Assessing the impact of imperfect adherence to artemether-lumefantrine on malaria treatment outcomes using within-host modelling

Challenger, Joseph D.; Bruxvoort, Katia; Ghani, Azra C.; Okell, Lucy

doi:10.1038/s41467-017-01352-3

Cited by 26 publications

(50 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The signi cantly higher malaria prevalence in 2 to 10 year-old children measured almost four months later during the 2019 MIS (Fig. 4) could be explained by higher parasite densities in children that are detectable for longer periods [14,15], by poorer adherence to treatment in this age-group following the test and treat intervention [16][17][18] or by a persistently high force of infection [19] driven by the high HBR observed, as is suggested by the data (Fig. 2C).…”

Section: Discussionmentioning

confidence: 67%

Malaria outbreak in Riaba district, Bioko Island – Lessons learned

Guerra

Fuseini

Donfack

et al. 2020

Preprint

View full text Add to dashboard Cite

At the beginning of 2019, a sudden surge of malaria cases was observed in the district of Riaba, Bioko Island. Between January and April, confirmed malaria cases increased 3.8-fold compared to the same period in 2018. Concurrently, anopheline human biting rate (HBR) increased 2.1-fold. During the outbreak, 82.2% of the district population was tested for malaria with a rapid diagnostic test; 37.2% of those tested had a detectable infection and were treated according to national guidelines. Vector control interventions, including indoor residual spraying and larval source management were scaled-up. After the interventions, the number of confirmed cases decreased by 70% and the overall parasite prevalence in the communities by 43.8%. Observed prevalence in a follow up malaria indicator survey, however, was significantly higher than elsewhere on the island, and higher than in previous years. There was no significant reduction in HBR, which remained high for the rest of the year. The surge was attributed to various factors, chiefly increased rainfall and a large number of anthropogenic anopheline breeding sites created by construction works. This case study highlights the need for sustained vector control interventions and multi-sector participation, particularly in malaria control and elimination settings with persistently high local malaria receptivity.

show abstract

Section: Discussionmentioning

confidence: 67%

Malaria outbreak in Riaba district, Bioko Island – Lessons learned

Guerra

Fuseini

Donfack

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…The modelling work developed for this analysis built on our previous published within-host model, which describes asexual parasite density over the course of an uncomplicated P. falciparum infection (details in Challenger et al 14). In that work, we described the dynamics of an untreated infection, including the immune response mounted against the parasite, using the malaria therapy dataset23 to calibrate the model.…”

Section: Methodsmentioning

confidence: 99%

“…The PK model was fitted to data from both children and adults, patients were provided with food and mothers were encouraged to breastfeed infant patients, as lumefantrine (LMF) is better absorbed with some fat. We also used this model to calibrate a PD model for AL against asexual parasites 14. In that work, we quantified how imperfect adherence can increase the probability that treatment with AL fails to clear the infection.…”

Section: Methodsmentioning

confidence: 99%

“…In previous work we developed a within-host model of uncomplicated P. falciparum malaria in order to obtain an estimate of the impact of imperfect adherence to AL on treatment outcomes 14. To do this we used data on the number of doses taken and their timings from an unsupervised cohort in Tanzania collected in 2012 15.…”

Section: Introductionmentioning

confidence: 99%

“…To assess the extent to which transmission increases due to delays to treatment and imperfect adherence, here we have extended our within-host model of asexual parasitaemia14 to also include sexual-stage parasites. We first modelled gametocytaemia in an untreated infection, and calibrated this model using data collected from neurosyphilis patients, who were infected with P. falciparum parasites to treat their syphilis infections 23.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 2019

Self Cite

View full text Add to dashboard Cite

IntroductionArtemether-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.MethodsWe 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.ResultsUsing 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.ConclusionUsing 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.

show abstract

Integration of Pharmacometrics and Pharmacoeconomics to Quantify the Value of Improved Forgiveness to Nonadherence: A Case Study of Novel Xanthine Oxidase Inhibitors for Gout

Hill‐McManus

Marshall

Soto

et al. 2019

Clin Pharma and Therapeutics

View full text Add to dashboard Cite

Linked pharmacometric and pharmacoeconomic models provide a structured approach for assessing the value of candidate drugs in development. The aim of this study was to assess the utility of such an approach for identifying the properties of xanthine oxidase inhibitors (XOi) providing improved forgiveness to nonadherence and estimate the maximum reimbursement price. The pharmacometric and pharmacoeconomic models were used to simulate the time course of serum uric acid concentrations and estimate quality‐adjusted life years and costs for the XOi febuxostat and a range of hypothetical analogues. Compounds with reduced clearance or increased potency were more forgiving to missed doses, however, even following relatively large changes in these properties the predicted maximum reimbursement prices represented an increase of only 19% above febuxostat 80 mg. Linked pharmacometric and pharmacoeconomic modeling methods have the potential to inform early drug development by providing an indication of pricing options that may permit reimbursement.

show abstract

Assessing the impact of imperfect adherence to artemether-lumefantrine on malaria treatment outcomes using within-host modelling

Cited by 26 publications

References 41 publications

Malaria outbreak in Riaba district, Bioko Island – Lessons learned

Malaria outbreak in Riaba district, Bioko Island – Lessons learned

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

Integration of Pharmacometrics and Pharmacoeconomics to Quantify the Value of Improved Forgiveness to Nonadherence: A Case Study of Novel Xanthine Oxidase Inhibitors for Gout

Contact Info

Product

Resources

About