The dynamic of asymptomatic Plasmodium falciparum infections following mass drug administrations with dihydroarteminisin-piperaquine plus a single low dose of primaquine in Savannakhet Province, Laos

Tiengkham Pongvongsa, Koukeo Phommasone, Bipin Adhikari, Gisela Henriques, Kesinee Chotivanich, Borimas Hanboonkunupakarn, Mavuto Mukaka, Pimnara Peerawaranun, Lorenz von Seidlein, Nicholas P J Day, Nicholas J White, Arjen M Dondorp, Mallika Imwong, Paul N Newton, Pratap Singhasivanon, Mayfong Mayxay, Sasithon Pukrittayakamee, Tiengkham Pongvongsa, Koukeo Phommasone, Bipin Adhikari, Gisela Henriques, Kesinee Chotivanich, Borimas Hanboonkunupakarn, Mavuto Mukaka, Pimnara Peerawaranun, Lorenz von Seidlein, Nicholas P J Day, Nicholas J White, Arjen M Dondorp, Mallika Imwong, Paul N Newton, Pratap Singhasivanon, Mayfong Mayxay, Sasithon Pukrittayakamee

Abstract

Background: The increase in multidrug resistant Plasmodium falciparum infections threatens the malaria elimination goals in countries within the Greater Mekong Sub-region. A multi-pronged approach assuring access to basic malaria control measures, including insecticide-treated bed nets and early diagnosis and treatment was followed by mass drug administrations (MDA) in southern Savannakhet Province, Laos. The main objective of this study was to evaluate the effectiveness and safety of mass drug administrations as well as their effects on the dynamic of asymptomatic P. falciparum infections in 4 malaria endemic villages.

Methods: Two villages were randomized to early MDA consisting of 3 rounds of a 3-day course of dihydroartemisinin-piperaquine with a single low dose of primaquine. In the other 2 villages MDA was deferred by 1 year. A total of 1036 residents were enrolled in early MDA villages and 883 in control villages (deferred-MDA). Tri-monthly parasitaemia surveys using uPCR were conducted for a year in the 4 villages.

Results: Eighty-four percent (872/1036) of the residents participated in the MDAs, of whom 90% (781/872) completed 3 rounds of MDA (9 doses). In intervention villages, the prevalence of asymptomatic P. falciparum infections decreased by 85% after MDA from 4.8% (95% CI 3.4-6.4) at baseline (month 0 or M0) to 0.7% (95% CI 0.3-1.6) at month 12. In control villages there was a decrease of 33% in P. falciparum prevalence between M0: 17.5% (95% CI 15.9-20.3) and M12: 11.6% (95% CI 9.3-14.2). In bivariate and multivariate analyses P. falciparum infections were significantly reduced with early MDA (adjusted incidence rate ratios (AIRR): 0.08, CI 0.01-0.091) and completion of 3 MDA rounds (AIRR: 0.06; CI 0.01-0.66). A quarter of participants (226/872) reported adverse events of which 99% were mild.

Conclusion: The study found a significant reduction in P. falciparum prevalence and incidence following MDA. MDA was safe, well tolerated, feasible, and achieved high population coverage and adherence. MDAs must be integrated in multi-pronged approaches such as vector control and preventive measures with a focus on specific risk groups such as mobile, migrant population and forest goers for a sustained period to eliminate the remaining parasite reservoirs. Trial registration ClinicalTrials.gov Identifier: NCT01872702.

Keywords: Asymptomatic parasitaemia; Elimination; Laos; MDA; P. falciparum; Savannakhet.

Figures

Fig. 1
Fig. 1
TME study sites in Savannakhet province of Laos
Fig. 2
Fig. 2
Study overview
Fig. 3
Fig. 3
Seasonal variation of asymptomatic P. falciparum parasitaemia prevalence during tri-monthly follow-up survey in MDA and non-MDA villages
Fig. 4
Fig. 4
Comparison of asymptomatic P. falciparum parasitaemia incidence per 1000 person-years between intervention villages (MDA) and control villages (non-MDA) at tri-monthly basis during a period of 1-year. The orange line is the tri-monthly mean of asymptomatic P. falciparum parasitaemia incidence (per 1000 person-years) 95% CI in non-MDA villages. The blue line is the tri-monthly mean of asymptomatic P. falciparum parasitaemia incidence 95% CI in MDA villages

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