Epidemiological and clinical features of 62 patients with visceral leishmaniasis / 中华传染病杂志

Objective:To analyze the epidemiological and clinical features of patients with visceral leishmaniasis (VL), and to improve the understanding of the disease and standardize the diagnosis and treatment.Methods:The clinical data and diagnosis and treatment process of 62 patients with VL admitted to The First Hospital of Lanzhou University from January 2010 to December 2020 were retrospectively analyzed. The clinical symptoms and laboratory data, including aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and procalcitonin (PCT) were compared between children and adults. Chi-square test was used for statistical analysis.Results:Of the 62 patients, 31(50.0%) patients were males, 38(61.3%) patients were children and 24(38.7%) were adults. There were 32 cases (51.6%) living in Longnan City, and 11 cases (17.7%) living in Gannan Tibetan Autonomous Prefecture. Forty-seven cases (75.8%) had a delay over 30 days from onset to diagnosis. All patients had fever and chills, 34 cases (54.8%) had fatigue and poor appetite, 30(48.4%) had cough and expectoration, 10 cases (16.1%) had headache and dizziness, 45 cases (72.6%) had splenomegaly, 40 cases (64.5%) had anemia, and 29 cases (46.8%) had hepatomegaly. There were 32 cases (51.6%) accompanied with respiratory infection, 11 cases (17.7%) accompanied with hemophagocytic lymphohistiocytosis and 10 cases (16.1%) accompanied with abnormal liver function. Of the 60 patients who received treatment, 14 were recurrent cases who had received at least one course of pentavalent antimony monotherapy before admission. Forty-six patients received standard antimony monotherapy, 14 patients received standard antimony combined with amphotericin B therapy. Thirteen patients discontinued amphotericin B due to impaired renal function, and 50 patients were followed up for half a year without recurrence. The proportions of splenomegaly and hepatomegaly in children were 86.8%(33/38) and 65.8%(25/38), respectively, and the corresponding numbers in adults were 50.0%(12/24) and 16.7%(4/24), respectively. The differences were statistically significant ( χ2=10.03 and 14.26, respectively, both P<0.050). Thirty-three cases (86.8%) in children and 14 cases (58.3%) in adults had a delay over 30 days from onset to diagnosis. The difference was statistically significant ( χ2=6.52, P=0.011). The proportions of patients who had elevated AST, LDH and PCT were 76.3%(29/38), 94.3%(33/35) and 73.9%(17/23) in children, respectively, while 45.8%(11/24), 71.4%(15/21) and 5/17 in adults, respectively, and the differences were all statistically significant ( χ2=5.97, 3.89 and 7.82, respectively, all P<0.050). Conclusions:Patients with VL are tend to have complications and be severe. Early diagnosis and standardized treatment are important measures to improve the prognosis. Patients who have failed antimony treatment can be treated with amphotericin B or combination therapy, but kidney injury and other adverse reactions should be closely monitored.

TERAPIA LARVAL CON Musca domestica EN EL TRATAMIENTO DE LA ÚLCERA LEISHMÁNICA EN UN MODELO MURINO / Larval therapy with Musca domestica in the treatment of leishmanian ulcer in a murine model

RESUMEN La leishmaniosis es una enfermedad con gran impacto en salud pública dado a las características de las lesiones tegumentarias. El tratamiento experimental con terapia larval (TL) ha mostrado su uso potencial para la cura de la leishmaniosis, sin embargo, se han utilizado especies de moscas para TL en heridas causadas por Leishmanial que no son de fácil colecta y cultivo bajo condiciones de laboratorio como Lucilia sericata o Calliphora vicina. El objetivo del presente trabajo fue usar una especie de mosca de fácil colecta, y de alta fecundidad como la Musca domestica para aplicarlas en TL de úlceras leishmánicas. Se realizó un estudio cuali-cuantitativo, de tipo descriptivo, mediante un diseño experimental empleado un modelo animal (Mesocricetus auratus), infectado con Leishmania amazonensis para evaluar el efecto terapéutico de la TL y comparar los resultados con el tratamiento químico antimonial de la droga experimental "Ulamina". Se evidencia cicatrización y cura de la úlcera leishmánica en el 66,66 % de los animales tratados con TL en aplicación simple y del 100 % en TL combinada con Ulamina. El uso combinado de TL+Ulamina, muestra un efecto potenciador de la cura clínica de las úlceras, pero con persistente inflamación. Se observó una efectividad óptima de la TL con M. domestica, sobre las úlceras, aunque no se evidenció un efecto sobre L. amazonensis dado a la presencia de amastigotes en los frotis y a los amplicones obtenidos de 480 bp desde las improntas de los animales.

ABSTRACT Leishmaniasis is a disease with significant impact on public health, given the characteristics of the tegumentary lesions. Experimental treatment with larval therapy (LT) has shown its potential use for the cure of leishmaniosis. However, fly species not easy to collect and/or colonize have been used. The objective of the present work was to use a fly of accessible collection and high fecundity, not a producer of human myiasis, such as Musca domestica. A qualitative-quantitative study of a descriptive type was carried out through an experimental design with an animal model (Mesocricetus auratus) with infection by Leishmania amazonensis to evaluate the therapeutic effect of LT and compare the results with the antimonial chemical treatment of the drug experimental "Ulamina". Scarring were observed with the use of LT in 66.66 % with TL-simple and 100 % with TL-combined. However, the combined use of LT + Ulamina, shows an enhancing effect of the clinical cure of the lesions, but with persistent inflammation. Optimal effectiveness of TL with M. domestica was observed on the ulcers; however, an effect on L. amazonensis was not observed given the presence of amastigotes in the smears and the 480 bp amplicons from the tissue of the ulcers of animals.

A randomized, open-label clinical trial comparing the long-term effects of miltefosine and meglumine antimoniate for mucosal leishmaniasis

Abstract INTRODUCTION: The treatment of mucosal leishmaniasis (ML) is difficult due to the toxicity and route of administration of standard drugs. Miltefosine is an oral agent used for leishmaniasis treatment; however, no data exist regarding its use for ML in Brazil. In this study, we aimed to evaluate the efficacy of miltefosine for ML treatment compared to that of pentavalent antimonial in a pilot study. METHODS: We performed a randomized clinical trial with two parallel groups. The tested intervention consisted of miltefosine 1.3-2 mg/kg/day (two capsules) for 28 days or intravenous 20 mg SbV/kg/day of meglumine antimoniate (N-MA) for 30 days. The final endpoint was defined as complete healing of the lesion four years after treatment. We also analyzed an early endpoint at 90 days after treatment. RESULTS: Forty patients were included in this study: each experimental group comprised 20 patients. Applying a multivariate model in an intention-to-treat analysis, we observed that patients treated with miltefosine had a cure probability 2.08 times greater (95% confidence interval [CI] = 1.03-4.18) than those treated with N-MA at 90 days after treatment. At the final endpoint, we observed no differences in cure probability between miltefosine and N-MA (relative risk = 0.66; 95% CI = 0.33-1.32). With respect to adverse reactions, significant differences between groups were related to gastrointestinal effects, which were more frequent in the miltefosine group. CONCLUSIONS: Miltefosine may be an interesting alternative for treating ML because of its oral administration and cure rate after long-term follow-up.

Potential utility of hyperbaric oxygen therapy and propolis in enhancing the leishmanicidal activity of glucantime / A utilidade da terapia de oxigenação hiperbárica e própolis em potencializar a atividade leishmanicida do glucantime

In this study we investigated the efficacy of hyperbaric oxygen (HBO) therapy, alone or combined with the pentavalent antimonial glucantime on Leishmania amazonensis infection. In parallel, the effect of Brazilian red propolis gel (propain) alone or combined with glucantime on L. amazonensis infection was evaluated. The inhibition of the infection in macrophages treated with glucantime in combination with HBO exposition was greater than that of macrophages treated with glucantime alone or HBO alone. The susceptible mouse strain BALB/c infected in the shaved rump with L. amazonensis treated with glucantime and exposed to HBO showed: time points in the course of the disease in which lesions were smaller than those of mice treated with glucantime alone and revascularization of the skin in the lesion site; interferon-gamma (IFN-g) levels were not elevated in lymph node cells from these animals. Propain alone was not efficient against lesions, although less exudative lesions were observed in animals treated with propain alone or combined with glucantime. These results reveal the potential value of HBO and red propolis in combination with glucantime for treating cutaneous leishmaniasis and encourage further studies on the effect of more aggressive HBO, propolis and glucantime therapies on different mouse models of leishmaniasis.

Nesse trabalho foi avaliada a eficácia da terapia da oxigenação hiperbárica (HBO), aplicada em combinação ou não com o tratamento com glucantime, durante a infecção com Leishmania amazonensis. O efeito de gel da própolis vermelha de origem brasileira (propaina) aplicado em combinação ou não com o tratamento com glucantime, também foi avaliado durante infecção com esse parasita. A inibição da infecção de macrófagos tratados com glucantime em combinação com HBO foi maior que a de macrófagos tratados apenas com glucantime ou HBO. A linhagem murina susceptível, BALB/c, infectada no dorso com L. amazonensis, tratada com glucantime e exposta a HBO, mostrou durante o curso da doença, fases em que as lesões eram menores do que a de camundongos apenas tratados com glucantime; observou-se revascularização da pele da lesão e baixa produção de interferon-gama em células de linfonodos desses animais. O tratamento com propaina não foi eficiente na cura das lesões, apesar de lesões menos exsudativas serem observadas em animais tratados com propaina ou propaina combinada ao tratamento com glucantime. Os resultados demonstram que tanto HBO como a própolis vermelha em combinação com glucantime, são promissoras no tratamento da leishmaniose cutânea. Novos estudos devem ser realizados para avaliar tratamentos e outros protocolos em diferentes modelos murinos da leishmaniose.

Meglumina en series terapéuticas de 10 días en niños con leishmaniosis tegumentaria americana / Meglumine therapeutic series of 10 days in children with american tegumentary leishmaniasis

La cátedra de Medicina Tropical de la Universidad Central de Venezuela viene empleando el antimoniato de meglumina en series terapéuticas de 10 días en el tratamiento de leishmaniosis tegumentaria americana, la cual continúa como problema de salud del medio rural venezolano. Se evalúa una experiencia con una dosis de 70 mg/kg/día de meglumina en niños con la enfermendad. A los pacientes con presunción diagnóstica de leishmaniosis tegumentaria americana (clínica y antecedentes epidemiológicos) se les efectuó la prueba de leishmania, la demostración de anticuerpos flurescentes antileishmania y la visualización de amastigotes en frotis teñidos con Giemsa. Los casos identificados ingresaron al Hospital Universitario (Pediatría médica infecciosa), recibieron 70 mg/kg/día de antimoniato de meglumina en series terapéuticas de 10 días con reposo intercalados por el mismo número de días. Se incluyeron 33 niños con la enfermedad, 21 de género femenino (64%) con promedio de edad 7,12 años y predominio de escolar (70%). Del Estado Miranda procedía el 85%, una sola úlcera la tenía el 88%, localizada en miembros inferiores (49%). La Leishmanina y los anticuerpos fluorescentes antileishmania fueron positivos en todos los pacientes y el frotis para amastigotes en 45%. Dos series de antimoniato de meglumina las recibió 91% de los pacientes; una de 10 días 6%. Egresaron con cicatrizaciones de sus procesos ulcerosos y fueron evaluados durante seis meses en la consulta de endemias rurales y no se evidenciaron recaídas. La variedad cutánea localizada de la enfermedad fue la única identificada, el Estado Miranda continúa aportando la mayoría de los pacientes atendidos en medicina tropical. El antimoniato de meglumina en leishmaniosis tegumentaria americana a la dosis de 70 mg/kg/día en series terapéuticas fue tan eficaz como la anterior de 100 mg/kg/día que dejó de administrarse hace ocho años.

The Tropical Medicine Department of the Universidad Central de Venezuela employs the meglumine pentavalent antimonial in series of 10 days of treatment for American Tegumentary Leishmaniosis, which continues being a health problem in the Venezuelan rural areas. We are reporting a clinical experience of treatment in children at a dose of 70 mg/kg/day. Patients with diagnostic suspición of American Tegumentary Leishmaniosis (clinical and epidemiologic antecedents) who attended the Rural Endemics Clinic at the Instituto de Medicina Tropical of the Universidad Central de Venezuela and to the Medical Infectious Pediatrics Service at the Hospital Universitario de Caracas (HUC), were tested for leishmanine, fluorescent antileishmania antibodies and for the presence of amastigotes of the parasite in smear for apposition from the ulcer that were treated by the Giemsa method. Patients hospitalized at the Medical Infectious Pediatric Service (Hospital Universitario de Caracas) received 70 mg/kg/day of meglumine pentavalent antimonial during 10 days, a rest period of 10 days without treatment and, if 20 days after ulcers were unhealed, was administred a new 10 days meglumine pentavalent antimonial series. We included 33 children with the disease with a mean age of 7,12 years, 70% in school age and 30% preschool children, and 21 (64%) were girls. The 85% of patients came from Miranda`s state, 88% had only ulcer and in 49% of them the lesions where localized in the legs. The apposition smear showed Leishmania amastigotes in 45% od cases. One series of treatment was given to 91% of cases, two children received two series and one three. At discharge from the hospital all ulcers were healed and follow-up control for a 6 months period showed no relapses. The cutaneous localized from was the clinical form of presentation in the children studied. The great majority of patients that assits to the Tropical Medicine Institute come from the Miranda`s state area...

Two cases of visceral leishmaniasis in Colombia resistant to meglumine antimonial treatment / Dois casos de leishmaniose visceral da Colômbia, resistentes ao tratamento com antimoniato de meglumina

Visceral leishmaniasis (VL) affects over 500 000 people worldwide each year. The disease occurs in the Mediterranean basin, Central and South America and is caused by Leishmania infantum (syn L. chagasi). VL is an endemic disease in Colombia, particularly along the Caribbean coast and the Magdalena River Valley and 90% of VL cases occur in children under the age of five. The first line of treatment is chemotherapy with pentavalent antimonial compounds, including sodium stibogluconate (Pentostam®) and meglumine antimoniate (Glucantime®). These compounds are the ones most used in Colombia, at a dose of 20 mg/kg/day for 28 days. Nevertheless resistance of L. infantum to pentavalent antimonials is becoming an important problem. No cases of VL resistant to pentavalent antimonial compounds have previously been reported from Colombia. This report describes the two cases of VL resistance to antimonial compounds in a girl and a boy who did not respond to previous treatment with Pentacarinat® and Glucantime® regimens but were treated successfully with liposomal amphotericin B. Based on our findings, we recommend liposomal amphotericin B as the first line of treatment for VL due to its low toxicity, shorter administration period and the low price obtained by WHO.

A leishmaniose visceral (VL) afeta aproximadamente 500000 pessoas anualmente no mundo. A doença ocorre no mediterrâneo, na América Central e na América do Sul, sendo causada por Leishmania infantum (syn. L. chagasi). Na Colômbia VL é uma doença endêmica, presente no litoral do Caribe e no Vale do rio Magdalena sendo que 90% de casos de VL ocorrem em crianças menores de cinco anos. O principal tratamento é a quimioterapia com compostos de antimoniais pentavalentes, incluindo stibogluconato de sódio (Pentostam®) e antimoniato de meglumina (Glucantime®). Estes compostos são os mais usados na Colômbia em dosagem de 20 mg/kg/dia durante 28 dias. Entretanto, a resistência de L. infantum aos antimoniais pentavalentes está se tornando problema importante. Na Colômbia não existiam relatos de casos de VL resistentes aos antimoniais pentavalentes. Este trabalho descreve os dois primeiros casos colombianos de VL resistentes aos compostos antimoniais em uma menina e um menino, que foram tratados com regime de Pentamidina e Glucantime®, e demonstra o sucesso obtido no tratamento com anfotericina B liposomal. Em conclusão, sugerimos como primeira opção de tratamento a anfotericina B liposomal porque é altamente efetiva no tratamento da VL, dada sua baixa toxicidade, curtos períodos de administração e o baixo preço obtido pela organização Médicos Sem Fronteiras.

Leishmaniose tegumentar na Região Metropolitana de Belo Horizonte: aspectos clínicos, laboratoriais, terapêuticos e evolutivos (1989-1995) / Cutaneous leishmaniasis in the Metropolitan Region of Belo Horizonte: clinical, laboratorial, therapeutic and prognosis features (1989-1995)

This study investigated clinical, laboratorial, therapeutic and prognostic aspects of American cutaneous leishmaniasis in Belo Horizonte in 358 patients with cutaneous leishmaniasis (CL) and 25 with mucocutaneous leishmaniasis (MCL). Compared to CL patients, the MCL patients reported longer duration of disease and higher frequency of other diseases, suggesting that debilitation caused by leishmaniasis or other conditions might contribute to activation and/or mucous dissemination of the parasite. The sensitivity of skin test, indirect immunofluorescence reactions and direct detection of parasites was 78.4, 79.3 and 68.3%, respectively. The treatment with meglumine antimoniate presented 100% efficacy, but 59% patients had side-effects. During two years of follow-up, there were 32/318 relapses after successful treatment. Most relapses (31/32) were of CL patients treated with 15 mg Sb5+/kg/day. The negative response to skin test was the only factor associated with a significant threefold increased risk of relapse. Higher dose or longer duration of treatment might improve the prognosis in these patients.

Foram investigados aspectos clínicos, laboratoriais, terapêuticos e evolutivos da leishmaniose tegumentar americana em Belo Horizonte. O estudo incluiu 358 pacientes com leishmaniose cutânea (LC) e 25 com leishmaniose mucosa (LM). Comparados aos pacientes com LC, aqueles com LM apresentaram maior tempo de doença e relato de outras doenças concomitantes, sugerindo que a debilitação pela leishmaniose e/ou outras doenças podem contribuir para a ativação e/ou disseminação mucosa do parasito. As sensibilidades das reações intradérmica, de imunofluorescência indireta e da pesquisa direta do parasito foram de 78,4, 79,3 e 68,3%, respectivamente. O tratamento com antimoniato de meglumina foi 100% eficaz, com 59% de efeitos colaterais ao longo do tratamento. A recidiva após tratamento ocorreu em 32 (10,1%) dos 318 casos seguidos por até dois anos. A maioria das recidivas (31 dos 32 casos) ocorreu em pacientes com LC tratados com 15mg Sb5+/kg/dia. Na investigação de critérios de cura, a reação intradérmica negativa foi o único fator associado a um risco três vezes maior de recidiva. Um aumento da dose ou do tempo de tratamento talvez melhore o prognóstico nestes pacientes.

Um caso de leishmaniose cutâneo-mucosa tratado com sucesso com baixa dose de antimonial pentavalente / A case of mucocutaneous leishmaniasis treated with success with a low dose of pentavalent antimonial

Os autores relatam um caso de leishmaniose cutâneo-mucosa em uma paciente de 89 anos, diabética e hipertensa, tratada inicialmente com alopurinol por 10 meses não havendo cicatrização das lesões. Posteriormente, recebeu antimoniato de N-metil glucamina (glucantime) por 4 dias, na dose total de 2.380mg do Sbv, mas desenvolveu cardiotoxicidade e hipocalemia, sendo suspenso o tratamento, entretanto, evoluiu com regressão clínica total das lesões, apesar de ter recebido pequena dose desta medicação.

The authors report a case of a 89 years-old woman with mucocutaneous leishmaniasis and previous diabetes mellitus and high blood pressure, who had been treated with allopurinol for 10 months without healing of lesions. Afterwards, she has been treated with meglumine antimonate, [quot ]glucantime[quot ] for 4 days, with a total dose 2,380 mg of Sbv, but developed cardiac side effects and hypokalemia, hence the treatment was withdrawn. However, this patient developed total clinical regression of lesions, in spite of she has been received low dose of this drug.

Avaliação da tolerância e nefrotoxicidade do antimonial pentavalente administrado na dose de 40 mg Sb V/kg/dia, de 12/12 h, por 30 dias na forma cutâneo-mucosa de leishmaniose / The evaluation of the tolerance and nephrotoxicity of pentavalent antimony administered in a dose of 40 mg Sb V/kg/day, 12/12 hr, for 30 days in the mucocutaneous form of leishmaniasis

Foi avaliada a função renal de 11 pacientes com leishmaniose cutâneo-mucosa tratados com antimonial pentavalente na dose de 40mg SbV/kg/dia aplicada de 12/12 horas, em esquema contínuo, durante trinta dias. No estudo, um paciente apresentou insuficiência renal reversível e dois desenvolveram alterações enzimáticas hepáticas e eletrocardiográficas sendo o esquema terapêutico interrompido. Nos demais pacientes observou-se efeitos nefrotóxicos tais como diminuição da taxa de filtração glomerular, diminuição da capacidade de concentração urinária, avaliada por um jejum hídrico de 16 horas e aumento na fração de excreção de sódio. No exame do sedimento urinário observou-se um aumento no número de leucócitos e cilindros. Os resultados encontrados neste estudo sugerem que o tratamento com antimonial pentavalente na dose de 40mg SbV/kg/dia foi menos tolerado em virtude de seus efeitos tóxicos, não parecendo apresentar índice de cura superior ao esquema atualmente preconizado de 20mg SbV/kg/dia.

The renal function of eleven patients with mucocutaneous leishmaniasis was analyzed in a prospective study realized at the School Hospital of University of Brasília. The patients were treated with doses of 40 mg/kg/day of pentavalent antimony (Sb V), in a continuous scheme during thirty days. In this study three patients were excluded, one patient with reversible renal failure and two patients with hepatic and cardiac malfunctions. In the other eight patients, severe nephrotoxic effects were observed, like reduction of glomerular filtration rate, reduction of the urinary concentration capacity, evaluated by a sixteen hours hydric fasting and an increase of sodium fractional excretion. An increase in the number of leucocytes and cylinders were observed at the urinary sediment exam. Finally, the results shows that the treatment with pentavalent antimony in doses of 40 mg Sb/kg/day was less tolerated on account of its renal toxic effects. This scheme seems not be superior than the currently preconized scheme of 20 mg of Sb V/kg/day during 30 days.