Browsing by Author "Mueller, I."
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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 The effect of dose on the antimalarial efficacy of artemether-lumefantrine: A systematic review and pooled analysis of individual patient data(The Lancet Infectious Diseases, 2015-06) Anstey, N.M.; Price, R.N.; Davis, T.M.E.; Karunajeewa, H.A.; Mueller, I.; D'Alessandro, U.; Massougbodji, A.; Nikiema, F.; Ouédraogo, J.-B.; Tinto, H.; Zongo, I.; Same-Ekobo, A.; Koné, M.; Menan, H.; Yavo, W.; Touré, A.O.; Kofoed, P.-E.; Alemayehu, B.H.; Jima, D.; Baudin, E.; Espié, E.; Nabasumba, C.; Pinoges, L.; Schramm, B.; Cot, M.; Deloron, P.; Faucher, J.-F.Background: Artemether-lumefantrine is the most widely used artemisinin-based combination therapy for malaria, although treatment failures occur in some regions. We investigated the effect of dosing strategy on efficacy in a pooled analysis from trials done in a wide range of malaria-endemic settings. Methods: We searched PubMed for clinical trials that enrolled and treated patients with artemether-lumefantrine and were published from 1960 to December, 2012. We merged individual patient data from these trials by use of standardised methods. The primary endpoint was the PCR-adjusted risk of Plasmodium falciparum recrudescence by day 28. Secondary endpoints consisted of the PCR-adjusted risk of P falciparum recurrence by day 42, PCR-unadjusted risk of P falciparum recurrence by day 42, early parasite clearance, and gametocyte carriage. Risk factors for PCR-adjusted recrudescence were identified using Cox's regression model with frailty shared across the study sites. Findings: We included 61 studies done between January, 1998, and December, 2012, and included 14 327 patients in our analyses. The PCR-adjusted therapeutic efficacy was 97·6% (95% CI 97·4-97·9) at day 28 and 96·0% (95·6-96·5) at day 42. After controlling for age and parasitaemia, patients prescribed a higher dose of artemether had a lower risk of having parasitaemia on day 1 (adjusted odds ratio [OR] 0·92, 95% CI 0·86-0·99 for every 1 mg/kg increase in daily artemether dose; p=0·024), but not on day 2 (p=0·69) or day 3 (0·087). In Asia, children weighing 10-15 kg who received a total lumefantrine dose less than 60 mg/kg had the lowest PCR-adjusted efficacy (91·7%, 95% CI 86·5-96·9). In Africa, the risk of treatment failure was greatest in malnourished children aged 1-3 years (PCR-adjusted efficacy 94·3%, 95% CI 92·3-96·3). A higher artemether dose was associated with a lower gametocyte presence within 14 days of treatment (adjusted OR 0·92, 95% CI 0·85-0·99; p=0·037 for every 1 mg/kg increase in total artemether dose). Interpretation: The recommended dose of artemether-lumefantrine provides reliable efficacy in most patients with uncomplicated malaria. However, therapeutic efficacy was lowest in young children from Asia and young underweight children from Africa; a higher dose regimen should be assessed in these groups. Funding: Bill & Melinda Gates Foundation. © 2015 Elsevier Ltd.Item The Malaria Genomic Epidemiology Network. A global network for investigating the genomic epidemiology of malaria(Nature 456(7223): 732-7, 2008) Achidi, E.A.; Agbenyega, T.; Allen, S.; Amodu, O.; Bojang, K.; Conway, D.; Corran, P.; Deloukas, P.; Djimde, A.; Dolo, A.; Doumbo, O.; Drakeley, C.; Duffy, P.; Dunstan, S.; Evans, J.; Farrar, J.; Fernando, D.; Tran, T.H.; Horstmann, R.; Ibrahim, M.; Karunaweera, N.; Kokwaro, G.; Koram, K.; Kwiatkowski, D.; Lemnge, M.; Makani, J.; Marsh, K.; Michon, P.; Modiano, D.; Molyneux, M.E.; Mueller, I.; Mutabingwa, T.; Parker, M.; Peshu, N.; Plowe, C.; Puijalon, O.; Ragoussis, J.; Reeder, J.; Reyburn, H.; Riley, E.; Rogers, J.; Wilson, M.; Ghansah, A.Large-scale studies of genomic variation could assist efforts to eliminate malaria. But there are scientific, ethical and practical challenges to carrying out such studies in developing countries, where the burden of disease is greatest. The Malaria Genomic Epidemiology Network (MalariaGEN) is now working to overcome these obstacles, using a consortial approach that brings together researchers from 21 countries.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 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).