Cost-Effectiveness of Focal Mass Drug Administration and Mass Drug Administration with Dihydroartemisinin-Piperaquine for Malaria Prevention in Southern Province, Zambia: Results of a Community-Randomized Controlled Trial

Abstract

Community-wide administration of antimalarial drugs in therapeutic doses is a potential tool to prevent malaria infection and reduce the malaria parasite reservoir. To measure the effectiveness and cost of using the antimalarial drug combination dihydroartemisinin-piperaquine (DHAp) through different community-wide distribution strategies, Zambia's National Malaria Control Centre conducted a three-armed community-randomized controlled trial. The trial arms were as follows: 1) standard of care (SoC) malaria interventions, 2) SoC plus focal mass drug administration (fMDA), and 3) SoC plus MDA. Mass drug administration consisted of offering all eligible individuals DHAP, irrespective of a rapid diagnostic test (RDT) result. Focal mass drug administration consisted of offering DHAP to all eligible individuals who resided in a household where anyone tested positive by RDT. Results indicate that the costs of fMDA and MDA per person targeted and reached are similar (US$9.01 versus US$8.49 per person, respectively, P = 0.87), but that MDA was superior in all cost-effectiveness measures, including cost per infection averted, cost per case averted, cost per death averted, and cost per disability-adjusted life year averted. Subsequent costing of the MDA intervention in a non-trial, operational setting yielded significantly lower costs per person reached (US$2.90). Mass drug administration with DHAp also met the WHO thresholds for "cost-effective interventions" in the Zambian setting in 90% of simulations conducted using a probabilistic sensitivity analysis based on trial costs, whereas fMDA met these criteria in approximately 50% of simulations. A sensitivity analysis using costs from operational deployment and trial effectiveness yielded improved cost-effectiveness estimates. Mass drug administration may be a cost-effective intervention in the Zambian context and can help reduce the parasite reservoir substantially. Mass drug administration was more cost-effective in relatively higher transmission settings. In all scenarios examined, the cost-effectiveness of MDA was superior to that of fMDA.

Conflict of interest statement

Disclosure: The funding source had no role in the conduct, analysis, or interpretation of results of the study. All authors had full access to all the data in the study.

Figures

Figure 1.

Map of Southern Province districts and health facility catchment areas included in the trial. This figure appears in color on page 8 of this issue and online at www.ajtmh.org.

Figure 2.

Total cost per health facility catchment area vs. households (HH) reached per health facility catchment area for focal mass drug administration (fMDA) and MDA (left) and cost vs. persons reached for fMDA and MDA (right).

Figure 3.

Scatterplots of cost vs. outcomes derived from probabilistic sensitivity analysis of trial results. Focal mass drug administration (fMDA) is shown in dark purple and MDA shown in light yellow; ellipses are 95% CI and are also shown in dark purple solid lines for fMDA and in light yellow dashed line for MDA (black for incremental analysis of MDA vs. fMDA). Squares represent the center of data clouds with light yellow for MDA and dark purple for fMDA. Rightmost chart is the incremental analysis of MDA compared with fMDA. Dashed black lines in disability-adjusted life year (DALY) chart represent a willingness to pay a threshold of 1,414 USD (approximately equivalent to the gross domestic product of Zambia per capita at the time of the trial). This figure appears in color at www.ajtmh.org.

Figure 4.

Cost-effectiveness acceptability curves for disability-adjusted life years (DALYs) averted using focal mass drug administration (fMDA) or MDA with analysis based on either infections averted—community cohort surveillance—or cases averted—passive health facility surveillance. Vertical dotted lines represent the WHO thresholds for highly cost-effective (lower willingness to pay [WTP]) and cost-effective (higher WTP) in Zambia. The probability that intervention can be considered cost-effective can be read for any WTP threshold by finding the WTP value on the x-axis and reading the corresponding y-axis value for the specific intervention and effectiveness measurement method shown in the legend. WHO thresholds are indicative for Zambia and represent 1× and 3× gross domestic product per capita in Zambia.