Large-scale Artemisinin–Piperaquine Mass Drug Administration With or Without Primaquine Dramatically Reduces Malaria in a Highly Endemic Region of Africa

Deng, Changsheng; Huang, Bo; Wang, Qi; Wu, Wanting; Zheng, Shaoqin; Zhang, Hongying; Li, Di; Feng, Danghong; Li, Guoming; Xue, Linlu; Yang, Tao; Tuo, Fei; Mohadji, Fouad; Su, Xin-zhuan; Xu, Qin; Wu, Zhibing; Li, Lin; Zhou, Jiuyao; Yan, Hong; Bacar, Affane; Abdallah, Kamal Said; Kéké, Rachadi A; Mliva, Ahamada M. S. A.; Mohamed, M.I.; Wang, Xinhua; Huang, Shiguang; Oithik, Fatihou; Li, Xiaobo; Lü, Fangli; Fay, Michael P.; Liu, Xiaohong; Wellems, Thomas E.; Shen, Jianping

doi:10.1093/cid/ciy364

Cited by 36 publications

(43 citation statements)

References 29 publications

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“…The authors called for more studies incorporating electrocardiogram measurements (4). Recent MDA programs using DHA-PQP in large populations have shown that this drug combination is safe to use due to the minimal occurrence of serious adverse events; however, electrocardiographic assessments were not performed to monitor cardiac side effects (18)(19)(20). Several secondary observations are worth noting, including sex-related differences in the measurements of QT-related parameters.…”

Section: Discussionmentioning

confidence: 99%

Electrocardiographic Safety of Repeated Monthly Dihydroartemisinin-Piperaquine as a Candidate for Mass Drug Administration

Millat-Martínez¹,

Ila²,

Laman³

et al. 2018

Antimicrob Agents Chemother

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Mass drug administration (MDA) of sequential rounds of antimalarial drugs is being considered for use as a tool for malaria elimination. As an effective and long-acting antimalarial, dihydroartemisinin-piperaquine (DHA-PQP) appears to be suitable as a candidate for MDA. However, the absence of cardiac safety data following repeated administration hinders its use in the extended schedules proposed for MDA. We conducted an interventional study in Lihir Island, Papua New Guinea, using healthy individuals age 3 to 60 years who received a standard 3-day course of DHA-PQP on 3 consecutive months. Twelve-lead electrocardiography (ECG) readings were conducted predose and 4 h after the final dose of each month. The primary safety endpoint was QT interval correction (QTc using Fridericia’s correction [QTcF]) prolongation from baseline to 4 h postdosing. We compared the difference in prolongations between the third course postdose and the first course postdose. Of 84 enrolled participants, 69 (82%) participants completed all treatment courses and ECG measurements. The average increase in QTcF was 19.6 ms (standard deviation [SD], 17.8 ms) and 17.1 ms (SD, 17.1 ms) for the first-course and third-course postdosing ECGs risk difference, −2.4 (95% confidence interval [95% CI], −6.9 to 2.1; P = 0.285), respectively. We recorded a QTcF prolongation of >60 ms from baseline in 3 (4.3%) and 2 (2.9%) participants after the first course and third course (P = 1.00), respectively. No participants had QTcF intervals of >500 ms at any time point. Three consecutive monthly courses of DHA-PQP were as safe as a single course. The absence of cumulative cardiotoxicity with repeated dosing supports the use of monthly DHA-PQP as part of malaria elimination strategies.

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Section: Discussionmentioning

confidence: 99%

Electrocardiographic Safety of Repeated Monthly Dihydroartemisinin-Piperaquine as a Candidate for Mass Drug Administration

Millat-Martínez¹,

Ila²,

Laman³

et al. 2018

Antimicrob Agents Chemother

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“…Overall, the findings obtained through the Magude project suggest that MDA could be considered a chemoprevention tool useful to accelerate towards malaria elimination in areas of low to moderate transmission intensity in Africa, where standard case management, vector control, and enhanced surveillance are in place, as reported in other low to moderate transmission areas of Sub-Saharan Africa [22,28,29,40,41]. The use of MDAs has at times been controversial, given the questions posed around its safety when distributing a drug with potential side effects to a large number of healthy individuals [42].…”

Section: Plos Medicinementioning

confidence: 99%

A multiphase program for malaria elimination in southern Mozambique (the Magude project): A before-after study

et al. 2020

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Background Malaria eradication remains the long-term vision of the World Health Organization (WHO). However, whether malaria elimination is feasible in areas of stable transmission in sub-Saharan Africa with currently available tools remains a subject of debate. This study aimed to evaluate a multiphased malaria elimination project to interrupt Plasmodium falciparum malaria transmission in a rural district of southern Mozambique. Methods and findings A before-after study was conducted between 2015 and 2018 in the district of Magude, with 48,448 residents living in 10,965 households. Building on an enhanced surveillance system, two rounds of mass drug administrations (MDAs) per year over two years (phase I, August 2015-2017), followed by one year of reactive focal mass drug administrations (rfMDAs) (phase II, September 2017-June 2018) were deployed with annual indoor residual spraying (IRS), programmatically distributed long-lasting insecticidal nets (LLINs), and standard case management. The four MDA rounds covered 58%-72% of the population, and annual IRS reported coverage was >70%. Yearly parasite surveys and routine surveillance data were used to monitor the primary outcomes of the study-malaria prevalence and incidence-at baseline and annually since the onset of the project. Parasite prevalence by rapid diagnostic test (RDT) declined from 9.1% (95% confidence interval [CI] 7.0-11.8) in May 2015 to 2.6% (95% CI 2.0-3.4), representing a 71.3% (95% CI 71.1-71.4, p < 0.001) reduction after

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“…The project was based on direct implementation of malaria interventions and was managed on a learning-by-doing basis, with resources for MDA delivery adjusted over time based on experience accumulation. Effectiveness results of the Magude project align with existing evidence [19,20], indicating that the package of interventions did not interrupt malaria transmission but drastically reduced malaria prevalence and incidence [22].…”

Section: Introductionmentioning

confidence: 62%

“…Although MDA was part of control and elimination strategies during the Global Malaria Eradication Programme (GMEP) in the 1950s and –60s, evidence on its effectiveness is limited [ 16 , 17 ]. Recent studies conducted in Comoros islands, Zambia and South East Asia [ 18 – 20 ] have reported that MDA using dihydroartemisinin piperaquine (DHAp) is effective in reducing—although not interrupting— P . falciparum malaria transmission to unprecedented low levels.…”

Section: Introductionmentioning

confidence: 99%

Moving towards malaria elimination in southern Mozambique: Cost and cost-effectiveness of mass drug administration combined with intensified malaria control

et al. 2020

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Background As new combinations of interventions aiming at interrupting malaria transmission are under evaluation, understanding the associated economic costs and benefits is critical for decision-making. This study assessed the economic cost and cost-effectiveness of the Magude project, a malaria elimination initiative implemented in a district in southern Mozambique (i.e. Magude) between August 2015-June 2018. This project piloted a combination of two mass drug administration (MDA) rounds per year for two consecutive years, annual rounds of universal indoor residual spraying (IRS) and a strengthened surveillance and response system on the back of universal long-lasting insecticide treated net (LLIN) coverage and routine case management implemented by the National Malaria Control Program (NMCP). Although local transmission was not interrupted, the project achieved large reductions in the burden of malaria in the target district. Methods We collected weekly economic data, estimated costs from the project implementer perspective and assessed the incremental cost-effectiveness ratio (ICER) associated with the

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Large-scale Artemisinin–Piperaquine Mass Drug Administration With or Without Primaquine Dramatically Reduces Malaria in a Highly Endemic Region of Africa

Cited by 36 publications

References 29 publications

Electrocardiographic Safety of Repeated Monthly Dihydroartemisinin-Piperaquine as a Candidate for Mass Drug Administration

Electrocardiographic Safety of Repeated Monthly Dihydroartemisinin-Piperaquine as a Candidate for Mass Drug Administration

A multiphase program for malaria elimination in southern Mozambique (the Magude project): A before-after study

Moving towards malaria elimination in southern Mozambique: Cost and cost-effectiveness of mass drug administration combined with intensified malaria control

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