***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 Background This study assessed the safety of the new World Health Organization ( WHO ) recommendation of adding a single low-dose of primaquine ( PQ ) to st and ard artemisinin-based combination therapy ( ACT ) , regardless of individual glucose-6-phosphate dehydrogenase ( G6PD ) status , for treatment of acute uncomplicated Plasmodium falciparum malaria in Tanzania . Methods Men and non-pregnant , non-lactating women aged ≥1 year with uncomplicated P. falciparum malaria were enrolled and r and omized to either st and ard artemether-lumefantrine ( AL ) regimen alone or with a 0.25 mg/kg single-dose of PQ . PQ was administered concomitantly with the first AL dose . All drug doses were supervised . Safety was evaluated between days 0 and 28 . G6PD status was assessed using rapid test ( CareStart ™ ) and molecular genotyping . The primary endpoint was mean percentage relative reduction in haemoglobin ( Hb ) concentration ( g/dL ) between days 0 and 7 by genotypic G6PD status and treatment arm . Results Overall , 220 patients , 110 per treatment arm , were enrolled , of whom 33/217 ( 15.2 % ) were phenotypically G6PD deficient , whereas 15/110 ( 13.6 % ) were genotypically hemizygous males , 5/110 ( 4.5 % ) homozygous females and 22/110 ( 20 % ) heterozygous females . Compared to genotypically G6PD wild-type/normal [ 6.8 , 95 % confidence interval ( CI ) 4.67–8.96 ] , only heterozygous patients in AL arm had significant reduction in day-7 mean relative Hb concentration ( 14.3 , 95 % CI 7.02 - 21.55 , p=0.045 ) , however , none fulfilled the pre-defined haemolytic threshold value of ≥25 % Hb reduction . After adjustment for baseline parasitaemia , Hb , age and sex the mean relative Hb reduction was not statistically significant in both heterozygous and hemizygous/homozygous patients in both arms . A majority of the adverse events ( AEs ) were mild and unrelated to the study drugs . However , six ( 4.4 % ) episodes , three per treatment arm , of acute haemolytic anaemia occurred between days 0 and 7 . Three occurred in phenotypically G6PD deficient patients , two in AL and one in AL + PQ arm , but none in genotypically hemizygous/homozygous patients . All patients with acute haemolytic anaemia recovered without medical intervention . Conclusion The findings support that the WHO recommendation of adding a single low-dose of PQ to st and ard AL regimen is safe for the treatment of acute uncomplicated P. falciparum malaria regardless of G6PD status in Tanzania . Trial registration number 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 Background Finding efficacious tools to decrease and interrupt malaria transmission is essential to sustain the gains in malaria control and contain the emergence of artemisinin resistance . Primaquine is effective against Plasmodium falciparum gametocytes and recommended for treatment campaigns in (pre-)elimination setting s. Safety concerns preclude its use in endemic African countries with variable proportions of glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals . The efficacy of the current recommended dose needs to be evaluated , particularly in individuals with an asymptomatic malaria infection . Methods / design This is a four-arm , open label , r and omized controlled trial that aims to determine and compare the effect of three different single doses of primaquine combined with dihydroartemisinin-piperaquine , an artemisinin-based combination therapy , on gametocyte carriage in asymptomatic , malaria infected , G6PD-normal individuals . Approximately 1,200 participants are enrolled and followed for 42 days , with the primary endpoint being the prevalence of Plasmodium falciparum gametocyte carriage at day 7 of follow-up determined by quantitative nucleic acid sequence based amplification assay . Direct membrane feeding experiments to determine infectiousness to mosquitoes are conducted as a biological secondary endpoint . Discussion Sub-Saharan Africa , with a relatively high but poorly characterized G6PD prevalence , could potentially benefit from the use of primaquine to further reduce or interrupt malaria transmission . However , G6PD screening may not be feasible given the cost and difficulties in interpreting test results in terms of risk of haemolysis . Because the haemolytic effect of primaquine is dose-dependent , determining the minimal gametocytocidal and transmission-blocking dose of primaquine is extremely important to help address public health concerns over its safety and vali date the efficacy of lower than recommended dosages . By including infectiousness to mosquitoes , the trial provides complementary evidence for the potential of the drug to interrupt transmission to mosquitoes . Trial registration Clinical Trials.gov : NCT01838902 ( 12 April 2013 ) 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  
    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