TY - JOUR
T1 - The Relative Effects of Artemether-lumefantrine and Non-artemisinin Antimalarials on Gametocyte Carriage and Transmission of Plasmodium falciparum
T2 - A Systematic Review and Meta-analysis
AU - Ippolito, Matthew M.
AU - Johnson, Julia
AU - Mullin, Christopher
AU - Mallow, Christopher
AU - Morgan, Nadia
AU - Wallender, Erika
AU - Li, Tianjing
AU - Rosenthal, Philip J.
N1 - Funding Information:
Acknowledgements. This review was initiated as coursework at the Johns Hopkins Bloomberg School of Public Health. We acknowledge the course director, Dr Kay Dickersin, and teaching assistants Nicole Fusco and Jimmy Le. We also thank Donna Hesson from the Johns Hopkins William H. Welch Medical Library for her assistance in developing the electronic search strategy.
Funding Information:
Financial support. M. M. I. and E. W. were supported by the National Institute of General Medical sciences (T32GM066691, T32GM007546), J. J. was supported by the National Heart, Lung, and Blood Institute (T32HL1252391), and N. M. was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (T32AR048522) of the National Institutes of Health.
Publisher Copyright:
© The Author 2017.
PY - 2017/8/1
Y1 - 2017/8/1
N2 - Background. Artemisinin-based combination therapies (ACTs) have been widely adopted as first-line agents to treat uncomplicated falciparum malaria due to their activity against multidrug resistant parasites. ACTs may also disrupt transmission through a direct antigametocyte effect, but the extent of this effect is uncertain. We assessed the evidence for and estimated the effects of the most widely-deployed ACT, artemether-lumefantrine (AL), relative to non-ACTs on gametocyte clearance and transmission interruption. Methods. We searched electronic databases for randomized controlled trials comparing AL to non-ACTs that reported gametocyte counts or results of mosquito-feeding assays. Two authors working independently assessed eligibility, extracted data, and evaluated the risk of bias. We conducted meta-analyses using a random-effects model. Results. We identified 22 eligible trials. The pooled odds of gametocytemia at 1 week were lower in AL-compared to non-ACT-treated participants (odds ratio [OR] 0.09; 95% confidence interval [CI], 0.06-0.15; I2 = 0.60, P <.01; 15 trials). The odds of transmission to mosquitoes were also lower in AL treatment groups (OR 0.06; 95% CI, 0.00-0.47, P <.01 at 7 days post-treatment; 1 trial; OR 0.56; 95% CI, 0.36-0.88, P =.01 at 14 days post-treatment; 1 trial). Conclusion. AL is superior to non-ACTs in reducing gametocytemia, and, based on limited evidence, abating transmission to mosquitoes. The transmission-limiting benefit of AL has relevance for policymakers planning optimal utilization of control strategies, including use of ACTs for malaria treatment and chemoprevention.
AB - Background. Artemisinin-based combination therapies (ACTs) have been widely adopted as first-line agents to treat uncomplicated falciparum malaria due to their activity against multidrug resistant parasites. ACTs may also disrupt transmission through a direct antigametocyte effect, but the extent of this effect is uncertain. We assessed the evidence for and estimated the effects of the most widely-deployed ACT, artemether-lumefantrine (AL), relative to non-ACTs on gametocyte clearance and transmission interruption. Methods. We searched electronic databases for randomized controlled trials comparing AL to non-ACTs that reported gametocyte counts or results of mosquito-feeding assays. Two authors working independently assessed eligibility, extracted data, and evaluated the risk of bias. We conducted meta-analyses using a random-effects model. Results. We identified 22 eligible trials. The pooled odds of gametocytemia at 1 week were lower in AL-compared to non-ACT-treated participants (odds ratio [OR] 0.09; 95% confidence interval [CI], 0.06-0.15; I2 = 0.60, P <.01; 15 trials). The odds of transmission to mosquitoes were also lower in AL treatment groups (OR 0.06; 95% CI, 0.00-0.47, P <.01 at 7 days post-treatment; 1 trial; OR 0.56; 95% CI, 0.36-0.88, P =.01 at 14 days post-treatment; 1 trial). Conclusion. AL is superior to non-ACTs in reducing gametocytemia, and, based on limited evidence, abating transmission to mosquitoes. The transmission-limiting benefit of AL has relevance for policymakers planning optimal utilization of control strategies, including use of ACTs for malaria treatment and chemoprevention.
KW - artemether-lumefantrine
KW - artemisinin-based combination therapy
KW - gametocytes
KW - malaria
KW - meta-analysis
UR - http://www.scopus.com/inward/record.url?scp=85027857982&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85027857982&partnerID=8YFLogxK
U2 - 10.1093/cid/cix336
DO - 10.1093/cid/cix336
M3 - Article
C2 - 28402391
AN - SCOPUS:85027857982
VL - 65
SP - 486
EP - 494
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
SN - 1058-4838
IS - 3
ER -
