The new england journal of medicine

review article

medical progress

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 in-

fections, 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 diseas-
es to new heights. Our purpose in this article is to examine contagion (from the Latin,
From the Medical Service, Infectious Dis-
ease Section, Michael E. DeBakey Veterans
Affairs Medical Center, and the Depart-
ments of Medicine and Molecular Virology
and Microbiology, Baylor College of Medi-
cine — both in Houston (D.M.M.); and
the Department of Medicine, University of
tangere, to touch) — direct human-to-human spread — of acute gastrointestinal illness, Pennsylvania School of Medicine, Philadel-
defined as a syndrome of vomiting, diarrhea, or both, that begins abruptly in otherwise phia (B.L.M.). Address reprint requests to
healthy persons and is most often self-limited. Dr. Daniel Musher at the Infectious Disease
Section, Veterans Affairs Medical Center,
Unlike agents that cause contagious respiratory infections,1 which are largely or ex- Houston, TX 77030, or at daniel.musher@
clusively indigenous to humans, agents that cause acute gastrointestinal illness (Table 1) med.va.gov.
may spread from person to person or may be acquired from a common food or envi-
N Engl J Med 2004;351:2417-27.
ronmental source, often water; they may also result from exposure to animals. Food or Copyright © 2004 Massachusetts Medical Society.
water may serve as a primary source of contagion or may, in turn, have been contami-
nated 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 dif-
ferent estimates of the frequency of acute gastrointestinal illness, leading to seemingly
contradictory results. Estimates based on extrapolation from isolation of known diar-
rheal 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 per-
son 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 Nether-
lands and the United Kingdom yielded similar results.3 On the basis of reports to pub-
lic 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 pro-
portion of foodborne and waterborne outbreaks are also ultimately attributable to hu-
man contamination.

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 The new england journal
bacterial causes
salmonella
Because many principles of contagion with respect
to enteric organisms were elucidated in studies of
typhoid fever, it seems appropriate to begin our dis-
cussion of causes of acute gastrointestinal illness
with Salmonella typhosa (S. enterica serotype typhi). Al-
though physicians do not always associate this or-
ganism with a typical syndrome of acute gastroin-
testinal 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 al-
ways 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 organ-
ism 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 ex-
creta 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 indus-
trial sewage. During the late 1990s, a breakdown of
the public health infrastructure in the former Sovi-
et Union led to a cessation of chlorination, the pi-
rating 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 colony-
forming 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 infec-
tivity 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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of medicine
Table 1. Agents That Commonly Cause Acute
Gastrointestinal Illness.*
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 gastrointesti-
nal infection in otherwise healthy children and adults in
developed countries. The frequency of infection is simi-
lar 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 pa-
tients to nurses and physicians in the era before an-
tibiotics,8 are consistent, at least in some instances
of natural infection, with low-inoculum contagion,
under the assumption that large numbers of organ-
isms 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 perma-
nent carriers of nontyphoidal salmonella identified
10 instances of transmitted infection.20 On the ba-
sis of epidemiologic studies, the infective dose of
nontyphoidal salmonella is thought to be small,
not exceeding 100 CFU.21,22 The paucity of docu-
mented instances of contagion may reflect the dif-
ficulty 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
december 2 , 2004
 medical progress

child) after direct contact or the ingestion of con-

Table 2. Factors That May Contribute to Contagion
taminated food. Shigellosis is highly contagious; as of Acute Gastrointestinal Illnesses within Day-Care
few as 200 CFU can cause infection,23 and the role Centers.*
of a small inoculum is supported by early observa-
Presence of one or more cases of acute gastrointestinal
tions, which emphasized spread by casual contact illness
and insect vectors.24 The high level of contagious- Lack of gloving or handwashing during or after diaper
ness of shigellosis may be inferred from the large changes or helping at toilet
Lack of policy to isolate or send home children with
number of secondary cases that follow a document- acute gastrointestinal illness
ed outbreak; persons who have varying degrees of Common area for diaper changing
contact with infected patients are likely, themselves, Larger groups of children
Carpeted flooring
to become infected.25 A very young child is the usu- Shared toys and classroom objects
al source.26
Not surprisingly, shigella readily spreads within * These factors are discussed in Pickering et al.30
families,24 in custodial institutions,27 and within
and among children’s day-care centers.28,29 Day-
care centers provide remarkable natural settings in escherichia coli o157:h7
which contagion in acute gastrointestinal illness can Transmission of Escherichia coli O157:H7 occurs pri-
be studied28 (Table 2). In these settings, shigellosis marily through the consumption of contaminated
(Tables 1 and 2) may affect from one third to two meat, but secondary infection does occur, and a
thirds of children,30 with severe diarrhea increasing small bacterial inoculum may lead to clinical illness.
the likelihood of contagion, reflecting high fecal For example, of 501 cases of E. coli–related diarrhea
counts of bacteria and increased chances of soil- linked to hamburger consumption in an epidemic
ing.26 At least one additional case of shigellosis is that occurred during 1992 and 1993, 48 infections
recognized in the families of about 25 percent of (about 10 percent) were secondary.42 Person-to-
infected children.28 The current widespread use of person transmission occurs in day-care centers,43
medications that reduce gastric acidity (which nor- among families,44 and in mental institutions45; an
mally eradicates salmonella and shigella) probably attack rate — the rate of appearance of symptoms
increases the risk of spread14 to parents of infected in exposed persons — of around 20 percent has
children or to adults who work in day-care centers. been reported. It is worth noting that this form of
acute gastrointestinal infection is associated with a
campylobacter substantial incidence of the hemolytic–uremic syn-
The epidemiology of infection due to campylobac- drome, affecting up to 13 percent of young chil-
ter, 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 environmen-
isms 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 hus-
ter,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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 The new england journal of medicine

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
viral causes of acute gastrointestinal illness in the United States
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-associ-
developed 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 vo-
tries 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 infec-
these numbers have steadily declined in the past tion. The extent of spread in such closed environ-
several 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
testinal illness. Although consumption of contaminated food
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-to-
Norwalk 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 sec-
novirus types 40 and 4155,56 and astroviruses57-59 ondary outbreaks62 indicate person-to-person, rath-
have 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-to-
Within families, acute gastrointestinal illnesses person spread (Fig. 1). In a large community out-
are 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 docu-
with, their parents and caregivers.50 As shown by mented in other circumstances as well. When Brit-
Dingle 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 medi-
symptoms 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 sin-
higher concentrations of infective particles. gle food source. Eleven members of an opposing

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

Quantity of Probability
Inoculum of Human-
to Cause Usual Mode Incubation Duration to-Human
Agent Disease of Transmission Period Usual Symptoms Diagnostic Methods of Symptoms Duration of Shedding Spread†
Salmonella typhi High Human contact, prepared 5–14 days Fever, abdominal Blood culture, 3–4 wk 2–6 wk, rarely lifetime High
(105 CFU)‡ food, contaminated water pain, diarrhea fecal culture
Salmonella Low Poultry, eggs, meat 24 hr Diarrhea, fever Fecal culture 2–4 days 5 wk, rarely lifetime Very low
(nontyphoidal) (102–103 CFU) (8–24 hr)
Shigella Low Human contact, prepared 3 days Diarrhea, fever Fecal culture 3 days Days to weeks Very high
(≤102 CFU) food, contaminated (1–7 days) (2–6)
water
Campylobacter Low Poultry, milk, tap water 3 days Diarrhea, fever Fecal culture 3 days 50% negative after 3 wk Very low

n engl j med 351;23

(1–7 days) (1–7)
Calicivirus Low Human contact (feces, 1 day Diarrhea, vomiting, RT-PCR 2 days 3 days (1 day to weeks) Very high
vomitus), prepared food (1–2 days) fever (1–3)
Rotavirus Very low Human contact 2 days Fever, vomiting, EIA, latex 4 days 4 days (2–7 days) Very high
diarrhea (in infants) agglutination (3–9)

www.nejm.org
Astrovirus Unknown Human contact 1–2 days Diarrhea EIA (not commer- 2–5 days 4 days (1 day to weeks) High
cially available) (1–14)
medical progress

Adenovirus types Unknown Human contact (feces, 2–3 days Diarrhea, vomiting, EIA (not commer- 2–4 days 5 days (3–11 days) Low
40 and 41 possibly vomitus) fever cially available) (1–7)
Giardia Low (≤102 Tap water, human contact 9 days Abdominal discomfort, Microscopical exam- 1–8 wk 3 wk–6 mo High
organisms) (1–2 wk) diarrhea ination of feces
Cryptosporidium Very low Tap water, human contact 7 days Diarrhea, abdominal Microscopical exam- 10–12 days 7 days Very low

december 2, 2004
(1–2 cysts) (1–14 days) pain, headache, ination of feces (3–60)
fever

* 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, al-

Copyright © 2004 Massachusetts Medical Society. All rights reserved.

though 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-tran-
scriptase–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.

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2421
 The new england journal of medicine

stances have been cited in other locales, such as

A Questionnaire
cruise ships,72 hospitals,73 and restaurants,74 which
120
suggests that a small inoculum can spread disease
100
by aerosol. Caliciviruses persist in an infective form
No. of Cases

80 in the environment75 and are resistant to deactiva-

60 tion by ordinary cleansing agents,76 although they
40
are inactivated by exposure to household bleach di-
luted 1:10.77 This explains why, once they are in the
20
environment, for example in a day-care setting or a
0 cruise ship, they are so difficult to eradicate.
0 1 2 3 4 5 6 7 8 9 10 11 12
Day of Outbreak
rotaviruses
B Infirmary Rotaviruses are a prominent cause of severe diar-
160 rheal disease in children under the age of two years.
Infection is highly contagious, indicating that a
140
very small inoculum is infectious, since the feces of
120 infected children usually contain no more than 100
No. of Cases

100 CFU per gram. When a rotavirus is introduced into

80
60
40
20
0 family, whereas most infections in very young chil-
0 1 2 3 4 5 6 7 8 9 10 11
Day of Outbreak
Figure 1. Contagion (Primary and Secondary Infection) in a Foodborne Out-
break 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 in-
firmary 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 in-
firmary 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 con-
taminated food (primary cases) to other students who did not ingest the con-
taminated 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 ger-
iatric facility in which 9 of 14 employees who con-
tracted acute gastrointestinal illness had no direct
contact with the feces of residents.71 Similar in-
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
12
dren are acquired outside the family — for exam-
ple, in day-care settings.28,81 Like caliciviruses, ro-
taviruses survive well on environmental surfaces82
and are difficult to inactivate,83 although diluted
household bleach seems to be effective.84 The con-
gruence 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 com-
mon cleansing agents renders this virus very diffi-
cult 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 per-
cent of all young children with acute gastrointesti-
nal illness.55,87,88 These viruses are readily trans-
mitted 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 or-
ganisms 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 pro-
longed outbreak of acute gastrointestinal illness in

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 medical progress

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
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 facili-
ties96 have been implicated, and pediatric97,98 and
geriatric92,99,100 hospital wards have been involved.
During outbreaks in day-care centers, 50 to 90 per-
cent 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 ap-
parently high rate of contagion belies results show-
ing disease in only a very small proportion of hu-
man volunteers after experimental ingestion of
astrovirus101; the lower rate in the study is perhaps
attributable to differences between naturally ac-
quired strains and those used experimentally.
protozoal causes
Cryptosporidium, Giardia lamblia, and Entamoeba his-
tolytica cause acute diarrheal disease, with transmis-
sion via a small inoculum (fewer than 100 organ-
isms).102-104 Once regarded as waterborne,105 these
organisms are now known to spread through day-
care centers by way of the fecal–oral route with a
substantial likelihood of secondary infection among
family members, especially women of childbear-
ing age.
cryptosporidium
Because it can be difficult to eradicate cryptospo-
ridium from drinking water, large outbreaks of
infection have occurred.106 Nevertheless, person-
to-person spread of cryptosporidium107 is well doc-
umented in homes, schools, and day-care centers.
Cryptosporidium may infect 40 percent of house-
hold members who have contact with young chil-
dren with diarrhea, but fewer than 10 percent of
household members whose contact is with asymp-
tomatic carriers become infected107 — again illus-
trating the importance of diarrhea in contagion.
When adults are infected, the risk for secondary in-
fection in families is less than 5 percent108; in part,
this low rate of risk is consistent with the better hy-
giene of adults, as compared with children, and, in
giardia
Outbreaks of infection with giardia in child-care
settings are associated with overall attack rates (in-
cluding clinical and subclinical cases) of 17 to 47
percent among attendees and 10 to 35 percent
among adult workers.110 When a young child be-
comes 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 com-
monly in young children and women of childbear-
ing age,111 probably reflecting host susceptibility
together with the effect of the size of the inoculum.
Giardia also spreads among participants in swim-
ming 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 docu-
mented in homes, schools, and day-care centers, as
well as among homosexual men.30,114,115 Never-
theless, somewhat surprisingly, documented spread
within families is unusual.116,117
prevention
In nearly all instances, transmission of acute gastro-
intestinal illness is due to organisms that are present
transiently on the hands.118 The distinction between
transient and resident flora is important in under-
standing apparent discrepancies relating to trans-
mission of acute gastrointestinal illness. Washing
the hands for 30 seconds with soap or detergent and
water may not substantially reduce the total num-
ber 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 con-
ditions122; 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 house-
hold soaps do not prevent acute gastrointestinal ill-
ness,126 additional field studies with alcohol-based

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 The new england journal of medicine

gels may be warranted in day-care centers and other
sites where the risk of person-to-person transmis-
sion 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 appli-
cation is not always practicable.
summary and conclusions
Acute gastrointestinal illness is exceedingly com-
mon; viruses, bacteria, and protozoa are the princi-
pal recognized causes. Some causative organisms,
such as calicivirus, rotavirus, astrovirus, adenovirus
types 40 and 41, S. typhi, and shigella, are indige-
nous to humans; person-to-person spread follows
direct contact or human contamination of food or
water. In contrast, nontyphoidal salmonella, cam-
pylobacter, 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 bacte-
rial agents. This lower rate of documentation may
reflect the difficulty, in an individual case, of deter-
mining whether some common food source is re-
sponsible 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 vi-
ral, acute gastrointestinal illnesses does not exclude
the possible link to an unrecognized foodborne out-
break. 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 per-
son to person. Although free-living protozoa, such
as cryptosporidia or giardia, are widespread in na-
ture, 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 in-
volved group, the intensity of the symptoms, the
concentration of organisms in the potentially in-
fective material, the likelihood that the organism
will survive direct transmission or survive in the en-
vironment, 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 affect-
ed persons are more contagious because they dis-
charge greater volumes of infective material that
contain large numbers of infectious particles. The
likelihood of contagion varies with the concentra-
tion of organisms in excreta, the capacity of the or-
ganisms to survive and replicate in food or persist
in the environment, and the number required to in-
fect. Spread of acute gastrointestinal illness is com-
mon 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 avoid-
ed. 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 trans-
mission. The use of diluted household bleach on
environmental surfaces may be necessary to inter-
rupt transmission of viral or protozoal agents.
Dr. Daniel Musher reports having received Merit Review Funding
from the Department of Veterans Affairs, grant support from Ro-
mark 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.

refer enc es
1. Musher DM. How contagious are com-
mon respiratory infections? N Engl J Med
2003;348:1256-66.
2. Mead PS, Slutsker L, Dietz V, et al. Food-
related illness and death in the United
States. Emerg Infect Dis 1999;5:607-25.
3. Imhoff B, Morse D, Shiferaw B, et al.
Burden of self-reported acute diarrheal ill-
ness in FoodNet surveillance areas, 1998-
1999. Clin Infect Dis 2004;38:Suppl 3:S219-
S226.
4. Lesser CF, Miller SI. Salmonellosis. In:
Braunweld E, Fauci AS, Kasper DL, Jameson
JL, eds. Harrison’s principles of internal med-
icine. 15th ed. New York: McGraw-Hill, 2001:
970-5.
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.

2424 n engl j med 351;23 www.nejm.org december 2, 2004

Downloaded from www.nejm.org at RUSH UNIVERSITY MEDICAL CENTER on November 7, 2008 .

Copyright © 2004 Massachusetts Medical Society. All rights reserved.

7. Leavitt JW. Typhoid Mary: captive to the
public’s health. Boston: Beacon Press,
1996.
8. Osler W. The principles and practice of
medicine. New York: D. Appleton, 1914.
9. Smith DT, Conant NF, eds. Zinsser mi-
crobiology. New York: Appleton-Century-
Crofts, 1960.
10. Typhoid fever — Washington. MMWR
Morb Mortal Wkly Rep 1972;21:290.
11. Mermin JH, Villar R, Carpenter J, et al.
A massive epidemic of multidrug-resistant
typhoid fever in Tajikistan associated with
consumption of municipal water. J Infect
Dis 1999;179:1416-22.
12. Davis BD, Dulbecco R, Eisen HN, Gins-
berg HS, Wood WBJ. Microbiology. New
York: Harper & Row, 1967.
13. Hornick RB, Greisman SE, Woodward
TE, DuPont HL, Dawkins AT, Snyder MJ. Ty-
phoid fever: pathogenesis and immunolog-
ic control. 2. N Engl J Med 1970;283:739-
46.
14. Idem. Typhoid fever: pathogenesis and
immunologic control. N Engl J Med 1970;
283:686-91.
15. Glynn JR, Hornick RB, Levine MM,
Bradley DJ. Infecting dose and severity of ty-
phoid: analysis of volunteer data and exami-
nation of the influence of the definition of
illness used. Epidemiol Infect 1995;115:23-
30.
16. Black RE, Levine MM, Clements ML,
Hughes TP, Blaser MJ. Experimental Cam-
pylobacter jejuni infection in humans. J In-
fect Dis 1988;157:472-9.
17. Ager EA, Top FH Sr. Salmonellosis. In:
Top FH Sr, Wehrle PF, eds. Communicable
and infectious diseases. St. Louis: C.V. Mos-
by, 1972:567-80.
18. Buchwald DS, Blaser MJ. A review of hu-
man salmonellosis: II. Duration of excretion
following infection with nontyphi Salmo-
nella. Rev Infect Dis 1984;6:345-56.
19. Newcomb S, Broadhurst L, Kissane K.
Salmonella outbreak in an American child
development center in Germany. Mil Med
1997;162:783-7.
20. Musher DM, Rubenstein AD. Perma-
nent carriers of nontyphosa salmonellae.
Arch Intern Med 1973;132:869-72.
21. A waterborne epidemic of salmonello-
sis in Riverside, California, 1965: epidemio-
logic aspects. Am J Epidemiol 1971;93:33-
48.
22. Kapperud G, Gustavsen S, Hellesnes I,
et al. Outbreak of Salmonella typhimurium
infection traced to contaminated chocolate
and caused by a strain lacking the 60-mega-
dalton virulence plasmid. J Clin Microbiol
1990;28:2597-601.
23. DuPont HL, Hornick RB, Snyder MJ, Li-
bonati JP, Formal SB, Gangarosa EJ. Immu-
nity in shigellosis. II. Protection induced by
oral live vaccine or primary infection. J Infect
Dis 1972;125:12-6.
24. Davison WC. A bacteriological and clin-
ical consideration of bacillary dysentery in
n engl j med 351;23
Downloaded from www.nejm.org at RUSH UNIVERSITY MEDICAL CENTER on November 7, 2008 .
Copyright © 2004 Massachusetts Medical Society. All rights reserved.
medical progress
adults and children. Medicine (Baltimore)
1922;1:389-580.
25. Wharton M, Spiegel RA, Horan JM, et al.
A large outbreak of antibiotic-resistant
shigellosis at a mass gathering. J Infect Dis
1990;162:1324-8.
26. Lewis JN, Gangarosa EJ. Shigellosis. In:
Top FH Sr, Wehrle PF, eds. Communicable
and infectious diseases. St. Louis: C.V. Mos-
by, 1972:585-91.
27. Levine MM, Dupont HL, Gangarosa EJ,
et al. Shigellosis in custodial institutions. II.
Clinical, immunologic and bacteriologic re-
sponse of institutionalized children to oral
attenuated shigella vaccines. Am J Epidemi-
ol 1972;96:40-9.
28. Pickering LK, Evans DG, DuPont HL,
Vollet JJ III, Evans DJ Jr. Diarrhea caused by
shigella, rotavirus, and giardia in day-care
centers: prospective study. J Pediatr 1981;
99:51-6.
29. Litwin CM, Leonard RB, Carroll KC,
Drummond WK, Pavia AT. Characterization
of endemic strains of Shigella sonnei by use
of plasmid DNA analysis and pulsed-field
gel electrophoresis to detect patterns of
transmission. J Infect Dis 1997;175:864-70.
30. Pickering LK, Bartlett AV, Woodward
WE. Acute infectious diarrhea among chil-
dren in day care: epidemiology and control.
Rev Infect Dis 1986;8:539-47.
31. Blaser MJ, Wells JG, Feldman RA, Pol-
lard RA, Allen JR. Campylobacter enteritis in
the United States: a multicenter study. Ann
Intern Med 1983;98:360-5.
32. Slutsker L, Ries AA, Greene KD, Wells
JG, Hutwagner L, Griffin PM. Escherichia
coli O157:H7 diarrhea in the United States:
clinical and epidemiologic features. Ann In-
tern Med 1997;126:505-13.
33. Kapperud G, Espeland G, Wahl E, et
al. Factors associated with increased and
decreased risk of Campylobacter infection:
a prospective case-control study in Norway.
Am J Epidemiol 2003;158:234-42.
34. Skirrow MB. Campylobacter. Lancet
1990;336:921-3.
35. Blaser MJ, Waldman RJ, Barrett T, Er-
landson AL. Outbreaks of Campylobacter
enteritis in two extended families: evidence
for person-to-person transmission. J Pediatr
1981;98:254-7.
36. Gillespie IA, O’Brien SJ, Adak GK, et al.
Point source outbreaks of Campylobacter
jejuni infection — are they more common
than we think and what might cause them?
Epidemiol Infect 2003;130:367-75.
37. Oosterom J, den Uyl CH, Banffer JR,
Huisman J. Epidemiological investigations
on Campylobacter jejuni in households with
a primary infection. J Hyg (Lond) 1984;93:
325-32.
38. Wolfs TF, Duim B, Geelen SP, et al.
Neonatal sepsis by Campylobacter jejuni:
genetically proven transmission from a
household puppy. Clin Infect Dis 2001;32:
E97-E99.
39. Gaudreau C, Michaud S. Cluster of
www.nejm.org december 2, 2004
erythromycin- and ciprofloxacin-resistant
Campylobacter jejuni subsp. jejuni from
1999 to 2001 in men who have sex with
men, Quebec, Canada. Clin Infect Dis 2003;
37:131-6.
40. Reller ME, Olsen SJ, Kressel AB, et al.
Sexual transmission of typhoid fever: a mul-
tistate outbreak among men who have sex
with men. Clin Infect Dis 2003;37:141-4.
41. Shigella sonnei outbreak among men
who have sex with men — San Francisco,
California, 2000–2001. MMWR Morb Mor-
tal Wkly Rep 2001;50:922-6.
42. Bell BP, Goldoft M, Griffin PM, et al.
A multistate outbreak of Escherichia coli
O157:H7-associated bloody diarrhea and
hemolytic uremic syndrome from hamburg-
ers: the Washington experience. JAMA
1994;272:1349-53.
43. Belongia EA, Osterholm MT, Soler JT,
Ammend DA, Braun JE, MacDonald KL.
Transmission of Escherichia coli O157:H7
infection in Minnesota child day-care facili-
ties. JAMA 1993;269:883-8.
44. Spika JS, Parsons JE, Nordenberg D,
Wells JG, Gunn RA, Blake PA. Hemolytic
uremic syndrome and diarrhea associated
with Escherichia coli O157:H7 in a day care
center. J Pediatr 1986;109:287-91.
45. Pavia AT, Nichols CR, Green DP, et al.
Hemolytic-uremic syndrome during an out-
break of Escherichia coli O157:H7 infec-
tions in institutions for mentally retarded
persons: clinical and epidemiologic obser-
vations. J Pediatr 1990;116:544-51.
46. Rowe PC, Orrbine E, Lior H, et al. Risk
of hemolytic uremic syndrome after sporad-
ic Escherichia coli O157:H7 infection: re-
sults of a Canadian collaborative study. J Pe-
diatr 1998;132:777-82.
47. Bartlett JG. Antibiotic-associated diar-
rhea. N Engl J Med 2002;346:334-9.
48. Johnson S, Adelmann A, Clabots CR,
Peterson LR, Gerding DN. Recurrences of
Clostridium difficile diarrhea not caused by
the original infecting organism. J Infect Dis
1989;159:340-3.
49. Kim K, DuPont HL, Pickering LK. Out-
breaks of diarrhea associated with Clostridi-
um difficile and its toxin in day-care centers:
evidence of person-to-person spread. J Pedi-
atr 1983;102:376-82.
50. Dingle JH, Badger GF, Jordan WS Jr. Ill-
ness in the home: a study of 25,000 illnesses
in a group of Cleveland families. Cleveland:
Press of Western Reserve University, 1964.
51. Allos BM, Moore MR, Griffin PM, Tauxe
RV. Surveillance for sporadic foodborne dis-
ease in the 21st century: the FoodNet per-
spective. Clin Infect Dis 2004;38:Suppl 3:
S115-S120.
52. Glass RI, Noel J, Ando T, et al. The epi-
demiology of enteric caliciviruses from
humans: a reassessment using new diag-
nostics. J Infect Dis 2000;181:Suppl 2:S254-
S261.
53. Hedlund KO, Rubilar-Abreu E, Svens-
son L. Epidemiology of calicivirus infections
2425
 The
in Sweden, 1994-1998. J Infect Dis 2000;
181:Suppl 2:S275-S280.
54. de Wit MA, Koopmans MP, Kortbeek
LM, et al. Sensor, a population-based cohort
study on gastroenteritis in the Netherlands:
incidence and etiology. Am J Epidemiol
2001;154:666-74.
55. Rodriguez WJ, Kim HW, Brandt CD, et
al. Fecal adenoviruses from a longitudinal
study of families in metropolitan Washing-
ton, D.C.: laboratory, clinical, and epidemio-
logic observations. J Pediatr 1985;107:514-
20.
56. Mistchenko AS, Huberman KH, Gomez
JA, Grinstein S. Epidemiology of enteric ad-
enovirus infection in prospectively moni-
tored Argentine families. Epidemiol Infect
1992;109:539-46.
57. Konno T, Suzuki H, Ishida N, Chiba R,
Mochizuki K, Tsunoda A. Astrovirus-associ-
ated epidemic gastroenteritis in Japan. J Med
Virol 1982;9:11-7.
58. Herrmann JE, Taylor DN, Echeverria P,
Blacklow NR. Astroviruses as a cause of gas-
troenteritis in children. N Engl J Med 1991;
324:1757-60.
59. Naficy AB, Rao MR, Holmes JL, et al. As-
trovirus diarrhea in Egyptian children. J In-
fect Dis 2000;182:685-90.
60. Waters V, Ford-Jones EL, Petric M, Fearon
M, Corey P, Moineddein R. Etiology of com-
munity-acquired pediatric viral diarrhea: a
prospective longitudinal study in hospitals,
emergency departments, pediatric practices
and child care centers during the winter ro-
tavirus outbreak, 1997 to 1998. Pediatr In-
fect Dis J 2000;19:843-8.
61. Fankhauser RL, Monroe SS, Noel JS, et
al. Epidemiologic and molecular trends of
“Norwalk-like viruses” associated with out-
breaks of gastroenteritis in the United
States. J Infect Dis 2002;186:1-7.
62. Norovirus activity — United States,
2002. MMWR Morb Mortal Wkly Rep 2003;
52:41-5. [Erratum, MMWR Morb Mortal
Wkly Rep 2003;52:113.]
63. Outbreaks of gastroenteritis associated
with norovirus on cruise ships — United
States, 2002. MMWR Morb Mortal Wkly
Rep 2002;51:1112-5.
64. Schreiber DS, Blacklow NR, Trier JS.
The mucosal lesion of the proximal small in-
testine in acute infectious nonbacterial gas-
troenteritis. N Engl J Med 1973;288:1318-23.
65. Parrino TA, Schreiber DS, Trier JS,
Kapikian AZ, Blacklow NR. Clinical immu-
nity in acute gastroenteritis caused by Nor-
walk agent. N Engl J Med 1977;297:86-9.
66. Adler JL, Zickl R. Winter vomiting dis-
ease. J Infect Dis 1969;119:668-73.
67. Kilgore PE, Belay ED, Hamlin DM, et al.
A university outbreak of gastroenteritis due
to a small round-structured virus: applica-
tion of molecular diagnostics to identify the
etiologic agent and patterns of transmis-
sion. J Infect Dis 1996;173:787-93.
68. Gotz H, Ekdahl K, Lindback J, de Jong
B, Hedlund KO, Giesecke J. Clinical spec-
2426 n engl j med 351;23
Downloaded from www.nejm.org at RUSH UNIVERSITY MEDICAL CENTER on November 7, 2008 .
Copyright © 2004 Massachusetts Medical Society. All rights reserved.
new england journal of medicine
trum and transmission characteristics of in-
fection with Norwalk-like virus: findings
from a large community outbreak in Swe-
den. Clin Infect Dis 2001;33:622-8.
69. Outbreak of acute gastroenteritis asso-
ciated with Norwalk-like viruses among
British military personnel — Afghanistan,
May 2002. MMWR Morb Mortal Wkly Rep
2002;51:477-9.
70. Becker KM, Moe CL, Southwick KL,
MacCormack JN. Transmission of Norwalk
virus during a football game. N Engl J Med
2000;343:1223-7.
71. Gellert GA, Waterman SH, Ewert D, et
al. An outbreak of acute gastroenteritis
caused by a small round structured virus in a
geriatric convalescent facility. Infect Control
Hosp Epidemiol 1990;11:459-64.
72. Ho MS, Glass RI, Monroe SS, et al. Viral
gastroenteritis aboard a cruise ship. Lancet
1989;2:961-5.
73. Sawyer LA, Murphy JJ, Kaplan JE, et al.
25- to 30-nm virus particle associated with a
hospital outbreak of acute gastroenteritis
with evidence for airborne transmission.
Am J Epidemiol 1988;127:1261-71.
74. Marks PJ, Vipond IB, Carlisle D, Deakin
D, Fey RE, Caul EO. Evidence for airborne
transmission of Norwalk-like virus (NLV) in
a hotel restaurant. Epidemiol Infect 2000;
124:481-7.
75. Kuusi M, Nuorti JP, Maunula L, et al.
A prolonged outbreak of Norwalk-like cali-
civirus (NLV) gastroenteritis in a rehabilita-
tion centre due to environmental contami-
nation. Epidemiol Infect 2002;129:133-8.
76. Gulati BR, Allwood PB, Hedberg CW,
Goyal SM. Efficacy of commonly used disin-
fectants for the inactivation of calicivirus on
strawberry, lettuce, and a food-contact sur-
face. J Food Prot 2001;64:1430-4.
77. Thurston-Enriquez JA, Haas CN, Jacan-
gelo J, Gerba CP. Chlorine inactivation of ad-
enovirus type 40 and feline calicivirus. Appl
Environ Microbiol 2003;69:3979-85.
78. Wenman WM, Hinde D, Feltham S,
Gurwith M. Rotavirus infection in adults: re-
sults of a prospective family study. N Engl J
Med 1979;301:303-6.
79. Rodriguez WJ, Kim HW, Brandt CD, et
al. Longitudinal study of rotavirus infection
and gastroenteritis in families served by a
pediatric medical practice: clinical and epi-
demiologic observations. Pediatr Infect Dis J
1987;6:170-6.
80. Koopman JS, Monto AS, Longini IM Jr.
The Tecumseh Study. XVI: Family and com-
munity sources of rotavirus infection. Am J
Epidemiol 1989;130:760-8.
81. Bartlett AV III, Reves RR, Pickering LK.
Rotavirus in infant-toddler day care centers:
epidemiology relevant to disease control
strategies. J Pediatr 1988;113:435-41.
82. Keswick BH, Pickering LK, DuPont HL,
Woodward WE. Survival and detection of ro-
taviruses on environmental surfaces in day
care centers. Appl Environ Microbiol 1983;
46:813-6.
www.nejm.org december 2, 2004
83. Abad FX, Pinto RM, Bosch A. Disinfec-
tion of human enteric viruses on fomites.
FEMS Microbiol Lett 1997;156:107-11.
84. Ojeh CK, Cusack TM, Yolken RH. Evalu-
ation of the effects of disinfectants on rota-
virus RNA and infectivity by the polymerase
chain reaction and cell-culture methods.
Mol Cell Probes 1995;9:341-6.
85. Vesikari T, Ruuska T, Bogaerts H, Delem
A, Andre F. Dose-response study of RIT
4237 oral rotavirus vaccine in breast-fed and
formula-fed infants. Pediatr Infect Dis 1985;
4:622-5.
86. Graham DY, Dufour GR, Estes MK.
Minimal infective dose of rotavirus. Arch Vi-
rol 1987;92:261-71.
87. Brandt CD, Kim HW, Rodriguez WJ, et
al. Adenoviruses and pediatric gastroenteri-
tis. J Infect Dis 1985;151:437-43.
88. Vizzi E, Ferraro D, Cascio A, Di Stefano
R, Arista S. Detection of enteric adenovirus-
es 40 and 41 in stool specimens by mono-
clonal antibody-based enzyme immunoas-
says. Res Virol 1996;147:333-9.
89. Richmond SJ, Caul EO, Dunn SM, Ash-
ley CR, Clarke SK, Seymour NR. An out-
break of gastroenteritis in young children
caused by adenoviruses. Lancet 1979;1:
1178-81.
90. Chiba S, Nakata S, Nakamura I, et al.
Outbreak of infantile gastroenteritis due to
type 40 adenovirus. Lancet 1983;2:954-7.
91. Van R, Wun CC, O’Ryan ML, Matson
DO, Jackson L, Pickering LK. Outbreaks of
human enteric adenovirus types 40 and 41 in
Houston day care centers. J Pediatr 1992;
120:516-21.
92. Dupuis P, Beby A, Bourgoin A, Lussier-
Bonneau MD, Agius G. Epidemic of viral
gastroenteritis in an elderly community.
Presse Med 1995;24:356-8. (In French.)
93. Oishi I, Yamazaki K, Kimoto T, et al.
A large outbreak of acute gastroenteritis as-
sociated with astrovirus among students
and teachers in Osaka, Japan. J Infect Dis
1994;170:439-43.
94. Mitchell DK, Monroe SS, Jiang X, Mat-
son DO, Glass RI, Pickering LK. Virologic
features of an astrovirus diarrhea outbreak
in a day care center revealed by reverse tran-
scriptase-polymerase chain reaction. J In-
fect Dis 1995;172:1437-44.
95. Belliot G, Laveran H, Monroe SS. Out-
break of gastroenteritis in military recruits
associated with serotype 3 astrovirus infec-
tion. J Med Virol 1997;51:101-6.
96. Oppermann H, Mueller B, Takkinen J,
Klauditz W, Schreier E, Ammon A. An out-
break of viral gastroenteritis in a mother-
and-child health clinic. Int J Hyg Environ
Health 2001;203:369-73.
97. Kurtz JB, Lee TW, Pickering D. Astrovi-
rus associated gastroenteritis in a children’s
ward. J Clin Pathol 1977;30:948-52.
98. Ashley CR, Caul EO, Paver WK. Astrovi-
rus-associated gastroenteritis in children.
J Clin Pathol 1978;31:939-43.
99. Lewis DC, Lightfoot NF, Cubitt WD,
 medical progress

Wilson SA. Outbreaks of astrovirus type 1
and rotavirus gastroenteritis in a geriatric
in-patient population. J Hosp Infect 1989;
14:9-14.
100. Gray JJ, Wreghitt TG, Cubitt WD, Elliot
PR. An outbreak of gastroenteritis in a home
for the elderly associated with astrovirus
type 1 and human calicivirus. J Med Virol
1987;23:377-81.
101. Kurtz JB, Lee TW, Craig JW, Reed SE.
Astrovirus infection in volunteers. J Med Vi-
rol 1979;3:221-30.
102. DuPont HL, Chappell CL, Sterling CR,
Okhuysen PC, Rose JB, Jakubowski W. The
infectivity of Cryptosporidium parvum in
healthy volunteers. N Engl J Med 1995;332:
855-9.
103. Overturf GD. Endemic giardiasis in the
United States — role of the daycare center.
Clin Infect Dis 1994;18:764-5.
104. Okhuysen PC. Traveler’s diarrhea due
to intestinal protozoa. Clin Infect Dis 2001;
33:110-4.
105. Marshall MM, Naumovitz D, Ortega Y,
Sterling CR. Waterborne protozoan patho-
gens. Clin Microbiol Rev 1997;10:67-85.
[Erratum, Clin Microbiol Rev 1998;11:404.]
106. Mac Kenzie WR, Hoxie NJ, Proctor
ME, et al. A massive outbreak in Milwaukee
of cryptosporidium infection transmitted
through the public water supply. N Engl J
Med 1994;331:161-7. [Erratum, N Engl J
Med 1994;331:1035.]
107. Heijbel H, Slaine K, Seigel B, et al. Out-
break of diarrhea in a day care center with
spread to household members: the role of
cryptosporidium. Pediatr Infect Dis J 1987;
6:532-5.
108. MacKenzie WR, Schell WL, Blair KA,
et al. Massive outbreak of waterborne cryp-
tosporidium infection in Milwaukee, Wis-
consin: recurrence of illness and risk of sec-
ondary transmission. Clin Infect Dis 1995;
21:57-62.
109. Quiroz ES, Bern C, MacArthur JR, et al.
An outbreak of cryptosporidiosis linked to a
foodhandler. J Infect Dis 2000;181:695-700.
110. Steketee RW, Reid S, Cheng T, Stoebig
JS, Harrington RG, Davis JP. Recurrent out-
breaks of giardiasis in a child day care cen-
ter, Wisconsin. Am J Public Health 1989;79:
485-90.
111. Lengerich EJ, Addiss DG, Juranek DD.
Severe giardiasis in the United States. Clin
Infect Dis 1994;18:760-3.
112. Harter L, Frost F, Grunenfelder G, Per-
kins-Jones K, Libby J. Giardiasis in an infant
and toddler swim class. Am J Public Health
1984;74:155-6.
113. Esfandiari A, Swartz J, Teklehaimanot
S. Clustering of giardiosis among AIDS pa-
tients in Los Angeles County. Cell Mol Biol
(Noisy-le-grand) 1997;43:1077-83.
114. Owen RL. Direct fecal-oral transmis-
sion of giardiasis. In: Erlander SL, Meyer EA,
eds. Giardia and giardiasis: biology, patho-
geneses, and epidemiology. New York: Ple-
num Press, 1984:329-39.
115. Addiss DG, Stewart JM, Finton RJ, et
al. Giardia lamblia and Cryptosporidium in-
fections in child day-care centers in Fulton
County, Georgia. Pediatr Infect Dis J 1991;
10:907-11.
116. Gatti S, Cevini C, Bruno A, Novati S,
Scaglia M. Transmission of Entamoeba his-
tolytica within a family complex. Trans R
Soc Trop Med Hyg 1995;89:403-5. [Erra-
tum, Trans R Soc Trop Med Hyg 1995;89:
537.]
117. Vreden SG, Visser LG, Verweij JJ, et al.
Outbreak of amebiasis in a family in The
Netherlands. Clin Infect Dis 2000;31:1101-4.
118. Steere AC, Mallison GF. Handwashing
practices for the prevention of nosocomial
infections. Ann Intern Med 1975;83:683-
90.
119. Larson EL, Gomez-Duarte C, Lee LV,
Della-Latta P, Kain DJ, Keswick BH. Micro-
bial flora of hands of homemakers. Am J In-
fect Control 2003;31:72-9.
120. Ansari SA, Sattar SA, Springthorpe VS,
Wells GA, Tostowaryk W. In vivo protocol
for testing efficacy of hand-washing agents
against viruses and bacteria: experiments
with rotavirus and Escherichia coli. Appl
Environ Microbiol 1989;55:3113-8.
121. Lin CM, Wu FM, Kim HK, Doyle MP,
Michael BS, Williams LK. A comparison of
hand washing techniques to remove Esche-
richia coli and caliciviruses under natural or
artificial fingernails. J Food Prot 2003;66:
2296-301. [Erratum, J Food Prot 2004;67(3):
following table of contents.]
122. de Wit JC, Kampelmacher EH. Micro-
biological aspects of washing hands in
slaughter-houses. Zentralbl Bakteriol Mik-
robiol Hyg [B] 1982;176:553-61.
123. Black RE, Dykes AC, Anderson KE, et
al. Handwashing to prevent diarrhea in day-
care centers. Am J Epidemiol 1981;113:445-
51.
124. Mohle-Boetani JC, Stapleton M, Fin-
ger R, et al. Communitywide shigellosis:
control of an outbreak and risk factors in
child day-care centers. Am J Public Health
1995;85:812-6.
125. Gibson LL, Rose JB, Haas CN, Gerba
CP, Rusin PA. Quantitative assessment of
risk reduction from hand washing with anti-
bacterial soaps. J Appl Microbiol 2002;92:
Suppl:136S-143S.
126. Larson EL, Lin SX, Gomez-Pichardo C,
Della-Latta P. Effect of antibacterial home
cleaning and handwashing products on in-
fectious disease symptoms: a randomized,
double-blind trial. Ann Intern Med 2004;
140:321-9.
127. Bresee JS, Widdowson MA, Monroe
SS, Glass RI. Foodborne viral gastroenteri-
tis: challenges and opportunities. Clin In-
fect Dis 2002;35:748-53.
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