{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:10:25Z","timestamp":1772169025778,"version":"3.50.1"},"update-to":[{"DOI":"10.12688\/wellcomeopenres.11958.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2017,9,26]],"date-time":"2017-09-26T00:00:00Z","timestamp":1506384000000}}],"reference-count":51,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2017,9,26]],"date-time":"2017-09-26T00:00:00Z","timestamp":1506384000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Wellcome Trust","award":["107769"],"award-info":[{"award-number":["107769"]}]},{"name":"Wellcome Trust","award":["084538"],"award-info":[{"award-number":["084538"]}]}],"content-domain":{"domain":["wellcomeopenresearch.org"],"crossmark-restriction":false},"short-container-title":["Wellcome Open Res"],"abstract":"<ns4:p>\n                    <ns4:bold>Background<\/ns4:bold>\n                    <ns4:bold>.<\/ns4:bold>\n                    Few hospitals in high malaria endemic countries in Africa have the diagnostic capacity for clinically distinguishing acute bacterial meningitis (ABM) from cerebral malaria (CM). As a result, empirical use of antibiotics is necessary. A biochemical marker of ABM would facilitate precise clinical diagnosis and management of these infections and enable rational use of antibiotics.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Methods.<\/ns4:bold>\n                    We used label-free protein quantification by mass spectrometry to identify cerebrospinal fluid (CSF) markers that distinguish ABM (n=37) from CM (n=22) in Kenyan children. Fold change (FC) and false discovery rates (FDR) were used to identify differentially expressed proteins. Subsequently, potential biomarkers were assessed for their ability to discriminate between ABM and CM using receiver operating characteristic (ROC) curves.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Results.<\/ns4:bold>\n                    The host CSF proteome response to ABM (\n                    <ns4:italic>Haemophilus<\/ns4:italic>\n                    <ns4:italic>influenza<\/ns4:italic>\n                    and\n                    <ns4:italic>Streptococcus<\/ns4:italic>\n                    <ns4:italic>pneumoniae<\/ns4:italic>\n                    ) is significantly different to CM. Fifty two proteins were differentially expressed (FDR&lt;0.01, Log FC\u22652), of which 83% (43\/52) were upregulated in ABM compared to CM. Myeloperoxidase and lactotransferrin were present in 37 (100%) and 36 (97%) of ABM cases, respectively, but absent in CM (n=22). Area under the ROC curve (AUC), sensitivity, and specificity were assessed for myeloperoxidase (1, 1, and 1; 95% CI, 1-1) and lactotransferrin (0.98, 0.97, and 1; 95% CI, 0.96-1).\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Conclusion.<\/ns4:bold>\n                    Myeloperoxidase and lactotransferrin have a high potential to distinguish ABM from CM and thereby improve clinical management. Their validation requires a larger cohort of samples that includes other bacterial aetiologies of ABM.\n                  <\/ns4:p>","DOI":"10.12688\/wellcomeopenres.11958.2","type":"journal-article","created":{"date-parts":[[2017,9,26]],"date-time":"2017-09-26T11:25:51Z","timestamp":1506425151000},"page":"47","update-policy":"https:\/\/doi.org\/10.12688\/wellcomeopenres.crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Cerebrospinal fluid markers to distinguish bacterial meningitis from cerebral malaria in children"],"prefix":"10.12688","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8524-9133","authenticated-orcid":false,"given":"James M.","family":"Njunge","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4304-2190","authenticated-orcid":false,"given":"Ian N.","family":"Oyaro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1980-2017","authenticated-orcid":false,"given":"Nelson K.","family":"Kibinge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7255-821X","authenticated-orcid":false,"given":"Martin K.","family":"Rono","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3934-5132","authenticated-orcid":false,"given":"Symon M.","family":"Kariuki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6999-5507","authenticated-orcid":false,"given":"Charles R.","family":"Newton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1236-849X","authenticated-orcid":false,"given":"James A.","family":"Berkley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5270-7492","authenticated-orcid":false,"given":"Evelyn N.","family":"Gitau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2017,9,26]]},"reference":[{"key":"ref-1","first-page":"S1-90","article-title":"Severe falciparum malaria. World Health Organization, Communicable Diseases Cluster.","volume":"94","year":"2000","journal-title":"Trans R Soc Trop Med Hyg."},{"key":"ref-2","doi-asserted-by":"publisher","first-page":"104","DOI":"10.3389\/fcimb.2014.00104","article-title":"The systemic pathology of cerebral malaria in African children.","volume":"4","author":"D Milner","year":"2014","journal-title":"Front Cell Infect Microbiol."},{"key":"ref-3","doi-asserted-by":"publisher","first-page":"2119-2142","DOI":"10.1093\/brain\/awu001","article-title":"Cerebral malaria in children: using the retina to study the brain.","volume":"137","author":"I MacCormick","year":"2014","journal-title":"Brain."},{"key":"ref-4","doi-asserted-by":"publisher","first-page":"600-609","DOI":"10.1093\/infdis\/jit500","article-title":"Value of Plasmodium falciparum Histidine-Rich Protein 2 level and malaria retinopathy in distinguishing cerebral malaria from other acute encephalopathies in Kenyan children.","volume":"209","author":"S Kariuki","year":"2014","journal-title":"J Infect Dis."},{"key":"ref-5","doi-asserted-by":"publisher","first-page":"309-318","DOI":"10.1093\/infdis\/jis371","article-title":"Plasma concentrations of parasite Histidine-Rich Protein 2 distinguish between retinopathy-positive and retinopathy-negative cerebral malaria in Malawian children.","volume":"206","author":"K Seydel","year":"2012","journal-title":"J Infect Dis."},{"key":"ref-6","doi-asserted-by":"publisher","first-page":"726-730","DOI":"10.1542\/peds.2007-3275","article-title":"Effect of antibiotic pretreatment on cerebrospinal fluid profiles of children with bacterial meningitis.","volume":"122","author":"L Nigrovic","year":"2008","journal-title":"Pediatrics."},{"key":"ref-7","doi-asserted-by":"publisher","first-page":"193-202","DOI":"10.1016\/S0163-4453(83)96980-3","article-title":"875 Cases of bacterial meningitis: Diagnostic procedures and the impact of preadmission antibiotic therapy Part III of a three-part series.","volume":"7","author":"V Bohr","year":"1983","journal-title":"J Infect."},{"key":"ref-8","doi-asserted-by":"publisher","first-page":"1753-1757","DOI":"10.1016\/S0140-6736(00)04897-2","article-title":"Diagnosis of acute bacterial meningitis in children at a district hospital in sub-Saharan Africa.","volume":"357","author":"J Berkley","year":"2001","journal-title":"Lancet."},{"key":"ref-9","doi-asserted-by":"publisher","first-page":"e713-719","DOI":"10.1542\/peds.2004-0007","article-title":"Indicators of acute bacterial meningitis in children at a rural Kenyan district hospital.","volume":"114","author":"J Berkley","year":"2004","journal-title":"Pediatrics."},{"key":"ref-10","doi-asserted-by":"publisher","first-page":"151-157","DOI":"10.1093\/qjmed\/92.3.151","article-title":"Cerebral malaria versus bacterial meningitis in children with impaired consciousness.","volume":"92","author":"J Berkley","year":"1999","journal-title":"QJM."},{"key":"ref-11","doi-asserted-by":"publisher","first-page":"211-218","DOI":"10.1016\/S0140-6736(02)09458-8","article-title":"Dexamethasone treatment in childhood bacterial meningitis in Malawi: a randomised controlled trial.","volume":"360","author":"E Molyneux","year":"2002","journal-title":"Lancet."},{"key":"ref-12","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/2047-2994-1-11","article-title":"Ready for a world without antibiotics? The Pensi\u00e8res Antibiotic Resistance Call to Action.","volume":"1","author":"J Carlet","year":"2012","journal-title":"Antimicrob Resist Infect Control."},{"key":"ref-13","doi-asserted-by":"publisher","first-page":"179-189","DOI":"10.1016\/j.jchromb.2004.06.044","article-title":"Proteomics analysis of human cerebrospinal fluid.","volume":"815","author":"X Yuan","year":"2005","journal-title":"J Chromatogr B Analyt Technol Biomed Life Sci."},{"key":"ref-14","doi-asserted-by":"publisher","first-page":"e10079","DOI":"10.1371\/journal.pone.0010079","article-title":"A proteomic approach for the diagnosis of bacterial meningitis.","volume":"5","author":"S Jesse","year":"2010","journal-title":"PLoS One."},{"key":"ref-15","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1186\/1475-2875-10-205","article-title":"Global proteomic analysis of plasma from mice infected with Plasmodium berghei ANKA using two dimensional gel electrophoresis and matrix assisted laser desorption ionization-time of flight mass spectrometry.","volume":"10","author":"E Gitau","year":"2011","journal-title":"Malar J."},{"key":"ref-16","doi-asserted-by":"publisher","first-page":"542-550","DOI":"10.1086\/654819","article-title":"Proteomic analysis of cerebrospinal fluid in pneumococcal meningitis reveals potential biomarkers associated with survival.","volume":"202","author":"U Goonetilleke","year":"2010","journal-title":"J Infect Dis."},{"key":"ref-17","doi-asserted-by":"publisher","first-page":"1494-1503","DOI":"10.1093\/infdis\/jit334","article-title":"Plasma and cerebrospinal proteomes from children with cerebral malaria differ from those of children with other encephalopathies.","volume":"208","author":"E Gitau","year":"2013","journal-title":"J Infect Dis."},{"key":"ref-18","doi-asserted-by":"publisher","first-page":"S11","DOI":"10.1186\/1471-2164-16-S5-S11","article-title":"Comparative proteomics of cerebrospinal fluid reveals a predictive model for differential diagnosis of pneumococcal, meningococcal, and enteroviral meningitis, and novel putative therapeutic targets.","volume":"16","author":"A Cordeiro","year":"2015","journal-title":"BMC Genomics."},{"key":"ref-19","doi-asserted-by":"publisher","first-page":"e251","DOI":"10.1371\/journal.pmed.0040251","article-title":"Defining childhood severe falciparum malaria for intervention studies.","volume":"4","author":"P Bejon","year":"2007","journal-title":"PLoS Med."},{"key":"ref-20","doi-asserted-by":"publisher","first-page":"1367-1372","DOI":"10.1038\/nbt.1511","article-title":"MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification.","volume":"26","author":"J Cox","year":"2008","journal-title":"Nat Biotechnol."},{"key":"ref-21","doi-asserted-by":"publisher","first-page":"1794-1805","DOI":"10.1021\/pr101065j","article-title":"Andromeda: A peptide search engine integrated into the MaxQuant environment.","volume":"10","author":"J Cox","year":"2011","journal-title":"J Proteome Res."},{"key":"ref-22","doi-asserted-by":"publisher","first-page":"207-214","DOI":"10.1038\/nmeth1019","article-title":"Target-decoy search strategy for increased confidence in large-scale protein identifications by mass spectrometry.","volume":"4","author":"J Elias","year":"2007","journal-title":"Nat Methods."},{"key":"ref-23","doi-asserted-by":"publisher","first-page":"5-32","DOI":"10.1023\/A:1010933404324","article-title":"Random Forests.","volume":"45","author":"L Breiman","year":"2001","journal-title":"Mach Learn."},{"key":"ref-24","doi-asserted-by":"publisher","first-page":"1-13","DOI":"10.18637\/jss.v036.i11","article-title":"Feature selection with the Boruta package.","volume":"36","author":"M Kursa","year":"2010","journal-title":"J Stat Softw."},{"key":"ref-25","doi-asserted-by":"publisher","first-page":"M111.011015","DOI":"10.1074\/mcp.M111.011015","article-title":"Mass spectrometry-based proteomics using Q Exactive, a high-performance benchtop quadrupole Orbitrap mass spectrometer.","volume":"10","author":"A Michalski","year":"2011","journal-title":"Mol Cell Proteomics."},{"key":"ref-26","doi-asserted-by":"publisher","first-page":"2513-2526","DOI":"10.1074\/mcp.M113.031591","article-title":"Accurate proteome-wide label-free quantification by delayed normalization and maximal peptide ratio extraction, termed MaxLFQ.","volume":"13","author":"J Cox","year":"2014","journal-title":"Mol Cell Proteomics."},{"key":"ref-27","doi-asserted-by":"publisher","first-page":"2155-9597","DOI":"10.4172\/2155-9597.1000e122","article-title":"Blood-Brain Barrier and Cerebral Malaria: The Road So Far.","volume":"5","author":"P Mauro","year":"2014","journal-title":"J Bacteriol Parasitol."},{"key":"ref-28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/2045-8118-11-1","article-title":"Host matrix metalloproteinases in cerebral malaria: new kids on the block against blood\u2013brain barrier integrity?","volume":"11","author":"M Polimeni","year":"2014","journal-title":"Fluids Barriers CNS."},{"key":"ref-29","doi-asserted-by":"publisher","first-page":"193-201","DOI":"10.4161\/viru.19013","article-title":"Cerebral malaria: mysteries at the blood-brain barrier.","volume":"3","author":"L R\u00e9nia","year":"2012","journal-title":"Virulence."},{"key":"ref-30","doi-asserted-by":"publisher","first-page":"285-292","DOI":"10.1111\/j.1365-3156.2004.01366.x","article-title":"Review Article: Blood\u2013brain barrier in falciparum malaria.","volume":"10","author":"E Gitau","year":"2005","journal-title":"Trop Med Int Health."},{"key":"ref-31","doi-asserted-by":"crossref","first-page":"383-389","DOI":"10.1111\/paa.1999.111.5.383","article-title":"Myeloperoxidase.","volume":"111","author":"S Klebanoff","year":"1999","journal-title":"Proc Assoc Am Physicians."},{"key":"ref-32","doi-asserted-by":"publisher","first-page":"693-698","DOI":"10.1056\/NEJM197803302981301","article-title":"Immunocytochemical Identification of Azurophilic and Specific Granule Markers in the Giant Granules of Chediak-Higashi Neutrophils.","volume":"298","author":"P Rausch","year":"1978","journal-title":"N Engl J Med."},{"key":"ref-33","doi-asserted-by":"publisher","first-page":"1532-1535","DOI":"10.1126\/science.1092385","article-title":"Neutrophil extracellular traps kill bacteria.","volume":"303","author":"V Brinkmann","year":"2004","journal-title":"Science."},{"key":"ref-34","doi-asserted-by":"publisher","first-page":"e0146288","DOI":"10.1371\/journal.pone.0146288","article-title":"Characteristic Cytokine and Chemokine Profiles in Encephalitis of Infectious, Immune-Mediated, and Unknown Aetiology.","volume":"11","author":"B Michael","year":"2016","journal-title":"PLoS One."},{"key":"ref-35","doi-asserted-by":"publisher","first-page":"1462-1470","DOI":"10.1373\/clinchem.2009.126029","article-title":"Myeloperoxidase: a useful biomarker for cardiovascular disease risk stratification?","volume":"55","author":"R Schindhelm","year":"2009","journal-title":"Clin Chem."},{"key":"ref-36","doi-asserted-by":"publisher","first-page":"659-676","DOI":"10.1111\/j.1432-1033.1984.tb08607.x","article-title":"Human lactotransferrin: amino acid sequence and structural comparisons with other transferrins.","volume":"145","author":"M Metz-Boutigue","year":"1984","journal-title":"Eur J Biochem."},{"key":"ref-37","first-page":"252-267","article-title":"Lactoferrin: a general review.","volume":"80","author":"P Levay","year":"1995","journal-title":"Haematologica."},{"key":"ref-38","first-page":"560-561","article-title":"Iron and Infection. Molecular, Physiological and Clinical Aspects.","volume":"61","author":"B Ratcliff","year":"1988","journal-title":"Yale J Biol Med."},{"key":"ref-39","doi-asserted-by":"crossref","first-page":"65-102","DOI":"10.1152\/physrev.1984.64.1.65","article-title":"Iron withholding: a defense against infection and neoplasia.","volume":"64","author":"E Weinberg","year":"1984","journal-title":"Physiol Rev."},{"key":"ref-40","doi-asserted-by":"publisher","first-page":"263-265","DOI":"10.1126\/science.327545","article-title":"A bactericidal effect for human lactoferrin.","volume":"197","author":"R Arnold","year":"1977","journal-title":"Science."},{"key":"ref-41","doi-asserted-by":"crossref","first-page":"987-992","DOI":"10.1542\/peds.103.5.987","article-title":"Levels of antimicrobial molecules defensin and lactoferrin are elevated in the cerebrospinal fluid of children with meningitis.","volume":"103","author":"F Maffei","year":"1999","journal-title":"Pediatrics."},{"key":"ref-42","doi-asserted-by":"publisher","first-page":"40-46","DOI":"10.1161\/01.STR.12.1.40","article-title":"Lactoferrin, lysozyme, and beta 2-microglobulin in cerebrospinal fluid. Elevated levels in patients with acute cerebrovascular lesions as indices of inflammation.","volume":"12","author":"A Terent","year":"1981","journal-title":"Stroke."},{"key":"ref-43","doi-asserted-by":"publisher","first-page":"569-572","DOI":"10.1111\/j.1651-2227.1986.tb10252.x","article-title":"Lactoferrin, C-reactive protein, alpha-1-antitrypsin and immunoglobulin GA in cerebrospinal fluid in meningitis.","volume":"75","author":"T Gutteberg","year":"1986","journal-title":"Acta Paediatr Scand."},{"key":"ref-44","first-page":"80-84","article-title":"[Level of lactoferrin in serum and cerebrospinal fluid of patients with meningitis].","author":"O Lykova","year":"2007","journal-title":"Zh Mikrobiol Epidemiol Immunobiol."},{"key":"ref-45","doi-asserted-by":"publisher","first-page":"599-603","DOI":"10.1515\/cclm-2014-0775","article-title":"Calprotectin and lactoferrin in the cerebrospinal fluid; biomarkers utilisable for differential diagnostics of bacterial and aseptic meningitis?","volume":"53","author":"M Dastych","year":"2015","journal-title":"Clin Chem Lab Med."},{"key":"ref-46","doi-asserted-by":"publisher","first-page":"143-145","DOI":"10.1038\/nm986","article-title":"Differentiating the pathologies of cerebral malaria by postmortem parasite counts.","volume":"10","author":"T Taylor","year":"2004","journal-title":"Nat Med."},{"key":"ref-47","doi-asserted-by":"crossref","first-page":"790-797","DOI":"10.4269\/ajtmh.2006.75.790","article-title":"Malarial retinopathy: a newly established diagnostic sign in severe malaria.","volume":"75","author":"N Beare","year":"2006","journal-title":"Am J Trop Med Hyg."},{"key":"ref-48","doi-asserted-by":"publisher","first-page":"349-355","DOI":"10.2217\/fmb.11.3","article-title":"Redefining cerebral malaria by including malaria retinopathy.","volume":"6","author":"N Beare","year":"2011","journal-title":"Future Microbiol."},{"key":"ref-49","doi-asserted-by":"publisher","first-page":"91-101","DOI":"10.1385\/CP:2:1:91","article-title":"Assessment of Protein Stability in Cerebrospinal Fluid Using Surface-Enhanced Laser Desorption\/Ionization Time-of-Flight Mass Spectrometry Protein Profiling.","volume":"2","author":"S Ranganathan","year":"2006","journal-title":"Clin Proteomics."},{"key":"ref-50","doi-asserted-by":"publisher","first-page":"467-492","DOI":"10.1128\/CMR.00070-09","article-title":"Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis.","volume":"23","author":"M Brouwer","year":"2010","journal-title":"Clin Microbiol Rev."},{"key":"ref-51","doi-asserted-by":"publisher","first-page":"223-226","DOI":"10.1038\/nbt.2839","article-title":"ProteomeXchange provides globally coordinated proteomics data submission and dissemination.","volume":"32","author":"J Vizca\u00edno","year":"2014","journal-title":"Nat Biotechnol."}],"container-title":["Wellcome Open Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/2-47\/v2\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/2-47\/v2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/2-47\/v2\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,16]],"date-time":"2020-05-16T11:55:45Z","timestamp":1589630145000},"score":1,"resource":{"primary":{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/2-47\/v2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9,26]]},"references-count":51,"URL":"https:\/\/doi.org\/10.12688\/wellcomeopenres.11958.2","relation":{"has-review":[{"id-type":"doi","id":"10.21956\/wellcomeopenres.13799.r26406","asserted-by":"subject"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.13799.r26405","asserted-by":"subject"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.13799.r26405","asserted-by":"object"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.13799.r26406","asserted-by":"object"}]},"ISSN":["2398-502X"],"issn-type":[{"value":"2398-502X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9,26]]},"assertion":[{"value":"Indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/2-47\/v2#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.21956\/wellcomeopenres.13799.r26406, Wilson L. Mandala, Malaria Immunology Group, Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi, 27 Sep 2017, version 2, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/2-47\/v2#referee-response-26406","order":0,"name":"referee-response-26406","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.13799.r26405, Clarissa Valim, Department of Osteopathic Medical Specialties, Michigan State University, East Lansing, MI, USA, 10 Nov 2017, version 2, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/2-47\/v2#referee-response-26405","order":1,"name":"referee-response-26405","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This work was supported by the Wellcome Trust [084538], Strategic Award; [107769], Strategic Award and Initiative to Develop African Research Leaders (IDeAL). JMN is a beneficiary of both Strategic Award and IDEAL early career post-doc, EG and MKR are beneficiaries of Strategic Award. NKK is a post-doc currently supported by IDeAL. 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"}]}}