Efficacy and safety of a single dose pentamidine (7mg/kg) for patients with cutaneous leishmaniasis caused by L. guyanensis: a pilot study

Abstract: BACKGROUND: There have been few studies on pentamidine in the Americas; and there is no consensus regarding the dose that should be applied. OBJECTIVES: To evaluate the use of pentamidine in a single dose to treat cutaneous leishmaniasis. METHODS: Clinical trial of phase II pilot study with 20 patients. Pentamidine was used at a dose of 7 mg/kg, in a single dose. Safety and adverse effects were also assessed. Patients were reviewed one, two, and six months after the end of treatments. RESULTS: there was no difference between the treatment groups in relation to gender, age, number or location of the lesions. Pentamidine, applied in a single dose, obtained an effectiveness of 55%. Mild adverse events were reported by 17 (85%) patients, mainly transient pain at the site of applications (85%), while nausea (5%), malaise (5%) and dizziness (5%) were reported in one patient. No patient had sterile abscess after taking medication at a single dose of 7mg/kg. CONCLUSIONS: Clinical studies with larger samples of patients would enable a better clinical response of pent amidine at a single dose of 7mg, allowing the application of more powerful statistical tests, thus providing more evidences of the decrease in the effectiveness of that medication. Hence, it is important to have larger studies with new diagrams and/or new medications.

Tegumentary leishmaniasis in the State of Amazonas: what have we learned and what do we need?

This study evaluated the occurrence of American tegumentary leishmaniasis (ATL) in the State of Amazonas, Brazil, in the last 30 years with emphasis on the last 10 years (2001 to 2010). The disease was predominantly observed in males (76.2%), in the 21- to 30-year-old age group (26.6%) and in extractive workers (43.7%); 3.3% of the cases were the mucosal form. The endemic channel shows the disease seasonality, with a predominance of cases at the beginning and end of each year. The number of cases by municipality in the period of 2001-2010 shows the maintenance of the endemic in the localities where the highest numbers of cases have always been registered, namely, Manaus, Rio Preto da Eva, Itacoatiara and Presidente Figueiredo. The comparison of data from 2001 to 2005 and from 2006 to 2010 showed the emergence of this disease in municipalities that had been previously unaffected. In the last years, there has been a significant increase in the activities of control, diagnosis and treatment of leishmaniasis in the State of Amazonas. In conclusion, the historical series of ATL analyzed in this study suggests that the transmission foci remain and are even expanding, though without continuous transmission in the intra- or peridomicile settings. Moreover, the disease will persist in the Amazon while the factors associated with infection acquisition relative to forest exploitation continue to have economic appeal. There is a real expectation of wide variations in disease incidence that can be influenced by climate and economic aspects.

A historical overview of leprosy epidemiology and control activities in Amazonas, Brazil

Leprosy is an ancient infectious disease caused by Mycobacterium leprae. According to comparative genomics studies, this disease originated in Eastern Africa or the Near East and spread with successive human migrations. The Europeans and North Africans introduced leprosy into West Africa and the Americas within the past 500 years. In Brazil, this disease arrived with the colonizers who disembarked at the first colonies, Rio de Janeiro, Salvador and Recife, at the end of the sixteenth century, after which it was spread to the other states. In 1854, the first leprosy cases were identified in State of Amazonas in the north of Brazil. The increasing number of leprosy cases and the need for treatment and disease control led to the creation of places to isolate patients, known as leprosaria. One of them, Colonia Antônio Aleixo was built in Amazonas in 1956 according to the most advanced recommendations for isolation at that time and was deactivated in 1979. The history of the Alfredo da Matta Center (AMC), which was the first leprosy dispensary created in 1955, parallels the history of leprosy in the state. Over the years, the AMC has become one of the best training centers for leprosy, general dermatology and sexually transmitted diseases in Brazil. In addition to being responsible for leprosy control programs in the state, the AMC has carried out training programs on leprosy diagnosis and treatment for health professionals in Manaus and other municipalities of the state, aiming to increase the coverage of leprosy control activities. This paper provides a historical overview of leprosy in State of Amazonas, which is an endemic state in Brazil.

Leishmaniasis and AIDS coinfection / Coinfeccao leishmaniose e AIDS

Cutaneous leishmaniasis and HIV coinfection has been reported in Brazil since the initial description of AIDS in the country. We report an HIV-positive patient under antiretroviral treatment who presented with cutaneous leishmaniasis which was successfully treated with meglumine antimoniate.

A coinfecção leishmaniose cutânea e HIV tem sido descrita no Brasil desde o início da endemia de Aids no país. É relatado caso de paciente masculino, HIV positivo, em uso de terapia antirretroviral, que apresentou quadro de leishmaniose cutânea, tratada com antimoniato de meglumina.

Primary multidrug-resistant tuberculosis and its control implications in the State of Amazonas, Brazil: report of 3 cases / Multirresistência primária da tuberculose e implicações no controle no Estado do Amazonas, Brasil: relato de três casos

The occurrence of tuberculosis with first-line multidrug resistance leads to the use of alternative medications, often at higher costs, longer treatment periods, and greater clinical complexity. Here, we report 3 patients with multidrug-resistant tuberculosis. One patient with human immunodeficiency virus died before the sensitivity test was performed. The early diagnosis of multidrug-resistant tuberculosis and appropriate treatment should be priorities of the National Tuberculosis Control Program in order to break the chain of transmission. In addition, the possibility of substituting the proportion method with more modern and faster techniques should be urgently evaluated.

O surgimento de resistência múltipla às drogas de primeira linha implica na utilização de fármacos de maior custo, com duração mais longa, maior complexidade e mais efeitos colaterais. Relatamos os casos de três pacientes com multirresistência primária aos tuberculostáticos. O portador de HIV evoluiu para óbito antes do resultado do teste de sensibilidade. Portanto, o diagnóstico precoce de tuberculose multirresistente e o tratamento adequado devem ser prioridades do Programa Nacional do Controle da Tuberculose, visando interromper a cadeia de transmissão. Além disto, é urgente que seja avaliada a substituição do método das proporções por técnicas mais modernas e mais rápidas.

Estudo clínico randomizado comparando antimoniato de meglumina, pentamidina e anfotericina B para o tratamento da leishmaniose cutânea ocasionada por Leishmania guyanensis / A randomized clinical trial comparing meglumine antimoniate, pentamidine and amphotericin B for the treatment of cutaneous leishmaniasis by Leishmania guyanensis

FUNDAMENTOS: O tratamento da leishmaniose tegumentar americana (LTA) ainda constitui desafio, pois a maioria dos medicamentos é injetável e têm-se poucos ensaios clínicos randomizados comparando a eficácia das drogas. Além disso, é provável que as espécies de Leishmania tenham influência nas respostas terapêuticas. OBJETIVOS: Avaliar e comparar a eficácia e a segurança dos esquemas de tratamento na LTA, ocasionada por Leishmania (Viannia) guyanensis. MÉTODOS: 185 pacientes foram selecionados, conforme critérios de elegibilidade, e distribuídos, aleatoriamente, em 3 grupos - 2 com 74 enfermos e outro com 37 - que receberam, respectivamente, antimoniato de meglumina, isotionato de pentamidina e anfotericina B em doses, períodos e vias de administração padronizados. Os enfermos foram reexaminados um, dois e seis meses após o final dos tratamentos. RESULTADOS: Não houve diferença entre os grupos terapêuticos em relação ao sexo, idade, número ou local das lesões. A análise por intenção de tratar (ITT) mostrou eficácias de 58,1 por cento para a pentamidina e 55,5 por cento para o antimoniato (p=0,857). O grupo da anfotericina B foi analisado separadamente, pois 28 (75,7 por cento) pacientes negaram-se a continuar no estudo após a randomização. Eventos adversos leves ou moderados foram relatados por 74 (40 por cento) pacientes, principalmente artralgia (20,3 por cento), para o grupo do antimoniato, e dor (35,1 por cento) ou enduração (10,8 por cento) no local das injeções para a pentamidina. CONCLUSÕES: A pentamidina tem eficácia similar ao antimonial pentavalente para o tratamento da LTA ocasionada por L. guyanensis. Face aos baixos resultados de eficácia apresentados por ambas as drogas, necessita-se, com urgência, investigar novas opções terapêuticas para esta enfermidade.

FUNDAMENTALS: American tegumentary leishmaniasis (ATL) treatment remains a challenge, since most available drugs are injectable and only a small number of comparative, randomized clinical trials have been performed to support their use. Moreover, treatment outcome may depend on the causative species of Leishmania. OBJECTIVES: To evaluate and compare the efficacy and tolerability of meglumine antimoniate, pentamidine isethionate, and amphotericin B in the treatment of ATL caused by Leishmania (Viannia) guyanensis. METHODS: 185 patients were selected according to the eligibility criteria and randomly allocated into three groups - two groups with 74 patients each, and one group with 37 patients, which underwent meglumine, pentamidine and amphotericin B treatment, respectively. Doses, mode of administration and time periods of treatment followed the current recommendations for each drug. Patients were re-examined one, two and six months after completion of treatment. RESULTS: No differences were observed among the therapeutic groups in relation to gender, age, number or site of lesions. Intention-to-treat (ITT) analysis showed efficacy of 58.1 percent for pentamidine and 55.5 percent for meglumine (p=0.857). The amphotericin B group was analyzed separately, since 28 patients (75.7 percent) in this group refused to continue participating in the study. Mild or moderate adverse effects were reported by 74 (40 percent) patients, especially arthralgia (20.3 percent) in the meglumine group, and pain (35.1 percent) or induration (10.8 percent) at the site of injection in the pentamidine group. CONCLUSION: Pentamidine and meglumine show similar efficacy in the treatment of ATL caused by L. guyanensis. Given the low efficacy of both drugs, there is an urgent need for new therapeutical approaches.

Combining diagnostic procedures for the management of leishmaniasis in areas with high prevalence of Leishmania guyanensis / Procedimentos diagnósticos combinados no manejo da leishmaniose em áreas com alta prevalência de Leishmania guyanensis

BACKGROUND: The Amazon region corresponds to approximately 40 percent of the cases of leishmaniasis in Brazil. We report a prospective study with 180 patients conducted in a health care unit that diagnoses 10 percent of the cases of leishmaniasis in the Brazilian Amazon. The study addresses how a combination of procedures improves diagnosis in areas with high prevalence of Leishmania guyanensis. OBJECTIVES: to evaluate diagnostic methods in areas with high prevalence of Leishmania guyanensis. METHODS: All subjects were amastigote-positive by direct microscopic examination of lesion scarifications. We conducted skin biopsy and histopathology, polymerase chain reaction and parasite cultivation. RESULTS: Polymerase chain reaction detected almost ninety percent of infections when two amplification protocols were used (mini-exon and HSP-70). HSP-70 specific polymerase chain reaction matched the sensitivity of parasite cultivation plus histopathology. CONCLUSION: The best combination was polymerase chain reaction plus histopathology, which increased diagnostic sensitivity to 94 percent. Species discrimination by polymerase chain reaction disclosed prevalence of human infections with Leishmania guyanensis of 94 percent and with Leishmania braziliensis of 6 percent for this region.

FUNDAMENTOS: O Amazonas corresponde a aproximadamente 40 por cento dos casos de leishmaniose do país. Nós reportamos um estudo prospectivo com 180 pacientes de uma unidade de saúde que diagnostica 10 por cento dos casos de leishmaniose da amazônia brasileira, com combinação de métodos diagnóstico em área de alta prevalência de Leishmania guyanensis. OBJETIVOS: avaliar métodos diagnóstico da Leishmaniose em área endêmica para Leishmania Amazonensis. MÉTODOS: Todos os pacientes tiveram exame direto positivo com presença de amastigotas. Foi feita também biópsia cutânea, com realização de exame histológico, reação em cadeia da polimerase e cultura. RESULTADO: A reação em cadeia da polimerase detectou aproximadamente 90 por cento de infecção quando foram usados duas técnicas de amplificação (mini-exon and HSP-70). A reação em cadeia da polimerase com HSP-70 foi mais sensível que a cultura associada à histopatologia. CONCLUSÃO: A melhor combinação foi a reação em cadeia da polimerase com histopatologia, com sensibilidade de 94 por cento. A discrimanação das espécies causadoras de infecção humana nessa região mostrou Leishmania guyanensis em 94 por cento dos casos e Leishmania brasiliensis em 6 por cento.

The use of polymerase chain reaction to confirm diagnosis in skin biopsies consistent with american tegumentary leishmaniasis at histopathology: a study of 90 cases / Uso da reação em cadeia da polimerase em biópsias de pele para confirmar o diagnóstico histopatológico consistente com leishmaniose tegumentar americana: um estudo de 90 casos

BACKGROUND: Cutaneous leishmaniasis is a chronic, infectious disease caused by protozoa of the genus leishmania. The incidence of this disease is high in Brazil, with 19,746 new cases having been detected in 2008. The presence of amastigotes in the cytoplasm of histiocytes constitutes diagnosis of the disease; however, their presence is rarely found in late lesions, making histological diagnosis difficult. Polymerase chain reaction has been shown to represent a highly sensitive and specific technique for the diagnosis of cutaneous leishmaniasis. OBJECTIVES: To use polymerase chain reaction to evaluate paraffin-embedded skin biopsies with histopathological features consistent with cutaneous leishmaniasis. MATERIAL AND METHODS: Polymerase chain reaction amplification of a 120-base-pair fragment of Leishmania kinetoplast DNA (kDNA) minicircles was performed on 90 skin biopsies. The male/female ratio was 75/15. Mean age was 32.36 years, with a median of 31 years, range 4-72 years. Samples were histologically compatible with cutaneous leishmaniasis but a definitive diagnosis could not be made since amastigotes were not found. All cases were histologically classified according to the patterns described by de Magalhães. RESULTS: According to the de Magalhães classification, the most common histological pattern was type IV (exudative granulomatous reaction), which was found in 65.6 percent of cases (56/90), followed by type I (exudative cellular reaction) in 21.1 percent of cases (19/90) and type III (exudative and necrotic granulomatous reaction) in 12.2 percent of cases (11/90). Leishmania DNA was found in 96.7 percent of the biopsies (87/90). CONCLUSION: Polymerase chain reaction performed by amplifying kDNA is able to confirm a diagnosis of cutaneous leishmaniasis with a high degree of sensitivity in cases in which histopathology is consistent with a diagnosis of cutaneous leishmaniasis but not definitive.

FUNDAMENTOS: Cutaneous leishmaniasis is a chronic, infectious disease caused by protozoa of the genus leishmania. The incidence of this disease is high in Brazil, with 19,746 new cases having been detected in 2008. The presence of amastigotes in the cytoplasm of histiocytes constitutes diagnosis of the disease; however, their presence is rarely found in late lesions, making histological diagnosis difficult. Polymerase chain reaction has been shown to represent a highly sensitive and specific technique for the diagnosis of cutaneous leishmaniasis. OBJECTIVES: To use polymerase chain reaction to evaluate paraffin-embedded skin biopsies with histopathological features consistent with cutaneous leishmaniasis. MATERIAL AND METHODS: Polymerase chain reaction amplification of a 120-base-pair fragment of Leishmania kinetoplast DNA (kDNA) minicircles was performed on 90 skin biopsies. The male/female ratio was 75/15. Mean age was 32.36 years, with a median of 31 years, range 4-72 years. Samples were histologically compatible with cutaneous leishmaniasis but a definitive diagnosis could not be made since amastigotes were not found. All cases were histologically classified according to the patterns described by de Magalhães. RESULTS: According to the de Magalhães classification, the most common histological pattern was type IV (exudative granulomatous reaction), which was found in 65.6 por cento of cases (56/90), followed by type I (exudative cellular reaction) in 21.1 por cento of cases (19/90) and type III (exudative and necrotic granulomatous reaction) in 12.2 por cento of cases (11/90). Leishmania DNA was found in 96.7 por cento of the biopsies (87/90). CONCLUSION: Polymerase chain reaction performed by amplifying kDNA is able to confirm a diagnosis of cutaneous leishmaniasis with a high degree of sensitivity in cases in which histopathology is consistent with a diagnosis of cutaneous leishmaniasis but not definitive.

Coinfecção histoplasmose e Aids / Histoplasmosis and AIDS co-infection

Apresenta-se um caso de coinfecção histoplasmose e Aids, com lesões cutâneas predominantemente papulosas e comprometimento sistêmico. O exame histopatológico e micológico de lesão cutânea confirmou o diagnóstico. Em doentes com Aids, a histoplasmose surge, principalmente, quando a contagem de células T-CD4-positivas é inferior a 50 células/mm³. Nesses casos, a histoplasmose pode ser grave e, se não tratada adequadamente, levar ao êxito letal, como no paciente relatado.

This report concerns an AIDS patient presenting systemic and cutaneous manifestations of histoplasmosis. A histopathological and mycological examination of the skin lesion confirmed the diagnosis. In AIDS patients histoplasmosis arises mainly when the T-CD4+ cell count is less than 50 cells/mm3. In such cases, histoplasmosis can be severe and if left untreated can lead to death, as occurred with this patient.

Eczema de contato após tatuagem com black henna: estudo de dois casos / Contact eczema after pseudotattooing with black henna: a study of two cases

Os autores apresentam dois casos de eczema de contato provocado por hena. Os dois pacientes, um com três e outro com cinco anos, desenvolveram o eczema 13 dias depois de ter feito tatuagem com hena. Por meio do teste de contato, verificou-se reação fortemente positiva à parafenilenodiamina, uma das substâncias químicas incorporadas à hena e, geralmente, não mencionada no rótulo do produto

Talidomida: indicaçöes e legislaçäo vigente / Thalidomide: indications and actual legislation

A talidomida, droga que tem ampla aplicaçäo clínica e potentes efeitos antiinflamatórios, qualifica-se como primeira escolha para tratamento de várias doenças. Seu efeito teratogênico, entretanto, limita seu uso clínico. Baseando-se neses conhecimentos, após estudo detalhado de cada um de seus efeitos, e avaliando-se cuidadosamente o risco/benefício de seu emprego, pretende-se indicar a talidomida para algumas situaçöes clínicas já bem estabelecidas. Säo elas: eritema nodoso hansênico, lúpus eritematoso discóide, estomatite aftosa recorrente, doença enxerto-verus-hospedeiro em sua fase crônica, úlceras dolorosas de mucosas em pacientes com HIV/Aids, prurigo nodular, síndrome de Behçet e prurigo actínico. A essas somam-se outras, em que seu uso só deve se indicado se outras drogas resultarem ineficazes. Complementando a avaliaçäo, foram consideradas as situaçöes nas quais a talidomida poderia ser eficaz, necessitando de estudo prévio das características da doença e do paciente para que se efetive sua utilizaçäo. O uso da talidomida deve sempre obedecer às portarias do Ministério da Saúde que regulamentam sua fabricaçäo, indicaçöes e dispensäo. Os principais pontos dessa legislaçäo seräo destacados, em especial a proibiçäo para uso em mulheres em idade fértil.

Tratamento da hanseníase: resultados preliminares com o esquema OMS/81 em pacientes tuberculoides e indeterminados / Treatment of hanseniasis: preliminary results with the scheme OMS/81 in patients tuberculoid and indeterminated forms

Foram tratados 264 doentes portadores de hanseníase tuberculóides e indeterminados, Mitsuda positivos, com o esquema OMS/81. Desse total, 223 faziam monoterapia com a sulfona e 41 eram virgens de tratamento. Todos foram medicados com DDS - 2mg/kg de peso por dia + rifampicina - 600mg/por mês, supervisionada, durante seis meses. Todos os pacientes estäo de alta medicamentosa há mais de 20 meses e, até o presente momento, näo houve recidiva em nenhum dos casos