Role of mass drug administration in elimination of Plasmodium falciparum malaria: a consensus modelling study

Abstract

Background: Mass drug administration for elimination of Plasmodium falciparum malaria is recommended by WHO in some settings. We used consensus modelling to understand how to optimise the effects of mass drug administration in areas with low malaria transmission.

Methods: We collaborated with researchers doing field trials to establish a standard intervention scenario and standard transmission setting, and we input these parameters into four previously published models. We then varied the number of rounds of mass drug administration, coverage, duration, timing, importation of infection, and pre-administration transmission levels. The outcome of interest was the percentage reduction in annual mean prevalence of P falciparum parasite rate as measured by PCR in the third year after the final round of mass drug administration.

Findings: The models predicted differing magnitude of the effects of mass drug administration, but consensus answers were reached for several factors. Mass drug administration was predicted to reduce transmission over a longer timescale than accounted for by the prophylactic effect alone. Percentage reduction in transmission was predicted to be higher and last longer at lower baseline transmission levels. Reduction in transmission resulting from mass drug administration was predicted to be temporary, and in the absence of scale-up of other interventions, such as vector control, transmission would return to pre-administration levels. The proportion of the population treated in a year was a key determinant of simulated effectiveness, irrespective of whether people are treated through high coverage in a single round or new individuals are reached by implementation of several rounds. Mass drug administration was predicted to be more effective if continued over 2 years rather than 1 year, and if done at the time of year when transmission is lowest.

Interpretation: Mass drug administration has the potential to reduce transmission for a limited time, but is not an effective replacement for existing vector control. Unless elimination is achieved, mass drug administration has to be repeated regularly for sustained effect.

Funding: Bill & Melinda Gates Foundation.

Figure 1

Sample simulated output from four different models of effect of mass drug administration on all-age PCR prevalence of Plasmodium falciparum infection From year −1 to year 0, the models are at equilibrium. The timing of each round of mass drug administration in each model is shown by coloured arrows. The four different models show the output under the standard intervention scenario (70% coverage, 2 years of mass drug administration, two rounds per year, 5 weeks between rounds, seasonal transmission [based on Zambia], and 5% mean annual prevalence pre-intervention by microscopy in 2–10-year-olds). DTK=Disease Transmission Kernel. MORU=Mahidol Oxford Tropical Medicine Research Unit.

Figure 2

Percentage reduction in mean annual all-age PCR prevalence of Plasmodium falciparum in the third year after mass drug administration Numbers in boxes are percentage reductions. The darker the colour, the larger the reduction. DTK=Disease Transmission Kernel. MORU=Mahidol Oxford Tropical Medicine Research Unit.

Figure 3

Overlap in coverage between rounds of mass drug administration and effect on PfPR_PCR (A) shows the proportion of the population receiving one or more treatment courses after two rounds of mass drug administration, each at 70% coverage, with either random participation or the same individuals participating each time. (B) shows the percentage reduction in PfPR_PCR 3 years after mass drug administration according to the proportion of the population not receiving treatment in any rounds in the baseline scenario. Blue triangles represent two rounds of mass drug administration randomly targeted at 30%, 50%, 70%, and 90% coverage; red dots represent the same two rounds of mass drug administration in which the same individuals are treated in each round. Results shown are from the OpenMalaria model. PfPR_PCR=Plasmodium falciparum parasite rate as measured by PCR.

Figure 4

Effect of MDA with artemisinin-combination therapy on malaria prevalence and the percentage of parasites that are artemisinin resistant Results shown are from the MORU model. Blue lines show parasite prevalence, whereas red lines show the percentage artemisinin resistant. Coverage was 70% per round. MDA=mass drug administration. MORU=Mahidol Oxford Tropical Medicine Research Unit.