Safety and effectiveness of mass drug administration to accelerate elimination of artemisinin-resistant falciparum malaria: A pilot trial in four villages of Eastern Myanmar.

Jordi Landier ,Olivo Miotto ,Stéphane Proux ,Lorenz Von Seidlein ,Clare Ling ,Jureeporn Duanguppama ,Jacher Wiladphaingern ,Benoît Malleret ,Dominique Cerqueira ,Arjen M Dondorp ,Daniel M Parker ,Julie A Simpson ,Victor Chaumeau ,Nicholas J White ,May Myo Thwin ,Mallika Imwong ,Suphak Nosten ,Laurent Rénia ,Ladda Kajeechiwa ,Vincent Corbel ,Krittaya Patumrat ,F Nosten

doi:10.12688/wellcomeopenres.12240.1

Abstract

Background: Artemisinin and partner drug-resistant falciparum malaria is expanding over the Greater Mekong Sub-region (GMS). Eliminating falciparum malaria in the GMS while drugs still retain enough efficacy could prevent global spread of antimalarial resistance. Eliminating malaria rapidly requires targeting the reservoir of asymptomatic parasite carriers. This pilot trial aimed to evaluate the acceptability, safety, feasibility and effectiveness of mass-drug administration (MDA) in reducing malaria in four villages in Eastern Myanmar. Methods: Villages with ≥30% malaria prevalence were selected. Long-lasting insecticidal bednets (LLINs) and access to malaria early diagnosis and treatment (EDT) were provided. Two villages received MDA immediately and two were followed for nine months pre-MDA. MDA consisted of a 3-day supervised course of dihydroartemisinin-piperaquine and single low-dose primaquine administered monthly for three months. Adverse events (AE) were monitored by interviews and consultations. Malaria prevalence was assessed by ultrasensitive PCR quarterly for 24 months. Symptomatic malaria incidence,entomological indices, and antimalarial resistance markers were monitored. Results: MDA was well tolerated. There were no serious AE and mild to moderate AE were reported in 5.6%(212/3931) interviews. In the smaller villages, participation to three MDA courses was 61% and 57%, compared to 28% and 29% in the larger villages. Baseline prevalence was higher in intervention than in control villages (18.7% (95%CI=16.1-21.6) versus 6.8%(5.2-8.7), p<0.0001) whereas three months after starting MDA, prevalence was lower in intervention villages (0.4%(0.04-1.3) versus 2.7%(1.7-4.1), p=0.0014). After nine months the difference was no longer significant (2.0%(1.0-3.5) versus 0.9%(0.04-1.8), p=0.10). M0-M9 symptomatic falciparum incidence was similar between intervention and control. Before/after MDA comparisons showed that asymptomatic P. falciparum carriage and anopheline vector positivity decreased significantly whereas prevalence of the artemisinin-resistance molecular marker remained stable. Conclusions: This MDA was safe and feasible, and, could accelerate elimination of P. falciparumin addition to EDT and LLINs when community participation was sufficient.

Highlights

Recent progress in the control of malaria is under threat because the two pillars of malaria control – antimalarial drugs and insecticides – are falling to resistance[1]
Artemisinin resistance has led to the failure of artemisinin based combination treatments (ACT)[3,4], the cornerstone of uncomplicated P. falciparum malaria therapy worldwide
We present a 24-month pilot study of the safety and effectiveness of mass-drug administration (MDA) in reducing P. falciparum incidence and prevalence in four villages with high prevalence of sub-microscopic infections located on the Thailand–Myanmar border, an area where artemisinin resistance is firmly established[16,17]

Summary

Introduction

Recent progress in the control of malaria is under threat because the two pillars of malaria control – antimalarial drugs and insecticides – are falling to resistance[1]. Detection and treatment of clinical cases at the community level is effective in preventing mortality and reduces P. falciparum transmission and the associated morbidity[5,6,7] This approach alone is unlikely to halt the rapid spread of artemisinin resistance because it fails to directly address foci of asymptomatic carriage of P. falciparum. This persistent reservoir represents the main obstacle to the rapid elimination of falciparum malaria in the GMS, where transmission is low, seasonal and unstable[8,9]. Eliminating malaria rapidly requires targeting the reservoir of asymptomatic parasite carriers This pilot trial aimed to evaluate the acceptability, safety, feasibility and effectiveness of mass-drug administration (MDA) in reducing malaria in four villages in Eastern Myanmar. Baseline prevalence was higher in intervention than in control villages (18.7% (95%CI=16.1-21.6) versus 6.8%(5.2-8.7), p

Methods

Results

Discussion

Conclusion