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Major Differences in the Spectrum of Gastrointestinal Infections Associated with
AIDS in India Versus the West: An Autopsy Study
D. N. Lanjewar, B. S. Anand, R. Genta,
M. B. Maheshwari, M. A. Ansari, S. K. Hira,
and H. L. DuPont
From the Department of Pathology, Grant Medical College and Sir J. J.
Group of Hospitals, Bombay, India; and the Department of Medicine,
Veterans Affairs Medical Center, and Center for Infectious Diseases,
University of Texas Health Science Center, School of Public Health,
Houston, Texas
The spectrum of bowel infections in patients with AIDS in India is not well characterized. To
examine this spectrum of infections, an autopsy study of 49 subjects was carried out. Multiple
sections were obtained from the gastrointestinal tract. A pathogenic organism was detected in 2S
(71%) of 3S patients with diarrhea vs. 4 (29%) of 14 patients without diarrhea (P < .01). The most
frequent pathogen was cytomegalovirus (in 13; 27%), followed by parasites (9; 18%), fungi (8; 16%)
and Mycobacterium tuberculosis (7; 14%).This is the first autopsy study of patients with AIDS in the
Indian subcontinent and shows important differences in the profile of their opportunistic infections
compared with those of such patients in the West. These findings will help define the optimal
diagnostic and therapeutic approaches to patients with AIDS, which, in view of the considerable
budgetary restrictions in developing countries, should be targeted toward the pathogens most frequently identified in such areas.
The first report on AIDS in India was published in 1986 [1].
Since then, several small series of clinical case studies have
been reported [2, 3]. However, the magnitude of the AIDS
epidemic in India, as in many other developing countries, is
uncertain.
A report issued by the National AIDS Control Organization
(Ministry of Health and Family Welfare, Government of India)
indicated that as of the end of September 1994, 2.1 million
people in India had been screened for HIV: 6,319 were found
to be seropositive and 849 had AIDS [4]. However, some
experts believe that these statistics represent a gross underestimation of the problem and that the true figures are closer
to 2 million HIV-infected people and 100,000 people with
AIDS [5]. Furthermore, it has been estimated that by the year
2000,30-50 million people in India will be infected with HIV
and 3-5 million will have AIDS [5].
Despite rapid growth in the incidence of AIDS in India, very
little is known about the spectrum of pathogenic infections in
these patients, and the present study was designed to examine
this issue. There are several reasons to believe that the opportunistic infections in patients with AIDS in India may be different
from those reported in the West. In India people live under
relatively poor hygienic and sanitary conditions, and malnutrition is rampant. These factors increase the risk of acquiring
infections and lower the ability to resist disease.
Received 20 October 1995; revised 10 April 1996.
Grant support: National Institutes of Health (no. ROIAI31356-01A3).
Reprints: Dr. D. N. Lanjewar, AIDS Research and Control Center (ARCON),
Skin and STD Building, J. 1. Hospital, Bombay 400 008, India.
Correspondence: Dr. B. S. Anand, Digestive Diseases Section (l11D),
V. A. Medical Center, 2002 Holcombe Boulevard, Houston, Texas 77030.
Clinical Infectious Diseases 1996; 23:482-5
© 1996 by The University of Chicago. All rights reserved.
1058--4838/96/2303-0010$02.00
This is borne out by the fact that the carrier rate of pathogenic
organisms, particularly those of the gastrointestinal tract, is very
high in India. Moreover, chronic infectious disorders such as
tuberculosis are highly prevalent, and most adults have dormant
infection that may manifest itself under unfavorable conditions.
Finally, the mode of transmission of HIV infection is different in India than in the West. In India heterosexual contact is
the most common route of HIV transmission, except in the
northeastern states bordering Burma, where 1%-2% of the
population are intravenous drug abusers and nearly one-half
of them are HIV-positive [4-6]. In the West, by contrast,
homosexual contact and, more recently, intravenous drug abuse
are the most common risk factors.
Materials and Methods
Autopsy studies were carried out on patients dying of AIDS
at the 1. 1. Group of Hospitals and Grant Medical College
(Bombay) between 1988 and 1993. All patients were seropositive for HIV, and all fulfilled the nonimmunologic-surveillance
case definition of AIDS established by the Centers for Disease
Control and Prevention. At autopsy the entire gastrointestinal
tract, from the esophagus to the rectum, was systematically
examined, in particular for the presence of mucosal inflammation, ulcerations, nodules, or masses. Irrespective of the presence or absence of gross lesions, a minimum of 18 tissue
sections were obtained: 3 each from the esophagus and the
stomach, as well as 2 each from the duodenum, jejunum, ileum,
appendix, colon, and rectum.
All the specimens were submitted for paraffin embedding,
and 4-micron-thick tissue sections were obtained for histologic
assessment. The slides were prepared with hematoxylin and
eosin, periodic acid-Schiff stain, mucicarmine, acid-fast stain
(Ziehl-Neelsen), Giemsa and Grocott-Gomori methenaminesilver nitrate stains, iron/Pruss ian blue, and Congo red.
eID 1996;23 (September)
AIDS in India
Table 1. Spectrum of pathogenic organisms identified at autopsy in
49 patients with AIDS in India.
Pathogenic organism
Cytomegalovirus
Parasite
Cryptosporidium species
Strongyloides stercoralis
Hookworm
Fungus
Candida albicans
Cryptococcus neoformans
Mycobacterium tuberculosis
None
Detection rate: no. (%) of patients
in whom organism was found
13 (27)
9 (18)
5 (10)
3 (6)
1 (2)
8 (16)
5 (10)
3 (6)
7 (14)
20 (41)
NOTE. A pathogenic organism was isolated from 29 (59%) of the 49 patients
autopsied; multiple organisms were detected in some patients.
Results
A total of 49 patients were examined in autopsies over a 5year period, including 37 men (75%) and 12 women (25%).
The majority of patients (40; 82%) were between the ages of
20 and 40 years; the age range was 18 years to 72 years. The
most common source of infection in patients of either sex was
heterosexual contact. Thirty-four (92%) of the 37 men acquired
the infection through heterosexual exposure; only one patient
reported a homosexual lifestyle. For the remaining two patients,
the mode of transmission was unclear. Eleven (92%) of the 12
women were prostitutes, while the one other female patient
was infected through blood transfusion.
Thirty- five (71%) of the 49 patients had a history of chronic
diarrhea. The diarrhea was usually present terminally and in
every case consisted of the passage of loose, watery stools;
none of the patients had a history of passing bloody stools. At
autopsy, an infectious agent was detected in 25 (71%) of these
35 patients; 4 were infected with multiple pathogens, while 21
were infected with a single agent. No pathogenic organism was
identified in the remaining 10 patients who had a history of
diarrhea.
In contrast, four (29%) of the 14 patients without a history
of diarrhea had a pathogenic organism isolated from the gastrointestinal tract. The difference in the infection rate between the
two groups was statistically significant (X 2 = 7.6; P < .01).
In the study group as a whole, a pathogen was detected in 29
(59%) of the 49 subjects.
The spectrum of pathogenic organisms identified is shown
in table 1. The most frequently detected organism was cytomegalovirus (CMV), which was observed in 13 patients (27%).
Evidence of CMV infection was noted in the esophagus (in 4
patients), stomach (7), small bowel (8), and colon (6). None
of the patients had macroscopic features of mucosal disease in
the form of mucosal hyperemia, ulceration, or hemorrhages.
At histology, enlargement of the infected cells showed intranuclear inclusions with the characteristic halo. Less frequently,
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intracytoplasmic inclusions were also seen. However, inflammatory response to the virus was nonexistent. Eleven (85%)
of the 13 patients with CMV infection had diarrhea.
Parasitic infections were observed in nine patients (18%).
Infection with a Cryptosporidium species was noted in five
patients, four of whom had diarrhea. The parasites were located
in either the duodenum or the colon; the round, hematoxylinophilic bodies (2-3 microns) were adjacent to or attached to
the mucosal surface of the epithelial cells.
Strongyloides stercoralis was noted in the small intestine of
three patients. The larvae had a characteristic appearance, with
a short esophagus and a large genital primordium. One patient
was infested with hookworms. These parasites were seen
attached to the small-bowel mucosa and were recognized by
their characteristic thick cuticle.
Fungal elements were detected in 8 patients (16%): 5 were
infected with Candida albicans and 3 with Cryptococcus neoformans. The most frequent site of candidal infection was the
esophagus (three patients). The other areas of infection were
the stomach, small bowel, and colon; all three were infected
in one patient, while another had isolated small-bowel involvement.
Candidal infection was diagnosed by the presence of yeastlike cells and pseudohyphae invading the tissues. These were
best detected by the periodic acid-Schiff staining technique.
No tissue reaction in the form of an inflammatory cellular
infiltrate was noted in any case. Three of the five patients with
candidal infection had diarrhea.
Cryptococcal infection of the gastrointestinal tract was seen
in three patients, all of whom had evidence of widespread
infection with multiorgan disease. Two had diffuse involvement of the entire gastrointestinal tract, while one had isolated
small-bowel disease. The pathogens were seen as aggregated
elements of encapsulated and nonencapsulated budding yeasts.
The yeast capsule stained red with mucicarmine and ranged in
size from 2 to 15 microns. Again, there was no inflammatory
response against the fungal infection. All three patients had a
history of diarrhea.
In 31 (63%) of the 49 patients, there was evidence of widespread tuberculosis. Involvement of the gastrointestinal tract,
which was part of the generalized disease process, was observed in seven patients. Five patients had typical caseating
granulomas. Two patients had acute necrotizing inflammation
with macrophage proliferation. The macrophages contained numerous acid-fast bacilli. Culture studies confirmed the presence
of Mycobacterium tuberculosis in one patient, while cultures
were not performed for the remaining patients. The acid-fast
bacilli in all patients were negative on periodic acid-Schiff
staining.
Other abnormalities of the gastrointestinal tract were rare.
One patient had Kaposi's sarcoma affecting the stomach and
small intestine. Another patient had diffuse amyloidosis involving the entire gastrointestinal tract as well as other organs,
including the kidneys, adrenal glands, liver, and spleen. Gastrointestinal lymphoma was not detected in any patient. Nonspe-
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Lanjewar et al.
cific histologic abnormalities were seen frequently: villous atrophy, plasmacytosis of the lamina propria, and presence of
atrophic lymphoid follicles.
Discussion
The spectrum of gastrointestinal infections in patients with
AIDS in the present study differs in several ways from the
findings reported in the West. The incidence of diarrhea in our
patients (71%) was higher than that in the West (30%- 50%)
but lower than that in some of the other developing countries
(90%) [7-9]. Our patients' diarrhea was watery, whereas patients with advanced AIDS in the West also have bloody diarrhea [10, 11]. A definite pathogen was detected in 71% (25)
of the 35 patients who had a history of diarrhea, which is
similar to the reported isolation rate of 68%-85% following
comprehensive workup for chronic diarrhea in patients in the
West [12, 13].
The most frequent pathogen was CMV, identified in 13 patients (27%). None of the patients had mucosal lesions in the
form of diffuse enteritis or ulcers. According to some experts,
the presence of cytomegalic inclusions and chronic inflammatory cellular response is essential for the diagnosis of CMVassociated gastrointestinal disease [12]. In the present study,
although cytomegalic inclusions were seen in every case, in
none of the patients was there evidence of surrounding inflammation or vasculitis.
It is possible that the viral inclusions in our patients simply
were due to commensal infection. Alternatively, the lack of an
inflammatory response may be an indication of advanced disease and may represent extreme immunosuppression. We were
unable to identify other viral infections of the gastrointestinal
tract, such as those due to herpes simplex virus or adenovirus,
which have been incriminated by some investigators as causes
of diarrhea in patients with AIDS [11, 14].
Parasitic infections were identified in nine patients. The most
frequent parasite was Cryptosporidium, found in five patients,
four of whom had chronic diarrhea. The cryptosporidium infection rate among patients with diarrhea (four of 35; 11%) was
similar to the detection rate (16%) in cases of AIDS-associated
diarrhea in the United States [8, 11]. By contrast, in Africa
and Haiti, Cryptosporidium was detected in nearly 50% of
patients with AIDS who had diarrhea [15].
In addition to invasion of the small bowel, which is the
most common site of infection by Cryptosporidium, we found
evidence of parasitic invasion in the colonic mucosa. Larvae
of S. stercora lis were seen in three patients, and an adult hookworm in one. However, despite careful search, we were unable
to detect other parasites such as microsporidia or Isospora belli,
which are frequently observed in the West in cases of AIDSrelated diarrhea [10].
Fungal infections were observed in 8 patients: 5 were infected with e. albicans and 3 with e. neoformans. Infection
with Candida species is common in patients with AIDS and
is considered one of the "minor signs" of this disease, ac-
em
1996;23 (September)
cording to the revised criterion of the World Health Organization [16]. The most frequent clinical presentation is oral and
esophageal candidiasis. Candida has generally not been shown
to cause mucosal disease of the lower gastrointestinal tract
[10]. However, in the present study, evidence of candidal infection was seen not only in the esophagus but also in the gastric,
small-bowel, and colonic mucosa.
e. neoformans is a yeastlike fungus identified by its characteristic polysaccharide capsule. The primary site of infection
is usually the lung, but in patients with AIDS such infection
is frequently inapparent. Hematogenous spreading results in
disseminated cryptococcal infection; almost any organ can be
affected, but the CNS and the meninges are predominantly
involved [17].
All three of our patients had evidence of widespread cryptococcal infection. There was diffuse invasion ofalmost the entire
gastrointestinal tract in two patients and isolated infection of
the small bowel in one. These findings are unusual, since
involvement of the digestive system has not been well documented.
Infection with M tuberculosis was identified in seven patients. The gastrointestinal tract in all seven was involved as
part of a disseminated process that was noted in 31 (63%) of
the 49 patients included in the study. The high incidence of
M. tuberculosis in our study is perhaps a reflection of the
nearly universal carrier rate of this bacterium in the general
population. Despite a careful search, the Mycobacterium avium
complex was not detected in any patient, which is in contrast
to the findings in the West, where M. avium complex is a
frequent cause of diarrhea in patients with terminal AIDS [10].
Other bacterial pathogens frequently isolated from patients with
AIDS-related diarrhea, such as Shigella species, Salmonella
species, and Campylobacter jejuni, also were not identified in
any patient.
In patients with AIDS, diarrhea may be caused by factors
other than pathogenic organisms. These patients are at an increased risk of developing unusual neoplasms of the gastrointestinal tract, such as Kaposi's sarcoma and non-Hodgkin's
lymphoma, both of which are AIDS-defining lesions in HIVpositive patients [18]. In the present study, we were able to
identify only one patient with Kaposi's sarcoma. This finding
is not surprising, since the condition occurs almost exclusively
in homosexual men-and even in this group, the incidence
has gradually declined in recent years [19].
Gastrointestinal lymphomas were not found in any patient.
The majority of lymphomas in patients with AIDS are highgrade tumors of B cell origin, similar to Burkitt's lymphoma
[20]. Involvement of the gastrointestinal tract is common, and
virtually any part, from the oral mucosa to the colon, may be
involved. It is surprising that these tumors developed in none
of our patients, since lymphomas are not limited to any single
risk group and have been noted in homosexuals, intravenous
drug abusers, and hemophiliacs [19].
A diagnosis of AIDS-related enteropathy essentially is made
on the basis of exclusion and is considered when, despite an
eID 1996;23 (September)
AIDS in India
extensive diagnostic workup, no pathogenic organism can be
identified in patients with diarrhea. The small-bowel mucosa
shows nonspecific abnormalities such as a decrease in villusto-crypt ratio and alterations in the numbers of intraepithelial
lymphocytes and crypt mitotic cells [21- 23]. The pathogenesis
of such enteropathy is unknown but is believed to be direct HIV
infection of the gastrointestinal mucosa. Although nonspecific
mucosal abnormalities were frequently seen in our patients, we
were unable to confirm a diagnosis of AIDS-related enteropathy
because of the lack of a pathognomonic histologic lesion associated with this condition.
The present report represents the largest autopsy study of
AIDS in the Indian subcontinent. Our observations showed
important differences from the findings reported from other
parts of the world. The pathogens identified in our patients
reflected the spectrum of organisms prevalent locally. For example, M. tuberculosis, CMV, Candida species, Cryptococcus
species, and S. stercoralis were identified frequently, while
organisms such as microsporidia, I. belli, C. jejuni, and
M. avium complex were not seen in a single patient. However,
it should be pointed out that since electron microscopy was
not performed, some infections with microsporidia may have
been missed. In the present study only one patient had Kaposi's
sarcoma and none had non-Hodgkin's lymphoma, both of
which are frequently identified in the West in patients with
terminal AIDS.
The present study has helped to define the spectrum of pathogenic organisms in patients with AIDS in the Indian subcontinent. Differences in the prevalence rates of infectious agents,
as related to geographical location, have been observed in association with AIDS. For example, rotavirus is detected in 18%
of patients with AIDS-related diarrhea in Australia but rarely
occurs in such patients in the United States [24]. Similarly,
I. belli and Cryptosporidium species are common in some developing countries but not in the West [11]. These observations
are important since, in developing countries with considerable
budgetary restrictions, the diagnostic workup and therapeutic
approach should be targeted toward the most frequently identified infectious agents in those areas.
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