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Publication Open Access Rapid clinical assessment to facilitate the triage of adults with falciparum malaria, a retrospective analysis.(2014-01-29) Hanson, Josh; Lee, Sue J.; Mohanty, Sanjib; Faiz, M. Abul; Anstey, Nicholas M.; Price, Ric N.; Prakaykaew Charunwatthana; ประกายแก้ว จรูญวรรธนะ; Yunus, Emran Bin; Mishra, Saroj K.; Tjitra, Emiliana; Ridwanur Rahman; Francois Nosten; Htut, Ye; Maude, Richard J.; Chau, Tran Thi Hong; Phu, Nguyen Hoan; Hien, Tran Tinh; White, Nicholas J.; Day, Nicholas P. J.; Dondorp, Arjen M.; Hanson, Josh; Mahidol University. Faculty of Tropical Medicine. Mahidol Oxford Tropical Medicine Research Unit.BACKGROUND: Most adults dying from falciparum malaria will die within 48 hours of their hospitalisation. An essential component of early supportive care is the rapid identification of patients at greatest risk. In resource-poor settings, where most patients with falciparum malaria are managed, decisions regarding patient care must frequently be made using clinical evaluation alone. METHODS: We retrospectively analysed 4 studies of 1801 adults with severe falciparum malaria to determine whether the presence of simple clinical findings might assist patient triage. RESULTS: If present on admission, shock, oligo-anuria, hypo- or hyperglycaemia, an increased respiratory rate, a decreased Glasgow Coma Score and an absence of fever were independently predictive of death. The variables were used to construct a simple clinical algorithm. When applied to the 1801 patients, this algorithm's positive predictive value for survival to 48 hours was 99.4 (95% confidence interval (CI) 97.8-99.9) and for survival to discharge 96.9% (95% CI 94.3-98.5). In the 712 patients receiving artesunate, the algorithm's positive predictive value for survival to 48 hours was 100% (95% CI 97.3-100) and to discharge was 98.5% (95% CI 94.8-99.8). CONCLUSIONS: Simple clinical findings are closely linked to the pathophysiology of severe falciparum malaria in adults. A basic algorithm employing these indices can facilitate the triage of patients in settings where intensive care services are limited. Patients classified as low-risk by this algorithm can be safely managed initially on a general ward whilst awaiting senior clinical review and laboratory data.Publication Open Access Genetic loci associated with delayed clearance of Plasmodium falciparum following artemisinin treatment in Southeast Asia.(2013-01-02) Takala-Harrisona, Shannon; Clark, Taane G.; Cummings, Michael P.; Miotto,Olivo; Dondorp, Arjen M.; Fukudaf, Mark M.; Nosten, Francois; Noedl, Harald; Mallika Imwong; มัลลิกา อิ่มวงศ์; Bethell, Delia; Se, Youry; Lon, Chanthap; Tyner, Stuart D.; Saunders, David L.; Socheat, Duong; Ariey, Frederic; Phyo, Aung Pyae; Starzengruber, Peter; Fuehrer, Hans-Peter; Swoboda, Paul; Stepniewska, Kasia; Flegg, Jennifer; Arze, Cesar; Cerqueira, Gustavo C.; Silva, Joana C.; Ricklefs, Stacy M.; Porcella, Stephen F.; Stephens, Robert M.; Adams, Matthew; Kenefic, Leo J.; Campino, Susana; Auburn, Sarah; MacInnis, Bronwyn; Kwiatkowski, Dominic P.; Su, Xin-zhuan; White, Nicholas J.; Ringwald, Pascal; Plowe, Christopher V.; Plowe, Christopher V.; Mahidol University. Faculty of Tropical Medicine. Mahidol-Oxford Research Unit.; Mahidol University. Faculty of Tropical Medicine. Department of Molecular Tropical Medicine and Genetics.; Mahidol University. Faculty of Tropical Medicine. Shoklo Malaria Research Unit.The recent emergence of artemisinin-resistant Plasmodium falciparum malaria in western Cambodia could threaten prospects for malaria elimination. Identification of the genetic basis of resistance would provide tools for molecular surveillance, aiding efforts to contain resistance. Clinical trials of artesunate efficacy were conducted in Bangladesh, in northwestern Thailand near the Myanmar border, and at two sites in western Cambodia. Parasites collected from trial participants were genotyped at 8,079 single nucleotide polymorphisms (SNPs) using a P. falciparum-specific SNP array. Parasite genotypes were examined for signatures of recent positive selection and association with parasite clearance phenotypes to identify regions of the genome associated with artemisinin resistance. Four SNPs on chromosomes 10 (one), 13 (two), and 14 (one) were significantly associated with delayed parasite clearance. The two SNPs on chromosome 13 are in a region of the genome that appears to be under strong recent positive selection in Cambodia. The SNPs on chromosomes 10 and 13 lie in or near genes involved in postreplication repair, a DNA damage-tolerance pathway. Replication and validation studies are needed to refine the location of loci responsible for artemisinin resistance and to understand the mechanism behind it; however, two SNPs on chromosomes 10 and 13 may be useful markers of delayed parasite clearance in surveillance for artemisinin resistance in Southeast Asia.