Research Area:	Global Health
Scientific Themes:	Tropical Medicine & Global Health
Web Links:	Podcast 'Severe Malaria'

Since November 2000, I work at the Mahidol-Oxford Tropical Medicine Research Unit in Bangkok, Thailand, where I am currently the Deputy Director and Head of Malaria Research.

Our research unit studies a diversity of aspects of infectious (and other) diseases that are causing significant morbidity and mortality in the tropics. For this purpose we have a large network of clinical sites in both Africa and Asia, including Thailand, Bangladesh, India, Cambodia, Mozambique and elsewhere.

My main research interests include the pathophysiology and treatment of severe malaria, antimalarial drug resistance and improvement of intensive care practice in developing countries. We showed in a large multinational trial in SE Asia in 1461 mainly adult patients that parenteral artesunate is superior to quinine in preventing death; an even larger trial comparing the same drugs in African children with severe malaria is under way. Studies on the microcirculation in patients with severe malaria have revealed the likely contribution of red cell rigidity to the impairment of microcirculatory flow. We were the first to apply a new method to visualise obstruction of the microcirculation in vivo in patients with severe malaria. We also developed a method to calculate the sequestered parasite biomass from plasma PfHRP2, a protein released by the parasite and showed that yet to be identified organic acids other than lactate are an important contributor to the metabolic acidosis in severe malaria and have strong prognostic significance. Our team was the first to perform a comparative trial which unambiguously showed resistance of P. falciparum to artemisinins in Western Cambodia and in collaboration with other international groups are now working on further characterization of this resistance phenotype and identify molecular determinants of artemisinin resistance. We are also involved in finding new treatments for these patients and in the containment efforts against this serious threat to global malaria control.

In addition to this focus on malaria, we are coordinating a dedicated effort to improve intensive care medicine in developing countries in Asia, through teaching as well as the systematic implementation of cost-effective interventions and their assessment. My vision is that true collaborations with enthousiastic and like minded doctors and researchers from all countries where we are active help to identify important research questions, improves the quality of research, and builds capacity as an inherent side effect. Our unit has unique expertise and possibilities to conduct research from bench to bedside, and is in the centre of an extensive network enabling to conduct large multinational trials when definite answers are sought for important research questions aimed at improving treatment and reducing morbidity and mortality of malaria and other diseases.

There are no collaborations listed for this principal investigator.

Dondorp AM, Nosten F, Yi P, Das D, Phyo AP, Tarning J, Lwin KM, Ariey F, Hanpithakpong W, Lee SJ, Ringwald P, Silamut K, Imwong M, Chotivanich K, Lim P, Herdman T, An SS, Yeung S, Singhasivanon P, Day NP, Lindegardh N, Socheat D, White NJ et al. 2009. Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med, 361 (5), pp. 455-467. Read abstract | Read more

Artemisinin-based combination therapies are the recommended first-line treatments of falciparum malaria in all countries with endemic disease. There are recent concerns that the efficacy of such therapies has declined on the Thai-Cambodian border, historically a site of emerging antimalarial-drug resistance. Hide abstract

Dondorp AM, Lee SJ, Faiz MA, Mishra S, Price R, Tjitra E, Than M, Htut Y, Mohanty S, Yunus EB, Rahman R, Nosten F, Anstey NM, Day NP, White NJ et al. 2008. The relationship between age and the manifestations of and mortality associated with severe malaria. Clin Infect Dis, 47 (2), pp. 151-157. Read abstract | Read more

The reported case-fatality rate associated with severe malaria varies widely. Whether age is an independent risk factor is uncertain. Hide abstract

Dondorp AM, Ince C, Charunwatthana P, Hanson J, van Kuijen A, Faiz MA, Rahman MR, Hasan M, Bin Yunus E, Ghose A, Ruangveerayut R, Limmathurotsakul D, Mathura K, White NJ, Day NP et al. 2008. Direct in vivo assessment of microcirculatory dysfunction in severe falciparum malaria. J Infect Dis, 197 (1), pp. 79-84. Read abstract | Read more

This study sought to describe and quantify microcirculatory changes in the mucosal surfaces of patients with severe malaria, by direct in vivo observation using orthogonal polarization spectral (OPS) imaging. Hide abstract

Dondorp AM, Desakorn V, Pongtavornpinyo W, Sahassananda D, Silamut K, Chotivanich K, Newton PN, Pitisuttithum P, Smithyman AM, White NJ, Day NP. 2005. Estimation of the total parasite biomass in acute falciparum malaria from plasma PfHRP2. PLoS Med, 2 (8), pp. e204. Read abstract | Read more

In falciparum malaria sequestration of erythrocytes containing mature forms of Plasmodium falciparum in the microvasculature of vital organs is central to pathology, but quantitation of this hidden sequestered parasite load in vivo has not previously been possible. The peripheral blood parasite count measures only the circulating, relatively non-pathogenic parasite numbers. P. falciparum releases a specific histidine-rich protein (PfHRP2) into plasma. Quantitative measurement of plasma PfHRP2 concentrations may reflect the total parasite biomass in falciparum malaria. Hide abstract

Dondorp AM, Newton PN, Mayxay M, Van Damme W, Smithuis FM, Yeung S, Petit A, Lynam AJ, Johnson A, Hien TT, McGready R, Farrar JJ, Looareesuwan S, Day NP, Green MD, White NJ et al. 2004. Fake antimalarials in Southeast Asia are a major impediment to malaria control: multinational cross-sectional survey on the prevalence of fake antimalarials. Trop Med Int Health, 9 (12), pp. 1241-1246. Read abstract | Read more

To assess the prevalence of counterfeit antimalarial drugs in Southeast (SE) Asia. Hide abstract

Dondorp AM, Chau TT, Phu NH, Mai NT, Loc PP, Chuong LV, Sinh DX, Taylor A, Hien TT, White NJ, Day NP. 2004. Unidentified acids of strong prognostic significance in severe malaria. Crit Care Med, 32 (8), pp. 1683-1688. Read abstract | Read more

To calculate, using the Stewart approach to acid-base disorders, the strong anion gap as an estimate for the contribution of unmeasured plasma anions other than lactate to the metabolic acidosis that characterizes severe falciparum malaria and to assess its relative prognostic significance. Hide abstract

Dondorp AM, Pongponratn E, White NJ. 2004. Reduced microcirculatory flow in severe falciparum malaria: pathophysiology and electron-microscopic pathology. Acta Trop, 89 (3), pp. 309-317. Read abstract | Read more

The pathophysiology of severe falciparum malaria is complex, but evidence is mounting that its central feature is the old concept of a mechanical microcirculatory obstruction. Autopsy studies, but also in vivo observations of the microcirculation, demonstrate variable obstruction of the microcirculation in severe malaria. The principal cause of this is cytoadherence to the vascular endothelium of erythrocytes containing the mature forms of the parasite, leading to sequestration and obstruction of small vessels. Besides, parasitized red cells become rigid, compromising their flow through capillaries whose lumen has been reduced by sequestered erythrocytes. Adhesive forces between infected red cells (auto-agglutination), between infected and uninfected red cells (rosetting) and between uninfected erythrocytes (aggregation) could further slow down microcirculatory flow. A more recent finding is that uninfected erythrocytes also become rigid in severe malaria. Reduction in the overall red cell deformability has a strong predictive value for a fatal outcome. Rigidity may be caused by oxidative damage to the red blood cell membrane by malaria pigment released at the moment of schizont rupture. Anti-oxidants, such as N-acetylcysteine can reverse this effect and are promising as adjunctive treatment in severe malaria. Hide abstract