***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 
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    Input: Background Sequential analysis enables repeated statistical analyses to be performed throughout a trial recruitment period , while maintaining a pre-specified power and type I error . Thus the trial can be stopped as soon as the information accumulated is considered sufficient to reach a conclusion . Sequential tests are easy to use and their statistical properties are especially suitable to trials with very straightforward objectives such as non-comparative phase II trials . We report on a phase II study based on the triangular test ( TT ) aim ing at assessing the effectiveness of azithromycin in preventing Plasmodium vivax relapses . Methods To test whether the P. vivax relapse rate was either < 12 % or ≥ 45 % in patients treated with azithromycin  , a sequential analysis based on the TT was as used . Patients infected with P. vivax were treated with azithromycin , 1.2 g daily , for 7 days . The onset of a relapse infection was monitored . Results Five patients presenting with an acute P. vivax infection were included in the study . All the patients were initially cured . Three patients reported mild gastrointestinal adverse effects . When the third patient relapsed , the sample path crossed the upper boundary of the TT , and the trial was stopped . Conclusions Using the triangular test , with only a small number of patients , we concluded that azithromycin was not effective enough in preventing P. vivax relapses to warrant further evaluation in phase III . It is suggested that a wider use of sequential analysis in phase II anti-infective drugs trials may have financial and ethical benefits 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 New drugs are needed for preventing drug-resistant Plasmodium falciparum malaria . The prophylactic efficacy of azithromycin against P. falciparum in malaria-immune Kenyans was 83 % . We conducted a double-blind , placebo-controlled trial to determine the prophylactic efficacy of azithromycin against multidrug-resistant P. falciparum malaria and chloroquine-resistant Plasmodium vivax malaria in Indonesian adults with limited immunity . After radical cure therapy , 300 r and omized subjects received azithromycin ( 148 subjects , 750-mg loading dose followed by 250 mg/d ) , placebo ( 77 ) , or doxycycline ( 75 , 100 mg/d ) . The end point was slide-proven parasitemia . There were 58 P. falciparum and 29 P. vivax prophylaxis failures over 20 weeks . Using incidence rates , the protective efficacy of azithromycin relative to placebo was 71.6 % ( 95 % confidence interval [ CI ] , 50.3 - 83.8 ) against P. falciparum malaria and 98.9 % ( 95 % CI , 93.1 - 99.9 ) against P. vivax malaria . Corresponding figures for doxycycline were 96.3 % ( 95 % CI , 85.4 - 99.6 ) and 98 % ( 95 % CI , 88.0 - 99.9 ) , respectively . Daily azithromycin offered excellent protection against P. vivax malaria but modest protection against P. falciparum malaria Background Individual malaria interventions provide only partial protection in most epidemiological situations . Thus , there is a need to investigate whether combining interventions provides added benefit in reducing mortality and morbidity from malaria . The potential benefits of combining  IPT in children ( IPTc ) with home management of malaria ( HMM ) was investigated . Methods During the 2008 malaria transmission season , 1,277 children under five years of age resident in villages within the rural Farafenni demographic surveillance system ( DSS ) in North Bank Region , The Gambia were r and omized to receive monthly IPTc with a single dose of sulphadoxine/pyrimethamine ( SP ) plus three doses of amodiaquine ( AQ ) or SP and AQ placebos given by village health workers ( VHWs ) on three occasions during the months of September , October and November , in a double-blind trial . Children in all study villages who developed an acute febrile illness suggestive of malaria were treated by VHWs who had been taught how to manage malaria with artemether-lumefantrine ( Coartem ™ ) . The primary aims of the project were to determine whether IPTc added significant benefit to HMM and whether VHWs could effectively combine the delivery of both interventions . Results The incidence of clinical attacks of malaria was very low in both study groups . The incidence rate of malaria in children who received IPTc was 0.44 clinical attacks per 1,000 child months at risk while that for control children was 1.32 per 1,000 child months at risk , a protective efficacy of 66 % ( 95 % CI -23 % to 96 % ; p = 0.35 ) . The mean ( st and ard deviation ) haemoglobin concentration at the end of the malaria transmission season was similar in the two treatment groups : 10.2 ( 1.6 ) g/dL in the IPTc group compared to 10.3 ( 1.5 ) g/dL in the placebo group . Coverage with IPTc was high , with 94 % of children receiving all three treatments during the study period . Conclusion Due to the very low incidence of malaria , no firm conclusion can be drawn on the added benefit of IPTc in preventing clinical episodes of malaria among children who had access to HMM in The Gambia . However , the study showed that VHWs can successfully combine provision of HMM with provision of IPTc . Trial Registration Clinical Trials.gov Background Recent studies have shown that intermittent preventive malaria treatment ( IPT ) in infants in areas of stable malaria transmission reduces malaria and severe anaemia incidence . However in most areas malaria morbidity and mortality remain high in older children . Methods To evaluate the effect of seasonal IPT with sulphadoxine pyrimethamine ( SP ) on incidence of malaria disease in area of seasonal transmission , 262 children 6 months-10 years in Kambila , Mali were r and omized to receive either IPT with SP twice at eight weeks interval or no IPT during the transmission season of 2002 and were followed up for 12 months . Subjects were also followed during the subsequent transmission season in 2003 to assess possible rebound effect . Clinical malaria cases were treated with SP and followed to assess the in vivo response during both periods . Results The incidence rate of malaria disease per 1,000 person-months during the first 12 months was 3.2 episodes in the treatment group vs. 5.8 episodes in the control group with age-adjusted Protective Efficacy ( PE ) of 42.5 % ; [ 95 % CI 28.6%–53.8 % ] . When the first 16 weeks of follow up is considered age-adjusted PE was 67.5 % [ 95 % CI 55.3 % – 76.6 % ] . During the subsequent transmission season , the incidence of clinical malaria per 1000 persons-days was similar between the two groups ( 23.0 vs 21.5 episodes , age-adjusted IRR = 1.07 [ 95 % CI , 0.90–1.27 ] ) . No significant difference was detected in in vivo response between the groups during both periods . Conclusion Two malaria intermittent treatments targeting the peak transmission season reduced the annual incidence rate of clinical malaria by 42.5 % in an area with intense seasonal transmission . This simple strategy is likely to be one of the most effectives in reducing malaria burden in such areas .Trial Registration Clinical trials.gov Background Insecticide treated nets ( ITNs ) and indoor residual spraying ( IRS ) are effective vector control tools that protect against malaria . There is conflicting evidence regarding whether using ITNs and IRS in combination provides additional benefit over using either of these methods alone . This study investigated factors that may modify the effect of the combined use of IRS and ITNs compared to using ITNs alone on  malaria infection prevalence . Methods Secondary analysis was carried out on data from a cluster r and omised trial in north-west Tanzania . 50 clusters received ITNs from a universal coverage campaign ; of these 25 were r and omly allocated to additionally receive two rounds of IRS in 2012 . In cross-sectional household surveys children 0.5–14 years old were tested for Plasmodium falciparum infections ( PfPR ) two , six and ten months after the first IRS round . Results IRS  protected those sleeping under nets ( OR = 0.38 , 95%CI 0.26–0.57 ) and those who did not ( OR = 0.43 , 95%CI 0.29–0.63 ) . The protective effect of  IRS  was not modified by community level ITN use ( ITN use<50 % , OR = 0.39 , 95%CI 0.26–0.59 ; ITN use > = 50 % , OR = 0.46 , 95%CI 0.28–0.74 ) . The additional protection from IRS  was similar in low ( < 10 % PfPR , OR = 0.38 , 95%CI 0.19–0.75 ) and high transmission areas ( ≥10 % PfPR , OR = 0.34 , 95%CI 0.18–0.67 ) . ITN use was protective at the individual-level regardless of whether the village had been sprayed ( OR = 0.83 , 95%CI 0.70–0.98 ) . Living in a sprayed village was protective regardless of whether the individual slept under an ITN last night ( OR = 0.41 , 95%CI 0.29–0.58 ) . Interpretation Implementing IRS in addition to ITNs was beneficial for individuals from villages with a wide range of transmission intensities and net utilisation levels . Net users received additional protection from IRS . ITNs were providing some individual protection , even in this area with high levels of pyrethroid insecticide resistance . These results demonstrate that there is a supplementary benefit of IRS even when ITNs are effective . Trial Registration Clinical Trials.gov A malaria intervention study was carried out using permethrin impregnated bed nets in the south- central part of Irian Jaya with perennial transmission , from April 1993 to April 1995 . Malariometric surveys were carried out periodically for parasite prevalence by species and for spleen rates . Prior to intervention , the  percentage of Plasmodium falciparum infected inhabitants  was significantly higher in Hiripau , where permethrin-impregnated bed nets were used during the study , than in the  placebo-treated control village , Kaugapu . After two years of intervention the situation was reversed and figures higher in the control village ( RR 0.19 , 95 % CI 0.10 - 0.36 , p < 0.0001 ) . Similarly , P. vivax infection rates , 12.4 % in Hiripau vs 5.7 % in Kaugapu in April 1993 . were reversed in April 1995 ( 3.6 % in Hiripau and 11.3 % in Kaugapu , p < 0.001 ) . In the treated village , pre-control hyperendemicity  was reduced to a low mesoendemic level ( spleen rate 12.5 % ) during two years of intervention , whereas the level was mesoendemic ( spleen rate 35.2 % ) in the control village . Impregnated bed nets were found an effective intervention both in moderate ( April 1993 through April 1994 , 1,626 mm rainfall ) and high ( April 1994 through April  
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Conclusion Current evidence is strong for the protective effect of ITN interventions in malaria prevention .
Even though ITNs were found to be the only preventive measure with statistical support for their effectiveness , the role of other malaria control measures may be important adjuncts in the global drive to eliminate malaria