***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 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 Pregnant women participating in a longitudinal immuno-epidemiologic survey in Lambaréné , Gabon , and presenting with Plasmodium falciparum parasitemia at monthly blood smear examinations were offered treatment with oral 7-day quinine monotherapy according to national health guidelines . A total of 50 pregnant women were offered 7-day oral quinine sulfate 10 mg/kg thrice daily . Clinical examinations and laboratory tests were performed on Days 28 and 56 to assess the effectiveness of this st and ard regimen . By Day 28 , the effectiveness of the 7-day quinine regimen was 60 % ( 95 % confidence interval : 46 - 72 % ) . We conclude that a 7-day course of quinine has a poor effectiveness and that alternative treatment regimens for malaria in pregnant women should be assessed BACKGROUND Artemisinin-based combination therapies are the recommended first-line treatments of falciparum malaria in all countries with endemic disease . There are recent concerns that the efficacy of such therapies has declined on the Thai-Cambodian border , historically a site of emerging antimalarial-drug resistance . METHODS In two open-label , r and omized trials , we compared the efficacies of two treatments for uncomplicated falciparum malaria in Pailin , western Cambodia , and Wang Pha , northwestern Thail and : oral artesunate given at a dose of 2 mg per kilogram of body weight per day , for 7 days , and artesunate given at a dose of 4 mg per kilogram per day , for 3 days , followed by mefloquine at two doses totaling 25 mg per kilogram . We assessed in vitro and in vivo Plasmodium falciparum susceptibility , artesunate pharmacokinetics , and molecular markers of resistance . RESULTS We studied 40 patients in each of the two locations . The overall median parasite clearance times were 84 hours ( interquartile range , 60 to 96 ) in Pailin and 48 hours ( interquartile range , 36 to 66 ) in Wang Pha ( P<0.001 ) . Recrudescence confirmed by means of polymerase-chain-reaction assay occurred in 6 of 20 patients ( 30 % ) receiving artesunate monotherapy and 1 of 20 ( 5 % ) receiving artesunate-mefloquine therapy in Pailin , as compared with 2 of 20 ( 10 % ) and 1 of 20 ( 5 % ) , respectively , in Wang Pha ( P=0.31 ) . These markedly different parasitologic responses were not explained by differences in age , artesunate or dihydroartemisinin pharmacokinetics , results of isotopic in vitro sensitivity tests , or putative molecular correlates of P. falciparum drug resistance ( mutations or amplifications of the gene encoding a multidrug resistance protein [ PfMDR1 ] or mutations in the gene encoding sarco-endoplasmic reticulum calcium ATPase6 [ PfSERCA ] ) . Adverse events were mild and did not differ significantly between the two treatment groups . CONCLUSIONS P. falciparum has reduced in vivo susceptibility to artesunate in western Cambodia as compared with northwestern Thail and . Resistance is characterized by slow parasite clearance in vivo without corresponding reductions on conventional in vitro susceptibility testing . Containment measures are urgently needed . ( Clinical Trials.gov number , NCT00493363 , and Current Controlled Trials number , IS RCT N64835265 . Objective To compare the effectiveness of oral quinine with that of artemether-lumefantrine in treating uncomplicated malaria in children . Design R and omised , open label effectiveness study . Setting Outpatient clinic of Ug and a ’s national referral hospital in Kampala . Participants 175 children aged 6 to 59 months with uncomplicated malaria . Interventions Participants were r and omised to receive oral quinine or artemether-lumefantrine administered by care givers at home . Main outcome measures Primary outcomes were parasitological cure rates after 28 days of follow-up unadjusted and adjusted by genotyping to distinguish recrudescence from new infections . Secondary outcomes were adherence to study drug , presence of gametocytes , recovery of haemoglobin concentration from baseline at day 28 , and safety profiles . Results Using survival analysis the cure rate unadjusted by genotyping was 96 % for the artemether-lumefantrine group compared with 64 % for the quinine group ( hazard ratio 10.7 , 95 % confidence interval 3.3 to 35.5 , P=0.001 ) . In the quinine group 69 % ( 18/26 ) of parasitological failures were due to recrudescence compared with none in the artemether-lumefantrine group . The mean adherence to artemether-lumefantrine  was 94.5 % compared with 85.4 % to quinine ( P=0.0008 ) . Having adherence levels of 80 % or more was associated with a decreased risk of treatment failure ( 0.44 , 0.19 to 1.02 , P=0.06 ) . Adverse events did not differ between the two groups . Conclusions The effectiveness of a seven day course of quinine for the treatment of uncomplicated malaria in Ug and an children was significantly lower than that of artemether-lumefantrine . These findings question the advisability of the recommendation for quinine therapy for uncomplicated malaria in Africa . Trial registration Clinical Trials.gov NCT00540202 BACKGROUND Artemisinin-based drug combinations are the mainstay in the fight against drug-resistant malaria in Africa . Currently available antimalarial drug combinations that include artemisinins are pharmacokinetically unmatched and are therefore potentially increasing the risk of selection of resistant mutants in areas in which the rate of transmission of malaria is high . We tested the potential value of artemisinin-based combination therapy with a short elimination half-life for the treatment of uncomplicated Plasmodium falciparum malaria in sub-Saharan Africa . METHODS We conducted an open-label , r and omized , controlled clinical trial to evaluate the efficacy and tolerability of oral artesunate-clindamycin therapy given twice daily for 3 days ( artesunate , 2 mg/kg , and clindamycin , 7 mg/kg , per dose ) , compared with a st and ard quinine-clindamycin regimen given twice daily for 3 days ( quinine , 15 mg/kg , and clindamycin , 7 mg/kg , per dose ) , for the treatment of uncomplicated falciparum malaria in 100 Gabonese children aged 3 - 12 years . The primary end point of the study was the polymerase chain reaction-corrected cure rate for the per- protocol population . RESULTS The activity of artesunate-clindamycin was comparable to that of quinine-clindamycin in the per- protocol analysis of cure rates at day 28 of follow-up ( 87 % versus 94 % ) . No serious adverse events were reported , and tolerability was good and was similar in both groups . Times to clearance of fever and clearance of parasites were significantly shorter in the artesunate-clindamycin group . CONCLUSIONS Artesunate-clindamycin and other matching artemisinin-based combinations with a short plasma half-life merit further attention for use in regions in which the rate of transmission of malaria is high ABSTRACT Therapeutic responses to clindamycin in combination with quinine were assessed in adult Thai patients with uncomplicated multidrug-resistant Plasmodium falciparum malaria . In total 204 patients were r and omized to receive a 7-day oral treatment regimen of quinine ( Q7 ) either alone ( n = 68 ) , in combination with clindamycin ( Q7C7;n = 68 ) , or in combination with tetracycline ( Q7T7 ; n = 68 ) . All patients had uncomplicated recoveries with no serious adverse effects . Fever clearance times for both of the two combination regimens ( median of 47 h and range of 8 to 120 h for Q7C7 and median of 36 h and range of 8 to 117 h for Q7T7 ) were significantly shorter than that for the Q7-only regimen ( median , 56 ; range , 4 to 152 h ) ( P = 0.002 ) . Parasite clearance times ( overall mean ± st and ard deviation , 78 ± 23 h ) were not significantly different between the three treatment groups ( P = 0.98 ) . The cure rates assessed at 28 days of follow-up were 100 % for Q7C7 and 98 % for Q7T7 , whereas the cure rate was 87 % for the Q7-only regimen ( P ≤ 0.04 ) . Clindamycin in combination with quinine is a safe and effective treatment for multidrug-resistant P. falciparum malaria . This combination may be of particular value in children and pregnant women , in whom tetracyclines are contraindicated ABSTRACT We conducted a r and omized , double-blind , placebo-controlled trial to compare a 3-day quinine-clindamycin regimen ( group QC ) with a 7-day quinine regimen ( group Q ) for the treatment of uncomplicatedPlasmodium falciparum malaria in travelers returning from the tropics . A total of 55 and 53 patients in groups Q and QC were analyzed , respectively .  Adverse effects were similar in both groups , although two patients in group Q had severe adverse reactions , leading to the cessation of treatment . The 28-day cure rate for the evaluated patients ( per- protocol analysis ) was 100 % for group QC , whereas it was 96.3 % for group Q ( P = 0.5 ) . The 28-day cure rate in the intention-to-treat analysis was 96.2 % for group QC , whereas it was 94.6 % for group Q ( P = 1 ) . There were no significant differences between the two regimens with regard to parasite and fever clearance times . Our study shows that the 3-day quinine-clindamycin regimen is well tolerated and compares favorably with a 7-day quinine treatment . This short-term regimen had previously been evaluated only in areas of endemicity . According to our results , the 3-day quinine-clindamycin regimen may be an alternative for the treatment of imported uncomplicated P. falciparum malaria in travelers returning from the tropics In this open r and omized trial comparing 3-day oral quinine-clindamycin versus st and ard mefloquine regimen for uncomplicated imported falciparum malaria , mefloquine treatment was associated with a higher risk of discontinuation of the treatment ( RR=1.8 , 95 % CI [ 1.1 - 2.8 ] ) related to mainly mild gastrointestinal adverse drug events . The poor tolerability of mefloquine sets a question mark against its use in out patients The frequency of  antibiotic-associated diarrhoea ( AAD ) and Clostridium difficile-associated diarrhoea ( CdAD ) was prospect ively determined in a population of 2462 patients recruited from five Swedish hospitals , including divisions for infectious diseases , orthopaedics , surgery , geriat 
    Output:
    
Adverse events were similar across treatment groups but were poorly reported .