The infection, known asZika fever or Zika virus disease, often causes no or only mild symptoms, similar to a very mild form ofdengue fever.[5] While there is no specific treatment,paracetamol (acetaminophen) and rest may help with the symptoms.[8] As of April 2019, no vaccines have been approved for clinical use, however a number of vaccines are currently in clinical trials.[9][10][11] Zika can spread from apregnant woman to her baby. This can result inmicrocephaly, severe brainmalformations, and other birth defects.[12][13] Zika infections in adults may result rarely inGuillain–Barré syndrome.[14]
Cross-section of Zika virus, showing the viral envelope composed of envelope proteins (red) and membrane proteins (purple) embedded in the lipid membrane (white): The capsid proteins (orange) are shown interacting with the RNA genome (yellow) at the center of the virus.[26]
Apositive-sense RNA genome can be directly translated into viral proteins. As in other flaviviruses, such as the similarly sized West Nile virus, the RNA genome encodes seven nonstructural proteins and three structural proteins in the form of a singlepolyprotein (Q32ZE1).[27] One of the structural proteins encapsulates the virus. This protein is the flavivirus envelope glycoprotein, that binds to the endosomal membrane of the host cell to initiate endocytosis.[28] The RNA genome forms anucleocapsid along with copies of the 12-kDa capsid protein. The nucleocapsid, in turn, isenveloped within a host-derived membrane modified with two viralglycoproteins. Viral genome replication depends on the making of double-stranded RNA from the single-stranded, positive-sense RNA (ssRNA(+)) genome followed by transcription and replication to provide viral mRNAs and new ssRNA(+) genomes.[29][30]
A longitudinal study shows that 6 hours after cells are infected with Zika virus, the vacuoles and mitochondria in the cells begin to swell. This swelling becomes so severe, it results in cell death, also known as paraptosis. This form of programmed cell death requires gene expression. IFITM3 is a trans-membrane protein in a cell that is able to protect it from viral infection by blocking virus attachment. Cells are most susceptible to Zika infection when levels of IFITM3 are low. Once the cell has been infected, the virus restructures the endoplasmic reticulum, forming the large vacuoles, resulting in cell death.[31]
There are two Zika lineages: the African lineage and the Asian lineage.[32] Phylogenetic studies indicate that the virus spreading in the Americas is 89% identical to African genotypes, but is most closely related to the Asian strain that circulated inFrench Polynesia during the 2013–2014 outbreak.[32][33][34]
The Asian strain appears to have first evolved around 1928.[35]
The vertebrate hosts of the virus were primarilymonkeys in a so-calledenzootic mosquito-monkey-mosquito cycle, with only occasional transmission to humans. Before 2007, Zika "rarely caused recognized 'spillover' infections in humans, even in highly enzootic areas". Infrequently, however, otherarboviruses have become established as a human disease and spread in a mosquito–human–mosquito cycle, like the yellow fever virus and the dengue fever virus (both flaviviruses), and thechikungunya virus (atogavirus).[36] Though the reason for the pandemic is unknown, dengue, a related arbovirus that infects the samespecies of mosquito vectors, is known in particular to be intensified byurbanization andglobalization.[37] Zika is primarily spread byAedes aegypti mosquitoes,[38] and can also be transmittedthrough sexual contact[39] orblood transfusions.[40] Thebasic reproduction number (R0, a measure of transmissibility) of Zika virus has been estimated to be between 1.4 and 6.6 .[41]
In 2015, news reports drew attention to the rapid spread of Zika in Latin America and the Caribbean.[42] At that time, thePan American Health Organization published a list of countries and territories that experienced "local Zika virus transmission" comprising 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.[43][44][45] By August 2016, more than 50 countries had experienced active (local) transmission ofZika virus.[46]
The true extent of the vectors is still unknown. Zika has been detected in many more species ofAedes, along withAnopheles coustani, Mansonia uniformis, andCulex perfuscus, although this alone does not incriminate them as vectors.[48] To detect the presence of the virus usually requires genetic material to be analysed in a lab using the techniqueRT-PCR. A much cheaper and faster method involves shining a light at the head and thorax of the mosquito, and detecting chemical compounds characteristic of the virus usingnear-infrared spectroscopy.[50]
Transmission byA. 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.[51] New outbreaks can occur if a person carrying the virus travels to another region whereA. albopictus is common.[52]
The potential societal risk of Zika can be delimited by the distribution of the mosquito species that transmit it. The global distribution of the most cited carrier of Zika,A. aegypti, is expanding due to global trade and travel.[53]A. aegypti distribution is now the most extensive ever recorded – on parts of all continents except Antarctica, including North America and even the European periphery (Madeira, the Netherlands, and the northeasternBlack Sea coast).[54] A mosquito population capable of carrying Zika has been found in aCapitol Hill neighborhood of Washington, DC, 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.[55] Zika virus appears to be contagious via mosquitoes for around a week after infection. The virus is thought to be infectious for a longer period of time after infection (at least 2 weeks) when transmitted viasemen.[56][57]
Research into its ecological niche suggests that Zika may be influenced to a greater degree by changes in precipitation and temperature than dengue, making it more likely to be confined to tropical areas. However, rising global temperatures would allow for the disease vector to expand its range further north, allowing Zika to follow.[58]
Zika can be transmitted from men and women to their sexual partners; most known cases involve transmission from symptomatic men to women.[39][59][60] As of April 2016, sexual transmission of Zika has been documented in six countries – Argentina, Australia, France, Italy, New Zealand, and the United States – during the 2015 outbreak.[14] ZIKV can persist in semen for several months, with viral RNA detected up to one year.[61] The virus replicates in the human testis, where it infects several cell types including testicular macrophages, peritubular cells and germ cells, thespermatozoa precursors.[62] Semen parameters can be altered in patients for several weeks post-symptoms onset, and spermatozoa can be infectious.[63] Since October 2016, the CDC has advised men who have traveled to an area with Zika should use condoms or not have sex for at least six months after their return as the virus is still transmissible even if symptoms never develop.[64]
Zika virus can spread byvertical (or "mother-to-child") transmission, during pregnancy or at delivery.[12][65] An infection during pregnancy has been linked to changes in neuronal development of the unborn child.[66] Severe progressions of infection have been linked to the development of microcephaly in the unborn child, while mild infections potentially can lead to neurocognitive disorders later in life.[67][68][69] Congenital brain abnormalities other than microcephaly have also been reported after a Zika outbreak.[70] Studies in mice have suggested that maternal immunity to dengue virus may enhance fetal infection with Zika, worsen the microcephaly phenotype and/or enhance damage during pregnancy, but it is unknown whether this occurs in humans.[71]
As of April 2016[update], two cases of Zika transmission throughblood transfusions have been reported globally, both from Brazil,[40] after which the USFood and Drug Administration (FDA) recommended screeningblood donors and deferring high-risk donors for 4 weeks.[72][73] A potential risk had been suspected based on a blood-donor screening study during the French Polynesian Zika outbreak, in which 2.8% (42) of donors from November 2013 and February 2014 tested positive for Zika RNA and were all asymptomatic at the time of blood donation. Eleven of the positive donors reported symptoms of Zika fever after their donation, but only three of 34 samples grew in culture.[74]
Zika virus replicates in the mosquito's midgut epithelial cells and then its salivary gland cells. After 5–10 days, the virus can be found in the mosquito's saliva. If the mosquito's saliva is inoculated into human skin, the virus can infect epidermal keratinocytes, skin fibroblasts in the skin and theLangerhans cells. The pathogenesis of the virus is hypothesized to continue with a spread tolymph nodes and the bloodstream.[21][75] Flaviviruses replicate in thecytoplasm, but Zika antigens have been found in infected cell nuclei.[76]
The viral protein numbered NS4A may lead to small head size (microcephaly) because it disrupts brain growth by hijacking a pathway which regulates growth of new neurons.[77] Specifically, Link et al. reported in 2019 that NS4A disrupted theasymmetric division ofneuronal precursors by the third larvalinstar inDrosophila fruit flies, and that these defects could be suppressed byheterologous expression of humanANKLE2, which NS4Ainteracts with, or by reducing expression of theVRK1homologue Bällchen or theLLGL1 homologue lethal (2) giant larvae.[77][78] Additionally, in fruit flies, both NS4A and the neighboring NS4B restrict eye growth.[79]
Zika fever (also known as Zika virus disease) is an illness caused by Zika virus.[80] Around 80% of cases are estimated to be asymptomatic, though the accuracy of this figure is hindered by the wide variance in data quality, and figures from different outbreaks can vary significantly.[81] Symptomatic cases are usually mild and can resembledengue fever.[80][82] Symptoms may includefever,red eyes,joint pain, headache, and amaculopapular rash.[80][83][84] Symptoms generally last less than seven days.[83] It has not caused any reported deaths during the initial infection.[82] Infection during pregnancy causesmicrocephaly and other brain malformations in some babies.[12][13] Infection in adults has been linked toGuillain–Barré syndrome (GBS) and Zika virus has been shown to infect humanSchwann cells.[82][85]
Diagnosis is by testing the blood, urine, or saliva for the presence of Zika virusRNA when the person is sick.[80][83] In 2019, an improved diagnostic test, based on research fromWashington University in St. Louis, that detects Zika infection in serum was granted market authorization by theFDA.[86]
Prevention involves decreasing mosquito bites in areas where the disease occurs, and proper use of condoms.[83][87] This highlights the importance of sexual health education and safe sex practices in areas like these. Efforts to prevent bites include the use ofDEET orpicaridin - basedinsect repellent, covering much of the body with clothing,mosquito nets, and getting rid ofstanding water where mosquitoes reproduce.[80] There is novaccine.[83] Health officials recommended that women in areas affected by the2015–2016 Zika outbreak consider putting off pregnancy and that pregnant women not travel to these areas.[83][88] Although unavailable to people of impoverished areas, using house screens, air-conditioning and removing yard/house debris help with prevention.[89]
There has been an innovation of genetically modifiedAe. aegypti mosquitoes containing an anti-Zika virustransgene. This transgene contains a group of small synthethicRNAs that are used to target the genome of Zika virus. The use of this modification has been found to reduce viral infection,dissemination and also transmission rates of this virus. There have been trials conducted using these mosquitoes in countries like the Cayman Islands, Malaysia and Brazil. A company calledOxitec Ltd, who genetically engineered this mosquito, set up a field study in Brazil in 2018 that resulted in suppression of up to 96% of disease-transmitting mosquitoes.[90]
While no specific treatment exists,paracetamol (acetaminophen) and rest may help with the symptoms.[83] Admission to a hospital is rarely necessary.[82]
Treatment of Zika includes getting plenty of rest, drinking a lot of fluids to stay hydrated, and over-the-counter medicines such as acetaminophen to relieve fever and pain. It is not recommended to take aspirin or other non-steroidal anti-inflammatory drugs until afterdengue infection is ruled out.[91] If the patient affected is already taking treatment for another medical condition it is advisable to inform your attending physician before taking any other drug or additional treatment.[92]
As of March 2016[update], 18 companies and institutions were developing vaccines against Zika, but they state a vaccine is unlikely to be widely available for about 10 years.[93][94]
In June 2016, the FDA granted the first approval for a human clinical trial for a Zika vaccine.[95] In March 2017, a DNA vaccine was approved for phase-2 clinical trials. This vaccine consists of a small, circular piece of DNA, known as a plasmid, that expresses the genes for the Zika virus envelope proteins. As the vaccine does not contain the full sequence of the virus, it cannot cause infection.[96] Since 2022, this DNA vaccine sponsored by the National Institute of Allergy and Infectious Diseases has completed phase 2.[97]
As of April 2017, both subunit and inactivated vaccines have entered clinical trials.[98] However, like vaccines for other arboviruses, it is difficult to counteract an epidemic of this virus due to how it can appear sporadically and unpredictably.[99]
Although Zika virus is mostly known for its association with birth defects such as microcephaly, it can also cause other pregnancy issues such as fetal loss, stillbirth and preterm birth. Furthermore, it has also been linked to a neurological disorder called Guillain-Barré syndrome. This disorder results in damage to nerve cells that may cause muscle weakness and even paralysis. Although these symptoms last temporarily and most people fully recover, some people affected may end up with permanent damage. Additionally, it is known that Zika viruses can rarely causeencephalitis,meningitis, ormyelitis. It may also rarely result in a blood disorder which can affect clotting time and cause increased bleeding.[100]
Countries that have past or current evidence of Zika transmission (as of January 2016)[101]Spread of Zika[34][102][103]Spread of Zika in Africa and Asia, based on molecular sequence data.[22]
Zika was first known to infect humans from the results of a serological survey in Uganda, published in 1952.[107] Of 99 human blood samples tested, 6.1% had neutralizing antibodies. As part of a 1954 outbreak investigation of jaundice suspected to be yellow fever, researchers reported isolation of the virus from a patient,[108] but the pathogen was later shown to be the closely relatedSpondweni virus.[109] Spondweni was also determined to be the cause of a self-inflicted infection in a researcher reported in 1956.[110]
Spread in equatorial Africa and to Asia, 1951–present
Subsequent serological studies in several African and Asian countries indicated the virus had been widespread within human populations in these regions.[106] The first true case of human infection was identified by Simpson in 1964,[111] who was himself infected while isolating the virus from mosquitoes.[106] From then until 2007, there were only 13 further confirmed human cases of Zika infection from Africa and Southeast Asia.[112] A study published in 2017 showed that the Zika virus, despite only a few cases were reported, has been silently circulated inWest Africa for the last two decades when blood samples collected between 1992 and 2016 were tested for the ZIKVIgM antibodies.[113]In 2017,Angola reported two cases of Zika fever.[114] Zika was also occurring in Tanzania as of 2016.[115]
In April 2007, the first outbreak outside of Africa and Asia occurred on the island ofYap in the Federated States of Micronesia, characterized by rash, conjunctivitis, and arthralgia, which was initially thought to be dengue,chikungunya, orRoss River disease.[116] Serum samples from patients in the acute phase of illness containedRNA of Zika. There were 49 confirmed cases, 59 unconfirmed cases, no hospitalizations, and no deaths.[117]
After October 2013 Oceania's first outbreak showed an estimated 11% population infected for French Polynesia that also presented with Guillain–Barre syndrome (GBS). The spread of ZIKV continued to New Caledonia, Easter Island, and the Cook Islands and where 1385 cases were confirmed by January 2014. During the same year, Easter Island acknowledged 51 cases. Australia began seeing cases in 2012. Research showed it was brought by travelers returning from Indonesia and other infected countries. New Zealand also experienced infections rate increases through returning foreign travelers. Oceania countries experiencing Zika today are New Caledonia, Vanuatu, Solomon Islands, Marshall Islands, American Samoa, Samoa, and Tonga.[118]
Image of a baby withmicrocephaly (left) compared to a normal baby (right). This is one of the potential effects of Zika virus. Signs of microcephaly may develop a few months after birth.
There was anepidemic in 2015 and 2016 in theAmericas. The outbreak began in April 2015 inBrazil, and spread to other countries inSouth America,Central America,North America, and theCaribbean. In January 2016, the WHO said the virus was likely to spread throughout most of the Americas by the end of the year;[119] 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 outbreak – aPublic Health Emergency of International Concern.[6][120][121][122] It was estimated that 1.5 million people were infected by Zika in Brazil,[123] with over 3,500 cases of microcephaly reported between October 2015 and January 2016.[124]
A number of countries issuedtravel warnings, and the outbreak was expected to significantly impact the tourism industry.[6][125] Several countries took the unusual step of advising their citizens to delay pregnancy until more was known about the virus and its impact on fetal development.[20] With the2016 Summer Olympics hosted inRio de Janeiro, health officials worldwide voiced concerns over a potential crisis, both in Brazil and when international athletes and tourists returned home and possibly would spread the virus. Some researchers speculated that only one or two tourists might be infected during the three-week period, or approximately 3.2 infections per 100,000 tourists.[126] In November 2016, theWorld Health Organization declared that Zika virus was no longer a global emergency while noting that the virus still represents "a highly significant and a long-term problem".[127]
As of August 2017 the number of new Zika virus cases in the Americas had fallen dramatically.[128]
On May 15, 2017, three cases of Zika virus infection in India were reported in the state ofGujarat.[130][131] By late 2018, there had been at least 159 cases inRajasthan and 127 inMadhya Pradesh.[132]
In July 2021, the first case of Zika virus infection in the Indian state ofKerala was reported. After the first confirmed case, 19 other people who had previously presented symptoms were tested, and 13 of those had positive results, showing that Zika had been circulating in Kerala since at least May 2021.[133] By August 6th 2021, there had been 65 reported cases in Kerala.[134]
On October 22, 2021, an officer in the Indian Air Force inKanpur tested positive for Zika virus, making it the first reported case in the Indian state ofUttar Pradesh.[135]
Between August and November 2016, 455 cases of Zika virus infection were confirmed inSingapore.[136][137]
In 2023, 722 Zika virus cases were reported in Thailand.[138] From 2019-2022 theRobert Koch-Institut reported 29 imported Zikavirus cases imported into Germany. Of the altogether 16 imported Zika virus cases in 2023, 10 were diagnosed after a trip to Thailand with 62% of all Zika virus cases a significant relative and absolute increase.[139]
In order to understand and effectively respond to the spread of Zika virus, it is important to consider a One Health approach. This approach includes strategies produced through the collaboration of experts in different disciplines.
Specifically, the integrated surveillance of human, animal, and environmental factors can help mitigate Zika virus.[140] A One Health perspective recognizes that human health is greatly impacted by the health of their environment around them, enforcing a multidisciplinary approach to disease prevention and control.
In August 2016, Singapore had an increase in cases of Zika virus causing rapid intervention by public health officials. Some researchers at that time endorsed that taking on a One Health approach is the best way to come up with ethical and effective solutions to contain the spread.[141]
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