Pandemic: Zika

By John McCormick

ALINE IS 23-YEARS-OLD. She has been married just two years to 25-year-old Bernardo She went into labor Monday evening and by Tuesday morning had given birth to Leandro; she is concerned; she has seen many babies in the Brazilian slum where they live, and only last week her friend and neighbor, Gianne, 18, had a baby who has already died and whose head very much resembled Leandro’s misshapen head.

Neither woman received very good prenatal treatment and both babies were born at home.

Here in the U.S., on Long Island, N.Y., Debbie, a 35-year-old successful attorney and single mother-to-be, doesn’t know it but, despite a carefully planned pregnancy and the best doctor and a delivery in a top hospital, her baby will also be born with microcephaly (meaning “small head”), a severe birth defect wherein the brain doesn’t develop normally and the skull is much smaller than normal.

What did these three women have in common? Two were living in a slum and the other had excellent medical care.

But all three were in Brazil during their pregnancies and all were bitten by a mosquito that had previously fed off another person infected with the Zika (ZIKV) virus. This pathogen is a member of the virus genus Flavivirus. It is transmitted by the Aedes mosquito. Its name comes from the descriptor “Zika Forest of Uganda,” where it was first isolated in 1947.

Gianne never had any symptoms. Debbie had what she thought was the flu and was grateful it was mild and happened just after she returned from her South American vacation. Aline had what she thought was a mild cold.

It is far from certain yet but it is believed the microcephaly birth defect occurring in large numbers in Brazil is being caused by a virus, specifically the Zika virus that is carried by a mosquito. One reason this is being suggested is that another virus, a cytomegalovirus, is known to also cause microcephaly.

If this were limited to a few slums it might not be of much interest in the U.S., but every indication is that the mosquito and the infection are both spreading at alarming rates to other countries, and Zika has already been found in the U.S.

Pandemics

Nothing in our general experience demonstrates the inevitability of mathematics more dramatically than does a developing pandemic. Some diseases, especially ones where there is little immunity in the population, no vaccine, and are easy to spread, grow exponentially. Exponentially means the number of infected people essentially grows at a rate that is most easily expressed with exponents. (A graph of such a rate would appear not as a straight line, but as a curve that continually becomes steeper.)

When an infectious disease spreads without any need for new infectious input from outside a population, that is, without more infected people or carriers such as fleas coming into the community, then it is considered to be endemic if each person infects just one other.

If an infected individual on average infects fewer than one other, then the disease will quickly die out in that population.

The problem comes when it is an easily spread virus and almost no immunity exists in the population—then one sick individual can sneeze in a crowd (or otherwise spread the infection) to many others. That’s when the disease spreads exponentially, spreads very quickly, and continues to spread until almost the entire population has become sick.

This happened in the Middle Ages with the plague, which wasn’t one hundred percent fatal and not everyone was susceptible, but still killed about half of the populations where it got a foothold.

Ebola is a recent example that was only slowed by a massive effort to segregate the infected population. The World Health Organization (WHO) recently announced that Ebola had finally been stopped and the epidemic was over; however, a new case was recently reported and only constant vigilance will prevent a new outbreak because the disease still exists in nature—it has only been eliminated temporarily in humans.

Ebola has killed more than 11,000 people in two years. Some epidemiologists feel the Zika virus could be an even bigger threat.

Zika

Zika is no more threat to the elderly, children or men, than the flu, probably less. It is only dangerous to pregnant women, and even then it doesn’t cause any severe symptoms in women; instead, it appears to cause severe birth defects—at least in the current South American epidemic it is thought to be the source of the birth defects.

There are five main reasons why Zika will be more difficult to control than Ebola and therefore perhaps a much bigger threat.

First, it is spread easily by a rapidly proliferating mosquito (Aedes aegypti) while Ebola spreads by exposure to bodily fluids from those who are infected. That makes Zika more like the plague that was spread by fleas.

Second, only about twenty percent of those who have contracted Zika have any symptoms significant enough that they even know they have caught anything. Diagnosis requires DNA analysis, which is expensive, time-consuming, and not available in many of the most affected regions.

Third, there has been almost no work on a vaccine; when a potential vaccine is developed it will have to be eventually tested on pregnant women, a very difficult proposition ethically and for which it will be difficult to find volunteers. Even if a researcher performs the trials, it would involve infecting the pregnant women.

A fourth factor is more speculative, but may be the biggest barrier of all to stopping the spread of Zika. This disease is most prevalent in tropical environments that are perfect breeding grounds for the mosquito, and are generally in poor countries.

The reason this is a very important factor is that only DDT is thought to be both an effective and inexpensive insecticide that can control the mosquito population in the most vulnerable areas. Unfortunately, DDT is almost as dangerous to people as the Zika virus itself.

Lastly, we come to sex. Yes, it is possible to transmit Zika via sexual contact. That was shown when one U.S. scientist recently returned from Africa and infected his wife. It isn’t yet known how easy it is to transmit sexually, but then little is currently known about Zika.

If all that wasn’t bad enough, the center of the new infection is Brazil, the location of an enormous annual Mardi Gras carnival, and this year the site of the 2016 Summer Olympics, both in Rio de Janeiro, which will draw upwards of a million people from around the world, many of whom could be infected and spread the virus to the rest of the world very quickly.

The first case of Zika in South America was reported in May, 2015, and by January, 2016, it had spread to twenty-two countries or territories in the Americas, including the U.S. It is expected that by the end of summer, 2016, the Zika virus will be endemic in every country in the Western Hemisphere except Canada and Chile, both of which are generally too cold for the mosquito-borne virus to spread.

The current vector (mosquito) only flies a few hundred meters during its entire lifetime so the spread of the Zika virus is due entirely to ever-increasing international travel; a person with the active infection travels to a new region and is in turn bitten by a mosquito—presto chango, we have a new center of infection.

Getting Tired—Now the Really, Really Bad News

It is thought that a rapidly spreading Asian tiger mosquito, A. albopictus, is also capable of carrying Zika, which opens up vast new territories for potential spread of the virus.

This is not just another “bird flu panic” situation; it is much more like the actual Ebola threat except that it was relatively easy to stop Ebola—people with the disease quickly developed a fever and also quickly died, which was terrible for them but great for those trying to prevent it spreading to the rest of the world.

According to “Science Magazine,” the tiger mosquito was first seen in Georgia, U.S., in 1983, but by 2008 it was already becoming common in thirty-two states.

And in yet another case of unintended consequences, the recycling movement has been responsible for the tiger mosquito’s rapid spread via used automobile tires! Tires are virtually designed to be breeding vessels for mosquitoes. If you’ve ever had one around the house you know how well tires trap stagnant water.

Japan and Germany in particular have strict rules about reusing tire carcasses for recapping and storage/disposal, so millions of used tires are annually shipped from Asia and Europe to the U.S.

[Transmission electron micrograph (TEM) of Zika virus, right, which is a member of the family Flaviviridae. Virus particles are 40 nm in diameter, with an outer envelope, and an inner dense core. The arrow identifies a single virus particle. Courtesy CDC/Cynthia Goldsmith.]

You might think that colder climates would slow the spread of this tropical insect but not so. It turns out that the tiger mosquito, almost exclusively of all the tropical insects, is well adapted to overwintering because its eggs can hibernate in cold weather.

The tiger mosquito is very aggressive, so much so that in southern Italy it is actually reducing tourism. It has, so to speak, come back to bite the Italians who failed to aggressively move to eradicate that particular mosquito in 1990 when it was discovered in a kindergarten in Genoa.

Of course it may turn out that the tiger mosquito, which is capable of hosting about a dozen viruses, won’t be a major vector for the spread of Zika but is still a threat because of other diseases it is known to spread.

“Science,” in 2014, reported, “The chikungunya virus, which causes rashes, fever, and agonizing, sometimes lasting, joint pains, is spreading rapidly in the Caribbean. More than 45,000 suspected and confirmed infections have already been reported. Now that it has arrived in the Western Hemisphere, the virus will spread as far as the southern United States and Argentina, scientists say, because its main vector, the mosquito species Aedes aegypti, is widespread. There are no drugs against chikungunya, but several vaccines are in various stages of development.”

The tiger mosquito is known to carry chikungunya. Tiger mosquitoes also carry dengue fever; watch for news stories about that threat this summer.

Zika Facts

But the big news today is about Zika, so let’s take a closer look at that virus.

Zika can only be confirmed through PCR Polymerase Chain Reaction DNA analysis and, as most people don’t even know they have been infected, most people will never be tested.

Even worse, the test only works if conducted within a few days of the infection. There is no use testing a pregnant woman who was bitten by a mosquito three weeks or months ago; the test simply won’t show anything (except possibly a “false” positive that can happen with any test and is meaningless).

Want a bit more bad news? The same test that could indicate an active Zika infection within a week of the first symptoms would also show positive if the person had dengue fever, which is widespread in Brazil.

That makes it extremely difficult to determine if the surge in reported cases of microcephaly birth defects in northern Brazil is actually due to Zika.

There is no treatment for Zika, as is true for most virus infections; fortunately even people who have a severe infection with strong symptoms are hardly more inconvenienced than they would be with the common cold. That means, other than the most vulnerable (elderly or otherwise weakened) individuals, few will require more than over-the-counter palliative treatments and if those are not available they will simply have a few uncomfortable days.

WHO reports, “People with Zika virus disease usually have a mild fever, skin rash (exanthema) and conjunctivitis. These symptoms normally last for two to seven days.” This is true even for pregnant women who may have no idea they have been infected. According to WHO the best (read only) method of prevention is to avoid mosquito bites.

Two severe birth defects have recently been linked to the virus, microcephaly and a little understood syndrome—Guillain-Barré. Any time something is termed a “syndrome” you know that little is known about it.

However, there have been large outbreaks of the Zika virus before, most notably in the Pacific—in particular in Yap (2007) and French Polynesia (2013)—and in neither outbreak were these microcephaly birth defects reported in significant numbers. Because microcephaly in particular is extremely obvious (the newborn’s head is misshapen and the brain is very much smaller than normal) it seems unlikely this could have been overlooked.

Therefore, there is still considerable doubt that the Zika virus is responsible for the surge of microcephaly or at least is not the only factor. So far the most severe microcephaly birth defects seem to be mostly in northern Brazil.

The earlier outbreaks did apparently lead to some neurological and autoimmune complications among either the children or the adults—the data aren’t clear.

Another thing which isn’t yet known is the incubation period for the Zika virus—that is, the time from initial infection until it develops—but this is thought to be relatively short, as is the duration of the symptoms.

Although it is currently thought that women need only avoid pregnancy for a few months after possible infection, this too is not really proven, nor is it known during what period of the pregnancy the fetus is vulnerable to the infection.

Laboratory DNA analysis is required to confirm Zika infections, but this is made much more complicated and less reliable by the fact that Zika is a flavivirus and test results are similar to the other infections in the same family that includes dengue and yellow fever, both relatively common in some of the same regions where Zika is seen.

Zika isn’t new despite the fact that very few people have heard of it until very recently. It was first identified in Uganda, Africa, in the late 1940s in rhesus monkeys and found in humans a few years later. Since then it has been found in Africa, the Americas, Asia, and the Pacific. There is no really accepted explanation of why it has started to spread extremely rapidly.

Testing for Zika

We hear the term DNA all the time, but just how is DNA studied in the laboratory and in particular how is a disease identified? During the first seven days of Zika, chikungunya, and dengue infection, viral RNA can often be identified in serum. RT-PCR is the preferred testing method.

Reverse-transcription polymerase chain reaction (RT-PCR) is one of many variants of polymerase chain reaction (PCR) that multiplies the amount of DNA available for testing. PCR itself is not a test in any sense; it was developed in 1983 and without PCR most DNA work, whether in medical research or criminal investigation, would be impossible.

PCR is also the reason why criminal cold cases are being reopened decades later.

Although the process is complex and requires a laboratory, in essence all it does is take DNA apart and use the parts to multiply in a bath of the necessary chemicals—including deoxynucleoside triphosphates (dNTPs), that provide the chemical building blocks the DNA polymerase uses to synthesize a new DNA strand—quite similar to the way DNA is replicated in cells.

The DNA is repeatedly heated to break it apart and then cooled to allow the duplication. The high temperature is about 80° C. and the heat-cool cycle is repeated from twenty to as much as fifty times to produce tens of thousands of copies, making enough for exhaustive testing.

In 1993, Kary Mullis shared the Nobel Prize in chemistry and won the Japan Prize for his work developing PCR.

Warning—Hard Science Ahead

Wikipedia describes the process: “Almost all PCR applications employ a heat-stable DNA polymerase, such as Taq polymerase (an enzyme originally isolated from the bacterium Thermus aquaticus). This DNA polymerase enzymatically assembles a new DNA strand from DNA building-blocks, the nucleotides, by using single-stranded DNA as a template and DNA oligonucleotides (also called DNA primers), which are required for initiation of DNA synthesis. The vast majority of PCR methods use thermal cycling, i.e., alternately heating and cooling the PCR sample through a defined series of temperature steps.

“In the first step, the two strands of the DNA double helix are physically separated at a high temperature in a process called DNA melting. In the second step, the temperature is lowered and the two DNA strands become templates for DNA polymerase to selectively amplify the target DNA. The selectivity of PCR results from the use of primers that are complementary to the DNA region targeted for amplification under specific thermal cycling conditions.”

There are twenty or more modern variations on the basic PCR procedure, in addition to RT-PCR used to identify the Zika virus, but all of them have the same potential for error—that is, the more steps involved the more chances there are for mistakes. 

John McCormick is a physicist, science/technology journalist, and author with more than 17,000 bylines to his credit. He is a member of The National Press Club and the AAAS. He recently launched the canine celebrating website, A to Z Dogs.