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@article{Challenger:2019:10.1136/bmjgh-2019-001856,
author = {Challenger, J and Goncalves, BP and Bradley, J and Bruxvoort, K and Tiono, AB and Drakeley, C and Bousema, T and Ghani, AC and Okell, LC},
doi = {10.1136/bmjgh-2019-001856},
journal = {BMJ Global Health},
title = {How delayed and non-adherent treatment contribute to onward transmission of malaria: a modelling study},
url = {http://dx.doi.org/10.1136/bmjgh-2019-001856},
volume = {4},
year = {2019}
}

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TY  - JOUR
AB  - IntroductionArtemether-lumefantrine (AL) is the most widely-recommended treatment for uncomplicatedPlasmodium falciparum malaria. Its efficacy has been extensively assessed in clinical trials. In routinehealthcare settings, however, its effectiveness can be diminished by delayed access to treatmentand poor adherence. As well as affecting clinical outcomes, these factors can lead to increasedtransmission, which is the focus of this study.MethodsWe extend a within-host model of Plasmodium falciparum to include gametocytes, the parasiteforms responsible for onward transmission. The model includes a pharmacokineticpharmacodynamic model of AL, calibrated against both immature and mature gametocytes usingindividual-level patient data, to estimate the impact that delayed access and imperfect adherence totreatment can have on onward transmission of the parasite to mosquitoes.ResultsUsing survey data from 7 African countries to determine the time taken to acquire antimalarialsfollowing 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 datafrom 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 treatmentfailure leading to chronic infection, rather than prolonged gametocytaemia in patients who haveslower, but still successful, clearance of parasites after imperfect adherence to treatment. Ourmodel estimated that the mean infectivity of untreated infections was 29-51 times higher than thatof treated infections (assuming perfect drug adherence), underlining the importance of improvingtreatment coverage.ConclusionUsing mathematical modelling, we quantify how delayed treatment and non-adherent treatmentcan increase transmission compared to prompt effective treatment. We also highlight thattransmission from the large proporti
AU  - Challenger,J
AU  - Goncalves,BP
AU  - Bradley,J
AU  - Bruxvoort,K
AU  - Tiono,AB
AU  - Drakeley,C
AU  - Bousema,T
AU  - Ghani,AC
AU  - Okell,LC
DO  - 10.1136/bmjgh-2019-001856
PY  - 2019///
SN  - 2059-7908
TI  - How delayed and non-adherent treatment contribute to onward transmission of malaria: a modelling study
T2  - BMJ Global Health
UR  - http://dx.doi.org/10.1136/bmjgh-2019-001856
UR  - http://hdl.handle.net/10044/1/74888
VL  - 4
ER  -

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