***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 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background The emergence of resistance against artemisinin combination treatment is a major concern for malaria control . ACTs are recommended as the rescue treatment , however , there is limited evidence as to whether treatment and re-treatment with ACTs select for drug-resistant P. falciparum parasites . Thus , the purpose of the present study is to investigate the impact of (re-)treatment using artesunate-amodiaquine ( ASAQ ) and artemether-lumefantrine ( AL ) on the selection of P. falciparum multidrug resistance-1 ( Pfmdr1 ) alleles in clinical setting s. Methods P. falciparum positive sample s were collected from children aged 12–59 months in a clinical trial in DR Congo and Ug and a. Pfmdr1 single nucleotide polymorphisms ( SNPs ) analysis at codons N86Y , Y184F , and D1246Y were performed at baseline and post-treatment with either AL or ASAQ as a rescue treatment using nested PCR followed by restriction fragment length polymorphism ( RFLP ) assays . Results The pre-treatment prevalence of Pfmdr1 N86 and D1246Y varied significantly between the sites , ( p>0.001 ) and ( p = 0.013 ) , respectively . There was borderline significant directional selection for Pfmdr1 184F in recurrent malaria infections after treatment with AL in Ug and a site ( p = 0.05 ) . Pfmdr1 NFD haplotype did not significantly change in post-treatment infections after re-treatment with either AL or ASAQ . Comparison between pre-treatment and post-treatment recurrences did not indicate directional selection of Pfmdr1 N86 , D1246 alleles in the pre- RCT , RCT and post- RCT phases in both AL and ASAQ treatment arms . Pfmdr1 86Y was significantly associated with reduced risk of AL treatment failure ( RR = 0.34 , 95 % CI:0.11–1.05 , p = 0.04 ) while no evidence for D1246 allele ( RR = 1.02 ; 95 % CI : 0.42–2.47 , p = 1.0 ) . Survival estimates showed that the Pfmdr1 alleles had comparable mean-time to PCR-corrected recrudescence and new infections in both AL and ASAQ treatment arms . Conclusion We found limited impact of (re-)treatment with AL or ASAQ on selection for Pfmdr1 variants and haplotypes associated with resistance to partner drugs . These findings further supplement the evidence use of same or alternative ACTs as a rescue therapy for recurrent P.falciparum infections . Continued monitoring of genetic signatures of resistance is warranted to timely inform malaria (re-)treatment policies and guidelines Background The emergence of artemisinin-resistant P. falciparum malaria in South-East Asia highlights the need for continued global surveillance of the efficacy of artemisinin-based combination therapies . Methods On the Kenyan coast we studied the treatment responses in 474 children 6–59 months old with uncomplicated P. falciparum malaria in a r and omized controlled trial of dihydroartemisinin-piperaquine vs. artemether-lumefantrine from 2005 to 2008 . ( IS RCT N88705995 ) Results The proportion of patients with residual parasitemia on day 1 rose from 55 % in 2005–2006 to 87 % in 2007–2008 ( odds ratio , 5.4 , 95%CI , 2.7–11.1 ; P<0.001 ) and from 81 % to 95 % ( OR , 4.1 , 95%CI , 1.7–9.9 ; P = 0.002 ) in the DHA-PPQ and AM-LM groups , respectively . In parallel , Kaplan-Meier estimated risks of apparent recrudescent infection by day 84 increased from 7 % to 14 % ( P = 0.1 ) and from 6 % to 15 % ( P = 0.05 ) with DHA-PPQ and AM-LM , respectively . Coinciding with decreasing transmission in the study area , clinical tolerance to parasitemia ( defined as absence of fever ) declined between 2005–2006 and 2007–2008 ( OR body temperature > 37.5 ° C , 2.8 , 1.9–4.1 ; P<0.001 ) . Neither in vitro sensitivity of parasites to DHA nor levels of antibodies against parasite extract accounted for parasite clearance rates or changes thereof . Conclusions The significant , albeit small , decline through time of parasitological response rates to treatment with ACTs may be due to the emergence of parasites with reduced drug sensitivity , to the coincident reduction in population -level clinical immunity , or both . Maintaining the efficacy of artemisinin-based therapy in Africa would benefit from a better underst and ing of the mechanisms underlying reduced parasite clearance rates . Trial Registration Controlled-Trials.com IS RCT Summary Background Artemisinin-based combination therapies ( ACTs ) are the most effective treatment for uncomplicated Plasmodium falciparum malaria infection . A commonly used indicator for monitoring and assessing progress in coverage of malaria treatment is the proportion of children younger than 5 years with reported fever in the previous 14 days who have received an ACT .  We propose an improved indicator that incorporates parasite infection status ( as assessed by a rapid diagnostic test [ RDT ] ) , which is available in recent household surveys . In this study we estimated the annual proportion of children younger than 5 years with fever and a positive RDT in Africa who received an ACT in 2003–15 . Methods Our modelling study used cross-sectional data on treatment for fever  and  RDT  status for children younger than 5 years compiled from all nationally available representative household surveys ( the Malaria Indicator Surveys , Demographic and Health Surveys , and Multiple Indicator Cluster Surveys ) across sub-Saharan Africa between 2003 and 2015 . Estimates for the proportion of children younger than 5 years with a fever within the previous 14 days and P falciparum infection assessed by RDT who received an ACT were incorporated in a generalised additive mixed model , including data on ACT distributions , to estimate coverage across all countries and time periods . We did r and om effects meta-analyses to examine individual , household , and community effects associated with ACT coverage . Findings We obtained data on 201 704 children younger than 5 years from 103 surveys ( 22 MIS , 61 DHS , and 20 MICS ) across 33 countries .  RDT results were available for 40 of these surveys including 40 261 ( 20 % ) children , and we predicted RDT status for the remaining 161 443 ( 80 % ) children . Our results showed that ACT coverage in children younger than 5 years with a fever and P falciparum infection increased across sub-Saharan Africa in 2003–15 , but even in 2015 , only 19.7 % ( 95 % CI 15.6–24.8 ) of children younger than 5 years with a fever and P falciparum infection received an ACT . In meta-analyses , children younger than 5 years were more likely to receive an ACT for fever and P falciparum infection if they lived in an urban area ( vs rural area ; odds ratio [ OR ] 1.18 , 95 % CI 1.06–1.31 ) , had household wealth above the national median ( vs wealth below the median ; OR 1.26 , 1.16–1.39 ) , had a caregiver with any education ( vs no education ; OR 1.31 , 1.22–1.41 ) , had a household insecticide-treated net ( ITN ; vs no ITN ; OR 1.21 , 1.13–1.29 ) , were older than 2 years ( vs ≤2 years ; OR 1.09 , 1.01–1.17 ) , or lived in an area with a higher mean P falciparum prevalence in children aged 2–10 years ( OR 1.12 , 1.02–1.23 ) . In the subgroup of children for whom treatment was sought , those who sought treatment in the public sector were more likely to receive an ACT ( vs the private sector ; OR 3.18 , 2.67–3.78 ) . Interpretation Despite progress during the 2003–15 malaria programme , ACT treatment for children with malaria remains unacceptably low . More work is needed at the country level to underst and how health-care access , service delivery , and ACT supply might be improved to ensure appropriate treatment for all children with malaria . Funding US President 's Malaria Initiative and Medicines for Malaria Venture Background Molecular tools for detection of low-density asymptomatic Plasmodium infections are needed in malaria elimination efforts . This study reports results from the hitherto largest implementation of loop-mediated isothermal amplification ( LAMP ) for central ized mass screening of asymptomatic malaria in Zanzibar . Methods Healthy individuals present and willing to participate in r and omly selected households in 60 villages throughout Zanzibar were screened for malaria by rapid diagnostic tests ( RDT ) . In 50 % of the study households , participants were asked to provide 60 μL of finger-prick blood for additional LAMP screening . LAMP was conducted in two central ized laboratories in Zanzibar , by trained technicians with limited or no previous experience of molecular methods . The LAMP assay was performed with LoopampTM MALARIA Pan/Pf Detection Kit ( Eiken Chemical Company , Japan ) . Sample s positive for Plasmodium genus (Pan)-LAMP were re-tested using Plasmodium falciparum-specific LAMP kits . Results Paired RDT and LAMP sample s were available from 3983 individuals .  The prevalence of asymptomatic malaria was 0.5 % ( CI 95 % 0.1 - 0.8 ) and 1.6 % ( CI 95 % 1.1 - 2.2 ) by RDT and Pan-LAMP , respectively . LAMP detected 3.4 ( CI 95 % 2.2 - 5.2 ) times more Plasmodium positive sample s than RDT . DNA contamination was experienced , but solved by repetitive decontamination of all equipment and reagents . Conclusions LAMP is a simple and sensitive molecular tool , and has potential in active surveillance and mass-screening programmes for detection of low-density asymptomatic malaria in pre-elimination setting s. However , in order to deploy LAMP more effectively in field setting s , protocol s may need to be adapted for processing larger numbers of sample s. A higher throughput , affordable closed system would be ideal to avoid contamination Background Plasmodium falciparum uncomplicated malaria can successfully be treated with an artemisinin-based combination therapy ( ACT ) . However resistance is spreading to the different ACT compounds ; the artemisinin derivative and the partner drug . Studies of P. falciparum polymorphisms associated with drug resistance can provide a useful tool to track resistance and guide treatment policy as well as an in-depth underst and ing of the development and spread of resistance . Methods The role of P. falciparum molecular markers in selection of reinfections was assessed in an efficacy trial comparing artesunate – amodiaquine fixed-dose combination with artemether – lumefantrine to treat malaria in Nimba County , Liberia 2008–2009 . P. falciparum polymorphisms in pfcrt 76 , pfmdr1 86 , 184 and 1246 , and pfmrp1 876 and 1466 were analysed by PCR-RFLP and pyrosequencing . Results High baseline prevalence of pfmdr1 1246Y was found in Nimba county ( 38 % ) . Pfmdr1 1246Y and pfmdr1 86 + 184 + 1246 haplotypes NYY and YYY were selected in reinfections in the artesunate – amodiaquine arm and pfcrt K76 , pfmdr1 N86 and pfmdr1 haplotype NFD were selected in artemether – lumefantrine reinfections . Parasites harbouring pfmdr1 1246Y could reinfect earlier after treatment with artesunate – amodiaquine and parasites carrying pfmdr1 N86 could reinfect at higher lumefantrine concentrations in patients treated with artemether – lumefantrine . Conclusions Although treatment is highly efficacious , selection of molecular markers in reinfections could indicate a decreased sensitivity or tolerance of parasites to the current treatments and the baseline prevalence of molecular markers should be closely monitored . Since individual drug levels and the day of reinfection were demonstrated to be key determinants for selection of reinfections , this data needs to be collected and taken into account for accurate evaluation of molecular markers for anti-malarial treatments . The protocol s for the clinical trial was registered with Current Controlled Trials , under the Identifier Number IS RCT N51688713 on 9 October Artemisinin derivative-based combination therapy is expected to suppress the development of Plasmodium falciparum drug resistance in Africa . We have performed an artemether-lumefantrine ( Coartem ; Novartis ) follow-up clinical trial in Zanzibar , in which pfcrt K76 T and pfmdr1 N86Y frequencies were determined before drug administration and in all recurrent parasites during a follow-up period of 42 days . A significant increase in pfmdr1 86 
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However , these trends could also be explained by a difference in initial SNP frequencies at the time of ACT introduction .
There were non-significant trends for faster selection of N86 and D1246 in areas with higher AL consumption and no trend with transmission intensity .
Recorded consumption of AS-AQ  was low in the locations and times Pfmdr1 data were collected .
SNP trends in countries with AL policies suggest a broad increase in sensitivity of parasites to AS-AQ  , by 7 - 10 years after AL introduction .