Changsheng Deng1, Bo Huang1, Qi Wang1,2, Wanting Wu2, Shaoqin Zheng2, Hongying Zhang2, Di Li2, Danghong Feng2, Guoming Li2, Linlu Xue2, Tao Yang2, Fei Tuo2, Fouad Mohadji3, Xin-Zhuan Su4, Qin Xu1, Zhibing Wu5, Li Lin5, Jiuyao Zhou6, Hong Yan2, Affane Bacar7, Kamal Said Abdallah7, Rachadi A Kéké7, Ahamada Msa Mliva3, Moussa Mohamed3, Xinhua Wang8, Shiguang Huang9, Fatihou Oithik3, Xiao-Bo Li2, Fangli Lu10,11, Michael P Fay12, Xiao-Hong Liu13, Thomas E Wellems4, Jianping Song1,2. 1. Institute of Tropical Medicine, People's Republic of China. 2. Science and Technology Park, Guangzhou University of Chinese Medicine, Guangdong, People's Republic of China. 3. Ministry of Health Comoros, Moroni, Union of Comoros, Bethesda, Maryland. 4. Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland. 5. First Affiliated Hospital, People's Republic of China. 6. Traditional Chinese Medicine College, Guangzhou University of Chinese Medicine, Guangdong, People's Republic of China. 7. National Malaria Control Programme, Moroni, Union of Comoros, People's Republic of China. 8. Guangzhou Medical University, People's Republic of China. 9. School of Stomatology, Jinan University, People's Republic of China. 10. Department of Parasitology, Zhongshan School of Medicine, People's Republic of China. 11. Key Laboratory of Tropical Disease Control in Ministry of Education, Sun Yat-sen University, Guangdong, People's Republic of China. 12. Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland. 13. First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangdong, People's Republic of China.
Abstract
Background: Mass drug administration (MDA), with or without low-dose primaquine (PMQLD), is being considered for malaria elimination programs. The potential of PMQLD to block malaria transmission by mosquitoes must be balanced against liabilities of its use. Methods: Artemisinin-piperaquine (AP), with or without PMQLD, was administered in 3 monthly rounds across Anjouan Island, Union of Comoros. Plasmodium falciparum malaria rates, mortality, parasitemias, adverse events, and PfK13 Kelch-propeller gene polymorphisms were evaluated. Results: Coverage of 85 to 93% of the Anjouan population was achieved with AP plus PMQLD (AP+PMQLD) in 2 districts (population 97164) and with AP alone in 5 districts (224471). Between the months of April-September in both 2012 and 2013, average monthly malaria hospital rates per 100000 people fell from 310.8 to 2.06 in the AP+PMQLD population (ratio 2.06/310.8 = 0.66%; 95% CI: 0.02%, 3.62%; P = .00007) and from 412.1 to 2.60 in the AP population (ratio 0.63%; 95% CI: 0.11%, 1.93%; P < .00001). Effectiveness of AP+PMQLD was 0.9908 (95% CI: 0.9053, 0.9991), while effectiveness of AP alone was 0.9913 (95% CI: 0.9657, 0.9978). Both regimens were well tolerated, without severe adverse events. Analysis of 52 malaria samples after MDA showed no evidence for selection of PfK13 Kelch-propeller mutations. Conclusions: Steep reductions of malaria cases were achieved by 3 monthly rounds of either AP+PMQLD or AP alone, suggesting potential for highly successful MDA without PMQLD in epidemiological settings such as those on Anjouan. A major challenge is to sustain and expand the public health benefits of malaria reductions by MDA.
Background: Mass drug administration (MDA), with or without low-dose primaquine (PMQLD), is being considered for malaria elimination programs. The potential of PMQLD to block malaria transmission by mosquitoes must be balanced against liabilities of its use. Methods:Artemisinin-piperaquine (AP), with or without PMQLD, was administered in 3 monthly rounds across Anjouan Island, Union of Comoros. Plasmodium falciparum malaria rates, mortality, parasitemias, adverse events, and PfK13 Kelch-propeller gene polymorphisms were evaluated. Results: Coverage of 85 to 93% of the Anjouan population was achieved with AP plus PMQLD (AP+PMQLD) in 2 districts (population 97164) and with AP alone in 5 districts (224471). Between the months of April-September in both 2012 and 2013, average monthly malaria hospital rates per 100000 people fell from 310.8 to 2.06 in the AP+PMQLD population (ratio 2.06/310.8 = 0.66%; 95% CI: 0.02%, 3.62%; P = .00007) and from 412.1 to 2.60 in the AP population (ratio 0.63%; 95% CI: 0.11%, 1.93%; P < .00001). Effectiveness of AP+PMQLD was 0.9908 (95% CI: 0.9053, 0.9991), while effectiveness of AP alone was 0.9913 (95% CI: 0.9657, 0.9978). Both regimens were well tolerated, without severe adverse events. Analysis of 52 malaria samples after MDA showed no evidence for selection of PfK13 Kelch-propeller mutations. Conclusions: Steep reductions of malaria cases were achieved by 3 monthly rounds of either AP+PMQLD or AP alone, suggesting potential for highly successful MDA without PMQLD in epidemiological settings such as those on Anjouan. A major challenge is to sustain and expand the public health benefits of malaria reductions by MDA.
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