Winter 2019
Melioidosis

synapse: University of Nevada, Reno School of Medicine

Dean Thomas Schwenk at UNR

The melioidosis research team. From left: Paul Brett, Ph.D., co-principal investigator and associate professor, microbiology and immunology; Laura Meadows, staff research associate III; James Pazar, molecular microbiology and immunology undergraduate student; Teresa Shaffer (seated), postdoctoral researcher; Lindsey Schmidt, cell and molecular biology graduate student; Caitlyn Orne, cell and molecular biology graduate student and Mary Burtnick, Ph.D., co-principal investigator and associate professor, microbiology and immunology. Photography by Brin Reynolds

Brett and Burtnick research team working to redefine the impact of a deadly global disease with the help f $4.1M in funding

By Tessa Bowen

Global health threats from infectious diseases emerge almost yearly. Epidemics are more likely to impact the poorest countries in the world who lack strong health care resources, especially in rural areas.

According to the World Health Organization, the world will be short 12.9 million health care workers by 2035; that figure currently stands around 7.2 million. A WHO report warns that the findings, if not addressed now, will have serious implications for the health of billions of people across all regions of the world.

Countries with a serious deficit of health workers and who are under-resourced economically have a harder time containing the spread of infectious diseases. The spread of outbreaks is not only explained by the pathology of the disease, but by economics.

melioidosis professor writing on a whiteboard

RECOGNIZING A PUBLIC HEALTH CRISIS

While most of the world's focus has been on well-known bacterial pathogens and viral epidemics such as cholera, plague, avian flu, Ebola and Zika, other lesser known pathogens with significant disease-causing potential continue to emerge with deadly effects leaving dangerous gaps where no vaccines exist.

One such under recognized and under reported disease is melioidosis, also called Whitmore's disease. "This emerging infectious disease is caused by Burkholderia pseudomallei, a bacterium found in contaminated water and soil, that is being increasingly recognized in tropical regions around the world," said Paul Brett, Ph.D., co-principal investigator and UNR Med associate professor of microbiology and immunology. "Bacteria thrive in environments such as rice paddies, still or stagnant waters, and moist soils."

While rare in the United States, melioidosis is causing a public health crisis in areas with tropical climates. Known to be endemic in northern Australia and at least 48 countries in Asia, the Middle East, Africa, Central America and South America, researchers at UNR Med predict that the disease may be more widespread than formerly known, due to being under reported.

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 of leptospirosis and dengue fever, highlighting the potential worldwide impact of the disease.

The bacterium responsible for causing melioidosis is naturally resistant to many commonly used antibiotics, which makes the disease difficult to treat. According to the Centers for Disease Control and Prevention (CDC), without treatment, up to 9 out of every 10 people who get it will die.

Humans can acquire infections through skin abrasions, inhalation of bacteria in aerosolized dust or water or ingestion of contaminated water. Diagnosing melioidosis can be difficult. Symptoms and conditions ranging from skin abscesses and muscle soreness to respiratory distress and septicemia can be mistaken for other diseases such as tuberculosis or pneumonia. Most infections occur in individuals with one or more risk factors, such as diabetes, alcoholism, chronic pulmonary disease, chronic renal disease or thalassemia, a blood disorder.

A diagnostic method for melioidosis was recently developed by David Aucoin, Ph.D., UNR Med associate professor and chair, microbiology and immunology. Aucoin has developed a rapid diagnosis test for the devastating bacterial infection. Prior to Aucoin's method, it took six days to diagnose the infection. Aucoin's test can diagnose the infection in 15 minutes so doctors can prescribe the right antibiotics.

While faster diagnoses has the potential to save thousands of lives, melioidosis treatments remain costly and time consuming. As a result, a significant need for a vaccine that does not exist has surfaced.

Lab TestingPROTECTING THOSE WHO PROTECT US

Along with tremendous consequences for local communities, infectious diseases also have a great impact to the military who serve there. Just like Americans rely on the U.S. military to keep them safe from humans who could do them harm, the U.S. military and Department of Defense often relies on academia and researchers to protect them from microscopic villains such as deadly viruses and bacteria.

U.S. service members often deploy to global areas with widespread infectious diseases and other dangerous pathogens. When troop infections happen, they require costly, time-consuming medical leave and hospitalizations. Effective new vaccines can ensure healthier troops, better-operating units and improved military readiness.

In addition to being an important public health concern, the bacteria that cause melioidosis could be used in a biological attack through intentional release of germs that can sicken or kill people or livestock. Burkholderia pseudomallei, the causative agent of melioidosis is considered a potential biological weapon and is currently categorized as a tier 1 select agent by the U.S. CDC.

"In the event of an intentional release, it is believed that the most likely mode of dissemination would be via infectious aerosols that would lead to respiratory disease," said Brett.

PRODUCING A LEAD VACCINE CANDIDATE

Since B. pseudomallei is resistant to many conventionally used antibiotics, treatment of melioidosis can be complicated. The development of medical countermeasures to combat melioidosis has become a priority for Brett, and co-principal investigator, Mary Burtnick, Ph.D., both associate professors of microbiology and immunology. Under their leadership, a UNR Med research team is well into the process of developing a novel melioidosis vaccine that currently does not exist anywhere in the world.

And it is demonstrating promising results. Brett and Burtnick's work is receiving $4.1 million in research funding over the next three years from the Defense Threat Reduction Agency (DTRA), a combat support and defense agency within the United States Department of Defense, to further the development of a vaccine.

"An ideal melioidosis vaccine would be one that provides long-term protection against the most severe forms of the disease, namely, acute pneumonia and septicemia, and broad-spectrum protection against multiple B. pseudomallei strains," said Brett.

Brett and Burtnick point out two primary motivators for developing and delivering quality medical capabilities for treating and sustaining the health of people living a half a world away. One is the significant morbidity and mortally rate of melioidosis, and two, is soldier protection. 

"The new DTRA contract will support efforts to advance our lead vaccine candidate towards human clinical trials which will hopefully result in a countermeasure for protecting service members deployed to endemic areas, as well as be useful as a public health vaccine," said Brett. "UNR Med is an excellent environment for us to conduct this type of research."

"Under recognition of melioidosis is due to most cases occurring in resource-poor countries with large rural populations and limited microbiological laboratory capabilities," said Brett.
Laboratory capabilities, the infrastructure for research development, along with the participation of both undergraduate and graduate student minds who infuse research work with creative new ideas and energy, are the foundation for a strong pipeline of next generation human capital.

It is all of that, which positions the University of Nevada, Reno and UNR Med for furthering cutting-edge research with national support and investment of DTRA's magnitude.
"Our Centers for Disease Control and Prevention (CDC) approved tier 1 biosafety level (BSL) 3 lab at UNR Med and our multidisciplinary research program is enabling collaborations between the School of Medicine and basic sciences, so the project is gaining a lot of momentum," said Brett.

That momentum, Burtnick added, includes a "very strong pool of students" across several disciplines. "What's really attractive for students is that our research is multidisciplinary. We use a variety of techniques including bacterial genetics, host pathogen interaction studies, glycobiology, chemistry and immunology. Students learn how to become proficient at melding microbiology and immunology together."

Individuals working on the melioidosis project include two cellular molecular biology graduate students, a molecular microbiology undergrad and a post doc. An additional post doc will be arriving in January, from Thailand who is choosing to join UNR Med to continue working on melioidosis and to learn about vaccine development.

"Another benefit of the DTRA contract is job creation," said Burtnick. We've filled four positions, giving us the opportunity to groom the next generation, which in turn further grows our research."
Student researchers are involved in assessing the immunogenicity of lead vaccine formulations in mice, as well as feeding the vaccine pipeline with new candidates. Burtnick said "during this process vaccine formulations are continuously being refined and optimized."

"The research led by Brett and Burtnick here at UNR Med is not only relevant for protecting our soldiers, but is positively impacting global health and improving the quality of life around the globe," said UNR Med Dean, Thomas L. Schwenk, M.D. "The support and investment of DTRA is further testament to the dedicated work they are doing and will continue to enhance the competitiveness of our faculty and the growth of our research, making a difference in the lives of many."