ORCID Profile
0000-0002-6523-185X
Current Organisations
Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences
,
University of Oxford
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Publisher: Oxford University Press (OUP)
Date: 12-2010
Publisher: Wiley
Date: 27-01-2009
DOI: 10.1111/J.1752-4571.2008.00067.X
Abstract: Understanding the evolution of drug resistance in malaria is a central area of study at the intersection of evolution and medicine. Antimalarial drug resistance is a major threat to malaria control and directly related to trends in malaria attributable mortality. Artemisinin combination therapies (ACT) are now recommended worldwide as first line treatment for uncomplicated malaria, and losing them to resistance would be a disaster for malaria control. Understanding the emergence and spread of antimalarial drug resistance in the context of different scenarios of antimalarial drug use is essential for the development of strategies protecting ACTs. In this study, we review the basic mechanisms of resistance emergence and describe several simple equations that can be used to estimate the probabilities of de novo resistance mutations at three stages of the parasite life cycle: sporozoite, hepatic merozoite and asexual blood stages we discuss the factors that affect parasite survival in a single host in the context of different levels of antimalarial drug use, immunity and parasitaemia. We show that in the absence of drug effects, and despite very different parasite numbers, the probability of resistance emerging at each stage is very low and similar in all stages (for ex le per‐infection probability of 10 −10 –10 −9 if the per‐parasite chance of mutation is 10 −10 per asexual ision). However, under the selective pressure provided by antimalarial treatment and particularly in the presence of hyperparasitaemia, the probability of resistance emerging in the blood stage of the parasite can be approximately five orders of magnitude higher than in the absence of drugs. Detailed models built upon these basic methods should allow us to assess the relative probabilities of resistance emergence in the different phases of the parasite life cycle.
Publisher: Springer Science and Business Media LLC
Date: 12-09-2012
Publisher: Public Library of Science (PLoS)
Date: 18-01-2013
Publisher: Springer Science and Business Media LLC
Date: 10-02-2017
Publisher: F1000 Research Ltd
Date: 24-04-2019
DOI: 10.12688/WELLCOMEOPENRES.15166.1
Abstract: Over the past decade, the countries of the Asia-Pacific region have made significant progress towards the goal of malaria elimination by the year 2030. It is widely accepted that for the region to meet this goal, an intensification of efforts supported by sustained funding is required. However, robust estimates are needed for the optimal coverage and components of malaria elimination packages and the resources required to implement them. In this collection, a multispecies mathematical and economic modelling approach supported by the estimated burden of disease is used to make preliminary estimates for the cost of elimination and develop an evidence-based investment case for the region.
Publisher: Wiley
Date: 09-12-2010
DOI: 10.1002/DDR.20344
Publisher: Springer Science and Business Media LLC
Date: 25-11-2016
Publisher: Public Library of Science (PLoS)
Date: 06-05-2015
Publisher: Public Library of Science (PLoS)
Date: 23-07-2020
Publisher: Environmental Health Perspectives
Date: 08-2013
DOI: 10.1289/EHP.1206001
Publisher: Springer Science and Business Media LLC
Date: 24-09-2014
Publisher: Brill | Wageningen Academic
Date: 2007
Publisher: Proceedings of the National Academy of Sciences
Date: 25-04-2023
Abstract: Policymakers must make management decisions despite incomplete knowledge and conflicting model projections. Little guidance exists for the rapid, representative, and unbiased collection of policy-relevant scientific input from independent modeling teams. Integrating approaches from decision analysis, expert judgment, and model aggregation, we convened multiple modeling teams to evaluate COVID-19 reopening strategies for a mid-sized United States county early in the pandemic. Projections from seventeen distinct models were inconsistent in magnitude but highly consistent in ranking interventions. The 6-mo-ahead aggregate projections were well in line with observed outbreaks in mid-sized US counties. The aggregate results showed that up to half the population could be infected with full workplace reopening, while workplace restrictions reduced median cumulative infections by 82%. Rankings of interventions were consistent across public health objectives, but there was a strong trade-off between public health outcomes and duration of workplace closures, and no win-win intermediate reopening strategies were identified. Between-model variation was high the aggregate results thus provide valuable risk quantification for decision making. This approach can be applied to the evaluation of management interventions in any setting where models are used to inform decision making. This case study demonstrated the utility of our approach and was one of several multimodel efforts that laid the groundwork for the COVID-19 Scenario Modeling Hub, which has provided multiple rounds of real-time scenario projections for situational awareness and decision making to the Centers for Disease Control and Prevention since December 2020.
Publisher: F1000 Research Ltd
Date: 08-08-2019
DOI: 10.12688/WELLCOMEOPENRES.14771.2
Abstract: Background: The Asia-Pacific region has made significant progress in combatting malaria since 2000 and a regional goal for a malaria-free Asia Pacific by 2030 has been recognised at the highest levels. External financing has recently plateaued and with competing health risks, countries face the risk of withdrawal of funding as malaria is perceived as less of a threat. An investment case was developed to provide economic evidence to inform policy and increase sustainable financing. Methods: A dynamic epidemiological-economic model was developed to project rates of decline to elimination by 2030 and determine the costs for elimination in the Asia-Pacific region. The compartmental model was used to capture the dynamics of Plasmodium falciparum and Plasmodium vivax malaria for the 22 countries in the region in a metapopulation framework. This paper presents the model development and epidemiological results of the simulation exercise. Results: The model predicted that all 22 countries could achieve Plasmodium falciparum and Plasmodium vivax elimination by 2030, with the People’s Democratic Republic of China, Sri Lanka and the Republic of Korea predicted to do so without scaling up current interventions. Elimination was predicted to be possible in Bangladesh, Bhutan, Malaysia, Nepal, Philippines, Timor-Leste and Vietnam through an increase in long-lasting insecticidal nets (and/or indoor residual spraying) and health system strengthening, and in the Democratic People’s Republic of Korea, India and Thailand with the addition of innovations in drug therapy and vector control. Elimination was predicted to occur by 2030 in all other countries only through the addition of mass drug administration to scale-up and/or innovative activities. Conclusions: This study predicts that it is possible to have a malaria-free region by 2030. When computed into benefits and costs, the investment case can be used to advocate for sustained financing to realise the goal of malaria elimination in Asia-Pacific by 2030.
Publisher: Oxford University Press (OUP)
Date: 10-05-2018
DOI: 10.1093/CID/CIY055
Abstract: The relative infectiousness of chronic malaria infections determines the likelihood of success of different malaria elimination strategies.
Publisher: Elsevier BV
Date: 10-2017
Publisher: Wiley
Date: 17-01-2016
DOI: 10.1002/HEC.3303
Publisher: F1000 Research Ltd
Date: 04-2019
DOI: 10.12688/WELLCOMEOPENRES.14771.1
Abstract: Background: The Asia-Pacific region has made significant progress in combatting malaria since 2000 and a regional goal for a malaria-free Asia Pacific by 2030 has been recognised at the highest levels. External financing has recently plateaued and with competing health risks, countries face the risk of withdrawal of funding as malaria is perceived as less of a threat. An investment case was developed to provide economic evidence to inform policy and increase sustainable financing. Methods: A dynamic epidemiological-economic model was developed to project rates of decline to elimination by 2030 and determine the costs for elimination in the Asia-Pacific region. The compartmental model was used to capture the dynamics of Plasmodium falciparum and Plasmodium vivax malaria for the 22 countries in the region in a metapopulation framework. This paper presents the model development and epidemiological results of the simulation exercise. Results: The model predicted that all 22 countries could achieve Plasmodium falciparum and Plasmodium vivax elimination by 2030, with the People’s Democratic Republic of China, Sri Lanka and the Republic of Korea predicted to do so without scaling up current interventions. Elimination was predicted to be possible in Bangladesh, Bhutan, Malaysia, Nepal, Philippines, Timor-Leste and Vietnam through an increase in long-lasting insecticidal nets (and/or indoor residual spraying) and health system strengthening, and in the Democratic People’s Republic of Korea, India and Thailand with the addition of innovations in drug therapy and vector control. Elimination was predicted to occur by 2030 in all other countries only through the addition of mass drug administration to scale-up and/or innovative activities. Conclusions: This study predicts that it is possible to have a malaria-free region by 2030. When computed into benefits and costs, the investment case can be used to advocate for sustained financing to realise the goal of malaria elimination in Asia-Pacific by 2030.
Publisher: Springer Science and Business Media LLC
Date: 14-07-2011
Publisher: Public Library of Science (PLoS)
Date: 30-08-2010
Publisher: Public Library of Science (PLoS)
Date: 25-05-2012
Publisher: Elsevier BV
Date: 07-2009
DOI: 10.1016/J.PREVETMED.2009.03.016
Abstract: A deterministic state-transition model for mastitis transmission was developed to explore population level effects of antibiotic treatment regimens targeting chronic subclinical mastitis caused by major gram-positive pathogens in lactating dairy cows. Behavior and sensitivity of model outputs to changes in key parameters were explored. Outcomes included the size of the state variables describing proportions of infected quarters and basic and effective reproductive numbers. Treatment effects were estimated by calculating proportional reductions in state variables at equilibrium for populations implementing a treatment program relative to populations with no intervention. In general the relationships between parameters were complex and non-linear, although the model outputs were especially sensitive to changes in the value of the transmission rate parameter. Interaction between the parameters resulted in large variations in treatment effect estimates. Effect estimates calculated from model outputs showed a quadratic curve with a clear optimum at low, but not the lowest, transmission rates. These results indicated that overall positive population level effects of lactation therapy would be realized for herds that have successfully implemented practices that reduce the transmission rate of pathogens. A key finding is that in herds with high transmission rates, treatment of chronically infected quarters was predicted to have little impact on the proportion of infected quarters and no positive population level effect in reducing the force of infection and new infection rates. Results of this study suggest that field trials to evaluate efficacy of antimicrobial treatment should include estimates of indirect treatment effects.
Publisher: Springer Science and Business Media LLC
Date: 24-04-2013
Publisher: The Royal Society
Date: 12-2015
Publisher: American Chemical Society (ACS)
Date: 28-12-2017
DOI: 10.1021/ACS.ANALCHEM.7B03933
Abstract: A facile and simple one-step method was developed to fabricate aptamer-decorated self-assembled organic dots with aggregation-induced emission (AIE) characteristics. With integration of the advantages of AIE aggregates with strong emission and the cell-targeting capability of aptamers, the as-prepared Apt-AIE organic nanodots can specifically target to cancer cells with good biocompatibility, high image constrast, and photostability. On the basis of this universal method, a variety of versatile organic fluorescent nanoprobes with high brightness, specific recognition, and clinical-transitional potential could be facilely constructed for biological sensing and imaging applications.
Publisher: F1000 Research Ltd
Date: 12-06-2018
DOI: 10.12688/WELLCOMEOPENRES.13751.1
Abstract: Background: Village Malaria Workers (VMWs) are lay people trained to provide a valuable role in frontline testing and treatment of malaria in rural villages in Cambodia. Emergence of artemisinin-resistant malaria highlights the essential role of such VMWs in surveillance and early treatment of malaria. Smartphone technology offers huge potential to support VMWs in isolated and resource-poor settings. Methods: We investigated the feasibility of issuing established VMWs with a smartphone, bespoke Android application and solar charger to support their role. 27 VMWs in K ong Cham and Kratie provinces participated. Results: 26/27 of the smartphones deployed were working well at study completion twelve months later. Interviews with VMWs using quantitative and qualitative methods revealed pride, ease of use and reports of faster communication with the smartphone. VMWs also expressed a strong wish to help people presenting with non-malarial fever, for which further potential supportive smartphone applications are increasingly available. Conclusions: As a result of this pilot study, two smartphone based reporting systems for malaria have been developed at the Cambodian National Malaria Center, and the programme is now being extended nationwide. The full code for the smartphone application is made available to other researchers and healthcare providers with this article. Smartphones represent a feasible platform for developing the VMW role to include other health conditions, thus maintaining the relevance of these important community health workers.
Publisher: Springer Science and Business Media LLC
Date: 10-02-2021
DOI: 10.1038/S41467-021-21134-2
Abstract: Dexamethasone can reduce mortality in hospitalised COVID-19 patients needing oxygen and ventilation by 18% and 36%, respectively. Here, we estimate the potential number of lives saved and life years gained if this treatment were to be rolled out in the UK and globally, as well as the cost-effectiveness of implementing this intervention. Assuming SARS-CoV-2 exposure levels of 5% to 15%, we estimate that, for the UK, approximately 12,000 (4,250 - 27,000) lives could be saved between July and December 2020. Assuming that dexamethasone has a similar effect size in settings where access to oxygen therapies is limited, this would translate into approximately 650,000 (240,000 - 1,400,000) lives saved globally over the same time period. If dexamethasone acts differently in these settings, the impact could be less than half of this value. To estimate the full potential of dexamethasone in the global fight against COVID-19, it is essential to perform clinical research in settings with limited access to oxygen and/or ventilators, for ex le in low- and middle-income countries.
Publisher: Public Library of Science (PLoS)
Date: 21-09-2012
Publisher: Public Library of Science (PLoS)
Date: 15-02-2019
Publisher: Proceedings of the National Academy of Sciences
Date: 20-12-2010
Abstract: Artemisinin-resistant Plasmodium falciparum malaria has emerged in western Cambodia. Resistance is characterized by prolonged in vivo parasite clearance times (PCTs) following artesunate treatment. The biological basis is unclear. The hypothesis that delayed parasite clearance results from a stage-specific reduction in artemisinin sensitivity of the circulating young asexual parasite ring stages was examined. A mathematical model was developed, describing the intrahost parasite stage-specific pharmacokinetic–pharmacodynamic relationships. Model parameters were estimated using detailed pharmacokinetic and parasite clearance data from 39 patients with uncomplicated falciparum malaria treated with artesunate from Pailin (western Cambodia) where artemisinin resistance was evident and 40 patients from Wang Pha (northwestern Thailand) where efficacy was preserved. The mathematical model reproduced the observed parasite clearance for each patient with an accurate goodness of fit (rmsd: 0.03–0.67 in log 10 scale). The parameter sets that provided the best fits with the observed in vivo data consist of a highly conserved concentration–effect relationship for the trophozoite and schizont parasite stages, but a variable relationship for the ring stages. The model-derived assessment suggests that the efficacy of artesunate on ring stage parasites is reduced significantly in Pailin. This result supports the hypothesis that artemisinin resistance mainly reflects reduced ring-stage susceptibility and predicts that doubling the frequency of dosing will accelerate clearance of artemisinin-resistant parasites.
Publisher: Elsevier BV
Date: 02-2011
Publisher: Research Square Platform LLC
Date: 10-02-2022
DOI: 10.21203/RS.3.RS-1345628/V1
Abstract: Previous mathematical models characterising the pharmacokinetic and pharmacodynamic properties of artemisinins in-vivo have not accounted satisfactorily for observed dose-response relationships. We present a new mathematical model of antimalarial pharmacodynamics which incorporates the hypothesis that parasites enter a transitional unresponsive state after contact with artemisinins, followed either by delayed death or reactivation. The model predictions are consistent with both in vitro and in vivo study results.
Publisher: Research Square Platform LLC
Date: 06-07-2023
DOI: 10.21203/RS.3.RS-1345628/V2
Abstract: Background The artemisinins are potent and widely used antimalarial drugs which are eliminated rapidly. A simple concentration-effect pharmacometric model does not explain why dosing more frequently than once daily fails to augment parasite clearance and improve therapeutic responses in-vivo. Artemisinins can induce a temporary non-replicative or “dormant” drug refractory state in Plasmodium falciparum malaria parasites which may explain recrudescences observed in clinical trials despite full drug susceptibility, but whether it explains the dosing-response relationship is uncertain. Objectives To propose a revised model of antimalarial pharmacodynamics which incorporates reversible asexual parasite injury and temporary drug refractoriness in order to explain the failure of frequent dosing to augment therapeutic efficacy. Methods The model was fitted using Bayesian Markov Chain Monte Carlo approach with the parasite clearance data from 39 patients with uncomplicated falciparum malaria treated with artesunate from western Cambodia and 40 patients from Northwestern Thailand reported previously. Results The model captured the dynamics of parasite clearance data. Its predictions are consistent with observed therapeutic responses. Conclusions A within-host pharmacometric model is proposed in which it is hypothesised that some malaria parasites enter a temporary drug refractory state after exposure to artemisinin antimalarials which is followed by delayed parasite death or reactivation. The model fitted the observed sequential parasite density data from patients with acute P. falciparum malaria, and it supported reduced ring stage activity in artemisinin resistant infections.
Publisher: Elsevier BV
Date: 07-2017
Publisher: Springer Science and Business Media LLC
Date: 20-02-2009
Publisher: Public Library of Science (PLoS)
Date: 26-06-2015
Publisher: Springer Science and Business Media LLC
Date: 30-09-2014
Publisher: F1000 Research Ltd
Date: 29-07-2019
DOI: 10.12688/WELLCOMEOPENRES.14770.2
Abstract: Leaders in the Asia-Pacific have endorsed an ambitious target to eliminate malaria in the region by 2030. The emergence and spread of artemisinin drug resistance in the Greater Mekong Subregion makes elimination urgent and strategic for the global goal of malaria eradication. Mathematical modelling is a useful tool for assessing and comparing different elimination strategies and scenarios to inform policymakers. Mathematical models are especially relevant in this context because of the wide heterogeneity of regional, country and local settings, which means that different strategies are needed to eliminate malaria. However, models and their predictions can be seen as highly technical, limiting their use for decision making. Simplified applications of models are needed to allow policy makers to benefit from these valuable tools. This paper describes a method for communicating complex model results with a user-friendly and intuitive framework. Using open-source technologies, we designed and developed an interactive application to disseminate the modelling results for malaria elimination. The design was iteratively improved while the application was being piloted and extensively tested by a erse range of researchers and decision makers. This application allows several target audiences to explore, navigate and visualise complex datasets and models generated in the context of malaria elimination. It allows widespread access, use of and interpretation of models, generated at great effort and expense as well as enabling them to remain relevant for a longer period of time. It has long been acknowledged that scientific results need to be repackaged for larger audiences. We demonstrate that modellers can include applications as part of the dissemination strategy of their findings. We highlight that there is a need for additional research in order to provide guidelines and direction for designing and developing effective applications for disseminating models.
Publisher: Oxford University Press (OUP)
Date: 06-2009
Publisher: F1000 Research Ltd
Date: 04-2019
DOI: 10.12688/WELLCOMEOPENRES.14770.1
Abstract: Leaders in the Asia-Pacific have endorsed an ambitious target to eliminate malaria in the region by 2030. The emergence and spread of artemisinin drug resistance in the Greater Mekong Subregion makes elimination urgent and strategic for the global goal of malaria eradication. Mathematical modelling is a useful tool for assessing and comparing different elimination strategies and scenarios to inform policymakers. Mathematical models are especially relevant in this context because of the wide heterogeneity of regional, country and local settings, which means that different strategies are needed to eliminate malaria. However, models and their predictions can be seen as highly technical, limiting their use for decision making. Simplified applications of models are needed to allow policy makers to benefit from these valuable tools. This paper describes a method for communicating complex model results with a user-friendly and intuitive framework. Using open-source technologies, we designed and developed an interactive application to disseminate the modelling results for malaria elimination. The design was iteratively improved while the application was being piloted and extensively tested by a erse range of researchers and decision makers. This application allows several target audiences to explore, navigate and visualise complex datasets and models generated in the context of malaria elimination. It allows widespread access, use of and interpretation of models, generated at great effort and expense as well as enabling them to remain relevant for a longer period of time. It has long been acknowledged that scientific results need to be repackaged for larger audiences. We demonstrate that modellers can include applications as part of the dissemination strategy of their findings. We highlight that there is a need for additional research in order to provide guidelines and direction for designing and developing effective applications for disseminating models.
Publisher: The Royal Society
Date: 17-08-2011
Abstract: Many women in resource-poor settings lack access to reliable gestational age assessment because they do not know their last menstrual period there is no ultrasound (US) and methods of newborn gestational age dating are not practised by birth attendants. A bespoke multiple-measures model was developed to predict the expected date of delivery determined by US. The results are compared with both a linear and a nonlinear model. Prospectively collected early US and serial symphysis-pubis fundal height (SFH) data were used in the models. The data were collected from Karen and Burmese women attending antenatal care on the Thai–Burmese border. The multiple-measures model performed best, resulting in a range of accuracy depending on the number of SFH measures recorded per mother (for ex le six SFH measurements resulted in a prediction accuracy of ±2 weeks). SFH remains the proxy for gestational age in much of the resource-poor world. While more accurate measures should be encouraged, we demonstrate that a formula that incorporates at least three SFH measures from an in idual mother and the slopes between them provide a significant increase in the accuracy of prediction compared with the linear and nonlinear formulae also using multiple SFH measures.
Publisher: Public Library of Science (PLoS)
Date: 30-03-2016
Publisher: Public Library of Science (PLoS)
Date: 17-03-2015
Publisher: BMJ
Date: 12-2020
DOI: 10.1136/BMJGH-2020-003126
Abstract: The SARS-CoV-2 pandemic has had an unprecedented impact on multiple levels of society. Not only has the pandemic completely overwhelmed some health systems but it has also changed how scientific evidence is shared and increased the pace at which such evidence is published and consumed, by scientists, policymakers and the wider public. More significantly, the pandemic has created tremendous challenges for decision-makers, who have had to implement highly disruptive containment measures with very little empirical scientific evidence to support their decision-making process. Given this lack of data, predictive mathematical models have played an increasingly prominent role. In high-income countries, there is a long-standing history of established research groups advising policymakers, whereas a general lack of translational capacity has meant that mathematical models frequently remain inaccessible to policymakers in low-income and middle-income countries. Here, we describe a participatory approach to modelling that aims to circumvent this gap. Our approach involved the creation of an international group of infectious disease modellers and other public health experts, which culminated in the establishment of the COVID-19 Modelling (CoMo) Consortium. Here, we describe how the consortium was formed, the way it functions, the mathematical model used and, crucially, the high degree of engagement fostered between CoMo Consortium members and their respective local policymakers and ministries of health.
Publisher: F1000 Research Ltd
Date: 14-01-2020
DOI: 10.12688/WELLCOMEOPENRES.14769.2
Abstract: Background: The Asia-Pacific region has made significant progress against malaria, reducing cases and deaths by over 50% between 2010 and 2015. These gains have been facilitated in part, by strong political and financial commitment of governments and donors. However, funding gaps and persistent health system challenges threaten further progress. Achieving the regional goal of malaria elimination by 2030 will require an intensification of efforts and a plan for sustainable financing. This article presents an investment case for malaria elimination to facilitate these efforts. Methods: A transmission model was developed to project rates of decline of Plasmodium falciparum and Plasmodium vivax malaria and the output was used to determine the cost of the interventions that would be needed for elimination by 2030. In total, 80 scenarios were modelled under various assumptions of resistance and intervention coverage. The mortality and morbidity averted were estimated and health benefits were monetized by calculating the averted cost to the health system, in idual households, and society. The full-income approach was used to estimate the economic impact of lost productivity due to premature death and illness, and a return on investment was computed. Results : The study estimated that malaria elimination in the region by 2030 could be achieved at a cost of USD 29.02 billion (range: USD 23.65-36.23 billion) between 2017 and 2030. Elimination would save over 400,000 lives and avert 123 million malaria cases, translating to almost USD 90 billion in economic benefits. Discontinuing vector control interventions and reducing treatment coverage rates to 50% will result in an additional 845 million cases, 3.5 million deaths, and excess costs of USD 7 billion. Malaria elimination provides a 6:1 return on investment. Conclusion: This investment case provides compelling evidence for the benefits of continued prioritization of funding for malaria and can be used to develop an advocacy strategy.
Publisher: Springer Science and Business Media LLC
Date: 14-09-2009
Publisher: Springer Science and Business Media LLC
Date: 11-11-2009
Publisher: Public Library of Science (PLoS)
Date: 19-08-2201
Publisher: F1000 Research Ltd
Date: 04-2019
DOI: 10.12688/WELLCOMEOPENRES.14769.1
Abstract: Background: The Asia-Pacific region has made significant progress against malaria, reducing cases and deaths by over 50% between 2010 and 2015. These gains have been facilitated in part, by strong political and financial commitment of governments and donors. However, funding gaps and persistent health system challenges threaten further progress. Achieving the regional goal of malaria elimination by 2030 will require an intensification of efforts and a plan for sustainable financing. This article presents an investment case for malaria elimination to facilitate these efforts. Methods: A transmission model was developed to project rates of decline of Plasmodium falciparum and Plasmodium vivax malaria and the output was used to determine the cost of the interventions that would be needed for elimination by 2030. In total, 80 scenarios were modelled under various assumptions of resistance and intervention coverage. The mortality and morbidity averted were estimated and health benefits were monetized by calculating the averted cost to the health system, in idual households, and society. The full-income approach was used to estimate the economic impact of lost productivity due to premature death and illness, and a return on investment was computed. Results : The study estimated that malaria elimination in the region by 2030 could be achieved at a cost of USD 29.02 billion (range: USD 23.65-36.23 billion) between 2017 and 2030. Elimination would save over 400,000 lives and avert 123 million malaria cases, translating to almost USD 90 billion in economic benefits. Discontinuing vector control interventions and reducing treatment coverage rates to 50% will result in an additional 845 million cases, 3.5 million deaths, and excess costs of USD 7 billion. Malaria elimination provides a 6:1 return on investment. Conclusion: This investment case provides compelling evidence for the benefits of continued prioritization of funding for malaria and can be used to develop an advocacy strategy.
Publisher: American Society for Microbiology
Date: 12-2017
DOI: 10.1128/AAC.00618-17
Abstract: Artemisinin resistance constitutes a major threat to the continued success of control programs for malaria, particularly in light of developing resistance to partner drugs. Improving our understanding of how artemisinin-based drugs act and how resistance manifests is essential for the optimization of dosing regimens and the development of strategies to prolong the life span of current first-line treatment options. Recent short-drug-pulse in vitro experiments have shown that the parasite killing rate depends not only on drug concentration but also the exposure time, challenging the standard pharmacokinetic-pharmacodynamic (PK-PD) paradigm in which the killing rate depends only on drug concentration. Here, we introduce a dynamic stress model of parasite killing and show through application to 3D7 laboratory strain viability data that the inclusion of a time-dependent parasite stress response dramatically improves the model's explanatory power compared to that of a traditional PK-PD model. Our model demonstrates that the previously reported hypersensitivity of early-ring-stage parasites of the 3D7 strain to dihydroartemisinin compared to other parasite stages is due primarily to a faster development of stress rather than a higher maximum achievable killing rate. We also perform in vivo simulations using the dynamic stress model and demonstrate that the complex temporal features of artemisinin action observed in vitro have a significant impact on predictions for in vivo parasite clearance. Given the important role that PK-PD models play in the design of clinical trials for the evaluation of alternative drug dosing regimens, our novel model will contribute to the further development and improvement of antimalarial therapies.
Publisher: Springer Science and Business Media LLC
Date: 05-03-2021
DOI: 10.1038/S41467-021-22038-X
Abstract: A Correction to this paper has been published: 0.1038/s41467-021-22038-x.
Location: China
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Lisa White.