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High parasitological failure rate of visceral leishmaniasis to sodium stibogluconate among HIV co-infected adults in Ethiopia.

ABSTRACT: Antimonials are still being used for visceral leishmaniasis (VL) treatment among HIV co-infected patients in East-Africa due to the shortage of alternative safer drugs like liposomal amphotericin B. Besides tolerability, emergence of resistance to antimonials is a major concern.This study was aimed at assessing the clinical outcome of VL-HIV co-infected patients when treated with sodium stibogluconate (SSG).Retrospective patient record analysis of VL-HIV co-infected patients treated at a clinical trial site in north-west Ethiopia was done. Patients with parasitologically confirmed VL and HIV co-infection treated with SSG were included. The dose of SSG used was 20 mg Sb5 (pentavalent antimony)/kg and maximum of 850 mg Sb5 for 30 days. The clinical outcomes were defined based on the tissue aspiration results as cure or failure, and additionally the safety and mortality rates were computed.The study included 57 patients treated with SSG and by the end of treatment only 43.9% of patients were cured. The parasitological treatment failure and the case fatality rate were 31.6% and 14.0% respectively. SSG was discontinued temporarily or permanently for 12 (21.1%) cases due to safety issues. High baseline parasite load (graded more than 4+) was significantly associated with treatment failure (odds ratio?=?8.9, 95% confidence interval?=?.5-51.7).SSG is not only unsafe, but also has low effectiveness for VL-HIV patients. Safe and effective alternative medications are very urgently needed. Drug sensitivity surveillance should be introduced in the region.

SUBMITTER: Diro E

PROVIDER: S-EPMC4031116 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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High parasitological failure rate of visceral leishmaniasis to sodium stibogluconate among HIV co-infected adults in Ethiopia.

Diro Ermias E Lynen Lutgarde L Mohammed Rezika R Boelaert Marleen M Hailu Asrat A van Griensven Johan J

PLoS neglected tropical diseases 20140522 5

<h4>Background</h4>Antimonials are still being used for visceral leishmaniasis (VL) treatment among HIV co-infected patients in East-Africa due to the shortage of alternative safer drugs like liposomal amphotericin B. Besides tolerability, emergence of resistance to antimonials is a major concern.<h4>Objectives</h4>This study was aimed at assessing the clinical outcome of VL-HIV co-infected patients when treated with sodium stibogluconate (SSG).<h4>Methods</h4>Retrospective patient record analys ...[more]

PMID: 24854196

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Project description:Background:Human visceral leishmaniasis (VL) is a life-threatening protozoan disease caused by parasites belonging to the Leishmania donovani complex. Ethiopia has the highest VL-HIV co-infection rate in the world, with several of these patients presenting with repeated episodes of VL disease (ie, relapse). However, we lack data on how HIV patients with multiple VL relapse present clinically, and whether they continue to respond to currently available medicines. Methods:The medical records of VL-HIV co-infected patients with multiple VL relapses at the Leishmaniasis Treatment and Research Center in Gondar, Ethiopia, between June 2012 and June 2016 were retrieved. Variables on their clinical and laboratory profiles were collected. Descriptive analysis was done to show the characteristics of the VL episodes. Result:A total of 48 VL episodes in 12 patients were identified, the median number of episodes per patient was 5 (interquartile range, 4-8 episodes). The median time to relapse was 5 months (interquartile range, 3-5.5 months). Splenomegaly was present in 47 of the episodes (98%), fever or other accompanying symptoms were present in only 66% (32 out of 48). The median tissue parasite grade at VL diagnosis was 6+ (interquartile range, 5+- 6+). All patients were on antiretroviral therapy. The median duration of treatment per episode was 2 months (interquartile range, 2-2 months). All patients achieved parasitological cure at discharge at each episode. Conclusions:Multiple recurrences of VL diseases were observed in HIV co-infected patients. With recurrent episodes, splenomegaly was found to be the main manifestation, whereas fever was less common. These patients came with recurrence of diseases in <6 months and required prolonged treatment to achieve cure.Further research on prediction, prevention, and better management options for recurrent VL is needed. ORCID ID: https://orcid.org/0000-0002-1410-0454. (Curr Ther Res Clin Exp. 2020; 81:XXX-XXX).

Project description:Visceral Leishmaniasis is a very dangerous form of leishmaniasis and, shorn of appropriate diagnosis and handling, it leads to death and physical disability. Depicting the spatiotemporal pattern of disease is important for disease regulator and deterrence strategies. Spatiotemporal modeling has distended broad veneration in recent years. Spatial and spatiotemporal disease modeling is extensively used for the analysis of registry data and usually articulated in a hierarchical Bayesian framework. In this study, we have developed the hierarchical spatiotemporal Bayesian modeling of the infected rate of Visceral leishmaniasis in Human (VLH). We applied the Stochastics Partial Differential Equation (SPDE) approach for a spatiotemporal hierarchical model for Visceral leishmaniasis in human (VLH) that involves a GF and a state process is associated with an autoregressive order one temporal dynamics and the spatially correlated error term, along with the effect of land shield, metrological, demographic, socio-demographic and geographical covariates in an endemic area of Amhara regional state, Ethiopia. The model encompasses a Gaussian Field (GF), affected by an error term, and a state process described by a first-order autoregressive dynamic model and spatially correlated innovations. A hierarchical model including spatially and temporally correlated errors was fit to the infected rate of Visceral leishmaniasis in human (VLH) weekly data from January 2015 to December 2017 using the R package R-INLA, which allows for Bayesian modeling using the stochastic partial differential equation (SPDE) approach. We found that the mean weekly temperature had a significant positive association with infected rate of VLH. Moreover, net migration rate, clean water coverage, average number of households, population density per square kilometer, average number of persons per household unit, education coverage, health facility coverage, mortality rate, and sex ratio had a significant association with the infected rate of visceral leishmaniasis (VLH) in the region. In this study, we investigated the dynamic spatiotemporal modeling of Visceral leishmaniasis in Human (VLH) through a stochastic partial differential equation approach (SPDE) using integrated nested Laplace approximation (INLA). Our study had confirmed both metrological, demographic, sociodemographic and geographic covariates had a significant association with the infected rate of visceral leishmaniasis (VLH) in the region.

Project description:In 2010, WHO recommended a new first-line treatment for visceral leishmaniasis (VL) in Eastern Africa. The new treatment, a combination of intravenous (IV) or intramuscular (IM) sodium stibogluconate (SSG) and IM paromomycin (PM) was an improvement over SSG monotherapy, the previous first-line VL treatment in the region. To monitor the new treatment's safety and effectiveness in routine clinical practice a pharmacovigilance (PV) programme was developed.A prospective PV cohort was developed. Regulatory approval was obtained in Sudan, Kenya, Uganda and Ethiopia. Twelve sentinel sites sponsored by the Ministries of Health, Médecins Sans Frontières (MSF) and Drugs for Neglected Diseases initiative (DNDi) participated. VL patients treated using the new treatment were consented and included in a common registry that collected demographics, baseline clinical characteristics, adverse events, serious adverse events and treatment outcomes. Six-monthly periodic safety update reports (PSUR) were prepared and reviewed by a PV steering committee.Overall 3126 patients were enrolled: 1962 (62.7%) from Sudan, 652 (20.9%) from Kenya, 322 (10.3%) from Ethiopia and 190 (6.1%) from Uganda. Patients were mostly male children (68.1%, median age 11 years) with primary VL (97.8%). SSG-PM initial cure rate was 95.1%; no geographical differences were noted. HIV/VL co-infected patients and patients older than 50 years had initial cure rates of 56 and 81.4%, respectively, while 1063 (34%) patients had at least one adverse event (AE) during treatment and 1.92% (n = 60) had a serious adverse event (SAE) with a mortality of 1.0% (n = 32). There were no serious unexpected adverse drug reactions.This first regional PV programme in VL supports SSG-PM combination as first-line treatment for primary VL in Eastern Africa. SSG-PM was effective and safe except in HIV/VL co-infected or older patients. Active PV surveillance of targeted safety, effectiveness and key VL outcomes such us VL relapse, PKDL and HIV/VL co-infection should continue and PV data integrated to national and WHO PV databases.

Project description:BACKGROUND:Visceral leishmaniasis (VL) in human immunodeficiency virus (HIV) co-infected patients requires special case management. AmBisome monotherapy at 40 mg/kg is recommended by the World Health Organization. The objective of the study was to assess if a combination of a lower dose of AmBisome with miltefosine would show acceptable efficacy at the end of treatment. METHODOLOGY/PRINCIPAL FINDINGS:An open-label, non-comparative randomized trial of AmBisome (30 mg/kg) with miltefosine (100 mg/day for 28 days), and AmBisome monotherapy (40 mg/kg) was conducted in Ethiopian VL patients co-infected with HIV (NCT02011958). A sequential design was used with a triangular continuation region. The primary outcome was parasite clearance at day 29, after the first round of treatment. Patients with clinical improvement but without parasite clearance at day 29 received a second round of the allocated treatment. Efficacy was evaluated again at day 58, after completion of treatment. Recruitment was stopped after inclusion of 19 and 39 patients in monotherapy and combination arms respectively, as per pre-specified stopping rules. At D29, intention-to-treat efficacy in the AmBisome arm was 70% (95% CI 45-87%) in the unadjusted analysis, and 50% (95% CI 27-73%) in the adjusted analysis, while in the combination arm, it was 81% (95% CI 67-90%) and 67% (95% CI 48-82%) respectively. At D58, the adjusted efficacy was 55% (95% CI 32-78%) in the monotherapy arm, and 88% (95% CI 79-98%) in the combination arm. No major safety concerns related to the study medication were identified. Ten SAEs were observed within the treatment period, and 4 deaths unrelated to the study medication. CONCLUSIONS/SIGNIFICANCE:The extended treatment strategy with the combination regimen showed the highest documented efficacy in HIV-VL patients; these results support a recommendation of this regimen as first-line treatment strategy for HIV-VL patients in eastern Africa. TRIAL REGISTRATION NUMBER:www.clinicaltrials.gov NCT02011958.

Dataset Information

High parasitological failure rate of visceral leishmaniasis to sodium stibogluconate among HIV co-infected adults in Ethiopia.

Publications

High parasitological failure rate of visceral leishmaniasis to sodium stibogluconate among HIV co-infected adults in Ethiopia.

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