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Perspectives
Anthrax of the Gastrointestinal
Tract
Thira Sirisanthana* and Arthur E. Brown†
*Chiang Mai University, Chiang Mai, Thailand; and †Armed Forces Research
Institute of Medical Sciences, Bangkok, Thailand
When swallowed,
anthrax spores may cause lesions from the oral cavity to the cecum.
Gastrointestinal anthrax is greatly underreported in rural disease-endemic
areas of the world. The apparent paucity of this form of anthrax reflects
the lack of facilities able to make the diagnosis in these areas. The
spectrum of disease, ranging from subclinical infection to death, has
not been fully recognized. In some community-based studies, cases of
gastrointestinal anthrax outnumbered those of cutaneous anthrax. The
oropharyngeal variant, in particular, is unfamiliar to most physicians.
The clinical features of oropharyngeal anthrax include fever and toxemia,
inflammatory lesion(s) in the oral cavity or oropharynx, enlargement
of cervical lymph nodes associated with edema of the soft tissue of
the cervical area, and a high case-fatality rate. Awareness of gastrointestinal
anthrax in a differential diagnosis remains important in anthrax-endemic
areas but now also in settings of possible bioterrorism.
The epidemiology of human anthrax has been described as agricultural
and industrial (1). In the agricultural setting, infections
occur from exposure to Bacillus anthracis spores on the skin or
the mucosal surfaces of the gastrointestinal (GI) tract. Primary infections
of the respiratory tract are rare in agricultural settings. Generally,
reports state that the cutaneous form of anthrax is much more common than
the GI form (2,3). We propose that the apparently overwhelming
predominance of the cutaneous form of anthrax is rather a reflection of
the difficulty of diagnosis of the GI form.
GI anthrax may be diagnosed on the basis of epidemiology or microbiologic,
pathologic, or serologic testing. Serologic diagnosis is available only
in a few research laboratories; pathologic evaluation requires surgery
or necropsy in an appropriate hospital; microbiologic testing requires
at least microscopy and preferably bacterial culture capacity; and epidemiology
requires a level of suspicion and an ability to properly perform outbreak
investigations. Herbivores, which provide most of the human exposure risk
for anthrax, become infected in rural parts of the world where spores
in the soil perpetuate endemicity. Mild cases of gastroenteritis attract
little attention, and people with severe infections, leading to death
within 2–3 days, may never reach a medical facility.
Areas endemic for anthrax exist in all continents containing tropical
and subtemperate regions. In the English published reports, deaths from
GI anthrax have been reported in Thailand (4–6), India
(7,8), Iran (9–11),
Gambia (12), and Uganda (13). Anthrax-contaminated
beef from a locally infected cow was eaten in Minnesota in 2000. Cooking
the meat may have prevented human cases (14). Despite
this wide distribution of endemicity, no large series of pathologically
described cases exists. Based on limited reports of GI anthrax, the disease
spectrum ranges from the asymptomatic to the fatal, by shock or sepsis.
When swallowed, anthrax spores may cause lesions from the oral cavity
to the cecum. Ulcerative lesions, usually multiple and superficial, may
occur in the stomach, sometimes in association with similar lesions of
the esophagus and jejunum (4,5,15).
These ulcerative lesions may bleed; hemorrhaging in severe cases may be
massive and fatal (4,5).
Reported cases indicate that lesions farther down the GI tract, in the
mid-jejunum, terminal ilium, or cecum, tend to develop around a single
site or a few sites of ulceration and edema, more analogous to cutaneous
lesions. These lesions may lead to hemorrhage (6,16),
obstruction (10,17,18), perforation
(17,18), or any combination of these. Ascites may complicate
GI anthrax (6,7,9,11,18,19). In some
patients, the fluid shift from the vascular compartment leads to shock
and death (6,7,9).
The pathologic examination of anthrax lesions with entry via the GI tract
shows that the mucosa is always involved, as are regional lymph nodes,
which are enlarged and hemorrhagic (15). The GI tract
may also be involved after disseminated infection in pulmonary and sometimes
cutaneous cases (20–22). In this situation,
the localization is in the submucosa as a result of its blood flow, and
the mucosa and regional lymph nodes become involved only secondarily.
These reports are biased toward the hospitalized patients with severe
cases. Thorough epidemiologic reports are scarce. One informative description
of an outbreak investigation and response comes from Uganda (13).
Gastroenteritis developed and death occurred in 155 persons who feasted
on an infected zebu (Asian ox); 2 days after exposure, the incident was
reported to authorities who flew in a multiministry team the next day.
Gastroenteritis developed in most (92%) of those exposed within 15–72
hours. All nine deaths were in children and occurred in the first 2 days;
all 12 asymptomatic cases were in adults. Authorities referred 134 symptomatic
people to the hospital for rehydration and treatment with antibiotics;
all recovered. Thus, for most people exposed, the syndrome was gastroenteritis;
a differential diagnosis would not normally have included anthrax. The
age differences suggest that in this setting previous exposure may have
occurred, leaving some adults with partial immunity.
Another community anthrax outbreak of note was investigated by officers
from the Field Epidemiology Training Program of the Thai Ministry of Public
Health (23). From January through June 1982, an outbreak
of human anthrax was recognized in two districts in Udon Thani Province
in northeastern Thailand after an outbreak in cattle that killed 36 water
buffalos (Bubalus bubalus) and 7 cows and bulls. Of the 102 patients,
28 had cutaneous anthrax and 74 gastrointestinal anthrax. The only symptom
in 67 of these 74 patients with gastrointestinal anthrax was acute diarrhea
(i.e., gastroenteritis). The other seven patients had additional symptoms
of nausea, vomiting, abdominal distention, and severe abdominal pain.
Three patients died; the case-fatality rate was 4%. Thus, in these two
community-based studies, the number of patients with GI anthrax far outnumbered
those with the cutaneous form of the disease.
In addition to lack of epidemiologic, microbiologic, pathologic, and
serologic expertise and facilities in the rural settings where anthrax
outbreaks take place, the oropharyngeal form is underreported because
few physicians are aware of the disease. Only six publications in the
MEDLINE database report anthrax lesions in the mouth or oropharynx (24–29).
Davies described a major epidemic of anthrax involving >9,000 patients
in Zimbabwe from 1978 to 1980 (24). He cited four cases
in which lesions were on the tonsil and the tongue but provided no details.
We reported an outbreak of human anthrax after anthrax was found in water
buffaloes in March–April 1982 in Chiang Mai, northern Thailand (25).
A total of 52 cases of cutaneous anthrax and 24 cases of oropharyngeal
anthrax were recognized in humans. All patients with oropharyngeal anthrax
had recently eaten water buffalo meat. The mean incubation period was
42 hours (range 2–144 hours). All but one patient were admitted to the
hospital. All patients sought medical attention because of painful neck
swelling, and all but one complained of fever. The other common symptoms
were sore throat, dysphagia, and hoarseness. The neck swelling was usually
marked and was caused by enlargement of cervical lymph nodes and soft
tissue edema (Figure 1). Mouth lesions were located
on the tonsils, posterior pharyngeal wall, or the hard palate. In severe
cases, the tonsillar lesions extended to involve the anterior and posterior
pillars of fauces, as well as the soft palate and uvula. Early lesions
were edematous and congested. By the end of the first week, central necrosis
and ulceration had produced a whitish patch (Figure
2). In the second week, this patch developed into a pseudomembrane
covering the ulcer (Figure 3). Diagnosis could
be made by culture taken from the lesion in the mouth. A Gram stained
smear from the lesion showed numerous polymorphonuclear leukocytes and
gram-positive bacilli. Studies of serum antibody to anthrax antigens confirmed
the diagnosis (27). Despite hospital admission and antibiotic
treatment, 3 of the 24 patients died, for a case-fatality rate of 12.4%.
In 1986, Doganay and colleagues reported six patients from Turkey with
essentially the same clinical syndrome (28). The case-fatality
rate in that study was 50%. The most recent case report, also from Turkey,
was in 1993 (29).
When cattle die of anthrax, the bacteremia is massive, and manifestations
of the infection are visible to the butcher. In some settings, people
may eat meat they know to be contaminated, as was the situation in a poor
village of Harijans (“untouchables”) in India (8). More
common may be the situation in which meat is sold to those unaware of
the animal disease as was the case in the Chiang Mai outbreak (25).
Only those who eat dishes that are raw or undercooked are exposed to infectious
material. Disease is likely related to a dose of viable spores and the
immune state of host. In contrast to the extreme susceptibility of cattle
to this infection and its bacteremia, studies in chimpanzees suggest that
primates are relatively resistant (30).
While the biowarfare and bioterrorist development of anthrax has focused
on inhalation, ingestion has been considered as well. The Japanese experiments
in China during the 1930s and 1940s included attempts to poison children
with chocolate impregnated with anthrax (31). More recently,
the apartheid government of South Africa had developed biological weapons,
including another attempt at anthrax-containing chocolate (32).
Given the large community outbreak of salmonellosis caused by an intentional
contamination of restaurant salad bars the in United States by the Rajneeshees
(33), awareness of the potential for GI anthrax due
to bioterrorism is important.
In conclusion, GI anthrax is probably greatly underreported in rural
disease-endemic areas of the world. The spectrum of disease, ranging from
no symptoms to death, has not been fully appreciated. Awareness of anthrax
in a differential diagnosis remains important in disease-endemic areas
and also in settings of possible bioterrorism.
Dr. Sirisanthana is professor of medicine and director of the Research
Insitute for Health Sciences, Chiang Mai University, Thailand. He received
his medical degree from Mahidol University in Bangkok and then trained
in internal medicine in infectious disease at Indiana University, the
University of Chicago and the Medical College of Wisconsin from 1975 to
1979.
LTC Brown is chief, Department of Retrovirology, at the Armed Forces
Research Institute for Medical Sciences in Bangkok. He is a fellow of
the Infectious Disease Society of American with training in tropical public
health. Dr. Brown’s research in tropical infectious diseases has been
based largely in Thailand for the past 20 years.
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