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.
There are two Zika lineages: the African lineage and the Asian lineage. 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 in French Polynesia during the 2013–2014 outbreak.
The Asian strain appears to have first evolved around 1928.
In 2015, news reports drew attention to the rapid spread of Zika in Latin America and the Caribbean. At that time, the Pan 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. By August 2016, more than 50 countries had experienced active (local) transmission of Zika virus.
The true extent of the vectors is still unknown. Zika 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 vectors. To detect the presence of the virus usually requires genetic material to be analysed in a lab using the technique RT-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 using near-infrared spectroscopy.
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. 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 northeastern Black Sea coast). A mosquito population capable of carrying Zika has been found in a Capitol 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. 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 via semen.
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.
Zika can be transmitted from men and women to their sexual partners; most known cases involve transmission from symptomatic men to women. 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. ZIKV can persist in semen for several months, with viral RNA detected up to one year. The virus replicates in the human testis, where it infects several cell types including testicular macrophages, peritubular cells and germ cells, the spermatozoa precursors. Semen parameters can be altered in patients for several weeks post-symptoms onset, and spermatozoa can be infectious. 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.
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 the Langerhans cells. The pathogenesis of the virus is hypothesized to continue with a spread to lymph nodes and the bloodstream. Flaviviruses replicate in the cytoplasm, but Zika antigens have been found in infected cell nuclei.
Zika fever (also known as Zika virus disease) is an illness caused by Zika virus. 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. Symptomatic cases are usually mild and can resemble dengue fever. Symptoms may include fever, red eyes, joint pain, headache, and a maculopapular rash. Symptoms generally last less than seven days. It has not caused any reported deaths during the initial infection. Infection during pregnancy causes microcephaly and other brain malformations in some babies. Infection in adults has been linked to Guillain–Barré syndrome (GBS) and Zika virus has been shown to infect human Schwann cells.
Diagnosis is by testing the blood, urine, or saliva for the presence of Zika virus RNA when the person is sick. In 2019, an improved diagnostic test, based on research from Washington University in St. Louis, that detects Zika infection in serum was granted market authorization by the FDA.
Prevention involves decreasing mosquito bites in areas where the disease occurs, and proper use of condoms. This highlights the importance of sexual health education and safe sex practices in areas like these. Efforts to prevent bites include the use of DEET or picaridin - based insect repellent, covering much of the body with clothing, mosquito nets, and getting rid of standing water where mosquitoes reproduce. There is no vaccine. Health officials recommended that women in areas affected by the 2015–2016 Zika outbreak consider putting off pregnancy and that pregnant women not travel to these areas. Although unavailable to people of impoverished areas, using house screens, air-conditioning and removing yard/house debris help with prevention.
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 after dengue infection is ruled out. 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.
In June 2016, the FDA granted the first approval for a human clinical trial for a Zika vaccine. 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. Since 2022, this DNA vaccine sponsored by the National Institute of Allergy and Infectious Diseases has completed phase 2.
As of April 2017, both subunit and inactivated vaccines have entered clinical trials. 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.
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 cause encephalitis, meningitis, or myelitis. It may also rarely result in a blood disorder which can affect clotting time and cause increased bleeding.
Zika was first known to infect humans from the results of a serological survey in Uganda, published in 1952. 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, but the pathogen was later shown to be the closely related Spondweni virus. Spondweni was also determined to be the cause of a self-inflicted infection in a researcher reported in 1956.
Subsequent serological studies in several African and Asian countries indicated the virus had been widespread within human populations in these regions. The first true case of human infection was identified by Simpson in 1964, who was himself infected while isolating the virus from mosquitoes. From then until 2007, there were only 13 further confirmed human cases of Zika infection from Africa and Southeast Asia. A study published in 2017 showed that the Zika virus, despite only a few cases were reported, has been silently circulated in West Africa for the last two decades when blood samples collected between 1992 and 2016 were tested for the ZIKV IgM antibodies.
In 2017, Angola reported two cases of Zika fever. Zika was also occurring in Tanzania as of 2016.
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. There were 49 confirmed cases, 59 unconfirmed cases, no hospitalizations, and no deaths.
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.
As of August 2017 the number of new Zika virus cases in the Americas had fallen dramatically.
On 22 March 2016, Reuters reported that Zika was isolated from a 2014 blood sample of an elderly man in Chittagong in Bangladesh as part of a retrospective study.
On May 15, 2017, three cases of Zika virus infection in India were reported in the state of Gujarat. By late 2018, there had been at least 159 cases in Rajasthan and 127 in Madhya Pradesh.
Between August and November 2016, 455 cases of Zika virus infection were confirmed in Singapore.
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. 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.
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