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 rationalise the control of drug resistant Plasmodium vivax by improving strategies to optimise its surveillance and management. To achieve this we are: i) defining the burden of vivax malaria in South East Asia with particularly attention to areas where chloroquine resistance is emerging, ii) conducting clinical studies to optimise the prevention and treatment of vivax malaria iii) developing ex vivo tools to improve the surveillance and characterisation of drug resistance in P. vivax and iv) 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, with partners in the Indonesian Ministry of Health. Our field site in Papua currently employs 15 full time staff, with a research agenda that spans epidemiology, health economics, clinical trials, pathophysiology, immunology, in vitro studies and molecular biology.

Current Projects:

  • Epidemiology studies of chloroquine resistant P. vivax.
  • Clinical trials of new treatments for drug resistant malaria.
  • Molecular and in vitro studies to characterise drug resistance in P. falciparum and P. vivax.
  • Impact and cost effectiveness studies of artemisinin combination therapy for drug resistant P. falciparum and P. vivax in Papua, Indonesia.

Name Department Institution Country
Prof Nicholas Anstey International Health Division, Menzies School of Health Research Australia
David Fidock Columbia University, NYC United States
Tim ANDERSON Southwest Foundation Texas United States
Qin Cheng Australian Malaria Institute, Brisbane Australia
Julie Simpson Melbourne University Australia
Emiliana Tjitra National Institue of Health Research and Development Indonesia

Achan J, Adam I, Arinaitwe E, Ashley EA, Awab GR, Ba MS, Barnes KI, Bassat Q et al. 2013. The Effect of Dosing Regimens on the Antimalarial Efficacy of Dihydroartemisinin-Piperaquine: A Pooled Analysis of Individual Patient Data PLOS MEDICINE, 10 (12), pp. e1001564-e1001564. Read abstract | Read more

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

Douglas NM, Lampah DA, Kenangalem E, Simpson JA, Poespoprodjo JR, Sugiarto P, Anstey NM, Price RN. 2013. Major burden of severe anemia from non-falciparum malaria species in Southern Papua: a hospital-based surveillance study. PLoS Med, 10 (12), pp. e1001575. Read abstract | Read more

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

Douglas NM, Simpson JA, Phyo AP, Siswantoro H, Hasugian AR, Kenangalem E, Poespoprodjo JR, Singhasivanon P et al. 2013. Gametocyte dynamics and the role of drugs in reducing the transmission potential of Plasmodium vivax. J Infect Dis, 208 (5), pp. 801-812. Read abstract | Read more

Designing interventions that will reduce transmission of vivax malaria requires knowledge of Plasmodium vivax gametocyte dynamics. Hide abstract

John GK, Douglas NM, von Seidlein L, Nosten F, Baird JK, White NJ, Price RN. 2012. Primaquine radical cure of Plasmodium vivax: a critical review of the literature. Malar J, 11 (1), pp. 280. Read abstract | Read more

Primaquine has been the only widely available hypnozoitocidal anti-malarial drug for half a century. Despite this its clinical efficacy is poorly characterized resulting in a lack of consensus over the optimal regimen for the radical cure of Plasmodium vivax. Hide abstract

Douglas NM, Nosten F, Ashley EA, Phaiphun L, van Vugt M, Singhasivanon P, White NJ, Price RN. 2011. Plasmodium vivax recurrence following falciparum and mixed species malaria: risk factors and effect of antimalarial kinetics. Clin Infect Dis, 52 (5), pp. 612-620. Read abstract | Read more

Plasmodium vivax malaria commonly follows treatment of falciparum malaria in regions of co-endemicity. This is an important cause of preventable morbidity. Hide abstract

Douglas NM, Anstey NM, Angus BJ, Nosten F, Price RN. 2010. Artemisinin combination therapy for vivax malaria. Lancet Infect Dis, 10 (6), pp. 405-416. Read abstract | Read more

Early parasitological diagnosis and treatment with artemisinin-based combination therapies (ACTs) are key components of worldwide malaria elimination programmes. In general, use of ACTs has been limited to patients with falciparum malaria whereas blood-stage infections with Plasmodium vivax are mostly still treated with chloroquine. We review the evidence for the relative benefits and disadvantages of the existing separate treatment approach versus a unified ACT-based strategy for treating Plasmodium falciparum and P vivax infections in regions where both species are endemic (co-endemic). The separate treatment scenario is justifiable if P vivax remains sensitive to chloroquine and diagnostic tests reliably distinguish P vivax from P falciparum. However, with the high number of misdiagnoses in routine practice and the rise and spread of chloroquine-resistant P vivax, there might be a compelling rationale for a unified ACT-based strategy for vivax and falciparum malaria in all co-endemic regions. Analyses of the cost-effectiveness of ACTs for both Plasmodium species are needed to assess the role of these drugs in the control and elimination of vivax malaria. Hide abstract

Poespoprodjo JR, Fobia W, Kenangalem E, Lampah DA, Hasanuddin A, Warikar N, Sugiarto P, Tjitra E, Anstey NM, Price RN. 2009. Vivax malaria: a major cause of morbidity in early infancy. Clin Infect Dis, 48 (12), pp. 1704-1712. Read abstract | Read more

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

Suwanarusk R, Chavchich M, Russell B, Jaidee A, Chalfein F, Barends M, Prasetyorini B, Kenangalem E et al. 2008. Amplification of pvmdr1 associated with multidrug-resistant Plasmodium vivax. J Infect Dis, 198 (10), pp. 1558-1564. Read abstract | Read more

Multidrug-resistant strains of Plasmodium vivax are emerging in Southeast Asia. Hide abstract

Tjitra E, Anstey NM, Sugiarto P, Warikar N, Kenangalem E, Karyana M, Lampah DA, Price RN. 2008. Multidrug-resistant Plasmodium vivax associated with severe and fatal malaria: a prospective study in Papua, Indonesia. PLoS Med, 5 (6), pp. e128. Read abstract | Read more

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

Poespoprodjo JR, Fobia W, Kenangalem E, Lampah DA, Warikar N, Seal A, McGready R, Sugiarto P, Tjitra E, Anstey NM, Price RN. 2008. Adverse pregnancy outcomes in an area where multidrug-resistant plasmodium vivax and Plasmodium falciparum infections are endemic. Clin Infect Dis, 46 (9), pp. 1374-1381. Read abstract | Read more

Plasmodium falciparum infection exerts a considerable burden on pregnant women, but less is known about the adverse consequences of Plasmodium vivax infection. Hide abstract

Russell B, Chalfein F, Prasetyorini B, Kenangalem E, Piera K, Suwanarusk R, Brockman A, Prayoga P et al. 2008. Determinants of in vitro drug susceptibility testing of Plasmodium vivax. Antimicrob Agents Chemother, 52 (3), pp. 1040-1045. Read abstract | Read more

In Papua, Indonesia, the antimalarial susceptibility of Plasmodium vivax (n = 216) and P. falciparum (n = 277) was assessed using a modified schizont maturation assay for chloroquine, amodiaquine, artesunate, lumefantrine, mefloquine, and piperaquine. The most effective antimalarial against P. vivax and P. falciparum was artesunate, with geometric mean 50% inhibitory concentrations (IC50s) (95% confidence intervals [CI]) of 1.31 nM (1.07 to 1.59) and 0.64 nM (0.53 to 0.79), respectively. In contrast, the geometric mean chloroquine IC50 for P. vivax was 295 nM (227 to 384) compared to only 47.4 nM (42.2 to 53.3) for P. falciparum. Two factors were found to significantly influence the in vitro drug response of P. vivax: the initial stage of the parasite and the duration of the assay. Isolates of P. vivax initially at the trophozoite stage had significantly higher chloroquine IC50s (478 nM [95% CI, 316 to 722]) than those initially at the ring stage (84.7 nM [95% CI, 45.7 to 157]; P < 0.001). Synchronous isolates of P. vivax and P. falciparum which reached the target of 40% schizonts in the control wells within 30 h had significantly higher geometric mean chloroquine IC50s (435 nM [95% CI, 169 to 1,118] and 55.9 nM [95% CI, 48 to 64.9], respectively) than isolates that took more than 30 h (39.9 nM [14.6 to 110.4] and 36.9 nM [31.2 to 43.7]; P < 0.005). The results demonstrate the marked stage-specific activity of chloroquine with P. vivax and suggest that susceptibility to chloroquine may be associated with variable growth rates. These findings have important implications for the phenotypic and downstream genetic characterization of P. vivax. Hide abstract

Ratcliff A, Siswantoro H, Kenangalem E, Maristela R, Wuwung RM, Laihad F, Ebsworth EP, Anstey NM, Tjitra E, Price RN. 2007. Two fixed-dose artemisinin combinations for drug-resistant falciparum and vivax malaria in Papua, Indonesia: an open-label randomised comparison. Lancet, 369 (9563), pp. 757-765. Read abstract | Read more

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

Price RN, Uhlemann AC, van Vugt M, Brockman A, Hutagalung R, Nair S, Nash D, Singhasivanon P et al. 2006. Molecular and pharmacological determinants of the therapeutic response to artemether-lumefantrine in multidrug-resistant Plasmodium falciparum malaria. Clin Infect Dis, 42 (11), pp. 1570-1577. Read abstract | Read more

Our study examined the relative contributions of host, pharmacokinetic, and parasitological factors in determining the therapeutic response to artemether-lumefantrine (AL). Hide abstract

Price RN, Uhlemann AC, Brockman A, McGready R, Ashley E, Phaipun L, Patel R, Laing K et al. 2004. Mefloquine resistance in Plasmodium falciparum and increased pfmdr1 gene copy number. Lancet, 364 (9432), pp. 438-447. Read abstract | Read more

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

Nosten F, van Vugt M, Price R, Luxemburger C, Thway KL, Brockman A, McGready R, ter Kuile F, Looareesuwan S, White NJ. 2000. Effects of artesunate-mefloquine combination on incidence of Plasmodium falciparum malaria and mefloquine resistance in western Thailand: a prospective study. Lancet, 356 (9226), pp. 297-302. Read abstract | Read more

Worsening drug resistance in Plasmodium falciparum malaria is a major threat to health in tropical countries. We did a prospective study of malaria incidence and treatment in an area of highly multidrug-resistant P. falciparum malaria. Hide abstract

Price RN, Nosten F, Luxemburger C, ter Kuile FO, Paiphun L, Chongsuphajaisiddhi T, White NJ. 1996. Effects of artemisinin derivatives on malaria transmissibility. Lancet, 347 (9016), pp. 1654-1658. Read abstract | Read more

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 ...

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