Foodborne Diseases.

Foodborne illness is a common, distressing, and sometimes life-threatening problem for millions of people in the United States and around the world. Persons infected with foodborne organisms can remain symptom-free or can develop symptoms ranging from mild intestinal discomfort to severe dehydrating or bloody diarrhea and death. Foodborne illness is also extremely costly; the estimated yearly cost of all foodborne diseases in this country is $5 to $6 billion in direct medical expenditures and lost productivity. Salmonella and Campylobacter infections alone account for $1 billion in direct and indirect medical costs. The National Institute of Allergy and Infectious Diseases (NIAID), a component of the National Institutes of Health (NIH), collaborates with other research institutions to conduct and support basic, clinical, and applied research aimed at understanding, detecting, treating, and preventing foodborne diseases. Those described below are among the more common and serious.

Enterohemorrhagic Escherichia coli Infection

Escherichia coli, commonly called E. coli, is just one of many bacteria that can cause diarrhea. While harmless strains of E. coil normally occur widely in nature, including the intestinal tracts of humans and other vertebrates, pathogenic types are a frequent cause of both enteric and urogenital tract infections. Several different types of pathogenic E. coli are capable of causing diarrheal disease. A particularly dangerous type is referred to as enterohemorrhagic E. coli, or EHEC. The first such strain was identified in the United States in 1982. Since then, EHEC strains have been associated with foodborne outbreaks traced to undercooked hamburgers, unpasteurized apple juice or cider, salad, salami, and unpasteurized milk. The strain of EHEC most commonly found in the United States is designated O157:H7; but others, including O26:H11 and O111 :H8, also have been found. EHEC strains produce toxins that have effects similar to those produced by bacteria of the Shigella genus. These enterotoxins can damage the lining of the intestine, cause anemia, stomach cramps and bloody diarrhea, and hemolytic uremic syndrome (HUS) leading to kidney failure. In North America, HUS is the most common cause of acute kidney failure in children.

Cattle are known to be a reservoir of EHEC, but other domestic and wild animals and birds can also harbor these bacteria. EHEC and its toxins are destroyed by heating; therefore, the best assurance against infection is eating only thoroughly cooked beef and beef products, avoiding unpasteurized juices, and thoroughly washing uncooked fresh foods. Good personal hygiene, including hand washing, and disinfecting work surfaces in the kitchen also are essential to prevent infection or the spread of this and other enteric diseases.

Salmonellosis

Salmonellosis is caused by Salmonella bacteria. The disease causes acute intestinal distress with sudden onset of headache, fever, abdominal pain, diarrhea, nausea, and sometimes vomiting.

These symptoms, along with loss of appetite, can persist for several days. Dehydration, especially among infants, can be severe. Salmonella is an invasive organism that can escape the confines of the intestine and become disseminated by the blood to other organs. It can become a chronic infection in some people, who can be symptom-free yet capable of spreading the disease to others. Ordinarily, deaths are uncommon except in those who are very young, elderly, or have weakened immune systems. Salmonella infections are increasing in the United States. In fact, recurrent opportunistic Salmonella bacteremia is considered an AIDS-defining illness.

Numerous types of Salmonella cause disease in both animals and people. While there is much variation in the relative prevalence of different types of Salmonella species from country to country, in the United States Salmonella typhimurium and Salmonella enteritidis are the two most commonly reported. A multidrug-resistant strain of Salmonella typhimurium, called Definitive Type 104 (DT104), first emerged in the United Kingdom in 1984 and was recently detected in the United States. Now it is the second most prevalent strain (after serotype enteritidis) of Salmonella isolated from humans. These DT104 isolates pose a significant new threat because they are resistant to several antibiotics normally used to treat people with salmonella infections including ampicillin, chloramphenicol, streptomycin, sulfonamides, and tetracycline.

Salmonellosis occurs worldwide, but it is most extensively reported in North America and Europe. Only a small proportion of infected people are tested and diagnosed, with as few as 1 percent of cases reported. Salmonellosis may occur in small, localized outbreaks in the general population or in large outbreaks in hospitals, restaurants, or institutions for children or the elderly.

Domestic and wild animals, including poultry, pigs, cattle and pets such as turtles, iguanas, chicks, dogs and cats, can harbor the Salmonella bacterium and, although symptomless, can pass on the infection.

Salmonellosis is caused most often by drinking raw milk or by eating undercooked poultry and poultry products such as eggs. In addition, other types of food prepared on surfaces contaminated by raw chicken or turkey can, in turn, become contaminated. Less often, the illness stems from food contaminated by a food worker.

Campylobacter Infections

Campylobacteriosis, caused by species of the Campylobacter genus of bacteria, is characterized by enteritis, diarrhea, nausea, vomiting, malaise, and fever. Campylobacter recently has been recognized as the leading cause of diarrheal disease in the United States. While some infections are asymptomatic, others may result in arthritis and, rarely, febrile convulsions or meningitis. Infection with Campylobacter also can be associated with the development of Guillain-Barre

Syndrome (GBS), the leading cause of acute paralysis in this country. GBS develops in a small number of persons two to four weeks after Campylobacter infection and usually after diarrheal symptoms have resolved. GBS is characterized by progressive paralysis of the limbs and, in more severe cases, development of respiratory failure requiring prolonged hospitalization. Campylobacter jejuni, C. fetus, and C. coli are the usual causes of campylobacteriosis in people.

Campylobacter organisms cause between 5 and 14 percent of all diarrheal illness worldwide. In industrialized countries, illness is more common in children younger than 2 years of age. In developing countries, older children and young adults have the highest incidence of infection. Most frequently, cattle and poultry are the sources of human infection, but puppies, kittens, pigs, sheep, rodents, and birds may also serve as reservoirs. Transmission usually occurs through ingestion of contaminated food or water or raw milk, or by contact with infected infants, pets or wild animals.

Shigella Infections

Shigellosis, also called bacillary dysentery, causes bloody diarrhea, fever, nausea, vomiting, and cramps. More than 32,000 cases were reported in the United States in 1995. Four main species of Shigella cause disease: Shigella dysenteriae, S. flexneri, S. boydii and S. sonnei. S. dysenteriae type 1, like EHEC, can lead to the development of hemolytic uremic syndrome.

Outbreaks may occur at tropical or temperate latitudes, especially under conditions of crowding, where personal hygiene is poor. S. sonnei is most common in developed countries. While outbreaks have occurred in primate colonies, the only significant reservoir is people. Shigella organisms are generally transmitted via the fecal-oral route. Like EHEC, the infectious human dose can be as few as 10 organisms, making good personal hygiene and proper food preparation procedures imperative in controlling infection with Shigella.

NIAID Research on Foodborne Diseases

Basic research is needed to better understand how the organisms that can be spread by contaminated food or water cause disease in humans. NIAID-supported researchers are studying the bacterial genes that play a role in colonization and pathogenesis of these organisms. For example, genes have been identified that appear to be involved in the signaling of immune system cells that cause inflammation, and which may contribute to the development of diarrhea. Other research sponsored by NIAID focuses on methods by which the organism grows and interacts in host cells. Scientists have discovered that some enteric bacteria recognize when they are in a human host and respond by activating a particular set of virulence genes that enable the organism to colonize the host and contribute to the disease process. Future studies will define new ways to intervene, whether by prevention or treatment, in the disease process.

In recent studies of EHEC and Shigella infections, NIAID-sponsored scientists have identified a gene in both types of bacteria that allows the organisms to resist the usually lethal effects of stomach acid. The great majority (85 percent, as shown in recent NIAID studies) of EHEC infections are caused by acid-resistant bacteria. The remaining 15 percent are caused by bacteria that have defects in a certain control gene common to all enteric bacteria. This gene turns on other genes and results in acid resistance. Isolating a gene that confers such a biological advantage is an important step toward improved treatment and prevention.

In other studies on EHEC, NIAID-sponsored investigators are further defining the mechanisms by which the toxins produced by EHEC and Shigella result in the kidney damage leading to hemolytic uremic syndrome. The primary goal of this research is to enhance understanding of physiological mechanisms underlying the progression of kidney vascular disease. Researchers are developing antitoxins that may be useful in preventing the development of hemolytic uremic syndrome in children who become infected. Researchers are also exploring vaccine approaches that would prevent EHEC and Shigella infections of animals or people.

Preliminary tests of live, attenuated Shigella flexneri vaccine candidates have resulted in the discovery of two new enterotoxins. Those toxins may contribute to the diarrhea associated with Shigella species. Studies are under way to elucidate the mechanism by which these toxins induce fluid loss. The findings will provide crucial information on how to improve attenuated vaccines to prevent shigellosis.

The NIAID enteric diseases program also supports basic and clinical research on Vibrio cholerae, Helicobacter pylori, Yersinia, Listeria, Clostridia, Bacteroides, Staphylococcus and enterotoxins.

NIAID supports an Enteric Pathogens Research Unit to carry out research on the mucosal immune response to infection with enteric pathogens. Because foodborne pathogens universally affect the intestinal mucosa, these studies will provide information needed to engineer vaccines or develop treatment for diseases caused by these organisms. The research includes clinical trials of vaccine candidates and the use of adjuvants, delivery systems, or dosing schedules that will help scientists determine how best to enhance the immune response to vaccines.

In addition to the organisms mentioned above, NIAID conducts research on other gastrointestinal pathogens such as Norwalk viruses, rotaviruses, and hepatitis A virus. Scientists at the NIAID Laboratory of Infectious Diseases devised the first method for detecting Norwalk virus particles and for measuring Norwalk virus-specific antibodies. They also developed a quadrivalent, live rotavirus vaccine for infants. Recent NIAID-supported clinical trials have shown this vaccine to be safe and 100 percent effective in preventing dehydrating disease or disease severe enough to require hospitalization. NIAID scientists also developed a recently licensed inactivated vaccine for hepatitis A virus infection.

As foodborne and waterborne diseases continue to have a major impact on health in the United States and elsewhere in the world, and with the emergence of drug-resistant strains of many organisms including Salmonella, biomedical research will continue to play a critical role in understanding the disease process, and in preventing and controlling these infections.

NIAID, a component of the National Institutes of Health, supports research on AIDS, malaria, tuberculosis and other infectious diseases, as well as allergies and immunology.

Prepared by:
Office of Communications
National Institute of Allergy and Infectious Diseases
National Institutes of Health
Bethesda, MD 20892

Public Health Service
U.S. Department of Health and Human Services
March 1998