Modelling the benefits of long-acting or transmission-blocking drugs for reducing Plasmodium falciparum transmission by case management or by mass treatment

Michael T Bretscher,Lucy C Okell,Azra C Ghani,Jamie T Griffin

doi:10.1186/s12936-017-1988-4

Michael T Bretscher, Lucy C Okell + Show 2 more

Open Access

https://doi.org/10.1186/s12936-017-1988-4

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Abstract

BackgroundAnti-malarial drugs are an important tool for malaria control and elimination. Alongside their direct benefit in the treatment of disease, drug use has a community-level effect, clearing the reservoir of infection and reducing onward transmission of the parasite. Different compounds potentially have different impacts on transmission—with some providing periods of prolonged chemoprophylaxis whilst others have greater transmission-blocking potential. The aim was to quantify the relative benefit of such properties for transmission reduction to inform target product profiles in the drug development process and choice of first-line anti-malarial treatment in different endemic settings.MethodsA mathematical model of Plasmodium falciparum epidemiology was used to estimate the transmission reduction that can be achieved by using drugs of varying chemoprophylactic (protection for 3, 30 or 60 days) or transmission-blocking activity (blocking 79, 92 or 100% of total onward transmission). Simulations were conducted at low, medium or high transmission intensity (slide-prevalence in 2–10 year olds being 1, 10 or 40%, respectively), with drugs administered either via case management or mass drug administration (MDA).ResultsTransmission reductions depend strongly on deployment strategy, treatment coverage and endemicity level. Transmission-blocking was most effective at low endemicity, whereas chemoprophylaxis was most useful at high endemicity levels. Increasing the duration of protection as much as possible was beneficial. Increasing transmission-blocking activity from the level of ACT to a 100% transmission-blocking drug (close to the effect estimated for ACT combined with primaquine) produced moderate impact but was not as effective as increasing the duration of protection in medium-to-high transmission settings (slide prevalence 10–40%). Combining both good transmission-blocking activity (e.g. as achieved by ACT or ACT + primaquine) and a long duration of protection (30 days or more, such as provided by piperaquine or mefloquine) within a drug regimen can substantially increase impact compared with drug regimens with only one of these properties in medium to high transmission areas (slide-prevalence in 2–10 year olds ~10 to 40%). These results applied whether the anti-malarials were used for case management or for MDA.DiscussionThese results emphasise the importance of increasing access to treatment for routine case management, and the potential value of choosing first-line anti-malarial treatment policies according to local malaria epidemiology to maximise impact on transmission. There is no indication that the optimal drug choice should differ between delivery via case management or MDA.

Highlights

Anti-malarial drugs are an important tool for malaria control and elimination
Anti-malarials are typically used in one of three ways: (A) for clinical management of symptomatic cases delivered by the public health system, private providers or community health workers; (B) to protect against infection in at-risk groups including in infants and pregnant women young children residing in areas with seasonal malaria and in travellers from non-endemic areas; and (C) to clear the parasite reservoir in endemic populations as a means to interrupt transmission either as mass drug administration (MDA) or via mass or focal screen and treat (MSAT, FSAT) [3, 4]
In a moderate transmission setting, (PR2–10 of 10%) at 80% case management coverage the reduction in clinical cases in 0–5 year olds using a drug with a duration of protection of 60 days is estimated to be 1.4 times higher than when using a drug with a duration of protection of 3 days, whereas in a high transmission setting (PR2–10 of 40%), the estimated impact is 5.6 times higher with the longer-acting drug

Summary

Introduction

Anti-malarial drugs are an important tool for malaria control and elimination Alongside their direct benefit in the treatment of disease, drug use has a community-level effect, clearing the reservoir of infection and reducing onward transmission of the parasite. Some anti-malarial compounds possess gametocytocidal activity, which reduces onward transmission to mosquitoes by killing the sexual stages of the parasite These can otherwise remain in the host for several weeks after clearance of the blood stage infection and continue to infect mosquitoes [5]

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