Serotype Diversity of Respiratory Human Adenoviruses amongst Pediatric Patients from Western Kenya, 2010-2012

Background: Respiratory illnesses are common among pediatric patients in Kenya, and many are attributed to viral causes. However, there is limited knowledge of the diversity of viral etiologies associated with these illnesses. Objective: To characterize respiratory adenoviruses isolates using serological and molecular approaches. Methods: A total of 1,879 samples were collected from symptomatic pediatric patients seeking medical care at New Nyanza Provincial General Hospital during the period of June 2010 to June 2012 and screened for adenoviruses as well as other respiratory viruses. Sixteen respiratory human adenoviruses (HAdVs) were isolated in Hep2 cell culture and characterized them using Immunofluorescence Assay, viral DNA amplification, sequencing and phylogenomics. Results: Phylogenetic characterization of the HAdVs using the hyper variable region 7 of the hexon gene identified HAdV B and C as the major species associated with respiratory infections during the study period. Amongst these, a single B-type and four C-type serotypes were identified.  The serotype distribution consisted of 31% HAdV B7, 25% HAdV C1, 25% HAdV C2, 6% HAdV C5, and 13% HAdV C6. Positive selection was observed in the nucleotide sequences from HAdV B7 and HAdV C5 signaling evolution of these two serotypes. Conclusion: These finding may be useful to policy makers regarding appropriate strain selection for vaccination in Kenya. Keywords: Respiratory Human adenovirus, Kenya, Pediatric, Serotype, Hexon, HVR-

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

Development of electrochemical immunosensor for quantitative detection of non-small cell lung cancer (NSCLC) biomaker YES1

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer accounting for 85% of all newly diagnosed cases. Its prognosis remains poor as most patients are diagnosed at an advanced stage. In this study, we report the development of an electrochemical immunosensor for quantitative detection of Yamaguchi sarcoma viral oncogene homolog 1 (v-YES1) protein, comprised of a glassy carbon electrode modified with gold nanoparticles (AuNP), thiolated protein G (TPG), YES1 antibody (AB1) and glutaraldehyde (GA), which was used as a cross linker. Cyclic voltammetry (CV) and Differential pulse voltammetry (DPV) were used to measure the response and characterization of the fabricated immunosensor. The fabricated immunosensor, glassy carbon electrode (GCE)/AuNP/TPG/GA/Ab1) was optimized for pH, response time, antibody concentration and temperature. Under optimum conditions, the immunosensor displayed high sensitivity, recording a limit of detection (LOD) of 0.0014 ng/mL and was noted to have negligible cross reactivity. The proposed immunosensor proved to be stable for up to 2 weeks, which means that it can be used as an alternative diagnostic tool for the rapid, sensitive and specific detection of YES1 antigen in clinical samples for clinical monitoring of cancer progression

Prescription patterns and adequacy of blood pressure control among adult hypertensive patients in Kenya; findings and implications.

Hypertension is a major cause of global morbidity and mortality, with high prevalence rates in Africa including Kenya. Consequently, it is imperative to understand current treatment approaches and their effectiveness in practice. Currently, there is paucity of such data in Kenya, which is a concern. The aim is to describe prescribing patterns and adequacy of blood pressure (BP) control in adult hypertensive patients to guide future practice.Retrospective study of patients attending a sub-county outpatient clinic combined with qualitative interviews.247 hypertensive patients, predominantly female, mean age 55.8 years on antihypertensive therapy for 1-5 years, were analyzed. ACEIs and thiazide diuretics were the most commonly prescribed drugs, mainly as combination therapy. Treatment typically complied with guidelines, mainly for stage 2 hypertension (75%). BP control was observed in 46% of patients, with a significant reduction in mean systolic (155 to 144 mmHg) and diastolic (91 to 83 mmHg) BP (P < 0.001). Patients on ≥2 antihypertensive drugs were more likely to have uncontrolled BP (OR:1.9, p = 0.021).Encouragingly good adherence to guidelines was helped by training. Poor blood pressure control in the majority needs to be addressed. Additional training of prescribers and follow-up of measures to improve BP control will be introduced and followed up

VISCERAL LEISHMANIASIS WITH CONCOMITTANT POST KALA-AZAR DERMAL LEISHMANIASIS RESPONDS TO ORAL SITAMAQUINE: CASE REPORT

SUMMARYWe report a rare case of visceral leishmanisis with concomitant post kala-azar dermalleishmaniasis as the initial presentation in a female patient from Baringo district, Rift valleyprovince, Kenya

Diagnostic tests for kala-azar: a multi-centre study of the freeze-dried DAT, rK39 strip test and KAtex in East Africa and the Indian subcontinent.

Three diagnostic tests for visceral leishmaniasis (VL), the freeze-dried direct agglutination test (FD-DAT), the rK39 dipstick and a urine latex antigen test (KAtex), were evaluated for use in primary care in East Africa and the Indian subcontinent. Clinical suspects were prospectively recruited and tissue, blood and urine samples were taken. Direct microscopic examination of tissue smear, and FD-DAT, rK39 and KAtex were performed. Sensitivity and specificity with 95% credible intervals were estimated using Bayesian latent class analysis. On the Indian subcontinent both the FD-DAT and the rK39 strip test exceeded the 95% sensitivity and 90% specificity target, but not so in East Africa. Sensitivity of the FD-DAT was high in Ethiopia and Kenya but lower in Sudan, while its specificity was below 90% in Kenya. Sensitivity of the rK39 was below 80% in the three countries, and its specificity was only 70% in Ethiopia. KAtex showed moderate to very low sensitivity in all countries. FD-DAT and rK39 can be recommended for clinical practice on the Indian subcontinent. In East Africa, their clinical use should be carefully monitored. More work is needed to improve existing formats, and to develop better VL diagnostics