Reduction of transmission from malaria patients by artemisinin combination therapies: a pooled analysis of six randomized trials.
BACKGROUND
Artemisinin combination therapies (ACT), which are increasingly being introduced for treatment of Plasmodium falciparum malaria, are more effective against sexual stage parasites (gametocytes) than previous first-line antimalarials and therefore have the potential to reduce parasite transmission. The size of this effect is estimated in symptomatic P. falciparum infections.


METHODS
Data on 3,174 patients were pooled from six antimalarial trials conducted in The Gambia and Kenya. Multivariable regression was used to investigate the role of ACT versus non-artemisinin antimalarial treatment, treatment failure, presence of pre-treatment gametocytes and submicroscopic gametocytaemia on transmission to mosquitoes and the area under the curve (AUC) of gametocyte density during the 28 days of follow up.


RESULTS
ACT treatment was associated with a significant reduction in the probability of being gametocytaemic on the day of transmission experiments (OR 0.20 95% CI 0.16-0.26), transmission to mosquitoes by slide-positive gametocyte carriers (OR mosquito infection 0.49 95% CI 0.33-0.73) and AUC of gametocyte density (ratio of means 0.35 95% CI 0.31-0.41). Parasitological treatment failure did not account for the difference between ACT and non-artemisinin impact. The presence of slide-positive gametocytaemia prior to treatment significantly reduced ACT impact on gametocytaemia (p < 0.001). Taking account of submicroscopic gametocytaemia reduced estimates of ACT impact in a high transmission setting in Kenya, but not in a lower transmission setting in the Gambia.


CONCLUSIONS
Treatment with ACT significantly reduces infectiousness of individual patients with uncomplicated falciparum malaria compared to previous first line treatments. Rapid treatment of cases before gametocytaemia is well developed may enhance the impact of ACT on transmission.
Okell
Lucy C
LC
Department of Infectious & Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK. lucy.okell@lshtm.ac.uk
Drakeley
Chris J
CJ
Ghani
Azra C
AC
Bousema
Teun
T
Sutherland
Colin J
CJ
D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D037621:Artemisinins / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D009033:Culicidae / Q000469:parasitology; D004359:Drug Therapy, Combination; D005714:Gambia; D006801:Humans; D007630:Kenya; D016778:Malaria, Falciparum / Q000635:transmission*; D015999:Multivariate Analysis; D018512:Parasitemia; D010963:Plasmodium falciparum / Q000187:drug effects*; D016032:Randomized Controlled Trials as Topic; D012044:Regression Analysis; D017211:Treatment Failure
D000962:Antimalarials; D037621:Artemisinins; C031327:artemisinin