VALID8

Dr Paul Brett is a Professor at the  University of Nevada, Reno School of Medicine. In this VALID8, Paul discusses his work on melioidosis, a disease so neglected it is still yet to be placed on the official list of Neglected Tropical Diseases.

1 - Who are you?

I am a VALIDATE Network Investigator, a Professor in the Department of Microbiology and Immunology at the University of Nevada, Reno School of Medicine, USA and an Adjunct Professor in the Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Thailand.

2 - What do you do? / What do you research?

Research in my laboratory is focused on elucidating the molecular mechanisms used by Burkholderia pseudomallei, the causative agent of melioidosis, to evade clearance by host immune defences. In particular, I am interested in determining how the lipopolysaccharides and capsular polysaccharides expressed by this important bacterial pathogen contribute to this process. The main goal of my research is to identify correlates of antigen-induced immunity against B. pseudomallei and use this information to develop safe, affordable and effective melioidosis vaccines.

3 - What is melioidosis?

Melioidosis is an emerging infectious disease that is being increasingly recognized in tropical regions around the world. Humans can acquire infections via several different routes including percutaneous inoculation, inhalation and ingestion. Clinical presentations of melioidosis are diverse, ranging from skin abscesses to acute pneumonia and septicemia which can make diagnosis difficult. The organism is also naturally resistant to a variety of antibiotics and there is high mortality associated with acute forms of the disease. At present, there are no licenced vaccines available to combat disease caused by B. pseudomallei.

4 - How does melioidosis affect developing countries?

Melioidosis is being increasingly recognized as an important cause of morbidity and mortality worldwide. In 2015, the estimated total global burden of human melioidosis was ∼165,000 cases with ∼89,000 deaths, which is equivalent to the number of deaths attributed to measles and exceeds the levels for leptospirosis and dengue virus infection, underscoring the impact of the disease worldwide. Under recognition of melioidosis is due, in part, to the fact that most cases occur in resource-poor countries with large rural populations and limited microbiological laboratory capabilities. B. pseudomallei infections can also be difficult to treat and require intravenous ceftazidime or meropenem for up to 2 weeks, followed by 3 to 6 months of oral trimethoprim sulfamethoxazole.

5 - What is the most interesting thing you have learned about melioidosis?

B. pseudomallei is a remarkable pathogen that causes severe disease in both humans and animals. It can infect virtually any tissue in the body and lead to a broad spectrum of diseases that can be easily mistaken for other illnesses. Because of this, B. pseudomallei has often been referred to as the “great imitator”.

6 - Why are vaccines important in the fight against melioidosis?

Vaccines are a triumph of medicine that has improved the lives of countless individuals worldwide. A safe and affordable melioidosis vaccine would be an effective means of reducing morbidity and mortality in areas of the world where B. pseudomallei is endemic thus helping to improve the quality of life of people living in these regions.

7 - What are the main challenges to your research?

B. pseudomallei is a facultative-intracellular, Gram-negative pathogen that exhibits both extracellular and intracellular lifestyles. Because of this, the development of effective melioidosis vaccines is quite challenging. Based on findings from my laboratory and others, it is likely that we will need to identify vaccine formulations that are capable of stimulating both protective humoral and cellular immune responses to achieve robust protection against B. pseudomallei infections.

8 - How does VALIDATE help you?

VALIDATE brings together a variety of vaccine experts from around the world. This provides me with an excellent opportunity to network and collaborate with others towards our common goal of developing safe and effective vaccines to prevent tuberculosis, leprosy, melioidosis and leishmaniasis. It also provides me with an opportunity to promote awareness of melioidosis which is so neglected that it is not even on the list of neglected tropical diseases.

Find out more

You can find more about Paul's research on his VALIDATE biography page.

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