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Usefulness of antimalarial drug concentrations in blood as a monitoring tool for evaluating population drug usage in relation to diagnosis and treatment environment

English title Usefulness of antimalarial drug concentrations in blood as a monitoring tool for evaluating population drug usage in relation to diagnosis and treatment environment
Applicant Genton Blaise
Number 149587
Funding scheme Project funding (Div. I-III)
Research institution Department of Epidemiology and Public Health Swiss Tropical and Public Health Institute Universität Basel
Institution of higher education University of Basel - BS
Main discipline Infectious Diseases
Start/End 01.05.2014 - 31.10.2017
Approved amount 474'000.00
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All Disciplines (2)

Discipline
Infectious Diseases
Pharmacology, Pharmacy

Keywords (9)

Simulation; Antimalarial drug; Drug concentration; Malaria; Modeling; Impact; Molecular marker; Drug resistance; Drug exposure

Lay Summary (French)

Lead
Previous assessments of the impact of new diagnosis or treatment strategies on anti-malarial drug use relied either on longitudinal recording of drug stocks, prescription rates in health facilities, or on histories of drug intake recorded by community interviews. These measures are potentially biased and do not provide accurate estimates of overall levels of circulating drug. This project aims at developing a model to predict levels of residual antimalarial drug in community surveys as a function of diagnosis and treatment practices. We will compare observed drug levels and model predictions for perfect adherence to obtain measures of over- or under- treatment, and assess this approach as a tool for evaluating adherence to policies on treatment and diagnosis.
Lay summary
 Habituellement, l’impact de l’introduction de nouvelles stratégies de diagnostic et de traitement était évalué par des enquêtes dans la communauté sous forme d’interviews ainsi que de collecte d’information chez les patients et dans les pharmacies des centres de santé. Ces mesures sont sujettes à de nombreux biais. L’évaluation de la concentration des médicaments antipaludéens dans le sang de personnes lors d’enquêtes de communauté permet de donner une image plus objective de la vraie consommation de médicaments dans une certaine zone. Ce projet a pour but de modéliser les concentrations attendues de médicaments antipaludéens dans un échantillon de la population générale en fonction de l’intensité de la transmission de la malaria et d’évaluer ainsi le degré d’adéquation de la mise en œuvre de nouvelles stratégies de diagnostic et de traitement. Nous allons comparer les concentrations observées de médicaments et les modèles de prédiction pour évaluer l’adhérence aux recommandations.
Direct link to Lay Summary Last update: 04.04.2014

Responsible applicant and co-applicants

Employees

Publications

Publication
LC-MS/MS method for the simultaneous analysis of seven antimalarials and two active metabolites in dried blood spots for applications in field trials: Analytical and clinical validation
Gallay J Prod'hom S Mercier T Bardinet C Spaggiari D Pothin E Buclin T Genton B Decosterd LA (2018), LC-MS/MS method for the simultaneous analysis of seven antimalarials and two active metabolites in dried blood spots for applications in field trials: Analytical and clinical validation, in J Pharm Biomed Anal., 154(May 30 ), 263-277.

Collaboration

Group / person Country
Types of collaboration
Division de pharmacologie clinique CHUV, Lausanne Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Ifakara Health Institute (IHI) Tanzania (Africa)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Center for Disease Control (CDC) Atlanta United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results

Associated projects

Number Title Start Funding scheme
179273 Residual antibiotic drug concentrations in blood as a monitoring tool for evaluating population medicine usage and the impact of antibiotic stewardship interventions 01.04.2019 Project funding (Div. I-III)

Abstract

1Summary of research planBackground and rationale Previous assessments of the impact of new diagnosis or treatment strategies on anti-malarial drug use relied either on longitudinal recording of drug stocks, prescription rates in health facilities, or on histories of drug intake recorded by community interviews. These measures are potentially biased and do not provide accurate estimates of overall levels of circulating drug, probably the most important driver of the development of drug resistance in pathogens. Objective measurements of drug concentration should provide more reliable assessments of the effects of interventions on drug pressure.GoalTo develop a model to predict levels of residual antimalarial drug in community surveys as a function of other variables available from malaria survey data. This model could be used as a tool to monitor diagnosis & treatment conditions and practices.Main objectives- to measure blood levels of residual antimalarial drugs (primarily lumefantrine) in a representative samples of people in malaria endemic areas, and determine how these relate to adherence to appropriate diagnosis and treatment practices- to relate blood levels of residual antimalarial drugs to frequencies of molecular markers of parasite resistance in order to estimate the contribution of local drug pressure to the selection of resistant strains - to validate existing simulation models of malaria case management and drug dynamics and use these models to determine how levels of residual antimalarial drug should depend on malaria endemicity at given levels of access to health care- to compare observed drug levels and model predictions for perfect adherence to obtain measures of over- or under- treatment, and assess this approach as a tool for evaluating adherence to policies on treatment and diagnosis MethodologyThis project will assess population use of antimalarials in five Tanzanian regions in different geographic, ecological and transmission intensity zones, and with different diagnosis and treatment conditions and practices.Field assessment will comprise two types of cross-sectional surveys conducted concurrently:1) Household (HH) based surveys conducted in a sub-sample of populations in order to collect i) information on prevalence of malaria, self-reported rates of morbidity, diagnosis and treatment seeking behavior, on diagnostic tests performed, on antimalarial and antibiotic use, and ii) filter paper blood samples for antimalarial concentration measurement by LC-MS/MS technology, and sequencing of molecular markers of parasite resistance to drugs.2) Health facilities (HF) based surveys serving the sampled HH. Information collected will include diagnosis availability (mainly mRDT and/or microscopy),treatment availability (mainly ACTs), and malaria morbidity.The field data will be used to validate micro-simulation models of malaria case management already developed by the investigators, and these models will then be used to determine what would be appropriate levels of drug usage for each of the settings, and hence to develop an algorithm for comparing reported with optimal levels of drug use. Analytical approachGeneralized linear models will be used to analyse how the prevalence of detectable lumefantrine in the blood varies with malaria prevalence, access, reported morbidity rates, as well as diagnosis and treatment practices. Microsimulations will be run using the OpenMalaria platform and used to predict target drug levels for each cluster in the field studies, for comparison with those observed. Graphical displays of target drug levels as functions of the main predictors will be used as the basis of a tool to advise health planners on the extent of under- or over- treatment. Relevance and impact of the projectFor Tanzania and developing countries (population and health policy perspective)- to provide a new standardized and reliable approach to quantify real antimalarial drug use and pressure at the community level, and assess the extent to which the level of treatment is appropriate, excessive or inadequate.- to provide a new tool to assess and monitor diagnosis and treatment practices; this tool should help health authorities planning of specific responses to problems of access. - to generate new knowledge on the relationship between antimalarial drug pressure and dynamic of parasite resistanceFor Switzerland and developed countries (individualized medication perspective)- to validate DBS as an easy blood collection procedure for therapeutic drug monitoring in patients with chronic disease
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