WHAT IS NOT KNOWN ABOUT ZIKA VIRUS

1. Zika virus
ELISHA JR
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3. • Zika virus is a member of the virus family Flaviviridae and the genus
Flavivirus. It is spread by daytime-active Aedes mosquitoes, such as A.
aegypti and A. albopictus. Its name comes from the Zika Forest of
Uganda, where the virus was first isolated in 1947. Zika virus is related
to dengue, yellow fever, Japanese encephalitis, and West Nile viruses.
• The infection, known as Zika fever, often causes no or only mild
symptoms, similar to a mild form of dengue fever. It is treated by rest.
Since the 1950s, it has been known to occur within a narrow
equatorial belt from Africa to Asia.
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4. • The virus spread eastward across the Pacific Ocean 2013–2014 Zika
virus outbreaks in Oceania to French Polynesia, New Caledonia, the
Cook Islands, and Easter Island, and in 2015 to Mexico, Central
America, the Caribbean, and South America, where the Zika outbreak
has reached pandemic levels. As of 2016, the illness cannot be
prevented by medications or vaccines. Zika fever in pregnant women
is associated with microcephaly but it is unclear whether the virus is
the cause. An association with the neurologic condition Guillain–
Barré syndrome has been found in adults.
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5. • In January 2016, the U.S. Centers for Disease Control and Prevention
(CDC) issued travel guidance on affected countries, including the use
of enhanced precautions, and guidelines for pregnant women
including considering postponing travel. Other governments or health
agencies also issued similar travel warnings, while Colombia, the
Dominican Republic, Ecuador, El Salvador, and Jamaica advised
women to postpone getting pregnant until more is known about the
risks.
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7. Virorogy
• The Zika virus belongs to Flaviviridae and the genus Flavivirus, and is thus
related to the dengue, yellow fever, Japanese encephalitis, and West Nile
viruses. Like other flaviviruses, Zika virus is enveloped and icosahedral and
has a nonsegmented, single-stranded, positive-sense RNA genome. It is
most closely related to the Spondweni virus and is one of the two viruses in
the Spondweni virus clade.
• A positive-sense RNA genome can be directly translated into viral proteins.
In other flaviviruses, such as the similarly sized West Nile virus, the RNA
genome genes encode seven nonstructural proteins and three structural
proteins. The structural proteins encapsulate the virus. The replicated RNA
strand is held within a nucleocapsid formed from 12-kDa protein blocks;
the capsid is contained within a host-derived membrane modified with two
viral glycoproteins. Replication of the viral genome would first require
creation of an anti-sense nucleotide strand.
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8. • There are two lineages of the Zika virus: the African lineage, and the
Asian lineage. Phylogenetic studies indicate that the virus spreading
in the Americas is most closely related to the Asian strain, which
circulated in French Polynesia during the 2013–2014 outbreak. The
complete genome sequence of the Zika virus has been published.
Western Hemisphere Zika virus is found to be 89% identical to African
genotypes, but is most closely related to the strain found in French
Polynesia during 2013–2014.
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9. Transmission
• The vertebrate hosts of the virus were primarily monkeys in a so-
called enzootic mosquito-monkey-mosquito cycle, with only
occasional transmission to humans. Before the current pandemic
began in 2007, Zika virus "rarely caused recognized 'spillover'
infections in humans, even in highly enzootic areas". Infrequently,
other arboviruses have become established as a human disease
though, and spread in a mosquito–human–mosquito cycle, like the
yellow fever virus and the dengue fever virus (both flaviruses), and
the chikungunya virus (a togavirus).
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11. Mosquito
• The Zika virus is spread by daytime-active mosquitoes. It is primarily
spread by the female Aedes aegypti in order to lay eggs, but has
been isolated from a number of arboreal mosquito species in the
Aedes genus, such as A. africanus, A. apicoargenteus, A. furcifer, A.
hensilli, A. luteocephalus and A. vittatus with an extrinsic incubation
period in mosquitoes of about 10 days.
• The true extent of the vectors is still unknown. The Zika virus has
been detected in many more species of Aedes, along with Anopheles
coustani, Mansonia uniformis, and Culex perfuscus, although this
alone does not incriminate them as a vector.
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12. • Transmission by A. albopictus, the tiger mosquito, was reported from
a 2007 urban outbreak in Gabon where it had newly invaded the
country and become the primary vector for the concomitant
chikungunya and dengue virus outbreaks. There is concern for
autochthonous infections in urban areas of European countries
infested by A. albopictus because the first two cases of laboratory
confirmed Zika virus infections imported into Italy were reported from
viremic travelers returning from French Polynesia.
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13. • The potential societal risk of Zika virus can be delimited by the
distribution of the mosquito species that transmit it. The global
distribution of the most cited carrier of Zika virus, A. aegypti, is
expanding due to global trade and travel. A. aegypti distribution is
now the most extensive ever recorded – across all continents
including North America and even the European periphery (Madeira,
the Netherlands, and the northeastern Black Sea coast). A mosquito
population capable of carrying the Zika virus has been found in a
Capitol Hill neighborhood of Washington, D. C., and genetic evidence
suggests they survived at least four consecutive winters in the region.
The study authors conclude that mosquitos are adapting for
persistence in a northern climate.
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14. • Since 2015, news reports have drawn attention to the spread of Zika
in Latin America and the Caribbean. The countries and territories that
have been identified by the Pan American Health Organisation as
having experienced "local Zika virus transmission" are Barbados,
Bolivia, Brazil, Colombia, the Dominican Republic, Ecuador, El
Salvador, French Guiana, Guadeloupe, Guatemala, Guyana, Haiti,
Honduras, Martinique, Mexico, Panama, Paraguay, Puerto Rico, Saint
Martin, Suriname, and Venezuela
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15. Sexual
• As of February 2016, there are three reported cases indicating that Zika virus
could possibly be sexually transmitted. In 2014, Zika virus capable of growth in lab
culture was found in the semen of a man at least two weeks (and possibly up to
10 weeks) after he fell ill with Zika fever. The second report is of a United States
biologist who had been bitten many times while studying mosquitoes in Senegal.
Six days after returning home in August 2008, he fell ill with symptoms of Zika
fever but not before having unprotected intercourse with his wife, who had not
been outside the US in 2008. She subsequently developed symptoms of Zika
fever, and Zika antibodies in both the biologist's and his wife's blood confirmed
the diagnosis. In the third case, in early February 2016 the Dallas County Health
and Human Services department reported that a person contracted Zika fever
after sexual contact with an ill person who had recently returned from a high risk
country. This case is still under investigation. Fourteen additional cases of
possible sexual transmission are under investigation. All cases involve
transmitting the Zika virus from men to women and it is unknown whether
women can transmit Zika virus to their sexual partners.
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16. • As of March 2016, the CDC updated its recommendations about length of
precautions for couples and advised that couples with men who have
confirmed Zika fever or symptoms of Zika should consider using condoms
or not having sex (i.e., vaginal intercourse, anal intercourse, or fellatio) for
at least 6 months after symptoms begin. This includes men who live in and
men who traveled to areas with Zika. Couples with men who traveled to an
area with Zika, but did not develop symptoms of Zika, should consider
using condoms or not having sex for at least 8 weeks after their return in
order to minimize risk. Couples with men who live in an area with Zika, but
have not developed symptoms, might consider using condoms or not
having sex while there is active Zika transmission in the area.
• The "incidence and duration of shedding in the male genitourinary tract is
limited to one case report" and "testing of men for the purpose of
assessing risk for sexual transmission is not recommended.
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17. During pregnancy
• In 2015, Zika virus RNA was detected in the amniotic fluid of two pregnant
women whose fetuses had microcephaly, indicating that the virus had crossed
the placenta and could have caused a mother-to-child infection. Up until
February 2016 the link was thought possible but unproven. Zika fever in pregnant
women is associated with intrauterine growth restriction including abnormal
brain development in their fetuses, which may result in miscarriage; Brain tissue
from two newborns with microcephaly who died within 20 hours of birth and
placenta and other tissue of two miscarriages (11 and 13 weeks) from Rio Grande
do Norte in Brazil tested positive for Zika virus by RT-PCR at the CDC.
• In a cohort study of pregnant, women in Rio de Janeiro, Zika virus infection was
associated with fetal death, placental insufficiency, fetal growth restriction, and
central nervous system (CNS) injury (microcephaly and/or ventricular
calcifications or other lesions) in 12 of 42 fetuses studied using ultrasound.
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18. • According to the World Health Organization (WHO) on 5 February 2016, a
causal link between the Zika virus and microcephaly was "strongly
suspected but not yet scientifically proven" and "Although the
microcephaly cases in Brazil are spatio-temporally associated with the Zika
outbreak, more robust investigations and research is needed to better
understand this potential link.“
• On 5 February 2016, the United States CDC updated its health care
provider guidelines for pregnant women and women of reproductive age.
The new recommendations include offering serologic testing to pregnant
women without Zika fever symptoms who have returned from areas with
ongoing Zika virus transmission in the last 2–12 weeks; and for pregnant
women without Zika symptoms living in such areas, they recommend
testing at the beginning of prenatal care and follow-up testing in the fifth
month of pregnancy
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20. Other, unproven
• As of February 2016 there are no confirmed cases of Zika virus
transmission through blood transfusions. A potential risk is supected
based on a study conducted between November 2013 and February
2014 during the Zika outbreak in French Polynesia, in which 2.8% (42)
of blood donors tested positive for the Zika virus RNA and were
asymptomatic at the time of blood donation. Eleven of those positive
donors reported symptoms of Zika fever after their donation, and
only three of 34 samples grew in culture. Since January 2014 nucleic
acid testing of blood donors was implemented in French Polynesia to
prevent unintended transmission.
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21. Pathogenesis
• Zika virus replicates in the mosquito's midgut epithelial cells and then
its salivary gland cells. After 5–10 days, ZIKV can be found in the
mosquito’s saliva which can then infect human. If the mosquito’s
saliva is inoculated into human skin, the virus infect epidermal
keratinocytes, skin fibroblasts in the skin and the Langerhans cells.
The pathogenesis of the virus is hypothesized to continue with a
spread to lymph nodes and the bloodstream., Flaviviruses generally
replicate in the cytoplasm, but Zika virus antigens have been found in
infected cell nuclei.
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22. Zika fever
• Common symptoms of infection with the virus include mild
headaches, maculopapular rash, fever, malaise, conjunctivitis, and
joint pains. Three well-documented cases of Zika virus were
described in brief in 1954, whereas a detailed description was
published in 1964; it began with a mild headache, and progressed to
a maculopapular rash, fever, and back pain. Within two days, the rash
started fading, and within three days, the fever resolved and only the
rash remained. Thus far, Zika fever has been a relatively mild disease
of limited scope, with only one in five persons developing symptoms,
with no fatalities, but its true potential as a viral agent of disease is
unknown.
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23. Treatment
• As of 2016, no vaccine or preventative drug is available. Symptoms
can be treated with rest, fluids, and paracetamol (acetaminophen),
while aspirin and other nonsteroidal anti-inflammatory drugs should
be used only when dengue has been ruled out to reduce the risk of
bleeding.
• There is a link between Zika fever and neurologic conditions in
infected adults, including cases of the Guillain–Barré syndrome
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25. Vaccine development
• Effective vaccines exist for several viruses of the flaviviridae family,
namely Yellow fever vaccine, Japanese encephalitis vaccine, and Tick-
borne encephalitis vaccine since the 1930s, and dengue fever vaccine
since the mid-2010s. WHO experts have suggested that the priority
should be to develop inactivated vaccines and other non-live
vaccines, which are safe to use in pregnant women and those of
childbearing age.
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26. • The NIH Vaccine Research Center began work towards developing a vaccine
for the Zika virus per a January 2016 report. Bharat Biotech International,
reported in early February 2016 that it was working on vaccines for the
Zika virus using two approaches: "recombinant", involving genetic
engineering, and "inactivated", where the virus is incapable of reproducing
itself but can still trigger an immune response with animal trials of the
inactivated version to commence in late February. As of March 2016, 18
companies and institutions internationally were developing vaccines
against Zika virus, but none had yet reached clinical trials. Nikos Vasilakis of
the Center for Biodefense and Emerging Infectious Diseases predicted that
it may take two years to develop a vaccine, but 10 to 12 years may be
needed before an effective Zika virus vaccine is approved by regulators for
public use
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27. Virus isolation in monkeys and mosquitoes,
1947
• The virus was first isolated in April 1947 from a rhesus macaque
monkey that had been placed in a cage in the Zika Forest of Uganda,
near Lake Victoria, by the scientists of the Yellow Fever Research
Institute. A second isolation from the mosquito A. africanus followed
at the same site in January 1948 When the monkey developed a fever,
researchers isolated from its serum a "filterable transmissible agent"
that was named Zika virus in 1948
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28. First evidence of human infection, 1952
• Zika virus had been known to infect humans from the results of
serological surveys in Uganda and Nigeria, published in 1952: Among
84 people of all ages, 50 individuals had antibodies to Zika, and all
above 40 years of age were immune. A 1952 research study
conducted in India had shown a "significant number" of Indians
tested for Zika had exhibited an immune response to the virus,
suggesting it had long been widespread within human populations.
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29. • It was not until 1954 that the isolation of Zika virus from a human was
published. This came as part of a 1952 outbreak investigation of jaundice
suspected to be yellow fever. It was found in the blood of a 10-year-old
Nigerian female with low-grade fever, headache, and evidence of malaria,
but no jaundice, who recovered within three days. Blood was injected into
the brain of laboratory mice, followed by up to 15 mice passages. The virus
from mouse brains was then tested in neutralization tests using rhesus
monkey sera specifically immune to Zika virus. In contrast, no virus was
isolated from the blood of two infected adults with fever, jaundice, cough,
diffuse joint pains in one and fever, headache, pain behind the eyes and in
the joints. Infection was proven by a rise in Zika virus-specific serum
antibodies.
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30. Spread in equatorial Africa and to Asia, 1951–
1983
• From 1951 through 1983, evidence of human infection with Zika virus
was reported from other African countries, such as the Central
African Republic, Egypt, Gabon, Sierra Leone, Tanzania, and Uganda,
as well as in parts of Asia including India, Indonesia, Malaysia, the
Philippines, Thailand, Vietnam and Pakistan. From its discovery until
2007, there were only 14 confirmed human cases of Zika virus
infection from Africa and Southeast Asia.
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31. Micronesia, 2007
• Main article: 2007 Yap Islands Zika virus outbreak
• In April 2007, the first outbreak outside of Africa and Asia occurred on
the island of Yap in the Federated States of Micronesia, characterized
by rash, conjunctivitis, and arthralgia, which was initially thought to
be dengue, chikungunya, or Ross River disease. Serum samples from
patients in the acute phase of illness contained RNA of Zika virus.
There were 49 confirmed cases, 59 unconfirmed cases, no
hospitalizations, and no deaths.
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32. 2013–2014
Oceania
• This section requires expansion. (February 2016)
• Main article: 2013–2014 Zika virus outbreaks in Oceania
• Between 2013 and 2014, further epidemics occurred in French
Polynesia, Easter Island, the Cook Islands, and New Caledonia.
• Other cases
• On 22 March 2016 Reuters reported that Zika virus was isolated from
a 2014 blood sample of an elderly man in Chittagong in Bangladesh as
part of a retrospective study.
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33. Americas, 2015–present
• Main article: Zika virus outbreak (2015–present)
• As of early 2016, a widespread outbreak of Zika virus is ongoing, primarily
in the Americas. The outbreak began in April 2015 in Brazil, and has spread
to other countries in South America, Central America, Mexico, and the
Caribbean. In January 2016, the WHO said the virus was likely to spread
throughout most of the Americas by the end of the year; and in February
2016, the WHO declared the cluster of microcephaly and Guillain–Barré
syndrome cases reported in Brazil – strongly suspected to be associated
with the Zika virus outbreak – a Public Health Emergency of International
Concern. It is estimated that 1.5 million people have been infected by Zika
virus in Brazil, with over 3,500 cases of microcephaly reported between
October 2015 and January 2016.
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34. • A number of countries have issued travel warnings, and the outbreak
is expected to significantly impact the tourism industry. Several
countries have taken the unusual step of advising their citizens to
delay pregnancy until more is known about the virus and its impact
on fetal development.
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36. References
• Goldsmith, Cynthia (18 March 2005). "Zika Virus". Centers for Disease
Control and Prevention. Retrieved 4 March 2016.
• Jump up ^ Sirohi, D.; Chen, Z.; Sun, L.; et al. (31 March 2016). "The 3.8 Å
resolution cryo-EM structure of Zika virus". Science.
doi:10.1126/science.aaf5316. ISSN 0036-8075.
• Jump up ^ "How to pronounce Zika". How To Pronounce.
• ^ Jump up to: a b "Etymologia: Zika Virus". Emerging Infectious Diseases 20
(6): 1090. June 2014. doi:10.3201/eid2006.ET2006. PMC 4036762. PMID
24983096.
• ^ Jump up to: a b c d e Malone, Robert W.; Homan, Jane; Callahan, Michael
V.; et al. (2 March 2016). "Zika Virus: Medical Countermeasure
Development Challenges". PLOS Neglected Tropical Diseases 10 (3):
e0004530. doi:10.1371/journal.pntd.0004530. ISSN 1935-2735.
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