Understanding the link between Zika Virus and Microcephaly (babies with small heads)

Baby with small head (microcephaly) born to a woman
infected with
Zika virus. Image credit to  CTV News

In the last few months, the world still recovering from the terror of the Ebola virus, has woken up to a new one in the shape of the Zika virus. And what makes this one a terrorist, unlike Ebola which kills its hosts and is very highly contagious, is the strongly emerging evidence of it being responsible for a condition called microcephaly in babies of mothers infected with the virus while they were pregnant (a medical condition in which babies are born with abnormally small heads) as the virus has been isolated from the umbilical cord of these babies and from their mothers' blood. Microcephaly results from either a small brain substance volume; the premature closure of the sutures of the skull bones, or defects in skull bone growth and development, all of which then limit the growth of the brain substance to below the normal size. While the cause of these problems leading to an abnormally small head is multi-factorial, ranging from hereditary genetic disorders to environmental players like inadequate intake of some vital supplements by the pregnant woman and exposure to radiation in pregnancy---it's very vital to work out, in the smallest of details, how the Zika virus has come to be a player and the various mechanisms with which it likely employs to achieve this mischievous feat.

And working this out will start with the origin of the virus. The first case was reported in monkeys in the Zika forest in Uganda in 1947, with the first human case reported in 1954 in Nigeria, and whether there was any incident of microcephaly then has to be investigated. But then, much scientific attention wasn't given to it because it never posed a global threat. However, it drew a small attention when there was a small outbreak in 2007 on the island of Yap. The Zika virus is spread by the mosquito specie Aedes aegypti that also spreads Yellow fever and dengue fever. Like its malaria-spreading family member, the Aedes aegypti mosquito breeds in stagnant waters; but unlike the malaria-spreading mosquito, it's mostly active during the day. 

Aedes aegypti mosquito that spreads
the Zika virus. Image credit to BBC

The next is the life cycle of the Zika virus between the time of infection of a human host to when its new offspring is taken up from this host by the Aedes aegypti mosquito to infect a new host. And while the structural growth and developmental changes will likely follow the typical virus type to which it belongs, it will be very important to work out the structural and functional alterations this virus imparts to the host cells it invades and the various responses the host may mount to these alterations, and the relationships between these alterations and responses and the clinical manifestations seen in the host.

While the above may not be carried out in humans currently because of the more important need to curb the spread of the virus via mosquito control, there's still an inevitable need to carry out these studies as currently there's no vaccine or treatment for the infection (and even the soonest vaccine will take two years to come off the ovens and may take additional eight years to get global regulatory approval for deployment). Hence, the studies have to start at least in animals--mice and higher mammals like monkeys--along with current research studies towards vaccine development which have been kicked off by scientists at the University of Texas Medical Branch.

With animal models of the life cycle of the virus and its varied clinical manifestations established, we can move on to studying the impact of the virus on pregnant monkeys, on the offspring of these infected monkeys to look out for microcephaly (baby monkeys with small heads). This aspect of the study would be approached by breaking down the study animals into groups based on the gestational ages of their pregnancy, from trimesters down to months and then weeks; and then infecting the trimester groups, the months groups and the weeks groups, taking serial blood samples from both the animals and their developing babies for genetic and molecular studies, while taking care of the animals till delivery to assess the outcome on the babies' brain growth and development.

The most important benefit of this research will be to reveal whether there's a window period in pregnancy during which Zika virus infection poses the absolute greatest risks to the unborn baby, while it may be harmless in other periods of pregnancy. Such a revelation of a catastrophic window, if also established through epidemiological studies in humans, in the face of no available vaccine or treatment, will ensure that pregnant women are put under strict holistic preventive health care surveillance during this window in areas of the world where both environmental efforts at mosquito control and all-round medical surveillance of pregnant women are facing stiff challenges in terms of funding, thereby effectively prioritizing limited resources to this critical catastrophic window period of Zika virus infection. In addition, the research will likely help in developing a rapid diagnostic test that can become part of the routine antenatal care for pregnant women.

And to perfectly understand the link between Zika virus and microcephaly, we can now directly infect animal embryos in vitro with Zika virus, tag genes involved in brain and skull bone growth and development with radioactive isotopes and then implant them into the respective animals for development to a viable foetus, while taking samples from the developing embryos and foetuses at different periods of gestation (developmental periods in the womb) for analysis of these genes and the various Zika viral components that may have contributed to the alterations of the genes.

The Zika virus outbreak is a global public health emergency mostly due to emerging link between it and microcephaly in babies and then Guillain Barre Syndrome, a disease of the nervous system characterized by ascending paralysis of the lower limbs that can progress to involve the muscles of the upper limbs, face and muscles of respiration which can lead to death; and about 30 million people are at risk of being infected, of which many of them will be asymptomatic and could travel to other parts of the world, spreading this virus. So, while the World Health Organisation map out strategies to battle this new disease terror and the search for a vaccine and treatment begin to sprout within the shells--- understanding and confirming the link between the virus and abnormally small heads in babies, down to the molecular level, and working out possible safety nets for unborn babies in affected areas of the world are necessary weapons that should be developed and added to the possible arsenal to fight this crisis in the medium and long term.