Zika Virus: A Comprehensive Review

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This assignment presents a thorough examination of Zika virus. It delves into the virus's transmission mechanisms, the range of symptoms it causes in infected individuals, its potential long-term health consequences, existing treatment options, and the latest advancements in research aimed at combating this emerging infectious disease.
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Zika Virus 1
ZIKA Virus
1) Introduction
Zika virus came from the flavivirus borne from the mosquito emerged from the spondweni group
which was at first identified in the monkeys of Uganda in 1947. Later in 1952, it was identified
in the people living in Uganda along with Nigeria and gradually the virus covered the USA, Asia
pacific countries, Arica, Tanzania and many other countries across the globe. In July 2015 Brazil
identified a relation between Guillain-Barre disorder (GBS) and Zika infection; it damages the
nervous system by the weakening of muscles affecting the immune system (Murray, 2016). In
October 2015 Brazil also reported a relationship between microcephaly and Zika infection. More
than 5600 cases of microcephaly reported in the year 2016 which is greater than 20 folds with
respect to average o past five years.
Zika virus along with the Spondweni creates a sub-branch into the genus flavivirus which
belongs to the flaviviridae family. It results in spondweni fever in human beings which is
characterized by fever with symptoms of nausea, headache, chills, and discomfort. Sponwei virus
was first identified in 1955 from mansonia uniformis mosquitoes which emerged from Lake
Simbu which is situated in Spondweni region of South Africa (Murray, 2016). This virus as
recently observed in sub regions of Saharan Africa and Papua New Guinea. Genes of this virus
are made up of complex ssRNA molecules which is having two non-coding regions by analogy.
It is a code for a polypeptide which is a combination of the capsid(C), envelope (E), precursor
membrane (prM) and non-structural proteins (NS) (Murray, 2016). This coding is responsible
for the recent outbreak in 2015. As per the recent reports published by WHO is widely spread in
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Zika Virus 2
the Caribbean and Latin American countries. Although the virus came into existence 60 years
back in Africa the awareness to cause possible threats was revealed in the recent years only. In
many countries, the detection of this virus is due to the circulation of the travellers who are
travelling from the countries where this virus is much active (Rawlinson, 2016). Recent reports
say that in India three cases of this virus have been introduced through reverse transcription
polymerase chain reaction (RT-PCR) by routine laboratory surveillance. It has been also reported
that many sub-tropical and tropical regions in the world are at risk of this virus in the form of
Chikungunya, yellow fever, and DENV (Joob & Wiwanitkit, 2017). Few studies suggest that
since the year 2007 to march 2017 total 84 countries across the world is affected by this virus.
ZIKV is an icosahedral, single stranded, enveloped, positive sense RNA virus with the non-
segmented genome. It is 40 nm in diameter having dense projection coated lipid envelope, which
consists of a membrane and envelope glycoproteins having a dense inner core. Virions which are
situated on the surface of cell membrane get entry into the host cell after which the mRNA
transcription takes place (Joob & Wiwanitkit, 2017). Whenever the virus from the mosquito is
transferred to the healthy human being it causes infection same is the case with the pregnant
mother, if the virus gets transferred from mother to fetus then there are chances of an infant born
with microcephaly.
2) Zika infection: a global threat to human population
Before 2015 ZIKV was not much in the notice as compared to another disease like EBOLA,
influenza. Vomiting, headache, joint pains, rashes, red eyes all are the symptoms of this infection
and is quite easy to detect as there is no specific therapy or vaccine available due to its treatable
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Zika Virus 3
and mild symptoms. But these two factors have taken this virus in the notice (Wang, Wang &
An, 2016). People did not gave much attention to this virus due to its low incidence and mildness
of symptoms. There are two factors due to which ZIKV infection has emerged as a global issue
for discussion.
2.1) Rapid transmission of the virus
In the year 1947, scientists detected this virus from the samples which were taken from a sentinel
rhesus monkey in ZIKA forests, Uganda. The first proof of this infection was identified when a
scientist fell ill while working on the strains collected from the mosquito; this discovered that
this virus can be spread to human beings (Wang, Wang & An, 2016). ZIKA virus is spreading at
an extraordinary speed, it has covered almost one fourth of the countries across the globe.
Dengue and Chikungunya are also the infections which have emerged from this virus.
2.1.1) Link with congenital birth defects
French and Brazilian countries have reported several incidences of spine malformation and
congenital brain specially microcephaly. Transmission of this virus from mother to her fetus has
resulted in microcephaly in infants which has to lead to the underdeveloped brain, leading to
developmental retardation and it can also cause death in some cases (Weltman, 2016). There are
different types of malformation due to infections, which have resulted in deaths but these cases
are never linked with ZIKA virus. On December 8th, 2015 Brazil reported 1762 incidence of
microcephaly whereas total 84 cases were reported in 2014. An infant born with microcephaly
tested positive for ZIKA virus died on 28th November. This case created panic in people of
Brazil; everyone was in fear due to this outbreak (Weltman, 2016). Many health organizations
came into action and confirmed that there is an increase in the number of cases of disorders in
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Zika Virus 4
central nerve system. These organizations advised people especially pregnant ladies to read
about the symptoms of this virus and take preventive measures to keep them away from
mosquito bites. Travellers were also warned that they should restrict their travelling to affected
areas (Sorbera & Stringer, 2017).
2.2) Lack of vaccine. No proper research and common symptoms
Another reason is that there is no vaccination available for ZIKA virus as of now. Scientists are
doing efforts to produce one, but testing and then producing a medicine takes years and is
expensive also. The virus was occurring occasionally and no research was done for this (Spivak,
2016). only few people were researching on ZIKA virus and none of them were aware of the fact
that how severe this virus is and it can spread how rapidly. Funding was being allotted to the
research done on many other infectious diseases; people were not at all prepared to respond
quickly to this virus. In the remote areas where there is a lack of resources and facility people did
not pay much attention to ZIKA until WHO has interfered. Another reason was that it has similar
symptoms to another infectious disease like Chikungunya, dengue and it is generally circulating
in the same regions where the other infections are circulating. As it is almost impossible to
prevent one from mosquito bites, WHO recommended pregnant ladies from not going to places
where this virus is active and ladies who are planning to become pregnant should consult their
doctors before visiting these places (Spivak, 2016). Lack of strong immunity system and
research labs in remote areas can also be one of the reasons from spreading this disease.
3) Major symptoms
Mild fever, skin rashes, red eyes, headache, joint pain, and conjunctivitis are the most common
symptoms of ZIKA infection and they appear after 3-12 days of biting of mosquito. It can
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Zika Virus 5
sometimes occur without symptom but often it has been observed that it has mild symptoms that
can last up to 7 days. Severe symptoms which can lead to hospitalization are very rare (Sheng et
al., 2017). ZIKA virus is transmitted by Ades Ageypti, a day biting mosquito. These mosquitoes
are active during morning and late morning and evening. These mosquitoes also transmit the
infection of yellow fever, Chikungunya, and dengue (Sheng et al., 2017). Whenever a female
Ades Ageypti bites any human, a virus presented in the salivary gland gets injected of the
infected mosquito into the wound where the anti-coagulants contained in her saliva facilitate
feeding, and without knowing the male mosquito also injects the ZIKA virus into the host. There
is another way through which the infection is transmitted from mother to fetus and when the
child is born he suffers from the underdeveloped brain (Du, Zhou & Jiang, 2017). Sexual
transmission is also one of the ways through which the infection is transferred from the male to
female or vice versa. Blood transfusion through organ transplant also results in the transmission
of infection (Sheng et al., 2017).
4) Diagnosis of ZIKV infection
Currently, there are no such medication and vaccines available for this virus, your immune
system is the best cure available till now but one can take precautions:
From mosquito bites- prevention from mosquito bites is the key measure to avoid this
virus from spreading. Using mosquito repellents, wearing full sleeves clothes, screened
windows will minimize the risk of affecting the virus. It is very much important for
children and old people to take precautions because there immune system is weak. People
who are travelling must avoid going to places which are affected from ZIKA and
pregnant ladies, if any has been infected by this virus then she should be immediately
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taken to hospital as this infection is transmissible and can affect her fetus (Slavov,
Otaguiri, Kashima & Covas, 2016). It is very much critical to prevent breeding of these
mosquitoes in houses as they breed and reproduce in stagnant water bodies, so one must
ensure to cover all the water filling containers and empty waste water and sprinkle the
pesticide timely to prevent breeding of mosquitoes.
Through sexual transmission- transmission through sexual activities has been confirmed
by many labs. In order to prevent one from the risk of sexual intermission and pregnancy
complications due to ZIKA virus contamination, one should indulge in safe sex or avoid
sexual activities during pregnancy if the partner is affected by ZIK infection (Gruber &
Krause, 2017). If anyone has come from the area which is affected by the virus then he
should avoid sexual intermission at least for 8 weeks although if there is no symptom
found.
5) ZIKV Recent epidemic status/ Role of agents
In the year 2015 Brazil and panama have reported many cases of microcephaly; Colombia
has also joined the league by detecting few cases which are linked with Zika virus. In other
countries, there are not enough research and evidence to prove the link of this case with Zika.
After the outbreak, Brazil has seen 20 times rise in the cases of the Zika infection where
babies are born to an infected mother with microcephaly (Slavov, Otaguiri, Kashima &
Covas, 2016). This virus is currently active in 38 countries and gradually increasing in other
countries by affecting infants causing fetal malformation and nervous disorders. If this goes
beyond control then it will be a serious health catastrophe for the world. Looking after this
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condition many health organizations have identified that there is an urgent need Point of Care
Testing (POCT (Slavov, Otaguiri, Kashima & Covas, 2016)). At present, there are 30
companies who are working on it and have developed an advanced version of diagnostic
tests. For vaccines total 23 proposals are being worked on by around 14 vaccine developer
companies located in India, France, Australia, and the US. Since these vaccinations are being
prepared for the pregnant ladies and the women of child bearing age, it must fulfil high
standards of safety (Zea-Vera & Parra, 2016). Potential results of five new tools of mosquito
control are also being tested by many experts among whom no one qualified for full scale
implementation. Some Brazilian experts were in doubt that Zika alone is responsible for
microcephaly or there are other factors which to be held responsible for the birth defects. As
on 5th August 2016 total of 185 travellers cases, two pregnant mother cases, and one sexually
transmitted case have been detected in Canada (Zea-Vera & Parra, 2016).
Traditionally, there is a TORCH agent which has four characteristics consisting of mild illness in
the mother who is infected, transmission of virus to fetus vertically, development of various
anomalies in the fetus and in some cases maternal therapy therefore this should be considered as
a severe TORCH agent which is threatening public health.
6) Drugs and vaccines available so far
There are many types of research on Zika virus vaccination but none of them made it to he
market. The target population is pregnant women and women bearing the age of the child so
it should be safe and effective. Only effective DNA vaccines would be preferred rather than
vaccines which are made out of weakened Zika virus to ensure safety measures (Zea-Vera &
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Zika Virus 8
Parra, 2016). The increasing number of cases which are affected by the virus is an alarming
situation so there is an urgent need for production of vaccines.
Clinical trials- few of the best clinical trials used were mice, rhesus macaques and
then human. Three different types of investigational vaccines were used, DNA based
vaccine, inactivated virus vaccine and adenovirus vector based vaccines. Each of the
three trials holds the possibility of designing effective Zika vaccine (Gowder, 2016).
Efforts with mouse model- research were conducted on mice and reported
six different Zika virus antibodies out of which four neutralized the strains
of mosquitoes transmitted from Africa, Asia, and America. NIAID
supported team x-ray crystal images of these four antibodies and extracted
Zika proteins which could be beneficial in producing vaccines (Martins, Dye
& Bavari, 2016). DNA vaccine or purified inactive virus vaccine provides
complete safety in mice against zikv in single immunization (Gowder,
2016).
Efforts with rhesus macaques- the above testing of inactivated Zika virus
vaccine were also done on 16 rhesus macaques. These animals were two
injections continuously for four weeks after which they did not show any
symptom of Zika virus another experiment was also done in which
researchers administered two doses of an experimental DNA and one dose of
adenovirus vector vaccine to three different groups of four monkeys each.
These monkeys were then kept in contact with Zika virus for four weeks
(White et.al, 2016). Both DNA and adeno virus vaccines provided complete
protection from infection. Both of them protected from infection, boost the
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Zika Virus 9
immune system and had no adverse side effect of vaccines. But due to the
huge gestational difference in rhesus macaques and human this experiment
needs to be done on a human to provide vaccines (Takasaki, 2016).
Efforts with human testing- the NIAID and NIH performed this test on 80
healthy candidates between the age of 18 to 35 years. DNA vaccine was
considered for the clinical trial in human. The first stage will identify the
response of immune system to the vaccine (Takasaki, 2016). Two new
technologies including synthetic pieces of DNA and electric pulse to open
immune cells were considered so that they take up vaccines better. As a
result, these vaccines were found safe and immune system was also
responding well. DNA or gene based vaccinations provides strong and
durable protection against disease (Takasaki, 2016). Phase 1 of this research
is still under process once the results show a positive outcome, the second
phase will start. US government has distributed a license to use these
vaccines and materials all over the world for research purpose (Du, Zhou &
Jiang, 2017).
6) Process of vaccine delivery
GLS-5700 the inovio Zika product is called DNA vaccine. In this vaccine, there is a protein
inbuilt that encircles the Zika virus. The site where injection has been injected is damaged using
a device that passes an electric pulse which guides DNA into the cells into the cells through a
process called electroporation (Nilika & Kamboj, 2016). The cells then the instruct immune
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system to consider Zika virus as foreign invader which needs to be attacked using antibodies to
fight against it. Several researchers and scientists are in competition to develop the vaccination
for Zika virus but there is a group of scientists who have found 24 FDA approved drugs which
have shown some potential to block Zika from infecting human cells. Few of the drugs which are
used for treating cancer and depression have also shown some positive signs of curing Zika virus
in pregnant women (Nilika & Kamboj, 2016). These researchers initially took 774 drugs out of
which 24 were found effective. Now, these drugs are being used for further studies to develop
vaccines against Zika virus from spreading.
7) Conclusion
Zika virus is an infection which has come from mosquito bite generally in the day time. It has
very mild symptoms and was first discovered in the year 1948.among all the countries Africa is
said to be the most affected country from this virus followed by south and North America. The
main reason for this global emergency is its link with congenital birth defects to an infected
mother and lack of vaccines available due to very limited researches done (Nilika & Kamboj,
2016). Another reason is the absence of population immunity. As there are no vaccines available
for this infection WHO has advised people to stay at home and prevent themselves from these
mosquito bites. It is the only option left with people to take corrective measures like use
mosquito repellent, use screened glass, wear full sleeves clothes by this way they can prevent
themselves from biting of mosquito (S, 2017). Specially pregnant ladies must take cares if they
are affected then there is cancer that it can affect their baby also which can cause congenital birth
defects in the baby in the form of underdeveloped brain or weak muscles or damaged nervous
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Zika Virus 11
system. Other prevention can also be taken by cleaning the house properly and don’t let the
mosquitoes breed. Tremendous information is available on the research being done on the Zika
virus, but says now there is no such vaccine came out which can prevent humans from this virus
(S, 2017).
This virus is currently active in 38 countries and gradually increasing in other countries by
affecting infants causing fetal malformation and nervous disorders. If this goes beyond control,
then it will be a serious health catastrophe for the world (Maslow, 2017). So keeping this in mind
various health organizations have issued information on how to prevent themselves from this
infection and what are the possible symptoms through which one can identify that they are
suffering from this infection (Şahiner, 2016). Mild fever, headache, reddish eyes, rashes on the
skin are some of the symptoms, but these symptoms are somewhat same as of Chikungunya,
yellow fever, and dengue. Many countries are working on identifying the correct vaccination for
this infection, which is safe and secure for pregnant women, but till now no such product has
come up in the market (Şahiner, 2016). The target population is pregnant women and women
bearing the age of the child so it should be safe and effective. Only effective DNA vaccines
would be preferred rather than vaccines which are made out of weakened Zika virus to ensure
safety measures.
The increasing number of cases which are affected by the virus is an alarming situation so there
is an urgent need for production of vaccines. It is up to humans how they prevent themselves
from this infection, numerous information has been provided by the health organizations now
depends on us, how do we use this information and prevent ourselves and our family and
surrounding (S, 2017). It is an alarming situation in the world and it is high time now that they
should seriously act on it and produce vaccines which can prevent this disease.
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References
Du, L., Zhou, Y., & Jiang, S. (2017). The latest advancements in Zika virus vaccine
development. Expert Review Of Vaccines, 16(10), 951-954.
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Gowder, S. (2016). Zika Virus - Vaccines and Management. International Journal Of Vaccines
& Vaccination, 2(1). http://dx.doi.org/10.15406/ijvv.2016.02.00019
Gruber, M., & Krause, P. (2017). Regulating vaccines at the FDA: development and licensure of
Zika vaccines. Expert Review Of Vaccines, 16(6), 525-527.
http://dx.doi.org/10.1080/14760584.2017.1324304
Joob, B., & Wiwanitkit, V. (2017). Human Zika and West Nile virus neurological
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Rawlinson, W. (2016). Pregnancy, the placenta and Zika virus (ZIKV) infection. Microbiology
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