***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 Many countries have implemented artemisinin-based combination therapy ( ACT ) for the first-line treatment of malaria . Although many studies have been performed on efficacy and tolerability of the combination arthemeter-lumefantrine ( AL ) or dihydroartemisinin-piperaquine ( DP ) , less is known of the effect of these drugs on gametocyte development , which is an important issue in malaria control . Methods and results In this two-arm r and omized controlled trial , 146 children were treated with either AL or DP .  Both groups received directly observed therapy and were followed for 28 days after treatment . Blood sample s were analysed with microscopy and NASBA . In comparison with microscopy NASBA detected much more gametocyte positive individuals . Moreover , NASBA showed a significant difference in gametocyte clearance in favour of AL compared to DP . The decline of parasitaemia was slower and persistence or development of gametocytes was significantly higher and longer at day 3 , 7 and 14 in the DP group but after 28 days no difference could be observed between both treatment arms . Conclusion Although practical considerations could favour the use of one drug over another , the effect on gametocytogenesis should also be taken into account and studied further using molecular tools like NASBA . This also applies when a new drug is introduced . Trial registration Current controlled trials IS RCT BACKGROUND Between 1995 and 2000 , KwaZulu-Natal province , South Africa , experienced a marked increase in Plasmodium falciparum malaria , fuelled by pyrethroid and sulfadoxine-pyrimethamine resistance . In response , vector control was strengthened and artemether-lumefantrine ( AL ) was deployed in the first Ministry of Health artemisinin-based combination treatment policy in Africa . In South Africa , effective vector and parasite control had historically ensured low-intensity malaria transmission . Malaria is diagnosed definitively and treatment is provided free of charge in reasonably accessible public-sector health-care facilities . METHODS AND FINDINGS We review ed four years of malaria morbidity and mortality data at four sentinel health-care facilities within KwaZulu-Natal 's malaria-endemic area . In the year following improved vector control and implementation of AL treatment , malaria-related admissions and deaths both declined by 89 % , and outpatient visits decreased by 85 % at the sentinel facilities . By 2003 , malaria-related outpatient cases and admissions had fallen by 99 % , and malaria-related deaths had decreased by 97 % . There was a concomitant marked and sustained decline in notified malaria throughout the province . No serious adverse events were associated causally with AL treatment in an active sentinel pharmacovigilance survey . In a prospect i ve study with 42 d follow up , AL cured 97/98 ( 99 % ) and prevented gametocyte developing in all patients . Consistent with the findings of focus group discussion s , a household survey found self-reported adherence to the six-dose AL regimen was 96 % . CONCLUSION Together with concurrent strengthening of vector control measures , the antimalarial treatment policy change to AL in KwaZulu-Natal contributed to a marked and sustained decrease in malaria cases , admissions , and deaths , by greatly improving clinical and parasitological cure rates and reducing gametocyte carriage Background Resistance of malaria parasites to chloroquine ( CQ ) and sulphadoxine-pyrimethamine ( SP ) is increasing in prevalence in Africa . Combination therapy can both improve treatment and provide important public health benefits if it curbs the spread of parasites harbouring resistance genes . Thus , drug combinations must be identified which minimise gametocyte emergence in treated cases , and so prevent selective transmission of parasites resistant to any of the partner drugs . Methods and Findings In a r and omised controlled trial , 497 children with uncomplicated falciparum malaria were treated with CQ and SP ( three doses and one dose respectively ; n = 91 ) , or six doses of artemether in fixed combination with lumefantrine ( co-artemether [ Coartem , Riamet ] ) ( n = 406 ) . Carriage rates of Plasmodium falciparum gametocytes and trophozoites were measured 7 , 14 , and 28 d after treatment . The infectiousness of venous blood from 29 children carrying P. falciparum gametocytes 7 d after treatment was tested by membrane-feeding of Anopheles mosquitoes . Children treated with co-artemether were significantly less likely to carry gametocytes within the 4 weeks following treatment than those receiving CQ/SP ( 30 of 378 [ 7.94 % ] versus 42 of 86 [ 48.8 % ] ; p < 0.0001 ) . Carriers in the co-artemether group harboured gametocytes at significantly lower densities , for shorter periods ( 0.3 d versus 4.2 d ; p < 0.0001 ) and were less infectious to mosquitoes at day 7 ( p < 0.001 ) than carriers who had received CQ/SP . Conclusions Co-artemether is highly effective at preventing post-treatment transmission of P. falciparum . Our results suggest that co-artemether has specific activity against immature sequestered gametocytes , and has the capacity to minimise transmission of drug-resistant parasites Background Presented here are the results of a comparative trial on the efficacy of three artemisinin-based combinations  conducted from May to October 2004 , in Pool Province , Republic of Congo . Methods The main outcome was the proportion of cases of true treatment success at day 28 . Recrudescences were distinguished from re-infections by PCR analysis . A total of 298 children of 6–59 months were r and omized to receive either artesunate + SP ( AS+SP ) , artesunate + amodiaquine ( AS+AQ ) or artemether + lumefantrine ( AL ) , of which 15 ( 5 % ) were lost to follow-up . Results After 28 days , there were 21/85 ( 25 % ) recurrent parasitaemias in the AS+SP group , 31/97 ( 32 % ) in the AS+AQ group and 13/100 ( 13 % ) in the AL group . The 28-day PCR-corrected cure rate was 90.1 % [ 95 % CI 80.7–95.9 ] for AS+SP , 98.5 % [ 95 % CI 92.0–100 ] for AS+AQ and 100 % [ 95.8–100 ] for AL , thereby revealing a weaker response to AS+SP than to AL ( p = 0.003 ) and to AS+AQ ( p = 0.06 ) . A potential bias was the fact that children treated with AL were slightly older and in better clinical condition , but logistic regression did not identify these as relevant factors . There was no significant difference between groups in fever and parasite clearance time , improvement of anaemia and gametocyte carriage at day 28 . No serious adverse events were reported . Conclusion Considering the higher efficacy of AL as compared to AS+SP and the relatively high proportion of cases with re-infections in the AS+AQ group , we conclude that AL is clinical ly more effective than AS+SP and AS+AQ in this area of the Republic of Congo . Implementation of the recently chosen new national first-line AS+AQ should be monitored closely Background In 2008 , artemether - lumefantrine ( AL ) and dihydroartemisinin - piperaquine ( DHAP ) were added to artesunate - amodiaquine ( AS-AQ ) as first-line drugs for uncomplicated malaria in Ghana . The introduction of new drugs calls for continuous monitoring of these drugs to provide timely information on trends of their efficacy and safety to enhance timely evidence -based decision making by the National Malaria Control Programme . In this regard , the therapeutic efficacy of AL was monitored from September 2010 to April 2011 in four sentinel sites representing the three main ecological zones of the country . Methods The study was a one-arm prospect i ve evaluation of clinical and parasitological responses to directly observed treatment for uncomplicated malaria among children aged 6 months to 59 months using the 2009 WHO protocol for surveillance of anti-malarial drug efficacy . Children recruited into the study received weight-based 20/120 mg AL at 0 , 8 , 24 , 36 , 48 , and 60 hrs . Parasitaemia levels were assessed on days 2 , 3 , 7 , 14 , 21 , 28 , and at any time a study child was brought to the clinic with fever . Results A total of 175 children were enrolled into the study : 56 in the savanna zone , 78 in the forest zone and 41 in the coastal zone . Per- protocol analysis showed that the overall PCR-corrected cure rates on day 14 and day 28 were 96.5 % ( 95 % CI : 92.1 , 98.6 ) and 95.4 % ( 95 % CI : 90.3 , 98.0 ) , respectively , with statistically significant differences between the ecological zones . The 90.4 % day-28 cure rate observed in the savannah zone ( 95 % CI : 78.2 , 96.4 ) was significantly the lowest compared with 100 % ( 95 % CI : 93.2 , 99.9 ) in the forest zone and 93.8 % ( 95 % CI : 77.8 , 98.9 ) in the coastal zone ( P = 0.017 ) . Fever and parasite clearance were slower among children enrolled in the savannah zone . Gametocytaemia after day-3 post-treatment was rare in all the zones . Conclusions The study has shown that AL remains efficacious in Ghana with significant ecologic zonal differences . The savannah zone may be a potential zone for any emergence of resistant alleles as a result of the slower parasite clearance observed in the zone The activities of artemether-lumefantrine and amodiaquine-sulfalene-pyrimethamine against sexual-stage parasites were evaluated in 42 of 181 Nigerian children with uncomplicated Plasmodium falciparum malaria who had gametocytaemia before , during or after treatment with the two combination therapies . The children were r and omized to the st and ard dose regimens .  Clinical recovery from illness occurred in all children who carried gametocytes . Gametocytaemia was detected in 20 patients ( 11 % ) before treatment and in another 22 patients ( 12.2 % ) after treatment . Game- tocyte carriage rates were similar in both combination treatment groups , but the area under the curve of gametocytaemia plotted against time was 8-fold higher in the amodiaquine-sulfalene-pyrimethamine-treated than in the artemether-lumefantrine-treated children . The pretreatment gametocyte sex ratio was female biased in both treatment groups . During follow-up , there was a short-lived but significant increase in the gametocyte sex ratio in children treated with amodiaquine-sulfalene-pyrimethamine but not in those treated with artemether-lumefantrine . These results indicate that both combination therapies had moderate effects on gametocyte carriage , but artemether-lumefantrine may be more potent at reducing transmissibility in P. falciparum malaria by exerting greater effects on post-treatment gametocyte density and gametocyte sex ratio Background Artesunate and amodiaquine ( AS&AQ ) is at present the world 's second most widely used artemisinin-based combination therapy ( ACT ) . It was necessary to evaluate the efficacy of ACT , recently adopted by the World Health Organization ( WHO ) and deployed over 80 countries , in order to make an evidence -based drug policy . Methods An individual patient data ( IPD ) analysis was conducted on efficacy outcomes in 26 clinical studies in sub-Saharan Africa using the WHO protocol with similar primary and secondary endpoints . Results A total of 11,700 patients ( 75 % under 5 years old ) , from 33 different sites in 16 countries were followed for 28 days . Loss to follow-up was 4.9 % ( 575/11,700 ) . AS&AQ was given to 5,897 patients . Of these , 82 % ( 4,826/5,897 ) were included in r and omized comparative trials with polymerase chain reaction ( PCR ) genotyping results and compared to 5,413 patients ( half receiving an ACT).AS&AQ and other ACT comparators result ed in rapid clearance of fever and parasitaemia , superior to non-ACT . Using survival analysis on a modified intent-to-treat population , the Day 28 PCR-adjusted efficacy of AS&AQ was greater than 90 % ( the WHO cut-off ) in 11/16 countries . In r and omized comparative trials ( n = 22 ) , the crude efficacy of AS&AQ was 75.9 % ( 95 % CI 74.6–77.1 ) and the PCR-adjusted efficacy was 93.9 % ( 95 % CI 93.2–94.5 ) . The risk ( weighted by site ) of failure PCR-adjusted of AS&AQ was significantly inferior to non-ACT , superior to dihydroartemisinin-piperaquine ( DP , in one Ug and an site ) , and not different from AS+SP or AL ( artemether-lumefantrine ) . The risk of gam 
    Output:
    
Despite the inherent difficulties in comparing data from a range of different studies that also utilized different diagnostic approaches to assess baseline gametocyte counts , the gametocytocidal effect of AL was proportionately consistent across the studies review ed , suggesting that AL will continue to play a vital role in the treatment of malaria and contribute to clearing the path towards malaria elimination .