Academic Profile : Faculty

Assoc Prof Yeo Tsin Wen.jpg picture
Assoc Prof Yeo Tsin Wen
Associate Professor, Infectious Disease, Lee Kong Chian School of Medicine
Associate Professor, Lee Kong Chian School of Medicine
Associate Professor Yeo Tsin Wen is an Associate Professor at the Lee Kong Chian School of Medicine, Nanyang Technological University. A/Prof 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.
The main areas of research of A/Prof 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.

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. A/Prof 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. A/Prof 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.

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. A/Prof 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.
 
  • Antibiotic SteWARdS
  • Evaluation of Novel Diagnostic Platforms and Pathogenic Mechanisms of Tuberculous Meningitis and Central Nervous System Infections
  • Prevalence of resistance to new tuberculosis drugs:bedaquiline and pretomanid at a population level in Myanmar
  • The Role of the Endothelial Glycocalyx and Extracellular Histones in the Pathogenesis of Sepsis