Risk factors of visceral leishmaniasis in East Africa: a case-control study in Pokot territory of Kenya and Uganda

BACKGROUND: In East Africa, visceral leishmaniasis (VL) is endemic in parts of Sudan, Ethiopia, Somalia, Kenya and Uganda. It is caused by Leishmania donovani and transmitted by the sandfly vector Phlebotomus martini. In the Pokot focus, reaching from western Kenya into eastern Uganda, formulation of a prevention strategy has been hindered by the lack of knowledge on VL risk factors as well as by lack of support from health sector donors. The present study was conducted to establish the necessary evidence-base and to stimulate interest in supporting the control of this neglected tropical disease in Uganda and Kenya. METHODS: A case-control study was carried out from June to December 2006. Cases were recruited at Amudat hospital, Nakapiripirit district, Uganda, after clinical and parasitological confirmation of symptomatic VL infection. Controls were individuals that tested negative using a rK39 antigen-based dipstick, which were recruited at random from the same communities as the cases. Data were analysed using conditional logistic regression. RESULTS: Ninety-three cases and 226 controls were recruited into the study. Multivariate analysis identified low socio-economic status and treating livestock with insecticide as risk factors for VL. Sleeping near animals, owning a mosquito net and knowing about VL symptoms were associated with a reduced risk of VL. CONCLUSIONS: VL affects the poorest of the poor of the Pokot tribe. Distribution of insecticide-treated mosquito nets combined with dissemination of culturally appropriate behaviour-change education is likely to be an effective prevention strategy

Geographical Variation in the Response of Visceral Leishmaniasis to Paromomycin in East Africa: A Multicentre, Open-Label, Randomized Trial

Visceral leishmaniasis (VL) is a fatal parasitic disease with 500,000 new cases each year according to WHO estimates. New and better treatment options are urgently needed in disease endemic areas due to the long courses, toxicity and development of resistance to current treatments. Recently, the antibiotic paromomycin was tested and registered in India to treat this disease. The current study describes a clinical trial to test the effectiveness of injectable paromomycin, either alone or in combination with the standard drug sodium stibogluconate in three East African countries—Sudan, Kenya and Ethiopia. The study showed that at the same paromomycin dose that was successfully used and registered in India, a far poorer outcome was obtained, particularly in Sudan, suggesting that there are either differences in the patients ability to respond to the drug or in the susceptibility of parasites in East Africa compared with those in India. However, no major safety concerns were noted with the treatment. Further research was initiated to see if a higher dose of paromomycin would perform better, especially in Sudan. The results of this and the performance of the combination arm will be reported later. Our study highlights the importance of considering geographical differences to treatment responses

Safety and efficacy of single dose versus multiple doses of AmBisome for treatment of visceral leishmaniasis in eastern Africa: a randomised trial.

BACKGROUND: Anti-leishmanial drug regimens that include a single dose AmBisome could be suitable for eastern African patients with symptomatic visceral leishmaniasis (VL) but the appropriate single dose is unknown. METHODOLOGY: A multi-centre, open-label, non-inferiority, randomized controlled trial with an adaptive design, was conducted to compare the efficacy and safety of a single dose and multiple doses of AmBisome for the treatment of VL in eastern Africa. The primary efficacy endpoint was definitive cure (DC) at 6 months. Symptomatic patients with parasitologically-confirmed, non-severe VL, received a single dose of AmBisome 7.5 mg/kg body weight or multiple doses, 7 times 3 mg/kg on days 1-5, 14, and 21. If interim analyses, evaluated 30 days after the start of treatment following 40 or 80 patients, showed the single dose gave significantly poorer parasite clearance than multiple doses at the 5% significance level, the single dose was increased by 2·5 mg/kg. In a sub-set of patients, parasite clearance was measured by quantitative reverse transcriptase (qRT) PCR. PRINCIPAL FINDINGS: The trial was terminated after the third interim analysis because of low efficacy of both regimens. Based on the intention-to-treat population, DC was 85% (95%CI 73-93%), 40% (95%CI 19-64%), and 58% (95%CI 41-73%) in patients treated with multiple doses (n = 63), and single doses of 7·5 (n = 21) or 10 mg/kg (n = 40), respectively. qRT-PCR suggested superior parasite clearance with multiple doses as early as day 3. Safety data accorded with the drug label. CONCLUSIONS: The tested AmBisome regimens would not be suitable for VL treatment across eastern Africa. An optimal single dose regimen was not identified. TRIALS REGISTRATION: www.clinicaltrials.govNCT00832208

Who Is a Typical Patient with Visceral Leishmaniasis? Characterizing the Demographic and Nutritional Profile of Patients in Brazil, East Africa, and South Asia

Drug-dosing recommendations for visceral leishmaniasis (VL) treatment are based on the patients' weight or age. A current lack of demographic and anthropometric data on patients hinders (1) the ability of health providers to properly prepare for patient management, (2) an informed drug procurement for disease control, and (3) the design of clinical trials and development of new drug therapies in the different endemic areas. We present information about the age, gender, weight, and height of 29,570 consecutive VL patients presenting to 20 locations in six geographic endemic regions of Brazil, East Africa, Nepal, and India between 1997 and 2009. Our compilation shows substantial heterogeneity in the types of patients seeking care for VL at the clinics within the different locations. This suggests that drug development, procurement, and perhaps even treatment protocols, such as the use of the potentially teratogenic drug miltefosine, may require distinct strategies in these geographic settings

Teaching cardiac electrophysiology modeling to undergraduate students: laboratory exercises and GPU programming for the study of arrhythmias and spiral wave dynamics

abstract: As part of a 3-wk intersession workshop funded by a National Science Foundation Expeditions in Computing award, 15 undergraduate students from the City University of New York(1) collaborated on a study aimed at characterizing the voltage dynamics and arrhythmogenic behavior of cardiac cells for a broad range of physiologically relevant conditions using an in silico model. The primary goal of the workshop was to cultivate student interest in computational modeling and analysis of complex systems by introducing them through lectures and laboratory activities to current research in cardiac modeling and by engaging them in a hands-on research experience. The success of the workshop lay in the exposure of the students to active researchers and experts in their fields, the use of hands-on activities to communicate important concepts, active engagement of the students in research, and explanations of the significance of results as the students generated them. The workshop content addressed how spiral waves of electrical activity are initiated in the heart and how different parameter values affect the dynamics of these reentrant waves. Spiral waves are clinically associated with tachycardia, when the waves remain stable, and with fibrillation, when the waves exhibit breakup. All in silico experiments were conducted by simulating a mathematical model of cardiac cells on graphics processing units instead of the standard central processing units of desktop computers. This approach decreased the run time for each simulation to almost real time, thereby allowing the students to quickly analyze and characterize the simulated arrhythmias. Results from these simulations, as well as some of the background and methodology taught during the workshop, is presented in this article along with the programming code and the explanations of simulation results in an effort to allow other teachers and students to perform their own demonstrations, simulations, and studies