***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 The Plasmodium vivax that was once prevalent in temperate climatic zones typically had an interval between primary infection and first relapse of 7–10 months , whereas in tropical areas P.vivax infections relapse frequently at intervals of 3–6 weeks . Defining the epidemiology of these two phenotypes from temporal patterns of illness in endemic areas is difficult or impossible , particularly if they overlap . Methods A prospect i ve open label comparison of chloroquine ( CQ ) alone versus CQ plus unobserved primaquine for either 5 days or 14 days was conducted in patients presenting with acute vivax malaria in Kolkata . Patients were followed for 15 months and primary and recurrent infections were genotyped using three polymorphic antigen and up to 8 microsatellite markers . Results 151 patients were enrolled of whom 47 ( 31 % ) had subsequent recurrent infections . Recurrence proportions were similar in the three treatment groups . Parasite genotyping revealed discrete temporal patterns of recurrence allowing differentiation of probable relapse from newly acquired infections . This suggested that 32 of the 47 recurrences were probable relapses of which 22 ( 69 % ) were genetically homologous . The majority ( 81 % ) of probable relapses occurred within three months ( 16 homologous , 10 heterologous ) and six genetically homologous relapses ( 19 % ) were of the long latency ( 8–10 month interval ) phenotype . Conclusions With long follow-up to assess temporal patterns of vivax malaria recurrence , genotyping of P.vivax can be used to assess relapse rates . A 14 day unobserved course of primaquine did not prevent relapse . Genotyping indicates that long latency P.vivax is prevalent in West Bengal , and that the first relapses after long latent periods are genetically homologous . Trial Registration Controlled-Trials.com IS RCT Objective In 2010 , the World Health Organization ( WHO ) published up date d guidelines emphasizing and exp and ing recommendations for a parasitological confirmation of malaria before treating with antimalarials . This study aim ed to assess differences in historic ( 2007–2008 ) ( cohort 1 ) and recent ( 2011–2012 ) ( cohort 2 ) hospital cohorts in the diagnosis and treatment of febrile illness in a low malaria prevalence area of northern Tanzania . Material s and Methods We analyzed data from two prospect i ve cohort studies that enrolled febrile adolescents and adults aged ≥13 years . All patients received quality -controlled aerobic blood cultures and malaria smears . We compared patients ' discharge diagnoses , treatments , and outcomes to assess changes in the treatment of malaria and bacterial infections . Results In total , 595 febrile in patients were enrolled from two referral hospitals in Moshi , Tanzania . Laboratory-confirmed malaria was detected in 13 ( 3.2 % ) of 402 patients in cohort 1 and 1 ( 0.5 % ) of 193 patients in cohort 2 ( p = 0.041 ) . Antimalarials  were prescribed to 201 ( 51.7 % ) of 389 smear-negative patients in cohort 1 and 97 ( 50.5 % ) of 192 smear-negative patients in cohort 2 ( p = 0.794 ) . Bacteremia was diagnosed from st and ard blood culture in 58 ( 14.5 % ) of 401 patients in cohort 1 compared to 18 ( 9.5 % ) of 190 patients in cohort 2 ( p = 0.091 ) . In cohort 1 , 40 ( 69.0 % ) of 58 patients with a positive blood culture received antibacterials  compared to 16 ( 88.9 % ) of 18 patients in cohort 2 ( p = 0.094 ) . In cohort 1 , 43 ( 10.8 % ) of the 399 patients with known outcomes died during hospitalization compared with 12 ( 6.2 % ) deaths among 193 patients in cohort 2 ( p = 0.073 ) . Discussion In a setting of low malaria transmission , a high proportion of smear-negative patients were diagnosed with malaria and treated with antimalarials despite up date d WHO guidelines on malaria treatment . Improved laboratory diagnostics for non-malaria febrile illness might help to curb this practice In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance . Risk of bias may vary across outcomes ( e.g. , loss to follow-up may be far less for all-cause mortality than for quality of life ) , a consideration that many systematic review s ignore . In deciding whether to rate down for risk of bias -- whether for r and omized trials or observational studies -- authors should not take an approach that averages across studies . Rather , for any individual outcome , when there are some studies with a high risk , and some with a low risk of bias , they should consider including only the studies with a lower risk of bias Background Vivax malaria remains a major cause of morbidity in the subtropics . To undermine the stability of the disease , drugs are required that prevent relapse and provide reservoir reduction . A 14-day course of primaquine ( PQ ) is effective but can not safely be used in routine practice because of its interaction with glucose-6-phosphate dehydrogenase ( G6PD ) deficiency for which testing is seldom available . Safe and effective use of PQ without the need for G6PD testing would be ideal . The efficacy and safety of an 8-week , once weekly PQ regimen was compared with current st and ard treatment ( chloroquine alone ) and a 14-day PQ regimen . Methods and Principal Findings 200 microscopically confirmed Plasmodium vivax patients were r and omly assigned to either once weekly 8-week PQ ( 0.75mg/kg/week ) , once weekly 8-week placebo , or 14-day PQ ( 0.5mg/kg/day ) in North West Frontier Province , Pakistan . All patients were treated with a st and ard chloroquine dose and tested for G6PD deficiency . Deficient patients were assigned to the 8-week PQ group . Failure was defined as any subsequent episode of vivax malaria over 11 months of observation . There were 22/71 ( 31.0 % ) failures in the placebo group and 1/55 ( 1.8 % ) and 4/75 ( 5.1 % ) failures in the 14-day and 8-week PQ groups , respectively . Adjusted odds ratios were : for 8-week PQ vs. placebo-0.05 ( 95%CI : 0.01 - 0.2 , p<0.001 ) and for 14-day PQ vs. placebo-0.01 ( 95%CI : 0.002 - 0.1 , p<0.001 ) . Restricted analysis allowing for a post-treatment prophylactic effect confirmed that the 8-week regimen was superior to current treatment . Only one G6PD deficient patient presented . There were no serious adverse events . Conclusions A practical radical treatment for vivax malaria is essential for control and elimination of the disease . The 8-week PQ course is more effective at preventing relapse than current treatment with chloroquine alone . Widespread use of the 8-week regimen could make an important contribution to reservoir reduction or regional elimination where G6PD testing is not available . Trial Registration Clinical Trials.gov ABSTRACT Radical cure of Plasmodium vivax infection applies blood schizontocidal therapy against the acute attack and hypnozoitocidal therapy against later relapse . Chloroquine and primaquine have been used for 60 years in this manner . Resistance to chloroquine by the parasite now requires partnering other blood schizontocides with primaquine . However , the safety and efficacy of primaquine against relapse when combined with other drugs have not been demonstrated . This r and omized , open-label , and relapse-controlled trial estimated the efficacy of primaquine against relapse when administered with quinine or dihydroartemisinin-piperaquine for treatment of the acute infection . Among 650 soldiers who had returned to their malaria-free base in Java , Indonesia , after 12 months in malarious Papua , Indonesia , 143 with acute P. vivax malaria were eligible for study . One hundred sixteen enrolled subjects were r and omized to these treatments : artesunate ( 200-mg dose followed by 100 mg/day for 6 days ) , quinine ( 1.8 g/day for 7 days ) plus concurrent primaquine ( 30 mg/day for 14 days ) , or dihydroartemisinin ( 120 mg ) plus piperaquine ( 960 mg ) daily for 3 days followed 25 days later by primaquine ( 30 mg/day for 14 days ) . Follow-up was for 12 months . One hundred thirteen subjects were analyzable . Relapse occurred in 32 of 41 ( 78 % ) subjects administered artesunate alone ( 2.71 attacks/person-year ) , 7 of 36 ( 19 % ) administered quinine plus primaquine ( 0.23 attack/person-year ) , and 2 of 36 ( 6 % ) administered dihydroartemisinin-piperaquine plus primaquine ( 0.06 attack/person-year ) . The efficacy of primaquine against relapse was 92 % ( 95 % confidence interval [ CI ] = 81 % to 96 % ) for quinine plus primaquine and 98 % ( 95 % CI = 91 % to 99 % ) for dihydroartemisinin-piperaquine plus primaquine . Antirelapse therapy with primaquine begun a month after treatment of the acute attack with dihydroartemisinin-piperaquine proved safe and highly efficacious against relapse by P. vivax acquired in Papua , Indonesia Background . Efficacy of st and ard dose of primaquine ( PQ ) as antirelapse for P. vivax has decreased . We aim ed to assess efficacy of different PQ regimens . Methods . It was an open label , r and omized , controlled , parallel group , assessor blind study comparing antirelapse efficacy of 3 PQ regimens ( B = 15 mg/day × 14 days , C = 30 mg/day × 7 days , and D = 30 mg/day × 14 days ) with no PQ group ( A ) in P. vivax patients . Paired primary and recurrence sample s were subjected to 3 methods : ( i ) month of recurrence and genotyping , ( ii ) by PCR-RFLP , and ( iii ) PCR sequencing , to differentiate relapse and reinfection . The rates of recurrence relapse and reinfection were compared . Methods were compared for concordance between them . Results . The recurrence rate was 16.39 % , 8.07 % , 10.07 % , and 6.62 % in groups A , B , C , and D , respectively ( P = 0.004 ) . The relapse rate was 6.89 % , 1.55 % , 4 % , and 3.85 % as per the month of recurrence ; 8.2 % , 2 % , 4.58 % , and 3.68 % ( P = 0.007 ) as per PCR-RFLP ; and 2.73 % , 1.47 % , 1.55 % , and 1.53 % as per PCR sequencing for groups A , B , C , and D , respectively . The concordance between methods was low , 45 % . Conclusion . The higher recurrence rate  in no PQ as compared to PQ groups documents PQ antirelapse activity . Regimens tested were safe . However , probable resistance to PQ warrants continuous monitoring and low concordance and limitations in the methods warrant caution in interpreting with the objective of evaluating shortened therapeutic outlines effective in vivax malaria treatment , we accomplished an open , prospect i ve study allocating 234 patients with vivax malaria distributed at r and om into eight therapeutic groups . Six groups used oral arthemisin as blood esquizonticide at different doses for one day and the other two groups received chloroquine in a single dose . The primaquine was used as a hypnozoiticide in all groups . They received a daily dose of 30 mg in the course of five or seven days in all groups . The clearance of parasitaemia in patients treated with arthemisin ( independent of dosage ) was faster than the chloroquine group ( p < 0.01 ) . Cure was acheived in 92.3 % and 80.2 % , in patients treated with primaquine for seven or five days , respectively ( p=0.0372 ) We evaluated the efficacy of three primaquine ( PQ ) regimes to prevent  relapses with Plasmodium vivax through an open-label r and omized trial in Loreto , Peru . Vivax monoinfe 
    Output:
    
Available evidence is insufficient to determine whether currently PQ regimens used as alternative rather than st and ard treatment have better efficacy and safety in preventing relapse of P. vivax .