***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: Pyrimethamine-sulfadoxine , the first choice for uncomplicated falciparum malaria in Africa , exerts strong selection pressure for resistance because of its slow elimination . It is likely that resistance will emerge rapidly , and there is no widely affordable replacement . Chlorproguanil-dapsone is cheap , rapidly eliminated , more potent than pyrimethamine-sulfadoxine , and could be introduced in the near future to delay the onset of antifolate resistance and as " salvage therapy " for pyrimethamine-sulfadoxine failure . A total of 448 children were r and omly allocated ( double blind ) to either a single dose of pyrimethamine-sulfadoxine or to one of two chlorproguanil-dapsone regimens : a single dose or three doses at 24-h intervals . Reinfections are clinical ly indistinguishable from recrudescence and are more likely after treatment with rapidly eliminated drugs ; we measured the incidence of parasitemia in 205 initially aparasitemic children to allow comparison with the three treatment groups . The patients and a community surveillance group were followed up for 28 days . At the study end point , 31.2 % ( 95 % confidence interval , 24.9 - 38.0 ) of the community surveillance group subjects were parasitemic , compared with subjects in the treatment groups , whose rates of parasitemia were 40.8 % ( 32.9 - 49.0 ; relative risk [ RR ] , 1.31 [ 0.99 - 1.73 ] ) after triple-dose chlorproguanil-dapsone , 19.7 % ( 13.5 - 27.2 ; RR , 0.63 [ 0.43 - 0.93 ] ) after pyrimethamine-sulfadoxine , and 65.6 % ( 57.5 - 73.0 ; RR , 2.10 [ 1.66 - 2.65 ] ) after single-dose chlorproguanil-dapsone . Pyrimethamine-sulfadoxine and triple-dose chlorproguanil-dapsone were effective treatments . Pyrimethamine-sulfadoxine provided chemoprophylaxis during follow-up because of its slow elimination . Triple-dose chlorproguanil-dapsone should now be developed in an attempt to reduce the rate of emergence of antifolate resistance in Africa and for affordable salvage therapy in cases of pyrimethamine-sulfadoxine failure BACKGROUND In areas of endemic transmission , malaria in pregnancy is associated with severe maternal anaemia and low-birthweight babies . We studied the efficacy of intermittent treatment doses of sulphadoxine-pyrimethamine in preventing malaria and severe anaemia in pregnancy in a double-blind placebo-controlled trial among primigravid women living in Kilifi District , Kenya . METHODS Between January , 1996 , and April , 1997 , 1264 primigravid women were recruited when they attended for antenatal care , and r and omly assigned sulphadoxine-pyrimethamine ( 640 ) or placebo ( 624 ) . Women received one , two , or three doses of study medication depending on the duration of gestation at enrolment . Primary outcome measures were severe anaemia ( haemoglobin < 8 g/dL ) and malaria parasitaemia , assessed at 34 weeks of gestation . Analyses were based on intention to treat among women who had study blood tests at 34 weeks . FINDINGS 30 ( 5.3 % ) of 567 women in the sulphadoxine-pyrimethamine group and 199 ( 35.3 % ) of 564 in the placebo group had peripheral parasitaemia ( protective efficacy 85 % [ 95 % CI 78 - 90 ] , p<0.0001 ) . 82 ( 14.5 % ) and 134 ( 23.7 % ) had severe anaemia ( protective efficacy 39 % [ 22 - 52 ] , p<0.0001 ) . Even women who booked late and received only one dose of sulphadoxine-pyrimethamine benefited significantly from the intervention . The effects were seen both in women who owned insecticide-treated bednets and in women who did not . INTERPRETATION Intermittent presumptive treatment with sulphadoxine-pyrimethamine is an effective , practicable strategy to decrease the risk of severe anaemia in primigravidae living in malarious areas Objectives : In the Gambia , the combination of chloroquine ( CQ ) and sulphadoxine-pyrimethamine ( SP ) has replaced CQ monotherapy for treatment of malaria caused by Plasmodium falciparum . We measured the efficacy of the combination CQ/SP , and the prevalence of parasites carrying alleles associated with resistance to CQ or SP . Design : We conducted a single-blind , r and omised , controlled trial to compare the efficacy of CQ/SP to that of SP or CQ alone . Setting : The study took place in the town of Farafenni and surrounding villages in the Gambia . Participants : Participants were children aged 12 mo to 10 y presenting as out patients with uncomplicated P. falciparum malaria . Interventions : 500 children were r and omised to receive CQ , SP , or CQ/SP as supervised treatment and actively followed over 28 d. Outcome Measures : Primary outcome was parasitaemia at any time during follow-up . Secondary outcomes were PCR-confirmed recrudescent infections among treatment failures , and clinical failure requiring rescue medication by day 28 . Pretreatment parasite isolates from 161 patients were tested for the presence of resistance-associated genetic markers . Results : The prevalence of parasitological failure by day 28 for the CQ group was 60.3 % , compared to 17.6 % for SP ( odds ratio [ OR ] , 0.106 ; 95 % confidence interval [ CI ] , 0.057–0.194 ; p < 0.001 ) and 13.9 % for CQ/SP ( OR versus CQ , 0.140 ; 95 % CI , 0.078–0.250 ; p < 0.001 ) . There was no difference between the SP and CQ/SP groups ( OR , 1.324 ; 95 % CI , 0.705–2.50 ) . The projected prevalence of PCR-corrected treatment failure was 30.2 , 6.06 , and 3.94 % in the CQ , SP , and CQ/SP groups , respectively . The pfdhfr-triple mutant and pfdhps-437 G mutation were common , with prevalences of 67.4 and 51.2 % , respectively . Pretreatment carriage of pfdhps-437 G and of multidrug-resistant parasite genotypes was associated with treatment failure in the SP group , but not in the CQ or CQ/SP groups . Conclusions : The combination of CQ/SP was an efficacious treatment for uncomplicated malaria in Gambian children in this study , but the frequent occurrence of multidrug-resistant parasites suggests that this observed efficacy is not sustainable Whether and when to replace chloroquine with other antimalarial drugs is an urgent public health question in much of Africa , where Plasmodium falciparum , which is increasingly resistant to chloroquine , continues to kill millions each year . Antimalarial drug efficacy has traditionally been measured as parasitologic resistance , but recent guidelines use both clinical and parasitologic criteria to monitor therapeutic efficacy . To assess the new efficacy protocol , we measured parasitologic and therapeutic outcomes in 514 patients treated with chloroquine for uncomplicated P. falciparum malaria in Mali . There was a general agreement between parasitologic and therapeutic outcomes at two sites , with 13 - 17 % parasitologic resistance rates and 10 - 15 % treatment failure rates . However , the new protocol overestimated early treatment failure rates ( 21 - 71 % of cases classified as early treatment failure had sensitive or RI parasitologic responses ) , particularly where resistance was rare , and missed low-level parasitologic resistance . Modifications of the protocol for monitoring antimalarial therapeutic efficacy are recommended Malarial infection during pregnancy increases the risks of severe sequelae for the pregnant woman and the risk of delivering a low birthweight baby . The aim of this intervention study was to reduce significantly the prevalence of malaria parasitaemia in adolescent parturients in Matola and Boane in Mozambique . The study was focused upon the most malaria-vulnerable group , adolescent nulliparous and primiparous women . After completing the usual antenatal clinic and giving informed consent , 600 pregnant women were r and omly chosen in a double blind manner to one of two regimens comparing the prevailing routine ( placebo ) for malaria prevention with a two dose regimen of sulphadoxine-pyrimethamine ( SP ) . The first dose was given at enrollment with a second dose at the beginning of the third trimester . At delivery maternal and placental malaria parasitaemia as well as birthweight and gestational duration were analysed . At booking the prevalence of malaria parasitaemia was 35.3 % in the placebo group and 30.6 % in the SP group . At the second dose , the prevalence of malaria parasitaemia in the placebo group and SP group was 19.7 % and 8.7 % , respectively . This implies a relative risk ( RR ) of 2.24 with 95 % CI ( 1.34 , 3.75 ) . The corresponding figures at delivery were 13.6 % and 6.3 % with an RR of 2.22 ( 1.07 , 4.60 ) and in placenta 13.3 % and 2.4 % with an RR of 4.87 ( 1.58 , 15.0 ) . Newborns with malaria within 7 days were significantly more frequent in the placebo group , 6.4 % and 0.7 % respectively , with an RR of 6.55 ( 1.20 , 35.7 ) . Almost all ( approximately 98 % ) of the women studied had Plasmodium falciparum , the remainder had P. malariae and P. ovale . The mean birthweight in the SP group was 3077 g and in the placebo group 2926 g. The estimated mean difference between the two groups was 151 g with 95 % CI ( 51 , 252 ) . The mean placental weight in the placebo group was 596 and 645 g in the SP group , implying a difference of 49 g with a 95 % CI ( 11 , 88 ) . The mean gestational duration was 6.1 days longer in the SP group , 95 % CI ( 1.5 , 10.6 ) . In the placebo group there were two cases of urticaria and one case of nausea ; in the SP group there was one case of vomiting . No newborn showed any sign of serious SP side-effect . Two doses of SP were enough to significantly reduce the prevalence of peripheral and placental malaria parasitaemia among young nulliparous and primiparous pregnant women in Matola and Boane BACKGROUND Malaria during pregnancy contributes to maternal anemia and low birth weight .  In East Africa , several studies have demonstrated that intermittent preventive treatment ( IPT ) with sulfadoxine-pyrimethamine ( SP ) is more efficacious than weekly chloroquine ( CQ ) chemoprophylaxis in preventing these adverse consequences . To our knowledge , there are no published trials evaluating IPT in West Africa . METHODS We undertook a r and omized controlled trial of weekly CQ chemoprophylaxis , 2-dose IPT with CQ , and 2-dose IPT with SP ;  1163 women were enrolled . RESULTS In multivariate analyses , when compared with weekly CQ , IPT/SP was associated with a reduction in third-trimester anemia ( adjusted odds ratio [ AOR ] , 0.49 ; P<.001 ) , placental parasitemia ( AOR , 0.69 ; P=.04 ) , and low birth weight ( < 2500 g ) ( AOR , 0.69 ; P=.04 ) . The prevalence of placental infection remained unexpectedly high , even in the IPT/SP group ( 24.5 % ) , possibly because of the intensity of seasonal transmission . There were no significant differences in stillbirths , spontaneous abortions , or neonatal deaths among the 3 groups . CONCLUSIONS In Mali , IPT with SP appears more efficacious than weekly chloroquine chemoprophylaxis in preventing malaria during pregnancy . These data support World Health Organization recommendations to administer at least 2 doses of IPT during pregnancy . In intensely seasonal transmission setting s in Mali , > 2 doses may be required to prevent placental reinfection prior to delivery To define an effective and deliverable antimalarial regimen for use during pregnancy , pregnant women at highest risk of malaria ( those in their first or second pregnancy ) in an area of Malawi with high transmission of chloroquine (CQ)-resistant Plasmodium falciparum were placed on CQ and /or sulfadoxine-pyrimethamine ( SP ) . Of 38 pregnant women who received CQ treatment followed by weekly CQ 
    Output:
    
In areas in which 1 of 4 treatments with sulfadoxine-pyrimethamine fail in children by day 14 , the 2-dose IPT with sulfadoxine-pyrimethamine regimen continues to provide substantial benefit to HIV-negative semi-immune pregnant women .
However , more frequent dosing is required in HIV-positive women not using cotrimoxazole prophylaxis for opportunistic infections