Zika virus [1][2][3][4] (
ZIKV) is a member of the
virus family Flaviviridae and the
genus Flavivirus,
transmitted 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.
[5] Zika virus is related to
dengue,
yellow fever,
Japanese encephalitis, and
West Nile viruses.
[6]
The infection, known as
Zika fever, often causes no or only mild symptoms, similar to a mild form of
dengue fever.
[6] It is treated by rest.
[7] Since the 1950s, it has been known to occur within a narrow equatorial belt from Africa to Asia.
The virus spread eastward across the
Pacific Ocean between 2013 and 2014 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.
[8] As of 2016, the illness cannot be prevented by drugs or vaccines.
[7] As of February 2016, there is evidence that Zika fever in pregnant women is associated with abnormal
brain development in their fetuses through
mother-to-child transmission of the virus, which may result in
miscarriage[9] or
microcephaly.
[10][11] There is however no proof yet that the Zika virus causes microcephaly.
[12] A link has been established with neurologic conditions in infected adults, including
Guillain–Barré syndrome.
[13]
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.
[14][15] Other governments or health agencies soon issued similar travel warnings,
[16][17][18]
while Colombia, the Dominican Republic, Ecuador, El Salvador, and
Jamaica advised women to postpone getting pregnant until more is known
about the risks.
[17][19]
Virology
A video explanation of Zika virus and Zika fever
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.
[20][21]
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.
[citation needed]
There are two lineages of the Zika virus: the African lineage, and the Asian lineage.
[22]
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 outbreak.
[22][23] The complete genome sequence of the Zika virus has been published.
[24] Western Hemisphere Zika virus is found to be 89% identical to African genotypes.
[25]
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).
[13]
Vector
Global
Aedes aegypti predicted distribution. The map depicts the probability of occurrence (blue=none, red=highest occurrence).
The Zika virus is transmitted by daytime-active mosquitoes as its
vector. It is primarily transmitted by the female
Aedes aegypti in order to lay eggs,
[26]:2 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.
[27]
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.
[28]
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.
[29] 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.
[30]
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.
[31] 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).
[32] 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.
[33]
Since 2015, news reports have drawn attention to the spread of Zika in Latin America and the Caribbean.
[34] 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.
[35][36][37]
Sexual
As of February 2016, there are three reported cases indicating that Zika virus could possibly be
sexually transmitted.
[38]
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.
[38][39]
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.
[38][40] 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.
[38][41]
Fourteen additional cases of possible sexual transmission are under investigation.
[42]
It is unknown whether women can transmit Zika virus to their sexual
partners. As of February 2016, the CDC recommends that men "who reside
in or have traveled to an area of active Zika virus transmission who
have a pregnant partner should abstain from sexual activity or
consistently and correctly use condoms during sex (i.e., vaginal
intercourse, anal intercourse, or fellatio) for the duration of the
pregnancy." Men who reside in or have traveled to an area of active Zika
virus transmission and their non-pregnant sex partners "might consider"
abstinence or condom use. The CDC did not specify how long these
practices should be followed with non-pregnant partners because the
"incidence and duration of shedding in the male genitourinary tract is
limited to one case report" and that "testing of men for the purpose of
assessing risk for sexual transmission is not recommended."
[38]
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.
[43] Up until February 2016 the link was thought possible but unproven.
[44][45][46]
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.
[9]
According to the 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."
[47]
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.
[48]
Other, unproven
As of February 2016 there are no confirmed cases of Zika virus transmission through
blood transfusions.
[49]
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.
[50] Since January 2014
nucleic acid testing of blood donors was implemented in French Polynesia to prevent unintended transmission.
[50]
Zika fever
Rash on an arm due to Zika virus
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 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.
[27]
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.
[51]
There is a link between Zika fever and neurologic conditions in infected adults, including cases of the
Guillain–Barré syndrome.
[13]
Vaccine development
Effective
vaccines exist for several flaviviruses. Vaccines for
yellow fever virus,
Japanese encephalitis, and
tick-borne encephalitis were introduced in the 1930s, while the vaccine for dengue fever only became available for use in the mid-2010s.
[52][53][54]
Work has begun in the USA towards developing a vaccine for the Zika virus, according to
Anthony Fauci, director of the
National Institute of Allergy and Infectious Diseases.
[55] The researchers at the
Vaccine Research Center
have extensive experience from working with vaccines for other viruses
such as West Nile virus, chikungunya virus, and dengue fever.
[55] 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.
[56]
An Indian company,
Bharat Biotech International, reported in early February 2016 that it was working on vaccines for the Zika virus.
[57] The company is working on two approaches to a vaccine: "
recombinant", involving genetic engineering, and "
inactivated", where the virus is incapable of reproducing itself but can still trigger an immune response. The company announced
animal trials of the inactivated version would commence in late February.
[58]
History
Countries that have past or current evidence of Zika virus transmission (as of January 2016)
[59]
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.
[63] A second isolation from the mosquito
A. africanus followed at the same site in January 1948.
[64] When the monkey developed a fever, researchers isolated from its
serum a
"filterable transmissible agent" that was named Zika virus in 1948.
[27][65]
First evidence of human infection, 1952
Zika virus had been known to infect humans from the results of
serological surveys in Uganda and Nigeria. A serosurvey of 84 people of
all ages showed 50 had antibodies, with all above 40 years of age being
immune.
[66]
It was not until 1954 that the successful 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.
[clarification needed] Infection was proven by a rise in Zika virus specific serum antibodies.
[66]
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.
[67]
Spread in equatorial Africa and to Asia, 1951–1981
From 1951 through 1981, 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, and Vietnam.
[27] From its discovery until 2007, there were only 14 confirmed human cases of Zika virus infection from Africa and Southeast Asia.
[68]
Micronesia, 2007
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.
[69]
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.
[70]
Oceania, 2013–2014
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This section requires expansion. (February 2016) |
Between 2013 and 2014, further epidemics occurred in
French Polynesia, Easter Island, the
Cook Islands, and
New Caledonia.
[4]
Americas, 2015–present
Since April 2015, a large, ongoing outbreak of Zika virus that began in Brazil has spread to much of
South and Central America and the Caribbean.
In January 2016, the CDC issued a level 2 travel alert for people
traveling to regions and certain countries where Zika virus transmission
is ongoing,
[71] and suggested that women thinking about becoming pregnant should consult with their physicians before traveling.
[72] Governments or health agencies of the United Kingdom,
[16] Ireland,
[17] New Zealand,
[73] Canada,
[18] and the
European Union[18] soon issued similar travel warnings. In Colombia,
Minister of Health and Social Protection Alejandro Gaviria Uribe
recommended avoiding pregnancy for eight months, while the countries of
Ecuador, El Salvador, and Jamaica have issued similar warnings.
[17][19]
End of January 2016, the authorities in
Rio de Janeiro, Brazil, announced plans to try to prevent the spread of the Zika virus during the
2016 Summer Olympic Games in that city.
[18]
Between October 2015 and January 2016, Brazilian health authorities
reported more than 3,500 microcephaly cases, some with a severe type and
some having died.
[74]
The worst affected region of Brazil is its poorest, consisting of the 3
Northeastern states Paraiba, Pernambuco and Bahia, where about 1
percent of newborns are suspected of being microcephalic.
[75]
As of February 2016 52 travel-associated Zika virus disease cases and
no locally acquired vector-borne cases had been reported from the US to
the CDC, though there were 9 local cases from US territories Puerto
Rico and the US Virgin Islands.
[76]
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