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...

word count:233 Main text word count: 3148 2 AbstractBackground: Limited health literacy (HL) may lead to poor health outcomes and inappropriate

Background: The CD103 integrin is present on CD4+ lymphocytes of the bronchial mucosa, but not on peripheral blood CD4+ lymphocytes. It has been hypothesized that CD4+ lymphocytes in pulmonary sarcoidosis originate from redistribution from the peripheral blood to the lung, and therefore do not bear the CD103 integrin. Some data suggest that a low CD103+ percentage among bronchoalveolar lavage fluid (BALF) CD4+ lymphocytes discriminates between sarcoidosis and other diagnoses. Objective: To determine the diagnostic value of BALF CD103+ to identify sarcoidosis among other causes of alveolar lymphocytosis in a large retrospective case series. Methods: Among 391 consecutive bronchoalveolar lavages performed at our institution and analyzed by flow cytometry, we identified 207 cases, which were grouped into nine diagnostic categories: sarcoidosis, tuberculosis, non-tuberculous infections, hypersensitivity pneumonitis, non-specific interstitial pneumonia, organizing pneumonia, drug-induced lung diseases, other interstitial lung diseases (ILDs), and other diagnoses. To assess the discriminative value of the CD103+CD4+/CD4+ ratio to distinguish sarcoidosis from other entities, areas under ROC curves (AUC) were calculated. Results: Sarcoidosis patients (n = 53) had significantly lower CD103+CD4+/CD4+ ratios than patients in other diagnostic categories. The AUC was 62% for sarcoidosis compared to all other diagnoses, and 69% for sarcoidosis compared to other ILDs. When combining CD103+CD4+/CD4+ and CD4+/CD8+ ratios, the AUC increased to 76 and 78%, respectively. When applying previously published cut-offs to our population, the AUC varied between 54 and 73%. Conclusions: The CD103+CD4+/CD4+ ratio does not accurately discriminate between sarcoidosis and other causes of lymphocytic alveolitis, neither alone nor in combination with the CD4+/CD8+ ratio, and is not a powerful marker for the diagnosis of sarcoidosis.

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