SummaryBackgroundrVSV-ZEBOV is a recombinant, replication competent vesicular stomatitis virus-based candidate vaccine expressing a surface glycoprotein of Zaire Ebolavirus. We tested the effect of rVSV-ZEBOV in preventing Ebola virus disease in contacts and contacts of contacts of recently confirmed cases in Guinea, west Africa.MethodsWe did an open-label, cluster-randomised ring vaccination trial (Ebola ça Suffit!) in the communities of Conakry and eight surrounding prefectures in the Basse-Guinée region of Guinea, and in Tomkolili and Bombali in Sierra Leone. We assessed the efficacy of a single intramuscular dose of rVSV-ZEBOV (2×107 plaque-forming units administered in the deltoid muscle) in the prevention of laboratory confirmed Ebola virus disease. After confirmation of a case of Ebola virus disease, we definitively enumerated on a list a ring (cluster) of all their contacts and contacts of contacts including named contacts and contacts of contacts who were absent at the time of the trial team visit. The list was archived, then we randomly assigned clusters (1:1) to either immediate vaccination or delayed vaccination (21 days later) of all eligible individuals (eg, those aged ≥18 years and not pregnant, breastfeeding, or severely ill). An independent statistician generated the assignment sequence using block randomisation with randomly varying blocks, stratified by location (urban vs rural) and size of rings (≤20 individuals vs >20 individuals). Ebola response teams and laboratory workers were unaware of assignments. After a recommendation by an independent data and safety monitoring board, randomisation was stopped and immediate vaccination was also offered to children aged 6–17 years and all identified rings. The prespecified primary outcome was a laboratory confirmed case of Ebola virus disease with onset 10 days or more from randomisation. The primary analysis compared the incidence of Ebola virus disease in eligible and vaccinated individuals assigned to immediate vaccination versus eligible contacts and contacts of contacts assigned to delayed vaccination. This trial is registered with the Pan African Clinical Trials Registry, number PACTR201503001057193.FindingsIn the randomised part of the trial we identified 4539 contacts and contacts of contacts in 51 clusters randomly assigned to immediate vaccination (of whom 3232 were eligible, 2151 consented, and 2119 were immediately vaccinated) and 4557 contacts and contacts of contacts in 47 clusters randomly assigned to delayed vaccination (of whom 3096 were eligible, 2539 consented, and 2041 were vaccinated 21 days after randomisation). No cases of Ebola virus disease occurred 10 days or more after randomisation among randomly assigned contacts and contacts of contacts vaccinated in immediate clusters versus 16 cases (7 clusters affected) among all eligible individuals in delayed clusters. Vaccine efficacy was 100% (95% CI 68·9–100·0, p=0·0045), and the calculated intraclass correlation coefficient was 0·035. Additionally, we defined 19 non-randomised cl...

In recent years, there have been several calls for rigorous health policy and systems research to inform efforts to strengthen health systems (HS) in low- and middle-income countries (LMICs), including the use of systems thinking concepts in designing and evaluating HS strengthening interventions. The objectives of this paper are to assess recent evaluations of HS strengthening interventions to examine the extent to which they ask a broader set of questions, and provide an appropriately comprehensive assessment of the effects of these interventions across the health system. A review of evaluations conducted in 2009-10 was performed to answer these questions. Out of 106 evaluations, less than half (43%) asked broad research questions to allow for a comprehensive assessment of the intervention's effects across multiple HS building blocks. Only half of the evaluations referred to a conceptual framework to guide their impact assessment. Overall, 24% and 9% conducted process and context evaluations, respectively, to answer the question of whether the intervention worked as intended, and if so, for whom, and under what circumstances. Almost half of the evaluations considered HS impact on one building block, while most interventions were complex targeting two or more building blocks. None incorporated evaluation designs that took into account the characteristics of complex adaptive systems such as non-linearity of effects or interactions between the HS building blocks. While we do not argue that all evaluations should be comprehensive, there is a need for more comprehensive evaluations of the wider range of the intervention's effects, when appropriate. Our findings suggest that the full range of barriers to more comprehensive evaluations need to be examined and, where appropriate, addressed. Possible barriers may include limited capacity, lack of funding, inadequate time frames, lack of demand from both researchers and research funders, or difficulties in undertaking this type of evaluation.