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Long term outcomes and prognostics of visceral leishmaniasis in HIV infected patients with use of pentamidine as secondary prophylaxis based on CD4 level: a prospective cohort study in Ethiopia.

ABSTRACT: BACKGROUND:The long-term treatment outcome of visceral leishmaniasis (VL) patients with HIV co-infection is complicated by a high rate of relapse, especially when the CD4 count is low. Although use of secondary prophylaxis is recommended, it is not routinely practiced and data on its effectiveness and safety are limited. METHODS:A prospective cohort study was conducted in Northwest Ethiopia from August 2014 to August 2017 (NCT02011958). HIV-VL patients were followed for up to 12 months. Patients with CD4 cell counts below 200/?L at the end of VL treatment received pentamidine prophylaxis starting one month after parasitological cure, while those with CD4 count ?200 cells/?L were followed without secondary prophylaxis. Compliance, safety and relapse-free survival, using Kaplan-Meier analysis methods to account for variable time at risk, were summarised. Risk factors for relapse or death were analysed. RESULTS:Fifty-four HIV patients were followed. The probability of relapse-free survival at one year was 50% (95% confidence interval [CI]: 35-63%): 53% (30-71%) in 22 patients with CD4 ?200 cells/?L without pentamidine prophylaxis and 46% (26-63%) in 29 with CD4 <200 cells/?L who started pentamidine. Three patients with CD4 <200 cells/?L did not start pentamidine. Amongst those with CD4 ?200 cells/?L, VL relapse was an independent risk factor for subsequent relapse or death (adjusted rate ratio: 5.42, 95% CI: 1.1-25.8). Except for one case of renal failure which was considered possibly related to pentamidine, there were no drug-related safety concerns. CONCLUSION:The relapse-free survival rate for VL patients with HIV was low. Relapse-free survival of patients with CD4 count <200cells/?L given pentamidine secondary prophylaxis appeared to be comparable to patients with a CD4 count ?200 cells/?L not given prophylaxis. Patients with relapsed VL are at higher risk for subsequent relapse and should be considered a priority for secondary prophylaxis, irrespective of their CD4 count.

SUBMITTER: Diro E

PROVIDER: S-EPMC6400407 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Long term outcomes and prognostics of visceral leishmaniasis in HIV infected patients with use of pentamidine as secondary prophylaxis based on CD4 level: a prospective cohort study in Ethiopia.

Diro Ermias E Edwards Tansy T Ritmeijer Koert K Fikre Helina H Abongomera Charles C Kibret Aderajew A Bardonneau Clélia C Soipei Peninah P Mutinda Brian B Omollo Raymond R van Griensven Johan J Zijlstra Eduard E EE Wasunna Monique M Alves Fabiana F Alvar Jorge J Hailu Asrat A Alexander Neal N Blesson Séverine S

PLoS neglected tropical diseases 20190221 2

<h4>Background</h4>The long-term treatment outcome of visceral leishmaniasis (VL) patients with HIV co-infection is complicated by a high rate of relapse, especially when the CD4 count is low. Although use of secondary prophylaxis is recommended, it is not routinely practiced and data on its effectiveness and safety are limited.<h4>Methods</h4>A prospective cohort study was conducted in Northwest Ethiopia from August 2014 to August 2017 (NCT02011958). HIV-VL patients were followed for up to 12 m ...[more]

PMID: 30789910

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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:BackgroundVisceral Leishmaniasis (VL) is a neglected tropical disease endemic to several countries including Ethiopia. Outside of Africa, kidney involvement in VL is frequent and associated with increased mortality. There is however limited data on acute kidney injury (AKI) in VL patients in East-Africa, particularly in areas with high rates of HIV co-infection. This study aims to determine the prevalence, characteristics and associated factors of AKI in VL patients in Northwest Ethiopia.MethodsA hospital based retrospective patient record analysis was conducted including patients treated for VL from January 2019 to December 2019 at the Leishmaniasis Research and Treatment Center (LRTC), Gondar, Ethiopia. Patients that were enrolled in ongoing clinical trials at the study site and those with significant incomplete data were excluded. Data was analyzed using SPSS version 20. P values were considered significant if < 0.05.ResultsAmong 352 VL patients treated at LRTC during the study period, 298 were included in the study. All were male patients except two; the median age was 23 years (IQR: 20-27). The overall prevalence of AKI among VL patients was 17.4% (confidence interval (CI): 13.6%-22.2%). Pre-renal azotemia (57%) and drug-induced AKI (50%) were the main etiologies of AKI at admission and post-admission respectively. Proteinuria and hematuria occurred in 85% and 42% of AKI patients respectively. Multivariate logistic regression revealed HIV co-infection (adjusted odds ratio (AOR): 6.01 95% CI: 1.99-18.27, p = 0.001) and other concomitant infections (AOR: 3.44 95% CI: 1.37-8.65, p = 0.009) to be independently associated with AKI.ConclusionAKI is a frequent complication in Ethiopian VL patients. Other renal manifestations included proteinuria, hematuria, and pyuria. HIV co-infection and other concomitant infections were significantly associated with AKI. Further studies are needed to quantify proteinuria and evaluate the influence of AKI on the treatment course, morbidity and mortality in VL patients.

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:BackgroundVisceral leishmaniasis (VL), a vector-borne disease caused by species of the L.donovani complex, has (re)-emerged in Ethiopia during the last two decades and is currently of increasing public health concern. However, very little is known about VL epidemiology in the Somali Region of Ethiopia. The aim of this study was to provide detailed epidemiological information on seroprevalence, associated factors and incriminated vectors of VL in Shebelle Zone and Ethiopian Somali Region in general.MethodsA cross-sectional epidemiological study was conducted between March and May 2016 in Gode and Adadle districts of Shebelle Zone, Ethiopian Somali Region. Two-stage semi-random sampling was applied for selecting study participants for the field survey. The study included structured questionnaire interviews, serological assays (rK39-immunochromatographic test), ELISA and entomological surveys.ResultsFrom a total of 361 participants, 57 (15.8%) were seropositive for VL including 46 (12.7%) rK39 positive and 11 (3.0%) positive by both rK39 and ELISA. VL seroprevalence was higher (P < 0.001) in Adadle (31.1%) compared to Gode (12.7%) district. The VL seroprevalence rate was higher in females than in males [rK39 (17.2 vs 14.0%) and ELISA (3.4 vs 2.5%)]. Children under the 15 years of age were the most highly affected group [rK39 (20.4%) and ELISA (4.4%)]. Increased VL risk was associated with presence of termite hills, study district, outdoor sleeping, Acacia trees and domestic animals [odds ratio (95% confidence interval): 12.58 (5.911-26.763), 5.40 (2.90-10.07), 5.31 (2.283-12.364), 2.37 (1.1190-4.728) and 0.199 (0.097-0.410), respectively]. The entomological survey identified 74 Phlebotomus [P. (Larroussius) orientalis (52/74), P. (Anaphlebotomus) rodhaini (14/74), P. (Paraphlebotomus) sergenti (8/74)] and 11 Sergentomyia sand flies. The average frequency of P. orientalis (3.06 ± 0.66) collected by all traps per night was higher than that of other species. The average frequency of total and specific (P. orientalis) female sand flies was higher in Adadle (1.89 ± 0.423 vs 1.11 ± 0.309) than in Gode (0.62 ± 0.324 vs 0.38 ± 0.183) district. The highest mean numbers of total (8 ± 1.5) and P. orientalis (6 ± 0.913) sand flies were collected in termite hills.ConclusionsThe present findings revealed potential new VL-transmission foci in the study districts. Therefore, the need for parasitological and molecular characterization of the parasite in humans and vector sand flies is of paramount importance to confirm transmission.

Dataset Information

Long term outcomes and prognostics of visceral leishmaniasis in HIV infected patients with use of pentamidine as secondary prophylaxis based on CD4 level: a prospective cohort study in Ethiopia.

Publications

Long term outcomes and prognostics of visceral leishmaniasis in HIV infected patients with use of pentamidine as secondary prophylaxis based on CD4 level: a prospective cohort study in Ethiopia.

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