@article{WWARN_Gametocyte_Study_Group2016-xr,

title = {Gametocyte carriage in uncomplicated Plasmodium falciparum 

 malaria following treatment with artemisinin combination therapy: 

 a systematic review and meta-analysis of individual patient data},

author = {WWARN Gametocyte Study Group},

year  = {2016},

date = {2016-05-01},

journal = {BMC Med.},

volume = {14},

pages = {79},

abstract = {BACKGROUND: Gametocytes are responsible for transmission of 

 malaria from human to mosquito. Artemisinin combination therapy 

 (ACT) reduces post-treatment gametocyte carriage, dependent upon 

 host, parasite and pharmacodynamic factors. The gametocytocidal 

 properties of antimalarial drugs are important for malaria 

 elimination efforts. An individual patient clinical data 

 meta-analysis was undertaken to identify the determinants of 

 gametocyte carriage and the comparative effects of four ACTs: 

 artemether-lumefantrine (AL), artesunate/amodiaquine (AS-AQ), 

 artesunate/mefloquine (AS-MQ), and dihydroartemisinin-piperaquine 

 (DP). METHODS: Factors associated with gametocytaemia prior to, 

 and following, ACT treatment were identified in multivariable 

 logistic or Cox regression analysis with random effects. All 

 relevant studies were identified through a systematic review of 

 PubMed. Risk of bias was evaluated based on study design, 

 methodology, and missing data. RESULTS: The systematic review 

 identified 169 published and 9 unpublished studies, 126 of which 

 were shared with the WorldWide Antimalarial Resistance Network 

 (WWARN) and 121 trials including 48,840 patients were included in 

 the analysis. Prevalence of gametocytaemia by microscopy at 

 enrolment was 12.1 % (5887/48,589), and increased with 

 decreasing age, decreasing asexual parasite density and 

 decreasing haemoglobin concentration, and was higher in patients 

 without fever at presentation. After ACT treatment, 

 gametocytaemia appeared in 1.9 % (95 % CI, 1.7-2.1) of 

 patients. The appearance of gametocytaemia was lowest after AS-MQ 

 and AL and significantly higher after DP (adjusted hazard ratio (AHR), 2.03; 95 % CI, 1.24-3.12; P = 0.005 compared to AL) and 

 AS-AQ fixed dose combination (FDC) (AHR, 4.01; 95 % CI, 

 2.40-6.72; P \< 0.001 compared to AL). Among individuals who had 

 gametocytaemia before treatment, gametocytaemia clearance was 

 significantly faster with AS-MQ (AHR, 1.26; 95 % CI, 1.00-1.60; P = 0.054) and slower with DP (AHR, 0.74; 95 % CI, 0.63-0.88; P = 0.001) compared to AL. Both recrudescent (adjusted odds ratio 

 (AOR), 9.05; 95 % CI, 3.74-21.90; P \< 0.001) and new (AOR, 3.03; 

 95 % CI, 1.66-5.54; P \< 0.001) infections with asexual-stage 

 parasites were strongly associated with development of 

 gametocytaemia after day 7. CONCLUSIONS: AS-MQ and AL are more 

 effective than DP and AS-AQ FDC in preventing gametocytaemia 

 shortly after treatment, suggesting that the non-artemisinin 

 partner drug or the timing of artemisinin dosing are important 

 determinants of post-treatment gametocyte dynamics.},

keywords = {Drug resistance; Gametocyte; Malaria; Plasmodium falciparum},

pubstate = {published},

tppubtype = {article}

}