***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 the Sahel and sub-Sahelian regions of Africa , malaria transmission is highly seasonal . During a short period of high malaria transmission , mortality and morbidity are high in children under age 5 years . We assessed the efficacy of seasonal intermittent preventive treatment-a full dose of antimalarial treatment given at defined times without previous testing for malaria infection . METHODS We did a r and omised , placebo-controlled , double-blind trial of the effect of intermittent preventive treatment on morbidity from malaria in three health-care centres in Niakhar , a rural area of Senegal . 1136 children aged 2 - 59 months received either one dose of artesunate plus one dose of sulfadoxine-pyrimethamine or two placebos on three occasions during the malaria transmission season . The primary outcome was a first or single episode of clinical malaria detected through active or passive case detection . Primary analysis was by intention-to-treat . This study is registered with , number NCT00132561 . FINDINGS During 13 weeks of follow-up , the intervention led to an 86 % ( 95 % CI 80 - 90 ) reduction in the occurrence of clinical episodes of malaria . With passive case detection , protective efficacy against malaria was 86 % ( 77 - 92 ) , and when detected actively was 86 % ( 78 - 91 ) . The incidence of malaria in children on active drugs was 308 episodes per 1000 person-years at risk , whereas in those on placebo it was 2250 episodes per 1000 person-years at risk . 13 children were not included in the intention-to-treat analysis , which was restricted to children who received a first dose of antimalarial or placebo . There was an increase in vomiting in children who received the active drugs , but generally the intervention was well tolerated . INTERPRETATION Intermittent preventive treatment could be highly effective for prevention of malaria in children under 5 years of age living in areas of seasonal malaria infection In a controlled trial of weekly malaria chemoprophylaxis  with chloroquine and pyrimethamine there were no significant differences in type and frequency of severe morbidity during chemoprophylaxis . Administration of chemoprophylaxis during the current and immediately preceding month was associated with significantly fewer episodes of severe morbidity in the chloroquine and pyrimethamine groups when each was compared with the control multivite group . After chemoprophylaxis had been stopped , significantly more episodes of severe morbidity occurred in the chloroquine group than the control group , but a similar trend in the pyrimethamine group was not statistically significant . In the control group most of the episodes of severe morbidity , including those episodes which were associated with heavy parasitaemia , occurred below the age of 4 years . In contrast , the children who received chemoprophylaxis continued to experience such illness at older ages . The difference between the chloroquine group and the control group in respect of age at time of severe morbidity was statistically significant A trial of suppression of malaria by administration of combined sulphadoxine-pyrimethamine tablets every 28 days was undertaken in West Malaysia during 1972 . One thous and subjects were followed over a 10-month period , including control groups on placebo and on weekly chloroquine . Subjects were examined monthly for parasitaemia , drug reactions , leucopenia , teratogenicity and haemolysis among the subjects deficient in glucose-6-phosphate dehydrogenase . Rates of new infections in the placebo group were 8.0 % with Plasmodium falciparum and 6.2 % with P. vivax ; in the group receiving weekly chloroquine , 5.1 % P. falciparum and 0.3 % P. vivax ; and in the group receiving monthly sulphadoxine-pyrimethamine , 0.3 % P. Falciparum and 1.0 % P. vivax . The effective rate of cure of new infections with P. falciparum by a single suppressive dose of combined sulphadoxine-pyrimethamine given the following month was 88.7 % . No serious side effects were observed After treatment with chloroquine and pyrimethamine/sulfadoxine , 118 school children aged 6 to 10 years living near the Kenyan coast were enrolled in a malaria chemoprophylaxis study and followed up for 20 weeks . Children were r and omly assigned to receive either chlorproguanil 20 mg weekly ( n = 78 ) or placebo ( n = 37 ) . The attack rate of Plasmodium falciparum infection was 42 % in chlorproguanil recipients ( 39.8 episodes per 1000 person-weeks of prophylaxis ) and 73 % in placebo recipients ( 69.2 episodes per 1000 person-weeks , p less than 0.02 ) . Sensitivity tests on 36 isolates successfully cultured in vitro showed that all 21 isolates from chloroproguanil recipients were resistant to dihydrofolate-reductase inhibitors , whereas only 3 of 15 isolates from the placebo group were resistant ( p less than 10(-6 ) ) . Chlorproguanil in a weekly adult dose of 40 mg does not provide adequate prophylaxis against P falciparum in Kenya , probably because drug levels between doses fall below those required to suppress parasites resistant to dihydrofolate-reductase inhibitors A double-blind , community-r and omized , placebo-controlled trial was conducted in a rural area of The Gambia between June and December 1999 to test whether a reduction in the infectious reservoir can reduce malaria transmission . Overall 14,017 ( 85 % ) individuals living in the study area were treated with either placebo or sulfadoxine-pyrimethamine ( SP ) combined with a single dose of artesunate ( AS ) . Following the mass drug administration ( MDA ) 1375 children aged 6 months to 10 years were kept under surveillance for clinical malaria in 18 villages throughout the 1999 malaria transmission season . During a 20-week surveillance period 637 episodes of malaria were detected . The mean incidence rate was 2.5/100 child-weeks in the placebo villages , and 2.3/100 child-weeks in villages that received SP + AS . The mean rate ratio , adjusted for individual and village-level covariates , was 0.91 ( 95 % CI 0.68 - 1.22 , P = 0.49 ) . During the first 2 months of surveillance , the malaria incidence was lower in treated villages . After 2 months the incidence was slightly higher in the MDA group but this was not statistically significant . Overall , no benefit of the MDA could be detected . The reason for the absence of an impact on malaria transmission is probably the very high basic reproductive number of malaria , and the persistence of mature gametocytes , which are not affected by AS treatment This study was aim ed at delineating characteristics of naturally acquired immunity against the merozoite surface antigen-1 ( MSP-1 ) of Plasmodium falciparum , a c and i date malaria vaccine antigen . A case/control study was performed on 75 case/control pairs of infants with febrile illness at the time of the first detected infection indicating a clinical case . The presence and level of antibodies at one month prior to the first infection and at the time of the first infection in the afebrile group was significantly higher than in the febrile group . Decreased parasite density and decreased infection-related loss of hemoglobin was seen in infants with anti-MSP-1(19kD ) IgG antibodies . In addition , mothers who were positive for the presence of these antibodies conferred protection against placental infection and infection in their infants . In this study , development of anti-MSP-1(19kD ) antibody responses in 24 infants were studied longitudinally using monthly serum sample s collected from birth until approximately one year of age . In addition , umbilical cord blood sera and respective mothers ' sera were analyzed . Longitudinal studies of antibody responses revealed several short-lived IgG and IgM peaks throughout an infant 's first year that correlated with detection of parasitemia . The protection against parasitemia and febrile illness was observed in infants when anti-MSP-1(19kD ) antibodies were present ; when infants were negative for IgG , they had a 10-times greater risk of becoming parasitemic . These data from a longitudinal and prospect i ve study of malaria suggest a protective role for anti-MSP-1(19kD ) antibodies in infants and pregnant women Stopping antimalarial chemoprophylaxis can be followed by increased risk of malaria , suggesting that it interferes with the development of antimalarial immunity . We report analysis of extended follow-up until age 2 years of a r and omised , placebo-controlled double-blind trial of intermittent preventive antimalarial treatment in infants . The rate of clinical malaria ( events per person-year at risk , starting 1 month after final dose of intermittent treatment ) was 0.28 in the sulfadoxine-pyrimethamine group and 0.43 in the placebo group ( protective effect 36 % , 95 % CI 11 - 53 ) . Intermittent treatment produced a sustained reduction in the risk of clinical malaria extending well beyond the duration of the pharmacological effects of the drugs , excluding a so-called rebound effect and suggesting that such treatment could facilitate development of immunity against Plasmodium falciparum BACKGROUND Intermittent preventive antimalarial treatment in infants ( IPTi ) with sulfadoxine-pyrimethamine reduces falciparum malaria and anemia but has not been evaluated in areas with intense perennial malaria transmission . It is unknown whether an additional treatment in the second year of life prolongs protection . METHODS A r and omized , double-blinded , placebo-controlled trial with administration of sulfadoxine-pyrimethamine therapy at 3 , 9 , and 15 months of age was conducted with 1070 children in an area in Ghana where malaria is holoendemic . Participants were monitored for 21 months after recruitment through active follow-up visits and passive case detection . The primary end point was malaria incidence , and additional outcome measures were anemia , outpatient visits , hospital admissions , and mortality . Stratified analyses for 6-month periods after each treatment were performed . RESULTS Protective efficacy against malaria episodes was 20 % ( 95 % confidence interval [ CI ] , 11%-29 % ) . The frequency of malaria episodes was reduced after the first 2 sulfadoxine-pyrimethamine applications ( protective efficacy , 23 % [ 95 % CI , 6%-36 % ] after the first dose and 17 % [ 95 % CI , 1%-30 % ] after the second dose ) . After the third treatment at month 15 , however , no protection was achieved . Protection against the first or single anemia episode was only significant after the first IPTi dose ( protective efficacy , 30 % ; 95 % CI , 5%-49 % ) . The number of anemia episodes increased after the last IPTi dose ( protective efficacy , -24 % ; 95 % CI , -50 % to -2 % ) . CONCLUSION In an area of intense perennial malaria transmission , sulfadoxine-pyrimethamine-based IPTi conferred considerably lower protection than reported in areas where the disease is moderately or seasonally endemic . Protective efficacy is age-dependent , and extension of IPTi into the second year of life does not provide any benefit In a r and omized controlled study of malaria prophylaxis , dapsone-pyrimethamine at a weekly dosage of dapsone 50 - 100 mg with pyrimethamine 6.25 - 12.5 mg or placebo was administered to 166 school children for 17 weeks . Fortnightly parasitological controls revealed 28 infections in the placebo group and none in the dapsone-pyrimethamine group . It is concluded that weekly dapsone-pyrimethamine is effective for the prophylaxis of falciparum malaria in Mozambique BACKGROUND Clinical malaria and severe anaemia are major causes of paediatric hospital admission and death in many malaria-endemic setting s. In the absence of an effective and affordable vaccine , control programmes continue to rely on case management while attempting the large-scale deployment of insecticide-treated nets . We did a r and omised , placebo-controlled trial to assess the efficacy and safety of intermittent sulphadoxine-pyrimethamine treatment on the rate of malaria and severe anaemia in infants in a rural area of Tanzania . METHODS We r and omly assigned 701 children living in Ifakara , southern Tanzania , sulphadoxine-pyrimethamine or placebo at 2 , 3 , and 9 months of age . All children received iron supplementation between 2 and 6 months of age . The intervention was given alongside routine vaccinations delivered through WHO 's Exp and ed Program on Immunisation ( EPI ) . The primary outcome measures were first or only episode of clinical malaria , and severe anaemia in the period from recruitment to 1 year of age . Morbidity monitoring through a hospital-based passive case-detection system was complemented by cross-sectional surveys at 12 and 18 months of age . Results were expressed in terms of protective efficacy ( 100 [ 1-hazard ratio]% ) and analysis was by intention to treat . FINDINGS 40 children dropped out ( 16 died , 
    Output:
    
Prophylaxis and intermittent treatment with antimalarial drugs reduce clinical malaria and severe anaemia in preschool children