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

Abstract Background 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. Different compou...

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Main Authors: Michael T. Bretscher, Jamie T. Griffin, Azra C. Ghani, Lucy C. Okell
Format: Article
Language:English
Published: BMC 2017-08-01
Series:Malaria Journal
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12936-017-1988-4
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author Michael T. Bretscher
Jamie T. Griffin
Azra C. Ghani
Lucy C. Okell
author_facet Michael T. Bretscher
Jamie T. Griffin
Azra C. Ghani
Lucy C. Okell
author_sort Michael T. Bretscher
collection DOAJ
description Abstract Background 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. 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. Methods A 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). Results Transmission 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. Discussion These 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.
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spelling doaj.art-ab3e8c35879b4fb5954c873d4cdc0cbb2022-12-21T18:38:22ZengBMCMalaria Journal1475-28752017-08-0116111210.1186/s12936-017-1988-4Modelling the benefits of long-acting or transmission-blocking drugs for reducing Plasmodium falciparum transmission by case management or by mass treatmentMichael T. Bretscher0Jamie T. Griffin1Azra C. Ghani2Lucy C. Okell3Department of Infectious Disease Epidemiology, MRC Centre for Outbreak Analysis & Modelling, Imperial CollegeSchool of Mathematical Sciences, Queen Mary University of LondonDepartment of Infectious Disease Epidemiology, MRC Centre for Outbreak Analysis & Modelling, Imperial CollegeDepartment of Infectious Disease Epidemiology, MRC Centre for Outbreak Analysis & Modelling, Imperial CollegeAbstract Background 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. 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. Methods A 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). Results Transmission 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. Discussion These 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.http://link.springer.com/article/10.1186/s12936-017-1988-4Mathematical modellingTransmissionTreatmentAnti-malarialMass drug administrationPrimaquine
spellingShingle Michael T. Bretscher
Jamie T. Griffin
Azra C. Ghani
Lucy C. Okell
Modelling the benefits of long-acting or transmission-blocking drugs for reducing Plasmodium falciparum transmission by case management or by mass treatment
Malaria Journal
Mathematical modelling
Transmission
Treatment
Anti-malarial
Mass drug administration
Primaquine
title Modelling the benefits of long-acting or transmission-blocking drugs for reducing Plasmodium falciparum transmission by case management or by mass treatment
title_full Modelling the benefits of long-acting or transmission-blocking drugs for reducing Plasmodium falciparum transmission by case management or by mass treatment
title_fullStr Modelling the benefits of long-acting or transmission-blocking drugs for reducing Plasmodium falciparum transmission by case management or by mass treatment
title_full_unstemmed Modelling the benefits of long-acting or transmission-blocking drugs for reducing Plasmodium falciparum transmission by case management or by mass treatment
title_short Modelling the benefits of long-acting or transmission-blocking drugs for reducing Plasmodium falciparum transmission by case management or by mass treatment
title_sort modelling the benefits of long acting or transmission blocking drugs for reducing plasmodium falciparum transmission by case management or by mass treatment
topic Mathematical modelling
Transmission
Treatment
Anti-malarial
Mass drug administration
Primaquine
url http://link.springer.com/article/10.1186/s12936-017-1988-4
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