The Newsroom • Published Wednesday, Oct. 30, 2013, 4:48 PM
The latest buzz on West Nile
The emergence of West Nile virus in the Western Hemisphere in 1999 poses an ongoing public health threat as the most common cause of epidemic encephalitis in the United States. Transmission occurs in a cycle involving mosquitoes, birds; horses, humans and other mammals. Human infections cause no symptoms in 80 percent of cases. West Nile fever develops in approximately 20 percent of infected patients. The fever can progress to neuroinvasive disease in a small number of cases. UTMB has been to studying the incidence of West Nile virus in the Houston metropolitan region for many years. Dr. Alan Barrett discusses recent findings with Jim Guidry of Guidry News Service.
The Newsroom • Published Friday, Aug. 23, 2013, 2:25 PM
A new treatment for tularemia
University of Texas Medical Branch at Galveston researchers have developed a new treatment that could be used against the bacteria that causes pulmonary tularemia, which has been identified as a potential bioterrorism agent.
Known as cystatin-9, the substance is one of a group of naturally occurring human proteins that function to moderate immune responses. In cell culture and mouse experiments, the researchers found that it also directly affected the bacteria responsible for tularemia, acting against them both in cultured macrophages (the immune cells that make up the first line of defense against invading bacteria) and mice.
“When we looked at cystatin-9 in the lungs with Francisella tularensis, we saw that it increased killing of the bacteria,” said associate professor Tonyia Eaves-Pyles, lead author of a paper on the work now online in Molecular Medicine. “Moreover, it did this without inducing the out-of-control immune response that generally accompanies tularemia 24 hours after the bacteria has been inhaled.”
That runaway immune response, Eaves-Pyles said, is more dangerous to the infected person than the infection itself, because it causes extensive tissue damage. But treatment with cystatin-9 moderates immune responses without completely shutting them down, allowing the immune system to continue fighting the bacterial invasion.
At the same time, cystatin-9 also has an effect on Francisella tularensis, disrupting the bacterial cell wall and making the bacteria less virulent. “So it’s two-fold,” Eaves-Pyles said. “Cystatin-9 is having effects on the host and it’s also having direct effects on the bacteria.”
Best known in connection with its natural hosts, rabbits, Francisella tularensis was weaponized by both the United States and the Soviet Union. Inhaling as few as 10 of the bacteria is enough to kill an untreated victim.
Prompt treatment with antibiotics can be effective, but the bacteria can go undetected by the host for 24 to 72 hours or longer after infection because the infection initially presents as cold or flu symptoms. This extended time allows the bacteria to replicate and spread out of the lungs, making it difficult to know in time whether a person has been exposed.
Eaves-Pyles envisions cystatin-9 being used as a prophylactic by U.S. military or other personnel in situations where they are likely to encounter aerosolized Francisella tularensis. The protein is small, easily produced and stable, making it particularly suitable for field applications.
In the lab, she expects it to lead to a better understanding of the interactions that govern immune responses to infection.
“Once we really start defining the mechanism of cystatin-9, we’re going to see how it affects protein changes., and those proteins may be able to be targeted specifically and used to better understand what is a protective immune response versus an unrestrained, damaging inflammatory response,” Eaves-Pyles said. “So I think it’s going to give us a lot of information not just about Francisella but other human pathogens as well.”
Other authors of the paper include research associates Jignesh Patel and Aaron Miller, associate professor Yingzi Cong, graduate students Anthony Cao and Eric Carlsen, professors Nisha Garg, Richard Pyles, Vsevolod Popov, Lynn Soong and Csaba Szabo, and postdoctoral fellow Ciro Coletta, all from UTMB; Emma Arigi and Igor Almeida of the University of Texas at El Paso; Bernard Arulanandam of the University of Texas at San Antonio; and Monisha Dhiman of the Central University of Punjab, India. This research was supported by the National Institutes of Health.
The Newsroom • Published Friday, Aug. 23, 2013, 2:23 PM
Tick by tick
When University of Texas Medical Branch at Galveston researchers set out to study Crimean-Congo hemorrhagic fever virus, they faced a daunting challenge.
The deadly virus requires biosafety level 4 containment, and it's carried by ticks. That meant that if scientists wanted to study the transmission of the virus, they had to do something that had never been done before: find a way to work safely with the tiny, tough bugs in a maximum containment “spacesuit lab.”
“It was completely new territory for us,” said UTMB assistant professor Dennis Bente, senior author of a paper describing the BSL4 tick work in Frontiers in Cellular and Infection Microbiology. “Ticks are very small, and in the BSL4 you have two pairs of gloves on, you have this bulky suit, you have the plastic visor-all these things are a huge handicap. So how do you make sure you contain them?”
The answer: step by painstaking step. Bente and his collaborators first attached small “feeding capsules” onto mice, and then placed ticks of a species that carries Crimean-Congo hemorrhagic fever virus into the capsules. Unlike mosquitoes that feed quickly and fly off, most ticks attach and feed slowly over the course of several days. Once the ticks were attached and began feeding, they and the mice were moved into a room in the Galveston National Laboratory BSL4 set aside for tick research.
There, in a sealed glove box lined with sticky tape to capture any ticks attempting to escape, the mice were inoculated with Crimean-Congo hemorrhagic fever virus. The feeding-capsule enclosed ticks, each of which, tick by tick, was individually accounted for at every stage of the experiment, then acquired the virus when they fed on the infected mice.
“We did hours upon hours of testing to get this system working,” Bente said. “We tested different types of sticky tape to determine the one that best inhibited the ticks' mobility, we tried different gloves, we tested the work flow, we checked to see how long a tick could last if you submerge it in disinfectant.” (The answer: more than 24 hours)
The result, Bente said, is a tool that will give researchers a crucial window into a virtually unknown aspect of one of the world's most widely distributed hemorrhagic fever viruses- a pathogen responsible for outbreaks from Greece to India to South Africa. “Ticks play such a vital role in the epidemiology of the disease - they're not only the vector but they are also the reservoir for the virus, yet nobody really knows what's happening to the virus in the ticks, because there's been no way to study it in the laboratory,” Bente said. “Now we can look at the complete transmission cycle in a controlled setting, examining how the virus is passed from infected animal to the uninfected tick, and from the infected tick to the uninfected animal. That's something that people studying this in the field haven't been able to do before now.”
Among other things, the new system will enable the researchers to study the virus' transmission by a variety of tick species. On the list are North American ticks, to investigate the possibility that Crimean-Congo hemorrhagic fever virus, like West Nile virus, could be introduced into the United States.
Other authors of the Frontiers in Cellular and Infection Microbiology paper include visiting scientist Aysen Gargili and assistant professor Saravanan Thangamani. This research was supported by the National Institutes of Health and the Department of Defense, National Biocontainment Training Center grant.
The Newsroom • Published Friday, Aug. 23, 2013, 2:38 PM
A virus changes its stripes
Outbreak in Panama brought Latin America’s first human cases of eastern equine encephalitis
In the summer of 2010, the eastern Panamanian province of Darien experienced a phenomenon that had never been seen before in Latin America: a human outbreak of eastern equine encephalitis.
The mosquito-borne virus that causes the disease is found all over the Americas, and infects horses throughout its range. Human infections are diagnosed every year in North America and are taken quite seriously; they carry a 50 percent chance of mortality, and can result in lifelong neurological damage. But 2010 marked a dramatic change in the way the virus behaved in Latin America.
“Until the Darien outbreak, we had become convinced that the virus in South America was fundamentally different in its ability to infect people and cause serious disease,” said University of Texas Medical Branch at Galveston professor Scott Weaver, senior author of a paper on the epidemic appearing in the August 22 issue of the New England Journal of Medicine. “This epidemic broke that dogma’s back very quickly.”
UTMB researchers collaborated with Panamanian scientists to investigate the outbreak, testing samples from 174 patients and many horses. In the end, they confirmed 13 human cases of eastern equine encephalitis and one case of dual infection of both eastern and Venezuelan equine encephalitis.
“We saw only about a one in 10 case-fatality rate in Panama, which is low by U.S. standards,” Weaver said. “Still, if this virus has changed and become more virulent for people, we need to know, number one, is it going to spread to other parts of Latin America or number two, are other Latin American strains likely to do the same thing?”
Weaver noted that earlier studies have shown that the eastern equine encephalitis virus is common in many Latin American locations where human exposure to virus-carrying mosquitoes is high. Since the virus is constantly mutating, it’s possible that a strain like the one seen in 2010 in Panama could take hold in an ecosystem in nearby Colombia, Ecuador or the Peruvian Amazon.
“With a situation where a lot of people are being exposed to the virus, there would be the potential for a lot of new disease,” Weaver said. “So it’s important to understand what’s happening in Panama both for the Panamanians and for people all over Latin America.”
Additional authors of the paper include Jean-Paul Carrera, Sandra Lopez-Vergés, Nestor Sosa, Yamilka Díaz, Davis Beltrán, Julio Cisneros and Alex Martínez-Torres of the Gorgas Memorial Institute of Health Studies, Panama; Ivan Abadía, Elizabeth Castaño, Carmen Báez and Dora Estripeaut of the Hospital del Niño, Panama; Hector Cedeño of the Ministry of Health, Panama; Humberto Hernandez of the Ministry of Agricultural Development, Panama; and UTMB assistant professor Naomi Forrester, research scientist Eryu Wang, postdoctoral fellows Amy Vittor and Andrew Haddow, research associate Amelia Travassos da Rosa and professor Robert Tesh. Support for this research was provided by the National Institutes of Health and the Secretaría Nacional de Ciencia, Tecnología e Innovación, Panama.
The Newsroom • Published Monday, Jul. 15, 2013, 2:32 PM
UT Regents names six UTMB ‘Outstanding Teachers’
The University of Texas System Board of Regents has awarded six faculty members at the University of Texas Medical Branch at Galveston with the board's highest honor in recognition of their performance in the classroom and their dedication to innovation and advancing excellence.
The Regents’ Outstanding Teaching Awards recognize faculty members at UT System institutions who have demonstrated extraordinary performance and innovation in the classroom and laboratory. The awards are among the largest in the nation, and given the depth and breadth of talent across the UT System, this awards program is also one of the nation’s most competitive.
“We are extremely proud of these members of our faculty,” said UTMB’s Dr. Danny O. Jacobs, executive vice president and provost, and dean of the School of Medicine. “They are committed to educational excellence and dedicated to our students.”
UT Regents chairman Gene Powell said the awards demonstrate the Board’s commitment to outstanding teaching. “These are world-class educators who are critical to the success of UT health institutions and who are critical to the ultimate success of their students. And the students they mentor and teach will become this state’s future outstanding health care providers,” he said.
This is the second year the Regents’ Outstanding Teaching Awards have been conferred to faculty at UT System’s six health institutions. Each of these faculty members will receive a $25,000 award.
Faculty members undergo a series of rigorous evaluations by students, peer faculty and external reviewers. The review panels consider a range of activities and criteria in their evaluations of a candidate’s teaching performance, including classroom expertise, curricula quality, innovative course development and student learning outcomes.
The Regents’ Outstanding Teaching Awards complement a wide range of system-wide efforts that underscore the Board of Regents’ commitment to ensuring the UT System is a place of intellectual exploration and discovery, educational excellence and unparalleled opportunity.
The UTMB Regents’ Outstanding Teaching Award recipients for 2013:
Dr. Judith F. Aronson
Professor and Vice Chairwoman for Education, Department of Pathology
My goals as a teacher are to instill enthusiasm for learning, to be a role model for lifelong learning and to provide moral support for learners. I aspire to be the "guide on the side," promoting active student engagement in tasks that yield a sense of discovery. I rejoice when a learner asks a question that I cannot answer, for it means that the learner has become curious about something and has formulated a detailed question with which to interrogate "the knowledge cloud."
Anne Hudson Jones
Professor and Harris L. Kempner Chair in the Humanities in Medicine, Institute for the
After decades of teaching I believe more than ever in the intrinsic worth and transformative potential of the humanities to help us understand what it means to be human, honor enduring values in a world of rapid technological change and aspire to virtue in our personal and professional lives. As a teacher, I am simultaneously an experienced guide and a fellow seeker who can learn from the thoughtful responses of others. Teaching and studying the humanities is an ongoing endeavor, the work and joy of a lifetime.
Brian T. Miller
Distinguished Teaching Professor, Division of Anatomy, Department of Neuroscience and Cell Biology
In my experience, the most effective teachers are those who possess a profound knowledge of their subject and have the ability to synthesize, organize and present complex information in an engaging and lucid manner. Moreover, such teachers continually strive to demonstrate how to develop and use the knowledge and skills that will be critical to their students’ professional success.
Linda R. Rounds
Professor, Betty Lee Evans Distinguished Professor in Nursing
Distinguished Teaching Professor, School of Nursing
I believe that education on any level is a collaborative process enriched by the experiences and contributions of both faculty and students. Faculty should be learners as well as teachers in this process. My goal is to create learning experiences that are interesting, innovative and stimulating such that the student develops an interest in continuing to learn more in a course or a lifetime.
Dr. Judith L. Rowen
Associate Dean for Educational Affairs and Professor, Department of Pediatrics
I love what I do, and as an infectious disease physician I believe enthusiasm is contagious. Whenever I teach, whoever the learners may be, I strive to make the encounter fun. By the same token, I hold my trainees to high standards. I believe it is an amazing privilege to be a physician and have patients invite us into their lives. I try to instill that same passion and sense of awe in those I teach.
Laura L. Rudkin
Professor, Preventive Medicine and Community Health
Academics who approach their teaching duties as a form of scholarship will think more carefully about the end goals of curricula. In our programs, we aim to produce competent and caring health care professionals and researchers who will act to improve individual and population health and reduce health disparities. To quote a Carnegie Foundation report, we educate students “to contribute to the life of their times.”
View all of the UT System award recipients at http://www.utsystem.edu/teachingawards/.
Newsroom • Published Thursday, Jun. 13, 2013, 10:12 AM
The UTMB researcher receives funding to study deadly viruses
Work will focus on vaccine for Ebola and Marburg and immune response
University of Texas Medical Branch at Galveston associate professor Alexander Bukreyev has embarked on two major federally funded investigations into the Ebola and Marburg viruses.
In the first, supported by a five-year $3.5 million grant from the National Institutes of Health, Bukreyev will work to develop a new needle-free aerosol vaccine designed to protect against both viruses. No effective vaccine or therapy currently exists for either Ebola or Marburg; both have high mortality rates and have been implicated in numerous recent outbreaks in Central Africa.
Also working with Bukreyev on the project will be UTMB professors Thomas Ksiazek and Thomas Geisbert.
Blood samples taken from survivors of Ebola and Marburg outbreaks will form the basis of Bukreyev’s second recently funded project, a five-year $1.8 million Defense Threat Reduction Agency contract to investigate human immune responses to infections by the viruses.
Bukreyev will be collaborating with Dr. James Crowe of Vanderbilt University on the project, in which monoclonal antibodies — copies of molecules made by the immune system to target specific pathogens — will be used to explore the natural defenses mounted by Ebola and Marburg survivors against the viruses.
“One of the most striking features seen in most Ebola and Marburg infections is the lack of protective immune response,” Bukreyev said. “Some patients do mount a successful response, however, and in the clinical component of this exciting study we’ll be investigating the molecular and genetic components involved in this process.”
The Newsroom • Published Wednesday, Jun. 12, 2013, 4:32 PM
What’s the buzz on this year’s West Nile season?
Last summer’s West Nile fever season came as a rude awakening for most Americans — and in particular, for residents of Dallas and Fort Worth, Texas.
The Dallas-Fort Worth area was the epicenter of 2012’s unprecedented resurgence of the mosquito-borne virus, which had been relatively inactive during the previous four years. Dallas-Fort Worth accounted for the majority of West Nile activity in Texas, and the Lone Star State had more than a third of the nation’s total West Nile infections.
Why Dallas-Fort Worth, and why Texas? And what should we expect from the virus in the coming summer?
The answer to the first question, according to researchers: it’s complicated. And to the second: we don’t know, but we should be ready anyway.
“When this happened there were immediate suggestions that some specific change must have caused this — that the virus had suddenly become more virulent, or that a particular environmental factor was to blame,” said University of Texas Medical Branch at Galveston associate professor David Beasley, the lead author of a commentary on the resurgence now online in Antiviral Research. “However, from what has been reported about the 2012 outbreak so far, it seems that not much had changed at all — we just got the right confluence of factors that were needed for more intense transmission of virus.”
Human West Nile infections arrive via a circuitous path that involves not just mosquitoes, but also birds. In fact, researchers consider the passage of West Nile from mosquito to bird and back again to be the virus’ primary cycle; humans are generally infected after being bitten by mosquitoes that have fed on birds, whose blood contains high concentrations of the virus.
According to Beasley, the North Texas West Nile outbreak likely involved both mosquito-friendly climate conditions that resulted in an abundance of the species of mosquitoes that carry West Nile in Texas and the presence of large numbers of birds capable of being infected by the virus. Add in reduced human concern about the risk of infection — a result, in part, of the four-year lull in West Nile activity — and you have everything you need for a viral version of a “perfect storm” in Dallas-Fort Worth.
“It could just as easily have happened in any number of U.S. cities,” Beasley said. “Ultimately, it comes down to having infected mosquitoes and having susceptible amplifying hosts, which are the birds, and putting them in the same place as a large number of people who aren’t really paying much attention to whether they’re being bitten or not.”
In essence, then, it’s a matter of complicated odds: if the climatological, ecological and behavioral factors line up right, you’ve got a good chance of a bad summer for West Nile. But, since so many different variables are involved, it’s nearly impossible to predict exactly what will happen in advance.
“It’s kind of like predicting the weather,” Beasley said. “You can have a general idea about what’s likely to happen, about what locations have higher overall risks based on historical data, and you might be able to detect the early indicators of something that’s out of the ordinary. But predicting with weeks or months advance notice that something bad will happen this year or next year in a particular geographic area is certainly beyond what we can do now.”
That uncertainty makes it all the more important that West Nile surveillance programs are maintained, even during long periods in which the virus seems to have become dormant.
“West Nile is not going to go away,” Beasley said. “Activity may decline for a while, but that doesn’t mean we can forget about it, because we’re going to periodically see this kind of resurgence, and we have to be able to detect increased activity to give public health people a chance to respond, whether that’s with mosquito control or by raising public awareness.”
The Newsroom • Published Thursday, May. 2, 2013, 1:42 PM
Ebola’s secret weapon revealed
Researchers have discovered the mechanism behind one of the Ebola virus’ most dangerous attributes: its ability to disarm the adaptive immune system.
University of Texas Medical Branch at Galveston scientists determined that Ebola short-circuits the immune system using proteins that work together to shut down cellular signaling related to interferon. Disruption of this activity, the researchers found, allows Ebola to prevent the full development of dendritic cells that would otherwise trigger an immune response to the virus.
“Dendritic cells typically undergo a process called ‘maturation’ when they’re infected by a virus — they change shape and present antigens on their surface that tell T-cells to attack that particular virus, thus generating an adaptive immune response,” said UTMB professor Alexander Bukreyev, senior author of a paper on the discovery now online in the Journal of Virology. “But Ebola prevents dendritic-cell maturation and produces a severe infection without an effective adaptive immune response. We found that its ability to do this depends on several specific regions of two different proteins.”
Bukreyev’s research group made the discovery after a series of procedures that started with a clone of the Ebola Zaire virus strain. Working under maximum-containment conditions in a biosafety level 4 facility in UTMB’s Galveston National Laboratory, the team introduced mutations into the virus’ genetic code at four locations thought to generate proteins that affected immune response.
They then infected human dendritic cells with each of the resulting new strains and compared the results with those produced by unmutated Ebola Zaire. Each of the four new viruses, they found, was unable to suppress dendritic-cell maturation.
“We saw two very interesting things,” Bukreyev said. “First, that these mutations restore maturation of dendritic cells very effectively, and second, that a mutation in even one of these genetic domains makes the virus unable to suppress maturation. That means that the virus needs multiple combined effects in order to undermine the immune system in this way.”
Ebola’s ability to evade the human immune response is one of the factors that accounts for its high mortality rate — up to 90 percent in humans — and the notoriety that it gained after its first appearance in Zaire in 1976, in an outbreak that killed 280 people. Zaire — now the Democratic Republic of the Congo — is the home country of Ndongala Lubaki, lead author on the paper and a postdoctoral fellow at UTMB.
Other authors of the Journal of Virology paper include postdoctoral fellow Phillipp Ilinykh, assistant research lab director Collette Pietzsch, research scientist Bersabeh Tigabu, assistant professor Alexander Freiberg and Richard Koup of the National Institute of Allergy and Infectious Diseases Vaccine Research Center. This research was supported by the John Sealy Memorial Endowment Fund and the James W. McLaughlin Endowment.