{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T07:29:22Z","timestamp":1778657362839,"version":"3.51.4"},"reference-count":49,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2019,11,20]],"date-time":"2019-11-20T00:00:00Z","timestamp":1574208000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001713","name":"European and Developing Countries Clinical Trials Partnership","doi-asserted-by":"publisher","award":["EDCTP-RIA2016V-1633"],"award-info":[{"award-number":["EDCTP-RIA2016V-1633"]}],"id":[{"id":"10.13039\/501100001713","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008196","name":"M\u00e9decins Sans Fronti\u00e8res","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011858","name":"African Academy of Sciences","doi-asserted-by":"publisher","award":["DEL-15-003"],"award-info":[{"award-number":["DEL-15-003"]}],"id":[{"id":"10.13039\/501100011858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["092654"],"award-info":[{"award-number":["092654"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["107769"],"award-info":[{"award-number":["107769"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001275","name":"Oak Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001275","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Tropical Network Fund, University of Oxford"}],"content-domain":{"domain":["wellcomeopenresearch.org"],"crossmark-restriction":false},"short-container-title":["Wellcome Open Res"],"abstract":"<ns3:p>\n                    <ns3:bold>Introduction:<\/ns3:bold>\n                    Yellow fever is endemic in specific regions of sub-Saharan Africa and the Americas, with recent epidemics occurring on both continents. The yellow fever vaccine is effective, affordable and safe, providing life-long immunity following a single dose vaccination. However, the vaccine production process is slow and cannot be readily scaled up during epidemics. This has led the World Health Organization (WHO) to recommend the use of fractional doses as a dose-sparing strategy during epidemics, but there are no randomized controlled trials of fractional yellow fever vaccine doses in Africa.\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Methods and analysis:<\/ns3:bold>\n                    We will recruit healthy adult volunteers, adults living with HIV, and children to a series of randomized controlled trials aiming to determine the immunogenicity and safety of fractional vaccine doses in comparison to the standard vaccine dose. The trials will be conducted across two sites; Kilifi, Kenya and Mbarara, Uganda. Recruited participants will be randomized to receive fractional or standard doses of yellow fever vaccine. Scheduled visits will include blood collection for serum and peripheral blood mononuclear cells (PBMCs) before vaccination and on various days \u2013 up to 2 years \u2013 post-vaccination. The primary outcome is the rate of seroconversion as measured by the plaque reduction neutralization test (PRNT\n                    <ns3:sub>50<\/ns3:sub>\n                    ) at 28 days post-vaccination. Secondary outcomes include antibody titre changes, longevity of the immune response, safety assessment using clinical data, the nature and magnitude of the cellular immune response and post-vaccination control of viremia by vaccine dose.\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Ethics and dissemination:<\/ns3:bold>\n                    The clinical trial protocols have received approval from the relevant institutional ethics and regulatory review committees in Kenya and Uganda, and the WHO Ethics Review Committee. The research findings will be disseminated through open-access publications and presented at relevant conferences and workshops.\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Registration:<\/ns3:bold>\n                    ClinicalTrials.gov\n                    <ns3:ext-link xmlns:ns4=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" ns4:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02991495\">NCT02991495<\/ns3:ext-link>\n                    (registered on 13 December 2016) and\n                    <ns3:ext-link xmlns:ns4=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" ns4:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04059471\">NCT04059471<\/ns3:ext-link>\n                    (registered on 15 August 2019).\n                  <\/ns3:p>","DOI":"10.12688\/wellcomeopenres.15579.1","type":"journal-article","created":{"date-parts":[[2019,11,20]],"date-time":"2019-11-20T09:35:05Z","timestamp":1574242505000},"page":"182","update-policy":"https:\/\/doi.org\/10.12688\/wellcomeopenres.crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Randomized, double-blinded, controlled non-inferiority trials evaluating the immunogenicity and safety of fractional doses of Yellow Fever vaccines in Kenya and Uganda"],"prefix":"10.12688","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6998-0700","authenticated-orcid":false,"given":"Derick","family":"Kimathi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6768-5874","authenticated-orcid":false,"given":"Aitana","family":"Juan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2135-7549","authenticated-orcid":false,"given":"Philip","family":"Bejon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5037-8218","authenticated-orcid":false,"given":"Rebecca F.","family":"Grais","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4911-6333","authenticated-orcid":false,"given":"George M.","family":"Warimwe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"YEFE and NIFTY vaccine trials teams","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2019,11,20]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"5751-5752","DOI":"10.1016\/j.vaccine.2017.06.087","article-title":"WHO position on the use of fractional doses - June 2017, addendum to vaccines and vaccination against yellow fever WHO: Position paper - June 2013.","volume":"35","year":"2017","journal-title":"Vaccine."},{"key":"ref-2","article-title":"Fractional dose yellow fever vaccine as a dose-sparing option for outbreak response","year":"2016"},{"key":"ref-3","doi-asserted-by":"publisher","first-page":"1459-68","DOI":"10.1016\/s1286-4579(02)00028-x","article-title":"The epidemiology of yellow fever in Africa.","volume":"4","author":"J Mutebi","year":"2002","journal-title":"Microbes Infect."},{"key":"ref-4","doi-asserted-by":"publisher","first-page":"e270-e278","DOI":"10.1016\/S2214-109X(18)30024-X","article-title":"Existing and potential infection risk zones of yellow fever worldwide: a modelling analysis.","volume":"6","author":"F Shearer","year":"2018","journal-title":"Lancet Glob Health."},{"key":"ref-5","doi-asserted-by":"publisher","first-page":"160-73","DOI":"10.1016\/j.jcv.2014.08.030","article-title":"Yellow fever.","volume":"64","author":"T Monath","year":"2015","journal-title":"J Clin Virol."},{"key":"ref-6","doi-asserted-by":"publisher","first-page":"340-341","DOI":"10.15585\/mmwr.mm6711e1","article-title":"Fatal Yellow Fever in Travelers to Brazil, 2018.","volume":"67","author":"D Hamer","year":"2018","journal-title":"MMWR Morb Mortal Wkly Rep."},{"key":"ref-7","doi-asserted-by":"publisher","first-page":"209-29","DOI":"10.1146\/annurev.ento.52.110405.091454","article-title":"Yellow fever: a disease that has yet to be conquered.","volume":"52","author":"A Barrett","year":"2007","journal-title":"Annu Rev Entomol."},{"key":"ref-8","first-page":"643-5","article-title":"Fever, jaundice, and multiple organ system failure associated with 17D-derived yellow fever vaccination, 1996-2001.","volume":"50","year":"2001","journal-title":"MMWR Morb Mortal Wkly Rep."},{"key":"ref-9","doi-asserted-by":"publisher","first-page":"e1001638","DOI":"10.1371\/journal.pmed.1001638","article-title":"Yellow Fever in Africa: estimating the burden of disease and impact of mass vaccination from outbreak and serological data.","volume":"11","author":"T Garske","year":"2014","journal-title":"PLoS Med."},{"key":"ref-10","doi-asserted-by":"publisher","first-page":"343-95","DOI":"10.1016\/s0065-3527(03)60009-6","article-title":"Pathogenesis and pathophysiology of yellow fever.","volume":"60","author":"T Monath","year":"2003","journal-title":"Adv Virus Res."},{"key":"ref-11","doi-asserted-by":"publisher","first-page":"434-44","DOI":"10.4269\/ajtmh.13-0264","article-title":"Efficacy and duration of immunity after yellow fever vaccination: systematic review on the need for a booster every 10 years.","volume":"89","author":"E Gotuzzo","year":"2013","journal-title":"Am J Trop Med Hyg."},{"key":"ref-12","doi-asserted-by":"publisher","first-page":"e0149871","DOI":"10.1371\/journal.pone.0149871","article-title":"A Single 17D Yellow Fever Vaccination Provides Lifelong Immunity; Characterization of Yellow-Fever-Specific Neutralizing Antibody and T-Cell Responses after Vaccination.","volume":"11","author":"R Wieten","year":"2016","journal-title":"PLoS One."},{"key":"ref-13","doi-asserted-by":"publisher","first-page":"427-48","DOI":"10.1586\/erv.12.6","article-title":"Review of the risks and benefits of yellow fever vaccination including some new analyses.","volume":"11","author":"T Monath","year":"2012","journal-title":"Expert Rev Vaccines."},{"key":"ref-14","first-page":"152-172","article-title":"Behavior of 17D yellow fever virus in rhesus monkeys: relation to substrain, dose and neural or extraneural inoculation.","volume":"38","author":"J Fox","year":"1943","journal-title":"Am J Epidemiol."},{"key":"ref-15","doi-asserted-by":"publisher","first-page":"5951-5955","DOI":"10.1016\/j.vaccine.2017.03.032","article-title":"Yellow fever live attenuated vaccine: A very successful live attenuated vaccine but still we have problems controlling the disease.","volume":"35","author":"A Barrett","year":"2017","journal-title":"Vaccine."},{"key":"ref-16","first-page":"1056-9","article-title":"Antibody response to 17D yellow fever vaccine in Ghanaian infants.","volume":"79","author":"M Osei-Kwasi","year":"2001","journal-title":"Bull World Health Organ."},{"key":"ref-17","doi-asserted-by":"publisher","first-page":"1479-92","DOI":"10.1586\/14760584.2015.1083430","article-title":"Current status and future prospects of yellow fever vaccines.","volume":"14","author":"A Beck","year":"2015","journal-title":"Expert Rev Vaccines."},{"key":"ref-18","doi-asserted-by":"publisher","first-page":"8236-45","DOI":"10.1016\/j.vaccine.2010.10.070","article-title":"WHO Working Group on Technical Specifications for Manufacture and Evaluation of Yellow Fever Vaccines, Geneva, Switzerland, 13-14 May 2009.","volume":"28","author":"M Ferguson","year":"2010","journal-title":"Vaccine."},{"key":"ref-19","doi-asserted-by":"publisher","first-page":"2904-2911","DOI":"10.1016\/S0140-6736(16)31838-4","article-title":"Fractional dosing of yellow fever vaccine to extend supply: a modelling study.","volume":"388","author":"J Wu","year":"2016","journal-title":"Lancet."},{"key":"ref-20","doi-asserted-by":"publisher","first-page":"301-3","DOI":"10.1056\/NEJMp1606997","article-title":"Yellow Fever in Angola and Beyond--The Problem of Vaccine Supply and Demand.","volume":"375","author":"A Barrett","year":"2016","journal-title":"N Engl J Med."},{"key":"ref-21","article-title":"Immunogenicity of Fractional-Dose Vaccine during a Yellow Fever Outbreak - Preliminary Report.","author":"S Ahuka-Mundeke","year":"2018","journal-title":"N Engl J Med."},{"key":"ref-22","first-page":"219-25","article-title":"Stability of yellow fever vaccine.","volume":"87","author":"T Monath","year":"1996","journal-title":"Dev Biol Stand."},{"key":"ref-23","article-title":"Recommendations to assure the quality, safety and efficacy of live attenuated yellow fever vaccines (Annex 5).","year":"2013"},{"key":"ref-24","article-title":"Yellow Fever vaccination: The potential of dose-sparing to increase vaccine supply and availability","year":"2013"},{"key":"ref-25","article-title":"Yellow Fever Situation Report.","year":"2016"},{"key":"ref-26","doi-asserted-by":"publisher","first-page":"444-454","DOI":"10.1056\/NEJMoa1710430","article-title":"Immunogenicity of Fractional-Dose Vaccine during a Yellow Fever Outbreak - Final Report.","volume":"381","author":"R Casey","year":"2019","journal-title":"N Engl J Med."},{"key":"ref-27","doi-asserted-by":"publisher","first-page":"1397-1399","DOI":"10.1056\/NEJMp1702172","article-title":"Yellow Fever - Once Again on the Radar Screen in the Americas.","volume":"376","author":"C Paules","year":"2017","journal-title":"N Engl J Med."},{"key":"ref-28","article-title":"Epidemiological Update: Yellow Fever.","year":"2018"},{"key":"ref-29","doi-asserted-by":"publisher","first-page":"879-88","DOI":"10.4161\/hv.22982","article-title":"17DD yellow fever vaccine: a double blind, randomized clinical trial of immunogenicity and safety on a dose-response study.","volume":"9","author":"R Martins","year":"2013","journal-title":"Hum Vaccin Immunother."},{"key":"ref-30","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1186\/1471-2334-14-391","article-title":"Subdoses of 17DD yellow fever vaccine elicit equivalent virological\/immunological kinetics timeline.","volume":"14","author":"A Campi-Azevedo","year":"2014","journal-title":"BMC Infect Dis."},{"key":"ref-31","doi-asserted-by":"publisher","first-page":"e1993","DOI":"10.1371\/journal.pone.0001993","article-title":"Intradermally administered yellow fever vaccine at reduced dose induces a protective immune response: a randomized controlled non-inferiority trial.","volume":"3","author":"A Roukens","year":"2008","journal-title":"PLoS One."},{"key":"ref-32","doi-asserted-by":"publisher","first-page":"77-82","DOI":"10.1016\/0092-1157(88)90034-0","article-title":"Studies on yellow fever vaccine. III--Dose response in volunteers.","volume":"16","author":"S Lopes Ode","year":"1988","journal-title":"J Biol Stand."},{"key":"ref-33","doi-asserted-by":"publisher","first-page":"603-605","DOI":"10.1056\/NEJMp1803433","article-title":"Fractional-Dose Yellow Fever Vaccination - Advancing the Evidence Base.","volume":"379","author":"K Vannice","year":"2018","journal-title":"N Engl J Med."},{"key":"ref-34","doi-asserted-by":"publisher","first-page":"pii: taz024","DOI":"10.1093\/jtm\/taz024","article-title":"Fractional-dose yellow fever vaccination: an expert review.","volume":"26","author":"A Roukens","year":"2019","journal-title":"J Travel Med."},{"key":"ref-35","doi-asserted-by":"publisher","first-page":"6166-6171","DOI":"10.1016\/j.vaccine.2017.09.047","article-title":"CHRONOVAC VOYAGEUR: A study of the immune response to yellow fever vaccine among infants previously immunized against measles.","volume":"35","author":"C Goujon","year":"2017","journal-title":"Vaccine."},{"key":"ref-36","doi-asserted-by":"publisher","first-page":"873-83","DOI":"10.1093\/infdis\/jir439","article-title":"Cytokine signatures of innate and adaptive immunity in 17DD yellow fever vaccinated children and its association with the level of neutralizing antibody.","volume":"204","author":"M Luiza-Silva","year":"2011","journal-title":"J Infect Dis."},{"key":"ref-37","doi-asserted-by":"publisher","first-page":"437-44","DOI":"10.1016\/j.trstmh.2012.04.002","article-title":"Immunogenicity and safety of yellow fever vaccine among 115 HIV-infected patients after a preventive immunisation campaign in Mali.","volume":"106","author":"M Sidibe","year":"2012","journal-title":"Trans R Soc Trop Med Hyg."},{"key":"ref-38","doi-asserted-by":"publisher","first-page":"721-33","DOI":"10.1016\/j.socscimed.2008.02.007","article-title":"Beginning community engagement at a busy biomedical research programme: experiences from the KEMRI CGMRC-Wellcome Trust Research Programme, Kilifi, Kenya.","volume":"67","author":"V Marsh","year":"2008","journal-title":"Soc Sci Med."},{"key":"ref-39","article-title":"Randomized, double-blinded, controlled non-inferiority trials evaluating the immunogenicity and safety of fractional doses of Yellow Fever vaccines in Kenya and Uganda.","author":"D Kimathi","year":"2019","journal-title":"figshare."},{"key":"ref-40","doi-asserted-by":"publisher","first-page":"6392-7","DOI":"10.1016\/j.vaccine.2008.08.074","article-title":"Comparison of plaque reduction neutralisation test (PRNT) and measles virus-specific IgG ELISA for assessing immunogenicity of measles vaccination.","volume":"26","author":"B Cohen","year":"2008","journal-title":"Vaccine."},{"key":"ref-41","doi-asserted-by":"publisher","first-page":"1247-51","DOI":"10.1016\/j.vaccine.2016.01.037","article-title":"Comparison of the PRNT and an immune fluorescence assay in yellow fever vaccinees receiving immunosuppressive medication.","volume":"34","author":"R Wieten","year":"2016","journal-title":"Vaccine."},{"key":"ref-42","doi-asserted-by":"publisher","first-page":"4054-60","DOI":"10.1128\/JCM.01799-12","article-title":"Advanced yellow fever virus genome detection in point-of-care facilities and reference laboratories.","volume":"50","author":"C Domingo","year":"2012","journal-title":"J Clin Microbiol."},{"key":"ref-43","doi-asserted-by":"publisher","first-page":"e36291","DOI":"10.1371\/journal.pone.0036291","article-title":"First international external quality assessment study on molecular and serological methods for yellow fever diagnosis.","volume":"7","author":"C Domingo","year":"2012","journal-title":"PLoS One."},{"key":"ref-44","doi-asserted-by":"publisher","first-page":"600-7","DOI":"10.1021\/js9504705","article-title":"Pharmacodynamic analysis of sparse data from concentration- and effect-controlled clinical trials guided by a pilot study. An investigation by simulations.","volume":"85","author":"T Fullerton","year":"1996","journal-title":"J Pharm Sci."},{"key":"ref-45","doi-asserted-by":"publisher","first-page":"441-57","DOI":"10.1007\/s10928-005-0034-2","article-title":"Some considerations on the design of population pharmacokinetic studies.","volume":"32","author":"S Duffull","year":"2005","journal-title":"J Pharmacokinet Pharmacodyn."},{"key":"ref-46","doi-asserted-by":"publisher","first-page":"pii: E77","DOI":"10.3390\/v9040077","article-title":"T Cell-Mediated Immunity towards Yellow Fever Virus and Useful Animal Models.","volume":"9","author":"A Watson","year":"2017","journal-title":"Viruses."},{"key":"ref-47","doi-asserted-by":"publisher","first-page":"e0132645","DOI":"10.1371\/journal.pone.0132645","article-title":"Seroprevalence of Infections with Dengue, Rift Valley Fever and Chikungunya Viruses in Kenya, 2007.","volume":"10","author":"C Ochieng","year":"2015","journal-title":"PLoS One."},{"key":"ref-48","doi-asserted-by":"publisher","first-page":"pii: e01566-18","DOI":"10.1128\/MRA.01566-18","article-title":"Complete Genome Sequences of Dengue Virus Type 2 Strains from Kilifi, Kenya.","volume":"8","author":"E Kamau","year":"2019","journal-title":"Microbiol Resour Announc."},{"key":"ref-49","doi-asserted-by":"publisher","DOI":"10.13140\/RG.2.2.20146.40649","article-title":"Assessing the serological antibody repertoire to Flaviviruses in the endemic population of the Zika forest in Uganda.","volume":"198","author":"A Demina","year":"2017","journal-title":"J Immunol."}],"container-title":["Wellcome Open Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/4-182\/v1\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/4-182\/v1\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/4-182\/v1\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,9]],"date-time":"2025-02-09T06:10:15Z","timestamp":1739081415000},"score":1,"resource":{"primary":{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/4-182\/v1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,20]]},"references-count":49,"URL":"https:\/\/doi.org\/10.12688\/wellcomeopenres.15579.1","relation":{"has-review":[{"id-type":"doi","id":"10.21956\/wellcomeopenres.17060.r37128","asserted-by":"subject"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.17060.r37125","asserted-by":"subject"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.17060.r37125","asserted-by":"object"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.17060.r37128","asserted-by":"object"}]},"ISSN":["2398-502X"],"issn-type":[{"value":"2398-502X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,20]]},"assertion":[{"value":"Indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/4-182\/v1#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.21956\/wellcomeopenres.17060.r37125, Anna H. E. Roukens, Department of Infectious Diseases, Leiden University Medical Centre, Leiden, 02 Dec 2019, version 1, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/4-182\/v1#referee-response-37125","order":0,"name":"referee-response-37125","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.17060.r37128, Akira Homma, Bio-Manguinhos (Institute of Technology in Immunobiology), Ministry of Health, Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, 19 Dec 2019, version 1, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/4-182\/v1#referee-response-37128","order":1,"name":"referee-response-37128","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"These trials have been supported by funding from the Foundation M\u00e9decins Sans Fronti\u00e8res, Wellcome Trust (grant no. 092654) and the European and Developing Countries Clinical Trials Partnership (EDCTP- RIA2016V-1633). GMW is supported by the Oak foundation fellowship. DK is a DPhil student at the University of Oxford supported by the Tropical Network Fund and the DELTAS Africa Initiative (DEL-15-003). The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS)'s Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa's Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust (107769). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":2,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}