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Contagious Acute Gastrointestinal Infections Daniel M. Musher, M.D., and Benjamin L. Musher, M.D.

i

n our ever-shrinking world, widespread media coverage of infections, ranging from the severe acute respiratory syndrome (also known as SARS) and influenza in Asia to acute gastroenteritis on cruise ships and outbreaks in day-care centers in the United States, has raised public interest in contagious diseases to new heights. Our purpose in this article is to examine contagion (from the Latin, tangere, to touch) — direct human-to-human spread — of acute gastrointestinal illness, defined as a syndrome of vomiting, diarrhea, or both, that begins abruptly in otherwise healthy persons and is most often self-limited. Unlike agents that cause contagious respiratory infections,1 which are largely or exclusively indigenous to humans, agents that cause acute gastrointestinal illness (Table 1) may spread from person to person or may be acquired from a common food or environmental source, often water; they may also result from exposure to animals. Food or water may serve as a primary source of contagion or may, in turn, have been contaminated by contact with an infected person or animal. Thus, the epidemiology of acute gastrointestinal illness is complex. Different ways of gathering, analyzing, and presenting data have generated very different estimates of the frequency of acute gastrointestinal illness, leading to seemingly contradictory results. Estimates based on extrapolation from isolation of known diarrheal pathogens and the numbers of stool samples submitted for study suggest that there might be 38 million cases of acute gastrointestinal illness each year.2 In contrast, a carefully conducted questionnaire survey asking about acute, self-limited illness characterized by vomiting, diarrhea, or both found that about 1.05 cases occur per person per year in the United States.2,3 When this number was reduced by 25 percent on the basis of estimates that a respiratory infection is the responsible agent in about one quarter of persons with symptoms of acute gastrointestinal illness, the resulting 0.79 case per person per year translated to 211 million cases of acute gastrointestinal illness nationally in 1997, the year for which data were available. Earlier data from the United States and questionnaire-based studies in the Netherlands and the United Kingdom yielded similar results.3 On the basis of reports to public health authorities and an exchange of information between the Centers for Disease Control and Prevention and a network of participating laboratories (FoodNet),2,3 there are thought to be about 76 million cases per year of foodborne infection. If this number and an additional 13 million cases of waterborne illness are subtracted,3 there may well be 122 million cases of acute gastrointestinal illness each year in the United States for which human-to-human transmission is responsible. As noted above, a varying proportion of foodborne and waterborne outbreaks are also ultimately attributable to human contamination.

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From the Medical Service, Infectious Disease Section, Michael E. DeBakey Veterans Affairs Medical Center, and the Departments of Medicine and Molecular Virology and Microbiology, Baylor College of Medicine — both in Houston (D.M.M.); and the Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia (B.L.M.). Address reprint requests to Dr. Daniel Musher at the Infectious Disease Section, Veterans Affairs Medical Center, Houston, TX 77030, or at daniel.musher@ med.va.gov. N Engl J Med 2004;351:2417-27. Copyright © 2004 Massachusetts Medical Society.

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Table 1. Agents That Commonly Cause Acute Gastrointestinal Illness.*

salmonella

Because many principles of contagion with respect to enteric organisms were elucidated in studies of typhoid fever, it seems appropriate to begin our discussion of causes of acute gastrointestinal illness with Salmonella typhosa (S. enterica serotype typhi). Although physicians do not always associate this organism with a typical syndrome of acute gastrointestinal illness,4 some studies suggest that diarrhea predominates in the majority of cases.5,6 S. typhi is highly adapted to humans. Infection is virtually always acquired by transmission from one person to another; an inviolable rule of epidemiology is that the occurrence of a case of typhoid fever implies an epidemiologic link to another person who either is actively infected or is chronically carrying the organism and shedding it in feces. When cases result from food ingestion, individual food handlers, such as the infamous cook known as Typhoid Mary,7 are usually found to be responsible. An infection from drinking contaminated water can also usually be traced to one or more infected persons whose excreta have entered the water supply.8-10 The current rarity of typhoid fever in the United States reflects good hygiene, lack of crowding, and high public health standards for home and industrial sewage. During the late 1990s, a breakdown of the public health infrastructure in the former Soviet Union led to a cessation of chlorination, the pirating of water lines with the use of substandard pipe fittings, and the crossing of these fittings by sewage lines, which culminated in an outbreak of 10,000 cases of typhoid fever.11 The likelihood of direct contagion depends on the number of organisms in feces or contaminated foods, their ability to survive, replicate, or both, and the infectivity of the species and the specific strain. Chronic carriers of S. typhi have 106 to 109 colonyforming units (CFU) per gram12 or more13 in their feces. In experimental studies, ingestion of 103 CFU of the Quailes strain of S. typhi was not infectious in volunteers, whereas nearly 50 percent of volunteers were infected by ingesting 105 or 107 CFU, and 96 percent were infected by ingesting 108 or more CFU.14,15 The results of these experimental studies indicate that a large inoculum is infective. However, infection in the real world will depend on the infectivity of the strain studied. In nature, such strains are almost certainly heterogeneous, as has been shown for other enteric16 and for respiratory1 pathogens.

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Bacteria Salmonella Shigella Campylobacter Escherichia coli O157:H7 Clostridium difficile Viruses Caliciviruses (Norwalk-like and related viruses) Rotavirus† Adenovirus types 40 and 41 Astrovirus Protozoa Giardia Cryptosporidium Entamoeba histolytica * These organisms commonly cause acute gastrointestinal infection in otherwise healthy children and adults in developed countries. The frequency of infection is similar among such countries — for example, the United States, United Kingdom, France, and Argentina. † Symptomatic disease usually occurs only in infants or very young children.

The early implications of the watchwords “fingers, food, and flies,” and the frequent spread from patients to nurses and physicians in the era before antibiotics,8 are consistent, at least in some instances of natural infection, with low-inoculum contagion, under the assumption that large numbers of organisms would not be transmitted in these situations. Infections with most other types of salmonella, except for S. paratyphi, derive from environmental sources, principally poultry and livestock. Despite the frequency with which these organisms cause acute gastrointestinal illness, there are remarkably few documented examples of person-to-person spread.17-19 An outbreak in a day-care facility was associated with an uncertain number of secondary cases,19 and long-term surveillance of 54 permanent carriers of nontyphoidal salmonella identified 10 instances of transmitted infection.20 On the basis of epidemiologic studies, the infective dose of nontyphoidal salmonella is thought to be small, not exceeding 100 CFU.21,22 The paucity of documented instances of contagion may reflect the difficulty of distinguishing person-to-person spread from that due to a common food source, rather than the true absence of human transmission. shigella

Like S. typhi, shigella has no reservoir in nature and spreads from person to person (usually child to

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child) after direct contact or the ingestion of contaminated food. Shigellosis is highly contagious; as few as 200 CFU can cause infection,23 and the role of a small inoculum is supported by early observations, which emphasized spread by casual contact and insect vectors.24 The high level of contagiousness of shigellosis may be inferred from the large number of secondary cases that follow a documented outbreak; persons who have varying degrees of contact with infected patients are likely, themselves, to become infected.25 A very young child is the usual source.26 Not surprisingly, shigella readily spreads within families,24 in custodial institutions,27 and within and among children’s day-care centers.28,29 Daycare centers provide remarkable natural settings in which contagion in acute gastrointestinal illness can be studied28 (Table 2). In these settings, shigellosis (Tables 1 and 2) may affect from one third to two thirds of children,30 with severe diarrhea increasing the likelihood of contagion, reflecting high fecal counts of bacteria and increased chances of soiling.26 At least one additional case of shigellosis is recognized in the families of about 25 percent of infected children.28 The current widespread use of medications that reduce gastric acidity (which normally eradicates salmonella and shigella) probably increases the risk of spread14 to parents of infected children or to adults who work in day-care centers.

Table 2. Factors That May Contribute to Contagion of Acute Gastrointestinal Illnesses within Day-Care Centers.* Presence of one or more cases of acute gastrointestinal illness Lack of gloving or handwashing during or after diaper changes or helping at toilet Lack of policy to isolate or send home children with acute gastrointestinal illness Common area for diaper changing Larger groups of children Carpeted flooring Shared toys and classroom objects * These factors are discussed in Pickering et al.30

escherichia coli o157:h7

Transmission of Escherichia coli O157:H7 occurs primarily through the consumption of contaminated meat, but secondary infection does occur, and a small bacterial inoculum may lead to clinical illness. For example, of 501 cases of E. coli–related diarrhea linked to hamburger consumption in an epidemic that occurred during 1992 and 1993, 48 infections (about 10 percent) were secondary.42 Person-toperson transmission occurs in day-care centers,43 among families,44 and in mental institutions45; an attack rate — the rate of appearance of symptoms in exposed persons — of around 20 percent has been reported. It is worth noting that this form of acute gastrointestinal infection is associated with a campylobacter substantial incidence of the hemolytic–uremic synThe epidemiology of infection due to campylobac- drome, affecting up to 13 percent of young chilter, perhaps now the most common bacterial cause dren with the infection.46 of acute gastrointestinal illness,31,32 is similar to that of nontyphoidal salmonella. Most infections clostridium difficile are traced to poultry, meat, dairy products, or con- Clostridium difficile is a major cause of nosocomial taminated water.33 Although fewer than 1000 CFU colitis, generally occurring after antibiotic-induced may cause infection,16 massive foodborne out- alterations of bowel flora.47 Although the disease in breaks are not often recognized, in part because this some persons results from the proliferation of an organism does not replicate in food34 and in part endogenous strain, infection is clearly contagious; because ingestion even of large numbers of organ- in hospitals, both human vectors and environmenisms may cause symptoms in only a small propor- tal contamination are implicated in the spread.48 tion of subjects.16 Contagion within the home has In day-care settings, an infection in one child may been described occasionally,35-37 and in one house- be followed by the spread of C. difficile to 50 percent hold, an infant was infected with the same strain of the classmates, in nearly all of whom diarrhea that caused diarrhea in a newly acquired puppy.38 As then develops49; contagion is greatly facilitated by with nontyphoidal salmonella, the paucity of de- the ingestion of antibiotics. Caregivers may acquire scriptions of human-to-human spread may reflect C. difficile colitis while caring for patients who have the difficulty of studying organisms that are present this disease. We treated an elderly woman for acute in so many food sources. Infection by campylobac- C. difficile colitis; she had been caring for her huster,39 as well as by S. typhi40 and shigella,41 has been band during his bout of C. difficile colitis, and she had shown to be contagious among homosexual men. not been taking antibiotics. Her stools contained

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C. difficile toxin, and she responded to treatment with caliciviruses metronidazole (unpublished data). Calciviruses, of which Norwalk-like viruses are the prototype, cause more than 90 percent of outbreaks of acute gastrointestinal illness in the United States viral causes and account for about 23 million cases of diarrheal At least since the end of the Second World War, in disease per year, according to the pathogen-assocideveloped countries, viruses have been thought to ated method of calculation.2,61 As already noted, if cause the vast majority of cases of acute gastroin- the same percentages are applied to cases of acute testinal illness, whether sporadic or part of an out- gastrointestinal illness identified by questionnaire, break. In the 1950s, a definitive family study by the incidence of calicivirus-induced infection is far Dingle et al.50 found no isolates of salmonella or greater; there may be a total of 74 million cases shigella in 77 cases of acute gastrointestinal illness; each year in the United States. Outbreaks have been these investigators concluded that most cases were reported in nursing homes and on military bases due to viruses, although, at the time, they were un- and school campuses, but Norwalk-like viruses on able to isolate them. At that time, techniques were cruise ships have made national headlines in the not available to identify campylobacter or E. coli past few years.62,63 Attack rates have been as high O157:H7. The relative infrequency of bacterial as 41 percent, reflecting the propensity of infection acute gastrointestinal illness in developed coun- with Norwalk-like viruses to cause emesis and votries was confirmed by prospective studies that iden- luminous stools, the large number of organisms in tified salmonella, shigella, campylobacter, and E. coli stools and vomitus, and the low inoculum (fewer O157:H7 each in 2 percent or less of fecal samples32; than 100 viral particles) required to produce infecthese numbers have steadily declined in the past tion. The extent of spread in such closed environseveral years.51 In contrast, in underdeveloped na- ments may involve nearly 100 percent of exposed tions, one of the aforementioned bacteria, vibrio, persons, since experimental ingestion of infectious enteropathogenic E. coli, protozoa, or intestinal par- material causes symptoms in only 50 to 80 percent asites cause the majority of cases of acute gastroin- of subjects.64,65 Although consumption of contaminated food testinal illness. In the United States, the United Kingdom, north- or water causes large outbreaks of infection with ern Europe, and Japan, caliciviruses such as the Norwalk-like virus, the importance of person-toNorwalk and Sapporo viruses are the most common person transmission has been recognized since the cause of sporadic acute gastrointestinal illness in initial identification of this organism in an outbreak patients of all age groups except infants and tod- that affected one third of family members and 50 dlers, in whom rotaviruses predominate.52-54 Ade- percent of school contacts.66 Well-documented secnovirus types 40 and 4155,56 and astroviruses57-59 ondary outbreaks62 indicate person-to-person, rathhave also been implicated. Caliciviruses and astrovi- er than foodborne, transmission. For example, in a ruses are more prevalent among outpatients, where- hyperacute outbreak67 traced to a food handler in a as rotavirus is a common cause of hospitalization.60 college dining hall, about 20 percent of all cases Features of contagion by these agents are summa- occurred after the dining hall was closed and were rized in Table 3. therefore thought to reflect secondary person-toWithin families, acute gastrointestinal illnesses person spread (Fig. 1). In a large community outare spread chiefly by young children, whose hygiene break in Sweden, secondary cases appeared in one is not as consistently good as that of adults and who third of the households in which a case occurred.68 are dependent on, and therefore in intimate contact Contagion by Norwalk-like viruses has been docuwith, their parents and caregivers.50 As shown by mented in other circumstances as well. When BritDingle et al.,50 20 percent of persons have sympto- ish soldiers with acute gastrointestinal illness were matic infection after exposure to a family member airlifted out of a combat zone, two flight medics and with acute gastrointestinal illness. The likelihood of one hospital staff member subsequently became ill; secondary infection increases from 10 percent when fecal samples from both the patients and the medisymptoms are mild to 30 percent if severe vomiting cal personnel contained Norwalk-like viruses.69 In and diarrhea are present, reflecting increased vol- another example, 43 members of a football team umes of infective excreta that presumably contain contracted acute gastrointestinal illness from a sinhigher concentrations of infective particles. gle food source. Eleven members of an opposing

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Very low (1–2 cysts)

Cryptosporidium

Tap water, human contact

Tap water, human contact

Human contact (feces, possibly vomitus)

Human contact

Human contact

Human contact (feces, vomitus), prepared food

Poultry, milk, tap water

Human contact, prepared food, contaminated water

Poultry, eggs, meat

Human contact, prepared food, contaminated water

Usual Mode of Transmission

RT-PCR

Fecal culture

Fecal culture

Fecal culture

Blood culture, fecal culture

Diagnostic Methods

Abdominal discomfort, diarrhea

Diarrhea, vomiting, fever

Diarrhea

Microscopical examination of feces

Microscopical examination of feces

EIA (not commercially available)

EIA (not commercially available)

Fever, vomiting, EIA, latex diarrhea (in infants) agglutination

Diarrhea, vomiting, fever

Diarrhea, fever

Diarrhea, fever

Diarrhea, fever

Fever, abdominal pain, diarrhea

7 days Diarrhea, abdominal (1–14 days) pain, headache, fever

9 days (1–2 wk)

2–3 days

1–2 days

2 days

1 day (1–2 days)

3 days (1–7 days)

3 days (1–7 days)

24 hr (8–24 hr)

5–14 days

Incubation Period Usual Symptoms

10–12 days (3–60)

1–8 wk

2–4 days (1–7)

2–5 days (1–14)

4 days (3–9)

2 days (1–3)

3 days (1–7)

3 days (2–6)

2–4 days

3–4 wk

7 days

3 wk–6 mo

5 days (3–11 days)

4 days (1 day to weeks)

4 days (2–7 days)

3 days (1 day to weeks)

50% negative after 3 wk

Days to weeks

5 wk, rarely lifetime

2–6 wk, rarely lifetime

Duration of Symptoms Duration of Shedding

Very low

High

Low

High

Very high

Very high

Very low

Very high

Very low

High

Probability of Humanto-Human Spread†

* This table is subject to the limitations of the medical literature (for some organisms, clinical studies are more detailed, whereas for other organisms the documentation may not exist, although the clinical syndromes may be very similar). In the entries in the columns “Incubation Period,” “Duration of Symptoms,” and “Duration of Shedding,” the numbers in parentheses indicate the range. “Shedding” is the time during which the infectious agent can be recovered from feces after the end of illness. CFU denotes colony-forming units, RT-PCR reverse-transcriptase–polymerase-chain-reaction assay, and EIA enzyme immunoassay. † This column reflects the authors’ assessment of the likelihood of human-to-human spread, based on all the available sources of information as presented in the text. ‡ Experimental studies show a high inoculum, but some clinical observations suggest a low inoculum.

Low (≤102 organisms)

Giardia

Unknown

Astrovirus Unknown

Very low

Rotavirus

Adenovirus types 40 and 41

Low

Low

Low (≤102 CFU)

Low (102–103 CFU)

High (105 CFU)‡

Calicivirus

Campylobacter

Shigella

Salmonella (nontyphoidal)

Salmonella typhi

Agent

Quantity of Inoculum to Cause Disease

Table 3. Relevant Features of Selected Acute Gastrointestinal Infections.*

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A Questionnaire 120

No. of Cases

100 80 60 40 20 0 0

1

2

3

4

5

6

7

8

9

10

11

12

Day of Outbreak

160 140

No. of Cases

120 100 80 60 40 20 0 1

2

3

4

5

6

7

8

9

10

11

12

Day of Outbreak

Figure 1. Contagion (Primary and Secondary Infection) in a Foodborne Outbreak of Infection. An outbreak of a presumed calicivirus infection was traced to a single food handler who prepared salads in a college dining hall.67 Panel A shows the number of cases of acute gastrointestinal infection that developed each day, as reported on a questionnaire by persons who ate or worked in the dining hall. Panel B shows the numbers of persons who presented to the college infirmary each day with symptoms of acute gastrointestinal disease. The dining hall was closed at the end of day 4. Patients who presented to the college infirmary on days 5 through 7 were presumed to have acquired the infection in the dining hall. The long “tail” on the right side in Panel B is thought to reflect transmission of infection from persons initially infected by ingestion of contaminated food (primary cases) to other students who did not ingest the contaminated food (secondary cases). The graphs are adapted from Kilgore et al.67

team (17 percent) later had acute gastrointestinal illness due to a Norwalk-like virus with an identical genogroup.70 Whereas bacteria causing diarrheal disease are presumably shed exclusively in feces, caliciviruses are detected in vomitus and feces,67 and contact with either source may result in infection. Airborne transmission may have caused an outbreak in a geriatric facility in which 9 of 14 employees who contracted acute gastrointestinal illness had no direct contact with the feces of residents.71 Similar in-

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stances have been cited in other locales, such as cruise ships,72 hospitals,73 and restaurants,74 which suggests that a small inoculum can spread disease by aerosol. Caliciviruses persist in an infective form in the environment75 and are resistant to deactivation by ordinary cleansing agents,76 although they are inactivated by exposure to household bleach diluted 1:10.77 This explains why, once they are in the environment, for example in a day-care setting or a cruise ship, they are so difficult to eradicate. rotaviruses

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Rotaviruses are a prominent cause of severe diarrheal disease in children under the age of two years. Infection is highly contagious, indicating that a very small inoculum is infectious, since the feces of infected children usually contain no more than 100 CFU per gram. When a rotavirus is introduced into a family, about 50 percent of exposed children and 15 to 30 percent of exposed adults become infected, although some proportion of infected children and most infected adults remain asymptomatic.28,78-80 Most adults who are infected become so within the family, whereas most infections in very young children are acquired outside the family — for example, in day-care settings.28,81 Like caliciviruses, rotaviruses survive well on environmental surfaces82 and are difficult to inactivate,83 although diluted household bleach seems to be effective.84 The congruence of the small size of the inoculum required for infection,85,86 the survival of the pathogen in the environment, and its resistance to most common cleansing agents renders this virus very difficult to control in closed populations; the same is true of the Norwalk-like viruses. adenovirus types 40 and 41

Enteric adenoviruses, types 40 and 41, which have been identified only recently by application of novel techniques, are found in the feces of about 3 percent of all young children with acute gastrointestinal illness.55,87,88 These viruses are readily transmitted from child to child, with disease developing in about half of infected children; most infected adults remain asymptomatic.89-91 In a prospective, five-year investigation,91 adenovirus type 40 or 41 was found in all 10 outbreaks in which other organisms had not been identified; 38 percent of all fecal samples studied were positive. Nevertheless, one family study suggested that this organism is much less contagious than rotavirus.55 In one prolonged outbreak of acute gastrointestinal illness in

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persons hospitalized for long periods, rotavirus and part, it may be due to other, uncertain causes. Food adenovirus type 40 or 41 were isolated in nearly handlers may also spread this organism.109 equal proportions.92 giardia astrovirus

Astroviruses, which are perhaps less well studied than the viruses already described, cause outbreaks of acute gastrointestinal illness — generally, but not always,93 by person-to-person spread. Day-care94 and kindergarten57 attendees, military recruits,95 and mothers and children in maternal-care facilities96 have been implicated, and pediatric97,98 and geriatric92,99,100 hospital wards have been involved. During outbreaks in day-care centers, 50 to 90 percent of children and up to 25 percent of adults may have disease57,94,96; secondary cases occur in the families of one third of affected children.57 This apparently high rate of contagion belies results showing disease in only a very small proportion of human volunteers after experimental ingestion of astrovirus101; the lower rate in the study is perhaps attributable to differences between naturally acquired strains and those used experimentally.

protozoal causes Cryptosporidium, Giardia lamblia, and Entamoeba histolytica cause acute diarrheal disease, with transmission via a small inoculum (fewer than 100 organisms).102-104 Once regarded as waterborne,105 these organisms are now known to spread through daycare centers by way of the fecal–oral route with a substantial likelihood of secondary infection among family members, especially women of childbearing age. cryptosporidium

Because it can be difficult to eradicate cryptosporidium from drinking water, large outbreaks of infection have occurred.106 Nevertheless, personto-person spread of cryptosporidium107 is well documented in homes, schools, and day-care centers. Cryptosporidium may infect 40 percent of household members who have contact with young children with diarrhea, but fewer than 10 percent of household members whose contact is with asymptomatic carriers become infected107 — again illustrating the importance of diarrhea in contagion. When adults are infected, the risk for secondary infection in families is less than 5 percent108; in part, this low rate of risk is consistent with the better hygiene of adults, as compared with children, and, in

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Outbreaks of infection with giardia in child-care settings are associated with overall attack rates (including clinical and subclinical cases) of 17 to 47 percent among attendees and 10 to 35 percent among adult workers.110 When a young child becomes infected, there is a 5 to 25 percent chance that one or more family members will contract the disease.28,110 Severe giardiasis occurs most commonly in young children and women of childbearing age,111 probably reflecting host susceptibility together with the effect of the size of the inoculum. Giardia also spreads among participants in swimming classes112 and among homosexual men.113 e. histolytica

Outbreaks of E. histolytica infection in schools are generally traced to contaminated water sources. Person-to-person spread has, however, been documented in homes, schools, and day-care centers, as well as among homosexual men.30,114,115 Nevertheless, somewhat surprisingly, documented spread within families is unusual.116,117

prevention In nearly all instances, transmission of acute gastrointestinal illness is due to organisms that are present transiently on the hands.118 The distinction between transient and resident flora is important in understanding apparent discrepancies relating to transmission of acute gastrointestinal illness. Washing the hands for 30 seconds with soap or detergent and water may not substantially reduce the total number of bacteria that are present on relatively clean hands119; in contrast, handwashing reduces by about 95 percent the numbers of bacteria or viruses that are applied to the hands experimentally120,121 or that are acquired exogenously under natural conditions122; and handwashing clearly reduces the spread of acute gastrointestinal illness in day-care and family settings.123-125 The explanation is that exogenously acquired organisms or transient flora (the ones that are likely to transmit infection) are removable by washing, whereas resident flora (the ones that are normally present) are not. Whereas the antibacterial substances in household soaps do not prevent acute gastrointestinal illness,126 additional field studies with alcohol-based

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gels may be warranted in day-care centers and other sites where the risk of person-to-person transmission is particularly high. As noted above, washing environmental surfaces with solutions containing diluted household bleach (1:10) greatly reduces the counts of bacteria and viruses that are implicated in acute gastrointestinal illness, but this type of application is not always practicable.

summary and conclusions Acute gastrointestinal illness is exceedingly common; viruses, bacteria, and protozoa are the principal recognized causes. Some causative organisms, such as calicivirus, rotavirus, astrovirus, adenovirus types 40 and 41, S. typhi, and shigella, are indigenous to humans; person-to-person spread follows direct contact or human contamination of food or water. In contrast, nontyphoidal salmonella, campylobacter, and pathogenic E. coli are prevalent in meat, poultry, and dairy foods; human-to-human spread is documented infrequently relative to the total number of cases of infection with these bacterial agents. This lower rate of documentation may reflect the difficulty, in an individual case, of determining whether some common food source is responsible or in distinguishing an environmental source from a human source. As a general matter, the failure to identify a common source for most sporadic, presumably viral, acute gastrointestinal illnesses does not exclude the possible link to an unrecognized foodborne outbreak. The essential point remains, however, that — even though the visibility of an outbreak tends to focus attention on foodborne infection — the great majority of cases are sporadic and spread from person to person. Although free-living protozoa, such as cryptosporidia or giardia, are widespread in nature, contagion is also well documented. The likelihood of contagion depends on the age and self-reliance of an infected person, the nature of the social interaction within the potentially involved group, the intensity of the symptoms, the

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concentration of organisms in the potentially infective material, the likelihood that the organism will survive direct transmission or survive in the environment, and other, less well understood factors. The immune status of the host undoubtedly plays a role in determining whether symptomatic disease or subclinical infection results, but the nature of such immune factors is poorly understood.127 Within families, young children are the usual source for contagion because of their exposure to other children, their imperfect personal hygiene, and their dependence on adults. Severely affected persons are more contagious because they discharge greater volumes of infective material that contain large numbers of infectious particles. The likelihood of contagion varies with the concentration of organisms in excreta, the capacity of the organisms to survive and replicate in food or persist in the environment, and the number required to infect. Spread of acute gastrointestinal illness is common and problematic in all closed environments such as day-care centers, schools, and cruise ships. Person-to-person transmission is best prevented by the practice of excellent personal hygiene both by infected persons and by those exposed to them. Fecal–oral transmission is the usual route of spread of acute gastrointestinal illness, but caliciviruses and probably adenoviruses are present in vomitus, so kissing or sharing utensils should also be avoided. Dilution by handwashing reduces the inoculum of causative organisms, greatly diminishing the risk of contagion. There is no apparent benefit from the antibacterial agents in soaps, although the regular use of alcohol-based gels will probably reduce transmission. The use of diluted household bleach on environmental surfaces may be necessary to interrupt transmission of viral or protozoal agents. Dr. Daniel Musher reports having received Merit Review Funding from the Department of Veterans Affairs, grant support from Romark Laboratories, and consulting fees from Aventis. We are indebted to Marsha Sullivan and the staff of the Medical Library at the Michael E. DeBakey Veterans Affairs Medical Center, Houston, for their help.

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ness in FoodNet surveillance areas, 19981999. Clin Infect Dis 2004;38:Suppl 3:S219S226. 4. Lesser CF, Miller SI. Salmonellosis. In: Braunweld E, Fauci AS, Kasper DL, Jameson JL, eds. Harrison’s principles of internal medicine. 15th ed. New York: McGraw-Hill, 2001: 970-5.

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5. Roy SK, Speelman P, Butler T, Nath S,

Rahman H, Stoll BJ. Diarrhea associated with typhoid fever. J Infect Dis 1985;151: 1138-43. 6. Mathieu JJ, Henning KJ, Bell E, Frieden TR. Typhoid fever in New York City, 1980 through 1990. Arch Intern Med 1994;154: 1713-8.

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