now that the whole of it has been sequenced, says Taubenberger. But, he adds, "it's the most avian-like of mammalian HI sequences. So probably, ultimately, it did come from a bird. The question is in the timing--how long ago?"

A clue might come from past studies that examined flu antibodies in the blood of people who were alive around the turn of the century. Some elderly people may have had antibodies to an ancestral H1N1 as early as 1905. So perhaps the virus skulked around for years before the Spanish flu erupted, sometimes getting into people but not yet capable of spreading easily or quickly. "Maybe," speculates Taubenberger, "a human and an avian virus reassorted, and then the avian-derived virus took some years to fully adapt to life in mammals. "Were we starting to see something similar last year in Hong Kong?" he muses. "Maybe Hong Kong last year was what was happening in 1905. It's worth thinking about."

In one respect, though, the 1918 flu virus is definitely not like the Hong Kong bird flu. In the chicken viruses H5 and H7, a simple mutation in the hemagglutinin gene can change a mild-mannered virus into an almost uniformly fatal pathogen. That mutation, a little genetic stutter, allows the virus access to cells beyond its normal range--not just in the bird's gut and respiratory tract but in its heart, kidneys, and brain. This worrisome mutation was one of the hallmarks of the avian virus that caused unusually severe illness or death in 18 people in Hong Kong. But Taubenberger found that the 1918 virus lacks this mutation.

This is not to say that mutations for virulence could not exist elsewhere--and Taubenberger has acquired another source of 1918 flu genes to investigate. In August 1997, Johan Hultin, a retired pathologist from San Francisco, quietly flew to Brevig, an Alaskan village nearly obliterated by influenza in 1918. With the villagers' permission and help from four local boys, he opened the graves of flu victims buried in permafrost, hoping to take samples of their lung tissues. One of them was an obese young woman. "She was lying on her back, and on her left and right were skeletons, yet she was amazingly well preserved. I sat on an upside-down pail, amid the icy pond water and the muck and fragrance of the grave," says Hultin, "and I thought, 'Here's where the virus will be found and shed light on the flu of 1918.'" The young woman has become Taubenberger's key "to sequencing the whole viral genome," he says. The cold, and an insulating layer of fat in her skin, helped preserve her lung tissue for 79 years.

Hultin's and Taubenberger's successes fanned interest in a much larger expedition to the polar north in August. Led by Kirsty Duncan, a Canadian geographer, the team traveled to Spitsbergen, an island off Norway, to exhume the bodies of six miners who died in Oct 1918. Ground-penetrating radar studies hinted that their graves might be below the permanent frost line. Though the odds of finding live virus in their tissue were almost nil, isolation suits were worn and biosafety precautions taken.

When the graves were found, however, they were just above the permafrost. "The GPR let us down a bit," says Webster, who's slated to do some of the laboratory analysis. "The good news is we got lots of samples. The bad news is the tissue was not frozen." At best, researchers will be contending with maddeningly short, degraded pieces of RNA, requiring two years to get "to where Jeffery is now."

To put the work in perspective, says Taubenberger, had live virus been found in Spitsbergen, the whole virus genome could have been sequenced in a week or two. In weeks, the Spitsbergen team would have been staring down the genes of one of the greatest killers on  Earth--perhaps even seeing the nature of the beast it came from. Chicken is on the menu again in Hong Kong, and the flu to worry about these days is not avian but financial, the current Asian contagion. There's no doubt in Shortridge's mind, though, that the world had a very close call. "I think Hong Kong made the right decision and averted a pandemic," he says. "And we did it largely by watching animals."

When agricultural authorities picked up a chicken-killing virus in the spring, it was identified as an H5 virus and passed along to a high-security lab in the United States. When public health officials spotted a peculiar virus in a sick little boy, they dispatched it to Dutch researchers interested in oddball viruses. And when it became clear that the chicken virus was the virus making humans deathly ill, Hong Kong did what it had to: it shut its markets and gassed the birds--not just chickens but ducks and geese as well, the aquatic birds that may have passed the virus to them. (The closest match so far for the hemagglutinin of the Hong Kong chicken virus is one from a Chinese goose.) Enormous changes have been wrought in the traditional market system. Chickens brought in from southern China, for example, are tested twice, once on either side of the border.

And no longer can chickens be mixed with live ducks and geese. In an almost unimaginable break with Chinese custom, aquatic birds are not only taken to a separate market but killed in advance and sold as dressed poultry.

To reduce the chances of animal viruses hopping into humans, it's vital to know which viruses spell trouble, and where the viruses are. For decades flu researchers have popped strains of interest into their freezers. These isolates now serve as a reference library to identify viruses and work out their family trees--the Dutch team used tests based on viruses from Webster's freezer to identify bird flu in the Hong Kong boy. Still, the Hong Kong experience makes it clear that current levels of surveillance are not good enough.

The ultimate reservoir of the Hong Kong chicken virus will probably be found among migrating waterbirds. "But you can't kill all the ducks and aquatic birds of the world--that would be absurd," says Webster. "It makes you realize that influenza is a non-eradicable disease." Antiviral drugs can work against flu, but our best protection against new viruses is vaccines (see "Beating Bird Flu," page 86). The tried-and-true way to make a vaccine is still to use a closely matched but safe version of the virus you want to combat. Right now, though, there are no good matches for the bird flu virus.

"It's one year after H5N1. And do we have a vaccine on the shelf in case we need it?" asks Webster testily. "No. And why not? Because we haven't found a good surrogate virus with which to make a vaccine. And why is that? Because we haven't done the necessary surveillance. We should be looking all over Southeast Asia."

At an NIH meeting in September, virologists and public health officials discussed the need for more surveillance in nature. And vaccines for all 15 subtypes, it was decided, should be readied lest an H5 virus--or another new virus subtype--take us by surprise. For now, researchers are catching their breath, immensely relieved that H5N1 was nipped in the bud. But Webster feels that another hop from birds to humans will occur in the near future. The Hong Kong outbreak, he adds, "served as a warning of what could happen. It was a killer--like 1918 on its way."

DISCOVER; JAN 1999 FEAR OF FLU By Patricia Gadsby, 

BEATING BIRD FLU. Vaccines work by giving the immune system warning about a pathogen, and flu vaccines usually do so by introducing signature flu proteins into the bloodstream. But vaccines for a bird flu virus, like the one implicated in the Hong Kong outbreak, pose a problem. The H5N1 virus kills chickens, and fertilized chicken eggs infected with flu are the nurseries in which flu proteins for conventional flu vaccines are produced. (Eggs are used because the virus grows quickly in a chick embryo, and eggs are abundant and inexpensive compared with other production systems.) Still, there is hope. A couple of groups are working on vaccines against H5N1. And one such vaccine--developed by Protein Sciences of Meriden, Connecticut--has been used among workers studying the H5N1 virus in high-level biosafety labs.

The Protein Sciences method uses caterpillar cells as nurseries for a virus engineered to produce the H5 protein--the hemagglutinin variant that is thought to allow H5N1 access to cells throughout the human body. The protein can be produced from caterpillar cells far more easily than from eggs. A vaccine made in this fashion not only protects chickens against H5N1 but is also safe in humans. Whether it can defend humans against H5N1 can't be known until someone is exposed to the bird flu--either by accident or outbreak. Another group, Aviron, in Mountain View, California, has recently created a live-virus human flu vaccine (delivered via nasal spray) and has also experimented with a live-virus vaccine against the H5N1 strain. First they inserted the H5 gene from the Hong Kong flu virus into the weakened strain they use in the human vaccine. Then they grew the resulting virus in chicken eggs, like a conventional flu vaccine. When chickens are vaccinated with this weakened live virus, it primes immune cells in their airways to fend off the H5N1 strain. This vaccine protects chickens, but its benefit to humans remains unknown. Other labs are hoping to concoct a vaccine from an avian flu virus that closely resembles H5N1 but doesn't cause disease. The closest match so far is a flu strain found in the Singapore duck.

Both Protein Sciences and Aviron say their methods permit them to start making vaccines within two months of getting a new flu strain to work with. If we face an outbreak a la HKG, and an appropriate new vaccine is on the shelf, it would be tested for safety first, then possibly distributed within three to four months. For now, researchers can only hope that the virus cannot move faster than that.

Best time to get flu shot is Oct-Nov. Best prevention is to stay away from crowds and wash hands often. Annual flu season runs from Dec-May.  Don't take it if allergic to eggs or in the first three months of pregnancy.

NYT 11/00 - Most years by this time, doctors would be almost finished inoculating the elderly and other vulnerable patients against the flu. This year the vaccine was delayed by manufacturing problems, and many doctors and hospitals, even those serving AIDS patients and others particularly vulnerable to flu, have only just begun.

Bronx-Lebanon Hospital Center ordered about 20,000 doses of flu vaccine this year, but their first shipment, a mere 1,800 doses, arrived only last week, said Dr. Edward Telzak, chief of the hospital's division of infectious diseases and director of its AIDS program. The vaccine, made from killed flu virus, must be designed each year to counter prevalent flu strains. 

Studies have shown that among the elderly, the vaccine cuts the chance of hospitalization by at least half and chance of death by four-fifths. Among healthy young adults, the vaccine is 70 percent to 90 percent effective at averting the flu entirely.

 Last month, the federal Centers for Disease Control and Prevention in Atlanta ordered 9 million additional doses — bringing the total production to 75 million shots, roughly the same number as last year. But only about a third of the vaccine has been delivered so far. The current shortfall has generated criticism over how the limited doses have been distributed, especially after reports that some corporations that offer flu shots to their employees, who are mostly young and healthy, received their allotments before doctors, hospitals and health depts.

 "We've spent years emphasizing the important of this annual ritual of getting a flu vaccine," Dr. Telzak said. "And there's no vaccine to give them." At this point, it is impossible to say whether the two-month delay in vaccine deliveries will merely irritate doctors and patients or threaten the nation's health. Which scenario plays out depends on two still unknown factors: when flu will strike this winter and whether the delay ultimately affects the number of people vaccinated. 

If the flu season follows its usual course of peaking in January or February and manufacturers deliver the vaccines by early December as currently planned, most people should receive the shots before the virus arrives. The vaccine induces the body to make antibodies to flu viruses, but the body's immune system takes one to two weeks after receiving the shot to churn them out. 

In 4 out of last 18 years, the flu has appeared in force in December. In a typical year, 1 out of 10 Americans comes down with the flu, about 110,000 people, mostly elderly, end up in the hospital and about 20,000 die. "My concern is we will have disease before the high-risk people are immunized," said Dr. Steven R. Mostow, who directs a training program at the University of Colorado Health Sciences Center in Denver for medical professionals in five states.

 "In the absence of vaccine, what I have predicted — and God I hope I'm wrong — I would predict double all those numbers." So far, health departments in half a dozen states have already reported sporadic flu cases — nothing unusual, according to the C.D.C. "Right now it seems to be tracking as a typical flu season," said a spokeswoman, Barbara Reynolds. Dr. Mostow disagrees. 

"In my opinion, they are earlier than normal," he said. "It's been around since late September. When we have earlier cases like this year, we tend to have earlier outbreaks. When enough people cough on each other who have not been immunized, the disease will spread." 

Dr. Mostow has been advising high-risk patients who cannot obtain vaccine that they can turn to antiviral drugs amantadine and rimantadine. However, instead of a one-time shot, the drugs need to be taken daily. "I'm trying to be very practical," Dr. Mostow said, "telling physicians and their patients, `Hey, don't panic, we have an alternative for you, and that is amantadine or rimantadine taken preventatively.' " 

The cause of the vaccine delay is part nature, part manufacturer. The flu virus continually mutates, and each spring, the C.D.C. chooses the strains it believes will be most widespread the following winter. To make the vaccine, the viruses are grown in eggs, then killed. But eggs are not the virus's natural environment, and "it takes a while to make them adapt properly to the eggs," said Dr. Fred Ruben, director of medical affairs at Aventis Pasteur, a unit of France's Aventis which will produce nearly half of the vaccine this year. 

One of the flu strains, known as Panama A, included in this year's vaccine mix proved particularly finicky, slowing down all of the manufacturers. In addition, the Food and Drug Admin had cited two of the vaccine makers for manf probs. One, Wyeth- Ayerst Labs, a division of American Home Products Corp, resolved the FDA's concerns about quality assurance checks to ensure its products met safety stds. Wyeth started shipping vaccine in mid-Oct. 

The other manufacturer, Parkedale Pharmaceuticals, part of King Pharmaceuticals Inc., was unable to fix more serious problems and said in late September that it was dropping out of the flu vaccine business this year. Last year, Parkedale accounted for 15 percent of the market. Guidelines issued by the C.D.C. in June called for high-risk people to be vaccinated first.

 But the hodgepodge of private companies and public agencies that distribute flu vaccines has been unable to ensure that the guidelines were followed. Aventis says it has informed customers of the C.D.C. guidelines, but did not prioritize its shipments. "As a supplier of the vaccine, we're not in best position to determine who is immunizing high-risk patients," said Len Lavenda, a company spokesman. 

Only a few customers specified in their contracts that they required early shipments, he said. Last week, Aventis revised its shipping schedule so that all customers would receive at least a quarter of their order by mid-November and that the remainder would be shipped by the first week of December. Doug Petkus, a spokesman for Wyeth-Ayerst, said, "We are targeting as best we can the high-risk groups." Wyeth will finish shipping in mid-December, he said.

 The shortages have been felt around the country. "It's very rare for the health professionals to have it," said Dr. Sarmistha Hauger, a pediatric infectious disease specialist at Children's Hospital in Austin, Tex. While the hospital does not expect to receive any vaccine until Thanksgiving, grocery chains in the area have obtained enough doses to run flu shot clinics, "which is very odd," she said. In Colorado, "Most primary care physicians do not have any vaccine at this time," Dr. Mostow said. "Our physicians are telling high-risk patiensts to go stand in line at a grocery store." 

Hospitals' vaccine fortunes also depend in part on which company they ordered from. For example, New York Presbyterian Hospital, which ordered from Aventis, received its first shipment of vaccine at the beginning of October. "Actually, we've done pretty well," said Karol Wollenburg, apothecary in chief for the hospital. 

On the other hand, Bronx-Lebanon and Mt Sinai Hosp ordered from Wyerth-Ayerst and did not receive any until the end of Oct, and unless they receive additional shipments this week, they expect to run out again soon. To help ensure that vaccines reach those at highest risk, NY may "perhaps do the Robin Hood thing," said city Health Commissioner Dr. Neal L. Cohen. "Take it from those who need it least and make sure it gets to those who need it most." 

The NYC Dep of Health is currently talking with corporations about giving their flu vaccine shipments to hospitals and doctors waiting for their shipments. The companies would then get the late shipments originally intended for the doctors. At the city's flu clinics, the vaccines have been distributed on a first-come-first-served basis. "We're asking people to respect to our priorities, but we're not turning people away," 

Dr. Cohen said. Young, otherwise healthy looking people might fall into one of the high-risk groups because of asthma or heart problems, Dr. Cohen said. For more information and location of New York City flu vaccine clinics, call 1-866- FLU-LINE. Health officials have another message, too: better late than never. "The challenge will be to make sure people don't neglect getting the flu shot later in the season falsely thinking it will be no benefit to them," Dr. Cohen said. "We want to remind people there is still time to receive protection from the flu vaccine."

Nov 7, 2000 Personal Health: Other Ways to Fight Flu While U.S. Waits for Vaccine By JANE E. BRODY 

Could the current delay in production of flu vaccine be a blessing in disguise? While some may get sick before getting a flu shot, the publicity given to the temporary shortage and to other methods of combating the flu may greatly increase public awareness and ultimately cause far more people to seek protection than did in years past. Public health officials report that only about 60 percent of those over 65 and only 30 percent of those with underlying illnesses that place them at high risk of developing serious, potentially fatal complications from the flu get the vaccine each year.

Trying to avoid exposure to flu viruses would require a form of hibernation for the next four or five months. Flu viruses spread easily — more easily than cold viruses — mainly from an infected person to a healthy one through virus-contaminated airborne droplets released by coughs, sneezes and even conversation. And it is not enough to avoid people who are sick, since the virus can be spread during the one- to three-day incubation period, before any symptoms appear. Once flu symptoms develop, a person remains contagious for up to five days. 

This year's vaccine will protect against a new variant of the Type A influenza virus, the more common and more virulent form and the type most likely to cause flu epidemics. But while flu vaccine offers the best and cheapest form of protection (a 70 percent to 90 percent reduction in risk at a cost of only $10 to $15), people at high risk for complications need not wait for the vaccine to reduce their chances of getting the flu or to curb its duration and severity. There are now four prescription drugs approved by the Food and Drug Administration that can help to diminish the effects of influenza for the 35 million people aged 65 or older, up to 39 million younger people with high-risk medical conditions and 2 million pregnant women. 

These drugs are not recommended for routine use for otherwise healthy people. Each drug comes with a set of cautions worth heeding. Furthermore, when used to treat the flu, the drugs must be started within the first two days of the illness. Before prescribing them, doctors now can do an in- office 20-minute test to determine if their patients have the flu. The drugs do not work against other viruses.

The Old Antivirals Two drugs, amantadine (Symmetrel) and rimantadine (Flumadine), have been around for a while. They are approved for use as preventives and treatments, but they are effective only against Type A flu. If you cannot get the vaccine in time and you face a high risk of serious complications, these drugs can help protect you. They can also help people who have been immunized but who need extra protection, like an elderly person with heart or lung disease. 

Used as a preventive, the drugs would have to be taken daily for the entire flu season. Although a five-day course of amantadine costs only $3.50 and a similar course of rimantadine costs $8.75 (based on wholesale prices), taking them for four months or so can cost from $100 to more than $600. As treatment, a seven-day course would cost about $6 to $37, but at best the drugs shorten the illness by only one or two days. Both drugs can sometimes cause unpleasant — and in rare cases, serious — side effects, and the flu virus can become resistant to them. 

Amantadine's possible adverse effects, which abate with time, include nausea, vomiting, dizziness, insomnia, anxiety, impaired concentration and seizures. It can also cause adverse interactions with other drugs, like antihistamines and nervous system stimulants. Rimantadine is less likely to interact with other drugs, but it can cause similar adverse effects.  

Two New Antivirals Zanamivir (Relenza) and oseltamivir (Tamiflu) are now approved only as treatments, not preventives, and used as such they can cost up to 15 times as much as amantadine. But unlike amantadine, they work against Type A and Type B influenza viruses and for most people they are associated with fewer adverse effects. Also, there is no evidence that the flu virus can become resistant to them and there are no known interactions with other drugs. 

Zanamivir, a powder that is inhaled, is used twice a day for five days at a cost of about $44. Possible side effects include nasal and throat discomfort, cough and headache. People with breathing disorders like asthma can develop bronchial spasms and should always have a fast-acting bronchial dilators on hand when using this drug. Although zanamivir is not yet approved for preventing flu, a study at the Univ of VA and the Univ of Mich, pub last week in The New England Jrnl of Med, showed that when flu victims' family members were given zanamivir once a day for 10 days, their flu risk dropped by 79 percent. 

For the flu victim, taking the drug twice a day for five days shortened the duration of symptoms by two and a half days.  Like zanamivir, oseltamivir, taken twice a day for five days, can reduce symptoms and shorten the flu duration by a day or more. Its most common adverse effects are nausea, vomiting and headache. At about $53 for a five-day supply, it is the most expensive flu treatment. 

In an experiment at the University of Virginia medical school in which healthy people were given infectious doses of flu virus, oseltamivir reduced the risk of infection by 61 percent and prevented the spread of flu virus in all cases. Both zanamivir and oseltamivir are intended for patients with uncomplicated cases of flu. But during the last flu season, there was serious concern about the misuse of these drugs in patients who had developed serious and in some cases fatal complications of the flu that should have been treated with antibiotics.

 Vaccines Now and Future Do not let the temporary shortage stop you from getting the flu vaccine as soon as the supply warrants. Even after the flu season is in full swing, it can protect you, though it takes two weeks to produce maximum immunity. And do not assume that because you were immunized last year, you will be protected this year. The immunity afforded by this killed-virus vaccine is short-lived and the virus keeps changing. Meanwhile, researchers have reported exciting results of studies of a not-yet-licensed flu vaccine administered as a nasal spray.

 The product, called FluMist by Aviron is prepared from live flu viruses modified to survive only in the nasal passages, not in the lower respiratory tract. Not only is this spray vaccine more suitable for children, providing 93 percent protection against flu and 98 percent protection against ear infections, a common complication in children who get the flu, it has also protected against flu virus variants that were not included in the vaccine. Aviron last week applied for licensing approval and expects FluMist to be available for the next flu season.


\11 Foot-and-Mouth 8/01

There are four vesicular diseases of pigs which are difficult or impossible to differentiate clinically: FMD, swine vesicular disease (SVD), vesicular exanthema (VES), and vesicular stomatitis (VS). Of these, FMD is the most widespread and important with SVD being of secondary importance in some regions (e.g. the EU). The other two have very limited distribution and VES has disappeared. 

FMD is the most important restraint to intl trade in animals and animal products. Consequently, large sums of money have been invested in control and eradication programmes and also into research. As a result more is known about the FMD virus than about almost any other animal infection. 

It generally produces severe disease in pigs and cattle.  FMD is so important because it is highly infectious, spreads rapidly throughout animal populations and over long distances on the wind and hence it is difficult and costly to control. Also because of its damaging and debilitating effect on cattle, a great deal of effort and tax-payers money has been spent keeping it out of large areas of the world. It would be highly irresponsible to let it back in. 

Susceptible Animals - Among farm animals, pigs, cattle, sheep, goats and deer are susceptible. In addition, wild and domestic cloven hooved animals such as hedgehogs and rats are also susceptible as are elephants. 

Early clinical signs - In cattle the early clinical signs are much more definitive or suggestive than in pigs. For example in a dairy herd several cows may suddenly show depressed milk yield, go off their feed, run a fever, have a dramatic drop in milk yield, and a little later start salivating profusely, the saliva running from their mouths (slavering). If you see such signs, jump into action, ring the vet. Veterinarians who have to deal with FMD say that if a farmer telephones to say that several cows are salivating profusely they think first "FMD?". 

If after cows have started salivating and smacking lips, vesicles are noticed on the lips, on the teats and around the coronets, the areas above hooves - your worst fears are probably true. The probability is that your pig herd has been infected too. 

In pigs early signs are lameness a drop in food consumption and some pigs appear depressed and have fevers of about 40.5ºC,(105ºF). In piglets sudden death due to cardiac failure is common. What should make you strongly suspicious is the appearance a little later of vesicles up to 30mm. diameter, similar to those described above for cattle. They are most plentiful around the coronets but are less plentiful on the nose and lips although this is where you are likely to see them first. 

They often appear on the teats of recently farrowed sows. By then the sows and some of the other pigs may be dribbling saliva and chomping their jaws. If they are on bedding they may not appear lame but if they are on concrete they probably will be. The early signs of swine vesicular disease (SVD) when it is severe, are indistin- guishable from FMD so you should suspect it too. 

If you farm near the coast of California where FMD and SVD are extremely unlikely, vesicular exanthema could be a possibility. If you farm in Georgia, the Carolinas or Central or South America and it is summer/autumn time perhaps you should think of vesicular stomatitis. The clinical signs of all four diseases are almost indistin- guishable. 

Within 24 hours many of the vesicles will have burst. On the lips and teats they may leave shallow erosions but on the coronets of the feet secondary infection and trauma may convert them into raw jagged-edged ulcers. 

If the pigs are not killed some may lose their complete hooves ("Thimbling"), sows may abort, as a result of fever, and in severe outbreaks some may die. Boars may go lame and stop serving sows, so there is an infertility side effect. There may also be an increase in mortality among suckled piglets. This is often the first sign. 

In endemic areas where vaccination is carried out routinely the disease is not a serious economic problem in pig herds. In fringe areas, particularly where vacci- nation is not allowed (e.g. in the EU) it is a serious problem because the herd will almost certainly be killed and although compensation is likely, the farm cannot be restocked for at least six weeks, it is therefore out of production and in a negative cash flow for a long time. 

Diagnosis - Rapid accurate diagnosis is essential. FMD cannot be distinguished from SVD on clinical grounds, or from VES in California, although SVD is often much milder. To differentiate these diseases and confirm the presumptive diagnosis, samples have to be sent to a lab capable of making a diagnosis. 

There are not many of these. The main one is the World Ref Lab at Pirbright near London, England. There is also one on Plum Island, NY and one near Melbourne, Australia. The samples sent are blood and pieces of the skin that overlay the blisters plus vesicular fluid if this is avail. Once the samples have been received by the lab diagnosis is fairly rapid. 

Tests called ELISAs are used for virus ID and if it is FMD they also indicate what serotype it is. The virus may also be grown in cell culture and the ID confirmed by other tests. A molecular genetic test called a PCR (poly- merase chain reaction) may also be used to 'fingerprint" the virus. The gene (genome or RNA) of FMD repeatedly undergoes minor changes as the virus spreads through animal populations so by identifying the precise sequence in the gene the laboratory staff are able to make an assumption where it may have come from by the most recent isolate with a similar sequence. 

Treatment - None. Animals should be destroyed. Management control and prevention, Vaccination (where applicable). In endemic and high risk areas routine vaccination may be practised mainly to protect the breeding stock. Most FMD vaccines are produced in cell suspension cultures and inactivated by ethylenamine derivatives. An adjuvant is added to make them more potent. Oily adjuvants are used in swine. 

Vaccination in pigs is problematical. This is because protection is short-lived lasting only about six months. It is also partly because there are seven serotypes of FMD and protection against one leaves animals susceptible to the others. Vaccines must be multivalent (several serotypes) in most endemic regions. Since FMD is largely a winter disease, vaccination should be carried out in the autumn. 

Serotypes - There are 7 main serotypes: A, O, C, SAT 1, SAT 2, SAT 3 and Asia 1. There are also many strains within serotypes. Careful selection of the strains for inc in vaccines is essential to ensure effectiveness. 

Precautions - Countries in free and fringe areas apply strictly enforced national preventative measures against the introduction of infection. The main features of these measures are control over the import of cloven-hoofed animals and of meat from such animals from counties in which FMD occurs. 

The virus does not survive rigor mortis but it can persist in bone marrow and lymph nodes of infected carcasses for several weeks. If the disease does enter a free or fringe area, a slaughter policy is implemented, all diseased and in-contact animals being slaughtered. A standstill on animal movement is imposed and tracings are carried out to check possible spread of the disease through previous contacts. Ring vaccination may be used around the affected region. 

--------------------------------------------------------- A contagious febrile disease of animals and, rarely, humans. It is also called hoof-and-mouth disease. Caused by a virus, it affects cloven-hoofed animals such as cattle, swine, sheep, goats, and deer, often causing epidemics. 

The disease is characterized by a sudden rise in temp, followed by an eruption of blisters occurring in the mouth, on areas of tender skin such as the udder in females, and on the feet; blisters may also appear in the nostrils. Salivation and frequent smacking of the lips accompany the eruption. The blisters grow larger and then break, exposing raw, eroded surfaces. Eating becomes difficult and painful, and because the soft tissues under the hoof are inflamed, the animal invariably becomes lame and may shed its hooves. 

Livestock raised for meat lose much weight, and dairy cattle and goats give less milk. Often the disease kills very young animals and causes pregnant females to abort. The crippling effect is extremely serious where oxen are used as draft animals. The US has experienced nine distinct epizootics; the most serious occurred in 1914, invading 22 states and the District of Columbia. The latest outbreak, which occurred in California in 1929, was quickly controlled.

Foot-and-mouth disease nevertheless remains a menace to livestock raisers and the meat-packing, dairy, leather, and wool industries. The Agricultural Research Service of the U.S. Department of Agriculture inspects all imported livestock, stock feed, and bedding at all points of entry. The dept is strict in enforcing quarantine regs.

Considerable progress has been made toward developing an effective vaccine against foot-and-mouth disease, but the cost (approximately $1 billion annually) of vaccinating all susceptible animals would be prohibitive. Moreover, the vaccine would not eradicate the disease. consequently killing of all exposed animals is the only presently effective countermeasure to foot-and-mouth disease. During the outbreak in the UK in 1967 and 1968, for example, more than 430,000 animals were slaughtered.

--------------------------------------------------------- A Foot-and-Mouth Primer by JESSICA REAVES Mar 14 2001 Europe is in near-panic and the U.S. has banned imports of European animal products. A TIME.com Q&A explains the issues involved. Until now, foot-and-mouth disease looked like a British problem. That was before the French government confirmed a case of the highly contagious virus in the northeastern corner of the country, sending European financial markets and farmers into barely controlled hysteria.

Roadblocks and embargoes were established, travelers were asked to disinfect their shoes, and thousands more animals were slaughtered and burned as French farmers scrambled to contain the devastating disease. Across the Atlantic, the US Agriculture Dept banned imports of all livestock, fresh meat and unpasteurized dairy products from all 15 countries in the European Union. While some E.U. countries expressed surprise at what they term "drastic" action, the Agriculture Department sees the ban as a necessary precaution. 

"There are some concerns that because of the way trade moves so freely within the E.U., suspect animals could be out there, even in countries where no clinical symptoms have manifested yet," USDA spokesman Jerry Redding told TIME.com. The USDA insists there is no need for undue concern among European nations concerned about their future as exporters. "This ban is temporary," Redding says. "We're going to see what develops, and if the disease doesn't pop up in new countries, we'll restructure the ban." 

Here, in an attempt to clarify some of the most pressing questions about the disease, is a TIME.com Q&A: 

What is foot-and-mouth disease? Foot-and-mouth disease (also known as hoof-and-mouth) is a highly communicable, much-dreaded virus that affects mainly cows and pigs but can also strike sheep, goats and deer. Farmers live in fear of the disease because it spreads so quickly and containing it often requires the destruction of costly livestock. 

What happens to an animal that gets the disease?  An animal with foot-and-mouth disease will develop a fever and blisterlike lesions on its tongue, lips and teats and between its hooves. Even if an animal recovers (and most do), the disease will dramatically reduce its ability to produce milk; in addition, the animal will grow more slowly, thus making it more expensive to bring to market as meat. 

How is it spread? The disease is highly mobile: It can be carried through the air, in animal by-products, on the dirt on people's shoes or on farm equipment. Foot-and- mouth thrives in dark, damp places, like barns, and can be destroyed with heat, sunlight and disinfectants. That's why pasteurized or cooked meats and dairy products are exempt from the U.S. ban. 

Can people get foot-and-mouth disease? It's possible, but extremely unlikely. And in the one documented case of human foot-and-mouth disease (diagnosed in 1966, in Britain), the symptoms were very mild and dissipated quickly. 

If the disease isn't dangerous to people, and isn't even fatal in most animals, why is everyone panicked about its reemergence? Foot-and-mouth isn't so much a health or safety threat, it's an economic threat. Farmers and governments alike are concerned about losing livestock that provide valuable milk and meat products. The USDA estimates an outbreak of foot-and-mouth in the U.S. — where the disease has not occurred since 1929 — could cost billions.
  How are European countries treating the outbreak?  Authorities are slaughtering and then incinerating infected animals and ones suspected to have been in contact. In Britain, 120,000 animals have been destroyed, and there are plans to burn at least 50,000 more. French authorities have decided to burn some 50,000 sheep that have either been in contact with British animals or have been imported. 

In addition, authorities have set up checkpoints and roadblocks, asking visitors to step in disinfectant and/or run their car wheels through a band of it in order to keep the disease from spreading. 

Is incinerating animals the only way to deal with the disease? During previous outbreaks in Eastern Europe, governments there chose to inoculate infected or exposed animals against foot-and-mouth. But, as critics point out, once an animal is inoculated, it's impossible to tell, without cutting-edge and rarely used tests, whether the animal is carrying the disease and is therefore highly contagious to other animals. 

--------------------------------------------------------- A Tenacious Disease Finds New Victims in British Herds By SARAH LYALL NYT LANGENNY, Wales, Aug. 2 01 Three months ago, running for re- election and anxious to improve public confidence in his government's agricultural policy, Prime Minister Tony Blair boldly declared that the country's foot-and-mouth crisis had turned the corner and was "in the home straight." 

Try telling that to John Morris, a farmer here who outwitted the disease until the morning of July 13, when he noticed with a jolt that one of his cows was unsure on her feet and drooling excessively, classic signs of foot-and-mouth. A veterinarian confirmed his hunch. The next day, a team of professional slaughterers came to the farm and shot dead his entire herd — 280 organically treated sheep and 19 cattle. 

Or try telling his neighbors, who have suddenly found themselves in the center of one of the worst new clusters of the disease to strike Britain this summer. In the last two weeks, 15 new cases have been confirmed here, and 13,000 animals on 55 farms have been destroyed. 

Now there are fears for the hills, where sheep have bloodlines going back more than 2,000 years and are hefted, meaning that they have learned down the generations how to stay within the unfenced boundaries of their spot on the hillside. Tens of thousands of sheep graze there, and farmers say their biggest fear is that they will all have to be slaughtered. 

And so people are recognizing that the elation of victory was premature and the disease is continuing its willful and unpredictable journey through the British countryside. 

The govt itself concedes that it will be months before Britain is free of foot-and-mouth. Three new cases a day are still being identified, on average. More than three and a half million animals from 8,998 farms have been slaughtered. More are still waiting to be culled. 

The cost to Britain's economy to the farming and tourist industries, and ancillary businesses is estimated at £1.2 billion, or $1.7 billion, so far. The eventual cost, the govt says, is likely to be £2.3 billion. Movement of animals except by special license is forbidden in most parts of the country; the export markets are still closed; and many farmers are still virtually isolated on their land. 

The disease, which strikes cloven-hoofed animals like sheep, cows, goats and pigs, is rarely fatal but can debilitate animals and makes them unfit for market. Although foot-and- mouth is endemic in parts of Asia, South Africa and South America, it was absent from Britain for 20 years before the current outbreak. European Union regulations require member countries with cases of foot- and-mouth to stop exporting animals until the disease has been wiped out.

Why has foot-and-mouth disease dug in this way, despite the govt's predictions? In part, said David Tyson, pres of the British Veterinary Assoc, it has become clear in hindsight that the disease was already inexorably spreading through the countryside when the first case at a slaughterhouse in Essex was announced by the govt on Feb. 21.

"We effectively had 96 separate disease starting points by the time it was disclosed that the pigs in the abattoir had come down with it," Mr. Tyson said. "The pigs there gave it to sheep about seven kms away, and the sheep had been transported around for between two and three weeks before we knew they had the disease. There were 20,000 of them, and they went everywhere. That's been the real horror, and that's what's made all the work a catch-up job ever since." 

That's where officials had to start. But farmers blame the disease's continued spread on the government, arguing that its policy of refusing to vaccinate healthy animals on the grounds, in part, that vaccinated animals are ineligible for export has clearly failed. The govt blames the farmers and other rural workers, saying they are neglecting to disinfect themselves and their equipment properly against foot- and-mouth disease.

"It's been spread by movements of people and vehicles and machinery," said Paula Harrington, a spokeswoman for the Department for the Environment, Food and Rural Affairs. To prevent what would be a disastrous blow to Britain's pig industry, she said, the government recently designated a section of North Yorkshire a so-called Biosecurity Intensification Area, meaning the farmers there are subject to tougher movement and disinfection regulations. 

Among other things, govt inspectors are being stationed on milk tankers that collect milk from dairy farms, to make sure the drivers properly disinfect the trucks before and after each visit. Farmers are also required to remove clothes they wear when handling livestock if they intend to leave their property. "These restrictions were voluntary, and clearly they didn't work," Ms. Harrington said. "Now they're mandatory."

Farmers like Mr. Morris are bitter about the implications of the government's accusations, saying that it is the government workers — the inspection teams, the haulers who transport the carcasses, the disinfection crews — who flout the regulations, allowing blood and urine from infected animal carcasses to seep out onto busy roads, for example. 

There is no question that the farmers here take the disease seriously. In agreeing to discuss their situation, for instance, Mr. Morris and his nearest neighbors, Gillian and Phillip Bromwell, arranged to meet by the side of the road, just past the sign on the Bromwells' fence warning of the foot-and-mouth restrictions.

When they were joined by a fourth farmer, Edwin Harris, it became clear how strange their lives had become. They could not meet at any of their houses, they said, because of fears of spreading the disease. Nor did they feel comfortable going to a nearby pub, or even when it became cold and damp sitting together in Mr Morris's car. As a result, the whole conversation took place next to the road. It was the first time in weeks that Mr Morris had seen the Bromwells, though he lives right next door. 

Since his animals came down with foot-and-mouth, he said, he has felt like a pariah. "I don't want to go into Crickhowell," he said, referring to the town that is just up the road, "in case people say, `I don't want to touch him.' " What jars most here these days is the eerie silence in a place that usually resounds with the gruff bleating of sheep. Now there is just wind, and traffic — mainly from government vehicles connected with the huge killing, cleanup and transporting operation. 

All around, businesses are floundering. At Llanwenarth House, a hotel in a 16th-century manor in nearby Govilon, a "for sale" sign sits outside, and the hotel, usually full this time of year, stands nearly empty. The hotel has been run for more than 20 years by Bruce and Amanda Weatherill; business has been so bad since foot-and-mouth struck that they can no longer sustain it. 

While farmers whose animals have been slaughtered are being compensated by the government, there has been no compensation for other businesses, like hotels, stores or pubs. In a region dependent on tourism, that has hit Wales especially hard. "The government doesn't seem particularly interested in the countryside," Mr. Weatherill said. 

It is a view that many of his neighbors share. So does the opposition Conservative Party, which has the fervent support of many rural Britons, though it has failed so far to transform countryside outrage into effective political capital. 

Mr. Bromwell, Mr. Morris's neighbor, said he felt from the beginning that Mr. Blair was putting too positive a spin on what has turned out to be a drawn-out epidemic. "Politicians don't like bad news around election time," he said. "Anybody on the ground can see what's really happening."


\12 Future of diseases

As we make headway against the old diseases, the ticking time bomb in the next century will be the new microbes--natural and man-made Remember in the movie Aliens when Hudson asked, "Is this gonna be a stand-up fight, sir, or another bug hunt?" Well, the 21st century is going to be one hell of a bug hunt. There's no doubt that eerie new infectious diseases will appear, and the struggles against some of them will make the fight against the AIDS virus look like the opening battle of a war. Of course, by then there will probably be a vaccine for AIDS, and the shot will cost a few dollars or be given for free. Today new viruses are coming out of nature and "discovering" the human species, while in hospitals and in jungle clinics exceedingly powerful mutant bacteria are emerging that can't be treated with antibiotics. In the past decade, at least 50 new viruses have appeared, including Ebola Ivory Coast, Andes virus, hepatitis G, Fakeeh, Pirital, Whitewater Arroyo, Hendra virus, Black Lagoon virus, Nipah and Oscar virus. This summer West Nile virus showed up for the first time in the western hemisphere, when it was discovered in New York City. Viruses are moving into the human species because there are more of us all the time. From a virus' point of view, we look like a free lunch that's getting bigger. My grandfather was born in 1899, on the eve of a new century, when there were 1.5 billion people on earth. He died in 1995, and by then there were almost 6 billion people. Thus in one lifetime the population quadrupled, and it's heading for 9 or 10 billion. In nature, when populations soar--and become densely packed--viral diseases tend to break out; then the population drops. This is nature's population-control mechanism. It happens with rodents, insects and even plants. There is no reason to think the human race is exempt from the laws of nature. Giving these laws an extra push will be the rise of tropical megacities--huge, densely packed cities in less developed nations. A U.N. study predicts that by the year 2015, there will be 26 extremely big cities on the planet, and 22 of them will be in less developed regions. The megacities will include Bombay (26 million people by 2015), Lagos (24 million), Dhaka (19 million) and Karachi (19 million). By 2030, almost 60% of the world's people will live in urban areas. By then, some megacities could have 30 million or more people. The population of California today is 35 million. Take all of California, cram those people into one city, remove most doctors and medical care, take away basic sanitation and hygiene, and what you have is a ticking biological time bomb. Now make eight or 10 such bombs and plant them around the world. Now wire the bombs together. People travel rapidly by airplane, carrying diseases with them as they fly. The human species has become a biological Internet with fast connections. The bionet will only get faster in the next century--that is, more people will travel by air more often, increasing the speed at which diseases move. If a tropical megacity gets hit with a new virus, New York City and Los Angeles will see it days or weeks later. Then there are the biological weapons. The 20th century saw the creation of great weapons based on the principles of nuclear physics; the 21st century will see great weapons based on the knowledge of DNA and the genetic code. During the 1980s, the Soviet Union used rudimentary genetic engineering to create incurable strains of Black Death (bubonic plague) that were resistant to drugs. This biotech Black Death was loaded into missile warheads aimed at the U.S. As biotechnology becomes more supple and powerful and as the genetic code of more organisms is unraveled, biologists will learn how to mix genes of different bugs to create deadly, unnatural strains that can be turned into deadly, effective weapons.

Scientists have found a type of bacterium that is virtually indestructible. It's called Deinococcus radiodurans ("terrible berry that survives radiation"). This bug can live in a blast of gamma rays that is the equivalent of thousands of lethal human doses--radiation so strong it cracks glass. Scientists have found "dead" radiodurans spores in Antarctica that have baked in UV light for 100 years. Yet when placed in a nutrient bath, the bug's DNA reassembles itself and proliferates. If radiodurans genes could be put into anthrax, they might produce an anthrax that's virtually impossible to kill. From a bioweaponeer's point of view, the future is bright. Biological weapons are a disgrace to biology. Most biologists haven't wanted to talk or even think about them. For years leading U.S. biologists were assuring themselves and the public that bioweapons don't work and aren't anything to worry about. It was a naive dream from the childhood of biology. The physicists lost their innocence when the first nuclear bomb went off in 1945. The biologists will lose their innocence when the first biological weapon spreads through the human species. Yet the 20th century lived with the nuclear bomb, and there was great economic and scientific progress and much human happiness. The same can be true in the next century. Our tools for defending against new diseases are improving all the time. Vaccines are getting better. Drugs to fight bugs are advancing. And new devices are coming that will identify an infectious agent in seconds. Our greatest weapon against the bugs will always be our mind. Dr. Jeffrey Koplan, director of the Centers for Disease Control and Prevention, predicts that in the end, the fight will come down to the same old sleuthing methods that disease hunters have always used to find bugs and stop them. "Shoe-leather epidemiology" is what Koplan calls it. "You wear out your shoes investigating an outbreak," he says. "You go around identifying the source of the disease and figuring out how it's being spread, and then you remove the source. Even if it's Vibram-soled epidemiology, we'll do it." No matter how great our technology, we'll still have to go mano a mano with the microbes. We may not completely win the 21st century bug hunt, but I am confident that we won't lose it. TEN TOP CAUSES OF DEATH AND DISABILITY

Projections by the Harvard School of Public Health
 19902020 1 Respiratory infections Heart disease 2 Diarrheal diseasesSevere depression 3 Complications of birth Traffic accidents 4 Severe depression Stroke 5 Heart disease Chronic pulmonary disease 6 StrokeRespiratory infections 7 TuberculosisTuberculosis 8 Measles War injuries 9 Traffic accidents Diarrheal diseases 10 Congenital anomaliesHIV/AIDS

By Richard Preston, best-selling author of The Hot Zone and The Cobra Event, is working on a book about microscopic life forms

