scholarly journals Visceral leishmaniasis in eastern Africa – current status

2007 ◽  
Vol 101 (12) ◽  
pp. 1169-1170 ◽  
Author(s):  
Richard Reithinger ◽  
Simon Brooker ◽  
Jan H. Kolaczinski
Keyword(s):  
Visceral Leishmaniasis ◽  
Eastern Africa ◽  
Current Status

scholarly journals Safety and Efficacy of Single Dose versus Multiple Doses of AmBisome® for Treatment of Visceral Leishmaniasis in Eastern Africa: A Randomised Trial

2014 ◽  
Vol 8 (1) ◽  
pp. e2613 ◽  
Author(s):  
Eltahir A. G. Khalil ◽  
Teklu Weldegebreal ◽  
Brima M. Younis ◽  
Raymond Omollo ◽  
Ahmed M. Musa ◽  
...  
Keyword(s):  
Single Dose ◽  
Visceral Leishmaniasis ◽  
Randomised Trial ◽  
Eastern Africa ◽  
Safety And Efficacy ◽  
Multiple Doses

scholarly journals Characterizing the non-linear pharmacokinetics of miltefosine in paediatric visceral leishmaniasis patients from Eastern Africa

2020 ◽  
Vol 75 (11) ◽  
pp. 3260-3268
Author(s):  
Semra Palić ◽  
Anke E Kip ◽  
Jos H Beijnen ◽  
Jane Mbui ◽  
Ahmed Musa ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Cumulative Dose ◽  
Drug Exposure ◽  
Compartment Model ◽  
Eastern Africa ◽  
Model Following ◽  
Two Compartment Model ◽  
Non Linear ◽  
Linear Elimination ◽  
Dosing Regimens

Abstract Background Conventional miltefosine dosing (2.5 mg/kg/day) for treatment of visceral leishmaniasis (VL) is less effective in children than in adults. A higher allometric dose (median 3.2 mg/kg/day) was therefore investigated in paediatric VL patients in Eastern Africa. Results of this trial showed an unforeseen, lower than dose-proportional increase in exposure. Therefore, we performed a pooled model-based analysis of the paediatric data available from both dosing regimens to characterize observed non-linearities in miltefosine pharmacokinetics (PK). Methods Fifty-one children with VL were included in this analysis, treated with either a conventional (n = 21) or allometric (n = 30) miltefosine dosing regimen. PK data were analysed using non-linear mixed-effects modelling. Results A two-compartment model following first-order absorption and linear elimination, with two separate effects on relative oral bioavailability, was found to fit these data best. A 69% lower bioavailability at treatment start was estimated, presumably due to initial malnourishment and malabsorption. Stagnation in miltefosine accumulation in plasma, hampering increased drug exposure, was related to the increase in cumulative dose (mg/kg/day). However, the allometric regimen increased exposure 1.7-fold in the first treatment week and reduced the time to reach the PK target by 17.4%. Conclusions Miltefosine PK in children suffering from VL are characterized by dose-dependent non-linearities that obstruct the initially expected exposure levels. Bioavailability appeared to be affected by the cumulative dose, possibly as a consequence of impaired absorption. Despite this, allometric dosing led to a faster target achievement and increased exposure compared with conventional dosing.

Visceral leishmaniasis: current status of control, diagnosis, and treatment, and a proposed research and development agenda

2002 ◽  
Vol 2 (8) ◽  
pp. 494-501 ◽  
Author(s):  
Philippe J Guerin ◽  
Piero Olliaro ◽  
Shyam Sundar ◽  
Marleen Boelaert ◽  
Simon L Croft ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Research And Development ◽  
Diagnosis And Treatment ◽  
Current Status ◽  
Development Agenda

scholarly journals Visceral Leishmaniasis in China: an Endemic Disease under Control

2015 ◽  
Vol 28 (4) ◽  
pp. 987-1004 ◽  
Author(s):  
Zhao-Rong Lun ◽  
Ming-Shui Wu ◽  
Yun-Fu Chen ◽  
Jun-Yun Wang ◽  
Xiao-Nong Zhou ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Rural Areas ◽  
Health Workers ◽  
Sand Fly ◽  
Current Status ◽  
Content Type ◽  
Control Programs ◽  
Treatment And Prevention ◽  
Special Value ◽  
The Government

SUMMARYVisceral leishmaniasis (VL) caused byLeishmaniaspp. is an important vector-borne and largely zoonotic disease. In China, three epidemiological types of VL have been described: anthroponotic VL (AVL), mountain-type zoonotic VL (MT-ZVL), and desert-type ZVL (DT-ZVL). These are transmitted by four different sand fly species:Phlebotomus chinensis,P. longiductus,P. wui, andP. alexandri.In 1951, a detailed survey of VL showed that it was rampant in the vast rural areas west, northwest, and north of the Yangtze River. Control programs were designed and implemented stringently by the government at all administrative levels, resulting in elimination of the disease from most areas of endemicity, except the western and northwestern regions. The control programs consisted of (i) diagnosis and chemotherapy of patients, (ii) identification, isolation, and disposal of infected dogs, and (iii) residual insecticide indoor spraying for vector control. The success of the control programs is attributable to massive and effective mobilization of the general public and health workers to the cause. Nationally, the annual incidence is now very low, i.e., only 0.03/100,000 according to the available 2011 official record. The overwhelming majority of cases are reported from sites of endemicity in the western and northwestern regions. Here, we describe in some depth and breadth the current status of epidemiology, diagnosis, treatment, and prevention of the disease, with particular reference to the control programs. Pertinent information has been assembled from scattered literature of the past decades in different languages that are not readily accessible to the scientific community. The information provided constitutes an integral part of our knowledge on leishmaniasis in the global context and will be of special value to those interested in control programs.

scholarly journals Antibody and cytokine levels in visceral leishmaniasis patients with varied parasitemia before, during, and after treatment in patients admitted to Arba Minch General Hospital, southern Ethiopia

2021 ◽  
Vol 15 (8) ◽  
pp. e0009632
Author(s):  
Dagimawie Tadesse ◽  
Alemseged Abdissa ◽  
Mekidim Mekonnen ◽  
Tariku Belay ◽  
Asrat Hailu
Keyword(s):  
Visceral Leishmaniasis ◽  
Leishmania Donovani ◽  
Serum Levels ◽  
High Serum ◽  
Eastern Africa ◽  
Southern Ethiopia ◽  
Ifn Γ ◽  
A Prospective Study ◽  
Antibody Levels ◽  
Tgf Β1

Background Visceral leishmaniasis is a disease caused by disseminated Leishmania donovani infection which affects almost half a million people annually. Most of the patients are reported from the Indian sub-continent, Eastern Africa and Brazil. In this study, we aimed to determine the levels of antibodies and cytokines in visceral leishmaniasis patients and to examine associations of parasitemia with the clinical states of patients. A prospective study was carried out, enrolling a total of 48 active VL patients who were evaluated before, during different time points and, three months after treatment. Serum cytokine concentrations, antibody levels, parasitemia, laboratory (hematologic and biochemical) measurements, and clinical parameters were assessed. Results Counts of WBC and platelets, and measurements of hemoglobin (Hb) increased during treatment (P ≤ 0.05). Elevated levels of circulating IL-10, IFN-γ, and TGF-β1 were measured before treatment. The observed increase in serum IL-10 remarkably declined within 7 days after the start of treatment. Anti-leishmanial antibody index (AI) was high in all VL patients irrespective of spleen aspirate parasite grade before treatment and at different times during treatment. However, a significant (P ≤ 0.05) decrease of AI was observed 120 days post-treatment. IL-2 serum levels were below the detection limit at all sampling points. Conclusions The present results suggest that IL-10, IFN-γ, and TGF-β1 can be used as markers of active visceral leishmaniasis. In addition, measuring circulating cytokines concentrations, particularly IL-10, in combination with other clinical evaluations, could be used as criteria for the cure. The observation that a high serum concentration of IFN-gamma at baseline was associated with low parasitemia deserves further investigations.

scholarly journals Serious adverse events following treatment of visceral leishmaniasis: A systematic review and meta-analysis

2021 ◽  
Vol 15 (3) ◽  
pp. e0009302
Author(s):  
Sauman Singh-Phulgenda ◽  
Prabin Dahal ◽  
Roland Ngu ◽  
Brittany J. Maguire ◽  
Alice Hawryszkiewycz ◽  
...  
Keyword(s):  
Systematic Review ◽  
At Risk ◽  
Clinical Trials ◽  
Visceral Leishmaniasis ◽  
Adverse Events ◽  
Amphotericin B ◽  
Treatment Initiation ◽  
Meta Analysis ◽  
Eastern Africa ◽  
Serious Adverse Events

Background Despite a historical association with poor tolerability, a comprehensive review on safety of antileishmanial chemotherapies is lacking. We carried out an update of a previous systematic review of all published clinical trials in visceral leishmaniasis (VL) from 1980 to 2019 to document any reported serious adverse events (SAEs). Methods For this updated systematic review, we searched the following databases from 1st Jan 2016 through 2nd of May 2019: PUBMED, Embase, Scopus, Web of Science, Cochrane, clinicaltrials.gov, WHO ICTRP, and the Global Index Medicus. We included randomised and non-randomised interventional studies aimed at assessing therapeutic efficacy and extracted the number of SAEs reported within the first 30 days of treatment initiation. The incidence rate of death (IRD) from individual treatment arms were combined in a meta-analysis using random effects Poisson regression. Results We identified 157 published studies enrolling 35,376 patients in 347 treatment arms. Pentavalent antimony was administered in 74 (21.3%), multiple-dose liposomal amphotericin B (L-AmB) in 52 (15.0%), amphotericin b deoxycholate in 51 (14.7%), miltefosine in 33 (9.5%), amphotericin b fat/lipid/colloid/cholesterol in 31 (8.9%), and single-dose L-AmB in 17 (4.9%) arms. There was a total of 804 SAEs reported of which 793 (including 428 deaths) were extracted at study arm level (11 SAEs were reported at study level only). During the first 30 days, there were 285 (66.6%) deaths with the overall IRD estimated at 0.068 [95% confidence interval (CI): 0.041–0.114; I2 = 81.4%; 95% prediction interval (PI): 0.001–2.779] per 1,000 person-days at risk; the rate was 0.628 [95% CI: 0.368–1.021; I2 = 82.5%] in Eastern Africa, and 0.041 [95% CI: 0.021–0.081; I2 = 68.1%] in the Indian Subcontinent. In 21 study arms which clearly indicated allowing the inclusion of patients with HIV co-infections the IRD was 0.575 [95% CI: 0.244–1.355; I2 = 91.9%] compared to 0.043 [95% CI: 0.020–0.090; I2 = 62.5%] in 160 arms which excluded HIV co-infections. Conclusion Mortality within the first 30 days of VL treatment initiation was a rarely reported event in clinical trials with an overall estimated rate of 0.068 deaths per 1,000 person-days at risk, though it varied across regions and patient populations. These estimates may serve as a benchmark for future trials against which mortality data from prospective and pharmacovigilance studies can be compared. The methodological limitations exposed by our review support the need to assemble individual patient data (IPD) to conduct robust IPD meta-analyses and generate stronger evidence from existing trials to support treatment guidelines and guide future research.

The Issues and Prospects for E-Governance in Eastern Africa

2015 ◽  
pp. 130-142
Author(s):  
Wilson Okaka
Keyword(s):  
Primary Education ◽  
Poor Quality ◽  
Instructional Materials ◽  
Eastern Africa ◽  
Current Status ◽  
Universal Primary Education ◽  
Published Evidence ◽  
Education Service ◽  
Key Issues ◽  
Digital Gap

This chapter discusses the issues, prospects, and challenges of e-governance in Africa with a focus on the progress of universal primary education in east Africa. It uses Uganda to showcase the need for e-governance of primary school education. The objectives are to describe the current status of the universal primary education, the key issues encountered in an effort to achieve MDG 2, and highlight the prospects of e-governance in achieving education. In this chapter, the authors collate published evidence on the performance of Uganda in implementing the MDG 2. There is a wide rural-urban digital gap, weak ICT infrastructures, and low awareness at the expense of quality UPE. There is limited access to ICT, ICT illiteracy, poor quality education, lack of e-books or ICT instructional materials to cut the costs of school administration like communication. E-governance has yet to achieve full deployment in education service delivery.

scholarly journals Developments in Diagnosis of Visceral Leishmaniasis in the Elimination Era

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Om Prakash Singh ◽  
Shyam Sundar
Keyword(s):  
Visceral Leishmaniasis ◽  
Parasitic Infection ◽  
Clinical Manifestations ◽  
Cost Effective ◽  
Current Status ◽  
Effective Control ◽  
Diagnostic Tools ◽  
High Morbidity ◽  
Symptomatic Disease ◽  
Primary Health Care Centers

Visceral leishmaniasis (VL) is the most devastating parasitic infection worldwide causing high morbidity and mortality. Clinical presentation of VL ranges from asymptomatic or subclinical infection to severe and complicated symptomatic disease. A major challenge in the clinical management of VL is the weakness of health systems in disease endemic regions. People affected by VL mostly present to primary health care centers (PHCs), often late in their therapeutic itinerary. PHC physicians face a major challenge: they do not deal with a single disease issue but with patients presenting with complaints pointing to several diagnostic possibilities. Risk exists when some patients having less clinical manifestations are misdiagnosed. Therefore, field based accurate, sensitive, and cost effective rapid diagnostic tools that can detect disease in its mildest form are essential for effective control and reaching the goal of VL elimination. In this review, we discuss the current status and challenges of various diagnostic tools for the diagnosis of VL and assess their application in resource poor settings.

scholarly journals Blood parasite load as an early marker to predict treatment response in visceral leishmaniasis in Eastern Africa

2021 ◽  
Author(s):  
Luka Verrest ◽  
Anke E Kip ◽  
Ahmed Musa ◽  
Gerard J Schoone ◽  
Henk D F H Schallig ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Visceral Leishmaniasis ◽  
Treatment Response ◽  
Oral Treatment ◽  
Parasite Load ◽  
Blood Parasite ◽  
Eastern Africa ◽  
Clinical Relapse ◽  
Treatment Regimens ◽  
Clinical Trial Simulations

Abstract Background In order to expedite the development of new oral treatment regimens for visceral leishmaniasis (VL), there is a need for early markers to evaluate treatment response and predict long-term outcomes. Methods Data from three clinical trials were combined in this study, where Eastern African VL patients received various antileishmanial therapies. Leishmania kinetoplast DNA was quantified in whole blood with real-time quantitative PCR (qPCR) before, during and up to six months after treatment. The predictive performance of pharmacodynamic parameters for clinical relapse was evaluated using receiver-operating characteristic curves. Clinical trial simulations were performed to determine the power associated with the use of blood parasite load as a surrogate endpoint to predict clinical outcome at six months. Results The absolute parasite density on day 56 after start of treatment was found to be a highly sensitive predictor of relapse within six months of follow-up at a cut-off of 20 parasites/mL (AUC 0.92, specificity 0.91, sensitivity 0.89). Blood parasite loads correlated well with tissue parasite loads (ρ= 0.80) and with microscopy gradings of bone marrow and spleen aspirate smears. Clinical trial simulations indicated a >80% power to detect a difference in cure rate between treatment regimens if this difference was high (>50%) and when minimally 30 patients were included per regimen. Conclusion Blood Leishmania parasite load determined by qPCR is a promising early biomarker to predict relapse in VL patients. Once optimized, it might be useful in dose finding studies of new chemical entities.

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