When the first patient came in complaining of joint pain, rash and conjunctivitis, or “red eyes,” W. Thane Hancock wasn’t sure what was causing the condition. He scribbled down “viral exanthem” as the diagnosis. (Exanthem is the medical term for rash.)

When another patient came in that same morning with identical symptoms, Hancock thought to himself, “that’s weird.” After lunch, a third patient presented with similar symptoms, he suspected something was going on. That’s when Hancock began to piece together what would become the world’s first reported outbreak of Zika virus infections.

It was 2007, and Hancock, who graduated in 2003 from the University of �鶹��ý at Mānoa (JABSOM), was only nine months into his job as a family doctor on the island of Yap, part of the Federated States of Micronesia. At the time he was the only U.S. trained physician working on the small Micronesian island.

Hancock, schooled in the “Problem-Based Learning” (PBL) curriculum at JABSOM, was accustomed to thinking broadly. When confronting a medical mystery, PBL students are taught not to rule out anything too early, but to list all possibilities, then plug away at eliminating possible causes one by one.

“The PBL process that encourages curiosity and a determination to find out what it is served me very well in Yap,” said Hancock, who grew up on �鶹��ý Island. “The curriculum at JABSOM emphasizes life-long learning,” said Hancock, and that is how he approaches every case.

For more on the story, .

—By Tina Shelton

Researchers at the (JABSOM) at the have successfully developed a vaccine candidate for the Zika virus, showing that it is effective in protecting both mice and monkeys from the infection.

Demonstrating the effectiveness of their vaccine candidate in monkeys (non-human primates) is an important milestone since it typically predicts whether the vaccine will work in humans, enabling further clinical development.

A strong global initiative to battle Zika has produced more than 30 vaccine candidates since outbreaks in 2015–2016 in Brazil linked the infection in some pregnant women to severe birth defects in their newborns. Zika is spread by the bite of infected mosquitos and through sex.

There is no treatment or cure for Zika nor is any vaccine currently approved for public use.

The proposed vaccine reported by scientists at JABSOM in the journals and , via the open access American Society for Microbiology journal, is a recombinant subunit vaccine that uses only a small part (protein) of the Zika virus, produced in insect cells.

“We believe our vaccine candidate shows much promise, particularly as it showed to require only two immunizations given three weeks apart and is a potentially safer alternative to other candidates already in clinical trials,” said , JABSOM assistant professor in and infectious diseases.

Lehrer thinks the vaccine his team proposes might be safer that other candidate vaccines, especially since pregnant women are a significant part of the target population for the Zika vaccine.

The JABSOM research team included two senior graduate students, and Albert To, who were lead authors of the scientific research papers.

Honolulu-based is a key partner in the vaccine development project with UH.

For the full story, see the .

—By Tina Shelton

A team has been awarded $484,750 to discover how Zika can hide in men’s bodies long after they are infected, posing a risk to their sexual partners. With the newly awarded funding, of the (JABSOM) and her team are partnering with Wake Forest University to study how “gatekeeper” cells that protect sperm cells succumb easily to Zika virus infection.

“As many as 56 percent of men still had the Zika virus in their seminal fluid for months after the virus had cleared other body fluids,” said Verma, an associate professor in JABSOM‘s . “That suggests the ability of the Zika virus to enter into the testes to establish persistent infection.”

This finding is alarming because typically the testes, so vital in reproduction, enjoy immunity from other viral infections.

Using cells made to resemble the testes at Wake Forest, the research team hopes to find a way to prevent Zika from breaking through immune barriers that normally stop viruses from infecting male reproductive organs.

“I believe that the key to curing testicular infection of viruses will be to know how the testes loses its unique immune privilege position in the human body,” explained Verma. “It is only when we understand the complexities of the interaction between the testis and testes-tropic viruses that we will be able to develop strategies and therapies to prevent or clear the infection quickly.”

The new funding is from the and the .

For the more, go to the .

—By Tina Shelton

With a $400,000 grant from the National Institutes of Health, infectious disease scientist , of the (JABSOM), will investigate the Zika virus in pregnant women. His goal is to develop strategies to prevent transmission of the disease to the fetus.

“We want to understand how the Zika virus is transmitted to the fetus, how the virus affects pregnancies and how Zika infection can impair infants, causing developmental delays and physical disorders,” said Kumar, an assistant professor with the at Mānoa JABSOM . He also will examine whether the timing of Zika virus infection during pregnancy affects the ability of the virus to cause fetal developmental abnormalities.

Kumar’s study builds upon his recent discovery that guinea pigs are susceptible to infection by a recent American strain of the Zika virus. His lab’s development of a guinea pig model is important because it indicates that Zika studies using guinea pigs should provide outcomes similar to those in humans.

“Ultimately, if the mechanisms by which the Zika virus transmits to the fetus and causes microcephaly are clarified, we can find a way to prevent in utero transmission of the Zika virus,” said Kumar.

�鶹��ý at risk for transmission

�鶹��ý is particularly at risk for transmission of Zika virus due to its year-round tropical climate favoring abundant mosquitoes, and attracting a high influx of visitors from all over the world including countries where Zika virus is endemic. Several cases of Zika virus have been reported in �鶹��ý. It is believed that these cases did not initially occur in �鶹��ý, yet the risk of mosquito transmission is real.

JABSOM scientists previously documented the first case of congenital Zika infection in the United States (born in �鶹��ý) in December 2015. In this case, a Zika virus-infected mother delivered a baby with microcephaly. The data also suggest the presence of Zika virus-positive cases and associated microcephaly in �鶹��ý as early as 2009, i.e., before the disease was medically recognized.

“The Zika virus research by Kumar and his tropical disease and pediatrics colleagues at the medical school is quite important for the health of the people and economy of �鶹��ý,” said , JABSOM dean. “We are very proud of these investigators’ dedication to reducing the devastating effects of Zika in unborn children around the world. And we are grateful for the support of �鶹��ý’s Congressional delegation to secure funding to promote this urgent goal.”

For full story please visit .

—By Tina Shelton

University of �鶹��ý at Mānoa (JABSOM) scientists have discovered that severe birth defects related to infection with the Zika virus (ZIKV) occurred much earlier than in 2016, when the connection was first made between the virus and an increased likelihood of microcephaly during outbreaks of ZIKV infection in Brazil and Puerto Rico.

UH scientists in the scientific journal , adding to the potential evidence of a link between ZIKV infection and microcephaly, a congenital condition associated with incomplete brain development and characterized by an abnormal smallness of the head.

• Related UH News story: , June 1, 2016

Patient information and blood samples were collected voluntarily from mothers in Honolulu who delivered babies between 2007 and 2013 at the , a �鶹��ý Pacific Health hospital affiliated with JABSOM. The samples were collected and stored at the (UHB) after obtaining written informed consent from the mothers.

“As per the information in the UHB, no mothers gave birth to babies with microcephaly in 2007 and 2008,” said , chair of the . “However, from 2009 onwards, we identified six mothers who gave birth to babies with microcephaly. Of the six, ZIKV antibodies were detected in three, fifty percent, of the mothers who delivered babies with microcephaly, suggesting presence of positive Zika virus cases and associated microcephaly in the United States as early as 2009.”

Potential changes to women’s health practices

Nerurkar believes the growing evidence of an association between ZIKV infection and the devastating brain damage in infants justifies a new practice in women’s health.

“We need to be more proactive in tracking pregnant women and testing for the ZIKV ahead of time (before birth),” he said. “It may be time for health care professionals to routinely caution newly pregnant mothers (or those planning to become pregnant) about the ZIKV, and offer pre-natal tests to detect for the presence of the virus.”

Ideally, Nerurkar said, families can plan for safe pregnancies by avoiding travel to areas of known ZIKV outbreaks. In 2016, the and have issued travel alerts about locations with confirmed, locally acquired Zika virus infections.

The UH researchers expressed their gratitude for the women who agreed to voluntarily donate blood and placenta samples to build the UH Biorepository archive. “This has been an indispensable resource in our research,” said Nerurkar.

Nerurkar leads a team of scientists at UH working to develop a vaccine for ZIKV infection as well as robust diagnostic assays to rapidly detect ZIKV and other mosquito-borne viral infections. After the award of a Zika emergency response grant this year from the , his team members are also working to understand how ZIKV infection in men makes them susceptible to transmit the virus to their sexual partners, even though the men may appear symptom-free.

• Related UH News story: , December 2, 2016

—By Tina Shelton

One of the newest, and potentially most worrisome, ways the Zika virus can spread is through unprotected sex. A scientist has received the first U.S. Zika-response funding in �鶹��ý to research how the Zika virus infection in men makes them susceptible to transmit the virus to their sexual partners, even though they may appear symptom-free.

“Clinical data shows that infectious Zika virus can be sexually transmitted by men long after the virus is cleared from their blood,” said Verma, an associate professor of with the . She believes Zika virus hides within specific cells unique to the testes, silently prolonging the infection.

Verma and her partners will work with human cells that form a blood-testes barrier. Normally, a blood-testes barrier protects the delicate germ cells from infection and resulting “immune attack” by the immune cells from the blood. They intend to demonstrate the extraordinary way by which the virus penetrates this barrier.

“We believe the Zika virus infects cells of the blood-testes barrier and induces inflammation. This response may trigger the disruption of the blood-testes barrier and allow the virus to eventually enter the inner compartment of the testes and establish persistent infection in the germ cells,” said Verma. “We have standardized an in vitro blood-testes barrier model that will be used as an innovative tool to address this study.”

Ultimately if the mechanism by which the Zika virus enters and remains persistent in the testes for several months is discovered, Verma wants to unlock a way for antiviral medicines to be used to clear Zika virus from the testes and being spread through sex.

“This tug of war between the mankind versus pathogen inspires me. The idea that new host or virus players continue to evolve in the microscopic battle between re-emerging viruses and human immune system fascinates me,” Verma said.

The grant was awarded by the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.

For more information, read the .

—By Tina Shelton

at the , has received a major grant to support his work to discover an effective treatment for Flavivirus infections, the leading cause of epidemic encephalitis (inflammation of the brain) worldwide.

There is no approved antiviral therapy available for treatment of flavivirus infections and they continue to spread globally, triggering illness and even death, including from infections tied to the West Nile, Japanese encephalitis, Zika and Dengue viruses.

This study will investigate the function of Schlafen4 in flavivirus infections and what causes these viruses to replicate and develop into disease. Results from this National Institutes of Health-funded study will delineate a new antiviral pathway and identify a novel host antiviral target for treatment of flavivirus encephalitis.

Kumar, an assistant professor at the and associate director of its Biocontainment facility, notes that �鶹��ý is particularly at risk for transmission of mosquito-borne viruses. “Our state’s year-round tropical climate favors abundant mosquitoes, and attracts a high influx of visitors from all over the world, including countries where these diseases are endemic,” said Kumar.

Kumar is collaborating with UH Mānoa colleagues , Chair of , and , Principal Investigator of the . , and are funding the study.

Developing therapeutic interventions

“Our long-term goal is to develop effective therapeutic interventions for the clinical management of mosquito-borne viruses,” said Kumar. Studies will be focused on development of specific SLFN4 inhibitor as a viable adjunct therapeutic option for clinical management of diseases caused by mosquito-borne viruses including West Nile virus, Japanese encephalitis, Dengue viruses and Zika virus.

Kumar is motivated in his research by close encounters with sufferers of these viruses, including among his family and close friends. “Having lived in the tropical climate my whole life, I have seen several cases of severe mosquito-borne illnesses, including deaths,” he said. “My goal has always been to use my expertise in the field of virology to develop effective therapeutics for these mosquito-borne illnesses.”

—By Tina Shelton

(NDPTC) at the University of �鶹��ý focuses on natural hazards like climate change and other threats to coastal and island communities. Under a cooperative agreement with the , , NDPTC has developed a short video in partnership with the and the University of �鶹��ý as part of its Just-in-Time Training initiative to promote awareness and deliver basic information about the Zika virus. The center has developed other Just-in-Time Training on tsunamis, volcanoes, and other emerging threats and hazards.

In this video, Sarah Park, state epidemiologist and chief of the �鶹��ý Department of Health’s Disease Outbreak Control Division, provides key information about the virus including its potential for spreading from an infected pregnant woman to her fetus causing birth defects and transmission via mosquitoes and through sexual contact.

Zika has been found in the Americas, Oceania/Pacific Islands, Africa and Asia. According to the Center for Disease Control, travel-associated cases of the Zika virus have been found in every U.S. state except Alaska and Wyoming, and in every U.S. territory except Guam and American Samoa. Locally acquired cases have been found in only Florida, American Samoa, Puerto Rico and U.S. Virgin Islands. It is spread by the bite of an infected Aedes species of mosquito (Aedes aegypti and Aedis albopictus). With the impact of climate change there has been a growth in regions that support mosquito habitats worldwide, increasing the world’s vulnerability to mosquito-borne diseases.

“We are particularly concerned about Zika and other mosquito-borne diseases because of their potential impacts on vulnerable, at-risk populations,” said , professor of at the and executive director of the National Disaster Preparedness Training Center. “We need to increase awareness of the disease but also work towards effective strategies for monitoring as well as combating Zika. As a global visitor destination, �鶹��ý needs a multi-pronged approach involving health care providers, urban planners, emergency responders, as well as households and businesses is needed to manage this health threat.”

Homeowners and businesses need to protect themselves against mosquitoes and implement effective programs for mosquito control. Training and education is needed to increase preparedness as well as response and mitigation capabilities.

NDPTC is committed to provide relevant and up-to-date training and education on the latest threats to our society.

The �鶹��ý State Board of Agriculture approved the University of �鶹��ý’s application to import live Zika virus so research into finding a vaccine can get under way at the (JABSOM).

The birth of two infants on Oʻahu in December 2015 to mothers infected with the Zika virus illustrated how little is understood about Zika, and sparked a sense of urgency among those who want to study and combat the virus. Of the two babies born in Honolulu—one born to a woman who was infected in American Samoa and the other to a woman infected in Brazil—only one infant had microcephaly, a condition that stunts the growth of the head, leaving inadequate room for the brain to fully develop and causing impairment to the child.

“What causes the virus in the mothers to cripple one baby and not the other?” asked , chair of the JABSOM Department of . “That is one of the mysteries we need to solve.”

Nerurkar and colleagues have applied for several grants through the National Institutes of Health and other agencies to begin their research in earnest. He expects to obtain the Zika virus sample within the next month or so. The sample will be kept in a highly secure laboratory and researchers will follow strictly enforced methods to ensure its safety as well as their own.

“We have a large department here at the Tropical Medicine, Medical Microbiology and Pharmacology, with a lot scientists and physicians who we work with in the community and at the Kapiʻolani Medical Center,” said Nerurkar. “Together we form a very good team and we have in-depth expertise of working with infectious diseases. I think this is a tremendous asset for the State of �鶹��ý. Our faculty, experts in virology and vaccines, also have a proven track record of collaboration with other institutions on the U.S. mainland. I believe strongly in collaborations and in hoping that these collaborations will lead to new vaccines.”

Read the .

—By Tina Shelton

The Zika virus is one of the latest threats the managed (PDC) is helping to combat with its global array of technological solutions and services.

The center has been monitoring and mapping outbreaks and providing regular products to the U.S. government as well as international agencies involved in the strategic response to the mosquito born disease. PDC’s DisasterAWARE platform includes not only easy visualization and integration of environmental and health data, but it’s also equipped with thousands of national and subnational infrastructure data, such as hospitals and airports, and observational data, such as accumulated rainfall.

The University of �鶹��ý was recently awarded a 5-year cooperative agreement by the to continue to serve as managing partner of the Pacific Disaster Center on Maui.

Helping �鶹��ý and the world

PDC delivers comprehensive disaster risk reduction solutions—including risk and vulnerability assessment and innovative tools and services—to disaster managers and the public to help avoid hazards becoming disasters and disasters becoming crises. The center’s software product is regularly used by primary disaster management agencies in �鶹��ý, by U.S. federal agencies such as the Departments of Defense, Homeland Security, and state, as well as by disaster management agencies in countries around the globe, and even by the United Nations. Customized versions of DisasterAWARE have also been delivered to agencies in Thailand, Vietnam, Indonesia and the Association of South East Asian Nations.

PDC Executive Director Ray Shirkhodai said, “This vote of confidence by the U.S. government in our work is a testament to the success of our entire team in advancing our mission. The capabilities of UH and RCUH have enabled us to meet the unique needs of our stakeholders and customers in �鶹��ý, throughout the U.S., among nations in Asia and beyond.”

Over the past nine years PDC has substantially increased its project funding beyond the base cooperative agreement, now matching its base funding each year through entrepreneurial business development with public and private partners in the U.S. and internationally. PDC has also expanded its services to include a new mobile application, Disaster Alert for Android and iOS, which has been downloaded more than 1.6 million times and is recognized globally as one of the premiere mobile apps for disaster information and management. PDC’s Global Hazards Atlas, a publicly available interactive map for hazard monitoring and early warnings, is another popular tool.

UH and PDC

UH has served as managing partner for PDC since 2006, when it was first selected through a competitive process to assume management responsibility. The agreement was again awarded to UH in 2009 for six years, and was renewed in 2015 for an additional five years. Additionally, based on the success of the program the new cooperative agreement was expanded from the base agreement of about $30 million to include a ceiling of $75 million for the performance period.

PDC principal investigator, UH System President David Lassner, noted, “This is a compelling example of how UH is helping �鶹��ý and the world. PDC offers some of the best high tech jobs on Maui, many of which go to our own student interns when they graduate. And every day the PDC team is making people safer through the deployment of PDC technologies, programs, education and training.”

For more photos, see the .

—By Kelli Trifonovitch