How delayed and non-adherent treatment contribute to onward transmission of malaria: a modelling study
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 treatme...
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BMJ Publishing Group
2019-12-01
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| Series: | BMJ Global Health |
| Online Access: | https://gh.bmj.com/content/4/6/e001856.full |
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| author | John Bradley Teun Bousema Joseph D Challenger Bronner P Gonçalves Katia Bruxvoort Alfred B Tiono Azra C Ghani Lucy C Okell |
| author_facet | John Bradley Teun Bousema Joseph D Challenger Bronner P Gonçalves Katia Bruxvoort Alfred B Tiono Azra C Ghani Lucy C Okell |
| author_sort | John Bradley |
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| description | 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 P. falciparum to include gametocytes, the parasite forms responsible for onward transmission. The model includes a pharmacokinetic–pharmacodynamic 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 seven 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 with 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 with 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 with prompt effective treatment. We also highlight that transmission from the large proportion of infections which never receive treatment is substantially higher than those treated. |
| format | Article |
| id | doaj-art-3f52ebc77bed4ef6b2fab24cbc0bef3e |
| institution | DOAJ |
| issn | 2059-7908 |
| language | English |
| publishDate | 2019-12-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Global Health |
| spelling | doaj-art-3f52ebc77bed4ef6b2fab24cbc0bef3e2025-08-20T02:39:26ZengBMJ Publishing GroupBMJ Global Health2059-79082019-12-014610.1136/bmjgh-2019-001856How delayed and non-adherent treatment contribute to onward transmission of malaria: a modelling studyJohn Bradley0Teun Bousema1Joseph D Challenger2Bronner P Gonçalves3Katia Bruxvoort4Alfred B Tiono5Azra C Ghani6Lucy C Okell7Clinical Research Department, London School of Hygiene and Tropical Medicine, London, UKDepartment of Medical Microbiology, Radboud University Nijmegen, Nijmegen, The Netherlands1 MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, Imperial College London, London, United KingdomDepartment of Comparative Biomedical Sciences, University of Surrey, Guildford, UK4 Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, California, USAGroupe de Recherche Action en Santé, Ouagadougou, Burkina Faso1 MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom1 MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, Imperial College London, London, United KingdomIntroduction 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 P. falciparum to include gametocytes, the parasite forms responsible for onward transmission. The model includes a pharmacokinetic–pharmacodynamic 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 seven 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 with 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 with 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 with prompt effective treatment. We also highlight that transmission from the large proportion of infections which never receive treatment is substantially higher than those treated.https://gh.bmj.com/content/4/6/e001856.full |
| spellingShingle | John Bradley Teun Bousema Joseph D Challenger Bronner P Gonçalves Katia Bruxvoort Alfred B Tiono Azra C Ghani Lucy C Okell How delayed and non-adherent treatment contribute to onward transmission of malaria: a modelling study BMJ Global Health |
| title | How delayed and non-adherent treatment contribute to onward transmission of malaria: a modelling study |
| title_full | How delayed and non-adherent treatment contribute to onward transmission of malaria: a modelling study |
| title_fullStr | How delayed and non-adherent treatment contribute to onward transmission of malaria: a modelling study |
| title_full_unstemmed | How delayed and non-adherent treatment contribute to onward transmission of malaria: a modelling study |
| title_short | How delayed and non-adherent treatment contribute to onward transmission of malaria: a modelling study |
| title_sort | how delayed and non adherent treatment contribute to onward transmission of malaria a modelling study |
| url | https://gh.bmj.com/content/4/6/e001856.full |
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