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RRJoMV (2019) 25-33 © STM Journals 2019. All Rights Reserved Page 25
Research & Reviews: A Journal of Microbiology and Virology
ISSN: 2230-9853 (Online), ISSN: 2349-4360 (Print)
Volume 9, Issue 2
www.stmjournals.com
A Review: Recent Outbreak of Zika Viruses in India, its
Vectorology and Virology
Akshita Srivastava, Neetu Kachhwaha*
Department of Zoology, University of Rajasthan, Jaipur, Rajasthan, India
Abstract
Zika virus is an arbovirus (arthropod-borne virus) which belongs to the family Flaviviridae that
was first isolated in 1947 from blood of a febrile rhesus macaque monkey during a yellow fever
study in the Zika forest of Uganda and later identified in Aedes africanus mosquito from the
same forest. But in 2007, the first major outbreak of Zika virus infection occurred in Yap Island
(Federated States of Micronesia), where, it was noticed as an outbreak of illness characterized
by rashes, conjunctivitis, subjective fever, arthralgia, and arthritis. Approximately 73% of the
population was infected and out of which 18% developed symptomatic disease. In 2015, an
estimated 1.5 million cases were reported in Brazil. In 2017, 305 cases were reported from
United Kingdom and in 2018, 109 cases from India (Rajasthan, Gujrat and Madhya Pradesh).
The best method to diagnose the disease is by RT-PCR and till date there is no vaccine or
specific treatment available. The most acceptable method for prevention is to reduce egg laying
sites of the adult mosquito. Continued researches of vaccine development, treatment,
medication and prevention strategies are in progress to eradicate the disease.
Keywords: Zika, Aedes, epidemic, Rajasthan, ZIKV
*Author for Correspondence E-mail: drneetu2011@gmail.com
INTRODUCTION
Since the rising of microbiology, researchers
have focused on pathogens that make us and
our domesticated animals and plants sick. As
the onset of symptoms was the best way to
identify about virus pathogenesis, but there was
problem in detecting some viruses that infect
humans without showing any symptoms.
In recent years, breakthrough in genomic
sciences has allowed researchers to detect
viruses living in and on the human body,
collectively called the human virome [1]. The
pathogenic viruses may become more virulent
by undergoing mutation and recombination [2].
So, by understanding the mode of pathogenicity
of viruses with constant monitoring in reference
to the human virome certainly, in the area of hot
spots where disease occurs frequently, may
provide a tool to early detect the virus before it
causes viral interaction and becomes pandemic.
This article focuses on the Zika virus which
received increased attention during the recent
years. This study hereby briefly outlines about
the basic biology, genomic structure,
epidemiology, clinical presentation and the
bases, to the extent it was understood, of how
these agents have emerged and the current risk
they represent.
The ZIKA virus was isolated from a pool of
Aedes africanus mosquitoes which were
collected in 1948 from the same region of the
Zika forest [3]. First three cases of human
infection were found in Nigeria, in the year
1954 [4]. The Zika virus has two families based
on the regions they were first identified;
African and Asian; isolated from enzootic
vectors Aedes spp. in Africa (A. africanus) and
Malaysia (A. aegypti) [5]. Earlier, symptomatic
Zika virus infections were limited to sporadic
cases or small clusters of patients. Since then,
Zika virus infection has spread rapidly. The
outbreaks have occurred in French Polynesia,
Cook Islands, Easter Island, and New
Caledonia [6].
In the beginning of February 2016, Zika virus
spread fast from Africa and Asia to the America
and Europe and the congenital Zika syndrome
incidence has caused the World Health
Review on Recent Outbreak of Zika Viruses in India Kachhwaha and Srivastava.
RRJoMV (2019) 25-33 © STM Journals 2019. All Rights Reserved Page 26
Organization (WHO) to concern about the zika
virus epidemic as a matter of public health [7].
Its genome was sequenced in the year 2006 and
found serologic overlapping between Zika virus
(ZIKV) and related flaviviruses, such as dengue
virus (DENV) and West Nile virus (WNV) [8].
Spondweni virus (SPONV) is an arbovirus, or
arthropod-borne virus, which is a member of
the family Flaviviridae and the genus
Flavivirus [9]. It is a part of the Spondweni
serogroup which includes two species, Zika
virus (ZIKV) and the Spondweni virus
(SPONV). Transmission of this virus into
humans can lead to a viral infection known as
Spondweni fever, with symptoms ranging from
headache and nausea to myalgia and arthralgia
[10]. However, SPONV is phylogenetically
very much similar to ZIKV, so, they are
sometimes misdiagnosed as ZIKV along with
other viral illnesses. The flavivirus consists of
Zika virus, yellow fever virus, West Nile virus,
and dengue virus, while hepatitis C virus forms
part of the Hepadnaviridae genus.
VIROLOGY
Zika virus is approximately 11 kb in length,
positive-sense, single-stranded RNA virus of
the genus Flavivirus [11, 12]. Some researchers
stated that the Zika virus genome consists of
10,794 nucleotides which encode for 3,419
amino acids and replicate their genetic material
in the host cell cytoplasm [13, 14]. Virion
particles of ZIKV are 40–60 nm in diameter,
and spherical in shape having icosahedral
symmetry covered by a lipid envelope. The
genome of ZIKV contains two flanking un-
translated regions (3′ and 5′ un-translated
regions) and a single long open reading frame
encoding a polyprotein that is infolded in capsid
(C), precursor of membrane (prM), envelope
(E) and seven non-structural (NS) proteins
NS1-NS2A-NS2B-NS3-NS4A-NS4B-NS5
[15–17, 12] (Figure 1).
PATHOGENESIS
The importance of mosquito starts when it
inoculates virus into the human host, its mode
of entry into the cell resembles to that of other
flaviviruses, whereby the virus enters the skin
cell through cellular receptors, enabling
migration to the lymph nodes and bloodstream
[2]. Few studies revealed that the Zika virus
infection enters into the other cells like skin
fibroblasts, keratinocytes, and immature
dendritic cells in human beings. Once the
flavivirus enters the cell, it replicates within
endoplasmic reticulum-derived vesicles.
However, it was found that Zika virus replicates
in nuclei of host cell and in this respect, it is
different from other flavivirus which is
significant in diagnosis and investigation of this
virus [18].
CLINICAL SYMPTOMS
The manifest of dengue, chikungunya and Zika
virus infections have a similar initial clinical
presentation and may be reported as any of the
first three of the following four monitored
syndromes: (i) acute fever and rash, (ii)
prolonged fever, (iii) influenza-like illness and
(iv) diarrhoea. The serological study of DENV
and ZIKV patients may be similar due to the
cross reaction between the members of same
family, Flavivirus group. Hence, the RNA
detection methods and genome sequencing are
the best methods used for the conformation of
the disease [6] (Figure 2).
The RT-PCR amplification test is positive if
sample is taken from the urine but not from
serum sample which shows that urine is better
as a sample material during diagnosis for RNA
detection of ZIKV, and indeed the viral load in
urine has been shown to be higher and easily
detectable for a longer period, as compared to
serum in parallel to dengue [19]. Another
unique characteristic of ZIKV is its high
homologous recombination activity. ZIKV
appears to have undergone multiple
recombination events between 1947 and 2007.
Such active recombination is uncommon
among flaviviruses and has been suggested as a
mechanism for the adaptation of ZIKV to the
Aedes dalzieli vector [20].
Research & Reviews: A Journal of Microbiology and Virology
Volume 9, Issue 2
ISSN: 2230-9853 (Online), ISSN: 2349-4360 (Print)
RRJoMV (2019) 25-33 © STM Journals 2019. All Rights Reserved Page 27
Fig. 1. Zika Virus: Icosahedral Symmetry [17].
Fig. 2. The Genome of Zika Virus [17].
Approximately about 80% of the ZIKV
infections may be asymptomatic [11]. Clinical
presentations of Zika fever vary from
asymptomatic infections to a self-limiting
febrile sickness, presenting as a “dengue-like”
syndrome with low fever, bilateral
conjunctivitis, maculopapular rash, headache,
retro-orbital pain and arthritis/arthralgia with
edema of the tiny joints of hands and feet,
myalgia, vertigo and asthenia [21–24].
Occasionally, sore throat, cough and loose
bowels are also been reported [25].
Conjunctivitis in Zika fever is non-purulent and
bilateral; the rash has reported to be
Review on Recent Outbreak of Zika Viruses in India Kachhwaha and Srivastava.
RRJoMV (2019) 25-33 © STM Journals 2019. All Rights Reserved Page 28
erythematous and generalized that spreads from
the face toward the limbs. There are some
important systemic symptoms that are
presented by high fever, chills, rigors, sore
throat, hypotension, cervical, submandibular,
axillary and/or inguinal lymphadenopathies. In
addition, digestive symptoms may also be
present including nausea, vomiting, diarrhea,
constipation, abdominal pain and aphthous
ulcers. Patients with genitourinary symptoms
including hematuria, dysuria, perineal pain and
hematospermia may also occur which usually
have quantifiable virus particles in urine and/or
semen [11].
Moreover, arthralgia in Zika fever is not as
much as those of chikungunya fever. These
presentations are not pathognomonic and
laboratory tests are required to exclude other
causes of febrile diseases. As a matter of fact,
Zika can be misdiagnosed during the acute
stage because of nonspecific signs and
symptoms. However, neurologic complications
including Guillain-Barré syndrome (GBS) have
been reported in some cases [19, 23].
TRANSMISSION
The transmission of Zika virus follows the
sylvatic transmission cycle through the bite of
mosquito from one vertebrate to another. The
virions exist in three forms; as non-infectious
immature, infectious mature, and host
membrane binding fusogenic/non-comparable.
Humans are incidental hosts in the lifecycle of
the virions. Monkeys and apes are the main host
to the virions, while some studies showed that
sheep, elephants, and goats had antibodies
against Zika virus which suggests that they may
be possible reservoir hosts as well. When a
blood-feeding adult female Aedes mosquito
bites into the skin of its mammalian host, it
allows, infection of Zika virus permissive cells
via specific receptors [15]. ZIKV replication
leads to activation of an antiviral innate
immune response and the production of type I
interferons in infected cells. Other nonvector
modes of Zika virus transmission include
congenital, perinatal, and sexual [26–29].
Possible transmission may also take place by
blood transfusion, animal bite, and laboratory
exposure [30–33].
DIAGNOSIS
The diagnosis of Zika virus infection is not only
based on clinical evaluation but laboratory
testing is also necessary for the diagnosis,
because other arbovirus can be clinically
overlapped with each other [34]. Researchers
reported that the Real time PCR (R-T PCR) is
the most preferred and reliable method for
testing Zika virus during acute illness <7 days
onset of symptoms [35, 36]. The second type of
diagnosis is based on the detection of antibodies
[37, 24]. The serum samples are examined by
immunoglobulin G (IgG) ELISA with ZIKV
antigen as well as the samples are tested by
immunoglobulin M (IgM) ELISA with the viral
antigens of Zika virus, Dengue virus, yellow
fever virus, Japanese encephalitis virus and
Murray Valley encephalitis virus [35].
Furthermore, some studies explored that the
plaque reduction neutralization assay has
improved specificity more than the
immunoassays but may still earn cross-reactive
results in secondary flavivirus infections [38,
39].
TREATMENT
There is no verified or clinically approved
preventive medication available for ZIKV.
Treatment of Zika fever is supportive and
includes acetaminophen for fever, headache or
myalgia. However, aspirin must be avoided
because of the risks of bleeding in those with
thrombocytopenia and increasing Reye's
syndrome in children [11, 12]. The non-
steroidal anti-inflammatory drugs are also not
suggested because of the increased risk of
hemorrhagic syndrome [39]. Enough
rehydration for fluid loss should be applied.
Based on earlier studies, some of the drugs that
target hepatitis C can have some special effects
on ZIKV. Anti-malarial hydroxychloroquine is
an autophagy inhibitor and in vitro testing has
shown inhibition of dengue virus. Moreover,
amodiaquine works via blockage of autophagy
and inhibits Zika virus pathogenicity.
Immunotherapeutic strategies may propose
hope for reducing clinical complications from
ZIKV including Guillain-Barre Syndrome [40].
PREVENTION
Currently no vaccine is available for Zika virus
infection and no specific treatment is known for
Research & Reviews: A Journal of Microbiology and Virology
Volume 9, Issue 2
ISSN: 2230-9853 (Online), ISSN: 2349-4360 (Print)
RRJoMV (2019) 25-33 © STM Journals 2019. All Rights Reserved Page 29
this infectious disease. The prevention should
be taken during the infection by using
antipyretics, and analgesic drugs [3]. Other
prevention from mosquito bites should be taken
care, like wearing full sleeve clothes and long
pants, light-colored clothing, using insect
repellants. Besides DEET as a repellant, use of
natural oils of lemon eucalyptus, lemongrass,
cedar, or soy and para-methane-diol, are also
effective but they are not recommended in case
of infants [41]. At community-level, mosquito
breeding sites should be eliminated to reduce
potential egg-laying by drying wet
environments or using insecticide treatment
[34]. Pregnant women residing in countries free
to Zika virus are advised not to travel the
affected areas or the country. The pregnant
women who have travelled the area with
ongoing ZIKV transmission should be tested
regularly and their fetus should be tested by
ultrasound to monitor fetal anatomy and its
growth.
EPIDEMIOLOGY
Epidemiology of Zika Virus around the
World
In 2015, an outbreak of ZIKV occurred in the
state of Rio Grande do Norte, Brazil; some
studies mentioned that this is because of Asian
lineage during FIFA World Cup. In March 2015,
another outbreak of ZIKV occurred in the state
of Bahia. It has been hypothesized that the virus
invaded Brazil through another event that was
held in Rio de Janeiro in August 2014, the “Va'a
World Sprint Championship canoe race” where
countries including French Polynesia, New
Caledonia, Cook Islands and Easter Islands
attended [42, 23].
In November 2017, 305 cases were reported in
the United Kingdom, all of them were
associated with travelling [43]. However,
between June 2015 and January 2017, 21
countries in the European Union reported 2133
confirmed cases of infection in which 106 cases
were of pregnant women [44]. WHO has
warned the risk of Zika virus transmission in
Europe is low to moderate, although three areas
are at high risk: the island of Madeira in
Portugal, Georgia, and the southern part of the
Russian Federation [45].
Most of the survey results were based on
serological studies using various tests like the
Complement Fixation (CF) test,
Hemagglutination Inhibition Test, cross
Neutralization Test (NT), Haemagglutination
Assay (HA), mouse protection test, and ELISA.
These studies contain valuable information
regarding ZIKV infection in Asia. As of
September 1, 2016 there have been reports of
imported or autochthonous ZIKV infections in
all Asian countries except Brunei, Hong Kong,
Myanmar, and Nepal [46].
Zika Virus Epidemic in India
In India, the Zika virus outbreaks were reported
in states of Rajasthan, Gujarat, and Madhya
Pradesh. The reports revealed that the number
of people infected with Zika virus was 109 in
Rajasthan till October, 2018. According to a
spokesperson of the State Medical and Health
Department, nine new cases were confirmed
from Jaipur, the capital of Rajasthan. However,
out of 109 Zika virus infected patients, 91 are
healthy now after getting proper treatment. The
affected areas were treated for larvicidal and
adulticidal activities against mosquito. Most of
the cases have been reported from densely
populated area of Shastri Nagar locality of the
Jaipur city. Because of this outbreak the Central
government of India rushed an Indian Council
of Medical Research (ICMR) team to the state
to intensify vector control measures. The team
of experts from ICMR who visited the affected
areas of Jaipur has changed the insecticides
which are being used in the city and
neighbouring districts to kill Aedes mosquitoes
under integrated mosquito management
programme. After the cases were reported, the
precautions were taken like, intense fogging
and other anti-larvae activities being carried out
in the areas from where cases had been reported
[47].
According to the recent report published by a
news channel, Zika virus is transmitted through
the vector mosquito, Aedes aegypti and causes
symptoms like fever, conjunctivitis, muscle and
joint pain, and skin rashes. It is harmful to
pregnant women, as it can lead to
microcephaly, a condition in which a baby's
head is significantly smaller than expected, in
newborn children. The State Health Department
Review on Recent Outbreak of Zika Viruses in India Kachhwaha and Srivastava.
RRJoMV (2019) 25-33 © STM Journals 2019. All Rights Reserved Page 30
suggested that pregnant women should not visit
the areas under epidemic alert. Besides recent
outbreaks discussed so far in 2018, the first
outbreak has already been reported a year ago
in Ahmedabad in January 2017 and secondly in
Tamil Nadu's (Krishnagiri district) in July 2017
of Zika virus in India. Both these outbreaks
were successfully managed through intensive
monitoring and the mosquito management [48].
On October 31, 2018 first case of Zika was
reported in Madhya Pradesh when AIIMS,
Bhopal diagnosed three positive cases from
three different regions Sehore, Bhopal and
Vidisha. The news updated that after three
weeks of Rajasthan Zika outbreak, another state
in Central India, Madhya Pradesh has been hit
by the vector-borne disease. About 89 people
were found to be positive for Zika as reported
in the latest outbreak in Madhya Pradesh. The
patients were recorded from four districts of the
State as, Bhopal, Sehore, Vidisha and Sagar.
Among 89 people positive for Zika virus, 17
were confirmed in pregnant women. Although
these cases included the death two people also
due to Zika infection, but the State Government
has not yet confirmed by saying that Zika itself
does not kill human beings. The Government
also stresses that Zika virus does not carry any
mutational changes which can cause fetal
microcephaly. The Ministry of Health and
Family Welfare, in their statement revealed that
Indian Council of Medical Research NIV, Pune
had confirmed the same. They have also
sequenced five Zika virus strains during the
outbreak in Jaipur and concluded that the
current Zika virus strain has no known
mutations linked to fetal microcephaly and high
transmissibility that has affected Rajasthan
[49].
CONCLUSION
In February 2016, World Health Organization
(WHO) declared ZIKV infection to be a public
health emergency [50]. The reason of spread of
the ZIKV infection in the regions where the
virus is not endemic is because of the ease of
presence of competent mosquito vectors [34].
But the patients with weak immunity can be
more vulnerable to develop severe disease if
infected with ZIKV. Symptoms become
elaborate after a bite by a Zika virus-infected
Aedes mosquito with an incubation period of 2–
14 days [37].
If ZIKV infections occur in a population with
DENV (or other flavivirus) also, cross-
reactivity of ZIKA with dengue may occur,
which could lead to the false conclusion that
dengue caused the epidemic. However, re-
examination of samples with RT-PCR for
laboratory diagnosis from infected areas may
provide a good result. More medication,
prevention and cure aspects are in progress,
including prototype multiplex molecular assays
that concurrently test for Zika virus,
Chikunguniya virus, and Dengue virus. The
simplest way to prevent the spread of ZIKA
virus, vector control should be considered as the
topmost priority. The World Health
Organization (WHO) and the Pan American
Health Organization (PAHO) have issued many
recommendations. Specifically, lower rates of
human crowding in urban areas, wider access to
air conditioning, use of mosquito repellents,
and waste management limit mosquito borne
transmission.
Continued epidemiologic study, combined with
research involving animal models, will offer
increased insight, which could lead to novel
prevention strategies in coming years [51].
ACKNOWLEDGEMENT
The authors give a deep sense of gratitude
towards all the online sources and researchers
from where the review article was made. The
author shows gratitude towards the anonymous
reviewers for reviewing the manuscript.
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Cite this Article
Akshita Srivastava, Neetu Kachhwaha. A
Review: Recent Outbreak of Zika Viruses in
India, its Vectorology and Virology. Research
& Reviews: A Journal of Microbiology and
Virology. 2019; 9(2): 25–33p.
