***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 WHO recommends that adults with uncomplicated P. falciparum successfully treated with a blood schizonticide receive a single dose of primaquine ( PQ ) 45 mg as a gametocytocidal agent . An earlier pilot study suggested that 75 mg of bulaquine ( BQ ) , of which PQ is a major metabolite , may be a useful alternate to PQ . Methods In a r and omized , partial blind study , 90 hospitalized adults with Plasmodium falciparum malaria that was blood schizonticide-responsive and a gametocytemia of > 55/μl within 3 days of diagnosis were r and omized to receive single doses of either PQ 45 mg or BQ 75 mg on day 4 . We assessed gametocytemia on days 8 , 15 , 22 and 29 and gametocyte viability as determined by exflagellation ( 2 ° end point ) on day 8 . Results On day 8 , 20/31 ( 65 % ) primaquine recipients versus 19/59 ( 32 % ) bulaquine recipients showed persistence of gametocytes ( P = 0.002 ) . At day 15 and beyond , all patients were gametocyte free . On day 8 , 16/31 PQ and 7/59 BQ volunteers showed gametocyte viability ( p = 0.000065 ) . Conclusion BQ is a safe , useful alternate to PQ as a Plasmodium falciparum gametocytocidal agent and may clear gametocytemia faster than PQ Abstract The prophylactic and sporontocidal efficacy of st and ard antimalarials was studied among non-immune adult male volunteers challenged by mosquitoes heavily infected with two strains of chloroquine resistant Plasmodium falciparum from Malaya . The Poo . strain from Trengganu broke through in 12 of 15 men receiving chloroquine 300 mg . ( base ) and primaquine 45 mg . ( base ) at weekly intervals , whereas 8 weeks of this treatment protected all 3 men challenged with the Tay . strain from Kota Tinggi , Johore State . The Poo . strain broke through in 5 men given amodiaquine base 300 mg . and DDS 300 mg . weekly . Proguanil 200 mg . ( 2·1–3·2 mg . per kg . body weight ) given daily for 8 weeks after challenge provided complete suppression of the Poo . strain in 4 men ( and probably a fifth ) , and also of the Tay . strain in 4 men , nor did parasitaemia develop after completion of the prophylactic course . Pyrimethamine 25 mg . given weekly failed to protect 2 of 3 men challenged with Poo . , and the Tay . strain also broke through in both men receiving this regimen . A single dose of 45 mg . ( base ) of primaquine was gametocytocidal for both strains and , in one case of Poo . infection studied , rendered gametocytes non-infective to an efficient vector mosquito fed on the patient 24 hours later ABSTRACT The current interest in malaria elimination has led to a renewed interest in drugs that can be used for mass administration to minimize malaria transmission . Primaquine ( PQ ) is the only generally available drug with a strong activity against mature Plasmodium falciparum gametocytes , the parasite stage responsible for transmission . Despite concerns about PQ-induced hemolysis in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals , a single dose of PQ may be safe and efficacious in clearing gametocytes that persist after conventional treatment . As part of a mass drug intervention , we determined the hemolytic effect of sulfadoxine-pyrimethamine ( SP ) plus artesunate ( AS ) plus a single dose of primaquine ( PQ ; 0.75 mg/kg of body weight ) in children aged 1 to 12 years . Children were r and omized to receive SP+AS+PQ or placebo ;  those with a hemoglobin ( Hb ) level below 8 g/dl were excluded from receiving PQ and received SP+AS .  The Hb concentration was significantly reduced 7 days after SP+AS+PQ treatment but not after placebo or SP+AS treatment . This reduction in Hb was most pronounced in G6PD-deficient ( G6PD A− ) individuals ( −2.5 g/dl ; 95 % confidence interval [ 95 % CI ] , −1.2 to −3.8 g/dl ) but was also observed in heterozygotes ( G6PD A ) ( −1.6 g/dl ; 95 % CI , −0.9 to −2.2 g/dl ) and individuals with the wild-type genotype ( G6PD B ) ( −0.5 g/dl ; 95 % CI , −0.4 to −0.6 g/dl ) . Moderate anemia ( Hb level of < 8 g/dl ) was observed in 40 % ( 6/15 individuals ) of the G6PD A− , 11.1 % ( 3/27 individuals ) of the G6PD A , and 4.5 % ( 18/399 individuals ) of the G6PD B individuals ; one case of severe anemia ( Hb level of < 5 g/dl ) was observed . PQ may cause moderate anemia when coadministered with artemisinins , and excluding individuals based on G6PD status alone may not be sufficient to prevent PQ-induced hemolysis ABSTRACT The activities of primaquine in combination with quinine or artesunate against asexual- and sexual-stage parasites were assessed in 176 adult Thai patients with uncomplicated Plasmodium falciparum malaria . Patients were r and omized to one of the six following 7-day oral treatment regimens : ( i ) quinine alone , ( ii ) quinine with tetracycline , ( iii ) quinine with primaquine at 15 mg/day , ( iv ) quinine with primaquine at 30 mg/day , ( v ) artesunate alone , or ( vi ) artesunate with primaquine .  Clinical recovery occurred in all patients . There were no significant differences in fever clearance times , rates of P. falciparum reappearance , or recurrent vivax malaria between the six treatment groups . Patients treated with artesunate alone or in combination with primaquine had significantly shorter parasite clearance times ( mean ± st and ard deviation = 65± 18 versus 79 ± 21 h ) and lower gametocyte carriage rates ( 40 versus 62.7 % ) than those treated with quinine ( P ≤ 0.007 ) . Primaquine did not affect the therapeutic response ( P > 0.2 ) . Gametocytemia was detected in 98 patients ( 56 % [ 22 % before treatment and 34 % after treatment ] ) . Artesunate reduced the appearance of gametocytemia ( relative risk [ 95 % confidence interval ] = 0.34 [ 0.17 to 0.70 ] ) , whereas combinations containing primaquine result ed in shorter gametocyte clearance times ( medians of 66 versus 271 h for quinine groups and 73 versus 137 h for artesunate groups ; P≤ 0.038 ) . These results suggest that artesunate predominantly inhibits gametocyte development whereas primaquine accelerates gametocyte clearance in P. falciparum malaria Background Effective mass drug administration ( MDA ) with anti-malarial drugs can clear the human infectious reservoir for malaria and thereby interrupt malaria transmission . The likelihood of success of MDA depends on the intensity and seasonality of malaria transmission , the efficacy of the intervention in rapidly clearing all malaria parasite stages and the degree to which symptomatic and asymptomatic parasite carriers participate in the intervention . The impact of MDA with the gametocytocidal drug combination sulphadoxine-pyrimethamine ( SP ) plus artesunate ( AS ) plus primaquine ( PQ , single dose 0.75 mg/kg ) on malaria transmission was determined in an area of very low and seasonal malaria transmission in northern Tanzania . Methods In a cluster-r and omized trial in four villages in Lower Moshi , Tanzania , eight clusters ( 1,110 individuals ; cluster size 47- 209 ) were r and omized to observed treatment with SP+AS+PQ and eight clusters ( 2,347 individuals , cluster size 55- 737 ) to treatment with placebo over three days . Intervention and control clusters were 1 km apart ; households that were located between clusters were treated as buffer zones where all individuals received SP+AS+PQ but were not selected for the evaluation . Passive case detection was done for the entire cohort and active case detection in 149 children aged 1 - 10 year from the intervention arm and 143 from the control arm . Four cross-sectional surveys assessed parasite carriage by microscopy and molecular methods during a five-month follow-up period . Results The coverage rate in the intervention arm was 93.0 % ( 1,117/1,201 ) . Parasite prevalence by molecular detection methods was 2.2 - 2.7 % prior to the intervention and undetectable during follow-up in both the control and intervention clusters . None of the slides collected during cross-sectional surveys had microscopically detectable parasite densities . Three clinical malaria episodes occurred in the intervention ( n = 1 ) and control clusters ( n = 2 ) . Conclusions This study illustrates the possibility to achieve high coverage with a three-day intervention but also the difficulty in defining suitable outcome measures to evaluate interventions in areas of very low malaria transmission intensity . The decline in transmission intensity prior to the intervention made it impossible to assess the impact of MDA in the chosen study setting .Trial Registration Clinical Trials.gov : Background P. falciparum gametocytes may persist after treatment with sulphadoxine-pyrimethamine ( SP ) plus artesunate ( AS ) and contribute considerably to malaria transmission . We determined the efficacy of SP+AS plus a single dose of primaquine ( PQ , 0.75 mg/kg ) on clearing gametocytaemia measured by molecular methods . Methodology The study was conducted in Mnyuzi , an area of hyperendemic malaria in north-eastern Tanzania . Children aged 3–15 years with uncomplicated P. falciparum malaria with an asexual parasite density between 500–100,000 parasites/µL were r and omized to receive treatment with either SP+AS or SP+AS+PQ . P. falciparum gametocyte prevalence and density during the 42-day follow-up period were determined by real-time nucleic acid sequence-based amplification ( QT-NASBA ) . Haemoglobin levels ( Hb ) were determined to address concerns about haemolysis in G6PD-deficient individuals . Results 108 individuals were r and omized . Pfs25 QT-NASBA gametocyte prevalence was 88–91 % at enrolment and decreased afterwards for both treatment arms . Gametocyte prevalence and density were significantly lower in children treated with SP+AS+PQ . On day 14 after treatment 3.9 % ( 2/51 ) of the SP+AS+PQ treated children harboured gametocytes compared to 62.7 % ( 32/51 ) of those treated with SP+AS  ( p<0.001 ) . Hb levels were reduced in the week following treatment with SP+AS+PQ and this reduction was related to G6PD deficiency . The Hb levels of all patients recovered to pre-treatment levels or greater within one month after treatment . Conclusions PQ clears su bmi croscopic gametocytes after treatment with SP+AS and the persisting gametocytes circulated at densities that are unlikely to contribute to malaria transmission . For individuals without severe anaemia , addition of a single dose of PQ to an efficacious antimalarial drug combination is a safe approach to reduce malaria transmission following treatment . Trial Registration Controlled-Trials.com IS RCT Background In areas of seasonal malaria transmission , treatment of asymptomatic carriers of malaria parasites , whose parasitaemia persists at low densities throughout the dry season , could be a useful strategy for malaria control . We carried out a r and omized trial to compare two drug regimens for clearance of parasitaemia in order to identify the optimum regimen for use in mass drug administration in the dry season . Methodology and Principal Findings A two-arm open-label r and omized controlled trial was conducted during the dry season in an area of distinct seasonal malaria in two villages in Gedarif State in eastern Sudan . Participants were asymptomatic adults and children aged over 6 months , with low-density P. falciparum infection detected by PCR . Participants were r and omized to receive artesunate/sulfadoxine-pyrimethamine ( AS+SP ) combination for three days with or without a dose of primaquine ( PQ ) on the fourth day . Parasitaemia detected by PCR on days 3 , 7 and 14 after the start of treatment and gametocytes detected by RT-PCR on days 7 and 14 were then recorded . 104 individuals who had low density parasitaemia at screening were r and omized and treated during the dry season . On day 7 , 8.3 % were positive by PCR in the AS+SP+PQ group and 6.5 % in the AS+SP group ( risk difference 1.8 % , 95%CI −10.3 % to + 13.8 % ) . At enrolment , 12 % ( 12/100 ) were carrying gametocytes . This was reduced to 6.4 % and 4.4 % by day 14 ( Risk 
    Output:
    
Authors ' conclusions In individual patients , PQ added to malaria treatments reduces gametocyte prevalence when given in doses greater than 0.4 mg/kg .
No included trials evaluated whether this policy has an impact on community malaria transmission either in low-endemic setting s approaching elimination , or in highly-endemic setting s where many people are infected but have no symptoms and are unlikely to be treated .
For the currently recommended low dose regimen , there is little direct evidence to be confident that the effect of reduction in gametocyte prevalence is preserved .
Most trials excluded people with G6PD deficiency , and thus there is little reliable evidence from controlled trials of the safety of PQ in single dose or short course .
Overall the safety of PQ given as a single dose was poorly evaluated across all studies , so these data do not demonstrate whether the drug is safe or potentially harmful at this dosing level