Antimalarial drug resistence and artemisinin based combination therapy : a bio-economic model for elucidating policy choices

Antimalarial drug resistance is a major cause of the increasing burden due to P. falciparum malaria. Artemisinin-based combination therapies (ACTs) are now recognised to be the ideal choice for the first-line treatment of uncomplicated malaria, in order to achieve two beneficial outcomes: improvement of treatment efficacy and delay in the development of drug resistance. However uncertainties remain about the current and future benefits, risks and costs of ACTs and in particular how these outcomes are affected by differences in malaria epidemiology, health care settings, human behaviour and implementation strategies. This thesis seeks to address these uncertainties by creating a comprehensive, dynamic, bio- economic model of malaria transmission and the spread of drug resistance, which incorporates vector factors, human immunity, human behaviour, drug characteristics and costs. Central to the model is a biological model, developed in collaboration with a mathematician, which outputs the proportion of drug resistant infections and the incidence of new and recrudescent infections. Parasite biomass is also tracked in order for human "infectiousness" to be measured and fed-back into the model. Sub-models are used to calculate severe malaria, deaths, costs and cost-effectiveness. Data were obtained to develop and populate the model. This included a community drug usage survey in Cambodia, which was undertaken in order to document the adherence and coverage rates to ACT following the implementation of locally blister-packaged ACT. Coverage was found to be extremely low, and the use of artemisinin derivatives on their own was widespread. However, both of these outcomes were improved by interventions to increase coverage, particularly village malaria volunteers. Application of the model in a low transmission setting suggests that with a 10-year time-frame, switching from monotherapy to an ACT is very cost-effective and results in overall cost savings in a range of scenarios. High coverage rates with an ACT are required to delay the spread of drug resistance if resistance has already arisen to one of the partner drugs. Running the model with data from Cambodia suggests that even in settings with low coverage, the change will be cost-effective and significant benefits are gained from the implementation of the specific delivery interventions. Strategies for optimising the implementation of ACTs are discussed in light of the findings

Antimalarial drug resistence and artemisinin based combination therapy : a bio-economic model for elucidating policy choices

Antimalarial drug resistance is a major cause of the increasing burden due to P. falciparum malaria. Artemisinin-based combination therapies (ACTs) are now recognised to be the ideal choice for the first-line treatment of uncomplicated malaria, in order to achieve two beneficial outcomes: improvement of treatment efficacy and delay in the development of drug resistance. However uncertainties remain about the current and future benefits, risks and costs of ACTs and in particular how these outcomes are affected by differences in malaria epidemiology, health care settings, human behaviour and implementation strategies. This thesis seeks to address these uncertainties by creating a comprehensive, dynamic, bio- economic model of malaria transmission and the spread of drug resistance, which incorporates vector factors, human immunity, human behaviour, drug characteristics and costs. Central to the model is a biological model, developed in collaboration with a mathematician, which outputs the proportion of drug resistant infections and the incidence of new and recrudescent infections. Parasite biomass is also tracked in order for human "infectiousness" to be measured and fed-back into the model. Sub-models are used to calculate severe malaria, deaths, costs and cost-effectiveness. Data were obtained to develop and populate the model. This included a community drug usage survey in Cambodia, which was undertaken in order to document the adherence and coverage rates to ACT following the implementation of locally blister-packaged ACT. Coverage was found to be extremely low, and the use of artemisinin derivatives on their own was widespread. However, both of these outcomes were improved by interventions to increase coverage, particularly village malaria volunteers. Application of the model in a low transmission setting suggests that with a 10-year time-frame, switching from monotherapy to an ACT is very cost-effective and results in overall cost savings in a range of scenarios. High coverage rates with an ACT are required to delay the spread of drug resistance if resistance has already arisen to one of the partner drugs. Running the model with data from Cambodia suggests that even in settings with low coverage, the change will be cost-effective and significant benefits are gained from the implementation of the specific delivery interventions. Strategies for optimising the implementation of ACTs are discussed in light of the findings.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Modelling the cost-effectiveness of introducing subsidised malaria rapid diagnostic tests in the private retail sector in sub-Saharan Africa.

BACKGROUND: Over the last 10 years, there has been a huge shift in malaria diagnosis in public health facilities, due to widespread deployment of rapid diagnostic tests (RDTs), which are accurate, quick and easy to use and inexpensive. There are calls for RDTs to be made available at-scale in the private retail sector where many people with suspected malaria seek care. Retail sector RDT use in sub-Saharan Africa (SSA) is limited to small-scale studies, and robust evidence on value-for-money is not yet available. We modelled the cost-effectiveness of introducing subsidised RDTs and supporting interventions in the SSA retail sector, in a context of a subsidy programme for first-line antimalarials. METHODS: We developed a decision tree following febrile patients through presentation, diagnosis, treatment, disease progression and further care, to final health outcomes. We modelled results for three 'treatment scenarios', based on parameters from three small-scale studies in Nigeria (TS-N), Tanzania (TS-T) and Uganda (TS-U), under low and medium/high transmission (5% and 50% Plasmodium falciparum (parasite) positivity rates (PfPR), respectively). RESULTS: Cost-effectiveness varied considerably between treatment scenarios. Cost per disability-adjusted life year averted at 5% PfPR was US$482 (TS-N) and US$115 (TS-T) and at 50% PfPR US$44 (TS-N) and US$45 (TS-T), from a health service perspective. TS-U was dominated in both transmission settings. CONCLUSION: The cost-effectiveness of subsidised RDTs is strongly influenced by treatment practices, for which further evidence is required from larger-scale operational settings. However, subsidised RDTs could promote increased use of first-line antimalarials in patients with malaria. RDTs may, therefore, be more cost-effective in higher transmission settings, where a greater proportion of patients have malaria and benefit from increased antimalarial use. This is contrary to previous public sector models, where RDTs were most cost-effective in lower transmission settings as they reduced unnecessary antimalarial use in patients without malaria

The spread of antimalarial drug resistance: A mathematical model with practical implications for ACT drug policies

Most malaria-endemic countries are implementing a change in antimalarial drug policy to artemisinin combination therapy (ACT). The impact of different drug choices and implementation strategies is uncertain. A comprehensive model was constructed incorporating important epidemiological and biological factors and used to illustrate the spread of resistance in low and high transmission settings. The model predicts robustly that in low transmission settings drug resistance spreads faster than in high transmission settings, and that in low transmission areas ACTs slows the spread of drug resistance to a partner drug, especially at high coverage rates. This effect decreases exponentially with increasing delay in deploying the ACT and decreasing rates of coverage. A major obstacle to achieving the benefits of high coverage is the current cost of the drugs. This argues strongly for a global subsidy to make ACTs generally available and affordable in endemic areas

The use of antimicrobials in global pig production: A systematic review of methods for quantification.

BACKGROUND: Overuse of antimicrobials in both humans and animals is recognized as one of the main drivers of Antimicrobial Resistance (AMR); and the optimisation of their use has been advocated as a key strategy for dealing with AMR. The measurement of antimicrobial use is vital for the design, monitoring and evaluation of such strategies. This systematic review describes and compares methods and measurements used to quantify antimicrobial use in pigs in order to inform efforts to standardize measurement. METHODS: The peer-reviewed literature was systematically searched using four online databases: MEDLINE, ScienceDirect, Scopus and Web of Science. Eligibility criteria for inclusion in the review included: articles published in English, involving pigs of any age and types of production, providing quantitative data on antimicrobial use, containing a clear description of the methodology, and having moderate to high rank in the quality assessment. RESULTS: Of 2,362 abstracts reviewed, a total of 25 studies were included based on the eligibility criteria. All studies were published between 2001 and 2017. Twenty of the studies were conducted in eight European countries. Twelve studies estimated antimicrobial use and eight studies were primarily methodological papers comparing different methods or variables, or developing new methods. The two main sources of antimicrobial use data were farm surveys and national sales data. A large variety of units of measurement was found. In this review, the ten measurements identified were categorized into four groups: 1) antimicrobials use measured by milligrams of active substance per animal weight; 2) antimicrobials use measured by daily dose per weight at treatment; 3) antimicrobial use measured by daily dose per treatment period; and 4) antimicrobials use measured by daily dose per period at risk of treatment. CONCLUSION: There is no global standardized measurement of antimicrobial use in pigs. Given the importance of monitoring the use antimicrobials, we recommend that at a minimum, all countries should develop macro-level monitoring using national sales data and report use by milligram of active ingredients per Population Correcting Unit. Monitoring in specific animal species requires the development of systems to capture prescription at national or farm level. Findings from monitoring antimicrobial use may help to guide effective interventions for optimising use of antimicrobials, as recommended by the WHO Global Action Plan on AMR

Patterns of antibiotic use in global pig production: A systematic review.

This review assesses the evidence for patterns of antibiotic use in pig on the basis of papers published in peer-reviewed journals in English between 2000 and 2017. Thirty-six articles were identified and reviewed, of which more than 85% of studies were conducted in Europe and North America. Penicillins and Tetracyclines groups were the most commonly used antibiotics in many countries. Oral medication in suckling and post-weaning periods were the most common applications of antibiotic administration in pig production. Antibiotic use is driven by age-specific diseases and the common pathogens causing these conditions where epidemiological profiles varied greatly across countries. In addition, the type and size of farm were associated with antibiotic use with finisher and larger farms using more antibiotics than farrow-to-finish and smaller farms. There is variation in the use of the highest priority critically important antimicrobials in humans across studies. However, this review indicates that they are still commonly used in pig production, for treatment and prevention of infection. This evidence calls for global efforts on the prudent use of antibiotics in response to the emergence of antimicrobial resistance (AMR) in the agricultural sector

GUARD study report: Good Use of Antimalarials and Rapid Diagnostic Tests in Cambodia study report

Using a mixed methods approach that included quality assessments, a mystery client study and qualitative research, we conducted a comprehensive evaluation of malaria Rapid Diagnostic Tests and in the private sector in 12 health centre catchment areas across Cambodia. In summary, we found that the RDTs collected from drug shops had maintained good quality and that storage and transport conditions were on the whole satisfactory. Uptake of RDTs appeared to highest in the most highly trained providers i.e. “cabinets”, and lowest in grocery shops, with pharmacies and drugs shops having some ambiguity around their role. Findings from the focus group discussions and the mystery client study suggest that some of the problems in uptake and interpretation relate to RDTs being on the margins of practice for these providers who see themselves as either providing a diagnosis and cure (pinit pchier bal) or simply selling drugs for symptomatic relief (lout tnam). Several problems with RDTs were identified in terms of their actual use, in particular relating to interpretation of results, blood safety, and problems related to the buffer and the blood collecting device. In summary this study provides a comprehensive assessment of malaria RDTs in one of the first countries to implement them in the private sector