The National Institute of Diabetes & Digestive & Kidney Diseases

Dr. Jay Hoofnagle, Director of the Division of Digestive Diseases and Nutrition and chair of the Coordinating Committee, welcomed attendees and guest speakers to this meeting on food safety and digestive diseases. He explained that the purpose of the meeting was to bring together proponents of the Federal government’s role in food safety, coordinate activities in this area, and advance understanding of the pathogenesis and treatment of diseases caused by food. Dr. Hoofnagle remarked that it is time for an NIDDK itiative on the topic of food safety. He then introduced the meeting’s first guest speaker, Dr. Patricia Griffin, Chief of the Foodbourne Diseases Epidemiology Section of CDC’s Foodborne and Diarrheal Branch, whose topic was CDC’s food safety programs.

Dr. Griffin outlined the topics of her discussion: the burden of foodborne illnesses, the emerging pathogens and new vehicles for transmission, CDC groups working on foodborne diseases, some new CDC approaches (FoodNet, PulseNet, NARMS), and ideas for future work.

A recent annual estimate of acute diarrhea from FoodNet data, she noted, indicates a reported 360 million cases. In most of these cases, the cause (food, water, other) is unknown. Old estimates of foodborne-related cases range from 6½ to 81 million per year. A 1987 estimate of foodborne related deaths, based on educated estimates but not hard data, totaled 9,100. Dr.Griffin explained that the lack of a good surveillance system is the reason there is so little reliable data. She noted that people who become sick may or may not see a physician. The physician may or may not obtain a stool culture; and if the physician does obtain a culture and confirm the cause of disease, that result may or may not be reported to health departments. As a result, Dr. Griffin characterized the number of reported cases as "the tip of the iceberg."

Dr. Griffin discussed the Salmonella infections reported from 1920 to 1993. In the early part of the century, typhoid was the most prevalent form of Salmonella; but improved hygiene, sewage, and water treatment brought it under control in the United States. A new vehicle for transmission emerged, the nontyphoidal Salmonella infections found in animals living in cities. Dr. Griffin noted that, for 47 percent of hepatitis A cases in the United States in 1993, the cause of transmission is unknown. It is suspected that some were the result of a waterborne outbreak; what portion resulted from a foodborne cause is not known. She also cited the following new and emerging pathogens: V cholera 0139, vibrio vulnificus, E coli 0157, helicobacter, arcobacter bulzieri, Salmonella typhimurium, Norwalk-like viruses, hepatitis E, Cryptosporidium, cyclospora, and Nitzchia pungens. She listed the following new vehicles and mechanisms of transmission: cryptosporidia from chlorinated, filtered water; Salmonella enteritidis from eggs laid by hens with ovarian infection; botulism from boxed soup stored on shelves; and pathogens from fruits and vegetables. The trend of Salmonella outbreaks from fruits and vegetables was first noted between the years 1990 and 1995.

Dr. Griffin outlined the major CDC divisions working on foodborne disease. The Foodborne and Diarrheal Diseases Branch, DBMD/NCID, works on bacterial diseases; the Epidemiology Branch, DPD/NCID, deals with parasitic diseases; and the Viral Gastroenteritis Section and Hepatitis Branch, DVD/NCID, focuses on viral diseases. With the advent of the new food safety initiatives, Dr. Griffin explained, the mission of the Foodborne and Diarrheal Diseases Branch is to prevent illness, disability, and death due to foodborne and diarrheal diseases. CDC plans to accomplish this mission by using surveillance, outbreak response, applied research, and training and by developing new prevention and control methods and collaborating with other health agencies.

FoodNet (the Foodborne Diseases Active Surveillance Network), Dr. Griffin noted, is an active surveillance network for foodborne disease that has four sources of foodborne disease data: a foodborne outbreak surveillance system, a lab-based surveillance for entero pathogens, epidemic investigations, and active surveillance. FoodNet’s primary objectives are to determine and monitor the burden of foodborne diseases, determine the proportion of foodborne diseases attributable to specific foods, develop a network to respond to emerging foodborne diseases, and improve outbreak response. Dr. Griffin explained that active surveillance investigates seven bacteria, including Campylobacter, E. coli 0157, Listeria, Salmonella, Shigella, Vibrio, and Yersinia, and two parasites, Cryptosporidium and cyclospora. She noted that foodborne disease is seasonal, with the trend high in the summer months.

FoodNet also monitors outcome data such as hospitalization and death rates. In 1997, Listeria and Salmonella were the most common causes of foodborne-related death. Active surveillance has limitations, Dr. Griffin noted, including the interpretation of trends; an example of why interpretation is difficult is the variations in lab practices.

Dr. Griffin described a physician survey performed in 1996. Out of 5,000 physicians surveyed, 44% had ordered a stool culture for the last patient with diarrhea, and 77% had done so if the patient had blood in the diarrhea. In a 1996 survey of 9,000 people, 11% reported having a diarrheal illness in the preceding month, and 8% of those individuals visited a health care provider for the illness; only 20% who visited a health care provider gave stool samples. Further, not all cases are ultimately reported to the health department, resulting in incomplete data. Dr. Griffin showed, however, how it is possible to use FoodNet data (e.g., 2,000 reported cases of Salmonella) and multipliers to arrive at an estimate of 1,400,000 cases of Salmonella in the United States.

FoodNet’s projects for 1998 are surveillance for the hemolytic uremic syndrome, foodhandler’s knowledge and practices, case-control studies, and site specific projects such as looking at the etiology of diarrhea among hospitalized patients. For more information, Dr. Griffin gave FoodNet’s Web site: http://www.cdc.gov/ncidod/dbmb/foodnet/foodnet.htm.

Another CDC tool, PulseNet, is used to understand outbreaks. PulseNet is a national network of public health labs that subtype foodborne bacteria. CDC’s objectives for PulseNet are to take action to warn consumers and to remove contaminated foods from the marketplace. Additional objectives are to learn the spectrum of illness of the pathogens and what factors in food production lead to contamination.

Dr. Griffin discussed the change in the typical foodborne disease outbreak from the old-style church suppers to the new-style outbreaks; the newer outbreaks are more difficult to detect because, although they are more widespread, they tend to involve small pockets of people in dispersed locations. Most outbreaks are buried in the sea of sporadic cases and are never recognized. The pathogens that are currently tracked are the E. coli 0157 and the Salmonella typhimurium.

The role of PFGE in outbreak identification and investigation is to provide data to determine whether a cluster of cases is from a common source, whether a particular case is linked to an outbreak, and whether the implicated food contains a common strain. Examples of the use of PFGE are the outbreak of E. coli 0157 infections from baby lettuce in Michigan and Virgina and E. Coli 0157 infections from commercial apple juice.

Another tool Dr. Griffin described is the National Antimicrobial Resistance Monitoring System (NARMS), which was initiated by CDC in 1995 in collaboration with the FDA and 16 state and local public health labs. The purpose of NARMS is to monitor antimicrobial resistance of human isolates of nontyphoidal Salmonella, E. coli 0157, and Campylobacter. Data for the years 1979-1989 show that resistance in Salmonella is increasing. The sources of isolates in clinical labs from patient specimens are Salmonella, E.coli 0157, and Campylobacter. Dr. Griffin indicated that one-third of Salmonella isolates are the resistant type defined by phage typing in the United Kingdom.

Dr. Griffin referred to the 1997 case-control study of ciprofloxacin-resistant Campylobacter, which indicated that 56% of subjects acquired their infections in the United States. NARMS is conducting a new study of resistance among enterococci to determine susceptibility of enterococci to 25 antimicrobial agents.

Some needs in the current food safety program, Dr. Griffin indicated, are to determine what proportion of diarrhea cases can be explained and to develop rapid and inexpensive diagnosis techniques for diarrheal pathogens as well as improved tests for cyclospora. Clinical labs encourage culturing for more than routine pathogens. We need to determine what slaughterhouse practices decrease contamination of ground beef and we need to conduct more applied research. Other needs in the current food safety program include improved detection of cyclospora in the environment and improved detection of viruses in food. Further investigations are needed to determine how E. coli 0157 persists on farms and what factors lead to the emergence of Shiga toxin-producing E. coli. Another need is farm guidelines for appropriate use of antibiotics.

In summary, Dr. Griffin indicated that the burden of foodborne illness is large, new pathogens are emerging, and there are established CDC groups such as FoodNet, PulseNet, and NARMS that are working on the problem. There are many opportunities for productive future work.

Dr. Hoofnagle asked about Salmonella infections that occur in children’s day care centers. Dr. Griffin replied that the vast majority of the infections are either foodborne or from animals, specifically reptiles.

Dr. Hoofnagle introduced the day’s second guest speaker, Dr. David Acheson, Assistant Professor of Medicine at the New England Medical Center at Tufts University. Dr. Acheson listed the topics he would discuss: specific foodborne pathogens, particularly Shiga toxin producing E. coli, as a cause of disease; the extent of the problem; issues related to the mechanisms of disease; food producing processes that contribute to the problem; food safety initiatives being pursued at the New England Medical Center; and future needs.

Dr. Acheson indicated that there is insufficient information about the number of infections from Shiga toxin-producing E. coli (STEC), the outcomes, how the the bacteria causes disease, and how we can best intervene. He mentioned the Jack in the Box incident in which 732 people developed significant disease from E. coli, 55 were hospitalized with the hemolytic syndrome, and 4 died. To investigate the extent of STEC in the United States, Dr. Acheson’s Center conducted an 11-site surveillance study in June-October 1997. The purposes of the study were to examine the prevalence of STEC in patients submitting stool samples for routine culture as well as the number of 0157 versus non-0157, and to compare the STEC infections with those from other foodborne pathogens (Salmonella, Campylobacter). Data show that of 3,624 stool samples analyzed, 33 were STEC isolates; 20 were 0157 and 13 non-0157. There were 83 Salmonella isolates and 73 Campylobacter isolates. The study did not collect outcome data.

Dr. Acheson briefly explained the pathogenesis of the Shiga toxin E-coli. First there is ingestion of STEC and then colonization of the lower intestinal tract, where Shiga toxins are produced. More speculative are the issues of absorption and movement of the Shiga toxin in the blood stream and the action of microvascular endothelial cells in sensitive sites.

Regarding the role of food production, Dr. Acheson raised the question: Is antimicrobial use in animals potentially increasing the number of STEC strains? He noted that Stx 1 and 2 are bacteriophage encoded; Trimethoprim and ciprofloxacin are antibiotics that induce Stx bacteriophage in vitro; and Stx bacteriophages can move horizontally in vivo.

In discussing the Food Safety Initiative (FSI) at the New England Medical Center, Dr. Acheson explained that the FSI program was established to research foodborne pathogens and their effects on people. It brings together a group of clinically oriented basic scientists with expertise on foodborne pathogens. They examine, among other areas, the clinical consequences in the short and long term of exposure to various foodborne pathogens as well as clinically relevant applied and basic research on foodborne pathogens. The program also aims to bring a clinical perspective to education.

FSI’s achievements to date include initiating a pilot project to look at enteric pathogens in children, exploring projects on foodborne pathogens in immunocompromised hosts, and producing a brochure on the group’s skills and distributing it nationally to those interested in food safety. Dr. Acheson mentioned that the group received start-up funding from NEMC and NIDDK.

Dr. Acheson explained FSI’s current goals, which include educating the public via publications and symposiums and generating further funding to pursue the FSI goals. Dr. Acheson’s goal for five years hence is for the Center’s FSI program to be recognized as a valuable resource for the public and industry on the basic science and clinical aspects of foodborne pathogens.

In closing, Dr. Acheson outlined some of the future needs: to obtain accurate data on food safety and digestive diseases; to determine which pathogens are causing what type of disease; to determine the mechanisms of diseases with foodborne causes; to better understand the role of food production in such disease; to document the outcome in relation to the type of exposure; and to focus on those pathogens that are causing the most clinical disease.

Regarding virulence factors, Dr. Acheson noted the need to further develop diagnostics, vaccines, and therapeutic strategies. In the area of food production, he mentioned the need to understand the original source of disease (food, water, other), the pathogen ecology in the animal host (e.g., the use of probiotics), and farming practices that may exacerbate the problem, such as the use of antibiotics.

Finally, Dr. Acheson cited the need to develop multidisciplinary collaborations in this area between and among groups with complementary expertise. Such groups include basic scientists, veterinarians, clinicians, and food processors.

Dr. Hoofnagle asked if members had anything new to report. Ms. Yeager from the House Appropriations Committee reported on increased funding for NIH. Dr Purohit of the National Institute on Alcohol Abuse and Alcoholism mentioned the mechanism of alcohol induced fibrosis and asked NIDDK for their interest in co-funding. Dr. Khan of the Division of Research Grants reported more activity on research grants for hepatitis C. Dr. Hoofnagle talked about further research on liver disease in minorities and women.

Dr. Hoofnagle noted in closing, the next meeting will take place on December 8, 1998.