Zika Virus: A Discussion with Dr. Myron (Mike) Cohen

Zika Virus: A Discussion with Dr. Myron (Mike) Cohen click to enlarge Myron Cohen, MD
Zika Virus: A Discussion with Dr. Myron (Mike) Cohen click to enlarge Ron Falk, MD

Falk: Hello, this is Ron Falk for the Department of Medicine at the University of North Carolina. Welcome to the Chair’s Corner. Today we’re going to be talking with Dr. Mike Cohen, who is a Distinguished Professor of Medicine in Microbiology, Immunology, and very much the head of Infectious Diseases in our Department of Medicine. Mike has been involved in a global perspective as he’s the Vice Chancellor for Global Health and the Director of the Institute for Global Health and Infectious Disease. Welcome, Mike Cohen.

Cohen: Good morning.

Falk: Today, we’re going to talk about the latest epidemic, the Zika virus. You’ve spent already a lot of time thinking about this infection. What do we know about the Zika virus?

Cohen: A brief summary: Zika is a flavivirus, which are well known, dengue and yellow fever are flaviviruses, are a species that we’ve had experience with. Zika was first discovered in Uganda in 1947. It’s been followed as a self-limited illness since that time. We’ve learned that it’s transmitted by mosquitoes-a species of mosquitoes. Once mosquitoes become infected with it, it has the ability to rapidly infect a population. Many outbreaks of Zika have been reported over the years. Historically, the problems that have been brought to people’s attention have been neurological diseases as a consequence of Zika, especially Guillain-Barre syndrome and other kind of demyelinating diseases, but the numerator and denominator are not really well established. In other words, we don’t know among the people who get Zika, which is self-limited and 4 out of 5 people are asymptomatic, the 1 out of 5 with symptoms have a self-limited illness of fever, headache, conjunctivitis, arthralgias, perhaps skin rash- we don’t understand among the universe of people who get Zika, how many of these have these neurological complications. Now I’ve summarized what we know. 

Falk: Now there has been tremendous media attention on the microcephaly that’s occurring primarily at the present moment, in Brazil.

Cohen: What’s transpired is - northern Brazil, for a variety of reasons-- the economy’s been bad and mosquito control has not been a priority for the Brazilian government – and northern Brazil, and all of Brazil have had a dengue epidemic for a very long time. Dengue can be a very serious infection. The lack of mosquito control has contributed to the spread of dengue. That causes breakbone fever, and in recurrent dengue infections, hemorraghic fever. So all of us in infectious diseases have been very concerned about Brazil and dengue. In northern Brazil, for a variety of reasons, have now had a Zika outbreak superimposed on the dengue outbreak. Same mosquitoes, another flavivirus, and in that universe, the physicians in northern Brazil have seen a disproportionate number of children with microcephaly, and a disproportionate amount of neurological disease. This brings us to association and correlation, not necessarily causation. It brings us to the conclusion that it is reasonable to be concerned that Zika outbreak, superimposed on all of the other things going on in northern Brazil, is contributing to these problems—microcephaly and greater neurological disease. So far, microcephaly and neurological disease have not been necessarily been observed in other parts of the Caribbean, but time will tell whether there’s something special about northern Brazil and time will tell the difference between association and causation, which for infectious disease specialists is extremely important because otherwise we go down terrifically wrong roads. So we’re at the very beginning of trying to understand whether Zika is causative of the problems being observed in northern Brazil. However, conservatively, and as a word of caution, all the normative bodies, WHO, the CDC, they’re leaping, properly, to the concern that we should assume potential causation and then deal with this as if it were true.

We have no idea about the following: We really don’t know the efficiency of acquisition of Zika after mosquito bites, we don’t know the prevalence of Zika in the mosquitoes anywhere in the world including Brazil, although they’re probably quite prevalent in northern Brazil. We don’t know when a pregnant woman acquires Zika, the probability that a child will have any problems. By the way, microcephaly is not the real issue, it’s following a child for a long period of time to make sure there are no other neurological complications of acquisition of Zika during pregnancy. That’s a much bigger concern than microcephaly. Microcephaly is the tip of an iceberg. We’ve now got to follow infants from northern Brazil for neurological development for a long period of time. We do not know that any of the numbers you think are evoking fear, that’s entirely correct. Which is why, in some ways, that government is willing to make a huge investment to get the numbers as quickly as possible.

What relaxes our species and reassures our species is knowing the rules. The rules of an infection. The probability of a transmission event, the consequences of a transmission event, and the interventions that are possible to prevent, treat or cure disease. Once we know the rules, fear is inevitable for an infectious disease, the moment we see an infectious disease. Influenza, SARS, MERS, Ebola—once the rules are set out, people start relaxing. The rules of Zika will be developed within a matter of weeks. We will know much more weeks or months from now, we will have a whole different approach towards this infection. 

Falk: On the news, the media has reported that there are Zika infections in the United States. So you see a map of the United States and various states pop up. What’s known about the infection in North America?

Cohen: First of all, there’s an iceberg issue here. We can only know of infections that are symptomatic. So when they say there are 12 infections in the United States, that’s probably wrong. Probably a substantial number of people have come from the endemic areas, the Caribbean and South America and return with asymptomatic Zika. We know of 12 people who’ve been tested whose antibodies have tested positive. All of those were acquired outside of the United States.

Now, wisely, the federal authorities and state authorities, including North Carolina, are concerned about preventing human-to-human through mosquito in the United States. So obviously the way to do that is mosquito control. So you’ll see ramped up efforts and mosquito control. There’s a tension between the environment and mosquito control. It brings us to the practical implications for recommendations, and obviously the number 1 recommendation is that every community would do well to have mosquito control. Number 2, people can restrain the number of mosquito bites in the simple ways we already do, with DEET, long sleeves, and appropriate other mosquito control measures.

Falk:  Let’s come back to the “hot spot,” or endemic areas. Are there any in North Carolina?

Cohen: No. There’s nowhere in the United States. The one place with the most worry would be Texas, Florida, Louisiana, swampy areas where it’s very difficult to not have massive numbers of mosquitoes. Those are the potential areas. But the species that can cause these diseases exist, but their ability to sustain an epidemic is restrained. How do we know this? Because dengue has been around for years and years and we’ve been ever-fearful of big dengue epidemics in Florida, Texas, Louisiana, and there’s been no dengue epidemic. We’re pretty confident that the environment does not sustain the probability of a big human-to-human Zika, or a vector-born—the right expression here is not human-to-human, it’s vector-born, where the mosquito is the intermediary between two humans.

The STD part of this: UNC of course, we are among the great STD investigatory groups in the country, and my own lab has focused for years on collection of genital secretion to understand the probability of a transmission event from one human to another. Like Ebola, the possibility of sustained replication of a viral agent in the genital tract is there, so you could call any of these infections- Mono, CMV, Ebola, Zika, they could all become sexually transmitted diseases along those lines. But that is very unlikely to be a major way in which diseases are spread. For Ebola, one of our research groups is working on sustained replication of Ebola in the genital tract, because Ebola is such a terrible epidemic that you want no cases. So working on Ebola has made a lot of sense. For Zika, I don’t think that will be a big concern, personally. 

Falk: Let’s come back to the issue of environmental control of mosquitoes and thus the decreased risk of transmission. Because decreased biting mosquitoes. Versus the possibility that communities will have wide-spread spraying programs to diminish the mosquito population. In the past when that’s occurred, depending on the agent that is used, there are all sorts of environmental downsides. How does one balance those kinds of problems, including the possibility that using a huge amount of mosquito repellant that also may carry a potential risk?

Cohen: You’re into a big topic. It kind of starts with Rachel Carson and "Silent Spring." And before that time we were using DDT, a very powerful insecticide to wipe out mosquito populations because many more people have died of mosquito-born infections in all the wars in the history of this planet. The tension started many, many decades ago, and DDT fell out of favor, and mosquito populations grew, and malaria became a bigger problem than it might have been had we used more DDT. But the tension is, fewer birds, fewer of everything, and perhaps other human environmental consequences from DDT. This whole thing is going to be played out again. When I was a child in Chicago, whole neighborhoods were fogged for mosquitoes. We’d ride our bikes through the fog! Most people of this generation have never seen fogging of neighborhoods.

What’s going on in Brazil is they’re using the military to eliminate standing water, and spray and spray and spray. What they’re spraying I’m not entirely sure.

The magical solution is infecting the mosquitoes with a bacteria that prevents them from transmitting viral infections. There is such a bacteria that’s been developed pretty aggressively by scientists, released in some parts of the world already to see whether mosquito populations can be rendered harmless through this bacterial infection. The GATES foundation has been very supportive of this biological approach. But we’re messing with Mother Nature, and so all of this has to play out.

Falk: What do you tell to a pregnant woman, because that’s a special population?

Cohen: Either pregnant women, or women of child-bearing age planning on getting pregnant. This gets into a hugely interesting discussion. The answer to your question is, the CDC, has made this a level 1 recommendation was that women of child-bearing age who intend to get pregnant, or pregnant women, should not put themselves at risk—these are US women of course, that’s who the recommendations are for—should defer all other than non-essential travel to the endemic areas. That’s a strong recommendation, and I kind of embrace that recommendation. Pregnancy is a rare event – most women only get pregnant a few times, and unless it’s absolutely essential, they might want to not go to a “hot zone.” But sometimes that is unavoidable.

The bigger issue is, what if you’re living in those countries? Then you’re going to become pregnant, and there are lots of mosquitoes and lots of pregnancies..What’s really fascinating is we’ve seen some countries start thinking about recommending that for a year no women should get pregnant. Now think about the implications of that. Why are they saying for a year? Because there’s a belief that Zika is so efficient to get to the community, that so many women get pregnant, that when mosquitoes come back a year later they’ll be immune. That’s called herd immunity. Now can our species restrain pregnancy for 12 months, or even a month? Then another recommendation is, be pregnant while it’s winter so there are no mosquitoes. All of these kind of structural plans are really interesting to infectious disease people. Because, should it be successful, it would be amazing.

Falk: What do you tell the citizen listening to this discussion to diminish the panic and fear? What message of calm do you have?

Cohen: There’s a couple things. There’s always going to be another infectious disease. At our annual meetings, unlike most annual meetings, we have a hole, and we put in the hole the thing that is most scary for that year. So I can tell you right now, in October: Zika. The year before that, Ebola. Years before that, Legionnaires' Disease. We are living on a planet..we are in homestasis with the microbial world, ad for a whole bunch of reasons, that homestasis is going to be disturbed. The calming feature is understanding the rules that govern the infection. Everything changes once the rules are put in front of you. The big advantage we have in 2016 is the speed which all of this transpires. With Legionnaires' Disease, the kind of fear and panic was massive, but it took months, if not years to understand what was governing Legionella. But when we see H1N1 Influenza, or Ebola, it’s just a matter of weeks before we get a really good idea of what our opportunities are for treatment, prevention, and cure. All of that will happen with ZIka in a matter of months. All of this will be calmed by understanding the rules.

For Zika, what’s going to happen, is we’re not going to have a treatment, because we don’t have any treatment for flaviviruses and I don’t see any on the horizon, unless passive immunity becomes a treatment—collecting antibodies from Brazil and making them available or a monoclonal antibody, that’s a possibility that was pursued very quickly with Ebola. Vaccines are already in development. Several groups are already working on a vaccine, and the issue is, how easy or difficult will it be to make a flavivirus vaccine. Dengue-we’ve had difficulty in making a vaccine that’s successful, yellow fever, we have a vaccine, but it’s a live vaccine that’s not easily administered. I haven’t looked very carefully yet into what’s required to make a vaccine for Zika but groups are already working on that. The mosquito control will be played out, and then we’ll know the rules, and then people will be calm probably by the summer.

What I don’t think will happen is I don’t think they’ll cancel the Olympics because of Zika, that makes no sense. I don’t think there’ll be any quarantine for Zika because 4 out of 5 people are asymptomatic. If we meet again 3 or 4 months from now a lot of things will be laid out for you: the prevalence of Zika infections in mosquitoes, the probability of Zika after a mosquito bite, the probability that a pregnant woman will have a baby with microcephaly from northern Brazil, the probability of Guillain Barre syndrome, the pathogenesis of these infections –all of this is going to be known, before your eyes faster than you can imagine, in the blink of a kidney doctor’s eye.

I think we’re wisely dealing with it very aggressively. The WHO was criticized for not being sufficiently aggressive about Ebola. You’re seeing kind of the flip side. From the US and the WHO, you’re seeing 1.3 billion dollars of US dollars are likely to be associated with Zika control. Which, by the way, will have broader benefits. It will help us with dengue, it will help us understand chikungunya, and Zika, it will be good to get ahead of this.

Falk: Lots of investigation is occurring at UNC. Tell me a little bit more about that.

Cohen: UNC, we are blessed over many years, the infectious disease community has come together involving all different kinds of people—pathologists, nurses, dentists, infectious disease specialists, epidemiologists, microbiologists—a huge community of people working together on this. So when something like Zika comes along we look at the faculty already committed to this. Among the universe of our faculty- I mention Ralph Baric, Mark Heise who work on viral infections and interventions for this…Aravinda de Silva, Micriobiologist and Epidemiologist who’s really been committed to dengue and vaccine development and his group. Helen Lazear is a young woman who was just recruited from Washington-St. Louis a year or so ago who works on Zika, that is her work. Her works is on mouse models and the pathogenesis of disease, in other words, how does Zika make mice or humans sick? She’s right in the epicenter of this. Ralph’s lab has been looking at changes in Zika genetics that might explain how ZIka might have evolved to be more pathogenic. So they sequence Zika sequentially year by year and they start seeing changes. They’re working on the fundamental, biological issues.

Maternal-Fetal medicine group in Obstetrics is a fantastically, well-organized and famous group of investigators, they’re thinking about ultrasound management of pregnant women. Once a woman has Zika she becomes a high-risk pregnant woman. We have Elizabeth Stringer, who’s an Infectious Disease Obstetrician who joined us a few years ago in that group with Bill Goodnight, and they’re working on this.

All of us work together with the state of North Carolina towards policy and interventions, that involves a lot of our Microbiology lab-Melissa Miller, is really quite famous for her work in diagnostics. That kind of lends us to the School of Public Health who do sensitivity and specificity of diagnostics. Also how you do case-control studies to understand the spectrum of disease. We have the cases of microcephaly with Zika, and then we have control groups. You put that together and determine what’s really going on in these diseases. Our epidemiologists are thinking about how you organize this. Those kinds of case-control studies are already going on in northern Brazil. It is a very, very large group of local investigators who have different ways to contribute to generating the information about the rules. What are the rules that govern this infection?

Watch Dr. Cohen's TED Talk he gave in 2013 on learning the rules of infection.

Read related story on UNC Lineberger web site, "Zika, emerging viruses focus of UNC virology seminar."

Ron Falk The Chair's Corner is an educational podcast hosted by Dr. Ron Falk, Department of Medicine Chair at the University of North Carolina School of Medicine. 

Previous episodes include topics related to acute respiratory distress syndrome, alpha-gal meat allergy, and autoimmune disease, and feature interviews with Dr. Falk and UNC physicians who specialize in those conditions.