• Genomic History of the seventh Pandemic of Cholera in Africa

      Weill, FX; Domman, D; Njamkepo, E; Tarr, C; Rauzier, J; Fawal, N; Keddy, KH; Salje, H; Moore, S; Mukhopadhyay, AK; et al. (American Association for the Advancement of Science, 2017-11-10)
      The seventh cholera pandemic has heavily affected Africa, although the origin and continental spread of the disease remain undefined. We used genomic data from 1070 Vibrio cholerae O1 isolates, across 45 African countries and over a 49-year period, to show that past epidemics were attributable to a single expanded lineage. This lineage was introduced at least 11 times since 1970, into two main regions, West Africa and East/Southern Africa, causing epidemics that lasted up to 28 years. The last five introductions into Africa, all from Asia, involved multidrug-resistant sublineages that replaced antibiotic-susceptible sublineages after 2000. This phylogenetic framework describes the periodicity of lineage introduction and the stable routes of cholera spread, which should inform the rational design of control measures for cholera in Africa.
    • A meta-analysis of clinical studies conducted during the West Africa Ebola virus disease outbreak confirms the need for randomized control groups

      Dodd, L; Follman, D; Proschan, M; Wang, J; Malvy, D; Horby, P; Gouel-Cheron, A; Ciglenecki, I; Davey, R; Lane, C; et al. (American Association for the Advancement of Science, 2019-11-27)
      Recent Ebola virus disease outbreaks affirm the dire need for treatments with proven efficacy. Randomized controlled clinical trials remain the gold standard but, during disease outbreaks, may be difficult to conduct due to ethical concerns and challenging field conditions. In the absence of a randomized control group, statistical modeling to create a control group could be a possibility. Such a model-based reference control would only be credible if it had the same mortality risk as that of the experimental group in the absence of treatment. One way to test this counterfactual assumption is to evaluate whether reasonable similarity exists across nonrandomized control groups from different clinical studies, which might suggest that a future control group would be similarly homogeneous. We evaluated similarity across six clinical studies conducted during the 2013-2016 West Africa outbreak of Ebola virus disease. These studies evaluated favipiravir, the biologic ZMapp, the antimalarial drug amodiaquine, or administration of convalescent plasma or convalescent whole blood. We compared the nonrandomized control groups of these six studies comprising 1147 individuals infected with Ebola virus. We found considerable heterogeneity, which did not disappear after statistical modeling to adjust for prognostic variables. Mortality risk varied widely (31 to 66%) across the nonrandomized control arms of these six studies. Models adjusting for baseline covariates (age, sex, and cycle threshold, a proxy for viral load) failed to sufficiently recalibrate these studies and showed that heterogeneity remained. Our findings highlight concerns about making invalid conclusions when comparing nonrandomized control groups to cohorts receiving experimental treatments.
    • Serology for SARS-CoV-2: Apprehensions, opportunities, and the path forward

      Bryant, JE; Azman, AS; Ferrari, MJ; Arnold, BF; Boni, MF; Boum, Y; Hayford, K; Luquero, FJ; Mina, MJ; Rodriguez-Barraquer, I; et al. (American Association for the Advancement of Science, 2020-05-19)
      Serological testing for SARS-CoV-2 has enormous potential to contribute to COVID-19 pandemic response efforts. However, the required performance characteristics of antibody tests will critically depend on the use case (individual-level vs. population-level).