***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 Afghanistan 's national guidelines recommend chloroquine for the treatment of Plasmodium vivax infection , the parasite responsible for the majority of its malaria burden . Chloroquine resistance in P. vivax is emerging in Asia . Therapeutic responses across Afghanistan have not been evaluated in detail . Methods Between July 2007 and February 2009 , an open-label , r and omized controlled trial of chloroquine and dihydroartemisinin-piperaquine in patients aged three months and over with slide-confirmed P. vivax mono-infections was conducted . Consistent with current national guidelines , primaquine was not administered . Subjects were followed up daily during the acute phase of illness ( days 0 - 3 ) and weekly until day 56 . The primary endpoint was the overall cumulative parasitological failure rate at day 56 after the start of treatment , with the hypothesis being that dihydroartemisinin-piperaquine was non-inferior compared to chloroquine ( Δ = 5 % difference in proportion of failures ) . Results Of 2,182 individuals with positive blood films for P. vivax , 536 were enrolled in the trial . The day 28 cure rate was 100 % in both treatment groups . Parasite clearance was more rapid with dihydroartemisinin-piperaquine than chloroquine . At day 56 , there were more recurrent infections in the chloroquine arm ( 8.9 % , 95 % CI 6.0 - 13.1 % ) than the dihydroartemisinin-piperaquine arm ( 2.8 % , 95 % CI 1.4 - 5.8 % ) , a difference in cumulative recurrence rate of 6.1 % ( 2-sided 90%CI + 2.6 to + 9.7 % ) . The log-rank test comparing the survival curves confirmed the superiority of dihydroartemisinin-piperaquine over chloroquine ( p = 0.003 ) . Multivariate analysis showed that a lower initial haemoglobin concentration was also independently associated with recurrence . Both regimens were well tolerated and no serious adverse events were reported . Conclusions Chloroquine remains an efficacious treatment for the treatment of vivax malaria in Afghanistan . In a setting where radical therapy can not be administered , dihydroartemisinin-piperaquine provides additional benefit in terms of post-treatment prophylaxis , reducing the incidence of recurrence from 4 - 8 weeks after treatment . Trial Registration The trial was registered at Clinical Trials.gov under identifier NCT00682578 Background Malaria is a very important cause of anaemia in tropical countries . Anaemia is assessed either by measurement of the haematocrit or the haemoglobin concentration . For comparisons across studies , it is often necessary to derive one measure from the other . Methods Data on patients with slide-confirmed uncomplicated falciparum malaria were pooled from 85 antimalarial drug trials conducted in 25 different countries , to assess the haemoglobin/haematocrit relationship at different time points in malaria . Using a linear r and om effects model , a conversion equation for haematocrit was derived based on 3,254 measurements from various time points ( ranging from day 0 to day 63 ) from 1,810 patients with simultaneous measurements of both parameters . Haemoglobin was also estimated from haematocrit with the commonly used threefold conversion . Results A good fit was obtained using Haematocrit = 5.62 + 2.60 * Haemoglobin . On average , haematocrit/3 levels were slightly higher than haemoglobin measurements with a mean difference ( ± SD ) of -0.69 ( ± 1.3 ) for children under the age of 5 ( n = 1,440 measurements from 449 patients ) . Conclusion Based on this large data set , an accurate and robust conversion factor both in acute malaria and in convalescence was obtained . The commonly used threefold conversion is also valid Background Radical cure of Plasmodium vivax malaria with 8-aminoquinolines ( primaquine or tafenoquine ) is complicated by haemolysis in individuals with glucose-6-phosphate dehydrogenase ( G6PD ) deficiency . G6PD heterozygous females , because of individual variation in the pattern of X-chromosome inactivation ( Lyonisation ) in erythroid cells , may have low G6PD activity in the majority of their erythrocytes , yet are usually reported as G6PD “ normal ” by current phenotypic screening tests . Their haemolytic risk when treated with 8-aminoquinolines has not been well characterized . Methods and Findings In a cohort study nested within a r and omised clinical trial that compared different treatment regimens for P. vivax malaria , patients with a normal st and ard NADPH fluorescent spot test result ( ≳30%–40 % of normal G6PD activity ) were r and omised to receive 3 d of chloroquine or dihydroartemisinin-piperaquine in combination with primaquine , either the st and ard high dose of 0.5 mg base/kg/day for 14 d or a higher dose of 1 mg base/kg/d for 7 d. Patterns of haemolysis were compared between G6PD wild-type and G6PD heterozygous female participants . Between 21 February 2012 and 04 July 2014 , 241 female participants were enrolled , of whom 34 were heterozygous for the G6PD Mahidol variant . Haemolysis was substantially greater and a larger proportion of participants reached the threshold of clinical ly significant haemolysis ( fractional haematocrit reduction > 25 % ) in G6PD heterozygotes taking the higher ( 7 d ) primaquine dose ( 9/17 [ 53 % ] ) compared with G6PD heterozygotes taking the st and ard high ( 14 d ) dose ( 2/16 [ 13 % ] ; p = 0.022 ) . In heterozygotes , the mean fractional haematocrit reductions were correspondingly greater with the higher primaquine dose ( 7-d regimen ) : −20.4 % ( 95 % CI −26.0 % to −14.8 % ) ( nadir on day 5 ) compared with the st and ard high ( 14 d ) dose : −13.1 % ( 95 % CI −17.6 % to −8.6 % ) ( nadir day 6 ) . Two heterozygotes taking the higher ( 7 d ) primaquine dose required blood transfusion . In wild-type participants , mean haematocrit reductions were clinical ly insignificant and similar with both doses : −5.8 ( 95 % CI −7.2 % to −4.4 % ) ( nadir day 3 ) compared with −5.5 % ( 95 % CI −7.4 % to −3.7 % ) ( nadir day 4 ) , respectively . Limitations to this nested cohort study are that the primary objective of the trial was design ed to measure efficacy and not haemolysis in relation to G6PD genotype and that the heterozygote groups were small . Conclusion Higher daily doses of primaquine have the potential to cause clinical ly significant haemolysis in G6PD heterozygous females who are reported as phenotypically normal with current point of care tests . Trial Registration Clinical Trials.gov NCT01640574 Background New antimalarials are needed for P. vivax and P. falciparum malaria . This study compared the efficacy and safety of pyronaridine-artesunate with that of chloroquine for the treatment of uncomplicated P. vivax malaria . Methods and Findings This phase III r and omized , double-blind , non-inferiority trial included five centers across Cambodia , Thail and , India , and Indonesia . In a double-dummy design , patients ( aged > 3–≤60 years ) with microscopically confirmed P. vivax mono-infection were r and omized ( 1∶1 ) to receive pyronaridine-artesunate ( target dose 7.2∶2.4 mg/kg to 13.8∶4.6 mg/kg ) or chloroquine ( st and ard dose ) once daily for three days . Each treatment group included 228 r and omized patients . Outcomes for the primary endpoint , Day-14 cure rate in the per- protocol population , were 99.5 % , ( 217/218 ; 95%CI 97.5 , 100 ) with pyronaridine-artesunate and 100 % ( 209/209 ; 95%CI 98.3 , 100 ) with chloroquine . Pyronaridine was non-inferior to chloroquine : treatment difference −0.5 % ( 95%CI −2.6 , 1.4 ) , i.e. , the lower limit of the 2-sided 95%CI for the treatment difference was greater than −10  % . Pyronaridine-artesunate cure rates were non-inferior to chloroquine for Days 21 , 28 , 35 and 42 . Parasite clearance time was shorter with pyronaridine-artesunate ( median 23.0 h ) versus chloroquine ( 32.0 h ; p<0.0001 ) , as was fever clearance time ( median 15.9 h and 23.8 h , respectively ; p = 0.0017 ) . Kaplan-Meier estimates of post-baseline P. falciparum infection incidence until Day 42 were 2.5 % with pyronaridine-artesunate , 6.1 % with chloroquine ( p = 0.048 , log-rank test ) . Post-baseline P. vivax or P. falciparum infection incidence until Day 42 was 6.8 % and 12.4 % , respectively ( p = 0.022 , log rank test ) . There were no deaths . Adverse events occurred in 92/228 ( 40.4 % ) patients with pyronaridine-artesunate and 72/228 ( 31.6 % ) with chloroquine . Mild and transient increases in hepatic enzymes were observed for pyronaridine-artesunate . Conclusion Pyronaridine-artesunate efficacy in acute uncomplicated P. vivax malaria was at least that of chloroquine . As pyronaridine-artesunate is also efficacious against P. falciparum malaria , this combination has potential utility as a global antimalarial drug . Trial registration Clinical trials.gov Background  Severe malaria ( SM )  is classically associated with Plasmodium falciparum infection . Little information is available on the contribution of P. vivax to severe disease . There are some epidemiological indications that P. vivax or mixed infections protect against complications and deaths . A large morbidity surveillance conducted in an area where the four species coexist allowed us to estimate rates of SM among patients infected with one or several species . Methods and Findings This was a prospect i ve cohort study conducted within the framework of the Malaria Vaccine Epidemiology and Evaluation Project . All presumptive malaria cases presenting at two rural health facilities over an 8-y period were investigated with history taking , clinical examination , and laboratory assessment . Case definition of SM was based on the World Health Organization ( WHO ) criteria adapted for the setting ( i.e. , clinical diagnosis of malaria associated with asexual blood stage parasitaemia and recent history of fits , or coma , or respiratory distress , or anaemia [ haemoglobin < 5 g/dl ] ) . Out of 17,201 presumptive malaria cases , 9,537 ( 55 % ) had a confirmed Plasmodium parasitaemia . Among those , 6.2 % ( 95 % confidence interval [ CI ] 5.7%–6.8 % ) fulfilled the case definition of SM , most of them in children < 5 y. In this age group , the proportion of SM was 11.7 % ( 10.4%–13.2 % ) for P. falciparum , 8.8 % ( 7.1%–10.7 % ) for P. vivax , and 17.3 % ( 11.7%–24.2 % ) for mixed P. falciparum and P. vivax infections . P. vivax SM presented more often with respiratory distress than did P. falciparum ( 60 % versus 41 % , p = 0.002 ) , but less often with anaemia ( 19 % versus 41 % , p = 0.0001 ) . Conclusion P. vivax monoinfections as well as mixed Plasmodium infections are associated with SM . There is no indication that mixed infections protected against SM . Interventions targeted toward P. falciparum only might be insufficient to eliminate the overall malaria burden , and especially severe disease , in areas where P. falciparum and P. vivax coexist Azithromycin has demonstrated activity in a prevention of Plasmodium vivax infection , but no controlled treatment studies have been performed . We conducted a double-blinded trial in P. vivax malaria in which patients were r and omized to either azithromycin 1,000 mg q.d . x 3 or chloroquine 600 mg q.d . x 2 then 300 mg on Day 3 followed by primaquine on Days 7 through 20 . Eighty-five of 97 ( 88 % ) of those on azithromycin and 10 
    Output:
    
Seven days after starting primaquine , G6PD normal patients had a 0.3 % ( 1/389 ) risk of clinical ly significant haemolysis ( fall in haemoglobin > 25 % to < 7 g/dL ) and a 1 % ( 4/389 ) risk of a fall in haemoglobin > 5 g/dL. Conclusions Primaquine has the potential to reduce malaria-related anaemia at day 42 and beyond by preventing recurrent parasitaemia .