***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: Abstract Background Emergence of artemisinin-resistant malaria in Southeast Asian countries threatens the global control of malaria . Although K13 kelch propeller has been assessed for artemisinin resistance molecular marker , most of the mutations need to be vali date d. In this study , artemisinin resistance was assessed by clinical and molecular analysis , including k13 and recently reported markers , pfarps10 , pffd and pfmdr2 . Methods A prospect i ve cohort study in 1160 uncomplicated falciparum patients was conducted after treatment with artemisinin-based combination therapy ( ACT ) , in 6 sentinel sites in Myanmar from 2009 to 2013 . Therapeutic efficacy of ACT was assessed by longitudinal follow ups . Molecular markers analysis was done on all available day 0 sample s. Results True recrudescence treatment failures cases and day 3 parasite positivity were detected at only the southern Myanmar sites . Day 3 positive and k13 mutants with higher prevalence of underlying genetic foci predisposing to become k13 mutant were detected only in southern Myanmar since 2009 and comparatively fewer mutations of pfarps10 , pffd , and pfmdr2 were observed in western Myanmar . K13 mutations , V127 M of pfarps10 , D193Y of pffd , and T448I of pfmdr2 were significantly associated with day 3 positivity ( OR : 6.48 , 3.88 , 2.88 , and 2.52 , respectively ) . Conclusions Apart from k13 , pfarps10 , pffd and pfmdr2 are also useful for molecular surveillance of artemisinin resistance especially where k13 mutation has not been reported . Appropriate action to eliminate the resistant parasites and surveillance on artemisinin resistance should be strengthened in Myanmar . Trial registration This study was registered with Clinical Trials.gov , identifier NCT02792816 Background Artemisinin-based combination therapy has been first-line treatment for falciparum malaria in Myanmar since 2005 . The wide extent of artemisinin resistance in the Greater Mekong sub-region and the presence of mefloquine resistance at the Myanmar-Thail and border raise concerns over resistance patterns in Myanmar . The availability of molecular markers for resistance to both drugs enables assessment even in remote malaria-endemic areas . Methods A total of 250 dried blood spot sample s collected from patients with Plasmodium falciparum malarial infection in five malaria-endemic areas across Myanmar were analysed for kelch 13 sequence ( k13 ) and pfmdr1 copy number variation . K13 mutations in the region corresponding to amino acids 210–726 ( including the propeller region of the protein ) were detected by nested PCR amplification and sequencing , and pfmdr1 copy number variation by real-time PCR . In two sites , a sub-set of patients were prospect ively followed up for assessment of day-3 parasite clearance rates after a st and ard course of artemether-lumefantrine . Results K13 mutations and pfmdr1 amplification were successfully analysed in 206 and 218 sample s , respectively . Sixty-nine isolates ( 33.5 % ) had mutations within the k13 propeller region with 53 of these ( 76.8 % ) having mutations already known to be associated with artemisinin resistance . F446I ( 32 isolates ) and P574L ( 15 isolates ) were the most common examples . K13 mutation was less common in sites in western border regions ( 29 of 155 isolates ) compared to sample s from the east and north ( 40 of 51 isolates ; p < 0.0001 ) . The overall proportion of parasites with multiple pfmdr1 copies ( greater than 1.5 ) was 5.5 % . Seven sample s showed both k13 mutation and multiple copies of pfmdr1 . Only one of 36 patients followed up after artemether-lumefantrine treatment still had parasites at day 3 ; molecular analysis indicated wild-type k13 and single copy pfmdr1 . Conclusion The proportion of P. falciparum isolates with mutations in the propeller region of k13 indicates that artemisinin resistance extends across much of Myanmar . There is a low prevalence of parasites with multiple pfmdr1 copies across the country . The efficacy of artemisinin-based combination therapy containing mefloquine and lumefantrine is , therefore , expected to be high , although regular monitoring of efficacy will be important Background Intensified efforts are urgently needed to contain and eliminate artemisinin-resistant Plasmodium falciparum in the Greater Mekong subregion . Médecins Sans Frontières plans to support the Ministry of Health in eliminating P. falciparum in an area with artemisinin resistance in the north-east of Cambodia . As a first step , the prevalence of Plasmodium spp . and the presence of mutations associated with artemisinin resistance were evaluated in two districts of Preah Vihear Province . Methods A cross-sectional population -based study using a two-stage cluster sampling was conducted in the rural districts of Chhaeb and Chey Saen , from September to October 2013 . In each district , 30 clusters of 10 households were r and omly selected . In total , blood sample s were collected for 1,275 participants in Chhaeb and 1,224 in Chey Saen . Prevalence of Plasmodium spp . was assessed by PCR on dried blood spots . Plasmodium falciparum positive sample s were screened for mutations in the K13-propeller domain gene ( PF3D7_1343700 ) . Result The prevalence of Plasmodium spp . was estimated at 1.49 % ( 95 % CI 0.71–3.11 % ) in Chhaeb and 2.61 % ( 95 % CI 1.45–4.66 % ) in Chey Saen . Twenty-seven sample s were positive for P. falciparum , giving a prevalence of 0.16 % ( 95 % CI 0.04–0.65 ) in Chhaeb and 2.04 % ( 95 % CI 1.04–3.99 % ) in Chey Saen . Only 4.0 % of the participants testing positive presented with fever or history of fever . K13-propeller domain mutant type alleles ( C580Y and Y493H ) were found , only in Chey Saen district , in seven out of 11 P. falciparum positive sample s with enough genetic material to allow testing . Conclusion The overall prevalence of P. falciparum was low in both districts but parasites presenting mutations in the K13-propeller domain gene , strongly associated with artemisinin-resistance , are circulating in Chey Saen . The prevalence might be underestimated because of the absentees – mainly forest workers - and the workers of private companies who were not included in the study . These results confirm the need to urgently develop and implement targeted interventions to contain and eliminate P. falciparum malaria in this district before it spreads to other areas BACKGROUND Artemisinin-based combination therapies are the recommended first-line treatments of falciparum malaria in all countries with endemic disease . There are recent concerns that the efficacy of such therapies has declined on the Thai-Cambodian border , historically a site of emerging antimalarial-drug resistance . METHODS In two open-label , r and omized trials , we compared the efficacies of two treatments for uncomplicated falciparum malaria in Pailin , western Cambodia , and Wang Pha , northwestern Thail and : oral artesunate given at a dose of 2 mg per kilogram of body weight per day , for 7 days , and artesunate given at a dose of 4 mg per kilogram per day , for 3 days , followed by mefloquine at two doses totaling 25 mg per kilogram . We assessed in vitro and in vivo Plasmodium falciparum susceptibility , artesunate pharmacokinetics , and molecular markers of resistance . RESULTS We studied 40 patients in each of the two locations . The overall median parasite clearance times were 84 hours ( interquartile range , 60 to 96 ) in Pailin and 48 hours ( interquartile range , 36 to 66 ) in Wang Pha ( P<0.001 ) . Recrudescence confirmed by means of polymerase-chain-reaction assay occurred in 6 of 20 patients ( 30 % ) receiving artesunate monotherapy and 1 of 20 ( 5 % ) receiving artesunate-mefloquine therapy in Pailin , as compared with 2 of 20 ( 10 % ) and 1 of 20 ( 5 % ) , respectively , in Wang Pha ( P=0.31 ) . These markedly different parasitologic responses were not explained by differences in age , artesunate or dihydroartemisinin pharmacokinetics , results of isotopic in vitro sensitivity tests , or putative molecular correlates of P. falciparum drug resistance ( mutations or amplifications of the gene encoding a multidrug resistance protein [ PfMDR1 ] or mutations in the gene encoding sarco-endoplasmic reticulum calcium ATPase6 [ PfSERCA ] ) . Adverse events were mild and did not differ significantly between the two treatment groups . CONCLUSIONS P. falciparum has reduced in vivo susceptibility to artesunate in western Cambodia as compared with northwestern Thail and . Resistance is characterized by slow parasite clearance in vivo without corresponding reductions on conventional in vitro susceptibility testing . Containment measures are urgently needed . ( Clinical Trials.gov number , NCT00493363 , and Current Controlled Trials number , IS RCT N64835265 . ABSTRACT Imported malaria has been a great challenge for public health in China due to decreased locally transmitted cases and frequent exchange worldwide . Plasmodium falciparum has been mainly responsible for the increasing impact . Currently , artesunate plus amodiaquine , one of the artemisinin combination therapies recommended by the World Health Organization , has been mainly used against uncomplicated P. falciparum malaria in China . However , drug resistance marker polymorphism in returning migrant workers has not been demonstrated . Here , we have evaluated the prevalence of pfmdr1 and pfcrt polymorphisms , as well as the K13 propeller gene , a molecular marker of artemisinin resistance , in migrant workers returned from Ghana to Shanglin County , Guangxi Province , China , in 2013 . A total of 118 blood sample s were r and omly selected and used for the assay . Mutations of the pfmdr1 gene that covered codons 86 , 184 , 1034 , and 1246 were found in 11 isolates . Mutations at codon N86Y ( 9.7 % ) were more frequent than at others , and Y86Y184S1034D1246 was the most prevalent ( 63.6 % ) of the four haplotypes . Mutations of the pfcrt gene that covered codons 74 , 75 , and 76 were observed in 17 isolates , and M74N75T76 was common ( 70.6 % ) in three haplotypes . Eight different genotypes of the K13 propeller were first observed in 10 sample s in China , 2 synonymous mutations ( V487V and A627A ) and 6 nonsynonymous mutations . C580Y was the most prevalent ( 2.7 % ) in all the sample s. The data presented might be helpful for enrichment of molecular surveillance of antimalarial resistance and will be useful for developing and updating antimalarial guidance in China The emergence of resistance to artemisinin derivatives in Southeast Asia , manifested as delayed clearance of Plasmodium falciparum following treatment with artemisinins , is a major concern . Recently , the artemisinin resistance phenotype was attributed to mutations in portions of a P. falciparum gene ( PF3D7_1343700 ) encoding kelch ( K13 ) propeller domains , providing a molecular marker to monitor the spread of resistance . The P. falciparum cysteine protease falcipain-2 ( FP2 ; PF3D7_1115700 ) has been shown to contribute to artemisinin action , as hemoglobin degradation is required for potent drug activity , and a stop mutation in the FP2 gene was identified in parasites selected for artemisinin resistance . Although delayed parasite clearance after artemisinin-based combination therapy ( ACT ) has not yet been noted in Ug and a and ACTs remain highly efficacious , characterizing the diversity of these genes is important to assess the potential for resistance selection and to provide a baseline for future surveillance . We therefore sequenced the K13-propeller domain and FP2 gene in P. falciparum isolates from children previously treated with ACT in Ug and a , including sample s from 2006–7 ( n = 49 ) and from 2010–12 ( n = 175 ) . Using 3D7 as the reference genome , we identified 5 non-synonymous polymorphisms in the K13-propeller domain ( 133 isolates ) and 35 in FP2 ( 160 isolates ) ; these did not include the polymorphisms recently associated with resistance after in vitro selection or identified in isolates from Asia . The prevalence of K13-propeller and F 
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Conclusion This review identified emergence of potential ART-resistance mediating k13 mutations in the African region .
Diversity of mutations in pfkelch13 gene is highest in African region compared to SEA .
Mutations outside the pfkelch13 propeller region associated with increased ART parasite clearance half-life occur in malaria-affected regions