Browsing by Author "White, N.J."
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Item Author Correction: The temporal dynamics and infectiousness of subpatent Plasmodium falciparum infections in relation to parasite density(Nature communications, 2019-06-11) Koram, K.; Slater, H.C.; Ross, A.; Felger, I.; Hofmann, N.E.; Robinson, L.; Cook, J.; Gonçalves, B.P.; Björkman, A.; Ouedraogo, A.L.; Morris, U.; Msellem, M.; Koepfli, C.; Mueller, I.; Tadesse, F.; Gadisa, E.; Das, S.; Domingo, G.; Kapulu, M.; Midega, J.; Owusu-Agyei, S.; Nabet, C.; Piarroux, R.; Doumbo, O.; Doumbo, S.N.; Koram, K.; Lucchi, N.; Udhayakumar, V.; Mosha, J.; Tiono, A.; Chandramohan, D.; Gosling, R.; Mwingira, F.; Sauerwein, R.; Paul, R.; Riley, E.M.; White, N.J.; Nosten, F.; Imwong, M.; Bousema, T.; Drakeley, C.; Okell, L.C.Item Malaria: Current status of control, diagnosis, treatment, and a proposed agenda for research and development(Lancet Infectious Diseases, 2002-09) Guerin, P.J.; Olliaro, P.; Nosten, F.; Druilhe, P.; Laxminarayan, R.; Binka, F.; Kilama, W.L.; Ford, N.; White, N.J.Rolling back malaria is possible. Tools are available but they are not used. Several countries deploy, as their national malaria control treatment policy, drugs that are no longer effective. New and innovative methods of vector control, diagnosis, and treatment should be developed, and work towards development of new drugs and a vaccine should receive much greater support. But the pressing need, in the face of increasing global mortality and general lack of progress in malaria control, is research into the best methods of deploying and using existing approaches, particularly insecticide-treated mosquito nets, rapid methods of diagnosis, and artemisinin-based combination treatments. Evidence on these approaches should provide national governments and international donors with the cost-benefit information that would justify much-needed increases in global support for appropriate and effective malaria control.Item An open dataset of Plasmodium falciparum genome variation in 7,000 worldwide samples(2021) MalariaGEN; Ahouidi, A.; Ali, M.; Almagro-Garcia, J.; Amambua-Ngwa, A.; Amaratunga, C.; Amato, R.; Amenga-Etego, L.; Andagalu, B.; Anderson, T.J.C.; Andrianaranjaka, V.; Apinjoh, T.; Ariani, C.; Ashley, E.A.; Auburn, S.; Awandare, G.A.; Ba, H.; Baraka, V.; Barry, A.E.; Bejon, P.; Bertin, G.I.; Boni, M.F.; Borrmann, S.; Bousema, T.; Branch, O.; Bull, P.C.; Busby, G.B.J.; Chookajorn, T.; Chotivanich, K.; Claessens, A.; Conway, D.; Craig, A.; D'Alessandro, U.; Dama, S.; Day, N.P.J.; Denis, B.; Diakite, M.; Djimdé, A.; Dolecek, C.; Dondorp, A.M.; Drakeley, C.; Drury, E.; Duffy, P.; Echeverry, D.F.; Egwang, T.G.; Erko, B.; Fairhurst, R.M.; Faiz, A.; Fanello, C.A.; Fukuda, M.M.; Gamboa, D.; Ghansah, A.; Golassa, L.; Goncalves, S.; Hamilton, W.L.; Harrison, G.L.A.; Hart, L.; Henrichs, C.; Hien, T.T.; Hill, C.A.; Hodgson, A.; Hubbart, C.; Imwong, M.; Ishengoma, D.S.; Jackson, S.A.; Jacob, C.G.; Jeffery, B.; Jeffreys, A.E.; Johnson, K.J.; Jyothi, D.; Kamaliddin, C.; Kamau, E.; Kekre, M.; Kluczynski, K.; Kochakarn, T.; Konaté, A.; Kwiatkowski, D.P.; Kyaw, M.P.; Lim, P.; Lon, C.; Loua, K.M.; Maïga-Ascofaré, O.; Malangone, C.; Manske, M.; Marfurt, J.; Marsh, K.; Mayxay, M.; Miles, A.; Miotto, O.; Mobegi, V.; Mokuolu, O.A.; Montgomery, J.; Mueller, I.; Newton, P.N.; Nguyen, T.; Nguyen, T.; Noedl, H.; Nosten, F.; Noviyanti, R.; Nzila, A.; Ochola-Oyier, L.I.; Ocholla, H.; Oduro, A.; Omedo, I.; Onyamboko, M.A.; Ouedraogo, J.; Oyebola, K.; Pearson, R.D.; Peshu, N.; Phyo, A.P.; Plowe, C.V.; Price, R.N.; Pukrittayakamee, S.; Randrianarivelojosia, M.; Rayner, J.C.; Ringwald, P.; Rockett, K.A.; Rowlands, K.; Ruiz, L.; Saunders, D.; Shayo, A.; Siba, P.; Simpson, V.J.; Stalker, J.; Su, X.; Sutherland, C.; Takala-Harrison, S.; Tavul, L.; Thathy, V.; Tshefu, A.; Verra, F.; Vinetz, J.; Wellems, T.E.; Wendler, J.; White, N.J.; Wright, I.; Yavo, W.; Ye, H.MalariaGEN is a data-sharing network that enables groups around the world to work together on the genomic epidemiology of malaria. Here we describe a new release of curated genome variation data on 7,000 Plasmodium falciparum samples from MalariaGEN partner studies in 28 malaria-endemic countries. High-quality genotype calls on 3 million single nucleotide polymorphisms (SNPs) and short indels were produced using a standardised analysis pipeline. Copy number variants associated with drug resistance and structural variants that cause failure of rapid diagnostic tests were also analysed. Almost all samples showed genetic evidence of resistance to at least one antimalarial drug, and some samples from Southeast Asia carried markers of resistance to six commonly-used drugs. Genes expressed during the mosquito stage of the parasite life-cycle are prominent among loci that show strong geographic differentiation. By continuing to enlarge this open data resource we aim to facilitate research into the evolutionary processes affecting malaria control and to accelerate development of the surveillance toolkit required for malaria elimination.Item Pre-referral rectal artesunate to prevent death and disability in severe malaria: a placebo-controlled trial(Elsevier Ltd, 2009) Gomes, M.F.; Faiz, M.A.; Gyapong, J.O.; Warsame, M.; Agbenyega, T.; Babiker, A.; Baiden, F.; Yunus, E.B.; Binka, F.; Clerk, C.; Folb, P.; Hassan, R.; Hossain, M.A.; Kimbute, O.; Kitua, A.; Krishna, S.; Makasi, C.; Mensah, N.; Mrango, Z.; Olliaro, P.; Peto, R.; Peto, T.J.; Rahman, M.R.; Ribeiro, I.; Samad, R.; White, N.J.Background: Most malaria deaths occur in rural areas. Rapid progression from illness to death can be interrupted by prompt, effective medication. Antimalarial treatment cannot rescue terminally ill patients but could be effective if given earlier. If patients who cannot be treated orally are several hours from facilities for injections, rectal artesunate can be given before referral and acts rapidly on parasites. We investigated whether this intervention reduced mortality and permanent disability. Methods: In Bangladesh, Ghana, and Tanzania, patients with suspected severe malaria who could not be treated orally were allocated randomly to a single artesunate (n=8954) or placebo (n=8872) suppository by taking the next numbered box, then referred to clinics at which injections could be given. Those with antimalarial injections or negative blood smears before randomisation were excluded, leaving 12 068 patients (6072 artesunate, 5996 placebo) for analysis. Primary endpoints were mortality, assessed 7-30 days later, and permanent disability, reassessed periodically. All investigators were masked to group assignment. Analysis was by intention to treat. This study is registered in all three countries, numbers ISRCTN83979018, 46343627, and 76987662. Results: Mortality was 154 of 6072 artesunate versus 177 of 5996 placebo (2·5% vs 3·0%, p=0·1). Two versus 13 (0·03% vs 0·22%, p=0·0020) were permanently disabled; total dead or disabled: 156 versus 190 (2·6% vs 3·2%, p=0·0484). There was no reduction in early mortality (56 vs 51 deaths within 6 h; median 2 h). In patients reaching clinic within 6 h (median 3 h), pre-referral artesunate had no significant effect on death after 6 h or permanent disability (71/4450 [1·6%] vs 82/4426 [1·9%], risk ratio 0·86 [95% CI 0·63-1·18], p=0·35). In patients still not in clinic after more than 6 h, however, half were still not there after more than 15 h, and pre-referral rectal artesunate significantly reduced death or permanent disability (29/1566 [1·9%] vs 57/1519 [3·8%], risk ratio 0·49 [95% CI 0·32-0·77], p=0·0013). Interpretation: If patients with severe malaria cannot be treated orally and access to injections will take several hours, a single inexpensive artesunate suppository at the time of referral substantially reduces the risk of death or permanent disability. Funding: UNICEF/UNDP/World Bank Special Programme for Research and Training in Tropical Diseases (WHO/TDR); WHO Global Malaria Programme (WHO/GMP); Sall Family Foundation; the European Union (QLRT-2000-01430); the UK Medical Research Council; USAID; Irish Aid; the Karolinska Institute; and the University of Oxford Clinical Trial Service Unit (CTSU).Item Setting Our Sights on Infectious Diseases(ACS Infectious Diseases, 2019-12-06) Amewu, R.K.; De Rycker, M.; Horn, D.; Aldridge, B.; Barry, C.E.; Buckner, F.S.; Cook, S.; Ferguson, M.A.J.; Gobeau, N.; Herrmann, J.; Herrling, P.; Hope, W.; Keiser, J.; Lafuente-Monasterio, M.J.; Leeson, P.D.; Leroy, D.; Manjunatha, U.H.; Miles, T.J.; Mizrahi, V.; Moshynets, O.; Niles, J.; Overington, J.P.; Pottage, J.; Rao, S.P.S.; Read, K.D.; Ribeiro, I.; Silver, L.L.; Southern, J.; Spangenberg, T.; Sundar, S.; Taylor, C.; Van Voorhis, W.; White, N.J.; Wyllie, S.; Wyatt, P.G.; Gilbert, I.H.In May 2019, the Wellcome Centre for Anti-Infectives Research (WCAIR) at the University of Dundee, UK, held an international conference with the aim of discussing some key questions around discovering new medicines for infectious diseases and a particular focus on diseases affecting Low and Middle Income Countries. There is an urgent need for new drugs to treat most infectious diseases. We were keen to see if there were lessons that we could learn across different disease areas and between the preclinical and clinical phases with the aim of exploring how we can improve and speed up the drug discovery, translational, and clinical development processes. We started with an introductory session on the current situation and then worked backward from clinical development to combination therapy, pharmacokinetic/pharmacodynamic (PK/PD) studies, drug discovery pathways, and new starting points and targets. This Viewpoint aims to capture some of the learningsItem The temporal dynamics and infectiousness of subpatent Plasmodium falciparum infections in relation to parasite density(Nature Communications, 2019) Slater, H.C.; Ross, A.; Felge, I.; Hofmann, N.E.; Robinson, L.; Cook, J.; Gonçalves, B.P.; Björkman, A.; Ouedraogo, A.L.; Morris, U.; Msellem, M.; Koepfli, C.; Mueller, I.; Tadesse, F.; Gadisa, E.; Das, S.; Domingo, G.; Kapulu, M.; Midega, J.; Owusu-Agyei, S.; Nabet, C.; Piarroux, R.; Doumbo, O.; Doumbo, S.N.; Koram, K.; Lucchi, N.; Udhayakumar, V.; Mosha, J.; Tiono, A.; Chandramohan, D.; Gosling, R.; Mwingira, F.; Sauerwein, R.; Riley, E.M.; White, N.J.; Nosten, F.; Imwong, M.; Bousema, T.; Drakeley, C.; Okell, L.C.Malaria infections occurring below the limit of detection of standard diagnostics are common in all endemic settings. However, key questions remain surrounding their contribution to sustaining transmission and whether they need to be detected and targeted to achieve malaria elimination. In this study we analyse a range of malaria datasets to quantify the density, detectability, course of infection and infectiousness of subpatent infections. Asymptomatically infected individuals have lower parasite densities on average in low transmission settings compared to individuals in higher transmission settings. In cohort studies, subpatent infections are found to be predictive of future periods of patent infection and in membrane feeding studies, individuals infected with subpatent asexual parasite densities are found to be approximately a third as infectious to mosquitoes as individuals with patent (asexual parasite) infection. These results indicate that subpatent infections contribute to the infectious reservoir, may be long lasting, and require more sensitive diagnostics to detect them in lower transmission settings. © 2019, The Author(s).