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International Journal of Infectious Diseases (2009) 13, e504—e507 http://intl.elsevierhealth.com/journals/ijid CASE REPORT Atypical disseminated leishmaniasis similar to post-kala-azar dermal leishmaniasis in a Brazilian AIDS patient infected with Leishmania (Leishmania) infantum chagasi: a case report Dimas Carnaúba Jr a, Cassiana Tami Konishi a, Valéria Petri b,c, Isabel Cristina Pedro Martinez c, Laura Shimizu c, Vera Lucia Pereira-Chioccola d,* a Centro de Referência em DST/AIDS de Santo Amaro, São Paulo, SP, Brazil Universidade Federal de São Paulo, São Paulo, SP, Brazil c Hospital Ipiranga, São Paulo, SP, Brazil d Laboratorio de Parasitologia, Instituto Adolfo Lutz, Av. Dr Arnaldo, 351, 8 andar, CEP 01246-000, São Paulo, SP, Brazil b Received 5 August 2008; received in revised form 14 January 2009; accepted 19 January 2009 Corresponding Editor: William Cameron, Ottawa, Canada KEYWORDS Leishmania (Leishmania) infantum chagasi; AIDS; Disseminated leishmaniasis Summary We report the case of an atypical disseminated leishmaniasis with similar clinical characteristics to post-kala-azar dermal leishmaniasis, an uncommon disease in South America. This occurred in a Brazilian patient with AIDS, 3 years after the first episode of American visceral leishmaniasis. # 2009 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved. Introduction Leishmaniases are endemic in 88 countries, 72 of which are developing countries. The worldwide prevalence of the disease is estimated at 12 million cases, with 400 000—600 000 new cases per year for visceral forms.1,2 In Brazil, approximately 2500—5000 cases are reported each year.3 * Corresponding author. Tel.: +55 11 3068 2991; fax: +55 11 3068 2890. E-mail address: [email protected] (V.L. Pereira-Chioccola). The genus Leishmania causes a wide spectrum of human diseases, ranging from self-limited cutaneous to the more severe diffuse cutaneous and visceral forms, as a consequence of the complex host immunological response.4,5 The causative agent of the American viscerotropic leishmaniasis in Latin-America is Leishmania (Leishmania) infantum chagasi included in the subgenus Leishmania.4,5 Despite some differences in cost of treatment, toxicity, drug resistance, and endemic region, treatment is usually based on the use of leishmanicidal drugs, principally injections of pentavalent antimony compounds.1,2,4,6 However, a significant proportion of the apparently cured 1201-9712/$36.00 # 2009 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.ijid.2009.01.022 Atypical disseminated leishmaniasis in an AIDS patient patients infected with Leishmania (Leishmania) donovani in India, Nepal, Bangladesh, and East African countries develop post-kala-azar dermal leishmaniasis (PKDL).7 This manifestation is a form of cutaneous leishmaniasis characterized by maculopapular or nodular lesions on the face, limbs or trunk, which appear after a symptom-free period following the end of visceral leishmaniasis treatment. The interval between kala-azar and PKDL is estimated as being months to years in India, but is considerably shorter in Africa (0—6 months).7—10 The association of Leishmania (Leishmania) infantum with PKDL is highly unusual in patients living in Europe11 and rarely present in patients infected with L. (L.) infantum chagasi in South America.12,13 Since the onset of the AIDS era, co-infection with HIV and leishmaniasis has become a high-priority emergent disease appearing throughout the world.2 In Brazil, both infections are highly prevalent. In the past, both target populations were geographically separated. Currently, overlap appears because of the expansion of leishmaniasis into urban areas and of HIV infection into rural ones. Despite antiretroviral therapy, approximately 100 cases of this co-infection are reported per year in Brazil.14,15 Here, we report an AIDS patient with visceral leishmaniasis caused by L. (L.) infantum chagasi. After recurrence and the development of an atypical disseminated leishmaniasis with PKDL-like appearance of skin lesions, the patient died. Table 1 e505 Case report The case is that of a 42-year-old male who had migrated to Sao Paulo City, Brazil from São José do Egito, Pernambuco, an area of Brazil endemic for visceral leishmaniasis, 27 years previously. He was found positive for HIV in1993 and had since undergone several different schedules of antiretroviral therapy. The overall clinical events, including CD4+ T cell counts, plasma viral load values, and treatments at each time period are shown in Table 1. Each event of antiretroviral therapy was made according to the guidelines of the previously established National Program of Sexual Diseases and AIDS of the Health Ministry of Brazil.16 Even on antiretroviral therapy, his CD4+ levels were found to have decreased and plasma viral load to have increased in May 2000. As a result, he had cerebral toxoplasmosis (July 2001) and hepatitis C (December 2002). In January 2004, his medication was again changed to stavudine, lamivudine and efavirenz because his CD4+ T cell count was decreased (144 cells/mm3) and his plasma viral load was 812 copies/ml. In November 2004 he was hospitalized after presenting with fever, weight loss, diarrhea, epistaxis, and hepatosplenomegaly (Figure 1A). The diagnosis of visceral leishmaniasis was confirmed due to the presence of amastigotes in the bone marrow aspirate. The specific leishmaniasis was treated with N-methylglucamine antimonate (glucantime, 20 mg/kg/day) for 13 days, when he developed acute pancreatitis. At this time, the glucantime was replaced with liposomal ampho- Main clinical events Period (month/year) Clinical event CD4+ T cell Plasma Treatment a count viral load (cells/mm3) (copies/ml) 02/93 07/96 01/97 04/97 05/00 07/01 12/02 01/04 11/04 385 612 697 388 104 352 168 144 181 NA NA NA 45 000 290 000 200 6860 812 <400 NA 72 NA <400 Positive for HIV/oral moniliasis ddI intolerance Cerebral toxoplasmosis Hepatitis C NA NA 10/06 Visceral leishmaniasisb (hepatosplenomegaly/cachexia/ diarrhea/fever) Ambulatory follow-up Visceral leishmaniasis (second episode) (hepatosplenomegaly/cachexia/diarrhea/fever) Visceral leishmaniasis (third episode) (severe anemia/ epistaxis/hepatosplenomegaly) Visceral leishmaniasis (fourth episode) 78 831 06/07 02/08 Multiple cutaneous lesions on face/thorax Death (visceral leishmaniasis) 66 09 <50 <50 01/05 05/05 12/05 AZT AZT/ddI AZT/3TC AZT/3TC d4T/NVP/SQV d4T/3TC/IDV/RTV d4T/3TC/SQV/RTV d4T/3TC/EFV d4T/3TC/EFV—glucantime,c amphotericin B d d4T/3TC/EFV—glucantime d4T/3TC/EFV—glucantime d4T/3TC/EFV—liposomal amphotericin d4T/3TC/ATV/RTV— liposomal amphotericin d4T/3TC/ATV/RTV d4T/3TC/ATV/RTV NA, not available; ATV, atazanavir; ddI, didanosine; EFV, efavirenz; IDV, indinavir; 3TC, lamivudine; NVP, nevirapine, RTV, ritonavir; SQV, saquinavir; d4T, stavudine; AZT, zidovudine. a Antiretroviral treatment was conducted as per the instructions established by the National Program of Sexual Diseases and AIDS of the Health Ministry of Brazil. b Confirmed by bone marrow aspirate examination. c For 13 days; developed acute pancreatitis. d Treatment replaced. e506 D.C. Jr et al. Figure 1 Visceral leishmaniasis: clinical and histopathological diagnosis, and species genotyping by PCR. (A) Hepatosplenomegaly. (B) Histopathological examination of the liver biopsy revealing amastigotes and chronic inflammation (hematoxylin—eosin staining). Non-pruritic, erythematous maculopapular lesions on (C) face and (D) thorax. (E) Species genotyping by PCR; the RV1—RV2 marker amplified a 145-bp product from the LT1 fragment of Leishmania donovani complex kDNA minicircles. The amplified PCR product was analyzed by electrophoresis on 2% agarose gel; lane 1, 100-bp ladder (the lowest band shown is 100 bp); lane 2, patient sample; lane 3, negative control. tericin B (50 mg/day for 3.2 weeks). After hospital discharge, in ambulatory follow-up, he took glucantime (81 mg) weekly. Over the course of two years he had three other recurrent episodes of visceral leishmaniasis (May 2005, December 2005, and October 2006) and was again treated with glucantime and liposomal amphotericin B. In October 2006, his antiretroviral therapy consisted of stavudine, lamivudine, atazanavir and ritonavir. His plasma viral load was becoming undetectable, but his CD4+ T cell count was still gradually decreasing (78 cells/mm3). In June 2007, his CD4+ T cell count was 66 cells/mm3 when he developed multiple cutaneous lesions on the face and thorax (Figure 1, C and D). Leishmania infection was also determined by the presence of amastigotes in histopathological examinations prepared from liver biopsies (Figure 1B) and skin lesions. The confirmation of American visceral leishmaniasis and species identification as L. (L.) infantum chagasi were made by PCR as previously described.17 The RV1—RV2 marker amplified a 145-bp sequence from the LT1 fragment of L. (L.) donovani complex kDNA minicircles18,19 (Figure 1E). He died of disseminated leishmaniasis in February 2008. Discussion Cutaneous manifestations of Leishmania and HIV co-infection have been described in some patients having visceral leishmaniasis or as the only clinical manifestation of the disease. Cutaneous dissemination is generally observed among severely immunocompromised patients, and lesions tend to localize symmetrically.11,20 In the present case, the patient developed visceral recurrent leishmaniasis, despite antiretroviral, liposomal amphotericin B, and glucantime thera- pies. As a result, he developed an atypical disseminated leishmaniasis with PKDL-like appearance of skin lesions (non-itchy maculopapular erythematous lesions on the face and thorax). The fact that the patient had a controlled viral load during the last five years, as determined in plasma, lead us to suppose that the antiretroviral therapy was efficient in accordance with the established guidelines.16 However, the low CD4+ T cell production was constant, suggesting a lack of immune function, and finally the patient died of disseminated visceral leishmaniasis. As the incidence of HIV increases in areas in which Leishmania species are endemic, visceral leishmaniasis is being recognized more frequently as an opportunistic infection in patients with AIDS. This case also emphasizes the potential use of PCR to confirm the diagnosis, for Leishmania species genotyping, and for clinical evaluation and follow-up of HIV patients undergoing antiretroviral therapy who have previously had leishmaniasis or patients living in leishmaniasis endemic areas. 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