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.
- 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.
|Nicholas Anstey||International Health Division, Menzies School of Health Research||Australia|
|David Fidock||Columbia University, NYC||USA|
|Tim ANDERSON||Southwest Foundation Texas||USA|
|Qin Cheng||Australian Malaria Institute, Brisbane||Australia|
|Julie Simpson||Melbourne University||Australia|
|Emiliana Tjitra||National Institue of Health Research and Development||Indonesia|
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
Background. Designing interventions that will reduce transmission of vivax malaria requires knowledge of Plasmodium vivax gametocyte dynamics.Methods. We analyzed data from a randomized controlled trial in Northwestern Thailand and two trials in Papua, Indonesia to identify and compare risk factors for vivax gametocytemia at enrolment and following treatment.Results. Overall 492 patients with P. vivax infections were evaluable from Thailand and 476 patients (162 with concurrent falciparum parasitemia) were evaluable from Papua. 84.3% (415/492) and 66.6% (209/314) of patients with monoinfection were gametocytemic at enrolment respectively. The ratio of gametocytemia to asexual parasitemia did not differ between acute and recurrent infections (p=0.48 in Thailand, p=0.08 in Papua). High asexual parasitemia was associated with an increased risk of gametocytemia during follow-up in both locations. In Thailand, the cumulative incidence of gametocytemia between days 7 and 42 following dihydroartemisinin+piperaquine was 6.92% versus 29.1% following chloroquine (p<0.001). In Papua, the incidence of gametocytemia was 33.6% following artesunate+amodiaquine, 7.42% following artemether+lumefantrine and 6.80% following dihydroartemisinin+piperaquine (p<0.001 for dihydroartemisinin+piperaquine versus artesunate+amodiaquine).Conclusions. Plasmodium vivax gametocyte carriage mirrors asexual stage infection. Preventing relapses, particularly in those with high asexual parasitemia, is likely to be the most important strategy for interrupting P. vivax transmission. Hide abstract
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
Plasmodium vivax malaria commonly follows treatment of falciparum malaria in regions of co-endemicity. This is an important cause of preventable morbidity. Hide abstract
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
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 strains of Plasmodium vivax are emerging in Southeast Asia. Hide abstract
PLOS MEDICINE, 5 (6), pp. 890-899. | Read more2008. Multidrug-resistant Plasmodium vivax associated with severe and fatal malaria: A prospective study in Papua, Indonesia
Plasmodium falciparum infection exerts a considerable burden on pregnant women, but less is known about the adverse consequences of Plasmodium vivax infection. Hide abstract
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
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
Our study examined the relative contributions of host, pharmacokinetic, and parasitological factors in determining the therapeutic response to artemether-lumefantrine (AL). 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
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
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