Association of mutations in the Plasmodium falciparum Kelch13 gene (Pf3D7_1343700) with parasite clearance rates after artemisinin-based treatments : a WWARN individual patient data meta-analysis
| Title: | Association of mutations in the Plasmodium falciparum Kelch13 gene (Pf3D7_1343700) with parasite clearance rates after artemisinin-based treatments : a WWARN individual patient data meta-analysis |
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| Authors: | Amaratunga, Chanaki; Andrianaranjaka, Voahangy Hanitriniaina; Ashley, Elizabeth; Bethell, Delia; Bjorkman, Anders; Bonnington, Craig A.; Cooper, Roland A.; Dhorda, Mehul; Dondorp, Arjen; Erhart, Annette; Fairhurst, Rick M.; Faiz, Abul; Fanello, Caterina; Fukuda, Mark M.; Guerin, Philippe; van Huijsduijnen, Rob Hooft; Hien, Tran Tinh; Hong, N. V.; Htut, Ye; Huang, Fang; Humphreys, Georgina; Imwong, Mallika; Kennon, Kalynn; Lim, Pharath; Lin, Khin; Lon, Chanthap; Mårtensson, Andreas; Mayxay, Mayfong; Mokuolu, Olugbenga; Morris, Ulrika; Ngasala, Billy E.; Amambua-Ngwa, Alfred; Noedl, Harald; Nosten, Francois; Onyamboko, Marie; Phyo, Aung Pyae; Plowe, Christopher V.; Pukrittayakamee, Sasithon; Randrianarivelojosia, Milijaona; Rosenthal, Philip J.; Saunders, David L.; Sibley, Carol Hopkins; Smithuis, Frank; Spring, Michele D.; Sondo, Paul; Sreng, Sokunthea; Starzengruber, Peter; Stepniewska, Kasia; Suon, Seila; Takala-Harrison, Shannon; Thriemer, Kamala; Thuy-Nhien, Nguyen; Tun, Kyaw Myo; White, Nicholas J.; Woodrow, Charles |
| Publisher Information: | Uppsala universitet, Internationell barnhälsa och nutrition; NIAID, Lab Malaria & Vector Res, Div Intramural Res, NIH, Rockville, MD USA; Inst Pasteur Madagascar, Malaria Res Unit, Antananarivo, Madagascar;Univ Antananarivo, Fac Sci, Antananarivo, Madagascar; MOCRU, Yangon, Myanmar;Univ Oxford, Ctr Trop Med & Global Hlth, Oxford, England; Armed Forces Res Inst Med Sci, Bangkok, Thailand; Karolinska Inst, Dept Mol Tumor & Cell Biol, Stockholm, Sweden; Shoklo Malaria Res Unit, Mae Sot, Thailand; Dominican Univ Calif, Dept Nat Sci & Math, San Rafael, CA USA; Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, WWARN, Oxford, England; Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, WWARN, Oxford, England;Mahidol Univ, Fac Trop Med, Mahidol Oxford Res Unit, Bangkok, Thailand; ITM Antwerp, Dept Publ Hlth, Antwerp, Belgium;Inst Trop Med, MRC Unit Gambia, Fajara, Gambia;Inst Trop Med, MRC Unit Gambia, Fajara, Gambia; Dev Care Fdn, Dhaka, Bangladesh; Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, Oxford, England;Mahidol Oxford Res Unit, Bangkok, Thailand; Med Malaria Venture, Geneva, Switzerland; Natl Inst Malariol Parasitol & Entomol, Hanoi, Vietnam; Dept Med Res, Yangon, Myanmar; Chinese Ctr Dis Control & Prevent, Natl Inst Parasit Dis, Shanghai, Peoples R China; Mahidol Univ, Fac Trop Med, Dept Mol Trop Med & Genet, Bangkok, Thailand;Mahidol Univ, Fac Trop Med, Mahidol Oxford Trop Med Res Unit, Bangkok, Thailand; Dept Med Res, Pyin Oo Lwin Branch, Anesakhan, Myanmar; Lao Oxford Mahosot Hospital, Wellcome Trust Res Unit, LOMWRU, Viangchan, Laos;Univ Hlth Sci, Minist Hlth, Fac Postgrad Studies, Viangchan, Laos;Churchill Hosp, Nuffield Dept Med, Ctr Trop Med & Global Hlth, Oxford, England; Univ Ilorin, Coll Hlth Sci, Dept Paediat & Child Hlth, Ilorin, Nigeria;Univ Ilorin, Teaching Hosp, Ctr Malaria & Other Trop Dis Care, Ilorin, Nigeria; Muhimbili Univ Hlth & Allied Sci, Dept Parasitol & Med Entomol, Dar Es Salaam, Tanzania; Inst Trop Med, MRC Unit Gambia, Fajara, Gambia; Med Univ Vienna, Inst Specif Prophylaxis & Trop Med, Vienna, Austria; Shoklo Malaria Res Unit, Mae Sot, Thailand;Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, Oxford, England;Mahidol Univ, Fac Trop Med, Mahidol Oxford Trop Med Res Unit, Bangkok, Thailand; Mahidol Oxford Res Unit, Bangkok, Thailand;Kinshasa Sch Publ Hlth, Kinshasa, DEM REP CONGO; Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, Oxford, England;Mahidol Univ, Fac Trop Med, Mahidol Oxford Trop Med Res Unit, Bangkok, Thailand; Duke Univ, Duke Global Hlth Inst, Durham, NC USA; Mahidol Univ, Dept Clin Trop Med, Bangkok, Thailand;Royal Soc Thailand, Bangkok, Thailand; Inst Pasteur Madagascar, Malaria Res Unit, Antananarivo, Madagascar;Univ Toliara, Fac Sci, Toliara, Madagascar; Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA;Univ Calif San Francisco, Div HIV Infect Dis & Global Med, San Francisco, CA 94143 USA; Armed Forces Res Inst Regenerat Med, Bangkok, Thailand;US Army Med Mat Dev Act, Ft Detrick, MD USA; Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, WWARN, Oxford, England;Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA; Myanmar Oxford Clin Res Unit, Yangon, Myanmar; Armed Forces Res Inst Med Sci, Dept Immunol & Med, Bangkok, Thailand; Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, WWARN, Oxford, England;CRUN, Ouaga, Burkina Faso; Natl Ctr Parasitol Entomol & Malaria Control, Phnom Penh, Cambodia; Med Univ Vienna, Inst Specif Prophylaxis & Trop Med, Vienna, Austria;Med Univ Vienna, Dept Lab Med, Div Clin Microbiol, Vienna, Austria; Univ Oxford, Ctr Trop Med & Global Hlth, WWARN, Oxford, England; Univ Maryland, Sch Med, Inst Global Hlth, Div Malaria Res, Baltimore, MD 21201 USA; Inst Trop Med, Antwerp, Belgium;Menzies Sch Hlth Res, Darwin, NT, Australia; Myanmar Oxford Clin Res Unit, Yangon, Myanmar;Def Serv Med Acad, Yangon, Myanmar; Mahidol Univ, Fac Trop Med, Mahidol Oxford Res Unit, Bangkok, Thailand;Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, Oxford, England |
| Publication Year: | 2019 |
| Collection: | Uppsala University: Publications (DiVA) |
| Subject Terms: | Infectious Medicine; Infektionsmedicin |
| Description: | Background: Plasmodium falciparum infections with slow parasite clearance following artemisinin-based therapies are widespread in the Greater Mekong Subregion. A molecular marker of the slow clearance phenotype has been identified: single genetic changes within the propeller region of the Kelch13 protein (pfk13; Pf3D7_1343700). Global searches have identified almost 200 different non-synonymous mutant pfk13 genotypes. Most mutations occur at low prevalence and have uncertain functional significance. To characterize the impact of different pfk13 mutations on parasite clearance, we conducted an individual patient data meta-analysis of the associations between parasite clearance half-life (PC1/2) and pfk13 genotype based on a large set of individual patient records from Asia and Africa. Methods: A systematic literature review following the PRISMA protocol was conducted to identify studies published between 2000 and 2017 which included frequent parasite counts and pfk13 genotyping. Four databases (Ovid Medline, PubMed, Ovid Embase, and Web of Science Core Collection) were searched. Eighteen studies (15 from Asia, 2 from Africa, and one multicenter study with sites on both continents) met inclusion criteria and were shared. Associations between the log transformed PC1/2 values and pfk13 genotype were assessed using multivariable regression models with random effects for study site. Results: Both the pfk13 genotypes and the PC1/2 were available from 3250 (95%) patients (n=3012 from Asia (93%), n=238 from Africa (7%)). Among Asian isolates, all pfk13 propeller region mutant alleles observed in five or more specific isolates were associated with a 1.5- to 2.7-fold longer geometric mean PC1/2 compared to the PC1/2 of wild type isolates (all p≤0.002). In addition, mutant allele E252Q located in the P. falciparum region of pfk13 was associated with 1.5-fold (95%CI 1.4-1.6) longer PC1/2. None of the isolates from four countries in Africa showed a significant difference between the PC1/2 of parasites with or without pfk13 ... |
| Document Type: | article in journal/newspaper |
| File Description: | application/pdf |
| Language: | English |
| Relation: | BMC Medicine, 2019, 17, s. 1-20; PMID 30651111; ISI:000455890500001 |
| DOI: | 10.1186/s12916-018-1207-3 |
| Availability: | http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-375814; https://doi.org/10.1186/s12916-018-1207-3 |
| Rights: | info:eu-repo/semantics/openAccess |
| Accession Number: | edsbas.53F191EF |
| Database: | BASE |