Trends in prevalence of multi drug resistant tuberculosis in sub-Saharan Africa: A systematic review and meta-analysis.

Multidrug resistant tuberculosis (MDR-TB), is an emerging public health problem in sub-Saharan Africa (SSA). This study aims to determine the trends in prevalence of MDR-TB among new TB cases in sub-Saharan Africa over two decades.We searched electronic data bases and accessed all prevalence studies of MDR-TB within SSA between 2007 and 2017. We determined pooled prevalence estimates using random effects models and determined trends using meta-regression.Results: We identified 915 studies satisfying inclusion criteria. Cumulatively, studies reported on MDR-TB culture of 34,652 persons. The pooled prevalence of MDR-TB in new cases was 2.1% (95% CI; 1.7-2.5%). There was a non-significant decline in prevalence by 0.12% per year.We found a low prevalence estimate of MDR-TB, and a slight temporal decline over the study period. There is a need for continuous MDR-TB surveillance among patients with TB

HIV-associated nephropathy: Protocol and rationale for an exploratory genotype-phenotype study in a sub-Saharan African population.

BackgroundHIV-positive persons of African descent are disproportionately affected by chronic kidney disease (CKD). Deterioration to end-stage kidney disease (ESKD) also occurs in this population at a higher frequency. There remains a lot to learn about the genetic susceptibility to CKD in HIV positive patients, and the pathophysiology of progression to ESKD.ObjectivesWe will conduct an exploratory genotype-phenotype study in HIV-positive persons with CKD in Aminu Kano Teaching Hospital, Nigeria, to determine blood-based differential gene expression biomarkers in different kidney risk groups according to the KDIGO 2012 criteria.MethodsWe will consecutively screen 150 HIV-positive adults (≥18 years of age) attending the HIV clinic of Aminu Kano Teaching Hospital, Kano, Nigeria, for CKD based on proteinuria and elevation of estimated glomerular filtration rate. Among these, two separate groups of 16 eligible participants each (n = 32) will be selected in the four (4) KDIGO 2012 kidney risk categories. The groups will be matched for age, sex, viral suppression level and antiretroviral (ARV) regimen. In the first group (n = 16), we will determine differential gene expression markers in peripheral blood mononuclear cells using mRNA-sequencing (RNA-Seq). We will validate the differential expression markers in the second group (n = 16) using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Using a systems-based approach, we will construct, visualize and analyze gene-gene interaction networks to determine the potential biological roles of identified differential expression markers based on published literature and publicly available databases.ResultsOur exploratory study will provide valuable information on the potential roles of differential expression biomarkers in the pathophysiology of HIV-associated kidney disease by identifying novel biomarkers in different risk categories of CKD in a sub-Saharan African population. The results of this study will provide the basis for population-based genome-wide association studies to guide future personalized medicine approaches.ConclusionValidated biomarkers can be potential targets for the development of stage-specific therapeutic interventions, an essential paradigm in precision medicine

Trim and filled funnel plot depicted study derived and data augmented prevalence of MDR-TB in new cases for SSA.

<p>Theta: the effect (prevalence) estimate, SE: standard error; diamond shapes represent study derived prevalence; diamond within square represent data augmented prevalence.</p

Meta-regression: Association between pooled prevalence of new MDR TB cases and study characteristics.

<p>Meta-regression: Association between pooled prevalence of new MDR TB cases and study characteristics.</p

PRISMA flow diagram showing study screening and selection procedure.

<p>PRISMA flow diagram showing study screening and selection procedure.</p

Meta-regression plot showing sub-Saharan African (S SA) trend in MDR-TB prevalence in new cases over two decades.

<p>P: MDR TB prevalence in new cases, circle size proportionate to size of studied population in each year.</p

Disaggregated prevalence of MDR-TB by study attributes and their measure of heterogeneity.

<p>Disaggregated prevalence of MDR-TB by study attributes and their measure of heterogeneity.</p

Acceptability and safety of hydroxyurea for primary prevention of stroke in children with sickle cell disease in Nigeria

Background: Nigeria has the highest prevalence of sickle cell disease (SCD), a common cause of pediatric ischemic stroke. In sub-Saharan Africa monthly blood transfusions for primary stroke prevention carries risks; hydroxyurea (HU) may be an alternative. We conducted the first, US NIH funded, SCD feasibility trial in sub-Saharan Africa (5R21NS080639-02) to: 1) assess the acceptability and willingness of families to participate in a HU trial; 2) develop a safety protocol for using HU in a trial setting in sub-Saharan Africa; and 3) prepare for a definitive phase III Trial. In the Sickle Cell Disease Stroke Prevention in Nigeria (SPIN) trial, our primary hypothesis in the internal feasibility trial is that 80% adherence for daily HU administration is feasible. Procedure: The internal pilot is a single site; single arm trial enrolling 40 children aged 5 to 12 years with hemoglobin SS or SB0 thalassemia at risk of developing stroke with a high transcranial Doppler (TCD) velocity in the middle cerebral artery (MCA) ≥ 200 cm/sec. Each participant is scheduled to receive low dose HU therapy (~20mg/kg/day) for 36 months. Acceptability was determined by the number of families who consented for screening. The adherence rate of HU was based on monthly parental assessment of the Morisky Medical Adherence Sore (MMAS) and monthly complete blood count (CBC) to monitor the serial change in mean corpuscular volume (MCV) from baseline level. Assessment of toxicity attributable to HU was based on comparing adverse events between the HU and control groups. Controls were identified as participants that met the criteria for the trial, but had TCD measurements &lt; 200 cm/sec. From Baby HUG, adverse events were defined as hospitalization for any cause, severe anemia and myelosuppression (severe neutropenia and thrombocytopenia based on monthly CBC). Results: A total of 269 participants were approached, of which 96% (23 of 24) and 86% (211 of 245) with an elevated or normal TCD measurement agreed to enroll in the HU therapy or control groups with a median age of 8 and 7.6 years, respectively. At the current milestone, 100% of the participants enrolled in the treatment arm demonstrated at least average to high monthly adherence rate (MMAS of 6-8 points). This adherence rate was consistent with an increase in MCV from baseline to 3 months after starting HU therapy with a minimum increase in MCV of at least 3 fl in 8 of 11 participants. One child on HU therapy was hospitalized for 5 days for hypovolemia and dehydration associated with cholera. The table below shows no excessive rate of adverse events when HU therapy and control groups are compared. Conclusion: These early results demonstrate the ability for a sub-Saharan African clinical research team to plan and initiate a complex SCD trial. Our preliminary data provide strong evidence for acceptability and potential safety of low dose HU therapy in Nigerian children with SCD. Completion of the internal pilot should provide sufficient evidence to pursue a phase III trial of low dose HU therapy to prevent strokes in children living in sub-Saharan Africa