Treatment of cutaneous leishmaniasis with a sequential scheme of pentamidine and tamoxifen in an area with a predominance of Leishmania (Viannia) guyanensis: A randomised, non-inferiority clinical trial.

OBJECTIVE: To determine whether a combination of a single intramuscular (IM) dose of pentamidine (7 mg/kg) followed by oral tamoxifen 40 mg/day for 20 days is non-inferior to three IM doses of pentamidine 7 mg/kg in the treatment of cutaneous leishmaniasis with a margin of 15%. METHODS: Phase II, randomised, controlled, open-label, non-inferiority clinical trial. Primary outcome was the complete healing of the lesions 6 months after starting treatment. Secondary outcomes were healing 3 months after starting treatment and determining the presence and severity of adverse effects (AE). RESULTS: The research was concluded with 49 patients; Leishmania (Viannia) guyanensis was the most frequent species isolated. In the primary outcome, 18 (72%) (95% CI: 52.4%-85.7%) of the 25 patients allocated to the intervention group and 24 (100%) (95% CI: 86.2%-100%) of the control group (p = 0.015) met the established criteria of cure. There was no AE with tamoxifen. CONCLUSION: Although a 72% cure rate presented by the combination of tamoxifen and pentamidine was lower than in the control group that achieved a 100% cure, it is still a safe and is a clinically relevant result. It indicates that the therapeutic scheme evaluated may be a promising option for populations in remote areas, however it should be further studied, in order to include a larger number of patients.

A Single Haplotype of IFNG Correlating With Low Circulating Levels of Interferon-γ Is Associated With Susceptibility to Cutaneous Leishmaniasis Caused by Leishmania guyanensis.

BACKGROUND: Interferon-γ (IFN-γ) plays an important role in the control of Leishmania infection. Blockade of IFN-γ signaling in mice increases lesion size and parasite load. In endemic areas of Leishmaniasis, only a fraction of the population develop the disease. This suggest that host genetics may play a role in this response. We investigated whether single nucleotide polymorphisms (SNPs) in IFNG may be associated with elevated or decrease risk in the development of cutaneous leishmaniasis (CL). METHODS: We assessed 9 SNP and cytosine-adenine (CA) repeats in IFNG by nucleotide sequencing in 647 patients with CL caused by Leishmania guyanensis and 629 controls. Circulating plasma IFN-γ levels were also assayed in 400 patients with CL and 400 controls. RESULTS: The rs2069705TT genotype is associated with elevated risk of developing CL compared with the rs2069705CC genotype (OR, 1.7; 95% CI, 1.3-2.4; P = .0008). There is a 70% chance that this genotype raises the risk of developing CL. In a dominant model, carriers of the rs2069705T allele compared with the rs2069705CC genotype showed a 50% (range, 20-100%) increased risk of developing CL (OR, 1.5; 95% CI, 1.2-2.0; P = .0004). Haplotype analysis showed 1 haplotype (H1) associated with low levels of IFN-γ presented an increased risk of 60% of developing CL (OR, 1.6; 95% CI, 1.3-1.9; P = 5 × 10-5) compared with non-H1. CONCLUSIONS: IFNG variant rs2069705 seems to be a genetic modifier of clinical outcome of Leishmania infection; individuals with the H1 haplotype, associated with low levels of IFN-γ, have a 60% risk of developing CL.

An open label randomized clinical trial comparing the safety and effectiveness of one, two or three weekly pentamidine isethionate doses (seven milligrams per kilogram) in the treatment of cutaneous leishmaniasis in the Amazon Region.

BACKGROUND: American Cutaneous Leishmaniasis (ACL), a vector borne disease, is caused by various species of Leishmania and in the Amazonas, Leishmania guyanensis is predominant. The recommended drugs for treatment of cutaneous leishmaniasis (CL) in Brazil are pentavalent antimonials, pentamidine isethionate (PI) and amphotericin B. Pentamidine was initially used as metanolsulfonate or mesylate (Lomidine) at a dose of 4 mg/kg/daily, containing 2.3mg of base. This drug was withdrawn from the market in the eighties, and currently is available as PI. The PI dose required to achieve an equivalent dose of pentamidine base is 7 mg/kg, rather than the 4 mg/kg that is currently recommended in Brazil. OBJECTIVES: The aim of this study was to evaluate the efficacy and safety of PI in a single dose, two or three doses of 7 mg/kg body weight, intramuscularly, with an interval of seven days between each dose. MATERIALS AND METHODS: This study was conducted as a controlled, randomized, open-label clinical trial for a total number of 159 patients with CL. Individuals aged 16-64 years with one to six lesions of confirmed CL based on amastigotes visualization in direct examination of Giemsa stained of dermal scraping from the border of the lesion with no previous treatment for CL and no abnormal values for liver enzymes were eligible to participate in the study. Patients with history of diabetes, cardiac, renal, and hepatic disease as well as pregnant women were excluded. Cure was defined as complete healing in the diameters of the ulcers and lesions skin six months after the end of the treatment. RESULTS: From November 2013 to December 2015, 159 patients were screened and allocated in three groups for treatment with PI: i) 53 patients were treated with a single dose intramuscularly injection of 7 mg/kg body weight; ii) 53 received two doses of 7 mg/kg within an interval of seven days; and iii) 53 were treated with three doses of 7mg/kg with an interval of seven days between each dose. In 120 patients, L. guyanensis was identified. A cure rate of 45%, 81.1% and 96.2% were observed in the first, second and third group, respectively. The cure in the three PI dose group was higher compared to the single-dose (p<0.0001) and two-dose groups (p = 0.03). No serious adverse events occurred. CONCLUSION: The present study shows that PI is a safe drug and its efficacy varied with the number of doses. The administration of PI in patients with ACL, predominantly caused by L. guyanensis, was mostly efficient in three or two doses of 7 mg/kg. TRIAL REGISTRATION: ClinicalTrials.gov NCT02919605.

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.

Sustained Presence of Cutaneous Leishmaniasis in Urban Manaus, the Largest Human Settlement in the Amazon.

The Amazon is responsible for approximately 40% of the American tegumentary leishmaniasis (ATL) in Brazil. Herein the sustained presence of ATL in Manaus, the largest settlement in the Amazon, was investigated. Records of notification of historic cases, and data from cases prospectively enrolled in the Tropical Medicine Foundation of the Amazonas State were used. Geographic coordinates of prospective patients' living sites were used to detect inner-city clusters of ATL. Infecting Leishmania species was determined by polymerase chain reaction. Among prospectively enrolled subjects, 94.8% were infected with Leishmania (Viannia) guyanensis, 76.7% were male, 30.2% were 0-20 years old, and 69.8% had an urban residence. Historic cases showed a profile similar to that of prospectively enrolled subjects. Several clusters of ATL, widely distributed within the city of Manaus, could be detected. In conclusion, there was a high frequency of disease in young age groups and cases clustered in urban neighborhoods. It cannot be determined from these data whether transmission of these cases occurred within or outside the city of Manaus.

Polymorphisms in the TOLLIP Gene Influence Susceptibility to Cutaneous Leishmaniasis Caused by Leishmania guyanensis in the Amazonas State of Brazil.

INTRODUCTION: The clinical outcome to Leishmania-infection is determined by the individual adaptive immune T helper cell responses and their interactions with parasitized host cells. An early development of a proinflammatory immune response (Th1 response) is necessary for Leishmania-infection resolution. The Toll-interacting protein (TOLLIP) regulates human Toll-like receptors signaling pathways by down regulating the proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) and inducing the ant-inflammatory cytokine interleukin-10 (IL-10). Polymorphisms in the TOLLIP gene are associated with infectious diseases. MATERIAL AND METHODS: The polymorphisms rs5743899 and rs3750920 in the TOLLIP gene were genotyped by polymerase chain reaction and restriction fragment length polymorphism (RFLP) analysis in 631 patients with cutaneous leishmaniasis (CL) caused by L. guyanensis and 530 individuals with no history of leishmaniasis. RESULTS: The G and T alleles of the rs5743899 and rs3750920 were more common in patients with CL than in healthy individuals (P = 2.6 x10(-8) ; odds ratio [OR], 1.7 [ 95% confidence interval (CI) 1.4-2.0] and P = 1.9 x10(-8) ; OR, 1.6 [95% CI 1.4-1.9] respectively). The r2 and D' linkage disequilibrium between the two polymorphisms are 0.05 and 0.473 with a confidence bounds of 0.37 to 0.57 respectively. CONCLUSION: The two polymorphisms are independently associated with an increased risk of developing CL.

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.

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.

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

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.

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.

Leishmaniasis and AIDS coinfection.

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.

Primary multidrug-resistant tuberculosis and its control implications in the State of Amazonas, Brazil: report of 3 cases.

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.

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.

The use of polymerase chain reaction to confirm diagnosis in skin biopsies consistent with American tegumentary leishmaniasis at histopathology: a study of 90 cases.

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% of cases (56/90), followed by type I (exudative cellular reaction) in 21.1% of cases (19/90) and type III (exudative and necrotic granulomatous reaction) in 12.2% of cases (11/90). Leishmania DNA was found in 96.7% 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.

Histoplasmosis and AIDS co-infection.

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.

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.

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.

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.