Clinicians Struggling With What to Advise About Zika

Alicia Ault

February 17, 2016

WASHINGTON, DC — With so little known about Zika virus, clinicians are struggling with how to guide their patients.

"I'm sitting in a very small room with a couple that wants answers," said Laura Elizabeth Riley, MD, director of Obstetrics and Gynecology Infectious Disease at Massachusetts General Hospital in Boston. She's relying on the Centers for Disease Control and Prevention's Zika guidance and her own knowledge, she said. "I'm trying to put it all together," but it's not enough.

Dr Riley told Medscape Medical News that she has had an uptick in patient visits. "It's a major panic," she said. She has conducted 50 immunoglobulin M antibody tests for Zika, with zero positives. Only four patients had symptoms suggestive of Zika.

She and other physicians have many questions, which they shared with attendees at the National Academies of Sciences' workshop held here yesterday on "Research Priorities to Inform Public Health and Medical Practice for Domestic Zika Virus."

How do they know that a negative antibody test in a pregnant woman who has been exposed to the Zika virus is truly a negative? How often should they repeat ultrasounds? What is the prognosis for a fetus with microcephaly? What can they tell patients about the potential for the virus to be transmitted through breast milk? Now that the virus has been found in semen, should they tell women to abstain from intercourse with a potentially infected partner? For how long?

Those are all "questions that clinicians need to be able to answer," said Lynn Goldman, MD, Michael and Lori Milken Dean of Public Health at the Milken Institute School of Public Health at George Washington University in Washington, DC, who led a group of physicians in formulating concerns and research recommendations.

More Unknowns Than Knowns

It was clear, however, that questions outweigh answers. Epidemiologists, infectious disease specialists, and zoonotic virus experts presented a blurry picture of what is known about Zika.

Only 14 cases had been documented from the virus' isolation in 1948 in monkeys in an Angolan forest until 2007. That year, an outbreak on the South Pacific island of Yap seems to have been the jumping off point for an ocean-spanning spread, with the virus infecting populations in Latin America who had no previous exposure, said Scott Weaver, PhD, John Sealy Distinguished University Chair in Human Infections and Immunity at the University of Texas Medical Branch in Galveston.

The virus, which is active in 33 countries and territories worldwide, continues to spread throughout Latin America, raising concern in the United States. Twenty-six countries and territories in Latin America and the Caribbean have reported Zika, said Marcos Espinal, MD, director of the Department of Communicable Disease and Health Analysis for the Pan American Health Organization. "We haven't seen the peak of this outbreak," he said.

In the United States, "we're not expecting outbreaks in millions of people," said Dr Weaver. The scenario could change, however, if new modes of transmission developed, he said.

The virus may be spreading because of lack of immunity or because it has adapted and is enhancing mosquito-borne transmission or human viremia, but these theories are not proven, said Dr Weaver. He said that genetically modified mosquitos are not responsible for the rise of Zika, and that there is no evidence to tie the use of larvicides to microcephaly.

Thomas Monath, MD, chief scientific officer of BioProtection Systems Corp, said that rising temperatures resulting from climate change could play a role, as they have widened the habitat for the two known Zika carriers: Aedes aegypti and Aedes albopictus mosquitoes.

Those mosquitos introduce Zika, a flavivirus, into skin cells, leading to the hallmark rash, fever, myalgia, and conjunctivitis seen with acute infection, said Michael Diamond, MD, professor of medicine, molecular microbiology, pathology, and immunology at the Washington University School of Medicine in St. Louis, Missouri.

It appears that the infection itself lasts from 3 to 7 days, but viral shedding can continue for up to 15 days in urine and 62 days in semen, said Albert Ko, MD, chair of the Epidemiology of Microbial Diseases at Yale University School of Public Health in New Haven, Connecticut. But nothing is written in stone yet. "We don't really know the duration of viremia or the implications of that viral shedding," said Dr Ko, who has been working with the Brazilian Health Ministry's Oswaldo Cruz Foundation in Salvador, the site of that country's first Zika cases in 2015.

The virus has been associated with Guillain-Barré syndrome, but a causal link has not been established. Overall, 100 to 200 cases have been documented in Brazil, where from 400,000 to 1 million individuals have been infected. Patients with Zika have also had other neurological issues, such as acute disseminated encephalomyelitis and isolated sensory disturbances, said Dr Ko.

Brazil is tracking 4000 cases of microcephaly, but some of those are likely caused by cytomegalovirus, toxoplasmosis, or syphilis, Dr Ko said. He added that computed tomography, ultrasound, and postmortem exams show healed-over brain lesions, suggesting that Zika might run its course early in fetal development.

With little to no data available on microcephaly prognosis, physicians are wondering how to care for the babies, said Dr Ko. In Salvador, infants are being admitted fairly quickly postpartum for hydrocephalus and seizures. "That is a major clinical concern," he said.

Physician Wish List

Clinicians' list of concerns include determining the biological underpinnings of microcephaly, including how — or if — Zika crosses the placental barrier, said Dr Goldman. More epidemiological studies are needed to assess long-term health outcomes in babies with the condition.

The physicians issued a call for more research on the potential infectivity of various bodily fluids, suggested putting all pregnant women being tested into a registry, and urged an assessment of pregnant women's knowledge, attitudes, and beliefs about the use of DEET or other insect repellants.

Physicians would also like tests that are faster and offer more sensitive and specific results for diagnosing acute infection and for gauging viremia further out from infection.

Dr Riley said she does not have a lot of confidence in the immunoglobulin M diagnostic, in part because it is not clear when antibody levels are supposed to drop with Zika virus. So a negative might not truly be a negative, she told Medscape Medical News.

It can also take up to a month to receive a result — a length of time she sees growing as more clinicians seek immunoglobulin M testing.

Time is of the essence, she said. If an ultrasound or amniocentesis detects abnormalities, there is not much to offer. "If you get the information back early enough, you could terminate your pregnancy," she said, but noted that termination was entirely dependent on abortion laws, which vary by state.

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