Symposium Updates Knowledge of Zika Virus and Countermeasures

Studies conducted over the past several years have produced remarkable strides pertaining to the Zika virus, and are driving research initiatives to combat future outbreaks, according to a symposium on the Zika virus presented on October 26 at the annual conference of the Infectious Diseases Society of America (IDSA) in New Orleans, Louisiana.

“Zika is the first virus that is known to cause birth defects in humans, and is the first mosquito-borne virus that is sexually transmitted,” Lyle Peterson, MD, MPH, director of Vector-Borne Diseases at the Centers for Disease Control and Prevention, in Atlanta, Georgia, said in his talk.

Zika has been around for a long time, with the first report dating back to 1947. Until 2007, only 14 cases had been reported. Subsequently, there have been three outbreaks, culminating with its arrival in the Americas in the 2015 epidemic in Brazil.

“Why is Zika spreading now? There are two reasons. The world’s population is becoming more urbanized and Aedes aegypti is an urban mosquito. The other is the number of international arrivals. In the 1950s, there [were] about 50 million international arrivals globally and now it is close to a billion, so it’s pretty easy to understand why a disease like Zika [is] spreading,” said Dr. Petersen.

Proven non-mosquito modes of Zika virus transmission include blood transmission; sexual contact involving male-to-female, female-to-male, and male-to-male; intrauterine transmission; and intrapartum transmission from a viremic mother to her newborn.

While Zika is infamous as a cause of microcephaly, the term congenital Zika syndrome was recently coined in recognition of other congenital anomalies associated with Zika virus infection during pregnancy, which also include intracranial calcifications. The pattern of onset of infection symptoms— including rash and newborn microcephaly– suggest that the first trimester of pregnancy is the time of highest vulnerability. Zika has also been linked with development of Guillain-Barré Syndrome.

“As of about a year ago we knew approximately nothing of Zika. The speed of development in this field in the past year has been astonishing. I think it is a testament to everyone involved, especially the interdisciplinary efforts,” said Helen Lazear, PhD, Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, during her talk.

In seeking to prevent the toll of future outbreaks, research by Dr. Lazaer and others has focused on revealing more of the characteristics of the infection, and on rapid and accurate means of detection. Detection has been hampered by the antigenic cross-reactivity that occurs between the Zika and Dengue viruses. The cross-reactivity may facilitate tissue invasiveness of the Zika virus, producing a more severe infection.

The jury is still out on whether contemporary Zika virus strains are more virulent than historical strains, but Dr. Lazear’s lab has identified a mutation present in the contemporary strain that may enhance invasiveness. Continued development and refinement of mouse models will help address the issue.

“There are lots of outstanding questions. What is the risk of Zika virus infection during pregnancy? How likely is viral transmission from mother to fetus? How does gestational age impact fetal outcome? What maternal factors contribute to fetal outcome? Can Zika virus cause neurological damage in adults? And why is a virus that used to be quite benign causing severe disease in this outbreak; does it involve host immunologic or genetic contributions, interactions with dengue virus antibody responses, or virus strain changes?” concluded Dr. Lazaer.

Countermeasures designed to prevent future outbreaks were discussed by Mark Mulligan, MD, director of The Hope Clinic Travel Well Center, Emory University, Atlanta, Georgia. These efforts require more knowledge. One initiative is the Zika in Infants and Pregnancy (ZIP) natural history study recently launched by the National Institutes of Health.

“In this study, 10,000 Latin American women will be enrolled. The study is enrolling now in Brazil and Puerto Rico. Women from other countries including Colombia will join. The impact of symptomatic and asymptomatic infections will be determined. Specimens will be collected monthly. [Researchers] will know when women become infected. They will track for maternal and fetal outcomes for up to a year after infection. This will be a really important study, I think, to get a better feel for what’s going on,” said Dr. Mulligan during the symposium.

One big goal is a vaccine to prevent infection with the Zika virus. “There is reason for optimism for a vaccine. We are not overconfident, but we are optimistic. One of the reasons is that there are a lot of other flavivirus vaccines,” said Dr. Mulligan.

Considerations for a vaccine include the effect of prior flavivirus immunity, vaccine-induced Guillain-Barré Syndrome, whether a vaccine will prevent viremia, which is important for pregnancy, and whether a vaccine can be developed in a timely manner.

Thinking ahead, in the early days after Zika vaccine development, if vaccine supplies are limited, Dr. Muligan suggested that recipients of a pre-pregnancy vaccine would include women of child-bearing age as well as their sexual partners. “We need to retool our thinking about Zika as a [sexually transmitted disease].” Once supplies became more robust, vaccination of the general population in an epidemic/endemic area could be contemplated, as could vaccination of travelers to these areas and commercial sex workers in these regions.

A phase I clinical trial is underway and is fully enrolled. The phase II VRC 705 randomized, placebo-controlled trial evaluating a DNA vaccine is slated to start at the beginning of 2017. Human studies assessing a vaccine preparation containing inactivated virus along with alum will begin soon. Other vaccines are in development.

Efforts to refine Zika diagnosis are challenged by a brief detection window of viral RNA and antibodies and the lack of distinctive symptoms between Zika, Dengue, and Chikingunya infections. PCR and molecular tests are being explored to surmount the diagnostic hurdle.

DISCLOSURES

All speakers: none

SOURCES

• Photos and tape of IDSA presentations
• CDC reports
• World Health Organization
• Donia MS et al. 2014. Cell 158:1402-1414
• Lee HH et al. 2010. Nature 467:82-85

PRESENTATIONS

Zika Symposium 1: Epidemiology, Virology & Countermeasures

• Zika Virus: Review of the Outbreak; Lyle R. Petersen, MD, MPH, Director, Division of Vector-Borne Diseases, United States Centers for Disease Control and Prevention
• Zika Virus: Virology & Pathogenic Mechanisms; Helen Lazear PhD, Department of Microbiology & Immunology, University of North Caroline School of Medicine, Chapel Hill, North Carolina
• Microbes, Infectious Disease, and the Future of Medicine; David Relman, MD, Stanford University School of Medicine, Stanford, California

Brian Hoyle, PhD, is a medical and science writer and editor from Halifax, Nova Scotia, Canada. He has been a full-time freelance writer/editor for over 15 years. Prior to that, he was a research microbiologist and lab manager of a provincial government water testing lab. He can be reached at hoyle@square-rainbow.com.