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April 8, 2016
‘PANDEMIC IN PROGRESS’
Zika Virus Re-Emerges as More Serious Global Threat

In Masur, NIAID director Dr. Anthony Fauci
discusses the Zika virus pandemic as it unfolds.
In Masur, NIAID director Dr. Anthony Fauci discusses the Zika virus pandemic as it unfolds.

With apologies to Ben Franklin: Nothing is certain in this world, except death and taxes…and outbreaks.

NIAID director Dr. Anthony Fauci confirmed that sentiment Mar. 18 in Masur Auditorium, quoting an article he wrote in 2008 about emerging infections (and recalled a year or so ago about Ebola): “This is a perpetual challenge that we have to be prepared for because it will come again. It may not come again in this degree of magnitude for who knows how long, but you can be absolutely sure it will come again.”

It has come again, although not yet—and with luck and preparation, not ever—in Ebola magnitude. This time it is the Zika virus.

“The bad news is that we have Zika; the good news is that Zika is a flavivirus and we have a lot of experience with flaviviruses,” said Fauci. “We’ve made vaccines against flaviviruses.”

In a lecture titled “Zika Virus: A Pandemic in Progress,” he told a capacity crowd about the virus’s background, the current outbreak in the Caribbean and Latin America, implications for Zika and the United States, and the role of research and development—diagnostics, vaccines and therapeutics.

First identified in 1947 in monkeys in the Zika forest in Uganda, Africa, and recognized in 1952 in Nigeria as a virus that can infect humans, Zika re-emerged in 2007 at outbreak levels in Micronesia.

In recent years, the virus has spread to South America, Central America and the Caribbean, bringing with it a still-unproven but almost-certain newly identified risk to pregnant women and their fetuses.

“This is a perpetual challenge of emerging and re-emerging diseases,” Fauci pointed out. “Every day, every week and every month we learn more and more about how this most unusual situation is evolving.”

Familiar Territory for Scientists

Unlike the situation more than 30 years ago, when we knew almost nothing about another quickly developing pandemic—HIV/ AIDS (and have yet to develop a vaccine against, Fauci noted), scientists have a head start on combatting Zika.

A single-stranded, enveloped RNA virus, Zika belongs to the Flaviviridae family and flavivirus genus. Related diseases include dengue fever, yellow fever and West Nile virus.

Zika is transmitted to humans primarily by two varieties of Aedes mosquitoes: africanus, which spread the virus in jungle regions, and aegypti, which are the most likely culprit in the epidemic’s urban environments.

The first Zika outbreak, in 2007 on the island of Yap in Micronesia, affected more than 70 percent of the people. Zika traveled then to French Polynesia in 2013, and moved steadily east along the southern hemisphere, mainly in hot, humid regions where mosquito populations thrive.

In 2015, Zika showed up in Brazil in a major way. As of mid-March 2016, there were 37 countries/territories with active Zika virus transmission.

Different from Ebola, a Zika diagnosis is not considered life-threatening, Fauci said.

In fact, “symptomatically, it is not a big problem,” he said. “Four of 5 people infected do not have symptoms [fever, rash, myalgia, arthralgia, conjunctivitis]…It is a disease that comes and goes. People get better. There is almost no mortality.”

There is no Zika-specific therapy. Instead doctors prescribe supportive treatment—fluids, rest, acetaminophen. One complication in treatment is that current tests do not distinguish between Zika and the other flaviviruses. Fauci said that’s important because taking NSAIDs or aspirin increases the risk of bleeding in patients with dengue. Zika generally runs its course in about a week.

“This would have been nobody’s real problem,” Fauci explained, “because generally it is a disease that is not as serious as dengue. Dengue can make you really sick and can kill you under certain circumstances. Zika almost never kills anybody the way we thought of it in general.”

Familiar sight. Fauci briefs a capacity venue on the topic of Zika infection, as he did for Ebola and HIV.
Familiar sight. Fauci briefs a capacity venue on the topic of Zika infection, as he did for Ebola and HIV.

PHOTOS: BILL BRANSON

Uncharted Ground

But in this latest outbreak, Zika began distinguishing itself from previous go-rounds.

“[In Brazil in 2015] we started to notice something very unusual—an uptick that was really more than an uptick—an explosion of microcephaly cases in pregnant women’s fetuses who are infected during pregnancy,” Fauci explained. Microcephaly is a congenital condition in which an individual’s head is unusually small due to abnormal development of the brain.

In the 5 years before 2015, Brazil saw no more than 175 cases of microcephaly per year; in 2015, the country reported more than 5,100 confirmed or suspected microcephaly diagnoses.

In addition, Fauci said, doctors reported “serious ocular involvement of Zika virus congenital infection.” Then scientists documented arthrogryposis—a distinctive, abnormal curling in the legs and arms—in children born to Zika-infected mothers.

Fauci stressed that investigators want more evidence to determine cause and effect conclusively, but most scientists already are convinced.

“Cohort studies and case control studies will be the way to definitively show that Zika virus is causing the microcephaly and other fetal abnormalities being reported,” Fauci noted, citing a New England Journal of Medicine cohort study of 88 pregnant women in Rio de Janeiro. Of those 88, 72 tested positive for ZIKV in blood, urine or both. Fetal abnormalities by ultrasound were seen in 29 percent of Zika-infected women and in none of the 16 pregnant women not infected with Zika virus.

Although not a large group study, “this is starting to be compelling evidence,” Fauci pointed out. “CDC is doing a case control study. We [NIAID and NICHD] are doing multiple cohort and case control studies. We are going to get the definitive answer and I think we all know what the definitive answer is going to be, but we want to prove it scientifically.”

Other unexplained situations have cropped up in this pandemic: 42 patients in French Polynesia were diagnosed with Guillain-Barré syndrome associated with Zika virus infection; a 15-year-old girl in Guadeloupe, French West Indies, was reported to have Zika-associated acute myelitis; an 81-year-old man in France who had been on a cruise in the Pacific tested positive for Zika and later died of meningoencephalitis.

Here, Now and in the Future

Moving closer to home, Fauci addressed Zika in the U.S., noting that health officials in this country are particularly “attentive and there is some concern that we are prepared for things that have happened in the past that are an indication of what may happen in the future.”

Two types of cases might occur here:

  • imported cases (About 40 million people a year travel to and from the U.S. and infected outbreak regions)

  • local spread (Aedes aegypti mosquitoes, which do exist in the U.S., especially in the southeastern part of the nation, bite recent travelers and then bite people who never left the U.S.)

“The critical issue is, what is the sustainability of that local spread,” said Fauci, describing aegypti as “a bad news mosquito” that CDC director Dr. Tom Frieden calls “the cockroach of mosquitoes, because…indoor, outdoor, they bite during the day. They bite during the night. It can breed in a capful of water.”

Aedes albopictus mosquitoes, which are far more prevalent in the U.S., are also a possibility for spreading Zika. “Certainly aegypti are not the only mosquitoes that can transmit this. We know about the africanus in Africa, but we don’t know the efficiency of the albopictus. We hope Zika does not adapt itself well to albopictus.”

Yet another unknown Zika variable worries health officials.

“Here is something that has really compounded the difficulty we are facing,” Fauci said. “Not only is this the first infection—to our knowledge—that is mosquito-borne that can cause a congenital abnormality, but sexual transmission is also an unusual situation.”

Although first reported in 2008, demonstration of Zika in semen was confirmed a month ago in Dallas. Six cases of sexual transmission of Zika virus have been documented in the U.S. as of mid-March. Investigators do not know how long the virus survives in semen and can be transmitted after an individual recovers from an acute infection. So far, scientists have documented as long as 62 days, but investigators do not have enough experience with Zika to know for certain.

In addition to mosquito bites and sexual contact with men (So far, “there is no evidence that Zika is sequestered in the genital area” of women, Fauci noted in response to a question), blood transfusions also can transmit the virus.

In terms of research under way, Fauci said investigators are close to developing improved diagnostics for Zika, using the framework already developed for other flaviviruses.

In addition, by employing a platform previously designed for West Nile virus, scientists have several concepts for a Zika vaccine, including one that is “shovel-ready.” NIAID is likely to start a phase I clinical trial with one candidate vaccine by September 2016, and to advance to a larger efficacy trial potentially by early 2017.

In the meantime, Fauci said, mosquito avoidance is essential, with biomedical research also actively investigating several novel ways of vector control. In addition, both the CDC and FDA have issued guidelines for travelers, particularly pregnant women and their partners, guidelines for avoidance of sexual transmission and recommendations for blood donation/ storage organizations.

Concluding the lecture, Fauci said, “I want to emphasize something that’s very challenging but also very exciting with infectious diseases: When I ended the talk on Ebola in this auditorium at this podium a year or so ago, I said, ‘We still have this challenge of Ebola, but this is not the end. There always will be another challenge.’ This proves that [statement] is true.”

View the entire presentation, including Q&As, online at https://videocast.nih.gov/summary.asp?Live=18734&bhcp=1.

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