***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 Drug resistance in Plasmodium falciparum poses a major threat to malaria control . Combination antimalarial therapy including artemisinins has been advocated recently to improve efficacy and limit the spread of resistance , but artemisinins are expensive and relatively untested in highly endemic areas . We compared artemisinin-based and other combination therapies in four districts in Ug and a with varying transmission intensity . Methods and Findings We enrolled 2,160 patients aged 6 mo or greater with uncomplicated falciparum malaria . Patients were r and omized to receive chloroquine ( CQ ) + sulfadoxine-pyrimethamine ( SP ) ; amodiaquine ( AQ ) + SP ; or AQ + artesunate ( AS ) . Primary endpoints were the 28-d risks of parasitological failure either unadjusted or adjusted by genotyping to distinguish recrudescence from new infections . A total of 2,081 patients completed follow-up , of which 1,749 ( 84 % ) were under the age of 5 y. The risk of recrudescence after treatment with CQ + SP was high , ranging from 22 % to 46 % at the four sites . This risk was significantly lower ( p < 0.01 ) after AQ + SP or AQ + AS ( 7%–18 % and 4%–12 % , respectively ) . Compared to AQ + SP , AQ + AS was associated with a lower risk of recrudescence but a higher risk of new infection . The overall risk of repeat therapy due to any recurrent infection ( recrudescence or new infection ) was similar at two sites and significantly higher for AQ + AS at the two highest transmission sites ( risk differences = 15 % and 16 % , p < 0.003 ) . Conclusion AQ + AS was the most efficacious regimen for preventing recrudescence , but this benefit was outweighed by an increased risk of new infection . Considering all recurrent infections , the efficacy of AQ + SP was at least as efficacious at all sites and superior to AQ + AS at the highest transmission sites . The high endemicity of malaria in Africa may impact on the efficacy of artemisinin-based combination therapy . The registration number for this trial is IS RCT N67520427 ( http://www.controlled-trials.com/is rct n/trial/|/0/67520427.html ) Background The treatment for Plasmodium falciparum malaria in Sudan has been in process of change since 2003 . Preceding the change , this study aim ed to determine which artemisinin-based combination therapies is more effective to treat uncomplicated malaria in Malakal , Upper Nile , Sudan . Methods Clinical trial to assess the efficacy of 2 antimalarial therapies to treat P. falciparum infections in children aged 6–59 months , in a period of 42 days after treatment . Results A total of 269 children were followed up to 42 days . Artesunate plus Sulfadoxine/Pyrimethamine ( AS+SP ) and Artesunate plus Amodiaquine ( AS+AQ ) were both found to be efficacious in curing malaria infections by rapid elimination of parasites and clearance of fever , in preventing recrudescence and suppressing gametocytaemia . The combination of AS+SP appeared slightly more efficacious than AS+AQ , with 4.4 % ( 4/116 ) versus 15 % ( 17/113 ) of patients returning with malaria during the 6-week period after treatment ( RR = 0.9 , 95 % CI 0.81–0.96 ) . PCR analysis identified only one recrudescence which , together with one other early treatment failure , gave efficacy rates of 99.0 % for AS+AQ ( 96/97 ) and 99.1 % for AS+SP ( 112/113 ) . However , PCR results were incomplete and assuming part of the indeterminate sample s were recrudescent infections leads to an estimated efficacy ranging 97–98 % for AS+SP and 88–95 % for AS+AQ . Conclusion These results lead to the recommendation of ACT , and specifically AS+SP , for the treatment of uncomplicated falciparum malaria in this area of Sudan . When implemented , ACT efficacy should be monitored in sentinel sites representing different areas of the country Background Artesunate-amodiaquine ( AS+AQ ) and artemether-lumefantrine ( AM-L ) are efficacious artemisinin combination therapy ( ACT ) regimens that have been widely adopted in sub-Saharan Africa . However , there is little information on the efficacy of these regimens on subsequent episodes beyond 28 days , or on the safety of repeated treatments . Methods Children aged six months to 14 years with uncomplicated malaria were r and omly assigned to treatment with AS+AQ ( n = 116 ) , or AM-L ( n = 111 ) . Recruited subjects were followed-up , initially for 28 days , and then monthly for up to one year . All subsequent attacks of uncomplicated malaria after 28 days were treated with the same regimen as at r and omization . Investigations aim ed at determining efficacy and side effects were conducted . Results Adequate clinical and parasitological response in subjects with evaluable end-points were , 97.1 % ( 100/103 ) and 98.2 % ( 107/109 ) on day 14 , and 94.2 % ( 97/103 ) and 95.3 % ( 102/107 ) on day 28 in the AM-L and AS+AQ groups , respectively . Similar results were obtained after PCR correction . The incidence of malaria attacks in the year following recruitment was similar between the two treatment groups ( p = 0.93 ) . There was a high incidence of potentially AQ-resistant parasites in the study area . The incidence of adverse events , such as pruritus , fatigue and neutropaenia were similar in the two treatment groups . No patient showed signs of hearing impairment , and no abnormal neurological signs were observed during one year of follow-up . Other adverse events were mild in intensity and overlapped with known malaria symptomatology . No adverse event exacerbation was observed in any of the subjects who received multiple treatment courses with these ACT regimens during one year follow-up . Conclusion AS+AQ and AM-L were efficacious for treatment of children with uncomplicated malaria in Ghana and drug-related adverse events were rare in treated subjects during one year of follow-up . The high prevalence of potentially AQ resistant parasites raises questions about the utility of AQ as a partner drug for ACT in Ghana . The efficacy of AS+AQ in Ghana requires , therefore , continuous monitoring and evaluation . Trial registration NCT 00406146 http://www . clinical BACKGROUND Antimalarial drug resistance is now well established in both Plasmodium falciparum and Plasmodium vivax . In southern Papua , Indonesia , where both strains of plasmodia coexist , we have been conducting a series of studies to optimize treatment strategies . METHODS We conducted a r and omized trial that compared the efficacy and safety of dihydroartemisinin-piperaquine ( DHP ) with artesunate-amodiaquine ( AAQ ) . The primary end point was the overall cumulative parasitological failure rate at day 42 . RESULTS Of the 334 patients in the evaluable patient population , 185 were infected with P. falciparum , 80 were infected with P. vivax , and 69 were infected with both species . The overall parasitological failure rate at day 42 was 45 % ( 95 % confidence interval [ CI ] , 36%-53 % ) for AAQ and 13 % ( 95 % CI , 7.2%-19 % ) for DHP ( hazard ratio [ HR ] , 4.3 ; 95 % CI , 2.5 - 7.2 ; P<.001 ) . Rates of both recrudescence of P. falciparum infection and recurrence of P. vivax infection were significantly higher after receipt of AAQ than after receipt of DHP ( HR , 3.4 [ 95 % CI , 1.2 - 9.4 ] and 4.3 [ 95 % CI , 2.2 - 8.2 ] , respectively ; P<.001 ) . By the end of the study , AAQ recipients were 2.95-fold ( 95 % CI , 1.2- to 4.9-fold ) more likely to be anemic and 14.5-fold ( 95 % CI , 3.4- to 61-fold ) more likely to have carried P. vivax gametocytes . CONCLUSIONS DHP was more effective and better tolerated than AAQ against multidrug-resistant P. falciparum and P. vivax infections . The prolonged therapeutic effect of piperaquine delayed the time to P. falciparum reinfection , decreased the rate of recurrence of P. vivax infection , and reduced the risk of P. vivax gametocyte carriage and anemia 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 Tanzania switched the antimalarial first line to sulphadoxine-pyrimethamine ( SP ) in 2001 from ineffective chloroquine ( CQ ) . By 2003 higher levels of SP resistance were recorded , prompting an urgent need for replacing the first line drug with ACT , as currently recommended by the World Health Organization . Despite this recommendation country-specific evidence -based data to support efficacy and safety profile of ACT is still limited . A study on the efficacy and safety of artesunate plus amodiaquine ( AS+AQ ) and artemether plus lumefantrine (AL)(Coartem ® ) was carried out in 2004 with the view of supporting the National Malaria Control Programme in the review of the policy in mainl and Tanzania . Methods An in vivo efficacy study was conducted at Ipinda and Mlimba health facilities between May and November 2004 . The study recruited children aged 6–59 months presenting with symptoms of uncomplicated malaria , history of fever or an axillary temperature ≥37.5 ° C ; mono infection with Pasmodium falciparum ( 2,000–200,000 parasites/μl ) . Patients were r and omized to received either SP or amodiaquine monotherapy or treated with st and ard doses of AS+AQ in Mlimba and Coartem in Kyela and followed-up for 28 days to assess treatment responses . This study reports results of the combination therapies . Results A total of 157 children ( 76 in Mlimba and 99 in Kyela ) who were enrolled in to the study and treated with either AL or AS+AQ were successfully followed-up . Both combinations were tolerated and effected rapid fever and parasite clearance . The crude ACPRs were 80 ( 87 % ) and 41 ( 63 % ) for AL and AS+AQ respectively . However , after PCR adjustments the corresponding figures raised to 100 % ( n = 86 ) and 93.8 % ( n = 45 ) in AL and AS+AQ groups , respectively . The mean haemoglobin improved moderately from day 0 to day 28 by 1 g/dl in AL and 0.4 g/dl in AS+AQ treatment group and was statistically significant ( p < 0.001 both ) . Conclusion These findings provide substantial evidence that AL is highly efficacious in areas of high resistance of SP and supported the country 's decision to switch from SP monotherapy to AL 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 
    Output:
    
Dihydroartemisinin-piperaquine is another effective first-line treatment for P. falciparum malaria .
The performance of the non-ACT ( amodiaquine plus sulfadoxine-pyrimethamine ) falls below WHO recommendations for first-line therapy in parts of Africa .
In areas where primaquine is not being used for radical cure of P. vivax , ACTs with long half-lives may provide some benefit