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Mass Drug Administrations With Dihydroartemisinin-Piperaquine and Single Low Dose Primaquine to Eliminate Plasmodium Falciparum Have Only a Transient Impact on Plasmodium Vivax: Findings From Randomised Controlled Trials

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Mass Drug Administrations With Dihydroartemisinin-Piperaquine and Single Low Dose Primaquine to Eliminate Plasmodium Falciparum Have Only a Transient Impact on Plasmodium Vivax: Findings From Randomised Controlled Trials

Koukeo Phommasone et al. PLoS One.

Abstract

Background: Mass administrations of antimalarial drugs (MDA) have reduced the incidence and prevalence of P. falciparum infections in a trial in the Greater Mekong Subregion. Here we assess the impact of the MDA on P. vivax infections.

Methods: Between May 2013 and July 2017, four villages in each Myanmar, Vietnam, Cambodia and Lao PDR were selected based on high prevalence of P. falciparum infections. Eight of the 16 villages were randomly assigned to receive MDA consisting of three-monthly rounds of three-day courses of dihydroartemisinin-piperaquine and, except in Cambodia, a single low-dose of primaquine. Cross-sectional surveys were conducted at quarterly intervals to detect Plasmodium infections using ultrasensitive qPCR. The difference in the cumulative incidence between the groups was assessed through a discrete time survival approach, the difference in prevalence through a difference-in-difference analysis, and the difference in the number of participants with a recurrence of P. vivax infection through a mixed-effect logistic regression.

Results: 3,790 (86%) residents in the intervention villages participated in at least one MDA round, of whom 2,520 (57%) participated in three rounds. The prevalence of P. vivax infections fell from 9.31% to 0.89% at month 3 but rebounded by six months to 5.81%. There was no evidence that the intervention reduced the cumulative incidence of P.vivax infections (95% confidence interval [CI] Odds ratio (OR): 0.29 to 1.36). Similarly, there was no evidence of MDA related reduction in the number of participants with at least one recurrent infection (OR: 0.34; 95% CI: 0.08 to 1.42).

Conclusion: MDA with schizontocidal drugs had a lasting effect on P. falciparum infections but only a transient effect on the prevalence of P. vivax infections. Radical cure with an 8-aminoquinoline will be needed for the rapid elimination of vivax malaria.

Conflict of interest statement

We declare no competing of interests in any form related to employment, consultancy, patents, products in development, or marketed product, etc. None of our authors is affiliated with a commercial entity.

Figures

Fig 1
Fig 1. Map of the Greater Mekong Subregion.
The areas highlighted in orange are study sites: Kayin (Karen) state, Myanmar; Battambang province, Cambodia; Savannakhet Province, Lao PDR; Binh Phuoc and Ninh Thuan province, Vietnam.
Fig 2
Fig 2. CONSORT flow diagram of MDA allocation and follow-up.
Fig 3
Fig 3. Changes in the prevalence of P. vivax infection during 12-month follow-up in the control and intervention villages.
The month 12 data from Myanmar are not included because the cross-over MDA in the control villages had to be conducted on M9 instead of M12. DiD, difference in difference, coefficient (95% confident interval).
Fig 4
Fig 4. Cumulative uPCR-derived incidences of P. vivax infection between intervention and control villages.
The month 12 data from Myanmar are not included because of logistic reasons, the cross-over MDA in the control villages had to be conducted on M9 instead of M12.
Fig 5
Fig 5. Forest plot of country odds ratios in the uPCR-derived incidence of P. vivax infections.

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Grant support

Funding for the TME project was obtained from Wellcome Trust (101148/Z/13/Z) to NJW and the Bill and Melinda Gates Foundation (OPP1081420) to AMD. The funder provided support including salaries for authors [KP, TJP,RT, TP, BA, LvS ], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.”. JAS is funded by an Australian NHMRC Senior Research Fellowship 1104975. We declare that none of authors in this paper is employed by commercial company.
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