Zika and Dengue

Zika and Dengue

May 12, 2016

May 11, 2016

Female mosquitoes have vampiristic tendencies. Their unquenchable thirst for blood drives them to hastily hunt for their next human meal. Once the mosquito lands on its host, it punctures the flesh and inserts its straw-like mouth below the skin, releasing saliva that prevents the blood from clotting. It then proceeds to probe around for a nearby blood vessel to feed from. When mosquitoes perform this routine survival act, they are simultaneously spreading diseases through human populations. Most mosquitoes prefer the taste of blood from humans over blood from animals, intensifying their capacity to spread diseases across the world.

 

The sheer devastation that mosquitoes inflict upon the human race is staggering; each year, mosquito-borne illnesses result in approximately 1 million deaths and roughly 300 to 500 million infections. The list of diseases that mosquitoes are capable of transmitting is extensive, including malaria, West Nile, yellow fever, and chikungunya. Most of these diseases are older and more well known, but there is always the possibility of a new disease emerging and wiping out millions of people.  

Susan Holechek, a professor at Arizona State University in the biology department, is an expert on mosquito-borne diseases, particularly, the virus known as dengue. She has spent years in Lima, Peru studying the effects of dengue on the population, following outbreaks of dengue virus disease.

Recently, the world has been buzzing about a new large-scale disease outbreak that started in Brazil in May, 2015. Cases started to pop up all over the region, home to various mosquito species that transmit diseases. Holechek describes the beginning of the outbreak: “patients started showing up and doctors initially thought that they had dengue because symptoms are very similar, and Brazil has all of the serotypes of dengue, and also chikungunya,” she said, referring to four variant forms of the dengue virus. Scientists soon figured out that the patients they were seeing had not been stricken with dengue or chikungunya, but rather, a virus known as Zika.

The Zika virus, whose effects have been primarily felt all across Central and South America, was discovered in 1947 in a rhesus monkey.  Zika has existed in Africa and Asia ever since. Records indicate that cases of Zika were relatively rare up until 2015. The recent, ongoing proliferation of this virus sparked global concern once Zika was shown to be strongly linked to the development of microcephaly in fetuses. Microcephaly is an abnormal smallness of the head, associated with incomplete brain development. A baby with microcephaly can experience a range of other problems, such as seizures, intellectual disabilities, and developmental delay. Sometimes, microcephaly is classified as severe, which increases the likelihood of the additional problems and can  be life-threatening

Both dengue and Zika are flaviviruses, transmitted by the Aedes aegypti and albopictus mosquitoes. The two viruses also share many of the same symptoms, though dengue symptoms tend to be severe compared with Zika. Fortunately, the dengue virus is structurally similar to Zika and this fact can aid in the development of a future vaccine against the Zika virus. Prior knowledge about dengue can serve as a sort of jumping-off point, so that scientists do not have to start from scratch.

It is common for people who are infected with Zika to be completely oblivious to their condition. This is due in part to the fact that the disease only inflicts symptoms on 20 percent of those infected. When symptoms do appear, they tend to be mild and flu-like. At most, sufferers will endure a fever, headache, and discomfort caused by joint pain and conjunctivitis. Most of these symptoms are similar to those caused by other infections, so a carrier might not even consider the possibility of Zika.

Becoming infected with the dengue virus is an entirely different story. Known as “breakbone fever,” the dengue virus is a serious and sometimes fatal disease. About ten days after being bitten by an infected mosquito, a typical carrier will notice that they suddenly have an unbearably high fever, which can sometimes linger for an entire week. On top of that, they will experience severe discomfort caused by joint pain in all parts of the body, as well as behind the eyes. Carriers are also more likely to bruise easily and bleed randomly from their nose or gums.  

When treating these illnesses, it is most important that scientists focus on the structure of each virus and figure out how to destroy it effectively. Symptoms are only important in identifying and diagnosing a case of a disease, but the virus itself is what doctors and scientists use to create treatments. Holechek explains that “the key point for identifying the cause of the illness is isolating the virus.”     

Compared to dengue, Zika appears to be a mild, non threatening mosquito-borne illness that does not inflict any severe symptoms onto its carriers. However, the scariest aspect of Zika, and the reason that it has raised such alarm all over the world, is not what the virus does directly to the carrier. What is truly terrifying is what the virus passes along to the offspring of an infected female.

Recently the CDC has confirmed that Zika causes microcephaly in developing fetuses of infected pregnant women. The virus is able to reach the fetus by traveling through the mother’s nervous system to the placenta. The virus then interferes with the development of the infant’s brain and head, which has lasting and damaging effects that the child will have to deal with for the rest of its life.

It is difficult to figure out which women are at risk for giving birth to microcephalic babies, since few adults will ever show symptoms of the Zika virus. If a pregnant woman is aware that she was infected with Zika, doctors may run amniotic fluid tests to determine whether or not the child has developed the disorder. Fortunately, a past infection with Zika should have no adverse side effects for a future pregnancy once the virus has been flushed out of the body.  

Another interesting, and rather alarming, fact about the Zika virus is that it can be transmitted from person to person through sexual contact. This is extremely rare among mosquito-borne viruses, as they usually require an animal or insect as a vector to transport the virus and spread it. In the US, there have been eight recorded incidences of this phenomenon occurring.

The Zika virus appears to also be a cause of Guillain-Barré syndrome, though a direct link between the virus and the autoimmune syndrome has not yet been confirmed. Researchers are still trying to determine whether or not the correlation between cases of Zika and cases of Guillain-Barré is meaningful.

Mosquito-borne illnesses, like Zika and dengue, are unusual compared to other types of diseases. For instance, they are transmitted by a vector that does not experience the disease it is passing along. The virus will simply replicate within the mosquito’s body until it is transmitted to a new host. There are numerous genetic factors at play when viruses are being transferred from mosquito to person, such as the DNA of the mosquitoes and of the humans they are feeding from. There are many opportunities for viruses to mutate, which is part of the reason why vaccine development is so difficult for scientists.  

There has been some success with a dengue vaccine, but the process of creating it took a long time due to the nature of the virus. Perhaps the biggest problem for scientists was addressing each of the conflicting genetic variants that can render a vaccine ineffective. Since there are four strains of the virus, the vaccine must be able to adequately defend against each of them. This is rather difficult, since the antibodies for one strain of dengue induce a much harsher second infection of another strain. This phenomenon is known as immune enhancement of infection. Basically, the antibodies from a primary dengue infection start by binding to the body of a second invading dengue virus of a different serotype. Then, after failing to neutralize the virus, the antibodies aid the virus in spreading the infection more efficiently. Scientists therefore had to create something that avoided this problem and did not make things worse for patients who received the vaccine.

Holechek elaborates, “[scientists] thought that because the yellow fever vaccine came so easily, and since yellow fever is also a flavivirus, that we would immediately have success with a dengue vaccine. But dengue got more complicated because of genetic variation and mutation.” Scientists had to work diligently for a very long time in order to create something that worked against all of the confounding variables. Holechek also pointed out that “some serotypes are more responsible for causing hemorrhagic fever than others when there is a secondary infection.” This means that the vaccine would need to be stronger against those specific serotypes of dengue.

The dengue vaccine, called Dengvaxia, was introduced to Mexico in 2015, and was intended to work on a three-dose schedule. At the time, the virus was in stage III of clinical studies. The World Health Organization recommended that only countries with high endemicity use the vaccine. Advocates for a Zika vaccine have been pushing for the past year, but it is unlikely that one will be ready for public use in the near future. A trial vaccine is currently in the works, but the clinical trial process could take years.  

Scientists do not yet know how Zika antibodies will behave when introduced to a future infection. It is possible that, as with dengue, Zika antibodies could perform immune enhancement of a secondary infection. However, scientists hypothesize that the antibodies will have protective functions instead.

Even though a cure for the Zika virus has not been found yet, there are several ways  to avoid contracting the disease in the first place. In countries that have a high disease prevalence, minor actions can make a major impact. The most common strategies include eliminating standing water where the mosquitoes primarily repopulate, wearing protective spray and clothing, and educating people about the dangers of mosquito-borne illnesses.

Scientists have also been working persistently to create diagnostic tests, and recently ASU has created a low-cost paper based test. By making the diagnosis of Zika relatively easy, scientists can expand their work and efforts to target treatment and further research.

New diseases are discovered all the time, so  researchers continue to wait with bated breath to see what the future could hold for mosquito-borne illnesses. When it comes to Zika, researchers still do not know the full range of  adverse effects of the virus.  The virus could remain relatively minor for initial infections, or new and startling symptoms may soon emerge.  Scientists also do not yet know how many strains of Zika will develop and evolve. “Right now, we are only talking about two Zika strains, but we don’t know what is going to happen later,” Holechek says. Only time will tell which direction the Zika virus will take.  


Emily Tanner is a science writing intern with the Biodesign Institute. She is graduating from Saguaro High School and the Math and Science Academy in Scottsdale this year and will begin her studies at ASU this fall semester. She hopes to pursue a future in biomedical engineering.




 

 

Written by: Emily Tanner