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How delayed and non-adherent treatment contribute to onward transmission of malaria: a modelling study

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Title: How delayed and non-adherent treatment contribute to onward transmission of malaria: a modelling study
Authors: Challenger, J
Goncalves, BP
Bradley, J
Bruxvoort, K
Tiono, AB
Drakeley, C
Bousema, T
Ghani, AC
Okell, LC
Item Type: Journal Article
Abstract: Introduction Artemether-lumefantrine (AL) is the most widely-recommended treatment for uncomplicated Plasmodium falciparum malaria. Its efficacy has been extensively assessed in clinical trials. In routine healthcare settings, however, its effectiveness can be diminished by delayed access to treatment and poor adherence. As well as affecting clinical outcomes, these factors can lead to increased transmission, which is the focus of this study. Methods We extend a within-host model of Plasmodium falciparum to include gametocytes, the parasite forms responsible for onward transmission. The model includes a pharmacokineticpharmacodynamic model of AL, calibrated against both immature and mature gametocytes using individual-level patient data, to estimate the impact that delayed access and imperfect adherence to treatment can have on onward transmission of the parasite to mosquitoes. Results Using survey data from 7 African countries to determine the time taken to acquire antimalarials following fever increased our estimates of mean total infectivity of a malaria episode by up to 1.5- fold, compared to patients treated after 24 hours. Realistic adherence behaviour, based on data from a monitored cohort in Tanzania, increased the contribution to transmission by 2.2 to 2.4-fold, compared to a perfectly-adherent cohort. This was driven largely by increased rates of treatment failure leading to chronic infection, rather than prolonged gametocytaemia in patients who have slower, but still successful, clearance of parasites after imperfect adherence to treatment. Our model estimated that the mean infectivity of untreated infections was 29-51 times higher than that of treated infections (assuming perfect drug adherence), underlining the importance of improving treatment coverage. Conclusion Using mathematical modelling, we quantify how delayed treatment and non-adherent treatment can increase transmission compared to prompt effective treatment. We also highlight that transmission from the large proportion of infections which never receive treatment is substantially higher than those treated.
Date of Acceptance: 10-Nov-2019
URI: http://hdl.handle.net/10044/1/74888
DOI: 10.1136/bmjgh-2019-001856
ISSN: 2059-7908
Publisher: BMJ Publishing Group
Journal / Book Title: BMJ Global Health
Volume: 4
Issue: 6
Copyright Statement: © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.
Sponsor/Funder: Medicines for Malaria Venture
Medical Research Council (MRC)
The Royal Society
Funder's Grant Number: PO14/00561
MR/R015600/1
DH140134
Keywords: malaria
mathematical modelling
pharmacology
treatment
Publication Status: Published online
Article Number: e001856
Online Publication Date: 2019-12-10
Appears in Collections:School of Public Health