Prof Richard Price
|Research Area:||Global Health|
|Scientific Themes:||Tropical Medicine & Global Health|
|Keywords:||malaria, epidemiology, drug resistance and clinical trials|
The main focus of our research programme is to improve the diagnosis and management of multidrug resistant malaria through an agenda that spans clinical trials, epidemiology, health economics, pathophysiology, in vitro studies and molecular biology. To achieve this we are:
- defining the burden of vivax malaria in South East Asia with particularly attention to areas where chloroquine resistance is emerging,
- conducting clinical studies to optimise the safe and effective radical cure of vivax malaria,
- developing ex vivo tools to improve the surveillance and characterisation of drug resistance in P. vivax,
- evaluating the impact and cost effectiveness of widespread deployment of artemisinin combination therapies on malaria related morbidity and mortality.
The programme is being conducted in collaboration with the Mahidol Oxford Research Unit (MORU) in Thailand and the Menzies School of Health Research (MSHR) in Darwin. Together we have recently embarked upon a large leading multicentred clinical trial in more than seven malaria endemic countries to compare different primaquine regimens for the radical cure of vivax malaria. I am head of the clinical module of the World Wide Antimalarial Resistance Network (WWARN) and co-chair the Vivax Working Group of the Asia-Pacific Malaria Elimination Network (APMEN).
- Defining the morbidity and mortality of Plasmodium vivax.
- Optimising the safe and effective radical cure of P. vivax
- Investigating new strategies for the diagnosis and mapping of G6PD deficiency
- Molecular characterisation of drug resistant malaria
- In vitro drug susceptibility of Plasmodium: phenotypic characterisation and testing novel antimalarial compounds
|Prof Nicholas Anstey||International Health Division, Menzies School of Health Research||Australia|
|Prof Nicholas J White FRS||Tropical Medicine||University of Oxford||United Kingdom|
|Prof François H Nosten||Tropical Medicine||University of Oxford||United Kingdom|
|Dr Rini Poespoprodjo||Papuan Health and Community Development Foundation, Papu||Indonesia|
|Dr Rintis Noviyanti||Eijkman Institute for Molecular Biology, Jakarta||Indonesia|
|Prof Qin Cheng||Australian Malaria Institute, Brisbane||Australia|
|Assoc. Prof. Julie Simpson||Melbourne University||Australia|
|Prof John Adams||University of South Florida||United States|
|Prof James McCarthy||Queensland Institute of Medical Research||University of Queensland||Australia|
Chloroquine is the first-line treatment for Plasmodium vivax malaria in most endemic countries, but resistance is increasing. Monitoring of antimalarial efficacy is essential, but in P. vivax infections the assessment of treatment efficacy is confounded by relapse from the dormant liver stages. We systematically reviewed P. vivax malaria treatment efficacy studies to establish the global extent of chloroquine resistance. Hide abstract
Background:Dihydroartemisinin-piperaquine (DP) is increasingly recommended for antimalarial treatment in many endemic countries; however, concerns have been raised over its potential under dosing in young children. We investigated the influence of different dosing schedules on DP's clinical efficacy.Methods and Findings:A systematic search of the literature was conducted to identify all studies published between 1960 and February 2013, in which patients were enrolled and treated with DP. Principal investigators were approached and invited to share individual patient data with the WorldWide Antimalarial Resistance Network (WWARN). Data were pooled using a standardised methodology. Univariable and multivariable risk factors for parasite recrudescence were identified using a Cox's regression model with shared frailty across the study sites. Twenty-four published and two unpublished studies (n = 7,072 patients) were included in the analysis. After correcting for reinfection by parasite genotyping, Kaplan-Meier survival estimates were 97.7% (95% CI 97.3%-98.1%) at day 42 and 97.2% (95% CI 96.7%-97.7%) at day 63. Overall 28.6% (979/3,429) of children aged 1 to 5 years received a total dose of piperaquine below 48 mg/kg (the lower limit recommended by WHO); this risk was 2.3-2.9-fold greater compared to that in the other age groups and was associated with reduced efficacy at day 63 (94.4% [95% CI 92.6%-96.2%], p<0.001). After adjusting for confounding factors, the mg/kg dose of piperaquine was found to be a significant predictor for recrudescence, the risk increasing by 13% (95% CI 5.0%-21%) for every 5 mg/kg decrease in dose; p = 0.002. In a multivariable model increasing the target minimum total dose of piperaquine in children aged 1 to 5 years old from 48 mg/kg to 59 mg/kg would halve the risk of treatment failure and cure at least 95% of patients; such an increment was not associated with gastrointestinal toxicity in the ten studies in which this could be assessed.Conclusions:DP demonstrates excellent efficacy in a wide range of transmission settings; however, treatment failure is associated with a lower dose of piperaquine, particularly in young children, suggesting potential for further dose optimisation.Please see later in the article for the Editors' Summary. © 2013 Price et al. Hide abstract
The burden of anemia attributable to non-falciparum malarias in regions with Plasmodium co-endemicity is poorly documented. We compared the hematological profile of patients with and without malaria in southern Papua, Indonesia. Hide abstract
Plasmodium vivax malaria commonly follows treatment of falciparum malaria in regions of co-endemicity. This is an important cause of preventable morbidity. Hide abstract
In areas where malaria is endemic, infants aged <3 months appear to be relatively protected from symptomatic and severe Plasmodium falciparum malaria, but less is known about the effect of Plasmodium vivax infection in this age group. Hide abstract
Multidrug-resistant Plasmodium vivax (Pv) is widespread in eastern Indonesia, and emerging elsewhere in Asia-Pacific and South America, but is generally regarded as a benign disease. The aim of the study was to review the spectrum of disease associated with malaria due to Pv and P. falciparum (Pf) in patients presenting to a hospital in Timika, southern Papua, Indonesia. Hide abstract
Plasmodium falciparum infection exerts a considerable burden on pregnant women, but less is known about the adverse consequences of Plasmodium vivax infection. Hide abstract
The burden of Plasmodium vivax infections has been underappreciated, especially in southeast Asia where chloroquine resistant strains have emerged. Our aim was to compare the safety and efficacy of dihydroartemisinin-piperaquine with that of artemether-lumefantrine in patients with uncomplicated malaria caused by multidrug-resistant P falciparum and P vivax. Hide abstract
The borders of Thailand harbour the world's most multidrug resistant Plasmodium falciparum parasites. In 1984 mefloquine was introduced as treatment for uncomplicated falciparum malaria, but substantial resistance developed within 6 years. A combination of artesunate with mefloquine now cures more than 95% of acute infections. For both treatment regimens, the underlying mechanisms of resistance are not known. Hide abstract
On the western border of Thailand the efficacy of mefloquine in the treatment of falciparum malaria has declined while gametocyte carriage rates have increased, which suggests increased transmissibility of these resistant infections. We compared the following antimalarial drugs in relation to subsequent Plasmodium falciparum gametocyte carriage: mefloquine, halofantrine, quinine, and the artemisinin derivatives. Hide abstract
Cost effectiveness of diagnostic and treatment strategies for Plasmodium vivax malaria in diverse epidemiological settings
Plasmodium vivax malaria causes approximately a quarter of a billion clinical episodes of illness per year with 40% of the world at risk of infection. Despite the heavy burden of disease, little is known about the cost-effectiveness of screening and treatment options for the management of P. vivax.Furthermore, a number of epidemiological, biological and behavioural factors will impact the cost effectiveness of these options. Unlike Plasmodium falciparum malaria, the radical cure of P. vivax ...
Impact of biological markers on antimalarial treatment outcomes
The Worldwide Antimalarial Resistance Network (WWARN - www.wwarn.org) is seeking a doctoral candidate to study and model the impact of biological markers and genotyping methods on treatment outcome in clinical trials assessing the efficacy of antimalarials. The project will be supervised by Dr Christian Nsanzabana, Professor Philippe Guerin and Professor Richard Price. The student will be based in Oxford, joining a dynamic team at the Centre for Tropical Medicine and Global Health to identify ...