Improving the diagnosis of severe malaria in African children using platelet counts and plasma Pf HRP2 concentrations

Watson, JamesJamesWatsonUyoga, SophieSophieUyogaWanjiku, PerpetualPerpetualWanjikuMakale, JohnstoneJohnstoneMakaleNyutu, GideonGideonNyutuMturi, NeemaNeemaMturiGeorge, ElizabethElizabethGeorgeWoodrow, CharlesCharlesWoodrowDay, NicholasNicholasDayBejon, PhilipPhilipBejonOpoka, RobertRobertOpokaDondorp, ArjenArjenDondorpJohn, ChandyChandyJohnMaitland, KathrynKathrynMaitlandWilliams, ThomasThomasWilliamsWhite, NicholasNicholasWhite2022-06-062022-07-20Science Translational Medicine, 2022, 14 (654), pp.1-101946-6234http://hdl.handle.net/10044/1/97194Severe falciparum malaria is difficult to diagnose accurately in children in high transmission settings. Using data from 2,649 patients enrolled in four studies of severe illness in three countries (Bangladesh, Kenya, and Uganda), we fitted Bayesian latent class models using two diagnostic biomarkers: the platelet count and the plasma PfHRP2 concentration. In severely ill patients with clinical features consistent with severe malaria, a combined platelet count ≤ 150,000 per µL and a plasma PfHRP2 concentration ≥ 1,000 ng/mL had an estimated sensitivity of 74% and specificity of 93% in identifying ‘true’ severe falciparum malaria. Compared to misdiagnosed children, patients with true severe malaria had higher parasite densities, lower hematocrits, lower rates of invasive bacterial disease, and a lower prevalence of both HbAS and HbSS. We estimate one third of African children enrolled in clinical studies of severe malaria in high transmission settings had another cause of severe illness.© 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government WorksAdultAntigens, ProtozoanBayes TheoremChildHumansMalariaMalaria, FalciparumPlasmodium falciparumPlatelet CountProtozoan ProteinsUgandaHumansPlasmodium falciparumMalariaMalaria, FalciparumProtozoan ProteinsAntigens, ProtozoanPlatelet CountBayes TheoremAdultChildUganda06 Biological Sciences11 Medical and Health SciencesImproving the diagnosis of severe malaria in African children using platelet counts and plasma Pf HRP2 concentrationsJournal Articlehttps://www.dx.doi.org/10.1126/scitranslmed.abn5040https://www.science.org/doi/10.1126/scitranslmed.abn5040091758/B/10/Z203077/Z/16/Z (C161)202800/Z/16/Z203077/C/16/ZG0601027209265/Z/17/Z