Disseminated histoplasmosis in a human immunodeficiency virus-infected African child.

Abstract

Progressive disseminated histoplasmosis (PDH), an opportunistic fungal infection caused by Histoplasma capsulatum, is recognized as a defining illness for AIDS.1 In the United States PDH with AIDS is being increasingly reported from areas that are endemic2 and nonendemic3 for the fungus. In Africa although the central and western regions of the continent are endemic, with the variant H. capsulatum var. duboisii being discovered in this area, there have been only a few cases in adults of AIDS-related H. capsulatum infection.4,5 We report here PDH in a HIV-infected African child, from an area that is not endemic for H. capsulatum. Case report. An 8-year-old girl from Kwazulu/Natal, South Africa, was admitted to King Edward VIII hospital with pyrexia and respiratory distress. The child had been ill with general malaise and fever for 3 weeks. She was pale and had generalized lymphadenopathy. A punched out painless ulcer was present on her left lower leg, and she had ulcerative lesions on the tip of her tongue and the angle of her mouth. She had a tender hepatomegaly and clinical signs of a pneumonia. A chest roentgenogram showed right upper lobe consolidation with early cavitation. The purified protein derivative tuberculin skin test was negative and no acid-fast bacilli were detected on three sputum samples taken on different days. A Western blot test for antibodies to HIV was positive. She had pancytopenia: hemoglobin 5.9 g/dl (corrected reticulocyte count, 0.6%), platelet count 64 × 109/l, total white blood cell count 3.4 × 109/l (22% band forms, neutrophil count 1.7 × 109/l and lymphocyte count 0.8 × 109/l). The total serum protein was 6.3 g/dl with serum albumin 2.5 g/dl and globulins 3.8 g/dl. Liver enzymes were marginally elevated: aspartate transaminase 134 IU; alanine transaminase 137 IU; and gamma-glutamyl transferase 97 IU. Ultrasonography of the liver did not reveal intrahepatic lesions. Direct immunofluorescence and culture of the oral lesions yielded herpes simplex type 1. Serologic tests for cytomegalovirus, Mycoplasma, hepatitis A and B and Coxsackieviruses were negative. There was evidence of past exposure to Epstein-Barr virus (viral capsid antigen IgM-negative and nuclear antigen IgG-positive). Blood culture yielded a coagulase-negative Staphylococcus from only the anaerobic bottle after 48 h of incubation; this was interpreted as contamination. The child was treated with parenteral acyclovir for herpesvirus infection, ceftriaxone for severe community-acquired pneumonia, and trimethoprim-sulfamethoxazole because Pneumocystis carinii infection was part of the clinical differential diagnosis. Bone marrow aspirate and trephine biopsy revealed yeast forms of H. capsulatum. The patient died on the second day of hospital admission, before antifungal therapy could be commenced. Postmortem specimens from lung, liver, lower limb skin lesion and lymph node demonstrated histoplasmosis with a high concentration of fungi in the skin biopsy (see Fig. 1).Fig. 1: Section of skin (×400) showing a large number of yeast forms (arrows) of Histoplasma capsulatum.Discussion.H. capsulatum is an intracellular pathogen that infects macrophages throughout the reticuloendothelial system leading to pathologic changes in multiple organs, which results in a variety of clinical syndromes in patients. The term progressive disseminated histoplasmosis is used to describe the presence of extrapulmonary disease, and the disease is often severe in patients with AIDS.6 Although PDH has been described in immunocompromised children from endemic areas in the United States7,8 this is the first report of PDH in an HIV-infected child from Africa from an area that is not recognized as endemic for the dimorphic fungus. Because HIV and H. capsulatum are common in Africa, it is possible that combined infections with these agents are underdiagnosed in children. H. capsulatum has been identified in South African caves and isolated cases of adults with pulmonary disease9 and systemic histoplasmosis10 have been reported, but not from Kwazulu/Natal. It is not surprising that there are isolated H. capsulatum infections in apparently nonendemic areas, because the fungus can survive for years in soil inhabited by chickens, birds and bats. PDH is often an endogenous infection in the immunocompromised patient and it is possible that our patient may have had primary exposure to H. capsulatum at an early stage in childhood and reactivated this yeast because of HIV-associated decline in cell-mediated immunity. Children with AIDS are susceptible to a large number of opportunistic pathogens. This case suggests that histoplasmosis should be added to the list of possible causes of disseminated infection in children from Africa. Thillagavathie Pillay, F.C.Paed. Devadas Ganesh Pillay, F.C.Path. Ashwin Bramdev, F.F.Path. Departments of Paediatrics and Child Health (TP), Medical Microbiology (DGP) and Anatomical Pathology (AB); Faculty of Medicine; University of Natal; Kwazulu/Natal, South Africa