Blood Parasite Load as an Early Marker to Predict Treatment Response in Visceral Leishmaniasis in Eastern Africa

Background: 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 3 clinical trials were combined in this study, in which Eastern African VL patients received various antileishmanial therapies. Leishmania kinetoplast DNA was quantified in whole blood with real-time quantitative polymerase chain reaction (qPCR) before, during, and up to 6 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 6 months. Results: The absolute parasite density on day 56 after start of treatment was found to be a highly sensitive predictor of relapse within 6 months of follow-up at a cutoff of 20 parasites/mL (area under the curve 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. Conclusions: 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.This work was supported by the European Union Seventh Framework Programme Africoleish (grant number 305178); the World Health Organization—Special Programme for Research and Training in Tropical Diseases (WHO-TDR); the French Development Agency, France (grant number CZZ2062); UK aid, UK; the Federal Ministry of Education and Research through KfW, Germany; the Medicor Foundation, Liechtenstein; Médecins Sans Frontières, International; the Swiss Agency for Development and Cooperation (SDC), Switzerland (grant number 81017718); the Dutch Ministry of Foreign Affairs (DGIS), the Netherlands (grant number PDP15CH21); the French Ministry for Europe and Foreign Affairs (MEAE), France; The Rockefeller Foundation, USA; BBVA Foundation, Spain; the European Union—AfriKADIA project of the Second European and Developing Countries Clinical Trials Partnership Programme (EDCTP2) (grant number RIA2016S1635); and ZonMw/Dutch Research Council (NWO) Veni grant (project number 91617140 to T. P. C. D.).S

Validation of Two Rapid Diagnostic Tests for Visceral Leishmaniasis in Kenya

BACKGROUND: Visceral leishmaniasis (VL) is a systemic parasitic disease that is fatal unless treated. In Kenya, national VL guidelines rely on microscopic examination of spleen aspirate to confirm diagnosis. As this procedure is invasive, it cannot be safely implemented in peripheral health structures, where non-invasive, accurate, easy to use diagnostic tests are needed. METHODOLOGY: We evaluated the sensitivity, specificity and predictive values of two rapid diagnostic tests (RDT), DiaMed IT LEISH and Signal-KA, among consecutive patients with clinical suspicion of VL in two treatment centres located in Baringo and North Pokot District, Rift Valley province, Kenya. Microscopic examination of spleen aspirate was the reference diagnostic standard. Patients were prospectively recruited between May 2010 and July 2011. PRINCIPAL FINDINGS: Of 251 eligible patients, 219 patients were analyzed, including 131 VL and 88 non-VL patients. The median age of VL patients was 16 years with predominance of males (66%). None of the tested VL patients were co-infected with HIV. Sensitivity and specificity of the DiaMed IT LEISH were 89.3% (95%CI: 82.7-94%) and 89.8% (95%CI: 81.5-95.2%), respectively. The Signal KA showed trends towards lower sensitivity (77.1%; 95%CI: 68.9-84%) and higher specificity (95.5%; 95%CI: 88.7-98.7%). Combining the tests did not improve the overall diagnostic performance, as all patients with a positive Signal KA were also positive with the DiaMed IT LEISH. CONCLUSION/SIGNIFICANCE: The DiaMed IT LEISH can be used to diagnose VL in Kenyan peripheral health facilities where microscopic examination of spleen aspirate or sophisticated serological techniques are not feasible. There is a crucial need for an improved RDT for VL diagnosis in East Africa

Sodium Stibogluconate (SSG) & Paromomycin Combination Compared to SSG for Visceral Leishmaniasis in East Africa: A Randomised Controlled Trial

Visceral leishmaniasis (VL) is a parasitic disease with about 500,000 new cases each year and is fatal if untreated. The current standard therapy involves long courses, has toxicity and there is evidence of increasing resistance. New and better treatment options are urgently needed. Recently, the antibiotic paromomycin (PM) was tested and registered in India to treat this disease, but the same dose of PM monotherapy evaluated and registered in India was not efficacious in Sudan. This article reports the results of a clinical trial to test the effectiveness of injectable PM either alone (in a higher dose) or in combination with sodium stibogluconate (SSG) against the standard SSG monotherapy treatment in four East African countries—Sudan, Kenya, Ethiopia and Uganda. The study showed that the combination of SSG &PM was as efficacious and safe as the standard SSG treatment, with the advantages of being cheaper and requiring only 17 days rather than 30 days of treatment. In March 2010, a WHO Expert Committee recommended the use of the SSG & PM combination as a first line treatment for VL in East Africa

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

Association of Substance Use and Gender Based Violence among Students in a Tertiary Institution in Kakamega County, Kenya

Background: Substance use among college and university students remains an important area of research due to the implications of early substance dependence on the future of the youth. Prior studies from various settings indicate relatively high rates of substance use among students in tertiary educational institutions. However most of these studies were based on tertiary institutions in urban settings, and few have examined substance use and its association with Gender based violence. Objective: Study aim was to establish the prevalence and factors associated with substance abuse among students, and their relationship with Gender Based Violence in a tertiary institution in a relatively rural setting. Methods: The study was conducted in November 2018 after obtaining the relevant approval from KEMRI and from the university administration. Quantitative and qualitative methods were used to collect the data. Quantitative data was collected using self-reported questionnaires across all the faculties among first to fourth year students. Focus group discussions were held with a group of students and Key informant interviews were also held with the institutional administrators and student leaders. Results: A total of 412 university students completed the questionnaires. Majority were males at 57.9% and average age was 21 years. The overall prevalence of substance use was 21.1% and the most commonly used substance was alcohol at 25%. The study found out that 90% of the participants had their first time use of substances between ages of 12-20 years with median age of 18 years

Response of coral assemblages to the interaction between natural temperature variation and rare warm-water events in Kenyan reef lagoons

We examined changes in coral assemblages in four back-reef locations across the warm 1998 E1 Niño–Southern Oscillation (ENSO) event based on annually collected line-transect data from 3 years before and after this event. The physical locations of the reefs differed such that there was a 120%–275% warm-season range in the SDs of seawater temperatures but only minor differences in mean temperatures, based on 2 non-ENSO years. We tested the predictions that (a) rare warm-water events would produce fewer changes in eurythermal than stenothermal coral assemblages; and (b) after the disturbance, the stenothermal assemblages would more closely resemble the eurythermal ones. The 1998 event produced fewer changes in coral cover and community similarity among the assemblages in the reefs with high variation in temperature than in those with low variation in temperature. Despite the initially lower taxonomic richness in the eurythermal assemblage, there was an additional loss of taxonomic richness in the high and none in the stenothermal reefs. There was some evidence for taxonomic convergence, of the stenothermal towards the eurythermal reefs and a general loss of some of the branching taxa, such as branching Porites, Pavona, and Stylophora, and a relative increase in massive Porites and Favia. There was, however, moderate site specificity that did not produce true convergence. The eurythermal assemblages maintained the basic community structure but lost taxonomic richness, whereas the opposite was true for the stenothermal assemblages

Evaluation of Effectiveness of Diethylcarbamazine/Albendazole Combination in Reduction of Wuchereria Bancrofti Infection using Multiple Infection Parameters

Article JournalTo evaluate the effect of multiple rounds of annual single dose of DEC (6 mg/kg) or albendazole (400 mg) given alone or in combination on Wuchereria bancrofti microfilaraemia, anti-filarial IgG1 and IgG4 and antigenaemia. A total of 170 participants were randomly assigned to albendazole (n = 62), DEC (n = 54), and DEC plus albendazole (DEC/ALB) combination (n = 54). Blood samples were collected at pre-treatment in 1998, at 1 week and 6 months after the first treatment and thereafter before subsequent treatments in 1999 and 2000. Effects of treatment on W. bancrofti infection were determined by changes in levels of microfilaraemia, antifilarial antibodies and circulating filarial antigen. Comparison of geometric mean microfilariae intensities between DEC/ALB combination and DEC or albendazole single therapy groups after two rounds of annual treatment and 24 months follow-up showed that combination therapy resulted in a greater reduction of microfilaraemia than single therapy with either albendazole (p < 0.001) or DEC alone (p = 0.146). The overall levels of anti-filarial antibodies decreased significantly (p = 0.028 for IgG1 and p < 0.043 for IgG4) in all treatment groups at 24 months follow-up. Additionally, overall reduction in geometric mean circulating filarial antigen levels at 24 months was 44%, 60% and 85% for albendazole, DEC and DEC/ALB groups, respectively.These study findings suggest that albendazole improved efficacy of DEC and mass administration of a combination of the two drugs would therefore enhance the interruption of transmission of W. bancrofti in endemic areas. This information has important implications for the ongoing Global Program for Elimination of Lymphatic Filariasis