Food-Related Illness and Death in the United States.

Abstract

To better quantify the impact of foodborne diseases on health in the United States, we compiled and analyzed information from multiple surveillance systems and other sources. We estimate that foodborne diseases cause approximately 76 million illnesses, 325,000 hospitalizations, and 5,000 deaths in the United States each year. Known pathogens account for an estimated 14 million illnesses, 60,000 hospitalizations, and 1,800 deaths. Three pathogens, Salmonella, Listeria, and Toxoplasma, are responsible for 1,500 deaths each year, more than 75% of those caused by known pathogens, while unknown agents account for the remaining 62 million illnesses, 265,000 hospitalizations, and 3,200 deaths. Overall, foodborne diseases appear to cause more illnesses but fewer deaths than previously estimated.

Editor's note: This paper was originally published in Emerging Infectious Diseases (EID) by National Center for Infectious Diseases of the Centers for Disease Control and Prevention. The format of the paper therefore varies from normal Journal of Environmental Health style. In EID, over 100 references accompanied the paper, as did a seven-page appendix describing the methods and assumptions behind the authors' pathogen-specific estimates. These sources were not reprinted in this issue of the Journal because of space limitations. Upon request, however, they are available from NEHA service representatives by fax or mail.

Introduction

More than 200 known diseases are transmitted through food (1). The causes of food-borne illness include viruses, bacteria, parasites, toxins, metals, and prions, and the symptoms of foodborne illness range from mild gastroenteritis to life-threatening neurologic, hepatic, and renalsyndromes. In the United States, foodborne diseases have been estimated to cause 6 million to 81 million illnesses and up to 9,000 deaths each year (2-5). However, ongoing changes in the food supply, the identification of new foodborne diseases, and the availability of new surveillance data have made these figures obsolete. New, more accurate estimates are needed to guide prevention efforts and assess the effectiveness of food safety regulations.

Surveillance of foodborne illness is complicated by several factors. The first is underreporting. Although foodborne illnesses can be severe or even fatal, milder cases are often not detected through routine surveillance. Second, many pathogens transmitted through food are also spread through water or from person to person, thus obscuring the role of foodborne transmission. Finally, some proportion of foodborne illness is caused by pathogens or agents that have not yet been identified and thus cannot be diagnosed. The importance of this final factor cannot be overstated. Many of the pathogens of greatest concern today (e.g., Campylobacter jejuni, Escherichia coli 0157:H7, Listeria monocytogenes, Cylospora cayetanensis) were not recognized as causes of foodborne illness just 20 years ago.

In this article, we report new estimates of illnesses, hospitalizations, and deaths due to foodborne diseases in the United States. To ensure their validity, these estimates have been derived by using data from multiple sources, including the newly established Foodborne Diseases Active Surveillance Network (FoodNet). The figures presented include estimates for specific known pathogens, as well as overall estimates for all causes of foodborne illness, known, unknown, infectious, and noninfectious.

Data Sources

Data sources for this analysis include the Foodborne Diseases Active Surveillance Network (FoodNet) (6), the National Notifiable Disease Surveillance System (7), the Public Health Laboratory Information System (8), the Gulf Coast States Vibrio Surveillance System (9), the Foodborne Disease Outbreak Surveillance System (10), the National Ambulatory Medical Care Survey (11), the National Hospital Ambulatory Medical Care Survey (12-14), the National Hospital Discharge Survey (15), the National Vital Statistics System (16), and selected published studies.

Established in 1996, FoodNet is a collaborative effort by the Centers for Disease Control and Prevention, the U.S. Department of Agriculture, the U.S. Food and Drug Administration, and selected state health departments. FoodNet conducts active surveillance for seven bacterial and two parasitic foodborne diseases within a defined population of 20.5 million Americans (6). Additional surveys conducted within the FoodNet catchment area provide information on the frequency of diarrhea in the general population, the proportion of ill persons seeking care, and the frequency of stool culturing by physicians and laboratories for selected foodborne pathogens.

The National Notifiable Disease Surveillance System (7) and the Public Health Laboratory Information System (8) collect passive national surveillance data for a wide range of diseases reported by physicians and laboratories. The Gulf Coast States Vibrio Surveillance System collects reports of Vibrio infections from selected states (9), and the Foodborne Disease Outbreak Surveillance System receives data from all states on recognized foodborne illness outbreaks (defined as two or more cases of a similar illness resulting from ingestion of a common food) (10).

As components of the National Health Care Survey, the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey measure health care use in various clinical settings, including physician offices and hospital emergency and outpatient departments (11-14). These surveys collect information on patient characteristics, patient symptoms or reasons for visit, provider diagnosis, and whether the patient was hospitalized. Up to three symptoms are recorded using a standard classification (17), and up to three provider diagnoses are recorded according to the International Classification of Diseases, 9th Revision, Clinical Modifications (ICD-9CM) (18) (Table 1).

The National Hospital Discharge Survey, another component of the National Health Care Survey, is a representative annual sample of discharge records from approximately 475 nonfederal short-stay hospitals (15). The information collected includes up to seven principal discharge diagnoses classified by ICD-9-CM codes (18). Because these data include information on condition at discharge, they can be used as a source of information on in-hospital deaths. Additional information on food-related deaths was obtained from the National Vital Statistics System, which collects death certificate data on causes of death classified by 3- or 4-digit ICD-9 codes (16).

In addition to information from these formal surveillance systems, we used data from two published population-based studies. The Tecumseh study was conducted from 1965 through 1971 in 850 households in Tecumseh, Michigan, with an emphasis on households with young children (19). Households were telephoned weekly to identify incident cases of self-defined diarrhea, vomiting, nausea, or stomach upset. The Cleveland study was conducted among a selected group of 86 families followed from 1948 through 1957 (20). A family member recorded occurrences of gastrointestinal illnesses and associated symptoms on a monthly tally sheet. Both studies also collected information on extraintestinal illnesses (e.g., respiratory illness). Other studies with similar designs were not included in our analysis, either because they were relatively small or because they did not provide information on the desired endpoints.

The Study

Food-Related Illness and Death from Known Pathogens

Total Cases

To estimate the total number of foodhorne illnesses caused by known pathogens, we determined the number of reported cases for each pathogen, adjusted the figures to account for underreporting, and estimated the proportion of illnesses specifically attributable to foodborne transmission. Although data from various periods were used, adjustments for changes in population size had minimal effect on the final estimates and were therefore omitted.

Cases may be reported in association with documented foodborne outbreaks, through passive surveillance systems (e.g., the National Notifiable Disease Surveillance System, the Public Health Laboratory Information System), or through active surveillance systems (e.g., FoodNet). Sporadic illness caused by some pathogens (e.g., Bacillus cereus, Clostridium perfringens, Staphylococcus aureus) is not reportable trough passive or active systems; hence, the only cases reported are those related to outbreaks. For these pathogens, we have assumed tat if diagnosed sporadic cases were reported, the total number would be 10 times the number of outbreak-related cases. This multiplier is based on experience with pathogens for which data are available on both sporadic and outbreak-associated cases (e.g., reported cases of Salmonella or Shigella, Table 2). For all pathogens, the number of outbreak-related cases was calculated as the average annual number of such cases reported to CDC from 1983 to 1992, the most recent years for which published outbreak data are available. For pathogens also under passive surveillance, we used the average number of cases reported to CDC from 1992 through 1997, and for pathogens under active surveillance through FoodNet, we used the average rate observed for the surveillance population from 1996 to 1997 and applied this to the total 1997 U.S. population (with some modification for E. coli O157:H7; Appendix).

Irrespective of the surveillance system, many cases of foodborne illness are not reported because the ill person does not seek medical care, the health-care provider does not obtain a specimen for diagnosis, the laboratory does not perform the necessary diagnostic test, or the illness or laboratory findings are not communicated to public health officials. Therefore, to calculate the total number of illnesses caused by each pathogen, it is necessary to account for underreporting, i.e., the difference between the number of reported cases and the number of cases that actually occur in the community For Salmonella, a pathogen that typically causes nonbloody diarrhea, the degree of underreporting has been estimated at [tilde]38 fold (Voetsch, manuscript in preparation) (21). For E. coli O157:H7, a pathogen that typically causes bloody diarrhea, the degree of underreporting has been estimated at [tilde]20 fold (22). Because similar information is not available for most other pathogens, we used a factor of 38 for pathogens tha t cause primarily nonbloody diarrhea (e.g., Salmonella, Campylobacter) and 20 for pathogens that cause bloody diarrhea (e.g., E. coli O157:H7, Shigella). For pathogens that typically cause severe illness (i.e., Clostridium botulinum, Listeria monocytogenes) , we arbitrarily used a far lower multiplier of 2, on the assumption that most cases come to medical attention. Details of the calculations for each specific pathogen and rationale are provided in the Appendix. Where information from both active and passive reporting was available, we used the figure from active surveillance when estimating the total number of cases.

Having estimated the number of cases caused by each pathogen, the final step was to estimate for each the percentage of illness attributable to foodborne transmission. The total number of cases was then multiplied by this percentage to derive the total number of illnesses attributable to foodhorne transmission. The rationale for each estimate is presented in the Appendix; although precise percentages are generally difficult to justify, in most instances there is ample support for the approximate value used.

Results are presented in Tables 2 and 3. Known pathogens account for an estimated 38.6 million illnesses each year, including 5.2 million (13%) due to bacteria, 2.5 million (7%) due to parasites, and 30.9 million (80%) due to viruses (Table 2). Overall, foodborne transmission accounts for 13.8 million of the 38.6 million illnesses (Table 3). Excluding illness caused by Listeria, Toxoplasma, and hepatitis A virus (three pathogens that typically cause nongastrointestinal illness), 38.3 million cases of acute gastroenteritis are caused by known pathogens, and 13.6 million (36%) of these are attributable to foodborne transmission. Among all illnesses attributable to foodborne transmission, 30% are caused by bacteria, 3% by parasites, and 67% by viruses.

Hospitalizations

To estimate the number of hospitalizations due to foodhorne transmission, we calculated for each pathogen the expected number of hospitalizations among reported cases by multiplying the number of reported cases by pathogen-specific hospitalization rates from FoodNet data (23,24), reported outbreaks (10,25), or other published studies (Appendix). Not all illnesses resulting in hospitalization are diagnosed or reported. Health-care providers may not order the necessary diagnostic tests, patients may have already taken antibiotics that interfere with diagnostic testing, or the condition leading to hospitalization may be a sequela that develops well after resolution of the actual infection (e.g., Campylobacter-associated Guillain-Barre syndrome). Therefore, to account for underreporting, we doubled the number of hospitalizations among reported cases to derive for each pathogen an estimate of the total number of hospitalizations. Finally we multiplied this figure by the proportion of infections attributable to foo dborne transmission. Because of gaps in the available data, this approach could not be used for some parasitic and viral diseases (Appendix).

Overall, the pathogens listed in Table 2 cause an estimated 181,177 hospitalizations each year, of which 60,854 are attributable to foodborne transmission (Table 3). Excluding hospitalizations for infection with Listeria, Toxoplasma, and hepatitis A virus, 163,015 hospitalizations for acute gastroenteritis are caused by known pathogens, of which 55,512 (34%) are attributable to foodborne transmission. Overall, bacterial pathogens account for 60% of hospitalizations attributable to foodborne transmission, parasites for 5%, and viruses for 34%.

Deaths

Like illnesses and hospitalizations, deaths are also underreported. Precise information on food-related deaths is especially difficult to obtain because pathogen-specific surveillance systems rarely collect information on illness outcome, and outcome-specific surveillance systems (e.g., death certificates) grossly underreport many pathogen-specific conditions. To estimate the number of deaths due to bacterial pathogens, we used the same approach described for hospitalizations: first calculating the number of deaths among reported cases, then doubling this figure to account for unreported deaths, and finally multiplying by the percentage of infections attributable to foodborne transmission. As with hospitalization, this approach could not be used for some parasitic and viral diseases.

Overall, the specified pathogens cause an estimated 2,718 deaths each year, of which 1,809 are attributable to foodborne transmission (Table 3). Excluding death due to Listeria, Toxoplasma, and hepatitis A virus, the number of deaths due to pathogens that cause acute gastroenteritis is 1,381, of which 931 (67%) are attributable to foodborne transmission. Bacteria account for 72% of deaths associated with foodborne transmission, parasites for 21%, and viruses for 7%. Five pathogens account for over 90% of estimated food-related deaths: Salmonella (31%), Listeria (28%), Toxoplasma (21%), Norwalk-like viruses (7%), Campylobacter (5%), and E. coli 0157:H7 (3%).

Food-Related Illness and Death from Unknown Pathogens

Some proportion of gastrointestinal illness is caused by foodborne agents not yet identified. This conclusion is supported by well-documented foodborne outbreaks of distinctive illness for which the causative agent remains unknown (e.g., Brainerd diarrhea) (26), by the large percentage of foodborne outbreaks reported to CDC for which no pathogen is identified (25), and by the large number of new foodborne pathogens identified in recent years.

To estimate food-related illness and death from unknown pathogens, we used symptom-based data to estimate the total number of acute gastrointestinal illnesses and then subtracted from this total the number of cases accounted for by known pathogens; this difference represents the illness due to acute gastroenteritis of unknown etiology. To determine how much of this illness was due to foodborne transmission, we used the percentages of foodborne transmission as determined above for acute gastroenteritis caused by known pathogens.

Total Cases

To determine the rate of acute gastroenteritis in the general population, we used data on the frequency of diarrhea from the 1996 to 1997 FoodNet population survey. This survey did not collect data on the rate of vomiting among persons without diarrhea, however, so we relied on the Tecumseh and Cleveland studies for information on the frequency of this symptom. Because young children were overrepresented in the Tecumseh and Cleveland studies relative to the current U.S. population, rates of illness for these studies were age-adjusted. For the Tecumseh data, we used the reported age- and symptom-specific rates. For the Cleveland study, we used the method described by Garthright (27) to derive an overall age-adjusted rate of gastrointestinal illness; we then multiplied this rate by the relative frequency of symptoms to derive age-adjusted rates for specific symptoms.

In the 1996-97 FoodNet population survey the overall rate of diarrhea was 1.4 episodes per person per year, and the rate of diarrheal illness, defined as diarrhea (3 loose stools per 24-hour period) lasting [greater than]1 day or interfering with normal activities, was 0.75 episodes per person per year (H. Herikstad, manuscript in preparation). We used the lower 0.75 rate for our analysis. To this we added the average age-adjusted rate of vomiting without diarrhea from the Tecumseh and Cleveland studies (0.30, Table 4) to derive an overall estimate of 1.05 episodes per person per year of acute gastrointestinal illness characterized by diarrhea, vomiting, or both.

Previous studies have shown that some cases of acute gastrointestinal illness are accompanied by respiratory symptoms; although the causes of these illnesses are generally unknown, such cases have traditionally been attributed to respiratory pathogens (20,27). Data on the frequency of concomitant respiratory symptoms were not collected in the 1996-9 7 FoodNet survey but were 20% to 27% among patients with acute gastroenteritis in the Tecumseh and Cleveland studies. Therefore, we adjusted downward our estimate of acute gastroenteritis by 25%, yielding a final estimate of 0.79 (1.05 X 0.75) episodes of acute gastroenteritis per person per year. Extrapolated to a population of 267.7 million persons, the U.S. resident population in 1997 (28), this rate is equivalent to 211 million episodes each year in the United States.

As determined previously, 38.3 million of these 211 million episodes of acute gastroenteritis are attributable to known pathogens. A small proportion of the remaining 173 million episodes can be accounted for by known, noninfectious agents (e.g., mycotoxins, marine biotoxins); however, most are attributable to unknown agents. Because we cannot directly ascertain how many of these illnesses of unknown etiology are due to foodhorne transmission, we used the relative frequency of foodborne transmission for known pathogens as a guide. For illnesses of known etiology, foodborne transmission accounts for 36% of total cases. Applying this percentage yields an estimate of 62 million cases of acute gastroenteritis of unknown etiology (36% of 173 million) due to foodborne transmission each year.

Hospitalizations

The National Ambulatory Medical Care Survey/National Hospital Ambulatory Medical Care Survey data were searched for visits due to symptoms of diarrhea, vomiting, or gastrointestinal infection (reason for visit classification (RVC) codes 1595, 1530, 1540) (17) and for visits resulting in a diagnosis of infectious enteritis (ICD-9-CM codes 001-009.3; Table 1). Visits associated with respiratory symptoms (RVC codes 1400-1499) or a diagnosis of influenza (ICD-9-CM code 487) were excluded. Data for the years 1992 to 1996 were combined before analysis. Overall, these criteria yielded an average of 15,810,905 visits annually from 1992 through 1996, of which an average of 1,246,763, or 7.9%, resulted in hospitalization. This figure is equivalent to a rate of 4.7 hospitalizations per 1,000 person-years.

The National Hospital Discharge Survey data were searched by using diagnostic codes for infectious gastroenteritis of known cause (ICD-9-CM codes 001-008; Table 1), with the exception of the code for Clostridium difficile colitis (ICD9 008.45), a common form of nosocomially acquired diarrhea. In addition, we included the nonspecific ICD-9-CM diagnosis codes 009 (infectious gastroenteritis) and 558.9 (other and unspecified noninfectious gastroenteritis and colitis). Despite the description, many of the illnesses attributed to ICD-9-CM code 558.9 are likely to be either infectious or due to agents possibly transmitted by food. For example, in the absence of laboratory testing, sporadic cases of viral gastroenteritis may be coded as 558.9. Under the previous ICD-8 classification, these same cases would have been assumed to be infectious and coded as 009 (29,30). Data for the years 1992 to 1996 were weighted according to National Center for Health Statistics criteria and averaged to derive national estimates of annual hospitalizations. Records with a diagnosis of respiratory illness were not excluded because of the high incidence of respiratory infections among hospitalized patients.

Considering all listed diagnoses, the National Hospital Discharge Survey data for the years 1992 to 1996 yielded an annual average of 616,337 hospital discharges with a diagnosis of gastrointestinal illness. Included in this figure are 193,084 cases of gastroenteritis with an identified pathogen and an additional 423,293 cases of gastroenteritis of unknown etiology (Table 5). Converted to a rate, the total number is equivalent to 2.3 hospitalizations per 1,000 person-years. Because these data depend on the recording of a diagnosis and not just a symptom, it is likely that they underestimate the rate of hospitalization for acute gastroenteritis. This view is supported by FoodNet population survey data indicating a rate of approximately 7.2 hospitalizations per 1,000 person-years for diarrheal illness (H. Herikstad, manuscript in preparation). These data were not included here because they omit hospitalizations for vomiting alone and are not easily adjusted for concomitant respiratory symptoms. Averaging the r ates from the National Ambulatory Medical Care Survey/National Hospital Ambulatory Medical Care Survey and National Hospital Discharge Survey yields a final estimate of 3.5 hospitalizations per 1,000 person-years, equivalent to 936,726 hospitalizations annually for acute gastroenteritis. As noted previously, 163,153 of these hospitalizations can be attributed to known causes of acute gastroenteritis, yielding an estimated 773,573 hospitalizations for acute gastroenteritis caused by unknown agents. Applying the relative frequency of foodborne transmission as determined for known pathogens yields an estimated 263,015 hospitalizations (34% of 773,573) for acute gastroenteritis due to foodborne transmission of unknown agents.

Deaths

Multiple-cause-of-death data (16) and information on in-hospital-death data (National Hospital Discharge Survey) were used. ICD-9-CM codes 001-008 were employed to identify deaths due to diagnosed infectious gastroenteritis and ICD-9-CM codes 009 and 558 to identify deaths due to gastroenteritis of unknown etiology.

Death certificate data for the years 1992 to 1996 yielded an annual average of 6,195 total deaths, of which 1,432 (23%) were due to specific causes of gastroenteritis and 4,763 (77%) to undiagnosed causes of gastroenteritis, For the same years and ICD-9-CM codes, the average annual in-hospital deaths for all-listed diagnoses totaled 6,608, of which 1,460 were due to specific and 5,148 (77%) undiagnosed causes of gastroenteritis (Table 5). Averaging the totals for all causes from death certificate and National Hospital Discharge Survey data and adjusting to the 1997 U.S. census estimates, we estimated that gastroenteritis contributed to the death of 6,402 persons in the United States in 1997.

A total of 1,386 of these deaths can be explained by known causes of acute gastroenteritis (see above). Thus an estimated 5,016 deaths from acute gastroenteritis are caused by unknown agents. Applying the relative frequency of foodborne transmission as determined for known pathogens yields an estimated 3,360 deaths (67% of 5,016) due to acute gastroenteritis caused by foodborne transmission of unknown agents.

Overall Food-Related Illness and Death

We summed illness attributable to foodborne gastroenteritis caused by known and unknown pathogens, yielding an estimate of 76 million illnesses, 318,574 hospitalizations, and 4,316 deaths. Adding to these figures the nongastrointestinal illness caused by Listeria, Toxoplasma, and hepatitis A virus, we arrived at a final national estimate of 76 million illnesses, 323,914 hospitalizations, and 5,194 deaths each year (Figure 1).

Conclusions

The nature of food and foodborne illness has changed dramatically in the United States over the last century. While technological advances such as pasteurization and proper canning have all but eliminated some disease, new causes of foodborne illness have been identified. Researchers have used various methods to estimate the illnesses and deaths due to foodborne diseases in the United States. In 1985, Archer and Kvenberg coupled information on underreporting of salmonellosis with data on other foodborne pathogens to derive estimates of 8.9 million illnesses due to known pathogens and 24 million to 81 million illnesses due to all foodborne agents (2). In 1987, Bennett et al. computed incidence figures for all known infectious diseases and determined the proportion of each due to various modes of transmission. Summing these figures, they concluded that foodborne transmission of known pathogens caused 6.5 million illnesses and up to 9,000 deaths each year (3). In 1989, Todd used a combination of methods, includi ng extrapolation from Canadian surveillance data, to derive an estimate of 12.5 million foodborne illnesses and 522 related deaths each year (4). Finally, in 1994, a task force convened by the Council for Agricultural Science and Technology (CAST) reviewed available studies and estimated the overall number of food-related illnesses at 33 million cases per year (5). These various estimates often refer to different entities. The estimates of 6.5 million and 8.9 million refer to illness caused by known pathogens, whereas the estimate of 33 million refers to all causes of foodborne illnesses, known and unknown, infectious and noninfectious.

Our estimates are based on data from a wide variety of sources and differ from previous estimates in several respects. For known pathogens, our estimate of 13.8 million illnesses per year is substantially higher than the previous estimates of 6.5 million and 8.9 million (2,3), an increase attributable largely to our inclusion of foodborne illness caused by Norwalk-like viruses. For foodborne illness of all etiologies, our estimate of 76 million illnesses is within the range proposed by Archer and Kvenberg (2) but considerably higher than the point estimate of 33 million presented in the CAST report (5). Both our estimate and the CAST estimate assume that foodborne transmission accounts for [tilde]35% of acute gastroenteritis cases caused by unknown agents. The disparity between the two stems from differences in the estimated annual frequency of acute gastroenteritis overall: 211 million cases for our estimate 99 million for the CAST estimate.

Whereas our estimates of illness are generally higher than those of previous studies, our estimates of death are generally lower We estimate that foodborne illness causes. 5,020 deaths annually (1,810 deaths due to known pathogens and 3,210 deaths due to unknown agents), a total that is slightly more than half the 9,000 deaths estimated by Bennett et al. (3). The Bennett estimate includes 2,100 deaths due to campylobacteriosis, 1,200 deaths due to staphylococcal food poisoning, and 1,000 deaths due to trichinosis: our total for all three of these diseases is 101 deaths. Our estimated case-fatality rates for several other diseases are also lower than those used in the Bennett report, either because better data are available or perhaps because treatment has improved.

Our analysis suggests that unknown agents account for approximately 81% of foodborne illnesses and hospitalizations and 64% of deaths. Among cases of foodborne illness due to known agents, Norwalk-like viruses account for over 67% of all cases 33% of hospitalizations, and 7% of deaths. The assumptions underlying the Norwalk-like viruses figures are among the most difficult to verify and these percentages should be interpreted with caution (Appendix). Other important causes of severe illness are Salmonella and Campylobacter, accounting for 26% and 17% of hospitalizations, respectively The leading causes of death are Salmonella, Listeria, and Toxoplasma, which together account for 1,427, or more than 75% of foodborne deaths caused by known pathogens. Many of the deaths due to toxoplasmosis occur in HIV-infected patients; recent advances in HIV treatment may greatly reduce deaths due to toxoplasmosis.

Of necessity our analysis entails a number of assumptions. The first major assumption concerns the degree of underreporting. Well-documented estimates of underreporting are not available for most pathogens; therefore, we relied on multipliers derived for salmonellosis and other diseases. For salmonellosis, the multiplier of 38 has been independently derived by investigators in the United States using different data sources. The U.S. figure is five to tenfold higher than multipliers for Salmonella and Campylobacter recently derived in Great Britain (31). However, this difference is nearly or wholly offset by far higher per capita rates of reported infections in Great Britain. Nevertheless, when extrapolated to other pathogens, these multipliers may result in under- or overestimates, and clearly studies such as those conducted for Salmonella are needed to develop better multipliers for these other diseases. However, in our analysis, changing the multipliers for individual diseases has a minimal effect on the o verall estimate of foodborne illness.

Our second set of assumptions concerns the frequency of foodborne transmission for individual pathogens. We have used published studies when available, but these are rare. As with underreporting multipliers, errors affect estimates for individual pathogens but have minimal effect on the estimate of overall illness and death from foodbome diseases. The one notable exception is the estimate for Norwalk-like viruses. Because these viruses account for an especially large number of illnesses, changes in the percentage attributed to foodborne transmission have a major effect on our overall estimates. For example, if the actual number of infections due to foodborne transmission were 30% rather than 40%, the overall estimate would decrease from 76 million to 63 million illnesses per year. Interestingly, our overall estimate is influenced far less by the Norwalk-like virus case estimate itself. It would require a 100-fold reduction in the estimated number of Norwalk-like virus cases to reduce the overall estimate from 76 million to 63 million.

A third assumption concerns the frequency of acute gastroenteritis in the general population. The rate we used is based in part on recent data from the FoodNet population survey a retrospective survey involving more than 9,000 households. The overall rate of diarrhea as recorded by the survey was 1.4 episodes per person per year; however, we used the survey's far lower rate of 0.75 episodes of diarrheal illness per person per year. Furthermore, we limited our definition of acute gastroenteritis to symptoms of diarrhea or vomiting and reduced the rate to account for concomitant respiratory symptoms. As a result, our final assumed rate of 0.79 episodes of acute gastroenteritis per person per year is very similar to respiratory-adjusted estimates derived from the prospectively conducted Tecumseh (0.74) and Cleveland (0.71) studies (27). All three studies are based on household surveys, and thus the rates of illness are not influenced by changes in health-care delivery. Compared with rates of diarrheal illness fr om studies conducted in Great Britain, our estimated rate is higher than in one recent study (31) but lower than another (32).

In addition to these assumptions, our analysis has several limitations. Differences in available surveillance information prevented us from using the same method to estimate illness and death from bacterial, parasitic, and viral pathogens. Furthermore, because of a paucity of surveillance information, we did not include specific estimates for some known, occasionally foodborne pathogens (e.g., Plesiomonas, Aeromonas, or Edwardsiella), nor did we develop specific estimates for known noninfectious agents, such as mushroom or marine biotoxins, metals, and other inorganic toxins. However, many of these agents cause gastroenteritis and are therefore captured in our overall estimate of foodborne illness. With the exception of a few important pathogens (Appendix), we have not estimated the number of cases of chronic sequelae, although these may he part of the overall burden of foodborne diseases. Finally, future research will refine our assumptions and allow for more precise estimates.

Methodologic differences between our analysis and previously published studies make it difficult to draw firm conclusions regarding overall trends in the incidence of foodborne illness. In general, the differences between our estimates and previously published figures appear to he due primarily to the availability of better information and new analyses rather than real changes in disease frequency over time. For example, E. coli 0157:H7 was estimated to cause 10,000 to 20,000 illnesses annually, based on studies of patients visiting a physician for diarrhea. Recent FoodNet data have allowed a more detailed estimation of mild illnesses not resulting in physician consultation. Our estimate of nearly 74,000 illnesses per year incorporates these milder illnesses and should not he misconstrued as demonstrating a recent increase in E. coli 0157:H7 infections. Whatever the limitations on retrospective comparisons, the estimates presented here provide a more reliable benchmark with which to judge the effectiveness o f ongoing and future prevention efforts.

Further refinements of foodborne disease estimates will require continued and improved active surveillance. Beginning in 1998, the FoodNet population survey was modified to capture cases of vomiting not associated with diarrhea; further enhancement to capture concomitant respiratory symptoms should refine the FoodNet survey data. Expansion of laboratory diagnostic capacity could lead to better detection of certain pathogens, estimates of the degree of underreporting for additional diseases, and estimates of the proportion of specific diseases transmitted through food. Heightened surveillance for acute, noninfectious food-borne diseases, such as mushroom poisoning and other illnesses caused by biotoxins, could further improve estimates of illness and death from foodborne illness. Emergency department-based surveillance systems (33) or poison control center-based surveillance might provide such information. Finally, identifying new causes of enteric illness and defining the public health importance of known ag ents (e.g., enteroaggregative E. coli) would improve foodborne disease prevention efforts.

Acknowledgements: We thank Fred Angulo, Beth Bell, Thomas Breuer, Cindy Friedman, Roger Glass, Eric Mintz, Steven Ostroff, Morris Potter, David Swerdlow, Tom Van Gilder, and two anonymous reviewers for their comments.

                 ICD-9-CM Codes and Associated Conditions
Code                      Condition
001                       Cholera
002                       Typhoid Fever
003                       Salmonella
004                       Shigellosis
005.0                     Staphyloccocal Food Poisoning
005.1                     Botulism
005.2-005.3               Other Clostridia
005.4                     Vibrio parahaemolyticus
005.8-005.9               Other and Unspecified Bacterial Food Poisoning
006                       Amebiasis
007.1                     Giardiasis
007.0, 007.2-007.9        Other Protozoal Intestinal Infections
008.00, 008.09            Misc. Escherichia coli
008.01                    Enteropathogenic E. coli
008.02                    Enterotoxigenic E. coli
008.03                    Enteroinvasive E. Coli
008.04                    Enterohemorrhagic E. coli
008.43                    Campylobacter
008.44                    Yersinia
008.41-2, 008.46-9, 008.5 Misc. Bacterial
008.61                    Rotavirus
008.62                    Adenovirus
008.63                    Norwalk Virus
008.64                    Other Small Round Structured Viruses
008.65                    Calicivirus
008.66                    Astrovirus
008.67                    Enterovirus
008.69, 008.8             Other Virus
009                       III-Defined Intestinal Infections
558.9                     Other Noninfectious Gastroenteritis
                  Reportered and Estimated [a] Illnesses,
                 Frequency of Foodborne Transmission, and
                  Hospitalization and Case-Fatality Rates
               for Known Foodborne Pathogens, United States
                                  Estimated    Reported Cases
                                      Total by Surveillance Type
Disease or Agent                      Cases        Active        Passive
Bacterial
   Bacillus cereus                   27,360                          720
   Botulism, Foodborne                   58                           29
   Brucella spp.                      1,554                          111
   Campylobacter spp.             2,453,926        64,577         37,496
   Clostridium perfringens          248,520                        6,540
   Escherichia coli 0157:H7          73,480         3,674          2,725
   E. Coli, Non-0157 STEC            36,740         1,837
   E. Coli, Enterotoxigenic          79,420                        2,090
   E. Coli, Other Diarrheogenic      79,420                        2,090
   Listeria monocytogenes             2,518         1,259            373
   Salmonella Typhi [b]                 824                          412
   Salmonella, Nontyphoidal       1,412,498        37,171         37,842
   Shigella spp.                    448,240        22,412         17,324
   Staphylococcus Food Poisoning    185,060                        4,870
   Streptococcus, Foodborne          50,920                        1,340
   Vibrio cholerae, Toxigenic            54                           27
   V. Vulnificus                         94                           47
   Vibrio, Other                      7,880           393            112
   Yersinia enterocolitica           96,368         2,536
Subtotal                          5,204,934
Parasitic
   Cryptosporidium parvum           300,000         6,630          2,788
   Cyclospora cayetanensis           16,264           428             98
   Giardia lamblia                2,000,000       107,000         22,907
   Toxoplasma gondii                225,000                       15,000
   Trichinella spiralis                  52                           26
Subtotal                          2,541,316
Viral
   Norwalk-like Viruses          23,000,000
   Rotavirus                      3,900,000
   Astrovirus                     3,900,000
Hepatitis A                          83,391                       27,797
Subtotal                         30,883,391
Grand Total                      38,629,641
                                               %
                                           Foodborne   Hospitalization
Disease of Agent                 Outbreak Transmission      Rate
Bacterial
   Bacillus cereus                     72     100           0.006
   Botulism, Foodborne                        100           0.800
   Brucella spp.                               50           0.550
   Campylobacter spp.                 146      80           0.102
   Clostridium perfringens            654     100           0.003
   Escherichia coli 0157:H7           500      85           0.295
   E. Coli, Non-0157 STEC                      85           0.295
   E. Coli, Enterotoxigenic           209      70           0.005
   E. Coli, Other Diarrheogenic                30           0.005
   Listeria monocytogenes                      99           0.922
   Salmonella Typhi [b]                        80           0.750
   Salmonella, Nontyphoidal         3,640      95           0.221
   Shigella spp.                    1,476      20           0.139
   Staphylococcus Food Poisoning      487     100           0.180
   Streptococcus, Foodborne           134     100           0.133
   Vibrio cholerae, Toxigenic                  90           0.340
   V. Vulnificus                               50           0.910
   Vibrio, Other                               65           0.126
   Yersinia enterocolitica                     90           0.242
Subtotal
Parasitic
   Cryptosporidium parvum                      10           0.150
   Cyclospora cayetanensis                     90           0.020
   Giardia lamblia                             10             n/a
   Toxoplasma gondii                           50             n/a
   Trichinella spiralis                       100           0.081
Subtotal
Viral
   Norwalk-like Viruses                        40             n/a
   Rotavirus                                    1             n/a
   Astrovirus                                   1             n/a
Hepatitis A                                     5           0.130
Subtotal
Grand Total
                                   Case
                                 Fatality
Disease of Agent                   Rate
Bacterial
   Bacillus cereus                0.0000
   Botulism, Foodborne            0.0769
   Brucella spp.                  0.0500
   Campylobacter spp.             0.0010
   Clostridium perfringens        0.0005
   Escherichia coli 0157:H7       0.0083
   E. Coli, Non-0157 STEC         0.0083
   E. Coli, Enterotoxigenic       0.0001
   E. Coli, Other Diarrheogenic   0.0001
   Listeria monocytogenes         0.2000
   Salmonella Typhi [b]           0.0040
   Salmonella, Nontyphoidal       0.0078
   Shigella spp.                  0.0016
   Staphylococcus Food Poisoning  0.0002
   Streptococcus, Foodborne       0.0000
   Vibrio cholerae, Toxigenic     0.0060
   V. Vulnificus                  0.3900
   Vibrio, Other                  0.0250
   Yersinia enterocolitica        0.0005
Subtotal
Parasitic
   Cryptosporidium parvum          0.005
   Cyclospora cayetanensis        0.0005
   Giardia lamblia                   n/a
   Toxoplasma gondii                 n/a
   Trichinella spiralis            0.003
Subtotal
Viral
   Norwalk-like Viruses              n/a
   Rotavirus                         n/a
   Astrovirus                        n/a
Hepatitis A                       0.0030
Subtotal
Grand Total
(a.)Numbers in italics are estimates; others are measured.
(b.)[greater than]70% of cases acquired abroad.
                Estimated Illnesses, Hospitalizations, and
                Deaths Caused by Known Foodborne Pathogens,
                               United States
                                   Illness
                                                      % of Total
Disease or Agent                     Total  Foodborne  Foodborne
Bacterial
  Bacillus cereus                   27,360     27,360        0.2
  Botulism, Foodborne                   58         58        0.0
  Brucella spp.                      1,554        777        0.0
  Campylobacter spp.             2,453,926  1,963,141       14.2
  Clostridium perfringens          248,520    248,520        1.8
  Escherichia coil 0157:H7          73,480     62,458        0.5
  E. coli, Non-0157 STEC            36,740     31,229        0.2
  E. coli, Enterotoxigenic          79,420     55,594        0.4
  E. coli, Other Diarrheogenic      79,420     23,826        0.2
  Listeria monocytogenes             2,518      2,493        0.0
  Salmonella Typhi                     824        659        0.0
  Salmonella, Nontyphoidal       1,412,498  1,341,873        9.7
  Shigella spp.                    448,240     89,648        0.6
  Staphylococcus Food Poisoning    185,060    185,060        1.3
  Streptococcus, Foodborne          50,920     50,920        0.4
  Vibrio cholerae, Toxigenic            54         49        0.0
  V. vulnificus                         94         47        0.0
  Vibrio, Other                      7,880      5,122        0.0
  Yersinia enterocolitica           96,368     86,731        0.6
Subtotal                         5,204,934  4,175,565       30.2
Parasitic
 Cryptosporidium parvum            300,000     30,000        0.2
 Cyclospora cayetanensis            16,264     14,638        0.1
 Giardia lamblia                 2,000,000    200,000        1.4
 Toxoplasma gondii                 225,000    112,500        0.8
 Trichinella spiralis                   52         52        0.0
subtotal                         2,541,316    357,190        2.6
Viral
  Norwalk-like Viruses          23,000,000  9,200,000       66.6
  Rotavirus                      3,900,000     39,000        0.3
  Astrovirus                     3,900,000     39,000        0.3
  Hepatitis A                       83,391      4,170        0.0
Subtotal                        30,833,391  9,282,170       67.2
Grand Total                     38,629,641 13,814,924      100.0
                                Hospitalizations                      Deaths
                                                           % of Total
Disease or Agent                      Total      Foodborne  Foodborne  Total
Bacterial
  Bacillus cereus                         8              8        0.0      0
  Botulism, Foodborne                    46             46        0.1      4
  Brucella spp.                         122             61        0.1     11
  Campylobacter spp.                 13,174         10,539       17.3    124
  Clostridium perfringens                41             41        0.1      7
  Escherichia coil 0157:H7            2,168          1,843        3.0     61
  E. coli, Non-0157 STEC              1,084            921        1.5     30
  E. coli, Enterotoxigenic               21             15        0.0      0
  E. coli, Other Diarrheogenic           21              6        0.0      0
  Listeria monocytogenes              2,322          2,298        3.8    504
  Salmonella Typhi                      618            494        0.8      3
  Salmonella, Nontyphoidal           16,430         15,608       25.6    582
  Shigella spp.                       6,231          1,246        2.0     70
  Staphylococcus Food Poisoning       1,753          1,753        2.9      2
  Streptococcus, Foodborne              358            358        0.6      0
  Vibrio cholerae, Toxigenic             18             17        0.0      0
  V. vulnificus                          86             43        0.1     37
  Vibrio, Other                          99             65        0.1     20
  Yersinia enterocolitica             1,228          1,105        1.8      3
Subtotal                             45,826         36,466       59.9  1,458
Parasitic
 Cryptosporidium parvum               1,989            199        0.3     66
 Cyclospora cayetanensis                 17             15        0.0      0
 Giardia lamblia                      5,000            500        0.8     10
 Toxoplasma gondii                    5,000          2,500        4.1    750
 Trichinella spiralis                     4              4        0.0      0
subtotal                             12,010          3,219        5.3    827
Viral
  Norwalk-like Viruses               50,000         20,000       32.9    310
  Rotavirus                          50,000            500        0.8     30
  Astrovirus                         12,500            125        0.2     10
  Hepatitis A                        10,841             90        0.9     83
Subtotal                            123,341         21,167       34.8    433
Grand Total                         181,117         60,854      100.0  2,718
                                          % of Total
Disease or Agent                Foodborne  Foodborne
Bacterial
  Bacillus cereus                       0        0.0
  Botulism, Foodborne                   4        0.2
  Brucella spp.                         6        0.3
  Campylobacter spp.                   99        5.5
  Clostridium perfringens               7        0.4
  Escherichia coil 0157:H7             52        2.9
  E. coli, Non-0157 STEC               26        1.4
  E. coli, Enterotoxigenic              0        0.0
  E. coli, Other Diarrheogenic          0        0.0
  Listeria monocytogenes              499       27.6
  Salmonella Typhi                      3        0.1
  Salmonella, Nontyphoidal            553       30.6
  Shigella spp.                        14        0.8
  Staphylococcus Food Poisoning         2        0.1
  Streptococcus, Foodborne              0        0.0
  Vibrio cholerae, Toxigenic            0        0.0
  V. vulnificus                        18        1.0
  Vibrio, Other                        13        0.7
  Yersinia enterocolitica               2        0.1
Subtotal                            1,297       71.7
Parasitic
 Cryptosporidium parvum                 7        0.4
 Cyclospora cayetanensis                0        0.0
 Giardia lamblia                        1        0.1
 Toxoplasma gondii                    375       20.7
 Trichinella spiralis                   0        0.0
subtotal                              383       21.2
Viral
  Norwalk-like Viruses                124        6.9
  Rotavirus                             0        0.0
  Astrovirus                            0        0.0
  Hepatitis A                           4        0.2
Subtotal                              129        7.1
Grand Total                         1,809      100.0
            Frequency of Gastrointestinal Illines in the General
                Population, in Episodes per Person per Year,
                       as Determined by Three Studies
                               FoodNet
                          Population Survey Tecumseh Study
Symptom                     Age Adjusted        Crude      Age Adjusted
Diarrhea or Vomiting             --              0.98          0.81
Diarrhea, Any                   0.75             0.63          0.52
Diarrhea Without Vomiting       0.61             0.40          0.33
Diarrhea With Vomiting          0.14             0.23          0.19
Vomiting Without Diarrhea        --              0.35          0.29
                          Cleveland Study
Symptom                        Crude      Age Adjusted
Diarrhea or Vomiting           1.28           0.87
Diarrhea, Any                  0.83           0.56
Diarrhea Without Vomiting      0.48           0.33
Diarrhea With Vomiting         0.35           0.23

Vomiting Without Diarrhea      0.45           0.31
              Average Annual Hospitalizations and Deaths for
             Gastrointestinal Illness by Diagnostic Category,
               National Hospital Discharge Survey, 1992-1996
                                 Fist Diagnosis               All Diagnoses
Cause of Enteritis [a]         Hospitalizations Deaths     Hospitalizations
Bacterial (001-005, 008-008.5)           27,987    148 [b]           54,953
Viral (008.6-008.8)                      82,149      0 [b]          132,332
Parasitic (006-007)                       2,806     82 [b]            5,799
Unknown Etiology (009, 558.9)           186,537    868 [b]          423,293
Total                                   299,479  1,898              616,377
Cause of Enteritis [a]         Deaths
Bacterial (001-005, 008-008.5)  1,139
Viral (008.6-008.8)               194 [b]
Parasitic (006-007)               127 [b]
Unknown Etiology (009, 558.9)   5,148
Total                           6,608
(a.)ICD-9-CM Code
(b.)Estimate Unreliable Due to Small Sample Size