Zika virus

This article is about the virus. For the disease, see Zika fever. For the 2015–16 outbreak, see Zika virus outbreak (2015–present).

Zika virus
Electron micrograph of Zika virus. Virus particles are 40 nm in diameter, with an outer envelope and a dense inner core (source: CDC).
Virus classification
Group: Group IV ((+)ssRNA)
Family: Flaviviridae
Genus: Flavivirus
Species: Zika virus

Zika virus /ˈziːkə, ˈzɪkə/[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. In 2014, the virus spread eastward across the Pacific Ocean to French Polynesia, then to Easter Island and in 2015 to Mexico, Central America, the Caribbean, and South America, where the Zika outbreak has reached pandemic levels.[8] The illness cannot yet be prevented by drugs or vaccines.[7] As of February 2016, there is evidence that Zika fever in pregnant women can cause abnormal brain development in their fetuses by mother-to-child transmission, which may result in miscarriage[9] or microcephaly.[10][11] It is not yet known whether 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.

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]

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

Aedes aegypti predicted distribution
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,[25]: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.[26]

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.[27]

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.[28] 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.[29]

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.[30] 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).[31] 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.[32]

Since 2015, news reports have drawn attention to the spread of Zika in Latin America and the Caribbean.[33] 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.[34][35]

Sexual

As of February 2016, three reported cases indicate that Zika virus could possibly be sexually transmitted. In 2014, Zika virus capable of reproducing itself 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.[36][37] 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.[36][38] 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.[36][39]

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."[36]

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.[40] Up until February 2016 the link was thought possible but unproven.[41][42][43] 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."[44]

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.[45]

Other, unproven

As of February 2016 there are no confirmed cases of Zika virus transmission through blood transfusions.[46] 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.[47] Since January 2014 nucleic acid testing of blood donors was implemented in French Polynesia to prevent unintended transmission.[47]

Zika fever

Main article: 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.[26]

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.[48]

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.[49][50][51]

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.[52] 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.[52] 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.[53]

An Indian company, Bharat Biotech International, reported in early February 2016 that it was working on vaccines for the Zika virus.[54] 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.[55]

History

Countries that have past or current evidence of Zika virus transmission (as of January 2016)[56]
Spread of the Zika virus[57]
This file is a candidate for speedy deletion. It may be deleted after Wednesday, 17 February 2016.

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.[58] A second isolation from the mosquito A. africanus followed at the same site in January 1948.[59] When the monkey developed a fever, researchers isolated from its serum a "filterable transmissible agent" that was named Zika virus in 1948.[26][60]

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.[61]

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 rhesusmonkey 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.[61] 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.[62]

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.[26] From its discovery until 2007, there were only 14 confirmed human cases of Zika virus infection from Africa and Southeast Asia.[63]

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.[64] 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.[65] More recently, epidemics have occurred in 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,[66] and suggested that women thinking about becoming pregnant should consult with their physicians before traveling.[67] Governments or health agencies of the United Kingdom,[16] Ireland,[17] New Zealand,[68] 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.[69] 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.[70]

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.[71]

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  68. ↑ Nina Burton (24 January 2016). "Zika virus prompts travel warning for Kiwis". 3News, New Zealand. Retrieved 24 January 2016. The New Zealand Government has followed Britain's lead. Official advice recommends any women who are pregnant or plan to conceive in the near future to delay travel to countries affected with the Zika virus.
  69. ↑ "Microcephaly in Brazil potentially linked to the Zika virus epidemic, ECDC assesses the risk". European Centre for Disease Prevention and Control. Retrieved 18 January 2016.
  70. ↑ "Brazil Zika outbreak: More babies born with birth defects". BBC. 21 January 2016.
  71. ↑ Zika virus disease in the United States, 2015–2016, as of February 10, 2016 Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID) Division of Vector-Borne Diseases, 11 February 2016 retrieved 13 February 2016.

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