***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 BACKGROUND Malaria remains a major cause of mortality and morbidity in Africa . Many approaches to malaria control involve reducing the chances of infection but little is known of the relations between parasite exposure and the development of effective clinical immunity so the long-term effect of such approaches to control on the pattern and frequency of malaria can not be predicted . METHODS We have prospect ively recorded paediatric admissions with severe malaria over three to five years from five discrete communities in The Gambia and Kenya . Demographic analysis of the communities exposed to disease risk allowed the estimation of age-specific rates for severe malaria . Within each community the exposure to Plasmodium falciparum infection was determined through repeated parasitological and serological surveys among children and infants . We used acute respiratory-tract infections ( ARI ) as a comparison . FINDINGS 3556 malaria admissions were recorded for the five sites . Marked differences were observed in age , clinical spectrum and rates of severe malaria between the five sites . Paradoxically , the risks of severe disease in childhood were lowest among population s with the highest transmission intensities , and the highest disease risks were observed among population s exposed to low-to-moderate intensities of transmission . For severe malaria , for example , admission rates ( per 1000 per year ) for children up to their 10th birthday were estimated as 3.9 , 25.8 , 25.9 , 16.7 , and 18.0 in the five communities ; the forces of infection estimated for those communities ( new infections per infant per month ) were 0.001 , 0.034 , 0.050 , 0.093 , and 0.176 , respectively . Similar trends were noted for cerebral malaria and for severe malaria anaemia but not for ARI . Mean age of disease decreased with increasing transmission intensity . INTERPRETATION We propose that a critical determinant of life-time disease risk is the ability to develop clinical immunity early in life during a period when other protective mechanisms may operate . In highly endemic areas measures which reduce parasite transmission , and thus immunity , may lead to a change in both the clinical spectrum of severe disease and the overall burden of severe malaria morbidity A group-r and omized controlled trial of insecticide (permethrin)-treated bed nets ( ITNs ) was conducted in an area of high perennial malaria transmission in western Kenya to test the effect of ITNs on  all-cause mortality in children 1 - 59 months of age . Child deaths were monitored over a two-year period by biannual household census in Asembo ( 1997 - 1998 ) and in Gem ( 1998 - 1999 ) . Overall , 1,722 deaths occurred in children 1 - 59 months followed for 35,932 child-years .  Crude mortality rates/1,000  child-years were 51.9 versus 43.9 in control and ITN villages in children 1 - 59 months old . The protective efficacy ( PE ) ( 95 % confidence interval ) adjusted for age , study year , study site , and season was 16 % ( 6 - 25 % ) . Corresponding figures in 1 - 11- and 12 - 59-month-old children in control and ITN villages were 133.3 versus 102.3 , PE = 23 % ( 11 - 34 % ) and 31.1 versus 28.7 , PE = 7 % ( -6 - 19 % ) . The numbers of lives saved/1,000 child-years were 8 , 31 , and 2 for the groups 1 - 59 , 1 - 11 , and 12 - 59 months old , respectively . Stratified analysis by time to insecticide re-treatment showed that the PE of  ITNs  re-treated per study protocol ( every six months ) was 20 % ( 10 - 29 % ) , overall and 26 % ( 12 - 37 % ) and 14 % ( -1 - 26 % ) in 1 - 11- and 12 - 59-month-old children , respectively . ITNs prevent approximately one in four infant deaths in areas of intense perennial malaria transmission , but their efficacy is compromised if re-treatment is delayed beyond six months The incidence density of infection and disease caused by Plasmodium falciparum in children aged six to 24 months living in the holoendemic Sahel of northern Ghana was measured during the wet and dry seasons of 1996 and 1997 . At the beginning of each season , a cohort composed of 259 and 277 r and omly selected children received supervised curative therapy with quinine and Fansidar and primaquine  for those with normal glucose-6-phosphate dehydrogenase activity . The 20 weeks of post-therapy follow-up consisted of three home visits weekly and examination of Giemsa-stained blood films  once every two weeks . Blood films were also taken from children brought to clinic with illness . The incidence density of parasitemia after radical cure was 4.7 infections/person-year during the dry season and 7.1 during the wet season ( relative risk = 1.51 , 95 % confidence interval [ CI ] = 1.25 - 1.81 ; P = 0.00001 ) . Although the mean parasitemia count at time of reinfection in the dry season ( 3,310/microl ) roughly equaled that in the wet season ( 3,056/microl ; P = 0.737 ) , the risk ratio for parasitemia > 20,000/microl during the wet season was 1.71 ( 95 % CI = 1.2 - 2.4 ; P = 0.0025 ) . The risk ratio for parasitemia > 20,000/microl with fever during the wet season was 2.45 ( 95 % CI = 1.5 - 4.1 ; P = 0.0002 ) . The risk ratio for anemia ( hemoglobin < 8 g/dl ) at first post-radical cure parasitemia showed no difference between seasons ( 1.0 ; 95 % CI = 0.73 - 1.4 ; P = 0.9915 ) . We did not see seasonal differences in anemia known to exist in this region , probably because the longitudinal cohort design using first parasitemia as an end point prevented the subjects from developing the repeated or chronic infections required for anemia induction . These findings bear upon the design of malaria drug and vaccine trials in holoendemic areas 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 Background Malaria control strategies are design ed as a solution for either the whole region or the whole country and are assumed to suit every setting . There is a need to shift from this assumption because transmission may be different from one local setting to another . The aim of this study was to assess the risk of clinical malaria given the village of residence among under-five children in rural north-western Burkina Faso . Methods 867 children ( 6–59 months ) were r and omly selected from four sites . Interviewers visited the children weekly at home over a one-year period and tested them for fever .  Children with fever were tested for malaria parasites . An episode of clinical malaria was defined as fever ( axillary temperature ≥ 37.5 ° C ) + parasites density ≥ 5,000 parasites/μl . Logistic regression  was used to assess the risk of clinical malaria among children at a given site of residence . Results Children accumulated 758 person years ( PYs ) . Overall , 597 episodes of clinical malaria were observed , giving an incidence rate of 0.79 per PY . The risk of clinical malaria varied amongst the four sites . Taking one village as reference the odds ratio for the other three sites ranged from 0.66 ; 95%CI : 0.44–0.98 to 1.49 ; 95%CI : 1.10–2.01 . Conclusion Malaria control strategies should be design ed to fit the local context . The heterogeneity of transmission should be assessed at the district level to allow cost-effective re source allocation that gives priority to locations with high risk . Functional routine health information systems could provide the necessary data for context specific risk assessment Insecticide treatment of bed nets ( " mosquito nets " ) may be a cheap and acceptable method of reducing the morbidity and mortality caused by malaria . In a rural area of The Gambia , bed nets in villages participating in a primary health-care ( PHC ) scheme were treated with permethrin at the beginning of the malaria transmission season . Additionally , children aged 6 months to 5 years were r and omised to receive weekly either chemoprophylaxis with maloprim or a placebo throughout the malaria transmission season . We measured mortality in children in PHC villages before and after the interventions described , and compared this with mortality in villages where no interventions occurred ( non-PHC villages ) . About 92 % of children in PHC villages slept under insecticide-treated bed nets . In the year before intervention , mortality in children aged 1 - 4 years was lower in non-PHC villages . After intervention , the overall mortality and mortality attributable to malaria of children aged 1 - 4 in the intervention villages was 37 % and 30 % , respectively , of that in the non-PHC villages . Among children who slept under treated nets , we found no evidence of an additional benefit of chemoprophylaxis in preventing deaths .  Insecticide-treated bed nets are simple to introduce and can reduce mortality from malaria A large-scale longitudinal cohort project was initiated in western Kenya in June 1992 . Between June 1992 and July 1 
    Output:
    
Clinical malaria incidence was relatively evenly distributed across the first 10 years of life for all transmission scenarios .
Hospital admissions with malaria were more concentrated in younger children , with this effect being even more pronounced for malaria-diagnosed deaths .
For all outcomes , the burden of malaria shifted towards younger ages with increasing transmission intensity , although marked seasonality moderated this effect .