***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 In Malawi , there has been a return of Plasmodium falciparum sensitivity to chloroquine ( CQ ) since sulfadoxine-pyrimethamine ( SP ) replaced CQ as first line treatment for uncomplicated malaria . When used for prophylaxis , Amodiaquine ( AQ ) was associated with agranulocytosis but is considered safe for treatment and is increasingly being used in Africa . Here we compare the efficacy , safety and selection of resistance using SP or CQ+SP or artesunate (ART)+SP or AQ+SP for the treatment of uncomplicated falciparum malaria . Methodology and Findings 455 children aged 1–5 years were recruited into a double-blinded r and omised trial comparing SP to the three combination therapies . Using intention to treat analysis with missing outcomes treated as successes , and without adjustment to distinguish recrudescence from new infections , the day 28 adequate clinical and parasitological response ( ACPR ) rate for SP was 25 % , inferior to each of the three combination therapies ( p<0.001 ) . AQ+SP had an ACPR rate of 97 % , higher than CQ+SP ( 81 % ) and ART+SP ( 70 % ) , p<0.001 . Nineteen children developed a neutropenia of ≤0.5 × 103 cells/µl by day 14 , more commonly after AQ+SP ( p = 0.03 ) . The mutation pfcrt 76 T , associated with CQ resistance , was detected in none of the pre-treatment or post-treatment parasites . The prevalence of the pfmdr1 86Y mutation was higher after treatment with AQ+SP than after SP , p = 0.002 . Conclusions The combination AQ+SP was highly efficacious , despite the low efficacy of SP alone ; however , we found evidence that AQ may exert selective pressure for resistance associated mutations many weeks after treatment . This study confirms the return of CQ sensitivity in Malawi and importantly , shows no evidence of the re-emergence of pfcrt 76 T after treatment with CQ or AQ . Given the safety record of AQ when used as a prophylaxis , our observations of marked falls in neutrophil counts in the AQ+SP group requires further scrutiny . Trial Registration Controlled-Trials.com IS RCT Background Sulphadoxine-pyrimethamine ( SP ) a widely used treatment for uncomplicated malaria and recommended for intermittent preventive treatment of malaria in pregnancy , is being investigated for intermittent preventive treatment of malaria in infants ( IPTi ) . High levels of drug resistance to SP have been reported from north-eastern Tanzania associated with mutations in parasite genes . This study compared the in vivo efficacy of SP in symptomatic 6–59 month children with uncomplicated malaria and in asymptomatic 2–10 month old infants . Methodology and Principal Findings An open label single arm ( SP ) st and ard 28 day in vivo WHO antimalarial efficacy protocol was used in 6 to 59 months old symptomatic children and a modified protocol used in 2 to 10 months old asymptomatic infants . Enrolment was stopped early ( 87 in the symptomatic and 25 in the asymptomatic studies ) due to the high failure rate . Molecular markers were examined for recrudescence , re-infection and markers of drug resistance and a review of literature of studies looking for the 581 G dhps mutation was carried out . In symptomatic children PCR-corrected early treatment failure was 38.8 % ( 95 % CI 26.8–50.8 ) and total failures by day 28 were 82.2 % ( 95 % CI 72.5–92.0 ) . There was no significant difference in treatment failures between asymptomatic and symptomatic children . 96 % of sample s carried parasites with mutations at codons 51 , 59 and 108 in the dhfr gene and 63 % carried a double mutation at codons 437 and 540 . 55 % carried a third mutation with the addition of a mutation at codon 581 in the dhps gene . This triple : triple haplotype maybe associated with earlier treatment failure . Conclusion In northern Tanzania SP is a failed drug for treatment and its utility for prophylaxis is doubtful . The study found a new combination of parasite mutations that maybe associated with increased and earlier failure . Trial Registration Clinical Trials.gov Intermittent preventive treatment in pregnancy ( IPTp ) is used to prevent Plasmodium falciparum malaria . However , parasites resistant to the IPTp drug sulfadoxine-pyrimethamine ( SP ) have emerged worldwide , and infections with mixed resistant and susceptible parasites are exacerbated by pyrimethamine in mice . In a prospect i ve delivery cohort in Muheza , Tanzania , we examined the effects of SP IPTp on parasite resistance alleles , parasite diversity , level of parasitemia , and inflammation in the placenta .  IPTp use was associated with an increased fraction of parasites carrying the resistance allele at DHPS codon 581 , an increase in the level of parasitemia , and more intense placental inflammation . The lowest mean level of parasite diversity and highest mean level of parasitemia occurred in women after recent IPTp use . These findings support a model of parasite release and facilitation , whereby the most highly resistant parasites out-compete less fit parasite population s and overgrow under drug pressure . Use of partially effective anti-malarial agents for IPTp may exacerbate  malaria infections in the setting of widespread drug resistance OBJECTIVE To assess the efficacy at individual level of intermittent preventive treatment with sulfadoxine-pyrimethamine ( IPTp-SP ) in primi- and secundigravidae in rural Burkina Faso . METHODS Data of 1441 women enrolled in a health centre r and omized trial and delivering a live-singleton between September 2004 and October 2006 were analysed at individual level . Prevalence of peripheral and placental parasitaemia , anaemia ( PCV < 33 % ) , low-birth weight ( < 2500 g ; LBW ) , mean packed cell volume ( PCV ) and birth weight were compared in relation to the number of directly observed SP doses . RESULTS Two or more doses of SP significantly reduced the risk of placental parasitaemia [ adjusted odds ratio ( AOR ) = 0.04 , 95%CI = 0.003 - 0.60 , P = 0.023 ] and anaemia at delivery ( AOR = 0.31 , 95%CI = 0.18 - 0.52 , P < 0.001 ) . IPTp was associated with reduced risk of LBW in primigravidae ( AOR = 0.11 , 95%CI = 0.07 - 0.17 , P < 0.001 ) but not secundigravidae ( AOR = 0.70 , 95%CI = 0.26 - 1.91 , P = 0.452 ) . For each increment in number of SP doses mean PCV increased by 1.0 % ( 95%CI = 0.4 - 1.7 , P = 0.005 ) at 32 weeks gestation , by 1.2 % ( 95%CI = 0.2 - 2.2 , P = 0.025 ) at delivery and mean birth weight by 220 g ( 95%CI = 134 - 306 P < 0.001 ) in primigravidae and by 102 g ( 95%CI = 55 - 148 , P = 0.001 ) in secundigravidae . CONCLUSION The risk of malaria infection was significantly reduced by IPTp with SP in primi- and secundigravidae in rural Burkina Faso . The impact on clinical outcomes is lower and mainly limited to primigravidae for LBW . Incomplete uptake of IPTp-SP and limited effect in low risk groups together may substantially dilute the measurable impact of effective interventions . This needs to be taken into account when evaluating interventions at community level Abstract .The safety and efficacy of a fixed 25 mg pyrimethamine-500 mg sulfadoxine combination supplemented with 15 mg folinic acid twice a week as primary prophylaxis of Pneumocystis carinii pneumonia ( PCP ) and toxoplasmic encephalitis was evaluated in 106 patients infected with the human immunodeficiency virus . All patients had a CD4 + T-lymphocyte count of less than 100 cells/μl at study entry . Efficacy in this single-arm open-label prospect i ve study was analyzed on an as-treated basis . No patient received highly active antiretroviral treatment , including protease inhibitors or non-nucleoside reverse transcriptase inhibitors , while on study medication . PCP developed in four patients , one of whom had been noncompliant . No PCP episode occurred in the first year . Probabilities of freedom from PCP were 0.97 ( 95%CI , 0.92–1 ) after 24 months and 0.93 ( 95%CI , 0.84–1 ) after 36 months . Of 74 ( 69.8 % ) patients positive for anti-toxoplasma IgG antibodies , one noncompliant patient developed toxoplasmic encephalitis after 24 months . Allergic reactions were observed in 18 ( 17 % ) patients and result ed in permanent discontinuation in 7 ( 6.6 % ) patients . One ( 0.9 % ) patient who had continued prophylaxis despite progressive hypersensitivity reactions developed a serious adverse reaction ( Stevens-Johnson syndrome ) . The median survival of study participants was 29 months , with relentless progression of AIDS accounting for most deaths . The prophylaxis regimen studied appeared safe and effective for primary prophylaxis of PCP and toxoplasmic encephalitis . Severe adverse events can likely be prevented by discontinuation of prophylaxis at the time allergic reactions are noted . Rechallenge frequently results in tolerance . Efficacy and safety compare favorably with previously studied regimens . This simple prophylactic regimen may provide a convenient alternative for patients failing or intolerant to approved regimens This study examines the relationship between malaria treatment failure after sulfadoxine-pyrimethamine ( S-P ) chemotherapy  and presence of mutations in the Plasmodium falciparum dihydropteroate synthase ( dhps ) and dihydrofolate reductase ( dhfr ) genes ( associated with resistance in vitro to S and P ) before treatment . In Kenya , 38 malaria patients in a holoendemic area , and 21 in an epidemic area , participated in the trial in 1997 - 98 . In the 2 areas , drug failure occurred in 76 % and 75 % of cases where any mutation in dhfr was seen ( positive predictive values 76 % and 75 % : P = 0.003 and 0.008 ) and an identical association was seen with dhfr Asn-108 . In the holoendemic area all occurrences of > or = 2 mutations in dhfr predicted drug failure . Only 3 instances were seen in the epidemic focus , but treatment failed in all . Only in the epidemic focus , 7 ( 88 % ) of 8 occurrences of > or = 1 mutations in dhps , and all occurrences of the Gly-437 allele of dhps , predicted failure . Association between mutations in dhps and mutations in dhfr was noted in the combined sites , irrespective of outcome . Although this makes the relationship of combined dhfr and dhps mutations to failure more difficult to interpret , it nevertheless supports S-P selection acting on both genes . In the holoendemic site , treatment success increased with age . In this location , acquired immunity may mask the impact of mutations in dhps , since sulfadoxine is a less effective treatment than pyrimethamine ABSTRACT Antifolate drugs have an important role in the treatment of malaria . Polymorphisms in the genes encoding the dihydrofolate reductase and dihydropteroate synthetase enzymes cause resistance to the antifol and sulfa drugs , respectively . Rw and a has the highest levels of antimalarial drug resistance in Africa . We correlated the efficacy of chlorproguanil-dapsone plus artesunate ( CPG-DDS+A ) and amodiaquine plus sulfadoxine-pyrimethamine ( AQ+SP ) in children with uncomplicated malaria caused by Plasmodium falciparum parasites with pfdhfr and pfdhps mutations , which are known to confer reduced drug susceptibility , in two areas of Rw and a. In the eastern province , where the cure rates were low , over 75 % of isolates had three or more pfdhfr mutations and two or three pfdhps mutations and 11 % had the pfdhfr 164-Leu polymorphism . In the western province , where the cure rates were significantly higher ( P < 0.001 ) , the prevalence of multiple resistance mutations was lower and the pfdhfr I164L polymorphism was not found . The risk of treatment failure following the administration of AQ+SP more than doubled for each additional pfdhfr resistance mutation ( odds ratio [ OR ] = 2.4 ; 95 % confidence interval [ CI ] = 1.01 to 5.55 ; P = 0.048 ) and each pfdhps mutation ( OR = 2.1 ; 95 % CI = 1.21 to  
    Output:
    
There appears to be a prevalence of 581 G above which IPTp-SP no longer protects against LBW .