A double-masked placebo-controlled trial of azithromycin to prevent child mortality in Burkina Faso, West Africa: Community Health with Azithromycin Trial (CHAT) study protocol.

BACKGROUND:Biannual, mass azithromycin distribution has previously been shown to reduce all-cause child mortality in sub-Saharan Africa. Subgroup analysis suggested that the strongest effects were in the youngest children, leading to the hypothesis that targeting younger age groups might be an effective strategy to prevent mortality. We present the methods of two randomized controlled trials designed to evaluate mass and targeted azithromycin distribution for the prevention of child mortality in Burkina Faso, West Africa. METHODS/DESIGN:The Child Health with Azithromycin Treatment (CHAT) study consists of two nested, randomized controlled trials. In the first, communities are randomized in a 1:1 fashion to biannual, mass azithromycin distribution or placebo. The primary outcome is under-5 all-cause mortality measured at the community level. In the second, children attending primary healthcare facilities during the first 5-12 weeks of life for a healthy child visit (e.g., for vaccination) are randomized in a 1:1 fashion to a single orally administered dose of azithromycin or placebo. The primary outcome is all-cause mortality measured at 6 months of age. The trial commenced enrollment in August 2019. DISCUSSION:This study is expected to provide evidence on two health systems delivery approaches (mass and targeted treatment) for azithromycin to prevent all-cause child mortality. The results will inform global and national policies related to azithromycin for the prevention of child mortality. TRIAL REGISTRATION:ClinicalTrials.gov, ID: NCT03676764. Registered on 19 September 2018; prospectively registered pre results

A four-month gatifloxacin-containing regimen for treating tuberculosis.

BACKGROUND: Shortening the course of treatment for tuberculosis would be a major improvement for case management and disease control. This phase 3 trial assessed the efficacy and safety of a 4-month gatifloxacin-containing regimen for treating rifampin-sensitive pulmonary tuberculosis. METHODS: We conducted a noninferiority, randomized, open-label, controlled trial involving patients 18 to 65 years of age with smear-positive, rifampin-sensitive, newly diagnosed pulmonary tuberculosis in five sub-Saharan African countries. A standard 6-month regimen that included ethambutol during the 2-month intensive phase was compared with a 4-month regimen in which gatifloxacin (400 mg per day) was substituted for ethambutol during the intensive phase and was continued, along with rifampin and isoniazid, during the continuation phase. The primary efficacy end point was an unfavorable outcome (treatment failure, recurrence, or death or study dropout during treatment) measured 24 months after the end of treatment, with a noninferiority margin of 6 percentage points, adjusted for country. RESULTS: A total of 1836 patients were assigned to the 4-month regimen (experimental group) or the standard regimen (control group). Baseline characteristics were well balanced between the groups. At 24 months after the end of treatment, the adjusted difference in the risk of an unfavorable outcome (experimental group [21.0%] minus control group [17.2%]) in the modified intention-to-treat population (1356 patients) was 3.5 percentage points (95% confidence interval, -0.7 to 7.7). There was heterogeneity across countries (P=0.02 for interaction, with differences in the rate of an unfavorable outcome ranging from -5.4 percentage points in Guinea to 12.3 percentage points in Senegal) and in baseline cavitary status (P=0.04 for interaction) and body-mass index (P=0.10 for interaction). The standard regimen, as compared with the 4-month regimen, was associated with a higher dropout rate during treatment (5.0% vs. 2.7%) and more treatment failures (2.4% vs. 1.7%) but fewer recurrences (7.1% vs. 14.6%). There was no evidence of increased risks of prolongation of the QT interval or dysglycemia with the 4-month regimen. CONCLUSIONS: Noninferiority of the 4-month regimen to the standard regimen with respect to the primary efficacy end point was not shown. (Funded by the Special Program for Research and Training in Tropical Diseases and others; ClinicalTrials.gov number, NCT00216385.)

Short-term forecasting of the prevalence of clinical trachoma: utility of including delayed recovery and tests for infection.

BACKGROUND: The World Health Organization aims to control blinding trachoma by 2020. Decisions on whether to start and stop mass treatments and when to declare that control has been achieved are currently based on clinical examination data generated in population-based surveys. Thresholds are based on the district-level prevalence of trachomatous inflammation-follicular (TF) in children aged 1-9 years. Forecasts of which districts may and may not meet TF control goals by the 2020 target date could affect resource allocation in the next few years. METHODS: We constructed a hidden Markov model fit to the prevalence of two clinical signs of trachoma and PCR data in 24 communities from the recent PRET-Niger trial. The prevalence of TF in children in each community at 36 months was forecast given data from earlier time points. Forecasts were scored by the likelihood of the observed results. We assessed whether use of TF with additional TI and PCR data rather than just the use of TF alone improves forecasts, and separately whether incorporating a delay in TF recovery is beneficial. RESULTS: Including TI and PCR data did not significantly improve forecasts of TF. Forecasts of TF prevalence at 36 months by the model with the delay in TF recovery were significantly better than forecasts by the model without the delay in TF recovery (p = 0.003). A zero-inflated truncated normal observation model was better than a truncated normal observation model, and better than a sensitivity-specificity observation model. CONCLUSION: The results in this study suggest that future studies could consider using just TF data for forecasting, and should include a delay in TF recovery. TRIAL REGISTRATION: Clinicaltrials.gov NCT00792922

Uncertain pasts and risk-sensitive futures in sub-Saharan urban transformation

This chapter explores the status and the scope for transition of risk- sensitive and transformative urban development in diverse cities of sub-Saharan Africa. Sub-Saharan Africa is important because of its large proportions of urban populations with high vulnerability and growing exposure to risks. High rates of urban growth pose increasing risks as we go into the future, yet there is also opportunity to reduce risk through integrating risk management into development. However, this opportunity space is often constrained by limited capacities to plan and manage the rapid urbanisation process, particularly in informal settlements. Limited capacities to prevent processes of risk accumulation pose threats to poverty reduction and sustainable development. In this context, there is an increasingly urgent need for squarely recognising and addressing the underlying vulnerabilities of urban populations and their root causes. Transitioning towards such sustainable urban pathways will require the strengthening of capacities and accountability of city authorities and broader governance systems, both formal and informal

Impairment in Activities of Daily Living and unmet need for care among older adults: A population-based study from Burkina Faso

OBJECTIVES: The importance of impairment in performing Activities of Daily Living (ADL) is likely to increase in sub-Saharan Africa since few care options for affected people exist. This study investigated the prevalence of ADL impairment, the extent to which care-need was met and described characteristics of people with ADL impairment and unmet need in Burkina Faso. METHODS: This study used data from the CRSN Heidelberg Aging Study, a population-based study among 3,026 adults aged over 40 years conducted in rural Burkina Faso. Information on six basic ADL items was sought, with a follow-up question asking whether care-needs were not met, partially met or met. Bivariable correlations and multivariable logistic regression were used to determine sociodemographic and health characteristics associated with ADL impairment and unmet need. RESULTS: ADL impairment of any kind was reported by 1,202 (39.7%) respondents and was associated with older age (Adjusted Odds Ratio: 1.05 [95% CI: 1.04-1.06]), being a woman (1.33 [1.06-1.60]) and reporting depressive symptoms (1.90 [1.65-2.18]). Among those with ADL impairment, 67.8% had at least one unmet need. Severe ADL impairment was found in 202 (6.7%) respondents, who reported lower prevalence of unmet need (43.1%). Severe ADL impairment was associated with depressive symptoms (2.55 [2.11-3.07]) to a stronger degree than any ADL impairment. DISCUSSION: Prevalence of ADL impairment and unmet need was high in this setting. Variation in impairment across the population highlighted key groups for future interventions. Unmet need for care was highest in middle-aged adults, indicating a gap in care provision

A Cluster-Randomized Trial to Assess the Efficacy of Targeting Trachoma Treatment to Children.

Background: The World Health Organization recommends annual treatment of entire trachoma-endemic communities, although children typically have a higher load, longer duration, and greater likelihood of infection. Methods: Forty-eight communities in Matameye, Niger, were randomized to annual oral azithromycin treatment of the entire community or biannual treatment of children aged 0-12 years only. Both children and adults were monitored for ocular chlamydial infection by polymerase chain reaction. Results: The prevalence of childhood infection was reduced in the annually treated arm from 21.2% (95% confidence interval [CI], 15.2%-28.0%) at baseline to 5.8% (95% CI, 3.2%-9.0%) at 36 months (P < .001) and in the biannual arm from 20.2% (95% CI, 15.5%-25.3%) to 3.8% (95% CI, 2.2%-6.0%; P < .001). Adult infection in the annual arm was reduced from 1.7% (95% CI, .9%-2.7%) to 0.3% (95% CI, .0%-.7%) and in the biannual arm from 1.2% (95% CI, .5%-2.2%) to 0.0% (95% CI, .0%-.7%; P = .005). The effect of biannual treatment of children compared with annual treatment of the entire community in both children (95% CI, -.04% to .02%) and adults (95% CI, .9%-2.7%) excluded the prespecified noninferiority threshold of 6% (P = .003 and P < .001, respectively). Conclusions: Periodic distribution of antibiotics to children in trachoma-endemic communities reduces chlamydial infection in both children and untreated adults, suggesting a form of herd protection. Biannual treatment of children was comparable to (specifically, noninferior to) annual treatment of the entire community, and may offer lower antibiotic use and other logistical advantages. Clinical Trials Registration: NCT00792922