Operational strategies of anti-malarial drug campaigns for malaria elimination in Zambia’s southern province: a simulation study

Abstract

BackgroundMalaria elimination requires reducing both the potential of mosquitoes to transmit parasites to humans and humans to transmit parasites to mosquitoes. To achieve this goal in Southern province, Zambia a mass test and treat (MTAT) campaign was conducted from 2011–2013 to complement high coverage of long-lasting insecticide-treated nets (LLIN). To identify factors likely to increase campaign effectiveness, a modelling approach was applied to investigate the simulated effect of alternative operational strategies for parasite clearance in southern province.MethodsOpenMalaria, a discrete-time, individual-based stochastic model of malaria, was parameterized for the study area to simulate anti-malarial drug administration for interruption of transmission. Simulations were run for scenarios with a range of artemisinin-combination therapies, proportion of the population reached by the campaign, targeted age groups, time between campaign rounds, Plasmodium falciparum test protocols, and the addition of drugs aimed at preventing onward transmission. A sensitivity analysis was conducted to assess uncertainty of simulation results. Scenarios were evaluated based on the reduction in all-age parasite prevalence during the peak transmission month one year following the campaign, compared to the currently-implemented strategy of MTAT 19 % population coverage at pilot and 40 % coverage during the first year of implementation in the presence of 56 % LLIN use and 18 % indoor residual spray coverage.ResultsSimulation results suggest the most important determinant of success in reducing prevalence is the population coverage achieved in the campaign, which would require more than 1 year of campaign implementation for elimination. The inclusion of single low-dose primaquine, which acts as a gametocytocide, or ivermectin, which acts as an endectocide, to the drug regimen did not further reduce parasite prevalence one year following the campaign compared to the currently-implemented strategy. Simulation results indicate a high proportion of low-density infections were missed by rapid diagnostic tests that would be treated and cleared with mass drug administration (MDA).ConclusionsThe optimal implementation strategy for MTAT or MDA will vary by background level of prevalence, by rate of infections imported to the area, and by ability to operationally achieve high population coverage. Overall success with new parasite clearance strategies depends on continued coverage of vector control interventions to ensure sustained gains in reduction of disease burden.

High levels of imported asymptomatic malaria but limited local transmission in KwaZulu-Natal, a South African malaria-endemic province nearing malaria elimination

“…Sustained effective coverage of efficacious vector control inventions is fundamental to the success of any elimination strategy [39]. The suboptimal IRS coverage driven by an increase in western-style homesteads and substandard spray quality detected in certain localities are potential obstacles to malaria elimination in KZN.…”

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

“…The models assessed represent four different ways of simulating malaria transmission and MDA, and a summary of their characteristics and functionality is given in table 2 11, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29Table 2Summary of models of malaria transmission EMOD DTK Imperial MORU OpenMalaria Institutional homeInstitute for Disease ModellingImperial College LondonMahidol Oxford Tropical Medicine Research UnitSwiss Tropical and Public Health InstituteType of model and referencesIndividual-based stochastic microsimulation16, 17Individual-based stochastic microsimulations of malaria in human beings linked to a stochastic compartmental model for mosquitoes 11 Deterministic compartmental model described by differential equations, 18 including drug action on each stage of the infectionSingle-location individual-based simulation of malaria in human beings 14 linked to deterministic model of malaria in mosquitoes 19 How infections are trackedTracks parasite densities of different surface-antigen typesTracks membership of categories of infection (symptomatic, asymptomatic, submicroscopic, treated)Tracks membership of categories of infectionTracks parasite densities corresponding to different infection eventsRelationship between entomological innoculation rate and prevalenceImmunity is acquired through cumulative exposure to different antigenic determinants, 20 with heterogeneity in individual biting rates includedImmunity is acquired through cumulative exposure to mosquito bites, with heterogeneity in individual biting rates includedSubdivides population into non-immune and immune classesSubmodels of infection of human beings 14 and of blood-stage parasite densities, with main immune effects controlling parasite densities 21 Duration of infectionsI...…”

Mathematical Modelling to Guide Drug Development for Malaria Elimination

“…By contrast, the gametocytocidal and mosquitocidal effects are predicted to be limited 23, 36, 37, 38, 39. This is because the proportion of the total infectious reservoir that is being treated is very small – the majority of onward transmission will be from asymptomatic (yet infectious) individuals who are not receiving treatment (Figure 1).…”

“…However, this argument is made from an individual perspective rather than considering the impact on the population as a whole. By contrast, modelling studies have demonstrated that drugs with a longer prophylactic period are likely to have a greater effect in reducing P. falciparum transmission by preventing all treated individuals from being reinfected 23, 36, 37, 38, 39. Whilst gametocytocidal activity can be beneficial, the same modelling studies have shown that this factor is less important, acting only to delay the resurgence by a few weeks.…”