We report a case of coinfection of visceral leishmaniasis and Mycobacterium avium-intracellulare in the same lesions in the small bowel and bone marrow of a 33-year-old man with acquired immunodeficiency syndrome who complained of abdominal pain and chronic diarrhea. The duodenal mucosa and bone marrow biopsy specimens showed numerous foamy macrophages packed with two forms of microorganisms that were identified histologically and ultrastructurally as Leishmania and Mycobacterium species. Visceral leishmaniasis is rarely suspected in patients residing in nonendemic countries including the United States. It should be included in the differential diagnosis for opportunistic infection in patients with acquired immunodeficiency syndrome. An appropriate travel history is important. To our knowledge, this is the first reported case showing coinfection of visceral leishmaniasis and Mycobacterium avium-intracelluulare in the same lesion in a patient with acquired immunodeficiency syndrome.

Gastrointestinal symptoms occur in 50% to 90% of patients infected with the human immunodeficiency virus (HIV).1 Although visceral leishmaniasis is an important opportunistic infection in patients infected with HIV in the endemic areas of Spain and South France,1–3 it is rarely encountered or suspected in nonendemic countries. Recently, visceral leishmaniasis has emerged as an important opportunistic infection in HIV-infected persons living in areas nonendemic for leishmaniasis, such as Germany.4 However, to our knowledge, no cases have been reported in the United States. We describe herein a case of coinfection of visceral leishmaniasis and Mycobacterium avium-intracellulare (MAI) in the same lesions in small bowel and bone marrow biopsy specimens of a 33-year-old man with acquired immunodeficiency syndrome (AIDS) with complaints of abdominal pain and chronic diarrhea. To our knowledge, this is the first reported case of coinfection with visceral leishmaniasis and MAI in the same lesion of a patient with AIDS.

A 33-year-old, white, homosexual man with AIDS complained of nausea, vomiting, vague abdominal pain, and chronic diarrhea with 7 to 10 loose bowel movements daily and a 13.5-kg weight loss during 9 months. These manifestations were putatively presumed to be due to toxoplasmosis and intestinal MAI infection based on clinical serologic testing, abdominal computed tomography, and endoscopy with small bowel biopsy. He had been diagnosed as having AIDS 18 months previously and had been followed up by his primary care physician. He previously had oral thrush, leukoplakia, and 2 episodes of pneumocystis pneumonia. The patient denied intravenous drug use. Physical examination was remarkable for bilateral neck and supraclavicular lymphadenopathy, upper abdominal guarding, and hepatosplenomegaly. Infection with MAI was demonstrated by both bone marrow and stool cultures. The results of the serologic test for toxoplasmosis were weakly positive. The patient recalled a trip to Spain and France approximately 7 years ago but denied any other trip abroad. His small bowel biopsy specimen was sent to our institute for further evaluation of possible Toxoplasma gondii vs Microsporidium species.

The small bowel biopsy specimen was fixed in 10% neutral-buffered zinc formalin, embedded in paraffin, sectioned in 3 to 4 μm in thickness, and routinely stained with hematoxylin-eosin. Additional tissue was fixed in 2.5% glutaraldehyde solution, embedded in plastic resin, cut in thick sections, and stained with toluidine blue after routine processing. There were numerous foamy macrophages packed with microorganisms present in the small bowel lamina propria (Figure 1). Ultrastructurally, 2 different forms of microorganisms were identified in the cytoplasm of the macrophages, with one bacilliform bacteria and the other round or ovoid protozoa (Figure 2). The protozoa were approximately 2 to 4 μm in diameter, and contained a single nucleus with a prominent nucleolus and an adjacent barlike kinetoplast and a flagellum, ultrastructurally consistent with amastigotes of Leishmania species (Figure 2, insert). The flagellum consisted of 9 doublets plus 2 central microtubules. An invagination of the cell membrane forming a pocketlike reservoir surrounding the flagellum was also identified. Peripheral fibrils along the inside wall of cell membranes were observed. Rare intracytoplasmic organelles, including mitochondria, rough endoplasmic reticulum, and fat globules, were present. The bacilliform bacteria were acid-fast stain positive and consistent with mycobacterial species, which were proven to be MAI complexes by bone marrow and stool cultures. The intestinal epithelial cells showed no evidence of microsporidium infection. Duodenal biopsy cultures were negative for virus and Cryptococcus. Both the bone marrow biopsy section and aspirate smears also demonstrated the presence of numerous foamy macrophages packed with both leishmanial and mycobacterial organisms.

Figure 1.

Small bowel biopsy specimen showing numerous foamy macrophages packed with microorganisms present in the lamina propria (toluidine blue stain, original magnification ×400)

Figure 1.

Small bowel biopsy specimen showing numerous foamy macrophages packed with microorganisms present in the lamina propria (toluidine blue stain, original magnification ×400)

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Figure 2.

Electron microscopy of small bowel mucosa showing a submucosal macrophage containing intracellular bacilli (long arrows) and protozoa (short arrows) (original magnification ×2000). Insert, A Leishmania amastigote with a characteristic kinetoplast (arrow) and a flagellum (curved arrow) (original magnification ×19 000).

Figure 2.

Electron microscopy of small bowel mucosa showing a submucosal macrophage containing intracellular bacilli (long arrows) and protozoa (short arrows) (original magnification ×2000). Insert, A Leishmania amastigote with a characteristic kinetoplast (arrow) and a flagellum (curved arrow) (original magnification ×19 000).

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Leishmaniasis is caused by Leishmania species and includes 4 major clinical syndromes: visceral leishmaniasis (kala azar), cutaneous leishmaniasis, mucocutaneous leishmaniasis, and diffuse cutaneous leishmaniasis in cell-mediated immunodeficiency status.5–7 ,Leishmania species is an intracellular protozoan that infects macrophages and may disseminate throughout the reticuloendothelial system. Classification of Leishmania is undergoing continual revision as isoenzyme techniques and analyses of genomic and kinetoplast DNA are applied to isolates. It is quite clear that there is considerable genetic diversity even within an accepted species.5–7 Clinical manifestations may be variable, and some species can cause more than one syndrome.6,7 For example, L chagasi, which usually causes visceral disease, has been isolated from patients with cutaneous leishmaniasis (dermatotropic strains), and strains of L tropica, a cause of cutaneous leishmaniasis, have produced visceral manifestations (viscerotropic strains).6,7 Visceral leishmaniasis is typically associated with several subspecies of L donovani, including L donovani donovani, L donovani infantum, L donovani chagasi, and L donovania archibaldi.

Visceral leishmaniasis is endemic in Mediterranean countries, southern Russia, Asia, India, Africa, and South America.2,5,6 The incubation period is usually between 3 and 8 months or longer. Whether the disease progresses depends on the capability of the host's T lymphocytes to activate macrophages to kill the parasites.5 Although a local nonulcerating nodule at the site of the bite may precede systemic manifestations, it is usually inapparent. The onset of symptoms may be acute or insidious. Fever often peaking twice daily with chills and sweats, weakness, anorexia, weight loss, cough, diarrhea, hepatosplenomegaly, and generalized lymphadenopathy are typical features found in subacute and chronic cases.6,7 Our patient presented with nausea, vomiting, vague abdominal pain, chronic diarrhea, a 13.5-kg weight loss during 9 months, and multiple episodes of concurrent infection. He also had massive hepatosplenomegaly and generalized lymphadenopathy. In acute cases, abrupt onset of high fever and chills, sometimes with a periodicity mimicking malaria, may be seen, and the spleen and liver typically become massively enlarged.6 Wasting is progressive, and death, often due to intercurrent infection, occurs within months to 1 to 2 years without treatment.7 A definitive diagnosis can be made by demonstration of amastigotes in tissue or isolation of the organism in culture.7 Depending on the availability, species-specific isoenzyme profiles or kinetoplast DNA probes can be used to identify the subspecies of Leishmania.5,6 

Three species of Trypanosoma are associated with 2 types of human disease. Trypanosoma brucei rhodesiense and T brucei gambiense are pathogens of African sleeping sickness that particularly involve the central nervous system and that have no amastigotes, whereas American trypanosomiasis (Chagas disease), caused by T cruzi, has intracellular amastigote forms that are similar to the amastigotes of Leishmania.5–7 However, Leishmania are smaller and found only in macrophages of bone marrow and small bowel and reticuloendothelial cells. The amastigotes of Trypanosoma may be found in many different cells, including the myocardium (in South American trypanosomiasis).5,6 Although toxoplasmosis was suspected in this infection, that parasite does not have a kinetoplast or a flagellum. These later characteristics rule out other intracellular organisms such as Histoplasma.

Gastrointestinal symptoms commonly occur in HIV-positive patients and can be caused by many opportunistic pathogens such as protozoa, bacteria, fungus, or virus.1,8 Massive infection of small bowel with MAI has been termed pseudo-Whipple disease and is not uncommon in HIV-infected patients.7–9 Acid-fast stain will distinguish this infection from Whipple disease when foamy macrophages are present in the lamina propria of small bowel. Toxoplasma antibody is found in about 55% of the US population.7 Toxoplasmosis is an important opportunistic infection either as a primary or reactivated one in patients with AIDS or cancer or those given immunosuppressive medications.7 The infection occurs most frequently in the brain but also may involve lung, heart, and liver or manifest as disseminated disease. However, since many HIV-infected patients will have incidental titers, a positive toxoplasma serologic test result does not necessarily confirm the diagnosis.7 Visceral leishmaniasis in HIV-positive patients, especially in nonendemic countries, is rarely encountered or suspected, although it has become an important opportunistic infection in HIV-positive patients residing in endemic areas.1–3 Its incidence has been estimated to be 1% to 3.2% in patients with AIDS in Spain.1,2 Recently, Lopez-Velez and colleagues3 conducted a large-series case study to compare the clinicoepidemiologic characteristics, prognostic factors, and survival rates of visceral leishmaniasis between HIV-infected patients and non–HIV-infected patients. They concluded that visceral leishmaniasis in patients with AIDS is a recurrent disease with high prevalence and that the clinical course is modified by HIV infection.3 Visceral leishmaniasis also has become an important opportunistic infection in HIV-infected persons with histories of travel in endemic areas.4 

In the present case, the patient had lived in the United States since birth but had traveled to Europe, including France and Spain, 7 years ago, where visceral leishmaniasis is endemic.1–3,5,6 

It is most likely that he was infected during his trip and that the infection remained latent until he developed AIDS and the opportunistic infection by MAI, although the 7-year period between exposure and onset of the disease is extraordinarily unusual. Parenteral transmission via needle sharing or sexual activity, a recognized mode of transmission in HIV-coinfected individuals in Spain,10 cannot be ruled out in our patient. To our knowledge, this is the first reported case of coexistence of visceral leishmaniasis and mycobacterial infection in the same lesion in a patient with AIDS. Coinfection with Leishmania and herpes zoster in an HIV-infected patient has been recorded.11 In conclusion, visceral leishmaniasis should be included in the differential diagnosis in HIV-infected patients with complaints of gastrointestinal symptoms, particularly those who live or have traveled to endemic areas.

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