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). The CDC defines a notifiable disease: "A notifiable disease is one for which regular, frequent, and timely information regarding individual cases is considered necessary for the prevention and control of the disease." The list of nationally notifiable diseases is revised periodically. For example, a disease might be added to the list as a new pathogen (an organism that causes disease) emerges, or a disease might be deleted as its incidence declines. Physicians, clinics, and hospitals must report any occurrences of these diseases to the CDC each week. Table 7.1 shows the nationally notifiable infectious diseases tracked in 2006.

MOST FREQUENTLY REPORTED DISEASES

Among the CDC's notifiable diseases the three most frequently reported infectious diseases in the United States in 2003 were chlamydia (877,478 cases—the highest it has been since voluntary reporting began in the mid-1980s), gonorrhea (335,104 cases), and acquired immune deficiency syndrome (AIDS; 44,232 cases), all sexually transmitted diseases. The remaining notifiable infectious diseases in the top ten were as follows:

• Salmonellosis—a foodborne disease causing fever and intestinal disorders (43,657 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) (34,270 cases)
• Shigellosis—foodborne and waterborne dysentery (23,581 cases)
• Lyme disease—a disease spread by ticks (21,273 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 (20,948 cases)
• Giardiasis—a common protozoal infection of the small intestine, spread via contaminated food and water and direct person-to-person contact (19,709 cases)

• Tuberculosis—an airborne disease that usually affects the lungs but also can affect the bones and other organs (14,874 cases)

Table 7.2 shows the number of cases of these and other notifiable diseases reported to the CDC each month in 2003.

RESISTANT STRAINS OF BACTERIA

Antibiotics generally have been considered "miracle drugs" that control or cure many bacterial infectious diseases. However, during the last decade nearly all major bacterial infections in the world have become increasingly resistant to the most commonly prescribed antibiotic treatments, primarily because of repeated and improper uses of antibiotics. 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% of patients treated to more than 30% of patients treated in 1996 (Jay C. Butler et al, "The Continued Emergence of Drug-Resistant Streptococcus Pneumoniae in the United States: An Update from the Centers for Disease Control and Prevention's Pneumococcal Sentinel Surveillance System," Journal of Infectious Diseases, vol. 174, no. 5, November 1996).

Investigators from the Department of Microbiology—a collaborative operation between Toronto Medical Laboratories and the Mount Sinai Hospital at the University of Toronto, Canada—made an even more alarming projection of pneumococcal resistance to penicillin in the United States from 2000 to 2004. The investigators developed a mathematical model that predicted that doubly resistant strains would increase from 8.6% in 1996 to an estimated 40.6% in 2004 (Allison McGeer and Donald E. Low, "Is Resistance Futile?" Nature Medicine, vol. 9, no. 4, April 2003, http://www.nature.com/nm/journal/v9/n4/full/nm0403-390.html).

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% coverage of noninstitutionalized adults age sixty-five and older for both influenza and pneumococcal vaccinations. In 2000 the U.S. Advisory Committee on Immunization Practices added adults age fifty to sixty-four 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), examined the medical records of more than five thousand babies born throughout the United States and found that E. coli infection rates had more than doubled from three per one thousand births to seven per one thousand 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% 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, an antibiotic 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.

Addressing the prevalence of infection attributable to antibiotic use, an April 2006 report from the National Institute of Allergy and Infectious Diseases (NIAID is one of the National Institutes of Health) asserted that antimicrobial resistance is driving up health care costs, increasing the severity of disease, and increasing mortality rates from selected infections. The institute found that more than 70% of the bacteria that cause hospital-acquired infections were resistant to at least one of the antibiotics most frequently used to treat them. Patients infected with antibiotic-resistant organisms were more likely to have longer hospital lengths of stay and require treatment with medications that were less effective, more toxic, and more costly ("The Problem of Antimicrobial Resistance," National Institute of Allergy and Infectious Diseases, http://www.niaid.nih.gov/factsheets/antimicro.htm).

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% of antibiotics prescribed in physicians' offices are for viral infections, which are not treatable with antibiotics. There are many reasons for this, including demand from patients, time pressures on physicians, and diagnostic uncertainty. Patients want to get back to work or get their children back to school, and physicians want their patients 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 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 parents makes a difference in the pediatrician's prescribing method. One study funded by a grant from the Robert Wood Johnson Foundation showed that doctors prescribe antibiotics 65% of the time if they feel that parents expect them, but only 12% of the time if they feel parents do not expect them (Rita Mangione-Smith et al., Presentation of UCLA Study at the May 6, 2002, Pediatric Academic Societies, Baltimore, MD). A study published in the October 2005 issue of the Journal of the American Academy of Nurse Practitioners found that nurse practitioners and physicians continue to prescribe inappropriate antibiotics to patients with viral upper-respiratory tract infections, a practice that may lead to increased rates of antimicrobial resistance. The researchers also found that highly marketed broad-spectrum antibiotics are being prescribed excessively to patients with diagnoses of viral illnesses despite the fact that it is well accepted that antibiotics offer no benefit in the treatment of these illnesses.

Reducing antibiotic use lowers rates of drug-resistant bacteria. Investigators in France tested two methods intended to reduce the rate of penicillin-resistant pneumococci present in kindergarten students (Didier Guillemot, Emmanuelle Varon, Claire Bernède, Philippe Weber, Laurence Henriet, Sylvie Simon, Cécile Laurent, Hervé Lecoeur, and Claude Carbon, "Reduction of Antibiotic Use in the Community Reduces the Rate of Colonization with Penicillin GNonsusceptible Streptococcus pneumo-niae," Clinical Infectious Diseases, vol. 41, no. 7, October 1, 2005). The first prescription-reduction method involved not prescribing antibiotics for respiratory tract infections that were thought to be viral, since antibiotics work against bacteria, not viruses. The second approach, a dose/duration method, entailed using only recommended doses of antibiotics for no longer than five days. The researchers also targeted physicians, pharmacists, parents, and children in the groups receiving both types of treatment with an information campaign about antibiotic resistance and appropriate antibiotic use. A control group of children and their doctors received no specific information about antibiotic use.

At the conclusion of the study, antibiotic use had declined by more than 15% in both treatment groups, compared with less than 4% in the control group. While colonization by regular pneumococci was higher in the treatment groups than in the control group, colonization by penicillin-resistant pneumococci was lower in the treatment groups than in the control group. The prescription-reduction group saw the greatest decline in penicillin-resistant colonization—from 53% to 35%—and the dose/duration group dropped from 55% to 44%. The control group remained virtually unchanged. This indicates that reduced antibiotic use permits drug-susceptible bacteria to re-establish themselves as dominant colonizers of the respiratory tract. The investigators concluded that reducing the number of prescriptions and the dose and duration of needed antibiotics has the potential to generate significant and rapid reductions of penicillin-resistant pneumococcal colonization in areas that have high rates of drug-resistant bacteria.

These findings highlight the need for professional and public awareness and understanding of the need to assume active roles in preventing antibiotic resistance. Consequences of failure of antibiotics to treat formerly treatable illnesses could be dire: longer-lasting illnesses, more physician office 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 fifteen 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 Table 2.1 in Chapter 2 for the 2006 schedule of childhood and adolescent immunizations. Table 7.3 lists the 2005–06 adult immunization recommendations.) The fifteen 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 infections 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.
• Meningitis—Meningococcal vaccine was added to the 2005–06 schedule for select populations such as college students living in dormitories to prevent bacterial meningitis caused by infection with Neisseria meningitides. Meningitis means inflammation of the meninges—the covering of the brain and the spinal cord, and it is characterized by fever, vomiting, intense headache, and stiff neck.
• 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. A global polio eradication initiative is spearheaded by the WHO, Rotary International, the CDC, and the United Nations Children's Fund (UNICEF), with the goal of global eradication by 2008.

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 Fahrenheit—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% of the population may contract influenza. Not surprisingly, people who are not healthy are considered at high risk for most strains of influenza and their 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 2003–04 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 noticeable reaction to the vaccine; 25% 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.

Pandemic Influenza

In "Pandemic Flu: Key Facts" the CDC defines pandemic flu as "a global outbreak of disease that occurs when a new influenza A virus 'emerges' in the human population, causes serious illness, and then spreads easily from person to person worldwide" (http://www.cdc.gov/flu/pandemic/pdf/pandemicflufacts.pdf). Pandemics are different from seasonal outbreaks or even epidemics of influenza. Seasonal outbreaks are caused by influenza viruses that already move from person to person, while pandemics are caused by new viruses, subtypes of viruses that have never passed between people, or subtypes that have not circulated among people for a very long time.

In the past, influenza pandemics have produced high levels of illness, death, social disruption, and economic loss. The twentieth century saw three pandemics. The CDC reports that the 1918–19 "Spanish flu" claimed one half million lives in the United States and as many as fifty million people throughout the world. Nearly half of the deaths were young, healthy adults. In 1957–58, "Asian flu" was responsible for seventy thousand deaths in the United States. The 1968–69 "Hong Kong flu" proved fatal for thirty-four thousand people in the United States. All three pandemics involved avian influenza, or bird flu. The 1957–58 and 1968–69 pandemics were caused by viruses containing a combination of genes from a human influenza virus and an avian influenza virus; the 1918–19 pandemic virus also appears to have been an avian flu.

Many scientists feel that it is inevitable that there will be another pandemic and that it is only a matter of time until the next influenza pandemic occurs. Although the severity of a future pandemic cannot be predicted, the CDC hypothesizes in "Pandemic Flu: Key Facts" that without effective vaccination against the flu or treatment for it, a "medium-level" pandemic in the United States could produce 89,000-207,000 deaths, 314,000-734,000 hospitalizations, 18-42 million outpatient visits, and another 20-47 million people being sick. Between 15% and 35% of the U.S. population could be affected, and the economic impact could be staggering—ranging from $71.3-$166.5 billion.

AVIAN INFLUENZA

Avian influenza 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. 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. The first cases in humans probably 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. An outbreak of avian flu has affected bird populations in countries throughout Asia and Europe. It has affected humans as well—as of 2006 human cases of influenza A (H5N1) infection had been reported in Cambodia, China, Indonesia, Thailand, Vietnam, and Turkey.

The spread of H5N1 virus from person to person has been rare and as of June 2006 had not continued beyond one family living in close quarters in Indonesia. There is still, however, considerable cause for concern and vigilance, because the recent avian flu outbreaks in Asia and Europe have killed more than half of those infected. Even more frightening, most cases have occurred in previously healthy children and young adults as opposed to the old and infirm who generally succumb to influenza. However, it is possible that the only cases currently being reported are those in the most severely ill people and that the full range of illness caused by the H5N1 virus has not yet been defined.

PREPARING FOR A PANDEMIC

A vaccine is rarely available in the early stages of a pandemic. When a new vaccine against an influenza virus is being developed, scientists around the world work together to select the virus strain that will offer the best protection against that virus. Manufacturers then use the selected strain to develop a vaccine. Once a potential pandemic strain of influenza virus is identified, it takes several months before a vaccine will be widely available. For example, research to test a vaccine to protect humans against H5N1 virus began in April 2005, and clinical trials were underway in 2006.

Four different influenza antiviral medications (amantadine, rimantadine, oseltamivir, and zanamivir) are approved by the U.S. Food and Drug Administration (FDA) for the treatment and/or prevention of influenza. All four usually work against influenza A viruses. But the drugs are not always effective because influenza virus strains can become resistant to one or more of these medications. For example, the influenza A (H5N1) viruses identified in humans in Asia in 2004 and 2005 have proven resistant to amantadine and rimantadine, as has the seasonal flu strain that circulated in the 2005–06 U.S. influenza season ("CDC Health Alert: CDC Recommends against the Use of Amantadine and Rimandatine for the Treatment or Prophylaxis of Influenza in the United States during the 2005–06 Influenza Season," January 14, 2006, http://www.cdc.gov/flu/han011406.htm).

The U.S. Department of Health and Human Services (HHS) supports pandemic influenza activities in the areas of surveillance, vaccine development and production, strategic stockpiling of antiviral medications, research, and risk communications. In May 2005 U.S. Secretary of HHS Mike Leavitt created a multiagency National Influenza Pandemic Preparedness and Response Task Group. This initiative involves the CDC and public and private agencies at every level (international, national, state, local, and private) in planning for a potential pandemic. By early 2006 pandemic flu planning was underway—national, state, and local municipality programs, plans for businesses and schools, and advice for families and individuals. Prepared by the CDC, Table 7.4 outlines steps individuals and families can take to prepare for a pandemic flu, such as stockpiling nonperishable food and regular prescription medication.

On January 12, 2006, Leavitt announced $100 million in funding for state and local pandemic flu preparedness. This funding is part of $350 million included in the recent emergency appropriation for combating pandemic influenza passed by Congress in December 2005. Each state will receive a minimum of $500,000, with additional allocation of funds by population. States and municipalities will use these funds to accelerate and intensify current planning efforts for pandemic influenza. Current planning emphasizes practical, community-based procedures that could prevent or delay the spread of pandemic flu and help to reduce the burden of illness communities would have to manage during an outbreak ("HHS Announces $100 Million to Accelerate State and Local Pandemic Influenza Preparedness Efforts," HHS Press Office, January 12, 2006, http://www.hhs.gov/news/press/2006pres/20060112.html).

TUBERCULOSIS

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 may be inhaled by someone sharing the same air.

Most TB (approximately 85%) 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% of infected people never show symptoms of TB. Nevertheless, 5% of people infected develop the disease in the first or second year after infection. Another 5% show symptoms later in life. For people with compromised immune systems, the risk of developing TB is much higher. For example, more than 10% of those infected with both TB and HIV (the virus that causes AIDS) develop full-blown TB symptoms within a year, according to Elizabeth L. Corbett et al in "The Growing Burden of Tuberculosis: Global Trends and Interactions with the HIV Epidemic" (Archives of Internal Medicine, vol. 163, no. 9, May 12, 2003).

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 (http://www.who.int/mediacentre/factsheets/who104/en/print.html). 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 2000 the WHO estimated that at least five million adults worldwide—primarily in sub-Saharan Africa, Latin America, and Asia—had been infected with both AIDS and M. tuberculosis. Corbett et al report that TB accounts for 11% 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 2004 it had decreased to 14,517. (See Table 7.5.)

The decline in the total number of TB cases reported to the CDC is attributable 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 African-Americans, both of which experience higher rates of TB. (See Table 7.6 and Figure 7.1.)

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. According to the CDC, in 2003, the most recent year for which drug-susceptibility data were available, there were 114 cases of MDR TB, and it was more common in foreign-born people (1.2%) than in U.S.-born residents (0.6%; http://www.cdc.gov/od/oc/media/pressrel/fs050317.htm). The CDC also reports that in 2000, 80.8% of patients with TB completed therapy in one year or less, and 92.2% completed therapy overall.

The CDC reports in Emerging Infectious Diseases (Anthony S. Fauci, Nancy A. Touchette, Gregory K. Folkers, "Emerging Infectious Diseases: A 10-Year Perspective from the National Institute of Allergy and Infectious Diseases," vol. 11, no. 4, April 2005, http://www.cdc.gov/ncidod/eid/vol11no04/pdfs/04-1167.pdf) that researchers are using genomic (science that studies the structure and function of genes) techniques to identify key molecular pathways that could be used to develop improved TB treatments and vaccines. In 2004, for the first time in sixty years, clinical trials of two new vaccines designed to prevent TB began. Many promising new anti-TB drug candidates also are now entering the drug pipeline. Derivatives of known anti-TB drugs, such as thiolactomycin and ethambutol, are currently being screened for activity against Mycobacterium tuberculosis, and another new anti-TB drug, SQ109, is under development.

March 24 of each year has been designated "World TB Day" by the 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 2006 more than 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, thirty-eight million were adults and about 2.3 million were children younger than age fifteen. Nearly five million people were newly infected with the virus in 2005. Two-thirds of all people infected with HIV lived in sub-Saharan Africa. In 2005 an estimated 25.8 million people in this region were living with HIV, and AIDS killed approximately 2.4 million people in the region the same year. 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—more than three-quarters (77%) of all women infected with HIV are in sub-Saharan Africa ("AIDS Epidemic Update," UNAIDS, WHO, December 2005, http://www.unaids.org/epi/2005/doc/report_pdf.asp).

Since the epidemic began, more than twenty-five million people have died of AIDS; more than three million died in 2005 alone. Of those, more than half a million were children.

In the United States

The CDC reports in HIV/AIDS Surveillance Report, 2004 (http://www.cdc.gov/hiv/stats/2004Surveillance Report.pdf) that by December 2004 there were an estimated 462,792 persons in the United States living with HIV/AIDS, in the thirty-five areas with confidential name-based HIV infection reporting since 2000. Of all HIV infections diagnosed in 2003, 39% progressed to AIDS within twelve months after HIV infection was diagnosed. In 2003 an estimated 43,171 diagnoses of AIDS in the United States were made. Adult and adolescent AIDS cases totaled 43,112, with 31,614 cases in males and 11,498 cases in females, and an estimated fifty-nine AIDS cases were diagnosed in children under age thirteen.

The HIV/AIDS Surveillance Report, 2004 also notes that from 2000 through 2004 the estimated number of AIDS cases increased about 7% among males and 10% among females. In 2004 males accounted for nearly three-quarters (73%) of all HIV/AIDS cases among adults and adolescents. Rates of AIDS cases in 2004 were 25.6 per one hundred thousand among males and nine per one hundred thousand among females. (See Table 7.7.) Since its recognition in 1981, the disease has killed more than half a million people in the United States.

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 7.8 shows the estimated numbers of those diagnosed with AIDS by year of diagnosis and selected characteristics of patients, including the ways in which they contracted the disease.

More than twenty-five 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 "AIDSdefining 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 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.

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.

Still, there are reasons for optimism in the battle against HIV/AIDS. The CDC reports in Emerging Infectious Diseases that since the use of combinations of drugs that target different proteins involved in HIV pathogenesis (a treatment strategy known as highly active antiretroviral therapy or HAART), rates of death and illness in the United States and other industrialized countries have been dramatically reduced—the death rate due to HIV/AIDS in Europe and North America has fallen by 80%. As of 2006 more than twenty antiretroviral medications were approved by the FDA that target HIV, and researchers were pursuing novel strategies for prevention and vaccine development. Although the first large-scale trial of an HIV vaccine reported in 2003 was disappointing, as of 2006 there were fifteen clinical trials of different vaccine strategies underway, including viral and bacterial vectors, DNA vaccines, virus-like particle vaccines, and peptide vaccines. Even if a cure for the disease is not imminent, new and better drugs used in various combinations have made HIV infection a chronic but manageable disease, much like diabetes.

COMPLICATIONS, COSTS, AND SIDE EFFECTS OF TREATMENT

Patients undergoing therapy with these anti-retroviral 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 never to 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 in excess of $155,000. According to Benjamin Young, MD, PhD, of the University of Colorado School of Medicine, the cost of HAART varies from $1,000 to $2,000 per month. Dr. Young observed that many variables are involved in calculating the actual cost to the

individual—insurance coverage, governmental assistance programs, and pharmaceutical company patient-assistance programs. For some patients, drug clinical trials offer access to these costly medications ("The Cost of HAART," in "Ask the Experts about Choosing Your Meds," The Body.com, http://www.thebody.com/Forums/AIDS/Starting/Current/Q140963.html). Government programs and private insurers alike are looking for ways to pay for, and in some cases, avoid paying for, these new therapies.

NEW, MORE EFFICIENT HIV TREATMENT

In January 2006, an international team of AIDS researchers determined that a once-daily combination of three antiretroviral drugs is more effective as initial treatment for HIV infection than the previous and widely used three-drug combination. The researchers found that after one year of treatment, a regimen of antiretroviral pills, called tenofovir DF (Viread) and emtricitabine (Emtriva), plus efavirenz (Sustiva), improved patients' ability to suppress the virus by 14%. Even more promising, the new regimen produced fewer side effects and researchers were optimistic that the simpler, more convenient regimen would encourage more people to seek treatment and increase adherence to prescribed treatment (Joel E. Gallant et al, "Tenofovir DF, Emtricitabine, and Efavirenz vs. Zidovudine, Lamivudine, and Efavirenz for HIV," New England Journal of Medicine, vol. 354, no. 3, January 19, 2006, http://content.nejm.org/cgi/content/abstract/354/3/251).

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% of people with TB were HIV-positive. Figure 7.2 shows the estimated percent of persons ages twenty-five to forty-four with TB that also are infected with HIV from 1993 to 2003.

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. (Vector-borne means the indirect transmission of an infectious agent that occurs when any animal that transmits human disease touches or bites an individual.) 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 since the early 1990s. In 2004 the CDC received reports of 19,804 cases of Lyme disease, with the majority of cases occurring in twelve northeastern and north central states—Connecticut, Rhode Island, New Jersey, New York, Pennsylvania, Delaware, Massachusetts, Wisconsin, Minnesota, Maine, New Hampshire, and Maryland. In these twelve states the average was 27.4 cases for every one hundred thousand persons.

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% 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 (WNV) 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. During 2003 and 2004 WNV caused approximately 12,400 cases of human illness, including more than 360 deaths in the United States (http://www.cdc.gov/ncidod/dvbid/westnile/qa/cases.htm).

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 119 people in 2005 (http://www.cdc.gov/ncidod/dvbid/westnile/surv& controlCaseCount05_detailed.htm). Figure 7.4 shows the distribution of human WNV cases by state as well as infection of birds, animals, or mosquitoes.

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.

In 2006 there were at least two promising vaccine candidates against WNV. One, based on a yellow fever vaccine virus that contains two WNV genes, was being evaluated in human clinical trials. A second vaccine developed at NIH uses a virus into which WNV genes have been inserted. This vaccine protects monkeys and horses against WNV infection, and a clinical trial was underway. Several novel therapies also were being tested to treat persons already infected with WNV. The protective effect of an immunoglobulin product was being tested in hospitalized patients who have WNV encephalitis (viral infection of the brain). Investigators also were evaluating many naturally occurring and laboratory-made compounds to find out if they can combat WNV. The CDC reports in Emerging Infectious Diseases that as of February 2005 fifteen hundred compounds had been screened for antiviral action against WNV, and 2-3% were shown to have antiviral activity against WNV. Other research is focusing on the roles of mosquitoes and animals in virus transmission and testing new mosquito control methods.

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 late 2002. 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 (more than 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 where the virus was present—contracted the disease.

In 2005 the NIAID applied its resources to developing diagnostics, vaccines, and identifying antiviral compounds to combat SARS-associated coronavirus (SARS-CoV). Among the many projects that have received NIAID support are the development of a "SARS chip," a DNA microarray to rapidly identify SARS sequence variants, and a SARS diagnostic test based on polymerase chain reaction (PCR) technology. (PCR is a technique for amplifying DNA sequences by as many as one billion times, and it is important in biotechnology, medicine, and genetic research.)

The CDC reports in Emerging Infectious Diseases that researchers have developed two candidate vaccines that protect mice against SARS. Another promising vaccine protects against infection in monkeys when delivered as a nasal spray. Passive immunization (immunity acquired by the transfer of antibodies from another individual) is also being assessed as a treatment for SARS. In 2004 screening of more than twenty thousand chemicals identified about fifteen hundred compounds with activity against SARS-CoV, and at least one has been deemed a candidate for further clinical development.

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.

More than sixty NIAID biodefense initiatives were funded in fiscal years 2002–05, the CDC reported in Emerging Infectious Diseases. Among them were funding for eight regional centers of excellence for biodefense and emerging infectious diseases research and construction of two national biocontainment laboratories and nine regional biocontainment laboratories. These facilities provide the secure space needed to carry out the nation's expanded biodefense research program. Researchers have sequenced the genomes of all biological agents considered to pose the most severe threats, and the NIAID has awarded contracts to screen new chemical compounds as possible treatments for bioterror attacks.

NIAID also has been active in vaccine development as a biodefense countermeasure. The institute has supported the development of a next-generation anthrax vaccine, known as recombinant protective antigen (rPA), which as of 2006 was undergoing clinical trials. Several new smallpox vaccines also were being tested for safety and efficacy. A clinical trial of a new DNA vaccine against Ebola virus and human testing of an adeno-virus-vectored Ebola vaccine began in 2005.

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.

INFECTIOUS DISEASES

CONCEPT

The history of the human species, it has been said, is the history of infectious disease. Over the centuries, humans have been exposed to a vast amount and array of contagious conditions, including the Black Death and other forms of plague, typhoid fever, cholera, malaria, influenza, and the acquired immunodeficiency syndrome, or AIDS. Only in the past few hundred years have scientists begun to have any sort of accurate idea concerning the origin of such diseases, through the action of microorganisms and other parasites. Such understanding has led to the development of vaccines and methods of inoculation, yet even before they made these great strides in medicine, humans had an unseen protector: their own immune systems.

HOW IT WORKS

Infection and Immunity

There are two basic types of disease: ones that are infectious, or extrinsic, meaning that they are contagious or communicable and can be spread by contact between people, and ones that are intrinsic, or not infectious. Diseases in general and noninfectious diseases in particular are discussed in essays devoted to those subjects. So, too, is infection itself, a subject separate from infectious diseases: a person can get an infection, such as tetanus or salmonella, without necessarily having a disease that can be passed on through contact with others in the same way that colds, malaria, or syphilis is spread.

The background on scientists' progressive understanding of the microorganisms that cause disease and the means of fighting these microorganisms are discussed in Infection. Among the leading figures in that history were the French chemist and microbiologist Louis Pasteur (1822-1895) and the German bacteriologist Robert Koch (1843-1910), who contributed greatly to what is known today as germ theory—the idea that infection and infectious diseases are brought about by microorganisms. In most cases, the organisms are too small to be seen with the naked eye. They include varieties of amoeba and worm, discussed in the essay Parasites and Parasitology, as well as viruses and some forms of bacteria and fungi, which together are known as pathogens, or disease-carrying parasites. Other terms related to infectious diseases, their agents, and the prevention and study of them are defined in the essay Infection.

IMMUNE MECHANISMS.

The human body has numerous mechanisms for protecting itself from infectious disease, the first line of defense being the skin. Skin shields us all the time from unseen attackers and generally is able to prevent pathogens from entering the body; however, any break in the skin, such as a cut or scrape, provides an opening for microorganisms to invade the body. Germs that normally would be prevented from entering the body are able to invade the bloodstream through such openings. This is why it is so very important, in any situation involving potential contact with infection, to protect the skin. With the advent of AIDS, doctors and members of other professions who are likely to touch people carrying diseases—including officers arresting addicts or prostitutes—are much more likely to do their work wearing heavy plastic gloves.

Suppose that a microorganism makes it through the barrier of skin, thanks to a cut or other opening; if so, the body puts into action a second defensive mechanism, the immune system. This system is a network of organs, glands, and tissues that protects the body from foreign substances. Without a properly functioning immune system, a person could die simply by walking out the door in the morning and coming into contact with an airborne infectant. Even in relatively healthy people, the immune system may be unable to react adequately to an invasion of microorganisms. In such cases, disease develops.

Transmission of Diseases

Infectious diseases, by definition, are transmitted easily from one person to another. We have all been told, for instance, not to drink after someone who has a cold. On a much more serious level, persons who are sexually active or potentially sexually active, but not settled in a monogamous (one-partner) relationship, are advised to avoid unprotected sexual contact so as not to contract AIDS or some other sexually transmitted disease (STD). In these and many other cases, microorganisms travel from the carrier of the disease to the uninfected person. (Actually, in the case of AIDS, the pathogen is a virus, which is not, strictly speaking, an organism or even a living thing; however, viruses usually are lumped in with bacteria, amoeba, and some fungi as microorganisms.)

Pathogens can be spread by many methods other than direct contact, including through water, food, air, and bodily fluids—blood, semen, saliva, and so on. For instance, any time a person with an infection coughs or sneezes, they may be transmitting illness. This is how diseases such as measles and tuberculosis are passed from person to person. AIDS and various STDs, as well as many other conditions, such as hepatitis, are transferred when one person comes into contact with the bodily fluids of another. This is the case not only with sexual intercourse but also with blood transfusions and any number of other interactions, including possibly drinking after someone. (Contrary to rumors that circulated in the early 1980s, when AIDS first made itself known, that particular syndrome cannot be transferred by saliva, but the common cold and other viral infections can be.)

Cholera, caused by a bacterium found in dirty wells and rivers from India to England (in the 1800s, at least), is an example of a waterborne disease. Many foodborne pathogens tend to bring about what would be more commonly thought of as an illness than a disease, since in everyday language the latter term implies a long-term affliction, whereas food poisoning usually lasts for a week or so. (Still, some forms of food poisoning can be fatal.) Bacterial contamination may occur when food is not cooked thoroughly, is left unrefrigerated, is prepared by an infected food handler, or otherwise is handled in an unsanitary or improper fashion. (The case of Typhoid Mary, discussed near the conclusion of this essay, is an extreme example of this form of transmission.)

Additionally, diseases may be transferred by vectors—animals (usually insects) that carry microorganisms from one person to another. Vectors may spread a disease either by mechanical or by biological means. Mechanical transmission occurs, for example, when flies transfer the germs for typhoid fever from the feces (stool) of infected people to food eaten by healthy people. Biological transmission takes place when an insect bites a person and takes infected blood into its own system. Once inside the insect's gut, the disease-causing organisms may reproduce, increasing the number of parasites that can be transmitted to the next victim. This is how the Anopheles mosquito vector, for instance, transfers malaria.

REAL-LIFE APPLICATIONS

A Tour of Diseases

The range of infectious diseases, from conditions that merely cause discomfort to those that bring about death, is truly staggering. Some have brought about vast epidemics that have wiped out huge populations, and many have changed the course of history, while others are hardly known to anyone outside the ranks of epidemiologists and the victims of the disease. Some, such as smallpox, have been eradicated or largely eradicated through inoculation campaigns, while others, most notably AIDS, continue to elude efforts to defeat them.

Diseases can be classified according to the systems or body parts affected. Some of those systems and parts, with examples of diseases relating to each, include the following.

• Upper respiratory tract: common cold, sinusitis, croup
• Lower respiratory tract: pneumonia, bronchitis
• Cardiovascular system: rheumatic fever
• Central nervous system: meningitis, encephalitis
• Genitourinary tract: sexually transmitted diseases (i.e., venereal diseases, such as syphilis, gonorrhea, and the herpes simplex viral infection)
• Gastrointestinal tract: cholera, salmonella, hepatitis
• Bones and joints: septic arthritis
• Skin: warts, candida
• Eyes: conjunctivitis (pink eye)

Another way to classify diseases is according to the types of organism that cause them: bacteria, viruses, or other forms of parasite, particularly worms, amoeba, and insects. The first two groups are discussed in further detail within Infection and the other varieties of parasite in Parasites and Parasitology.

Bacterial infections include anthrax, botulism, tetanus (lockjaw), leprosy, tuberculosis, diphtheria, whooping cough, plague, and a variety of pneumococcal, staphylococcal, and streptococcal illnesses. Among viral illnesses and diseases are the common cold, influenza, infectious mononucleosis, smallpox, chicken pox, measles, mumps, rubella (or German measles), yellow fever, poliomyelitis (i.e., polio), rabies, herpes simplex, and AIDS. Diseases related to other varieties of parasite include malaria, Rocky Mountain spotted fever, trichinosis, scabies, and river blindness. Nonmicroscopic parasites, particularly such worms as hookworm and pin-worm, bring about disease-like forms of parasitic infestation within the body.

Plagues

From earliest times infectious diseases have wreaked havoc on the human species, and this was particularly so with the various plagues that struck Europe in ancient and medieval times. As noted in Infection, a plague in the fifth century b.c. helped bring an end to the golden age of Greek civilization. A thousand years later, another plague befell Greece, which by then dominated what remained of the Roman Empire. Based in Byzantium (Constantinople) this realm became known to history as the Byzantine (Eastern Roman), Empire, though its citizens saw themselves simply as "Romans" and thus as the inheritors of Roman civilization. Italy itself had fallen under the control of nomadic invaders, the Visigoths, but Emperor Justinian I (483-565) undertook a vast and costly campaign to wrest control of the Italian peninsula from the barbarians. Had he succeeded, the entire course of medieval history in Western Europe might have been different; he did not, largely because of a plague that swept Constantinople in 541.

Through a series of interconnected events, the plague permanently weakened Byzantium and left the Mediterranean world ripe for conquest by a new power: Islam. Both directly and indirectly, the plague of 541 served to divide Eastern and Western Europe. Not only was the Roman Empire never truly reunited, meaning that the two halves of the continent grew increasingly separate, but the rise of Islam made possible the Crusades (1095-1291). The latter sowed further discord between the East and the West, owing to the fact that Western European crusaders overran Byzantium and incited trouble between the Byzantines and Arabs. Ultimately, the split between Eastern and Western Europe, which became particularly pronounced during the years of Communism and the Iron Curtain (1945-1990), can be traced to the plague of 541.

The Black Death

The Byzantine plagues (there were several, occurring at intervals of a few generations), killed millions of people, yet for sheer scope of destruction—and, perhaps, historical impact—they were dwarfed by the plague that devastated Europe in the years 1347-1351. This one became known as the Plague (with a capital P ) or by another name that gave some hint of the terror that was as much a part of the epidemic as the ghastly physical symptoms it brought on: the Black Death.

It began in Asia and quickly made its way to the shores of the Black Sea, where it erupted in September 1346. The first outbreak in Western Europe occurred 13 months later, in October 1347, at the Sicilian port of Messina, from whence it was an easy jump to the Italian mainland. By the following April all of Italy was infected; meanwhile, the Plague had reached Paris in January 1348, and within a year, 800 people a daywere dying in that city alone. Quickly it penetrated the entire European continent and beyond, from North Africa to Scandinavia and from England to the hinterlands of Russia. By 1351 it hadspread so far and wide that sailors arriving in Greenland found its ports deserted.

The only merciful thing about the Black Death was that death came quickly. Victims typically died within four days—a hundred hours of agony. If they caught a strain of bubonic plague, their lymph glands swelled; if it was pneumonicplague, the lungs succumbed first. Either way, as the end approached, the victim turned purplish-black from respiratory failure—hence the name Black Death.

SOCIAL IMPACT OF THE PLAGUE.

Lacking any modern concept of what causes disease, people looked for spiritual explanations. Some believed that the world was coming to an end, while others joined sects of flagellants, religious enthusiasts who wandered the countryside, beating themselves with lashes as a way of doing penance. The flagellants were tied closely tied to a rising trend toward anti-Semitism: searching for someone to blame, Europeans found a convenient scapegoat in the Jews, who, they claimed, had started the Plague by poisoning the wells of Europe.

The Black Death aptly illustrates how infectious diseases can have an impact on history in ways both big and small. In just five years the disease killed about 30% of Europe's population, which had been 100 million in 1300 but which would not reach that level again until 1500. All over the continent, farms were emptied and villages abandoned, leading to scarcity and higher prices. In the short run, these economic conditions spurred peasant revolts, but in the long run, the shortage of workers brought about higher wages and contributed to the emergence of the working and middle classes. Neither popes nor priests, neither kings nor noblemen, were any more equipped than the common people to confront the fearsome disease, and this, too, helped provoke the rise of competing classes and new centers of power in European society.

THE ETIOLOGY OF THE PLAGUE.

The Black Death, in short, may be regarded as the beginning of the end of the Middle Ages—a hideously painful event that nevertheless carried positive consequences, which might hardly have been achieved without it. The irony was that the force at the center of all this devastation and change was too small to be seen by the naked eye. Although the disease was carried by rats, the cause of the Black Death was actually a bacillus known today as Pastuerella pestis or Yersinia pestis, which uses fleas as a vector. Modern medicines such as streptomycin, a variety of antibiotic developed after World War II, would have stopped the Plague, but such concepts were a long time in coming. Although the worst phase of the epidemic ended in 1351, it continued to spread, reaching Moscow by 1353; the next five centuries saw occasional outbreaks of the disease. As late as 1894 a strain of plague killed more than six million people in Asia over the course of 14 years.

The Changing Face of Disease

The many biblical passages dealing with leprosy illustrate the role that infectious disease has played in human life from the earliest times. The fact that leprosy causes the victim's skin to turn ghostly white and brings about a gradual withering away of body parts must certainly have seemed like a curse from God. In fact, leprosy, also known as Hansen disease, is caused by the bacillus Mycobacterium leprae, and despite the many fears throughout the ages associated with touching lepers, it is not very contagious. A scene in the 1973 blockbuster Papillon illustrates this fact. The title character, a prison escapee played by Steve McQueen, takes a drag from a cigar offered to him by a leper, who then asks him if he knew that leprosy is not contagious. Papillon says no, indicating that he simply intended to build a sense of shared risk with someone who he hoped would aid his escape.

The example of leprosy shows something about the many curiosities involved in diseases and their study: for example, the fact that a disease can be infectious without being significantly contagious. Leprosy is by definition infectious, inasmuch as it is caused by a pathogen known as Mycobacterium leprae, but the latter is unusual for a number of reasons, including the fact that it is extremely slow in dividing, unlike most bacteria. After years of study, researchers are still not clear as to how leprosy is transmitted, and many believe that genetics may play a role. Thanks to increased understanding of the disease, the stigma that used to go with leprosy—including the reference to people with the disease as "lepers"—has largely been lifted. Yet places such as the leprosy facilities at Carville, Louisiana, and Molokai, Hawaii, continued to exist for many years, if only because the disfigurement associated with the disease influenced the separation of leprosy sufferers from the rest of society. In 1998, with only about 6,000 victims of the disease left in the entire country, the federal government closed the facilities at Carville and Molokai.

Leprosy remains a threat, with some two million cases of the disease worldwide, primarily in nations of Asia, Africa, and Latin America that are both underdeveloped and located in tropical zones. It has, however, ceased to be the worldwide danger that it once was, and as such it joins ranks with numerous other afflictions that formerly held all of humankind in the grip of terror. For example, tuberculosis, caused by a bacillus that attacks the lungs, afflicted a huge population in the nineteenth century, bringing an end to the careers of figures that ranged from the great English poet John Keats to the American gunslinger Doc Holliday. Holliday, in fact, traveled to Tombstone, Arizona, where he and Wyatt Earp participated in the infamous shootout at the O.K. Corral, because he thought the climate would help his condition. Their story has been portrayed in countless films; for example, in Tombstone (1993), Val Kilmer gives an extremely convincing portrayal of the debilitating effects that Holliday's tuberculosis (aggravated by his lifestyle) must have had on him. Today, tuberculosis is not nearly the scourge that it once was, though it remains a problem, particularly because of patients' increasing resistance to the antibiotics used to treat it. (See Infection for more about antibiotics.)

VACCINATION AND CONTINUING THREATS.

When Europeans invaded the lands of Native Americans, they brought with them a host of microorganisms to which they had developed an immunity but to which the Indians were completely vulnerable. Although Europeans and their descendants had developed immunities to various diseases, thanks to generations of exposure to pathogens, they and the rest of the world remained vulnerable to a host of contagious disease, including cholera, smallpox, chicken pox, measles, mumps, yellow fever, polio, malaria, and many others. Today, vaccines have virtually eradicated many of these contagious diseases and keep others at bay. (Anyone who has ever had a cholera vaccine, which causes the patient's body to become miserably sore, achy, and tender for about 48 hours, has some idea of just how awful the disease itself must be.) Polio, which once posed an enormous threat to American children and crippled one of America's greatest leaders, President Franklin D. Roosevelt, is an artifact of history, thanks to vaccines developed after World War II.

Yet some killers never really die. For instance, malaria, caused by a protozoan parasitic genus known as Plasmodium and spread by mosquito biological vectors, infects from 300 to 500 million people annually and kills up to 2.7 million people every year. Although the substance known as quinine showed some promise as a treatment during most of the nineteenth and twentieth centuries, Plasmodium has become increasingly resistant to it. In the search for a cure for what has been called "the most devastating disease in history," some 100,000 drugs have been tested.

Some Other Killers

The twentieth century saw its own version of the Plague, in the form of the 1918-1920 influenza epidemic. Carried to all corners of the globe by soldiers returning from World War I, "the Influenza," as it came to be known (again with a capital letter to distinguish it as the greatest outbreak of a particular disease), killed 20 million people—more than the war itself. Then there is the greatest epidemic of the latter part of the twentieth century and the early twenty-first century: AIDS. This disease is linked to the human immunodeficiency virus (HIV), a retrovirus (see Infection for an explanation of retrovirus) that causes a gradual breakdown of the victim's immune system.

People do not die of AIDS per se but of the illnesses—particularly pneumonia or Kaposi's sarcoma, a cancer of the tissues—to which AIDS makes them susceptible. The disease is transmitted primarily by sexual contact and intravenous drug use. A smaller number of particularly tragic cases result from no actions on the part of the victim, who in this case is either the recipient of infected blood or the child of a mother with AIDS. Since the disease first came to public attention in 1981, 21.8 million people worldwide (and about 750,000 in the United States) have died from it. The vast majority of deaths have been in sub-Saharan Africa, and 90% of all AIDS cases are in developing countries. Worldwide, approximately 36.1 million people have either HIV or AIDS. (For more about AIDS, see Immunity and Immunology.)

THE EBOLA VIRUS.

AIDS was not the only infectious condition to come out of central Africa and terrorize the world in the late twentieth century. Beginning in about 1975, numerous viruses, previously unknown and terrifyingly lethal, emerged from tropical regions of Africa, South America, and Asia. So great was the rise of new infectious diseases that some epidemiologists believed this was tied with economic development: as humans cultivated previously undeveloped lands and delved into more isolated parts of the world, they might be exposing new viruses.

Few of these inspired as much terror as the Ebola virus, and the fear is understandable, given the effects of the disease. Three to nine days after the illness enters the body, the victim begins to experience fever and other flu-like symptoms, sudden exhaustion, sore throat, muscle pain, and headache. Vomiting and diarrhea soon follow, and the vomit and stools are black with blood. Soon hemorrhaging occurs, with blood flowing from the nose, ears, and even the eyes. Internal organs begin to liquefy, and within three weeks of contracting the virus, the victim is usually dead.

An almost unbelievably hideous condition, Ebola might seem at first glance a great deal like the Black Death. Why, then, has it not ravaged whole populations the way the Plague did? It is certainly not because scientists have a cure for Ebola; the best doctors can hope to do, if they detect the disease early enough, is to provide supportive care, such as blood transfusions, that may save the patient's life. Yet even the worst outbreaks of the disease have not occurred on anything like the scale of the Plague: the worst known outbreak of Ebola, in Uganda in 2000-2001, killed 425 people.

Part of the reason Ebola is not capable of spreading rapidly is, ironically, because it is such an efficient killer: it kills its human victims before they have a chance to spread it to many other victims. Other than nonfatal incidents in laboratories in the United States, England, and Italy, as well as one case in a monkey export facility in the Philippines—various primates are carriers—all Ebola cases and outbreaks have been in Africa, primarily in Zaire (now Democratic Republic of the Congo), Sudan, and Gabon. Many times, local conditions, situations, and practices have exacerbated the spread of the disease. For example, in 1996, a group of people in Gabon found a dead chimpanzee in the forest and ate it; as a result, 37 people died. The Uganda outbreak became much worse than it might have been because locals, lacking education as to antiseptic procedures, failed to take proper precautions. Many died as a result of attending funerals of Ebola victims at which bodies were not disposed of properly.

TYPHOID MARY.

Sometimes a single person can be a walking epidemic, as in the case of the Irish cook Mary Mallon (1869-1938), better known as "Typhoid Mary." Mallon was an example of the fact that some people, because of genetic characteristics or other specifics, can act as carriers of a disease without ever contracting it themselves. Even though Typhoid Mary had Salmonella typhosa bacteria in her system, she did not get sick; still, she was highly contagious, and her profession as cook made her particularly dangerous. At least three deaths and 53 cases of typhoid fever were linked directly to her, with thousands of other probable cases of infection indirectly caused by this human vector.

Part of what made her so notorious—hence her nickname, given to her by the press—was the fact that Mallon did not seem to care how many people she infected. In the first decade of the twentieth century, authorities tracked her down as the cause of, or at least a contributing factor in, an outbreak of typhoid in the New York City area. Instead of cooperating with officials, Mallon repeatedly escaped before being caught and confined to Riverside Hospital on New York's North Brother Island in 1910. She served three years in isolation there before her release, after which she promptly went back to work as a cook—despite explicit orders not to do so. It was this (and an outbreak of typhoid fever at her place of work, which happened to be a hospital) that earned her the nickname by which she became known to history. She was caught again in 1915 and spent the remainder of her life on North Brother Island.

THE THREAT OF BIOLOGICAL WARFARE.

Infinitely more despicable than Typhoid Mary are terrorists and rogue nations that would willingly unleash infectious disease on large, unsuspecting civilian populations. One such pathogen is Bacillus anthracis, the cause of anthrax, a deadly bacterial disease of cattle and other grazing animals. Under the right circumstances, anthrax can kill a human in about 36 hours, though a number of antibiotic treatments are effective in the early stages of the disease.

During the late twentieth century, the United States and Soviet Union experimented with the use of anthrax in biological warfare, and an accidental release of anthrax spores at a Soviet lab in 1979 led to some 68 deaths. Following the September 11, 2001, terrorist attacks on the World Trade Center in New York City and on the Pentagon, a series of letters containing anthrax spores showed up around the United States, and exposure to the disease led to a handful of deaths. Although the attacks were linked initially to Osama bin Laden and his al-Qaeda organization, authorities increasingly began to suspect that home-grown terrorists were simply exploiting the September 11 attacks as cover for their own deeds.

Still, there was little doubt that bin Laden, the Iraqi dictator Saddam Hussein, or North Korea's ruling clique would use biological agents if the opportunity arose. One threat that loomed in the aftermath of September 11 was the possibility that bin Laden's followers would reintroduce the smallpox virus, which had been eradicated by worldwide vaccinations during the 1970s. The reason why smallpox could pose such a great threat is precisely that it has been eliminated, and few Americans born after 1973 have received vaccines. Unless they gained access to one of the two labs worldwide (one in the United States and one in Russia) where smallpox virus is stored for the purpose of making vaccines, however, terrorists would be unable to obtain a sample. (It is this matter of access that led authorities to suspect that the anthrax attacks were an "inside job.")

Another biological agent that poses a threat is Clostridium botulinum, which causes botulism, a toxic condition that can result in paralysis. Members of the fanatic Japanese cult Aum Shinrikyo attempted unsuccessfully to launch botulism attacks in Tokyo on three occasions in 1995. The Japanese government itself—that is, the Axis Japanese government of World War II—experimented with another biological agent, tularemia, or Francisella tularensis. The pathogen, which causes lung inflammation and death, is considered one of the most dangerous forms of biological weapon, because it is extremely efficient and easy to spread. America's military, borrowing an idea from its former enemy, developed its own F. tularensis strain in the late 1960s but destroyed its stockpile in 1973.

WHERE TO LEARN MORE

Centers for Disease Control and Prevention (Web site). <http://www.cdc.gov/>.

Cranmer, Hilarie. Anthrax Infection. Emedicine.com (Web site). <http://www.emedicine.com/emerg/topic864.htm>.

DeSalle, Rob. Epidemic!: The World of Infectious Disease. New York: New Press, 1999.

Everything You Need to Know About Diseases. Spring-house, PA: Springhouse Corporation, 1996.

Ewald, Paul W. Plague Time: How Stealth Infections Cause Cancers, Heart Disease, and Other Deadly Ailments. New York: Free Press, 2000.

Hoff, Brent H., Carter Smith, and Charles H. Calisher. Mapping Epidemics: A Historical Atlas of Disease. New York: Franklin Watts, 2000.

Infection and Immunity. University of Leicester Microbiology and Immunology (Web site). <http://wwwmicro.msb.le.ac.uk/MBChB/MBChB.html>.

Marr, Lisa. Sexually Transmitted Diseases: A Physician Tells You What You Need to Know. Baltimore, MD: Johns Hopkins University Press, 1998.

Oldstone, Michael B. A. Viruses, Plagues, and History. New York: Oxford University Press, 1998.

Shein, Lori. AIDS. San Diego: Lucent Books, 1998.

KEY TERMS

EXTRINSIC:

A term for a disease that is communicable or contagious and comes from outside the body. Compare with intrinsic.

GERM THEORY:

A theory in medicine, widely accepted today, that infections, contagious diseases, and other conditions are caused by the actions of microorganisms.

IMMUNE SYSTEM:

A network of organs, glands, and tissues that protects the body from foreign substances.

IMMUNITY:

The condition of being able to resist a specific disease, particularlythrough means that prevent the growth and development or counteract the effects of pathogens.

INFECTION:

A state or condition in which parasitic organisms attach themselves to the body or to the inside of the body of another organism, causing contamination and disease in the host.

INTRINSIC:

A term for a disease that is not communicable or contagious and comes from inside the body. Compare with extrinsic.

PATHOGEN:

A disease-carrying parasite, usually a microorganism.

STD:

Sexually transmitted disease.

VECTOR:

An organism, such as aninsect, that transmits a pathogen to the body of a host.

Infectious diseases

Definition

Infectious diseases are caused by microbes—primarily bacteria, viruses , protozoa, and fungi—that can be passed to or among humans by various means.

Description

Infectious diseases are a major cause of illness and death in older people and may exacerbate other medical conditions. Pneumonia , influenza (flu), and septicemia are among the top ten causes of death in older adults. Pneumonia is a lung infection caused by bacteria, viruses, or fungi. Influenzas are respiratory illnesses caused by highly contagious viruses. Septicemia, also called blood poisoning, occurs when a microorganism enters the bloodstream and causes infection throughout the body. Septicemia can damage the circulatory system, cause severe low blood pressure , and lead to infections in other organs such as the lungs or brain.

Other infectious diseases that are particularly dangerous in older people include:

• food poisoning caused by the bacterium Escherichia coli (E. coli)
• tuberculosis (TB), in seniors usually resulting from reactivation of a latent infection by Mycobacterium tuberculosis
• chickenpox caused by the Varicella zoster virus
• West Nile virus infection
• acquired immunodeficiency syndrome (AIDS) caused by the human immunodeficiency virus (HIV).

Other common infectious diseases in older adults include:

• colds
• bronchitis, an inflammation of the main air passages to the lungs usually resulting from a respiratory virus infection
• urinary tract infections, usually involving the bladder or kidneys
• infections of the skin and soft tissues, often called cellulitis
• bacterial infections of the gut, including diverticulitis, appendicitis, infectious diarrhea, gall bladder infection, or abdominal abscesses
• gastroenteritis, an intestinal infection
• bacterial infections of the bones and joints
• infectious endocarditis, an inflammation of the heart valves
• bacterial meningitis, which causes inflammation of the membranes lining the brain
• shingles or herpes zoster, a reactivation of the virus that causes chickenpox
• Lyme disease, caused by the bacterium Borrelia burgdorferi.

Another way to classify the infections caused by microbial diseases is based on the onset and duration of the illness. Infections fall into three general categories:

• Acute infections, including influenza and many forms of pneumonia, developing within hours or days. The illness may last from hours to a couple of weeks and may range from mild to life-threatening.
• Chronic infections, such as some forms of bone infection, typically lasting from weeks to years. Chronic infection can sometimes develop from acute infection or may develop very slowly.
• Latent infections, such as certain forms of tuberculosis, can remain hidden in the body for many years without causing symptoms. These germs may become active, cause symptoms, and be transmissible to others months or years after the initial infection occurred.

Demographics

Susceptibility

Infectious diseases are responsible for more deaths worldwide than any other cause, and seniors are particularly susceptible, in large part due to age-related changes in the immune system . The majority of elderly people have 30 to 50% less immunity than the young or middle-aged, a condition called immunosenescence. With age, specific types of immune cells become less able to produce antibodies to fight infection. In addition the skin and mucous membranes lining the gastrointestinal, respiratory, and urinary tracts become less effective barriers to infectious organisms entering the body. Nevertheless some older people have immune responses that are almost as effective as those of much younger people.

The effectiveness of the immune response also depends on overall health and is adversely affected by such factors as the following:

• poor nutrition
• smoking
• alcohol consumption
• environmental pollutants
• the presence of another disease, referred to as comorbidity
• medications used to treat a concurrent disease

Other factors that can increase the susceptibility of older adults to infectious diseases include:

• stress
• age-related changes in the lungs—especially the collapse of small airways and stiffening of lung tissue—that increase the risk of respiratory infection
• inability to cough strongly enough to clear the airways of phlegm and mucus
• difficulty swallowing, which increases the risk of inhaling or aspirating foods or liquids
• a reduced response to vaccines against pneumonia and flu
• an inability to completely empty the bladder, leaving urine in which bacteria can grow
• changes in urine or prostate secretions that affect their antibacterial properties
• common skin conditions such as blisters and pressure ulcers
• general immobility, as may occur after a stroke or surgery
• exposure to infectious organisms, such as in a hospital or nursing home
• use of catheters or other tubes, such as for kidney dialysis, that remain in the body for long periods.

The presence of other diseases or physical conditions, such as kidney or heart disease , can greatly reduce the body's ability to fight infections. Chronic obstructive lung disease decreases mucus clearance from the airways, increasing the risk of pneumonia. Nerve damage and slow wound healing associated with diabetes increase the risk of serious infection, especially in the limbs. Complications from surgery and surgical wounds—and hospitalization itself—increase the risk of infection.

Transmission

The microbes that cause many infectious diseases, such as common cold and flu viruses and M. tuberculosis, can be transmitted through the air from the coughs or sneezes of an infected person. Other infectious diseases are transmitted by close personal contact, including kissing, sexual intercourse, or accidental transfer from feces to hand to mouth. Some organisms can be transmitted by handshaking or touching a contaminated surface. Some infectious diseases—including salmonella enterocolitis (an infection of the intestine), and severe acquired respiratory syndrome (SARS), a serious viral pneumonia—can be transmitted either directly or indirectly from animals, including household pets. Other diseases, such as Rocky Mountain spotted fever or malaria, are transmitted through the bite of a vector, such as a mosquito, flea, or tick, or via contaminated food or water. International travel can expose people to infectious diseases from other parts of the world. People can carry infectious organisms and transmit them even without having symptoms of disease.

Incidence

People aged 65 and older, especially women and the very elderly, account for more than half of all cases of pneumonia in the United States. Influenza, which infects 5 to 20% of the U.S. population annually, results in some 200,000 hospitalizations and 36,000 deaths each year, primarily in older adults. Septicemia is a common cause of hospitalizations among older adults and is the sixth leading cause of death among black women aged 85 and older.

Pneumonia and other infectious diseases are very common in hospitals and nursing homes . Older adults are particularly susceptible to hospital infections from open wounds and tubes inserted in the body. The incidence of serious infections by group B Stretococcus (strep) bacteria increases with age, especially in those with other medical conditions such as bedsores, diabetes, liver disease, or a history of stroke or cancer .

Strep B infections often occur in older adults after a trauma or surgery.

About 1.7 billion people worldwide, including 16 million Americans, are infected with M. tuberculosis, the leading cause of death from a single infectious organism. In the United States 25% of all active cases of TB are in adults aged 65 and older, and up to 50% of older nursing-home residents have a positive reaction to a TB test, indicating previous exposure. Most of these people were infected in the early 1900s when it is estimated that 80% of the population was exposed to TB by the age of 30.

Initially HIV infections in older people were limited to those who had received transfusions with infected blood. However, the number of older Americans who are contracting HIV through sexual activity is increasing as of 2008, and many older adults remain unaware of the risk of HIV infection. About 10% of all new AIDS diagnoses in the United States are in older people, and in 2004 people aged 50 and over accounted for almost 20% of newly diagnosed cases. Older people with HIV are at particular risk of complications, due to immuno senescence.

Urinary tract infections affect more than 10% of older adults each year. Urinary tract infections are much more common in women than in men. Between 15% and 40% of older women have bacteria in their urine without symptoms of illness.

Older adults are at risk for bone and joint infections because conditions such as arthritis, gout , or artificial joints cause tissue damage. Bacteria can reach the bones and joints through the blood, from wounds, or from nearby infected tissues. Bacteria from pressure ulcers or diabetic foot infections are also common sources of bone and joint infections, particularly among nursing-home residents.

Infectious endocarditis is particularly common in the first two months after surgical implantation of an artificial heart valve. Bacteria can attach to the diseased or artificial valves and spread to the heart lining, the blood, and other organs.

Gastroenteritis and shingles are particularly common among nursing-home residents. Shingles affects at least one million Americans annually, most of them over age 60.

Causes and symptoms

Infectious diseases in seniors often follow other illnesses that have compromised the immune system.

Bacterial pneumonia often follows an infection such as the flu that damages the lungs. Common causes of septicemia include:

• strep and other bacteria that cause pneumonia or other infections of the respiratory system, urinary tract, or skin
• Salmonella
• medical devices such as catheters that provide bacteria an entry point into the body
• surgically implanted prosthetic devices, including artificial joints, pacemakers, heart valves, and eye lenses. Bacteria can reach the prosthesis during surgery or later through the blood or nearby infection and grow on the implanted device.

The most common causes of urinary infections in older people are urinary catheters and conditions such as fecal incontinence that allow gut organisms to enter the urinary tract. In older men prostate disease and difficulty emptying the bladder are the primary causes of urinary tract infections.

Older adults do not necessarily exhibit typical signs of infection. The most common symptom of a serious infection is fever; however, as many as 50% of older people do not have a fever even with a serious infection such as pneumonia. This is probably due to an age-related loss in the ability to regulate body temperature and to the generally lower body temperature of older people. The definition of a fever in a person over 75 should be lowered by about one half of a degree. In addition the fever response to infection and inflammation, as with other stress responses, may lessen with age. Therefore, in older adults the symptoms of infection may be general or unusual:

• a sudden loss in wellbeing or function for no apparent reason
• loss of appetite
• falling
• confusion

Symptoms of infectious disease that require a physician's attention include:

• a cough lasting more than a week
• difficulty breathing
• fever
• a rash, particularly if accompanied by fever
• swelling
• vomiting
• open sores or pus draining from anywhere in the body
• episodes of rapid heartbeat
• change in urination habit or in the appearance or odor of the urine

Diagnosis

Some infectious diseases can be diagnosed by a medical history and physical exam. Rapid blood, urine, or x-ray tests may provide helpful information. However, the most definitive tests for infection are bacterial cultures, in which a sample of blood, urine, sputum, spinal fluid, tissue, drainage from a wound, or a swab from the throat or other body part is placed in special material at the laboratory. These tests usually require one or more days to complete. Bacteria that grow usually signify the presence of infection and are tested to determine sensitivity to antibiotics . Viral and fungal infections can be diagnosed by more complicated types of cultures or other tests.

Blood tests can detect signs of inflammation, such as a high white blood cell count. However, many conditions can cause such results and older people may not have elevated white blood cells in response to infection. Other diagnostic tools include:

• x rays
• ultrasound
• body scans
• biopsies, in which a piece of tissue is removed for examination

Treatment

Some infectious diseases, such as colds, are treated by bed rest and drinking plenty of liquids and are allowed to run their course, although symptoms may be treated with cold medications.

Bacterial infections are usually treated with antibiotics. Intravenous antibiotics may be administered for severe infections. However, the increase in drug-resistant bacteria due to the overuse of antibiotics is a worldwide health problem, especially in hospitals. Active TB requires months of treatment with multiple drugs. Infections associated with implanted medical devices may require removing the device before antibiotic treatment. Certain gastrointestinal, soft tissue, and bone and joint infections, and infectious endocarditis may require surgical treatment.

Fungal infections of the skin and nails may be treated with topical or oral medicines. Many topical antifungal medications are sold over-the-counter as treatment for athlete's foot. Oral antifungals usually require a prescription.

Nutrition/Dietetic concerns

It has been estimated that about half of adults over age 65 do not ingest the calories, vitamins , and minerals needed to maintain a healthy immune system to fight infection. This tendency is particularly true for nursinghome residents. However, older adults living independently may also be malnourished, particularly if they are depressed, have poorly controlled diabetes, side effects from medications, or medical conditions that interfere with appetite or metabolism. Although a 2007 study found that multivitamin and mineral supplements may not reduce the risk of infection among older nursing-home residents, other studies have found that nutritional supplements—particularly those containing antioxidants , B vitamins, selenium, and zinc—benefit both the immune system and the general health of those aged 65 and over.

Prognosis

Seniors are much more likely than younger people to die of an infectious disease. Of the at least 45,000 Americans who die of pneumonia or flu each year, 90% are 65 or older. The first wave of SARS was fatal in more than 50% of victims over age 65. Septicemia also has a poor prognosis in older adults, even with proper treatment, and the death rate from invasive strep B infections is 15–25% for adults aged 65 and over.

Older adults usually respond as well as younger people to anti-retroviral drugs that prevent symptoms of AIDS. However, older people with untreated HIV tend to deteriorate very rapidly. Other infectious diseases can damage organs and cause various other complications. Although the shingles rash usually goes away on its own in two to four weeks, for about one in five, the severe pain continues, a condition known as postherpetic neuralgia .

Prevention

Hand washing is one of the easiest and most effective ways to prevent infectious disease. Scrubbing the hands vigorously with soap and water for 15 seconds will wash away many disease-causing organisms, including cold viruses and Staphylococcus and strep bacteria. It is particularly important to wash the hands:

• before preparing or eating food
• after coughing or sneezing into the hand
• after using the toilet
• after changing a diaper

Septicemia can be prevented by cleanliness and sterile techniques, such as cleaning the area with iodine before inserting an intravenous line. Patients should insist that doctors, nurses, and other healthcare workers wash their hands before touching them.

Other preventions against infectious disease include:

• cooking meat thoroughly
• avoiding unpasteurized juices
• washing cuts immediately with soap and water
• cleansing skin that is not exposed to the air, such as the groin and under the breasts
• seeing a dentist regularly and replacing toothbrushes every three months.

Vaccines

Many infectious diseases can be prevented with vaccines. Most adult Americans are immune to the infectious diseases that they had as children. However, since childhood diseases can be far more serious in older people, adults who did not have diseases such as measles or chickenpox in childhood should be vaccinated against them. Adults should also be vaccinated regularly against tetanus and diphtheria. Before traveling abroad Americans should receive vaccines against infectious diseases that are common in areas they will visit.

It is recommended that all adults aged 50 and older get annual flu vaccinations in October or November before the height of the flu season. A 2006 study found that higher doses of the vaccines are safe for older adults, significantly increase antibodies against the flu virus, and afford additional protection against the disease. People over age 64 should also get a one-time vaccination against Streptococcus pneumoniae, which often causes pneumonia and meningitis in older adults. This vaccine can be given at any time of the year. A single-dose shingles vaccine became available in 2006 and is recommended for adults aged 60 and over.

Medications

Antibiotics are sometimes prescribed as a preventative against bacterial infections such as TB. People testing positive for TB for the first time are usually treated with isoniazid for nine months as a preventative therapy. Those at high risk for infectious endocarditis or for infection from certain implanted devices are sometimes given antibiotics before dental cleanings or medical procedures to prevent bacteria from entering the blood and infecting the heart or medical device. Antiviral medications are effective in preventing some viral infections.

QUESTIONS TO ASK YOUR DOCTOR

• How will my disease be diagnosed?
• Can I transmit this disease to others?
• What precautions should I take to prevent transmitting this disease?
• What is the treatment for this disease?
• How should I take my medications?
• What are the side effects of the medications?
• Will these medications interact with others that I am taking?
• What else can I do to recover faster?
• What is the prognosis?

Caregiver concerns

Caregivers can help prevent the spread of infectious diseases by washing their hands frequently and fully cooking food. Older people with dementia or other mental loss may not wash properly or refrigerate their food or may do other things that increase the risk of infectious disease. They may forget to take their medications, take the wrong ones or in the wrong dosage, or take them at the wrong time. This can cause an infection to linger or for other complications to develop. Antibiotics should be taken with plenty of water and with or without food, depending on the specific drug. It is very important that the entire course of antibiotics be taken, even if the patient feels better.

Older adults with mental difficulties may have trouble communicating symptoms of infection. Caregivers should take the following steps:

• watch for signs and symptoms of infection, such as fever, chills, cough, change in urination habit, and especially a change in the ability to engage in normal activities
• reduce fevers with acetaminophen and cold washcloths to the forehead after calling a doctor
• encourage intake of fluids by frequently offering small amounts of clear liquid, ice cubes, or popsicles.

KEY TERMS

Comorbidity —Simultaneous presence of more than one—usually independent—medical conditions.

E. coli —Escherichia coli; a bacterium that usually resides harmlessly in the lower intestine but can spread to cause infection elsewhere; also, some infectious strains produce a toxin that causes intestinal illness.

Endocarditis —Inflammation of the lining of the heart or the heart valves that can be caused by an infectious microorganism.

Herpes zoster —Shingles; an acute nerve inflammation resulting in a rash and pain, caused by the reactivation of latent chickenpox virus in the body.

Immunosenescence —Loss of immune system function with age.

Influenza —Flu; any of several highly contagious respiratory diseases caused by strains of three different species (A, B, or C) of orthomyxoviruses.

Meningitis —A bacterial or viral infection that causes inflammation of the membranes surrounding the brain and spinal cord.

Pneumonia —A lung disease usually caused by an infectious bacterium, virus, or fungus.

Salmonella —A genus of bacteria that causes food poisoning, acute gastrointestinal inflammation, typhoid fever, and septicemia.

Septicemia —Blood poisoning; an infection of the bloodstream by a virulent bacterium, virus, or fungus, causing acute systemic illness.

Shingles —Herpes zoster; an acute nerve inflammation resulting in a rash and pain, caused by the reactivation of latent chickenpox virus.

Staphylococcus —Staph; a genus of bacteria that causes various diseases, including food poisoning, skin infections, and endocarditis.

Streptococcus—Strep; a genus of bacteria that causes various diseases; Group B strep organisms cause pneumonia, septicemia, and meningitis.

Resources

BOOKS

Anderson, Mary Ann. Caring for Older Adults Holistically, 4th ed. Philadelphia: F. A. Davis, 2007.

Lerner, Brenda Wilmoth, and K. Lee Lerner. Infectious Diseases: In Context. Farmington Hills, MI: Thomson Gale, 2008.

PERIODICALS

Arnst, Catherine. “Roll Up Your Sleeve, Gramps; A Graying Population May Create a Huge Market for Vaccines that Buttress Aging Immune Systems.” Business Week no. 4055 (October 22, 2007): 90.

Kendall, Patricia A., et al. “Food Safety Guidance for Older Adults.” Clinical Infectious Diseases 42, no. 9 (May 1, 2006): 1298–1304.

Langkamp-Henken, Bobbi, et al. “Nutritional Formula Improved Immune Profiles of Seniors Living in Nursing Homes.” Journal of the American Geriatrics Society 54, no. 12 (December 2006): 1861–1870.

Liu, Barbara A., et al. “Effect of Multivitamin and Mineral Supplementation on Episodes of Infection in Nursing Home Residents: A Randomized Placebo Controlled Study.” Journal of the American Geriatrics Society 55, no. 1 (January 2007): 35–42.

OTHER

“Aging in the Know: Infectious Diseases.” The AGS Foundation for Health in Aging. May 23, 2005 [cited March 31, 2008]. http://www.healthinaging.org/agingintheknow/chapters_ch_trial.asp?ch=44.

“Beyond Newborns and Mothers—Some Facts About Group B Strep Disease in the Rest of the Population.” Group B Strep Prevention. October 4, 2006 [cited March 31, 2008]. http://www.cdc.gov/groupBstrep/general/gen_public_adult.htm.

“Fight Flu and Pneumonia.” Health Information. June 20, 2007 [cited March 31, 2008]. http://www.medicare.gov/health/fludetails.asp.

“NAIAD Study Finds Higher Dose of Flu Vaccine Improves Immune Response in the Elderly.” NIH News. May 22, 2006 [cited March 31, 2008]. http://www3.niaid.nih.gov/news/newsreleases/2006/elderdose.htm.

[March 31, 2008]. http://www3.niaid.nih.gov/healthscience/healthtopics/microbes/PDF/microbesbook.pdf.

ORGANIZATIONS

AGS Foundation for Health in Aging, Empire State Building, 350 Fifth Ave., Suite 801, New York, NY, 10118, (212) 755-6810, (800) 563-4916, (212) 832-8646, http://www.healthinaging.org.

Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA, 30333, (404) 498-1515, (800) 311-3435, http://www.cdc.gov.

National Institute of Allergy and Infectious Diseases, 6610 Rockledge Dr., MSC 6612, Bethesda, MD, 20892-6612, (301) 496-5717, (866) 284-4107, (301) 402-3573, http://www3.niaid.nih.gov.

Margaret Alic Ph.D.

infectious diseases are the result of damaging microorganisms obtaining access to the body, and not being repelled or destroyed by the immune system. Their relationship to man is that of parasite and host, and is continually adjusting. Numerous different types of bacteria, viruses, and other organisms may cause disease, and infection may take place through close contact with an infected person, or through the respiratory, digestive, or genito-urinary systems, depending on the organism and the disease involved. Infection may also occur by transmission from an animal, or via an insect vector. Organisms can damage the body by their multiplication in or around its cells, or by the widespread poisonous effects of substances (toxins) which they release. Many infectious diseases are of a self-limiting character, ending in either full recovery or death. While certain of them may occasionally have long-term sequelae, the body, if its defences win, for the most part returns to normal, often retaining a lifelong subsequent immunity against that specific infection. Other infections, such as syphilis, are, however, chronic, and eventually fatal if untreated.

Diseases included in the category ‘infectious’ include colds and influenza; the familiar infectious illnesses of childhood, and the more serious conditions such as poliomyelitis, diphtheria and meningitis, typhoid, typhus, cholera, dysentery, and smallpox. Tuberculosis is also an infectious disease, although its clinical progress is chronic rather than acute.

Most of these diseases have a very ancient history. While many only emerge as identifiable entities in the medical writings of the seventeenth and eighteenth centuries, others can be demonstrated to have been present in antiquity. Smallpox, for example, which was declared eradicated by the World Health Organisation in 1977, can clearly be identified by characteristic lesions on the mummified corpses of ancient Egyptians, while a stele of the same civilization, dating from 1580–1350 bc, shows a young man displaying a withered and shortened left leg, held in the ‘equinus position’ characteristic of paralysis possibly caused by poliomyelitis. Infectious diseases also occur in the animal kingdom, and some, such as anthrax and yellow fever, are transmissible to man.

Understanding

While the closely allied concepts of infection and contagion (transmission of disease from one person to another by direct or indirect contact) are probably almost as old as mankind, it was only in the mid nineteenth century, with the development of accurate microscopes and of laboratory research, that these processes began to be scientifically elucidated. Several observers indicated the likelihood of microorganisms as causal agents of disease, and even detected their paths of transmission, such as the faecal–oral route for typhoid and cholera, but it was Louis Pasteur who, in the early 1860s, first gave a coherent account of the process of infection in what is popularly known as the germ theory of disease. In 1876, Robert Koch identified the causal organism of anthrax, and within a few years had also identified the agents of tuberculosis and cholera. By 1900, the specific agents of numerous diseases had been identified, and the diverse routes of transmission — of infection and contagion — were beginning to be mapped out.

Infectious diseases are often ‘crowd diseases’, which depend for the most part on reservoirs of susceptible people to maintain themselves. Person to person infections, for example, are thought to have become more apparent between 3000 and 500 bc, when urban centres grew large enough to support them. These diseases soon established an endemic character in such centres, meaning that the diseases or infectious agents were constantly present in that area. City populations, exposed early in life, acquired high levels of immunity to them, compared with rural populations. Rapid and unregulated urban growth brought a great escalation in the incidence of and mortality from many of these diseases in Western Europe and North America during the nineteenth century, and several, including tuberculosis, typhoid, measles, and whooping cough, were responsible for much human misery and many thousands of deaths. Recurrent gastro-intestinal infections, in particular, helped to undermine the health, and natural resistance to infection, of babies and young children, and indeed of adults also. By 1830, annual death rates of over 30 per 1000 living persons were commonplace in Western cities, while infant mortality rates rivalled those of under-developed nations today.

Prevention

Beginning in the 1830s, public health movements began to develop in many Western states in response to this crisis of mortality. For example, in Britain — one of the first nations to begin to adopt public health measures — early reformers such as Edwin Chadwick stressed the enormous economic costs of such a wastage of life. At this period, notions of contagion marched in parallel with a belief that gases generated by rotting organic matter were productive of epidemics, and early attempts at preventing premature deaths focused on environmental improvement. Slowly and painfully, through the following decades, filtered and piped water systems, mains drainage, systematic scavenging, and slum clearance brought about cleaner, healthier urban environments, and disrupted the transmission routes of a number of important infections, notably of water-borne typhoid and cholera and of louse-borne typhus.

The development of specific methods of prevention came late in the history of the infectious diseases. Smallpox, one of the most ancient and most hideous diseases, was the first to be tackled in this way. At some point, the Chinese had discovered that by introducing matter taken from smallpox vesicles into a scratch on the normal healthy body, controlled, immunizing infections could be established. This method, the inoculation of material containing the living organism, itself was not foolproof, since it was not possible to ensure a mild rather than a virulent infection, which might prove fatal. Nonetheless, knowledge of the technique spread along trade routes to Turkey, and thence to Europe in the early eighteenth century. In 1796, a Gloucestershire medical practitioner, Edward Jenner, picked up on local lore which suggested that infections with cow-pox would protect against smallpox, and demonstrated that this was indeed the case. This practice, vaccination (from vaccinus: pertaining to a cow) was later refined, and, encouraged by many European governments, the introduction of the modified or related organism displaced inoculation as the principal preventive against smallpox. At this stage, however, the processes and principles which made vaccination effective were still not understood.

Smallpox vaccination represented an ideal for disease eradication which provided an important model for future medical research. Louis Pasteur, for example, set out in his later career to investigate the principles of immunology with a view to understanding how vaccination worked. Pasteur's breakthrough with the principle of attenuating viruses — reducing their virulence — came in 1876. This meant that the body's immunity to subsequent infection by a virulent organism could be actively provoked in response to a non-threatening form of the same strain; Pasteur proceeded to develop immunizations against various animal diseases, including anthrax and rabies. It was his reluctant application of rabies vaccine to the boy Joseph Meister in 1883 that first alerted the general public to the eventual possibilities of immunology.

As the discipline developed through the work of Pasteur, his colleagues, and his successors, new therapeutic and preventive indications emerged. Early successes came for diphtheria in 1894 with anti-toxin therapy (the use of material produced by the inoculation of animals with toxins produced by bacteria), and for both diphtheria and tetanus with the development of active immunization (the production of protective antibodies by stimulating the body's immune system). In 1896, Almroth Wright succeeded in producing an anti-typhoid vaccine using killed bacteria, thus extending the theoretical options for vaccine development. In the interwar period, successful vaccines were developed against diphtheria and tuberculosis, and, in the years following World War II, they were developed against most of the principal childhood infections — whooping cough, poliomyelitis, German measles, and measles, and eventually against mumps and chicken-pox as well.

Since 1870, there has been an enormous decline in death rates from infectious diseases in developed countries. This decline has been hastened by the availability of immunizations, but in most cases had begun well before such protection was available. Rising living standards — including smaller families, better housing, improved domestic hygiene, a reduced incidence of gastro-intestinal infections, and better nutrition — together with public health measures contributed largely to this reduction. Many childhood diseases remain serious in poor and under-developed countries. Immunization, although a valuable resource with some diseases, is by no means a viable prospect for all infections; despite decades of research, no vaccine has yet been approved for malaria, one of the world's most serious infections.

New infections

New infectious diseases are still emerging, and there is no room for complacency in this regard. The emergence of poliomyelitis as a serious killer and maimer between about 1911 and 1962 was partly attributable to improved hygienic standards in the West, which meant that children were no longer harmlessly exposed to the virus as babies. Lassa fever, exemplar of a whole new generation of sinister tropical fevers, emerged in Nigeria in 1969, while Legionnaires' disease was identified in the US in the 1970s. The rapid global spread of HIV infection since 1980 echoes that of syphilis in Europe in the fifteenth century. Epidemics of the terrifying Ébola virus in Zaire, and of bubonic plague in India in the early 1990s, indicate that both new and old infections retain the potential for major human tragedy. One consequence of global warming could possibly be the reappearance of malaria as an indigenous infection in parts of the world which have been free of it for many decades. Relentless human exploitation of tropical resources, uncontrolled human reproduction, increased travel, and unregulated technological development all create the potential for unleashing fresh manifestations of new and old infections by disturbing global environmental equilibrium.

Anne Hardy

Bibliography

Garrett, L. (1996). The coming plague: newly emerging diseases in a world out of balance. Penguin Books, London.
McNeill, W. H. (1979). Plagues and peoples. Penguin Books, Harmondsworth.