***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 Plasmodium falciparum resistance to anti-malarial drugs remains a major obstacle to malaria control and elimination . The parasite has developed resistance to every anti-malarial drug introduced for wide-scale treatment . However , the spread of resistance may be reversible . Malawi was the first country to discontinue chloroquine use due to widespread resistance . Within a decade of the removal of drug pressure , the molecular marker of chloroquine-resistant malaria had disappeared and the drug was shown to have excellent clinical efficacy . Many countries have observed decreases in the prevalence of chloroquine resistance with the discontinuation of chloroquine use . In Zambia , chloroquine was used as first-line treatment for uncomplicated malaria until treatment failures led the Ministry of Health to replace it with artemether-lumefantrine in 2003 . Specimens from a recent study were analysed to evaluate prevalence of chloroquine-resistant malaria in Nchelenge district a decade after chloroquine use was discontinued . Methods Parasite DNA was extracted from dried blood spots collected by finger-prick in pregnant women who were enrolling in a clinical trial . The specimens underwent pyrosequencing to determine the genotype of the P. falciparum chloroquine resistance transporter , the gene that is associated with CQ resistance . Results Three-hundred and two specimens were successfully analysed . No chloroquine-resistant genotypes were detected . Conclusion The study found the disappearance of chloroquine-resistant malaria after the removal of chloroquine drug pressure . Chloroquine may have a role for malaria prevention or treatment in Zambia and throughout the region in the future Background Artemisinin-based combination therapy ( ACT ) is the first-line malaria treatment throughout most of the malaria-endemic world . Data on ACT availability , price and market share are needed to provide a firm evidence base from which to assess the current situation concerning quality -assured ACT supply . This paper presents supply side data from ACTwatch outlet surveys in Benin , the Democratic Republic of Congo ( DRC ) , Madagascar , Nigeria , Ug and a and Zambia . Methods Between March 2009 and June 2010 , nationally representative surveys of outlets providing anti-malarials to consumers were conducted . A census of all outlets with the potential to provide anti-malarials was conducted in clusters sample d r and omly . Results 28,263 outlets were censused , 51,158 anti-malarials were audited , and 9,118 providers interviewed . The proportion of public health facilities with at least one first-line quality -assured ACT in stock ranged between 43 % and 85 % . Among private sector outlets stocking at least one anti-malarial , non-artemisinin therapies , such as chloroquine and sulphadoxine-pyrimethamine , were widely available ( > 95 % of outlets ) as compared to first-line quality -assured ACT ( < 25 % ) . In the public/not-for-profit sector , first-line quality -assured ACT was available for free in all countries except Benin and the DRC ( US$ 1.29 [ Inter Quartile Range ( IQR ) : $ 1.29-$1.29 ] and $ 0.52[IQR : $ 0.00-$1.29 ] per adult equivalent dose respectively ) . In the private sector , first-line quality -assured ACT was 5 - 24 times more expensive than non-artemisinin therapies . The exception was Madagascar where , due to national social marketing of subsidized ACT , the price of first-line quality -assured ACT  ( $ 0.14 [ IQR : $ 0.10 , $ 0.57 ] ) was significantly lower than the most popular treatment ( chloroquine , $ 0.36 [ IQR : $ 0.36 , $ 0.36 ] ) .  Quality -assured ACT accounted for less than 25 % of total anti-malarial volumes ; private-sector quality -assured ACT volumes represented less than 6 % of the total market share . Most anti-malarials were distributed through the private sector , but often comprised non-artemisinin therapies , and in the DRC and Nigeria , oral artemisinin monotherapies .  Provider knowledge of the first-line treatment was significantly lower in the private sector than in the public/not-for-profit sector . Conclusions These st and ardized , nationally representative results demonstrate the typically low availability , low market share and high prices of ACT , in the private sector where most anti-malarials are accessed , with some exceptions . The results confirm that there is substantial room to improve availability and affordability of ACT treatment in the surveyed countries . The data will also be useful for monitoring the impact of interventions such as the Affordable Medicines Facility for malaria In the absence of definite marker for artemisinin ( ART ) resistance , molecular monitoring of its partner drug sulfadoxine pyrimethamine ( SP ) in artemisinin based combination therapy ( ACTs ) together with chloroquine ( CQ ) for which ART is negatively correlated , may predict the effectiveness of ACT . We analyzed 201 Plasmodium falciparum field isolates for drug resistance markers for  CQ ( pfcrt and pfmdr1 ) , pyrimethamine ( pfdhfr ) and sulfadoxine ( pfdhps ) . Our study reveals high prevalence and non-r and om association of resistant mutants ( K76 T and N86Y ) of CQ markers ( pfcrt and pfmdr1 ) . The predominance of highly resistant pfdhfr genotypes for SP with intragenic and intergenic pair-wise linkage disequilibrium between single nucleotide polymorphisms of resistant mutants of pfdhfr ( C59R and S108N ) and pfdhps ( S436A , A437 G , K540E ) warn on further inclusion of SP in ACT . These findings suggest the replacement of SP in ACT with alternative partner drug for better efficacy 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 BACKGROUND Worsening drug resistance in Plasmodium falciparum malaria is a major threat to health in tropical countries . We did a prospect i ve study of malaria incidence and treatment in an area of highly multidrug-resistant P. falciparum malaria . METHODS We assessed incidence of P. falciparum malaria and the in-vivo responses to mefloquine treatment over 13 years in two large camps for displaced Karen people on the northwest border of Thail and . During this time , the st and ard mefloquine dose was first increased , and then combined artesunate and mefloquine was introduced as first-line treatment for uncomplicated P. falciparum malaria . FINDINGS Early detection and treatment controlled P. falciparum malaria initially while mefloquine was effective ( cure rate with mefloquine [ 15 mg/kg ] and sulphadoxine-pyrimethamine in 1985 , 98 % [ 95 % CI 97 - 100 ] ) , but as mefloquine resistance developed , the cure rate fell ( 71 % [ 67 - 77 ] in 1990 ) . A similar pattern was seen for high-dose ( 25 mg/kg ) mefloquine monotherapy from 1990 - 94 . Since the general deployment of the artesunate-mefloquine combination in 1994 , the cure rate increased again to almost 100 % from 1998 onwards , and there has been a sustained decline in the incidence of P. falciparum malaria in the study area . In-vitro susceptibility of P. falciparum to mefloquine has improved significantly ( p=0.003 ) . INTERPRETATION In this area of low malaria transmission , early diagnosis and treatment with combined artesunate and mefloquine has reduced the incidence of P. falciparum malaria and halted the progression of mefloquine resistance . We recommend that antimalarial drugs should be combined with artemisinin or a derivative to protect them against resistance Background The predominance of chloroquine-susceptible falciparum malaria in Malawi more than a decade after chloroquine 's withdrawal permits contemplation of re-introducing chloroquine for targeted uses . We aim ed to compare the ability of different partner drugs to preserve chloroquine efficacy and prevent the re-emergence of resistance . Methodology /Principal Findings Children with uncomplicated malaria were enrolled at a government health center in Blantyre , Malawi . Part 
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Conclusion The prevalence of chloroquine resistance alleles among Plasmodium falciparum parasites have steadily declined since discontinuation of chloroquine use .
However , Pfcrt K76 T and Pfmdr-1 N86Y mutations still persist at moderate frequencies in most malaria affected countries