Associate Professor Yeo Tsin Wen

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​Associate Professor Yeo Tsin Wen
Associate Professor of Infectious Disease
Principal Investigator, Malaria, Tuberculosis and Global Health Laboratory

Dr Yeo Tsin Wen is an Associate Professor at the Lee Kong Chian School of Medicine, Nanyang Technological University. Dr Yeo graduated from the National University of Singapore, and went on to complete an internal medicine residency at the University of Hawaii as well as an infectious disease fellowship at the University of Utah. He did his PhD at the Menzies School of Health Research and University of Queensland on the treatment and pathogenesis of severe malaria based in Indonesia Papua. Upon completion of his PhD, he worked as a research fellow at the Menzies School of Health Research and as an infectious physician at Royal Darwin Hospital in Australia.

Research Focus

The main areas of research of Dr Yeo’s laboratory include clinical and epidemiological studies of malaria including the three species most prevalent in South East Asia, namely Plasmodium falciparum, Plasmodium vivax and Plasmodium knowlesi. Other ongoing interests include clinical studies of central nervous system infections with a focus on developing improved diagnostic strategies and delineating the pathogenic mechanisms of tuberculous meningitis. These studies are being conducted in Bangladesh, Indonesia, Malaysian Borneo and Tanzania, in collaboration with various institutions including the Malaysian and Sabah Ministry of Health; Menzies School of Health Research, Darwin, Australia; Duke University, USA; University of Utah, USA; Queensland Institute of Medical Research, Brisbane, Australia; London School of Hygiene and Tropical Medicine and the Mahidol-Oxford Research Unit, Bangkok, Thailand.

Research Aims in Plasmodium falciparum

Severe falciparum malaria has a mortality rate of 15 to 20 percent and is responsible for 600,000 deaths annually despite anti-malaria therapy. Developing adjunctive agents could lead to improved outcomes but will require identification of targets by improved delineation of the pathogenic mechanisms of severe malaria which remains unclear. Dr Yeo’s laboratory intends to conduct clinical and bedside studies in endemic countries to better describe the microvascular, metabolic and immunological perturbations that may mediate disease severity in falciparum malaria. Dr Yeo also intends to conduct clinical trials of adjunctive agents to improve mortality in falciparum malaria focusing on methods to improve the vascular and systemic bioavailability of nitric oxide (NO), which are found to be decreased in severe disease.

Research Aims in Plasmodium knowlesi

Plasmodium knowlesi is a simian malaria only recently discovered in 2004 to cause widespread infections in humans. Clinical infections of patients with Plasmodium knowlesi have been described in South-East Asian and Southern China countries. During this short time, it has become the major cause of human malaria in both Peninsular Malaysia and Malaysian Borneo with over 2000 cases annually. In studies from Malaysia, patients infected with P. knowlesi had a higher risk of severe disease compared to P. falciparum, which was thought to be the most lethal form of malaria. Dr Yeo laboratory’s current studies are conducted in Malaysian Borneo and they include:

1) The first randomised control trial comparing artemisinin combination therapy (ACT) and chloroquine for the treatment of uncomplicated knowlesi malaria. Currently there are no clinical studies evaluating the efficacy of these antimalarials in the knowlesi malaria. There are also no recommendations in the World Health Organization Guidelines on the treatment of knowlesi malaria.

2) Studies to better understand the pathogenic mechanisms of severe disease in knowlesi malaria and to compare these to falciparum. The studies will include combined host studies including measurements of microvascular disease, rheological alterations, and immune and cytokine responses. Genomic analysis of the host and pathogenic responses to look at the host and parasite factors that may mediate infectivity and disease severity. This can also be used to assess for the possibility of human to human transmission which has been demonstrated under experimental conditions.

3) A case control study to identify the epidemiological risks factors which increase the risk of being infected with Plasmodium knowlesi. This study is being done as part of a multi-disciplinary study which includes entomology, primatology, land use and the social sciences.
Tuberculous Meningitis

This is the most severe form of extra-pulmonary tuberculosis with a mortality rate of 30-40 percent. Our research aims include:

1) Developing techniques to improve the diagnosis of tuberculous meningitis including metabolic assays to identify novel identifiers in the cerebrospinal fluid

2) To deepen the understanding of pathogenic mechanisms of tuberculous meningitis including vascular thrombosis, which is a late complication. This will be done by measuring in the cerebrospinal fluid of patients with tuberculous meningitis, various inflammatory mediators including cytokines and matrix metalloproteases which may mediate early inflammation, and neutrophil extracellular traps which may a play a role in thrombosis.
Key Publications

1. Yeo TW, Lampah DA, Gitawati R, Tjitra E, Kenangalem E, McNeil Y , Darcy C, Lopansri B, Granger DL, Weinberg JB, Price RN, Duffull SB, Celermajer DS, Anstey NM. (2007).  Impaired nitric oxide bioavailability and L-arginine reversible endothelial dysfunction in adults with falciparum malaria. Journal of  Experimental Medicine. 204:2693-2704.

2. Yeo TW, Daniel A Lampah, Retno Gitawati, Emiliana Tjitra, Enny Kenangalem, Kim Piera, Ric N Price, Stephen B Duffull, David S Celermajer, Nicholas M Anstey. (2008). Angiopoietin-2 is associated with decreased endothelial nitric oxide and poor clinical outcome in severe falciparum malaria. Proceedings of the National Academy of Science. 105:17097-17102.

3. Yeo TW, Lampah DA, Tjitra E, Gitawati R, Darcy CJ, Kenangalem E, McNeil YR, Granger DL, Lopansri B, Weinberg JB, Price RN, Duffull SB, Celermajer DS, Anstey NM. (2010). Increased asymmetric dimethylarginine in severe falciparum malaria: Association with impaired nitric oxide bioavailability and fatal outcome. PLoS Pathogens. 6:e1000868.

4. Bridget E Barber, Timothy William, Matthew J Grigg,  Uma Parameswaran,  Kim A Piera, Ric N Price, Tsin W Yeo, Nicholas M Anstey. (2014). Parasite biomass-related inflammation and endothelial activation, microvascular dysfunction and disease severity in vivax malaria. PLoS Pathogens. (In Press).

5. Barber BE, William T, Grigg MJ, Menon J, Auburn S, Marfurt J, Anstey NM, Yeo TW. (2013). A prospective comparative study of knowlesi, falciparum and vivax malaria in Sabah, Malaysia: High proportion of severe disease from Plasmodium knowlesi and P. vivax but no mortality with early referral and artesunate therapy. Clinical Infectious Diseases. 56: 383-97.

6. William T, Menon J, Rajahram G, Chan L, Ma G, Donaldson S, Khoo S, Frederick C, Jelip J, Anstey NM, Yeo TW. (2011). Severe Plasmodium knowlesi malaria in a tertiary care hospital, Sabah, Malaysia. Emerging Infectious Diseases.17; 1248-55.

7. Yeo TW, Lampah DA, Gitawati R, Tjitra E, Kenangalem E, McNeil Y , Darcy C, Lopansri B, Granger DL, Weinberg JB, Price RN, Duffull SB, Celermajer DS, Anstey NM. (2008). Recovery of endothelial function in severe falciparum malaria is associated with improvement in plasma L-arginine and blood lactate concentrations. Journal of Infectious Diseases. 198:602-8.

8. Yeo TW, Lampah DA, Tjitra E, Gitawati R, Kenangalem E, Piera K, Granger DL, Lopansri B, Weinberg JB, Price RN, Duffull SB, Celermajer DS, Anstey NM. (2009). Relationship of cell-free hemoglobin to impaired endothelial nitric oxide bioavailability and perfusion in severe falciparum malaria. Journal of Infectious Diseases. 200:1522-9.

9. Yeo TW, Lampah DA, Tjitra E, Piera K, Gitawati R, Kenangalem E, Price RN, Anstey NM. (2010). Greater endothelial activation, Weibel-Palade body release and host inflammatory response to Plasmodium vivax, compared with Plasmodium falciparum: A prospective study in Papua, Indonesia. Journal of Infectious Diseases. 202:109-112.

10. Yeo TW, Lampah DA, Kenangalem E, Tjitra E, Price RN, Anstey NM. (2013). Impaired skeletal muscle microvascular function and increased skeletal muscle oxygen consumption in severe falciparum malaria. Journal of Infectious Diseases. 207: 528-36.