By Aileen Marshall
What should you know about the Zika virus? It’s been around for over 50 years, but it’s only recently that it’s spread has increased around the world, especially in South America. The Zika virus is spread by mosquitoes, but for most people it only causes a mild infection. However, an infection in pregnant women can cause a birth defect called microcephaly, in which the skull and brain don’t fully develop. At this point, there’s limited diagnostic tests and no cure, so labs are scrambling to develop these products.
The Zika virus was discovered in 1947 in the Zika Forest of Uganda. It was isolated from the blood of a rhesus monkey there, as part of a Yellow Fever monitoring program. It was then found in an Aedes africanus mosquito from the same area, a year later. The first human infected was found in 1952 in Uganda and Tanzania. A study in India that year found a significant number of Indians who had antibodies to Zika, an indication that it had been prevalent in that population. There were sporadic outbreaks of Zika over the later years in equatorial areas of Africa and Asia. Then in 2007, an outbreak of what initially appeared to be dengue or chikungunya occurred in the French Polynesian island of Yap. It was later confirmed to be Zika, the first outbreak outside of Africa or Asia. By 2013 it had spread to other South Pacific islands with some patients who also had neurological effects and there were some cases of microcephaly. In March of 2015, health officials in Brazil noted an increase in Zika-like symptoms and rash in the northeast part of the country. By that summer, there was a great increase in the number of children born with microcephaly, especially in that same area. By later that year, there were confirmed cases of Zika infections in other South and Central American countries, and the Caribbean. On February 1 of this year, the World Health Organization declared it a public health emergency of international concern.
The Zika virus belongs to the same family, Flaviviridae, as dengue, chikungunya, yellow fever and West Nile viruses, which is why the antibodies often cross-react in diagnostic tests. It has a single strand positive sense RNA genome, which means it replicates in one step. The strain in this recent outbreak has been sequenced and it has found to be the same strain from the South Pacific outbreak.
It is transmitted by a couple of species of mosquitoes under the Aedes genus of mosquitoes. These tend to be relatively aggressive biters who bite during the day and like to stay indoors. If a mosquito bites someone with an active Zika infection, the insect can then pass it on to the next person it bites. Evidence of the virus has been found in blood, semen, saliva and urine. There have been some cases of person-to-person transmission by blood and semen. It is not known whether it can be transmitted by a person’s saliva, or kissing. The mechanism of maternal to fetal transmission is also not known. According to Claudia Dos Santos of the Instituto Carlos Chagas/Fiocruz in Brazil, it is found in Hofbauer cells, a type of white blood cell found in the placenta. “It’s possible that Zika virus can cross the placenta and infect the brains of fetuses” says Melody Li, of our own Rice lab.
One in five people who are bitten by a mosquito carrying the Zika virus will get sick. Of those, the majority have mild symptoms and recover in about a week. The symptoms are a rash, fever, joint aches, headache, conjunctivitis (pink eye), and edema behind the ears. There have been some cases where a person develops neurological complications and some develop Guillain-Barré syndrome. In this syndrome, one develops various degrees of paralysis, which resolves within months. The most adverse effect of a Zika infection is the birth defect microcephaly. While the evidence is not yet definitive, it seems to happen if a woman is infected while pregnant, or a couple of weeks before. Many of these pregnancies end in miscarriage or still birth. The children that are born usually have a very short life span and many cognitive problems. As of this writing, more than 4,000 cases of microcephaly have been reported in northeastern Brazil within the past year. This is a rate ten times higher than normal. There is a hypothesis that prior infection with dengue, which is prevalent in northeast Brazil, causes that outcome.
There are two different tests available for diagnosis, but no commercially-available blood test. The blood test done in most institutions is an in-house derived test for Zika antibodies in the blood. The problem is that there are often cross reactions with antibodies to other Flaviviruses like dengue, chikungunya and West Nile. which are often endemic in the same areas where Zika exists. Because these are in-house tests, there is no coordinated validation or quality control. There is a Polymerase Chain Reaction (PCR) test that directly detects the Zika RNA. While more reliable, only the Center for Disease Control (CDC) has this test, it is expensive and the RNA can only be measured during or within a few days of symptoms. The virus clears the blood in about three to four days and the antibodies appear after day five.
There is no vaccine for Zika. The focus has been on prevention. This past January, the CDC issued a travel warning to women of child bearing age to countries with reports of Zika. For all those areas, they recommend removing sources of standing water, using screens on all doors and windows, wearing long sleeve shirts and pants and using insect repellant. Brazil and the governments of some other Zika affected countries encourage people to delay getting pregnant until the virus is under control. Human rights groups have pointed out that some of these same governments don’t provide access to contraception and safe abortion. It is not expected that Zika will be as much of a problem in the New York area as it is in some of these other areas. We only have a limited summer season, and a good infrastructure where standing water is not as common. Most people in the United States also have doors and windows with screens. The concern is for the upcoming Summer Olympic Games in Rio de Janeiro this August.
There has been a surge in biomedical research now on the Zika virus around the world. The United States and most international regulations require that the virus only be handled in a Bio-Safety Level 3 facility. There is no currently existing animal model for Zika, which also makes research difficult. There is work being done to develop a mouse model at Washington University in St. Louis. Rockefeller’s own Rice lab will be one of several in this country working on Zika.