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VISCERAL LEISHMANIASIS IN A BRAZILIAN CHILD INFECTED PERINATALLY WITH HUMAN IMMUNODEFICIENCY VIRUS

2001; Lippincott Williams & Wilkins; Volume: 20; Issue: 2 Linguagem: Inglês

10.1097/00006454-200102000-00024

1532-0987

Elizabeth Ferreira, Sheila Cunha Lucena, Guacira Fonseca, Tereza Cristina Barbosa, Regina B Aquino, John S. Lambert, Susie Andries Nogueira,

Leptospirosis research and findings

This report describes a Brazilian child perinatally infected by HIV who presented visceral leishmaniasis. She showed the classic clinical features, and diagnosis was made by demonstration of amastigote forms of Leishmania in bone marrow aspirate. She responded well to traditional treatment with meglubine. Visceral leishmaniasis (VL), caused by the protozoan Leishmania and transmitted through the bite of a sandfly (Phlebotomus sp.), 1 is endemic in 82 countries. Ninety percent of reported cases are in Africa, Sudan, Ethiopia, Kenya, Asia, India, Bangladesh and Nepal (Leishmania donovani) and from South America, Brazil (Leishmania chagasi). The disease occurs mainly in children from rural and semirural areas. 2 Since 1980 ∼90% of reported cases worldwide of VL occurring in persons with HIV infection have been identified in Mediterranean Europe, namely Spain, Italy and France (Leishmania infantum). These cases are primarily in men who are intravenous drug users and coinfected with HIV. 3–5 The first reported case of an HIV-1-infected child with VL was in a 12-year-old boy from Spain, and the first case of HIV-2 coinfection was a 10-year-old African girl from Guinea Bissau. 6 Leishmaniasis in HIV-infected patients presents either as a latent infection reactivated by immune system suppression or as a primary Leishmania infection which takes advantage of the lymphopenia caused by HIV infection. The immunologic perturbations produced by infection with VL and HIV-1 have similarities that can be enhanced if they occur concomitantly. 4, 5 Based on the finding of VL in the setting of HIV immunosuppression, it has been proposed that it be included in the list of HIV-associated opportunistic infections. VL is a dynamic infection with a continuously changing epidemiologic pattern in recent years. As the HIV epidemic rapidly spreads to rural areas 7 and as leishmaniasis moves into the urban centers of Brazil, 8 as a result of population movement and of the deterioration of the socioeconomic situation, many have predicted an overlapping of these 2 infections and an increasing number of coinfected patients. In Brazil, according to Rabello et al. 9 54 cases of leishmaniasis and HIV were reported between 1986 and 1999, comprised of 18 (33.3%) with VL and 36 with cutaneous form, all cases being in adults, primarily men. This report describes the first Brazilian case of VL in a young perinatally infected child with HIV-1, from the city of Rio de Janeiro. Case description. The infant was born on July 23, 1995, in a suburb of the western zone of the city of Rio de Janeiro. At the time of admission to Hospital Raphael de Paula Souza (HRPS) on March 3, 1997, the child was 1 year and 7 months old and was referred from a county hospital with high fever, cough, dyspnea and recurrent diarrhea for 2 months. She had been diagnosed with pneumonia and treated with ampicillin without clinical improvement. During this time she developed purulent otitis media and anemia. Antibiotics were changed without response, at which time she was transferred to HRPS with a suspicion of pulmonary tuberculosis. Her past history included birth by vaginal delivery; birth weight of 2500 g and height of 51 cm. She was exclusively breast-fed until 3 months of age, followed by mixed breast-feeding and formula until 19 months, the time of her initial presentation. The mother had not received prenatal care and acknowledged many sexual partners but denied intravenous drug use. During the first year of life the child had been admitted many times to hospitals because of infectious problems including varicella, otitis, pneumonia (three occurrences) and diarrhea. Physical examination on admission in HRPS was that of an 19-month-old child whose weight was 8.6 kg and whose height was 77 cm. She was undernourished (second degree), hypoactive and anemic. She had oral candidiasis, generalized lymph node enlargement and disseminated scabies. Other findings included hepatomegaly (liver measured 5 cm below the right coastal margin) and splenomegaly (spleen measured 7 cm below the left coastal border). The child was dyspneic with rales auscultated in both lungs. Nervous system examination detected retarded neurodevelopment. She was unable to walk. No meningeal or focal neurologic signs were identified. Laboratory evaluation at entry included a chest roentgenogram showing alveolar infiltration in the left lung. A gastric lavage specimen was negative by stain and culture for acid-fast bacilli. Hematology evaluation included hematocrit of 29.7%, hemoglobin of 9.3 g/dl, platelet count of 252 000/mm 3 and total white blood cell count of 6100/mm 3. Blood cultures were sterile. Serologic tests for syphilis and toxoplasmosis were negative. Serology for cytomegalovirus and rubella was IgM-negative but IgG-positive. The aspartate aminotransferase was 48 units/l, alanine aminotransferase was 30 units/l, total protein was 5.7 g/dl and albumin was 3.1 g/dl. CD4 was 322 cells/mm 3 (23%) and CD8 was 826 cells/mm 3 (59%). Anti-HIV enzyme-linked immunosorbent assay and Western blot were both positive and HIV PCR DNA was positive. Immunofluorescence of the patient’s serum for Leishmania antibody was positive at a titer of 1/45, and a bone marrow aspirate revealed the presence of the amastigote form of Leishmania (Fig. 1).Fig. 1: Bone marrow aspirate showing macrophage with amastigote form of L. chagasi (Giemsa stain).The mother’s serology was positive for HIV, and one brother, who was 7 years old, tested negative for HIV but positive by immunofluorescence for Leishmania, titer 1/360, but the child had no clinical signs or symptoms of disease. The other three sisters were negative for anti-Leishmania antibodies and anti-HIV negative. The child’s clinical course consisted of initial treatment with oxacillin and ceftriaxone. After 12 days, she had persistent fever and worsening respiratory deterioration. At that time trimethoprim-sulfamethoxazole therapy was initiated to treat the suspicion o f Pneumocystis carinii pneumonia. Didanosine and zidovudine were also administered once the diagnosis of HIV infection was confirmed by serology and by PCR DNA. With this change in therapy her pulmonary condition improved but she remained febrile, anemic and with hepatosplenomegaly. With the availability of the result of the bone marrow aspirate 25 days into her hospitalization, the diagnosis of visceral leishmaniasis was established, at which time the pentavalent antimonial, meglubine antimoniate (Glucantime; 20/mg/kg) was administered iv for 30 days. She showed clinical response to Glucantime, with reduction in hepatosplenomegaly, anemia and fever. During hospitalization she also developed multidermatomal herpes zoster and was successfully treated with a 10-day course of iv acyclovir. After a total of 55 days of hospitalization, she was discharged to receive a regimen including zidovudine-didanosine and trimethoprim-sulfamethoxazole. Follow-up after discharge was erratic, but during the first year she had no relapse of VL. The following year she was less adherent to clinic appointments and died in 1999, with sepsis and strongyloidiasis during a short period of hospitalization. Discussion. The endemicity, geographic distribution and transmission of leishmaniasis are a function of the distribution and abundance of vectors, the presence of a reservoir and the susceptibility of the host. In Brazil the reservoir of VL is the domestic dog, and the endemic areas of VL historically were mainly in the rural area of the Northeast and Southeast states of Brazil. However, in the last decade outbreaks have been described in new urban locales including São Luiz (North), Teresina (Northeast) and São Paulo and Rio de Janeiro (Southeast). These expanding populations, living in overcrowded and inadequate conditions, with the poor living in slums in the periurban area allied to favorable breeding conditions for the vector and the frequent presence of domestic animals living with the families, create ideal conditions for the transmission of L. chagasi and the urbanization of VL in Brazilian cities. 9 The clinical pictures of the two previously mentioned pediatric cases of VL and HIV infection were atypical because hepatosplenomegaly and lymphadenomegaly were lacking, and the prominent features were fever and anemia. 6 VL is one of the major causes of fever of unknown origin in adult patients with AIDS in Southern Europe. The typical clinical presentation of VL, even in coinfected patients with HIV infection, is found in 75% of all patients (fever, hepatosplenomegaly and pancytopenia). 4, 5, 10, 11 However, it is thought that decreased CD4 cells counts and reduced production of interferon-gamma can facilitate the spread of Leishmania organisms, resulting in diffuse visceral spread of the parasite. Our patient showed the classic clinical picture of VL including severe malnutrition, which is not rare in Brazilian children with VL. Nutritional derangement and immunologic abnormalities associated with HIV coinfection 5 may have further compromised this child’ s immune system. Once the suspicion of VL was raised in our patient, it was not difficult to find the amastigote Leishmania in her bone marrow aspirate; however, the immunofluorescence serologic test titer was low. Usually in immune competent patients with VL the titer is higher. The serologic test for VL has low sensitivity in patients coinfected with HIV, 1, 11 and the demonstration of the parasite by Giemsa stain is the standard diagnostic test. 4, 10 Our patient’s fever and hepatosplenomegaly improved only after initiation of specific treatment for VL 1, 2, 5 and showed no relapse in the following year after completion of therapy. Glucantime is still the main treatment for VL in Brazil; most of our strains of L. chagasi are susceptible. Amphotericin B and pentamidine are alternatives for patients with Leishmania strains resistant to Glucantime 1, 11 or for relapses, which are more common (60%) in patients coinfected by HIV. 3 Acknowledgment. We thank Dr. Carmello Conti, the hematologist who performed the bone marrow aspirate and gave us the picture of the smear with the amastigote form of L. chagasi.