A Rapidly Evolving Threat: The Zika Virus in Review

Nathan Weber
Abstract: Since 2015, the poorly understood and largely ignored Zika virus has been the subject
of intense research as a result of major recent outbreaks in both the Pacific and the Americas. As
this research has developed, alarming new trends regarding the Zika virus have emerged, most
notably its ability to cause microcephaly (abnormally small head size) in newborns. It was also
recently discovered to potentially cause the degenerative nerve disease Guillain Barre Syndrome
in adults, causing further alarm amongst researchers and governments. The spread of the virus
has now reached the Americas, but projections suggest that much of the worlds population on all
continents is at risk as it is spread by a very prevalent, hard to eradicate genus of mosquito. By
synthesizing current research on the virus we are able to paint a picture of what it is, why it
spreads and how, as well as evaluate the particularly alarming claims rearding microcephaly
and Guillain Barre Syndrome in the context of recent research. By all accounts, more research is
needed on the nature of Zika in order to prevent a potential public health disaster.
1. Introduction
Zika Virus (ZIKV) has recently come to the forefront of the publics attention as
surprising revelations regarding its spread and potential effects continue to emerge at a rapid
pace. While much is yet to be discovered regarding these effects and the nature of the virus itself,
the shock they have caused throughout societies around the world has caused widespread
concern and in some cases dramatic governmental action.
Most notable is the association between ZIKV infection and the development of
microcephaly (abnormally small head size) in newborns and more recently, a potential link to
infection and the development of the degenerative nerve disease Guillain-Barre Syndrome
(GBS).
Since its discovery in the 1950s Zika has been nearly unknown as a virus, affecting
humans very rarely and having little research conducted on it. According to a mathematical
analysis conducted by Martinez-Pulgarin et al. (2016) the entirety of scholarly literature
generated pertaining to Zika amounted to a paltry 169 articles between 1952 and 2015. The

lack of research and potential major public health implications associated with ZIKV have
caused an explosion in interest and research over the last year, with governments pledging
hundreds of millions of dollars in a race to discover a potential cure.
The aim of this review article is to synthesize the most recent studies conducted
on the Zika virus in order to provide background for further research to build upon, and present a
picture of our current understanding of the virus that is easily accessible.
2. Early History
The first recorded isolation of Zika virus occurred in Uganda in 1947 in a study
conducted by Dick et al. (1952). In this same study, the virus was also isolated from local
mosquito populations, and the relationship between mosquitos and its transmission was
postulated.
In a conference on the epidemiology of the viruses Dick had discovered, the presence of
Zika antibodies in the human population near the forest was also outlined (Dick et al., 1952).
Aside from some surveillance studies conducted on the presence of various viruses in west
Africa during the 1960s and 70s where it was detected (Lanciotti et al., 2008), ZIKV went
unnoticed, and faded into obscurity.
3. Biological Profile
Zika is a member of the viral family Flaviviridae and of the genus flavivirus (Lanciotti et
al., 2008). The flavivirus family consists of single stranded RNA viruses that are dependent on
mosquitoes for transmission and is known to contain some of the deadliest viruses currently
known, including Japanese Encephalitis, Dengue Fever and West Nile Virus (Chang et al., 2016).
These viruses are also known as arboviruses, essentially meaning insect transmitted virsues.
The primary known species capable of transmitting the virus are mosquitoes of the Aedes family.

The
virus itself had its entire genome sequenced in a study done by Lanciotti et al., (2008) as a result
of the most recent outbreaks in the eastern Pacific. Over its lifetime, the virus has undergone
multiple mutations, jumping between different species of primates including humans. One
specific variation found in the virus currently affecting the Americas and eastern Pacific was the
presence of a new 12 nucleotide long genetic sequence not present in the earlier forms identified
in Africa (Lanciotti et al, 2008.). This difference may have led to the increased virulence we have
seen in the current virus, but this is yet to be determined.
4. Global Spread
After initially spreading from Africa to southeast Asia during the 1970s the virus lay
dormant, until a series of recent outbreaks on islands in the Pacific during the mid 2000s
brought it back into the public eye . The map below taken from Chang et al. (2015) outlines the
path of the virus from its discovery in Africa in the 1947 to the current outbreaks in Brazil and
the United States.

4.1 Similarity to Spread of Other Viruses

According to an analysis conducted by Musso (2015), Zika followed a path across the
Pacific very similar to that of two other mosquito borne viruses in its clade, Chikungunya
(CHIKV) and Dengue Fever (DENV). Both CHIKV and DENV infected various island nations
before reaching the Americas and Europe, and now currently infect all continents on the planet
where people reside. With the current trends Zika is establishing, it seems likely that it too will
take this same path.
5. Signs and Symptoms
The initial clinical presentation of the ZIKV is fairly benign and similar to other viruses
within its family. The most common symptom is a rash followed by headache, fever and joint
pain (Cerbino-Neto, 2016). According to the same source, no patients treated were hospitalized
as a result of the illness. Due to the fact that these symptoms are not uncommon amongst

viruses, it became increasingly necessary to develop new methods of testing that could
comprehensively determine whether or not a patient had contracted Zika.
6. Development of Testing Methods
Because of its nearly six decades in obscurity, prior to the major outbreak encountered in Yap no
comprehensive system had been created in order to detect the Zika virus in patients. Specific
tests known as RT-PCR were developed in order to determine the presence of ZIKV in the field
(Lanciotti et al., 2008). RT-PCR stands for Real-Time Polymerase Chain Reaction. In short,
the method detects ZIKV by finding it in solution and replicating it millions of times in order to
demonstrate its presence. As far as methods for diagnosing ZIKV in the field are concerned, RTPCR is the most useful and widely used.
7. Detection
7.1 Detection in Blood
During the 2013/14 French Polynesia outbreak, extensive serological samples were collected
and analyzed using RT-PCR.. According to a study conducted by Musso et al. (2015) 28.1% of
patients were determined to have ZIKV present in their blood. As ZIKV was a virus fairly new
on the scene, with little known about the optimal method needed to test for its presence, other
possible methods of detection were explored beyond just blood samples.
7.2 Detection in Saliva
In this same study, saliva samples were taken from the same patients and tested using the same
RT-PCR method. The results were far more dramatic, with 57.1% of saliva tests registering as
positive for the presence of the virus (Musso et al., 2015).
7.3 Detection in Breastmilk
In a study conducted by Dupont-Rouzeyrol et al. (2016) ZIKV was detected within the
breastmilk of a recent mother. The initial results from the child were deemed inconclusive,

however the breastmilk showed the presence of ZIKV particles. The researcher goes on to say
that more research is needed concerning this topic, but transmission of arboviruses through
breastmilk has been postulated before and should be of concern for doctors managing the spread
of the disease.
7.4 Detection in Seminal Fluid
In another study conducted by Musso et al. (2015), ZIKV was detected in the semen a man
who had traveled to Tahiti. The man returned home and exhibited hematospermia (blood in the
sperm) then went to the hospital. While in hospital RT-PCR was conducted on his seminal
samples and ZIKV was detected in high quantities. The detection of ZIKV in seminal samples
has obvious implications for its route of transmission.
8. Transmission
Mosquito based transmission has been described as the initial source of ZIKV infection in
humans since the 1950s in the aforementioned Dick et al. (1952) studies, however sexual
transmission has only been postulated fairly recently in light of results like those of Musso et al.
(2015).
In Musso et al (2015) article titled Potential Sexual Transmission of the Zika
Virus one man returned to the United States after displaying the normal clinical symptoms of
the virus in Senegal. The day he returned he engaged in sexual intercourse with his partner and
exhibited hematospermia. He immediately went to the hospital and serologic analysis of blood
and saliva from both he and his wife confirmed that they were both infected with ZIKV.
Transmission through breastmilk is the latest in the revelations regarding
ZIKV transmission but also carries with it specific dangers, including the risk of spreading the
disease to infants by unknowing mothers. Little is known concerning this method of transmission

but research is needed in order to shed light on whether or not it is feasible as a route of
transmission.
9. Link to Microcephaly
One of the more recent developments concerning ZIKV concerns the link between women
who were pregnant while infected with the disease giving birth to microcephalic, or abnormally
small headed babies. In Brazil, 1672 babies were confirmed to have been born with
microcephaly, with 4100 reported (Teixera et al., 2016) as of January 2016. Another study
conducted by Cauchernez et al, (2016) used statistical examinations of the French Polynesia
outbreak to establish the link between ZIKV and microcephaly, with conclusive results. Both
failed to make projections for future illness due to lack of data, but according to Teixera the
expectations are bleak. The ever growing evidence for the link between ZIKV and
microcephaly is undoubtedly the greatest source of concern regarding the virus and it is currently
being studied at length.
10. Link to Guillain-Barr Syndrome
Guillain-Barr Syndrome is an auto-immune degenerative nerve disorder that often leads
to death in its sufferers. It is the most recent discovery concerning ZIKV related illnesses and its
implications are grave. In an article by Derraik and Slaney (2016) it is outlined that 38 cases of
GBS have occurred during the French Polynesia outbreak, far higher than the normal average,
lending credibility to the claim that it is caused by ZIKV.
In the Presidents Column of Elseviers Journal of the Neurological Sciences, a
call to action is made to neurologists in order to combat the debilitating effects of the disease in
impoverished areas (Shakir, 2016). It operates under the assumption that not only is ZIKV linked

to GBS, but that it is an impending disaster waiting to happen.

11. Prevention and Conclusion
The Brazilian government has recommended to its citizens to refrain from having
children until the ZIKV crisis is sorted out in order to mitigate its effects. There are increasing
efforts to eradicate the Aedes mosquitoes carrying the virus by removing their favored breeding
grounds, however this is exceedingly difficult as they are very versatile. Studies conducted on
the Aedes mosquitos current and future habitat place most of south America, the western and
southern US, southern Europe, most of China, Malaysia and Indonesia as well as southern India
at risk for future spread via mosquito (Proestos et al., 2015).
ZIKVs ability to spread as an STD is also cause for concern, as it can spread
beyond these areas without the need for mosquitoes. The link between ZIKV and microcephaly
in infants and GBS in adults is alarming and spurring continued research in many countries
across the globe. We can only hope that future studies show these links to be less conclusive, or
the end results could be catastrophic.

Works Cited

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