CHAPTER 7
INFECTIOUS DISEASES

Pursue him to his house, and pluck him thence;
Lest his infection, being of a catching nature,
Spread further.

—William Shakespeare, Coriolanus, 1608

Infectious (contagious) diseases are caused by microorganisms—viruses, bacteria, parasites, or fungi—transmitted from one person to another through casual contact, such as influenza; through bodily fluids, such as HIV (human immunodeficiency virus); or via contaminated food, air, or water supplies. Infectious diseases also may spread by vectors of disease such as insects or arthropods that carry the infectious agent.

Infectious diseases are a leading cause of death worldwide, according to the World Health Organization (WHO). Not long ago, the U.S. government and medical experts believed that widespread use of vaccines, antibiotics, and public health measures had effectively eliminated the public health threat of infectious diseases. Throughout the world, however, new and rare diseases are emerging, and old diseases are resurfacing. Some of these infections reflect changes associated with increasing population, growing poverty, urban migration, drug-resistant microbes, and expanding international travel.

The mistaken belief that infectious diseases were problems of the past prompted the governments of many countries, including the United States, to neglect public health programs aimed at preventing and treating infectious disease. By 1994, however, enough troubling new diseases had arisen and old ones recurred that a federal commission recommended that the United States spend $125 million to implement a plan to respond to and contain infections.

The Centers for Disease Control and Prevention (CDC) tracks certain infectious diseases ("notifiable diseases") for the U.S. Public Health Service (PHS). Physicians, clinics, and hospitals must report any occurrences of these diseases to the CDC each week. Table 7.1 shows the infections tracked in 2001.

MOST FREQUENTLY REPORTED DISEASES

In 2001 the three most frequently reported infectious diseases in the United States were chlamydia (783,242 cases—the highest it has been since voluntary reporting began in the mid 1980s), gonorrhea (361,705 cases), and acquired immune deficiency syndrome (AIDS; 41,868 cases), all sexually transmitted diseases. The remaining notifiable infectious diseases in the top 10 were as follows:

• Salmonellosis—a foodborne disease causing fever and intestinal disorders (40,495 cases)
• Syphilis, all stages—a sexually transmitted disease that occurs in three stages; it can be congenital (an infant can be born with the disease) (32,221 cases)
• Varicella (chicken pox)—a disease (usually of childhood) marked by a vesicular rash on the face and body caused by the herpes varicella zoster virus (22,536 cases)
• Shigellosis—foodborne and waterborne dysentery (20,221 cases)
• Lyme disease—a disease spread by ticks (17,029 cases)
• Tuberculosis—an airborne disease that usually affects the lungs but also can affect the bones and other organs (15,989 cases)
• Hepatitis A—a foodborne and waterborne disease causing inflammation of the liver (10,609 cases)

Table 7.2 shows the number of cases of these and other notifiable diseases reported to the CDC each month in 2001.

Resistant Strains of Bacteria

Antibiotics generally have been considered "miracle drugs" that control or cure many bacterial infectious diseases. However, in the last decade almost all major bacterial infections in the world are becoming increasingly resistant to the most commonly prescribed antibiotic treatments mainly because of repeated and improper uses of antibiotics, according to the CDC. Decreasing inappropriate antibiotic use is the best way to control this resistance.

Bacteria such as pneumococcus, which causes pneumonia and children's ear infections—diseases long considered common and treatable—are evolving into strains that are proving to be untreatable with commonly used antibiotics. Pneumococcal bacteria cause many hundreds of thousands of cases of pneumonia, bacterial meningitis (inflammation of the tissue covering the brain and spinal cord), and almost half of the more than twenty-five million annual visits to American pediatricians for otitis media (middle ear infections). Since the 1980s, national rates of penicillin resistance have soared from less than 5 percent of patients treated to more than 30 percent of patients treated in 1996.

Between February and June 1997, 1,047 strains of pneumococcus obtained from thirty-four hospitals in the United States and Canada were tested for susceptibility to nineteen antibiotics. Among the 845 U.S. samples, only 56 percent were fully susceptible to penicillin, another 28 percent were moderately susceptible, and 16 percent were fully resistant.

To treat patients with penicillin-resistant pneumococcus infections, physicians use a combination of other antibiotics, such as vancomycin, imipenem, and rifampin for resistant pneumonia and clindamycin or cefuroxime for ear infections. One of the national health goals for 2010 is to achieve 90 percent coverage of non-institutionalized adults aged sixty-five years and older for both influenza and pneumococcal vaccinations. In 2000 the U.S. Advisory Committee on Immunization Practices added adults aged fifty to sixty-four years to the universal recommendations for influenza vaccination. Many public health professionals are advocating widespread use of the pneumococcal vaccine in the hope that it will produce "herd immunity"—when a large proportion of the population is immune, the likelihood of person-to-person spread is so small that the disease does not proliferate and even nonimmune individuals are protected from disease.

Increase in Escherichia Coli Infection Caused by Antibiotics

On July 25, 2002, a study funded by the National Institutes of Health (NIH) reported increasing rates of Escherichia coli (E. coli) infection attributable to antibiotic use among premature infants. The study, published in the New England Journal of Medicine (vol. 347, no. 4), looked at the medical records of more than 5,000 babies born throughout the United States and found that E. coli infection rates had more than doubled from three per 1,000 births to seven per 1,000 births. E. coli and group B streptococci are bacteria that frequently exist in the gastrointestinal tract and cause no medical problems. If, however, they are passed at birth from a pregnant mother to

her unborn child, then the infant's immune system may be unable to effectively combat the infection.

The study found that rates of group B strep infection among infants decreased by almost 75 percent during the 1990s, probably in response to increasing use of antibiotics during labor and delivery (the birthing process) to prevent mother-to-infant spread of the infection. The antibiotic most often used was amoxicillin, a drug that combats strep but does not harm E. coli. As a direct result of the effort to reduce strep infections, E. coli infections increased. The researchers observed that E. coli had surpassed group B strep as the most commonly occurring infection among premature infants. This finding is considered troubling because E. coli infection is potentially more dangerous than strep infection.

EDUCATING PHYSICIANS AND PATIENTS ABOUT APPROPRIATE USE OF ANTIBIOTICS.

According to the CDC, antibiotic resistance is among the most urgent public health problems in the world. In 1995 the CDC Division of Bacterial and Mycotic Diseases began a national campaign to reduce antimicrobial resistance by encouraging appropriate use of antibiotics. In 1999 the CDC worked with several medical professional societies to develop educational programs for medical students, physicians, and patients. In a published statement, Dr. Richard Besser, medical director of the CDC's National Campaign for Appropriate Antibiotic Use, called for physician and public support to tackle the problem. Dr. Besser asserted:

The biggest problem is inappropriate prescribing of antibiotics. Up to 40 percent of antibiotics prescribed in doctors' offices are for viral infections, which are not treatable with antibiotics. There are many reasons for this, including demand from patients, time pressure on physicians, and diagnostic uncertainty. The patient wants to get back to work or get their child back to school, and the doctor wants the patient to feel satisfied with treatment. The result is over-prescribing of antibiotics, resulting in the development of resistant bacteria. The best way to combat this practice is to educate the physicians and the public to decrease both demand and over-prescribing. In addition, providing clinicians with better means of diagnosing respiratory infections may remove some of the uncertainty that promotes over-prescribing.

In February 2004 the CDC reported that pressure from the parent makes a difference to the pediatrician's prescribing method. One study showed that doctors prescribe antibiotics 65 percent of the time if they feel that parents expect them, but only 12 percent of the time if they feel parents do not expect them. This emphasizes the need for public awareness and understanding of the need to take part in preventing antibiotic resistance. Consequences of failure of antibiotics to treat formerly treatable illnesses could be dire: longer-lasting illnesses, more doctor visits or longer hospital stays, the need for more expensive and toxic medications, and even death.

PREVENTION THROUGH IMMUNIZATION

Many infectious diseases can be prevented by immunizations. According to the National Immunization Program of the CDC, there are fourteen diseases that can be prevented by vaccination and for which vaccinations are recommended. Some other diseases are preventable by vaccination, but vaccination is not recommended for everyone because the risk of contracting these diseases is not great enough to warrant widespread immunization. They include anthrax, meningococcal infection, rotavirus, and smallpox. (See Figure 2.1 in Chapter 2 for a schedule of childhood immunizations and Figure 7.1 for immunizations recommended for adolescents and adults.) The fourteen vaccine-preventable diseases are as follows:

• Diphtheria—This bacterial infection causes potentially fatal respiratory infections that are treated with antibiotics. People diagnosed with diphtheria are isolated until cultures are negative to prevent the spread of the disease.
• Haemophilus influenza type b (Hib)—This bacterial infection causes respiratory infections and other diseases, such as meningitis.
• Hepatitis A—The virus is spread through fecal (stool) or oral routes, though it may also be transmitted via blood or sexual contact. Outbreaks usually occur from contaminated food and water; military workers, children in day care centers, and their care providers are considered at high risk.
• Hepatitis B—It is transmitted by blood, sexual contact, or from mother to unborn child; intravenous drug users, gay men, and health care workers are at high risk.
• Influenza (flu)—This viral infection produces sudden fever, muscle aches, and respiratory infection symptoms.
• Lyme Disease—This bacterial disease is spread by infected ticks and produces fever, headache, joint and muscle pain, swollen lymph nodes, and a distinctive circular skin rash. It may be treated with antibiotics or prevented by vaccine.
• Measles—This highly contagious viral disease produces red circular spots on the skin.
• Mumps—This highly contagious viral disease produces swelling of the parotid glands.
• Pertussis (whooping cough)—This bacterial infection causes illness marked by spasms of coughing.
• Pneumococcal—This bacteria causes pneumonia, an inflammation of the lungs.
• Poliomyelitis (polio)—A viral disease, polio causes fever, atrophy (wasting) of skeletal muscles, and paralysis.
• Rubella (German measles)—This viral infection is usually mild in children but can seriously harm an unborn child when contracted by a woman early in her pregnancy.
• Tetanus—Bacteria produce a toxin that causes victims to have painful muscle spasms.
• Varicella (chickenpox)—This is a highly contagious viral disease marked by skin eruptions of fluid-filled lesions that itch.

Until the 1960s, for example, poliomyelitis (polio) was a serious threat to children, adolescents, and even adults. After the discovery of vaccines to prevent this disease, massive worldwide immunization programs were carried out, and by 1994 an international health commission declared that indigenous (in-country) transmission of wild (not developed in laboratories or contained in vaccines) poliovirus had been stopped in the Western hemisphere. The last reported case of polio documented in the United States was 1979, and the goal for global eradication is 2005.

The incidence of polio also has decreased greatly in other parts of the world. At one time, polio killed or crippled 500,000 people worldwide every year. The number of reported cases worldwide has decreased dramatically because most governments had made great strides toward tracking new infections and vaccinating children against the disease. The last isolate of type 2 polio was found in India in 1999.

INFLUENZA

Influenza (the flu) is a contagious respiratory disease caused by a virus. When a person infected with the flu sneezes, coughs, or even talks, the virus is expelled in droplets into the air and may be inhaled by anyone nearby. It also can be transmitted by direct hand contact. The flu primarily affects the lungs, but the whole body experiences symptoms. The infected person usually becomes acutely ill, with fever; chills; weakness; loss of appetite; and aching muscles in the head, back, arms, and legs. The person with influenza infection also may have a sore throat, a dry cough, nausea, and burning eyes. The accompanying fever increases quickly—sometimes reaching 104 degrees—but usually subsides after two or three days. Influenza leaves the patient exhausted.

For healthy individuals, the flu is typically a moderately severe illness, with most adults and children back to work or school within a week. For the very young, the very old, and people who are not in good general health, however, the flu can be very severe and even fatal. Complications such as secondary bacterial infections may develop, taking advantage of the body's weakened condition and lowered resistance. The most common bacterial complication is pneumonia, but sinuses, bronchi (lung tubes), or inner ears also can become secondarily infected with bacteria. Less common but very serious complications include viral pneumonia, encephalitis (inflammation of the brain), acute renal (kidney) failure, and nervous system disorders. These complications can be fatal.

Who Gets the Flu?

Anyone can get the flu, especially if there is an epidemic in the community. (An epidemic is a period when the number of cases of a disease exceeds the number expected based on past experience.) During an epidemic year, 20–30 percent of the population may contract influenza. Not surprisingly, people who are not healthy are considered at high risk for flu and its complications. The high-risk population includes those who have chronic lung conditions, such as asthma, emphysema, chronic bronchitis, tuberculosis, or cystic fibrosis; those with heart disease, chronic kidney disease, diabetes, or severe anemia; people residing in nursing homes; those older than age sixty-five years; and some health care workers.

Vaccines

Influenza can be prevented by inoculation with a current influenza vaccine, which is formulated annually so that it contains the influenza viruses expected to cause the flu the next year. The viruses are killed or inactivated to prevent those who are vaccinated from getting influenza from the vaccine. After being immunized, the person develops antibodies to the influenza viruses. The antibodies are most effective after one or two months. High-risk people should be vaccinated early in the fall because peak flu activity usually occurs around the beginning of the new calendar year. The flu season usually runs from October to May and peaks in December and January.

Each year's flu vaccine protects against only the viruses that were included in its formulation. If another strain of flu appears, people still can catch the new strain although they were vaccinated for the primary expected strains. The 2003–2004 flu season was one of the worst in recent memories, with a nationwide shortage of vaccine early in the season, a time when the virus was peaking, and children were dying from the illness (at least 142 individuals under eighteen years old).

Most people have little or no reaction to the vaccine; 25 percent may have a swollen, red, tender area where the vaccination was injected. Children may suffer a slight fever for twenty-four hours or have chills or a headache. Those who already suffer from a respiratory disease may experience worsened symptoms. Usually, these reactions are temporary. Because the egg in which the virus is grown cannot be completely extracted, people with egg protein allergies should consult their physicians before receiving the vaccine and, if vaccinated, should be closely observed for any indications of an allergic reaction.

Avian Influenza

Avian influenza, or bird flu, is an infectious disease of birds caused by type A strains of the influenza virus. The disease, which was first identified in Italy more than one hundred years ago, occurs worldwide. An outbreak of bird flu has affected bird populations in countries throughout Asia. It has affected humans as well—as of March 2004, the death toll from avian influenza was twenty-four people. According to the CDC, it is believed that the cases in humans resulted from contact with infected birds or surfaces contaminated with excretions from infected birds. The disease usually only affects birds and pigs; the first documented infection of humans occurred in Hong Kong in 1997.

Because these viruses usually do not infect humans, there is little or no immune protection against them. If an avian influenza virus infected people and gained the ability to spread easily from person to person an "influenza pandemic" could begin. To help prevent this from occurring, sick and exposed birds are killed and infected people are treated and isolated.

TUBERCULOSIS (TB)

Tuberculosis (TB), a communicable disease caused by the bacterium Mycobacterium tuberculosis, is spread from person to person through the inhalation of airborne particles containing M. tuberculosis. The particles, called droplet nuclei, are produced when a person with infectious TB of the lungs or larynx forcefully exhales, such as when coughing, sneezing, speaking, or singing. These infectious particles can remain suspended in the air and can be inhaled by someone sharing the same air.

Most TB (approximately 85 percent) occurs in the lungs (pulmonary TB). Risk of transmission is increased where ventilation is poor and when susceptible people share air for prolonged periods with a person who has untreated pulmonary TB. The disease, however, may occur at any site of the body, such as the larynx, the lymph nodes, the brain, the kidneys, or the bones. This type of TB infection, which occurs outside the lungs, is referred to as extrapulmonary. With the exception of laryngeal TB, people with extrapulmonary TB are usually not considered infectious to others.

TB does not develop in everyone infected with the bacteria. In the United States, about 90 percent of infected people never show symptoms of TB. Nevertheless, 5 percent of people infected develop the disease in the first or second year after infection. Another 5 percent show symptoms later in life. For people with compromised immune systems, the risk of developing TB is much higher. For example, 8 percent of those infected with both TB and HIV (the virus that causes AIDS) develop full-blown TB symptoms within a year.

Ancient Enemy and Continuing Threat

Each year, two million people worldwide die from TB, according to the WHO, and more than eight million people become sick with TB annually. Overall, one-third of the world's population is infected with the TB bacillus. This has increased dramatically since the HIV/AIDS epidemic swept through many countries. In 1992 the WHO estimated that at least four million adults worldwide—primarily in sub-Saharan Africa, Latin America, and Asia—had been infected with both AIDS and M. tuberculosis. TB accounts for 11 percent of deaths from AIDS worldwide.

After several decades of decline, TB made a comeback in the United States in the late 1980s and early 1990s. From 1985 to 1993, more than 64,000 new TB cases were reported. In 1992 the CDC reported 26,673 cases of TB, up from 22,201 in 1985. Since 1992 the number of cases has declined steadily, and by 2001 it had decreased to 15,989. (See Table 7.3.)

During 2003, a total of 14,871 TB cases were reported to the CDC, which was a 1.4 percent decrease in cases and a 1.9 percent decline in the rate from 2002. This decline is attributed to new public health programs that monitor the complicated drug-treatment protocols for patients with TB. The success of prevention and treatment programs varies depending on the location and population. Despite these overall national declines in TB incidence, substantial disparities exist between rates in the majority of U.S. residents and rates in two U.S. populations—foreign-born people and U.S.-born non-Hispanic blacks, both of which experience higher rates of TB.

Treatment has become increasingly difficult because new strains of multidrug-resistant (MDR) TB have developed. If the disease is not properly treated or if treatment is not completed, some TB can become resistant to drugs, making it much harder to cure. In 2003 MDR TB was more common in foreign-born people (1.2 percent) than in U.S.-born residents (0.6 percent). According to the CDC, in 2000, 80.8 percent of patients with TB completed therapy in one year or less, and 92.2 completed therapy overall.

The increase in TB cases in the 1980s and the emergence of antibiotic-resistant strains of TB prompted Congress to increase the NIH budget for TB research. The research budget of the National Institute of Allergy and Infectious Diseases (NIAID) soared from $3.1 million in 1991 to $35 million in 1996. In 2001 NIAID budgeted nearly $10 million for TB vaccine research and also funded basic research, epidemiology research, drug development and treatment efforts, and training to improve the number and skills of researchers and health care practitioners.

March 24 of each year has been designated "World TB Day" by NIAID to recognize the global threat to health posed by the disease. If the disease is not controlled and treatment is not improved, it is estimated that between 2002 and 2020, approximately one billion people will be newly infected with TB, more than 150 million people will get sick from TB, and thirty-six million will die of TB, according to the WHO.

HIV/AIDS

AIDS is the late stage of an infection caused by HIV, a retrovirus that attacks and destroys certain white blood cells, which weakens the body's immune system and makes it susceptible to infections and diseases that ordinarily would not be life threatening. AIDS is considered a bloodborne, sexually transmitted disease because HIV is spread through contact with blood, semen, or vaginal fluids from an infected person.

Around the World

AIDS and HIV were virtually unknown before 1981, when testing and reporting of the disease became mandatory, but awareness grew as the annual number of diagnosed cases and deaths steadily increased. By the end of 2003, approximately forty million people worldwide were estimated to be living with HIV/AIDS, according to the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the WHO. Of those infected, 37.5 million were adults and about 2.5 million were children younger than age fifteen. Seventy percent of people infected with HIV lived in sub-Saharan Africa. In 2003, an estimated 26.6 million people in this region were living with HIV, including the 3.2 million who became infected during the previous year. AIDS killed approximately 2.3 million people in 2003 there. Unlike women in other regions in the world, African women are much more likely (about twice as much) than men to be infected with HIV.

Since the epidemic began, 21.8 million people have died of AIDS; an estimated three million died in 2003 alone. Of those, approximately 700,000 were children younger than fifteen years of age.

In the United States

According to the CDC, by December 2002 there were 384,906 people in the United States living with AIDS. Of all cases of HIV infection in 2001, 39 percent progressed to AIDS within twelve months after the diagnosis of HIV infection. Diagnoses of HIV/AIDS in the United States increased 3.2 percent from 2001 (25,643) through 2002 (26,464). However, from 1998 to 2002 the estimated number of deaths among people with AIDS declined 14 percent as a result of highly active antiretroviral therapy that became widespread during 1996.

In 2002, 71 percent of all individuals with HIV in the reporting areas in the United States were male. However, worldwide, AIDS was more evenly divided between men

and women. Table 7.4 shows the number of AIDS cases reported in the United States as of December 2002, by age category, exposure category, and sex. Table 7.5 provides comparable information about cases of HIV infection. Figure 7.2 shows the number of AIDS cases, deaths, and people living with AIDS between 1985 and 2002.

How Is AIDS Spread?

HIV/AIDS is not transmitted through casual contact with an infected person. The CDC has identified several behavioral risk factors that greatly increase the likelihood of a person's chances of being infected. Table 7.6 shows the estimated numbers of those diagnosed with AIDS by year of diagnosis and selected characteristics of patients, including the way in which they contracted the disease.

More than twenty years of research and observation have definitively concluded that the HIV infection can only be transmitted by the following methods:

• By oral, anal, or vaginal sex with an infected person; worldwide, heterosexual sex is the most common mode of transmission

• By sharing drug needles or syringes with an infected person
• From an infected mother to her baby at the time of birth and possibly through breast milk
• By receiving a transplanted organ or bodily fluids, such as blood transfusions or blood products, from an infected person

Because avoiding these methods of transmission virtually eliminates the possibility of becoming infected with HIV, unlike some other infectious diseases, AIDS is considered almost entirely preventable.

High concentrations of HIV have been found in blood, semen, and cerebrospinal fluid. Concentrations one thousand times less have been found in saliva, tears, vaginal secretions, breast milk, and feces. There have been no reports, however, of HIV transmission from saliva, tears, or human bites. In fact, in 1995 the National Institute of Dental Research in Bethesda, Maryland, reported that a small protein found in human saliva actually blocks the virus from entering the system.

Opportunistic Infections

Once HIV has destroyed the immune system, the body can no longer protect itself against bacterial, fungal, parasitic, or viral agents that take advantage of the compromised condition, causing opportunistic infections (OIs). OIs are illnesses caused by organisms that would not normally harm a healthy person. Because the patient is considered to have AIDS if at least one OI appears, OIs

are considered "AIDS-defining events." OIs are not the only AIDS-defining events; the diagnosis of malignancies such as Kaposi's sarcoma, Burkitt's lymphoma, invasive cervical cancer, and primary brain lymphoma also are considered AIDS-defining events.

One of the most common opportunistic infections is Pneumocystis carinii pneumonia, a lung infection caused by a fungus. Other infections to which patients with AIDS are susceptible are toxoplasmosis (a contagious disease caused by a one-cell parasite); oral candidiasis (thrush); esophageal or bronchial candidiasis; extrapulmonary cryptococcosis; pulmonary TB; extrapulmonary TB; Mycobacterium avium complex (MAC), a serious bacterial infection that can occur in one part of the body, such as the liver, bone marrow, and spleen, or can spread throughout the body; and cytomegalovirus disease (CMV), a member of the herpes virus group.

Treatment of AIDS

The first drug thought to delay symptoms was zidovudine (earlier known as AZT, later as ZDV), but its effects have been found to be temporary at best. Several other drugs work on the same principle as ZDV, but until the advent of protease inhibitors (PIs), a new class of drugs that became available in the mid-1990s, it seemed that there was no way of stopping HIV. Protease inhibitors appear to keep HIV from reproducing, unlike ZDV and similar drugs, which help keep HIV out of the cell's chromosomes. Even if the PIs are not entirely effective long term in reducing patients' viral "loads," they have improved patients' prospects simply by creating more roadblocks for HIV. Unfortunately, HIV mutates so rapidly that it eventually becomes resistant to most drugs when they are used alone. Even if a cure is never found, new and better drugs used in various combinations may make HIV infection a chronic but manageable disease, much like diabetes.

Treatment recommendations change rapidly in response to the development of new drugs and clinical trials indicating the effectiveness of different combinations of antiretroviral drugs. Researchers are acting quickly to develop new mixtures of the recently approved and older drugs. Because HIV mutates to resist any drug it faces,

including all PIs, researchers have found that varying the combination of drugs prescribed can "fool" the virus before it has time to mutate.

COMPLICATIONS, COSTS, AND SIDE EFFECTS OF TREATMENT.

Patients undergoing therapy with these new drugs or drug combinations must be highly disciplined. For instance, Crixivan must be taken on an empty stomach, every eight hours, not less than two hours before or after a meal, and with large amounts of water to prevent development of kidney stones. Patients also must be careful to never skip doses of Crixivan; otherwise, HIV will quickly grow immune to its effect. (Crixivan has been found to generate cross-resistance, meaning it made patients resistant to other PIs.) Invirase must be taken in large doses. Norvir must be carefully prescribed and administered because it interacts negatively with some antifungals and antibiotics used by patients with AIDS. Because there are a variety of minor and serious risks associated with use of these drugs, patients must be closely monitored by health care practitioners.

The drug regimens are complicated, produce severe side effects in a substantial number of patients, and are costly. The cost of protease inhibitors, such as Viracept and Crixivan, ranges from $4,800 to $8,000 for a year's supply. When combined with ZDV or any of the other commonly used antiretroviral drugs—such as lamivudine (3TC), zalcitabine (ddC), didanosine (ddI), or stavudine (d4T)—the cost is approximately $18,000 per year. Lifetime treatment costs for HIV/AIDS are estimated to be about $155,000. Government programs and private insurers alike are looking for ways to pay for, and in some cases, avoid paying for, these new therapies. As Moises Agosto of the National Minority AIDS Council in Washington, D.C., noted: "We may have all these drugs approved, but if the programs can't afford them, who's going to have access to them?"

HIV and Tuberculosis

TB occurs with increasing frequency among people infected with HIV. In fact, HIV infection has become one of the strongest known risk factors for the progression of TB from infection to disease. A 1996 report from the Conference on Retroviruses and Opportunistic Infections concluded that the decline in CD4+ T-cells is greater in patients with HIV who develop TB than in those who remain free of the disease. In some geographic areas as many as 58 percent of people with TB were HIV-positive.

Of the many diseases associated with HIV infection, TB is one of the few that is transmissible, treatable, and preventable. It is important to note that HIV is a blood-borne infection and cannot be spread through air. A person with HIV who has TB can spread TB nuclei through the air, but they cannot spread HIV this way.

LYME DISEASE

Spread by the bites of infected deer ticks, Lyme disease is the most commonly reported vector-borne disease in the United States. Lyme disease is caused by the Borrelia burgdorferi organism and produces early symptoms such as skin rashes, headache, fever, and general illness; if untreated, the disease can cause arthritis and heart damage.

The CDC began to track Lyme disease in 1982, and the disease was added to the list of nationally notifiable diseases in 1990. Figure 7.3 shows the dramatic increase in the number of reported cases from 1982 to 2000. In 2000 the CDC received reports of 17,730 cases of Lyme disease from forty-four states and the District of Columbia, with the majority of cases occurring in the northeastern and north central states. In 2002, 23,763 cases of Lyme disease were reported to the CDC. Twelve states—Connecticut, Rhode Island, New Jersey, New York, Pennsylvania, Delaware, Massachusetts, Wisconsin, Minnesota, Maine, New Hampshire, and Maryland—accounted for 95 percent of the total cases reported in 2002.

In December 1998 the FDA announced approval for the world's first vaccine against Lyme disease. Doctors warned, however, that although the vaccine, LYMErix, developed by SmithKline Beecham, would help prevent Lyme disease, it would not eliminate the threat entirely. To achieve the best immunity, a person must receive a series of three shots over the course of a full year.

Because LYMErix is not 100 percent protective, the FDA warned that people still must take precautions against ticks. Wearing long-sleeved shirts and long pants, tucking pants legs into socks, and spraying the skin and/or clothing with tick repellents can keep ticks away from the skin. If a tick is found on the body, it should be removed promptly, and the affected individual should be alert for early symptoms of the disease. Immediate medical treatment is imperative to prevent long-term health damage from Lyme disease.

WEST NILE VIRUS

West Nile virus is common in Africa, West Asia, and the Middle East, and it can infect birds, mosquitoes, horses, humans, and other mammals. It is spread by bites from infected mosquitoes, and although most people who become infected have few or no symptoms, some develop serious and even fatal illnesses. The virus first was reported in the United States in 1999, and the CDC has tracked its westward spread across the United States.

According to the CDC, the presence of West Nile virus in either humans or infected mosquitoes is permanently established in the United States. Although human illness from the virus is relatively rare, the disease, which is more likely to be fatal in elderly people and young children, was responsible for the death of 264 people in 2003. The CDC advises taking precautions against mosquito bites, such as using insect repellent; wearing long pants and long-sleeved shirts treated with insect repellents; remaining indoors during dawn, dusk, and early evening, the hours when mosquitoes are most likely to bite; and removing standing water to prevent mosquitoes from laying eggs and breeding near homes and other populated buildings.

SEVERE ACUTE RESPIRATORY SYNDROME

Severe acute respiratory syndrome (SARS) is a viral respiratory illness caused by a coronavirus that first was reported in Asia in February 2003. The illness spread to more than two dozen countries in North America, South America, Europe, and Asia before the global outbreak was contained in July 2003. SARS seems to be transmitted primarily by person-to-person contact, through respiratory droplets, which travel via coughs or sneezes to the mucous membranes of other people or to surfaces that others touch. Symptoms of the disease may include high fever (over 104 degrees Fahrenheit), body aches, malaise (overall discomfort), diarrhea, and mild respiratory symptoms; after two to seven days, the infected person may develop a dry cough. The disease then progresses to pneumonia in most people.

According to the WHO, 8,098 people worldwide became sick with SARS during the outbreak, and 774 died. In the United States eight people—all of whom had traveled to parts of the world with the virus—contracted the disease.

RESPONDING TO BIOLOGIC TERRORISM: INTENTIONAL EPIDEMICS

In September and October 2001, in an unprecedented event, twenty-two letters containing Bacillus anthracis spores sent through the U.S. Postal Service caused anthrax outbreaks in seven states: Connecticut, one case; Florida, two cases; Maryland, three cases; New Jersey, five cases; New York City, eight cases (includes a case of a New Jersey resident exposed in New York City); Pennsylvania, one case; and Virginia, two cases. Five of the letters resulted in fatal cases of anthrax.

These anthrax attacks "starkly exposed the vulnerability of the United States and the rest of the world to bioterrorism," according to the NIAID. Accordingly, the organization has devoted one third of its research portfolio to accelerated programs to prevent, diagnose, and treat possible intentional epidemics. Efforts focus on "Category A" agents considered to be the worst bioterror threats (smallpox, anthrax, botulinum toxin, plague, tularemia, and hemorrhagic fever viruses such as Ebola) and on Category B and C priority agents that also pose significant threats to human health.