Hemophagocytic lymphohistiocytosis secondary to visceral leishmaniasis in an endemic area in the north of Minas Gerais, Brazil

Abstract INTRODUCTION Visceral leishmaniasis (VL) is an ill-studied disease that is endemic to several regions of Brazil. It is often complicated by hemophagocytic lymphohistiocytosis (HLH), a potentially fatal disorder resulting from excessive non-malignant activation/proliferation of T lymphocytes and macrophages. Considering the overlapping clinical and laboratory characteristics of these diseases, diagnosing HLH is a challenge. Therefore, tracking the association between VL and HLH is necessary in endemic areas. Although HLH can be inapparent and resolve with antileishmanicides, this may not always occur. HLH causes high lethality; therefore, immunosuppressive therapy should be instituted immediately in order to avoid a fatal outcome. METHODS: We described the epidemiological, clinical, laboratory, and therapeutic profile of this association in a region of Brazil endemic for VL. RESULTS We presented 39 patients with this association in a retrospective cohort of 258 children who were admitted from January 2012 to June 2017. Of the 39 patients, 31 were from urban areas (79.5%), and 21 (53%) were males. The mean age and weight were 2.86 (2.08) years and 14.03 (5.96) kg, respectively. The main symptoms were fever (100%), hepatosplenomegaly (100%), pallor of the skin and mucosa (82.5%), edema (38.5%), bleeding (25%), and jaundice (7.5%). Hemophagocytosis was identified in 16/37 (43.24%) patients, and direct examination revealed that 26/37 (70.27%) patients were positive for VL. The patients were treated as recommended by the Ministry of Health. CONCLUSIONS It was observed that HLH is a common complication in endemic areas, and its diagnosis must consider the overlapping of clinical characteristics and pancytopenia.

Evaluation of cross reactivity between Trypanosoma cruzi and Leishmania infantum in serologically ineligible blood donors due to chagas diseas

Inconclusive serological screening for Trypanosoma cruzi has been a problem for blood banks. This study examined the performance of serological techniques for Chagas disease in reagent samples from blood bank screenings and verified the possibilities of cross reactivity with visceral leishmaniasis. 68 samples of reagent donors tested with ELISA for Chagas disease were evaluated by other techniques and for the detection of anti-Leishmania antibodies. Four donors (5.9%) with positive results for T. cruzi were positive for ELISA Kalazar Detect (visceral leishmaniasis),three of which were confirmed by Western blot. This study confirms the specificity of the tests for Chagas disease in blood banks and reinforces the urgent adoption of measures to assess the real risk of transfusion transmission of visceral leishmaniasis

Poor response to azithromycin in cutaneous leishmaniasis leading to a premature interruption of a multicentric phase III clinical trial in Brazil

Introduction Parenteral antimony-based compounds are still the standard of care for cutaneous leishmaniasis (CL) treatment in many countries, despite their high toxicity. Previous studies showed that oral azithromycin could be an option for CL treatment. The aim of this study was to evaluate efficacy and safety of oral azithromycin (AZ) for CL treatment compared with injectable meglumine antimoniate (MA). Methods This was a randomized, open-label, 2-arm, non-inferiority clinical trial. Treatment-naïve patients with localized CL were treated with MA (15mg/kg/day up to 1,215mg) or AZ (500mg/day) during 20 consecutive days. The primary efficacy end point was a CL cure 90 days after treatment completion. The analysis was performed with intention-to-treat (ITT) and per protocol (PP) analyses. After an anticipated interim analysis, the study was interrupted due to the high failure rate in the azithromycin group. Results Twenty-four volunteers were included in each group. The MA group had a higher cure rate than the AZ group with the ITT and PP analyses, which were 54.2% versus 20.8% [relative risk (RR) 1.97; 95% confidence intervals (95%CI) 1.13-3.42] and 72.2% versus 23.8% (RR 3.03; 95%CI 1.34-6.87), respectively. No unexpected adverse events were observed. Conclusions ...

Immunohistochemical profile of HIF-1α, VEGF-A, VEGFR2 and MMP9 proteins in tegumentary leishmaniasis / Estudo da expressão imunohistoquímica das proteínas HIF-1α, VEGF-A, VEGFR2 e MMP9 em leishmaniose tegumentar americana

BACKGROUND: Leishmaniasis is one of the most important infectious diseases worldwide. Our study can provide more knowledge about angiogenic and hypoxic events in leishmaniasis. We attempted to verify whether the HIF-1 α protein expression may be associated to VEGF-A, VEGFR2 and MMP9 in leishmanial lesions. OBJECTIVES: Besides understanding the pathway, we performed the correlation of VEGF-A, VEGFR2 and MMP9 proteins. METHODS: In this study, we gathered 54 paraffin blocks taken from skin lesions in patients from northern Minas Gerais, Brazil, with confirmed diagnosis of tegumentary leishmaniasis. Immunohistochemistry was used to evaluate the expression of the proteins. The expression of HIF-1α was categorized into two groups according to the median: HIF-1 α lower and HIF-1 α higher. RESULTS: We observed increase of VEGFR2 and MMP9 protein expressions in HIF-1 α higher group of epithelial cells. Spearman analyses in epithelial cells showed correlation between VEGF-A and MMP9, VEGFR2 and MMP9 protein expression. CONCLUSIONS: HIF-1 α higher group showed increase of VEGFR2 and MMP9 proteins. In epithelial cells, VEGF-A was correlated to MMP9 protein. Furthermore, considering leukocyte cells, VEGFR2 was negatively correlated to MMP9 protein levels. This pathway possibly prepares the cells for a higher activity in a hypoxic or an angiogenic microenvironment. Other in vitro and in vivo studies may clarify the activation mechanism and the response from the proteins HIF-1 α, VEGFR2 and MMP-9 in tegumentary leishmaniasis.

FUNDAMENTOS: A leishmaniose é uma das mais importantes doenças infecciosas em todo o mundo. Em leishmaniose, tem sido sugerido que muitas características da lesão está associado a eventos de hipóxia, podendo este ter um papel fundamental na evolução da doença. OBJETIVO: O presente estudo pode fornecer dados acerca do fenômeno hipóxia e da angiogênese em leishmaniose tegumentar americana. Buscou-se verificar se a expressão da proteína HIF-1 α associa-se à expressão das proteínas VEGF-A, VEGFR2 e MMP9 em lesões de Leishmania sp. MÉTODOS: Neste estudo retrospectivo, foram utilizados 54 blocos de parafina de lesões de leishmaniose tegumentar americana de pacientes do norte de Minas Gerais, Brasil, com diagnóstico confirmado de leishmaniose tegumentar americana. A técnica de imunohistoquimica foi utilizada para avaliação da expressão das proteínas. A expressão da HIF-1α foi categorizada em dois grupos de acordo com a mediana: HIF-1 α abaixo e HIF-1 α acima da mediana. RESULTADOS: Observamos aumento das expressões das proteínas VEGFR2 e MMP9 no grupo HIF-1 α acima da mediana. A análise de Spearman demonstrou correlação entre as proteínas VEGF-A e MMP9, VEGFR2 e MMP9. CONCLUSÃO: Os dados aqui apresentados indicam uma alta expressão da proteína HIF-1 α em LTA. O grupo HIF-1α acima da mediana apresentou maior expressão das proteínas VEGFR2 e MMP9. Foi demonstrada correlação entre as proteínas VEGF-A e MMP9, VEGFR2 e MMP9. Outros estudos in vitro e in vivo devem ser realizados a fim de esclarecer o mecanismo de ativação e resposta das proteínas HIF-1 α, VEGFR2 e MMP-9 em leishmaniose tegumentar americana.

Profile of pregnant women and children treated at a reference center for congenital toxoplasmosis in the northern state of Minas Gerais, Brazil / Perfil de mulheres grávidas e crianças atendidas em um centro de referência para toxoplasmose congênita no norte do estado de Minas Gerais, Brasil

INTRODUCTION: To describe the clinical and epidemiological profile of pregnant women and children treated at a reference outpatient clinic for congenital toxoplasmosis. METHODS: Pregnant women potentially exposed to Toxoplasma gondii were observed. Diagnoses were made using serologic tests compatible with acute toxoplasmosis. Children presenting with: Toxoplasma-specific antibodies (IgM or IgA or ascending IgG titers higher than maternal titers in the first 3 months of life) coupled with toxoplasmosis symptoms; intracranial calcifications (by transfontanelar ultrasound or cephalic segment tomography); or retinochoroiditis (by fundoscopy examination) in the first 8 months of life were also included in the study. RESULTS: Fifty-eight mother-child pairs were observed (mean age of the mothers was 22.1 years). Most patients lived in urban areas (86.2 percent) and had attended less than 8 years of school (51.7 percent). Diagnosis was made after birth in 19 (32.8 percent) children. Thirty-four (58.6 percent) women received some type of treatment during pregnancy. Most (72.4 percent) of the children did not present with clinical alterations at birth. The main findings were ophthalmological: 20 (34.5 percent) children with retinochoroiditis, 17 (29.3 percent) with strabismus, and 7 (12.1 percent) with nystagmus. Of the children with retinochoroiditis, 9 presented with subnormal vision. Ten (32.3 percent) out of 31 children presented with intracranial calcifications by cephalic segment congenital toxoplasmosis, and 9 (42.9 percent) children presented with delayed psychomotor development. CONCLUSIONS: Our results highlight a critical situation. Protocols for follow-up of pregnant women and their children must be created to improve medical care and minimize sequelae.

INTRODUÇÃO: Descrever o perfil clínico e epidemiológico de gestantes e crianças atendidas em um centro de referência para toxoplasmose congênita. MÉTODOS: Gestantes potencialmente expostas ao Toxoplasma gondii foram estudadas. Os diagnósticos foram feitos através de testes sorológicos compatíveis com toxoplasmose aguda. Crianças que apresentaram anticorpos específicos (IgM e IgA ou títulos ascendentes de IgG, superiores aos títulos maternos nos primeiros três meses de vida), juntamente com os sintomas da toxoplasmose, calcificações intracranianas (ultrassom transfontanela ou tomografia do segmento cefálico), ou retinocoroidite (fundoscopia) nos primeiros oito meses de vida, também foram estudadas. RESULTADOS: Foram estudados 58 pares mãe-filho (a média de idade das mães foi de 22,1 anos). A maioria (86,2 por cento) das mães residia em áreas urbanas e tinham até 8 anos de escolaridade (51,7 por cento). O diagnóstico foi feito após o nascimento para 19 (32,8 por cento) crianças; 34 (58,6 por cento) mulheres receberam algum tipo de tratamento durante a gravidez. A maioria (72,4 por cento) das crianças não apresentou alterações clínicas ao nascimento. Os principais achados foram oftalmológicos: 20 (34,5 por cento) crianças com retinocoroidite, 17 (29,3 por cento) com estrabismo e 7 (12,1 por cento) com nistagmo. Das crianças com retinocoroidite, 9 apresentaram visão subnormal. Calcificações intracranianas estiveram presentes em 10 (32,3 por cento) das 31 crianças que realizaram toxoplasmose congênita de segmento cefálico e 9 (42,9 por cento) crianças apresentaram atraso do desenvolvimento psicomotor. CONCLUSÕES: Os resultados mostram uma situação crítica. Protocolos para acompanhamento de gestantes e seus filhos devem ser criados para melhorar o atendimento médico e minimizar sequelas.

Genetic diversity of Leishmania infantum field populations from Brazil

Leishmania infantum (syn. Leishmania chagasi) is the etiological agent of visceral leishmaniasis (VL) in Brazil. The epidemiology of VL is poorly understood. Therefore, a more detailed molecular characterization at an intraspecific level is certainly needed. Herein, three independent molecular methods, multilocus microsatellite typing (MLMT), random amplification of polymorphic DNA (RAPD) and simple sequence repeats-polymerase chain reaction (SSR-PCR), were used to evaluate the genetic diversity of 53 L. infantum isolates from five different endemic areas in Brazil. Population structures were inferred by distance-based and Bayesian-based approaches. Eighteen very similar genotypes were detected by MLMT, most of them differed in only one locus and no correlation was found between MLMT profiles, geographical origin or the estimated population structure. However, complex profiles composed of 182 bands obtained by both RAPD and SSR-PCR assays gave different results. Unweighted pair group method with arithmetic mean trees built from these data revealed a high degree of homogeneity within isolates of L. infantum. Interestingly, despite this genetic homogeneity, most of the isolates clustered according to their geographical origin.

Achados oculares em crianças com toxoplasmose congênita / Ocular findings in children with congenital toxoplasmosis

OBJETIVO: Conhecer as lesões oculares mais frequentes encontradas em crianças expostas à toxoplasmose congênita. MÉTODOS: Trata-se de um estudo retrospectivo, a partir de uma coorte histórica, de abordagem quantitativa. Foram avaliadas crianças encaminhadas de um serviço de infectologia pediátrica e inseridas apenas aquelas com diagnóstico confirmado de toxoplasmose congênita. A avaliação oftalmológica incluiu o mapeamento de retina sequencial, sob dilatação pupilar. RESULTADOS: Das 58 crianças presumivelmente expostas ao risco de doença durante a gestação, 20 apresentaram lesões oftalmológicas ao longo do primeiro ano de vida (34 olhos). Destas, 12 estavam assintomáticas ao nascimento. Estrabismo foi registrado em 14 crianças (70 por cento). Em uma criança observou-se ptose palpebral e em outra diminuição da fenda palpebral (microftalmia). Retinocoroidite foi a complicação mais frequente, presente em todas as 20 crianças. Sete crianças apresentaram alterações unilaterais (35 por cento) e 13 crianças apresentaram alterações bilaterais (65 por cento), prevalecendo a localização no polo posterior e mácula. CONCLUSÃO: Retinocoroidite e estrabismo destacaram-se como importantes sequelas da toxoplasmose congênita.

PURPOSE: This study aimed to know the most common ocular findings in children with congenital toxoplasmosis. METHODS: This is a retrospective study carried out from a historical cohort, with a quantitative approach. We evaluated children referred to a pediatric infectious disease service and included only those with confirmed diagnosis of congenital toxoplasmosis. The ophthalmologic evaluation included regular fundus examination under pupil dilation. RESULTS: Of 58 children presumably exposed to risk of the disease during the pregnancy, 20 had ocular lesions during the first year of life (34 eyes). Of these, 12 were asymptomatic at birth. Strabismus was noted in 14 children (70 percent). In one child there was ptosis, and another had decrease in the palpebral fissure (microphthalmia). Retinochoroiditis was the most common complication, present in all 20 children. Seven children (35 percent) showed unilateral changes and 13 children showed bilateral changes (65 percent), with emphasis on the location in the posterior pole and macula. CONCLUSION: Retinochoroiditis and strabismus were outstanding as important sequelae of congenital toxoplasmosis.

Perfil epidemilógico dos acidentes causados por serpentes venenosas no norte do estado de Minas Gerais, Brasil / Epidemiological profile of accidents caused by venomous snakes in the northern part of the state of Minas Gerais, Brasil

Introdução: os acidentes causados por serpentes venenosas são importante problema de saúde pública devido à sua elevada morbimortalidade. Objetivo: descrever o perfil epidemiológico dos acidentes ofídicos causados por serpentes venenosas no nortedo estado de Minas Gerais. Métodos: foram analisadas informações sobre acidentes ofídicos relativas ao período compreendido entre janeiro de 2002 e dezembro de 2006, por meio de dados obtidos dos bancos SINAN WINDOWS e SINAN NET. Resultados: foram notificados 816 casos; 695 (85%) devidos às serpentes do gênero Bothrops; 334(41%) no primeiro trimestre; 593 (73%) na região de Montes Claros; 701 (86%) na zona rural; 328 (40%) picadas nos pés; 695 (85%) receberam soroterapia; 297 (36%) demoraram uma a três horas, em média, após o acidente, para receberam tratamento; e em 681 (83%) a cicatrização da ferida não apresentou sequelas. Conclusões: os dadosclínico-epidemiológicos permitem reconhecer vários aspectos que possibilitam atitudes médicas de prevenção e abordagem terapêutica adequada ao acidente ofídico no norte de Minas Gerais.

Introduction: the casualties related to venomous snakes are important public health issue due to its high morbidity and mortality. Objective: to describe the epidemiological profile of the casualties due to venomous snakes in the northern part of the State of Minas Gerais. Methods: information about snakebites casualties in the period between January 2002 and December 2006 were analyzed, through database from SINAN WINDOWS and SINAN NET. Results: 816 cases were reported; 695 (85%) due to snakes of the kind Bothrops; 334 (41%) in the first quarter of the year; 593 (73%) in the region of Montes Claros; 701 (86%) in the countryside; 328 (40%) bites on the feet; 695 (85%) received sorotherapy; 297 (36%) took one to three hours on average to receive treatment, and in 681 (83%) wound healing showed no sequels. Conclusions: clinic-epidemiological data allow the recognition of various aspects that enable preventive medical attitudes and appropriate therapeutic approach to snakebite in northern Minas Gerais.

Perfil dos acidentes ofídicos no norte do Estado de Minas Gerais, Brasil / Profile of snakebite accidents in the north of the State of Minas Gerais, Brazil

O objetivo deste estudo foi descrever o perfil epidemiológico dos acidentes ofídicos da macrorregião de saúde do Norte do Estado de Minas Gerais, Brasil. Foram analisadas informações sobre os acidentes ofídicos relativos ao período compreendido entre janeiro de 2002 a dezembro de 2006, por meio de bancos de dados. Os resultados demonstraram 10.553 casos notificados, com ênfase para a maior casuística em meses de tempo quente e chuvoso, em áreas urbanas (54,1 por cento), faixa etária menor de 20 anos (39,7 por cento), acometendo mais homens e estudantes (53,1 por cento e 29,1 por cento) respectivamente. Os membros inferiores (pé, dedo do pé, perna e coxa) foram os locais mais afetados (35,9 por cento), as serpentes prevalentes foram do gênero Bothrops (82,9 por cento) e a gravidade da maioria dos acidentes foi leve (66,2 por cento). Observou-se nesse estudo um importante impacto da sazonalidade, urbanização, subnotificação das espécies envolvidas nesses acidentes e busca rápida pelo pronto atendimento. Espera-se que os dados inéditos da casuística obtida possam servir de substrato para o planejamento e execução de medidas voltadas para vigilância em saúde e atendimento.

The aim of this study was to describe the epidemiological profile of snakebite accidents in the healthcare macroregion of the north of the State of Minas Gerais, Brazil. Database information on snakebite accidents covering the period from January 2002 to December 2006 was analyzed. It was found that 10,553 cases were notified, and that the samples were noticeably larger in the months of hot and rainy weather, in urban areas (54.1 percent), at ages less then 20 years (39.7 percent) and among men and students (53.1 percent and 29.1 percent) respectively. The lower limbs (feet, toes, legs and thighs) were the locations most affected (35.9 percent). The most prevalent snakes were in the genus Bothrops (82.9 percent) and most of the accidents were mild (66.2 percent). In this study, it was seen that the seasonality, urbanization and undernotification of the species involved in these accidents had a notable impact, along with seeking walk-in care. It is expected that the new data obtained from this sample may serve as the substrate for planning and implementing measures for healthcare surveillance.