Recurrent kala-azar: report of two cured cases after total splenectomy

In Latin America, the causative agent of kala-azar is the intracellular protozoan Leishmania infantum. Most cases in South America are reported in Brazil. Worldwide, it mainly affects Bangladesh, Ethiopia, India, South Sudan and Sudan. Despite the high morbidity and lethality of kala-azar, most infections are asymptomatic. However, a small portion of patients evolves with recurrence of kala-azar becoming symptomatic even after all available drug treatments. Kala-azar is not a formal indication for splenectomy in adults. Splenectomy is recommended as a saving measure, when kala-azar is associated with symptomatic hypersplenism and for drug-resistant cases. In the study, we report two cases of kala-azar with splenomegaly that presented several hospitalizations due to the recurrence of the kala-azar, in addition to hospitalizations for normalizing the blood count. After splenectomy, kala-azar cases and the effects of hypersplenism are cured. Thus, splenectomy should be seen as a surgical treatment option with a curative purpose in patients with recurrent kala-azar, in whom the possibilities of drug therapy have been exhausted and even so they progressed with hypersplenism and clinical repercussions

The performance of serological tests for Leishmania infantum infection screening in dogs depends on the prevalence of the disease

Dogs are considered the main reservoir of Leishmania infantum. This protozoan causes visceral leishmaniasis (VL), an uncontrolled urban zoonosis in Brazil. Serological tests and polymerase chain reaction (PCR) on peripheral blood were performed to identify infected dogs in scenarios of higher and lower prevalence of the disease (Teresina and Vitória). One-hundred infected and 57 non-infected animals from Teresina and 100 non-infected animals from Vitória were studied. Animal selection was not dependent on previous serology. The sensitivity (Teresina) and specificity (Teresina and Vitória) were as follows: indirect antibody fluorescence (IFAT) cut-off of 1:40 (IFAT 1:40): 96%, 18%, and 76%; IFAT 1:80: 90%, 33%, and 93%; direct agglutination test (DAT): 96%, 33%, and 98%; fast agglutination screening test (FAST): 93%, 68%, and 100%; immunochromatographic assay with a recombinant rK39 antigen (rK39): 88%, 74%, and 98%; enzyme linked immunosorbent assay (ELISA): 91%, 79%, and 98%; rapid dual-path platform test (TR DPP®): 98%, 60%, and 98%; and blood PCR: 29%, 93%, and 97%, respectively. In the high transmission area, none of the tests adequately discriminated L. infantum-infected from non-infected dogs. However, in the high transmission city, the area under the receiver operating characteristic (ROC) curve of FAST, DAT, ICrK39, ELISA and TR DPP® was high

Guillain-Barré syndrome and dengue-like disease in 2015: temporal relationship in Piauí state and implications on Zika virus surveillance

Secretaria de Estado da Saúde do Piauí. Instituto de Doenças Tropicais Natan Portella. Teresina, PI, Brasil / Fundação Municipal de Saúde de Teresina. Diretoria de Vigilância em Saúde. Teresina, PI, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Secretaria de Estado da Saúde do Piauí. Gerência de Vigilância em Saúde. Teresina, PI, Brasil.Universidade Federal do Piauí. Departamento de Medicina Especializada. Teresina, PI, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Secretaria de Estado da Saúde do Piauí. Gerência de Vigilância em Saúde. Teresina, PI, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Belém, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Belém, PA, Brasil.Fundação Municipal de Saúde de Teresina. Diretoria de Vigilância em Saúde. Teresina, PI, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Belém, PA, Brasil

Natural Resistance of Leishmania infantum to Miltefosine Contributes to the Low Efficacy in the Treatment of Visceral Leishmaniasis in Brazil

In India visceral leishmaniasis (VL) caused by Leishmania donovani has been successfully treated with miltefosine with a cure rate of > 90%. To assess the efficacy and safety of oral miltefosine in L. infantum-causing Brazilian VL patients, a phase II, open-label, dose-escalation study of oral miltefosine was conducted in children (ages 2-12) and adolescent-adults (ages 13-60). Definitive cure was assessed at a 6 month follow-up visit. The cure rate was only 42% (6 out of 14 patients) with the recommended 28 days of therapy and 68% (19 out of 28 patients) with an extended treatment of 42 days. The in vitro miltefosine susceptibility profile of intracellular amastigote stages of the pre-treatment isolates, from cured and relapsed patients, showed a positive correlation with clinical outcome. The IC50 mean (SEM) of eventual cures was 5.1 (0.4) µM whereas that of eventual failures was 12.8 (1.9) µM (P = 0.0002). An IC50 below or above 8.0 µM predicts cure or failure, respectively with 82% sensitivity and 100% specificity. The finding of L. infantum amastigotes resistant to miltefosine in isolates from patients who eventually failed treatment, strongly suggests natural resistance to this drug, as miltefosine had never been used in Brazil before this trial was carried out

High seroprevalence of Leishmania infantum is linked to immune activation in people with HIV: a two-stage cross-sectional study in Bahia, Brazil

Visceral leishmaniasis is an opportunistic disease in HIV-1 infected individuals, unrecognized as a determining factor for AIDS diagnosis. The growing geographical overlap of HIV-1 and Leishmania infections is an emerging challenge worldwide, as co-infection increases morbidity and mortality for both infections. Here, we determined the prevalence of people living with HIV (PWH) with a previous or ongoing infection by Leishmania infantum and investigated the virological and immunological factors associated with co-infection. We adopted a two-stage cross-sectional cohort (CSC) design (CSC-I, n = 5,346 and CSC-II, n = 317) of treatment-naïve HIV-1-infected individuals in Bahia, Brazil. In CSC-I, samples collected between 1998 and 2013 were used for serological screening for leishmaniasis by an in-house Enzyme-Linked Immunosorbent Assay (ELISA) with SLA (Soluble Leishmania infantum Antigen), resulting in a prevalence of previous or ongoing infection of 16.27%. Next, 317 PWH were prospectively recruited from July 2014 to December 2015 with the collection of sociodemographic and clinical data. Serological validation by two different immunoassays confirmed a prevalence of 15.46 and 8.20% by anti-SLA, and anti-HSP70 serology, respectively, whereas 4.73% were double-positive (DP). Stratification of these 317 individuals in DP and double-negative (DN) revealed a significant reduction of CD4+ counts and CD4+/CD8+ ratios and a tendency of increased viral load in the DP group, as compared to DN. No statistical differences in HIV-1 subtype distribution were observed between the two groups. However, we found a significant increase of CXCL10 (p = 0.0076) and a tendency of increased CXCL9 (p = 0.061) in individuals with DP serology, demonstrating intensified immune activation in this group. These findings were corroborated at the transcriptome level in independent Leishmania- and HIV-1-infected cohorts (Swiss HIV Cohort and Piaui Northeast Brazil Cohort), indicating that CXCL10 transcripts are shared by the IFN-dominated immune activation gene signatures of both pathogens and positively correlated to viral load in untreated PWH. This study demonstrated a high prevalence of PWH with L. infantum seropositivity in Bahia, Brazil, linked to IFN-mediated immune activation and a significant decrease in CD4+ levels. Our results highlight the urgent need to increase awareness and define public health strategies for the management and prevention of HIV-1 and L. infantum co-infection