INTRODUCTION:

Zika virus (ZIKV) infection in humans was first described in Nigeria (Africa) in1954, after the virus was isolated from a rhesus monkey in 1947. Fewer people have died in the last half-century. More than 20 human infections have been observed, with the majority of them occurring in children. The information originated from the yellow fever virus (YFV) surveys on sero surveys.¹ Although the virus was first discovered in Asia in 1966, its potential impact on public health was not recognised until outbreaks in the Pacific from 2007 to 2015, when it travelled throughout the Americas. The ability of ZIKV to induce congenital abnormalities in fetuses and babies, as demonstrated by the microcephaly pandemic in Brazil, is a first for a mosquito-borne viral illness.² Several significant human diseases are caused by flaviviruses, including Dengue, West Nile, and Yellow fevers, Japanese encephalitis, and tick-borne infections. In recent years, Zika virus infections have attracted the attention of international medical community, chiefly of their rolein causing microcephaly and other neurodevelopmental abnormalities which occur as a consequence of maternal infections.³

Origin and history of Zika virus:

The Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) belonging to the Flavivirus genus and the Flaviviridae family. Aedes mosquito species such as Aedes aegypti, Aedes albopict us, and Aedes africanus transmit the disease to humans. Zika virus (ZIKV) is a single-stranded, positive-sense RNA virus with a genome of 10.7 kb that encodes a single polyprotein that is cleaved into three structural proteins and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5)⁴Zika, a flavivirus spread mostly by mosquitos of the species Aedes, was first found in Uganda in 1947.⁵The first large ZIKV outbreak outside of Africa occurred on Yap Island in 2007, with about three-quarters of the population over the age of three suspected of being sick.⁶ ZIKV expanded quickly throughout the Americas, starting in Brazil.⁸The Zika virus continued to spread in the Americas and the Pacific in 2015–16, with outbreaks first recorded in the continental United States, Africa, and Southeast Asia.⁹

Emergence of Zika virus:

Zika virus (ZIKV) is a flavivirus spread by mosquitos that has emerged as a global health threat due to its capacity to cause congenital illness in the setting of infection during pregnancy and the potential to trigger explosive epidemics.⁷ In 2007, the first large-scale epidemics of ZIKV infection involving more than a few people were discovered.¹⁰ This first large ZIKV outbreak outside of Africa and Asia happened on Yap Island in the Federated States of Micronesia, which is located in the northwest Pacific Ocean. Fever, rash, arthralgia, and conjunctivitis were all reported during the outbreak.¹¹ It was just a matter of time until it spread to other parts of the world as a vector-borne disease associated to Aedes mosquitoes that are found all over the world.¹² ZIKV spread quickly throughout the Americas, starting in Brazil. In Asia, 2 outbreaks have been reported in Singapore and Vietnam.⁸ “Variances in African and Asian lineage, as well as differences in Zika virus genetic evolution,” Porrino said, “could possibly provide an explanation for the emergence of current epidemics and their diverse presentation.”¹³ Notably, despite the presence of a large number of susceptibles in the native population, ZIKV circulation in Brazil declined in 2017 and 2018. Vaccines are also promise for future ZIKV epidemics, including one in Brazil that is now through phase III testing.¹⁴

Epidemiology:

Sero surveys undertaken starting in the 1950s revealed that ZIKV was circulating in a number of African and Asian nations. In the first 60 years, only about 20 human infections were confirmed.¹⁵In 2007 on Yap island total of 49 confirmed and 59 probable cases were identified using a combination of RT-PCR and serological tests, with significant uncertainty in the latter test interpretations due to the presence of dengue virus. Rather than from Yap island, followed by spread to several other islands in Oceania including New Caledonia, the Cook Islands, and Easter Island.¹⁰ Local ZIKV transmission have been observed in 72 countries and territories since about August 31, 2016. Up to September 1, 2016, about 500 000 locally acquired cases had been detected in the Americas alone.¹⁶The Zika virus (ZIKV) outbreak in 2016 sparked widespread alarm, particularly in Latin American and Caribbean countries, with an estimated 440 000–1300 000 cases in Brazil.¹⁷

Pathogenesis of Zika virus:

The life cycle of ZIKV is poorly understood, with the majority of information derived from understanding of closely related flaviviruses. ZIKV is spread between humans through the bite of female Aedes spp. mosquitoes in the urban cycle. Following the re-emergence of ZIKV as a possible pathogen for severe CNS developmental problems in 2015, research quickly moved forward in three directions: clinical case reports and epidemiological studies, animal models, and cell culture models.¹⁸Zika virus can infect a variety of cell types after being transmitted by a mosquito bite, including skin keratinocytes, dermal fibroblasts, and dendritic cells (DCs) In vitro experiments on fibroblasts exposed to the Zika virus revealed that these cells had significant infection rates 24 to 48 hours after infection.³

Zika virus transmission types:

1. ZIKV vector born transmission:

The probable vectors for ZIKV virus transmission by biting are Aedes aegypti, Aedes polynesiensis, and Aedes albopictus. DENV and CHIKV are transmitted by the mosquito Aedes aegypti. The major vector of lymphatic flariasis transmission in French Polynesia is Aedes polynesiensis. Following the outbreak in French Polynesia, these mosquito species were collected and tested for ZIKV infection using RT-PCR; only one Aedes aegypti mosquito was found to have ZIKV RNA; experimental investigations revealed that the French Polynesian strain of Aedes aegypti can replicate the French Polynesian ZIKV strain. However, there is still a chance that ZIKV will spread to other countries. It's possible that fewer countries did not report transmission due to a lack of detection.

2. Non vector born transmission:

ZIKV infection can spread non-vectored during childbirth (from mother to kid), organ transplants, blood transfusions, and sexual contact. Serosurvey investigations found antibodies against ZIKV in goats, rats (Merioneshurrianae and Tateraindica), sheep, and bats. According to these investigations, there is no apparent link between ZIKV and a specific animal species. It is transmitted to people through the bite of infected Aedes aegypti mosquitoes. ZIKV has been found to have a high RNA load in breast milk, indicating that transmission can occur through breast feeding. ZIKV can also be transferred by blood transfusions, as reported in Brazil in December 2015, the first instance of ZIKV blood transfusion transmission. ZIKV is adopted to transmit by enzootic and sub Urban cycle in enzootic setting this involves mosquitoes of Aedes species and non-human primates, however transmission in Urban setting involves human and mosquitoes of Aedes species demonstrate vector and non-vector borne transmission of ZIKV.¹⁹

Diagnosis:

The mainstays of the routine diagnosis of Zika virus infection are the detection of viral nucleic acid by RT-PCR and the detection of IgM antibodies by IgM-capture enzyme-linked immunosorbent assay (MAC-ELISA). The detection of viral nucleic acid in serum provides a definitive diagnosis; however, in most instances viremia is transient, and diagnosis by RT-PCR has been most successful within 1 week after the onset of clinical illness.^20,21 In contrast, viral RNA was detected in serum approximately 10 weeks after infection in a pregnant woman whose foetus had evidence of congenital infection.²² Although the precise timing of the onset and the duration of the IgM antibody response to Zika virus that is detectable by MAC-ELISA have not yet been defined, extensive experience with other, related flaviviruses suggests that IgM will appear as viremia wanes within the first week after symptom onset and will persist for several months.²³

The greatest challenge with serologic cross-reactivity arises from the “original antigenic sin” phenomenon.²⁵For patients who have previously been exposed to a heterologous flavivirus by natural infection or vaccination, the antibody response to the previous infecting flavivirus will be more vigorous than the response to the current one.²¹ Even the PRNT cannot reliably establish a diagnosis in such patients. This is particularly problematic in areas in which dengue is endemic, where more than 90% of the population may have had previous exposure to dengue virus²⁶ and dengue and Zika viruses may be cocirculating.

Limited data suggest that Zika virus RNA can be detected longer in urine than in serum; if verified, this would extend the period during which a definitive diagnosis of Zika virus infection can be established by RT-PCR.^27,28,29

Symptoms and Route of Transmission:

Symptoms:

Many people infected with Zika virus won’t have symptoms or will only have mild symptoms. The most common symptoms of Zika are

·Fever

·Rash

·Headache

·Joint pain

·Conjunctivitis (red eyes)

·Muscle pain

Route of Transmission:

Through mosquito bites:

Zika virus is transmitted to people primarily through the bite of an infected Aedes species mosquito (Ae. aegypti and Ae. albopictus). These are the same mosquitoes that spread dengue and chikungunya viruses. These mosquitoes typically lay eggs in or near standing water in things like buckets, bowls, animal dishes, flower pots, and vases. They prefer to bite people, and live indoors and outdoors near people. Mosquitoes that spread chikungunya, dengue, and Zika bite during the day and night.

A mosquito gets infected with a virus when it bites an infected person during the period of time when the virus can be found in the person’s blood, typically only through the first week of infection. Infected mosquitoes can then spread the virus to other people through bites.

From mother to child:

A pregnant woman can pass Zika virus to her foetus during pregnancy. A pregnant woman already infected with Zika virus can pass the virus to her foetus during the pregnancy or around the time of birth.

Zika virus has been found in breast milk. Possible Zika virus infections have been identified in breastfeeding babies, but Zika virus transmission through breast milk has not been confirmed. Additionally, we do not yet know the long-term effects of Zika virus on young infants infected after birth. Because current evidence suggests that the benefits of breastfeeding outweigh the risk of Zika virus spreading through breast milk.

Through sex:

Zika can be passed through sex from a person who has Zika to his or her partners. Zika can be passed through sex, even if the infected person does not have symptoms at the time. Though not well documented, the virus may also be passed by a person who carries the virus but never develops symptoms. Studies are underway to find out how long Zika stays in the semen and vaginal fluids of people who have Zika, and how long it can be passed to sex partners. We know that Zika can remain in semen longer than in other body fluids, including vaginal fluids, urine, and blood.

Through blood transfusion:

To date, there have not been any confirmed blood transfusion transmission cases in the United States. There have been multiple reports of possible blood transfusion transmission cases in Brazil. During the French Polynesian outbreak, 2.8% of blood donors tested positive for Zika and in previous outbreaks, the virus has been found in blood donors.

Through laboratory and healthcare setting exposure:

There are reports of laboratory acquired Zika virus infections, although the route of transmission was not clearly established in all cases. To date, no cases of Zika virus transmission in healthcare settings have been identified in the United States. Recommendations are available for healthcare providers to help prevent exposure to Zika virus in healthcare settings.

Risks:

Anyone who lives in or travels to an area with risk of Zika and has not already been infected with Zika virus can get it from mosquito bites. Once a person has been infected, he or she is likely to be protected from future infections.³⁰

Treatment, Prevention, and Control:

As with the other mosquito-borne flaviviruses, treatment for uncomplicated Zika virus infection focuses on symptoms. No Zika virus vaccine exists; thus, prevention and control measures center on avoiding mosquito bites, reducing sexual transmission, and controlling the mosquito vector. Potentially effective methods of prevention that are focused on reducing infections among pregnant women include avoiding unnecessary travel to areas of on going. Permethrin treatment for clothing, bednets, window screens, and air conditioning.^{32, 33.}The most effective A. Dengue control programs make extensive use of peridomestic insecticide spraying during outbreaks, but little evidence supports its efficacy as a single control intervention.³⁴ Given these limitations, an integrated prevention and vector-control approach combined with timely detection of illness, communication of up-to-date and correct information, and development of a rapid response that involves the community are recommended.³⁵

Pregnancy Outcomes in Infection:

Pregnant women living in or traveling to areas with local mosquito-borne Zika virus transmission are at risk for Zika virus infection, which can lead to severe fetal and infant brain abnormalities and microcephaly. In February 2016, CDC recommended³⁶routine testing for Zika virus infection of asymptomatic pregnant women living in areas with ongoing local Zika virus transmission at the first prenatal care visit, retesting during the second trimester for women who initially test negative, and testing of pregnant women with signs or symptoms consistent with Zika virus disease (e.g., fever, rash, arthralgia, or conjunctivitis) at any time during pregnancy. To collect information about pregnant women with laboratory evidence of recent possible Zika virus infection and outcomes in their fetuses and infants, CDC established pregnancy and infant registries.³⁷Among completed pregnancies with positive nucleic acid tests confirming Zika infection identified in the first, second, and third trimesters, the percentage of fetuses or infants with possible Zika-associated birth defects was 8%, 5%, and 4%, respectively. Among liveborn infants, 59% had Zika laboratory testing results reported to the pregnancy and infant registries.³⁸

Zika in body Fluids:

ZIKV Infection can be diagnosed through detection of ZIKV RNA in blood, urine, and other body fluids by reverse-transcriptase-polymerase-chain-reaction-assay. ZIKV RNA also detected in semen, urine, saliva, cerebrospinal fluid, vaginal or cervical secretions and other body fluids. ZIKV RNA is present in serum for a longer period than expected. ZIKV also diagnosed by detection of anti-ZIKV IgM antibodies.³⁹ ZIKV RNA is prone to defradation in urine with loss of detectable virus even when specimens are frozen at -80 degree celcius for 10 days. Detection of ZIKV positive urine samples, particularly those containing low ZIKV titers may be aided with the addition of nucleic acid stabilizer during urine specimen processing. ZIKV RNA levels in urine declined steadily at room temperature.

Possible Treatments and Drug development strategies:

A commonly used approach for antiviral drug development involves targeting specific vulnerable stages of life cycle of pathogen in order to disrupt its propagation within cells, effectively protecting cells and their neighbors from viral spreading. In drug discovery, structure based guidance is for better understanding of the unique ZIKV pathology and selective drug design. No clinically approved vaccine or drug is currently available for ZIKV. This unmet medical need has motivated a global effort to develop countermeasures. Several promising ZIKV vaccine candidates have already entered clinical trials. In contrast, antiviral development of ZIKV is lagging behind. Here, the overall strategies for ZIKV drug discovery, including (i) repurposing of clinically approved drugs, (ii) viral replication-based phenotypic screening for inhibitors, and (iii) targeted drug discovery of viral proteins. Along with vaccines, the development of antiviral treatment will provide a complementary means to control ZIKV infections.⁴⁰ Previously, curcumin exhibited antiviral properties against several viruses, including dengue virus and hepatitis C virus, among others. The antiviral effect of curcumin on Zika and chikungunya viruses, two mosquito-borne outbreak viruses. Both viruses responded to treatment of cells with up to 5μm cumin without impacting cellular viability. Direct treatment of

virus with curcuma reduced infectivity of virus in a dose- and time-dependent manner for these enveloped viruses, as well as vesicular stomatitis virus.⁴¹

Recent developments in zika antiviral treatment:

Non-steroidal anti-inflammatory drugs (NSAIDs) should be avoided and individuals should seek medical advice before taking additional medication if they are already taking medicines for another medical condition. During epidemics homeopathic pharmaceuticals are more effective in reduction of mortality and morbidity as compare to conventional system of medicines At the present time, no effective antiviral treatments are available for Zika virus infection. In order to block the viral entry into the cell, various strategies have been used. The other approaches include the inhibition of endosomal fusion using compounds that reduce the acidity of endo-lysosomal vesicles like chloroquine (an anti-malaria drug) and disrupting the electrostatic interaction between cell and virus membrane using squalamine (a cationic chemical). Despite the many studies done on Zika antiviral treatments, so far no FDA approved category A drug has been found safe to use in mothers and foetuses.³

Vaccine development:

ZIKV vaccine development is advancing rapidly thanks to collaborations among academia, governments, and industry. Current knowledge gaps related to the properties, epidemiology, and pathology of ZIKV increase the complexity of vaccine development, but historical success in developing other flavivirus vaccines encourages optimism. An ongoing epidemic in the Americas and the impact of ZIKV congenital syndrome (ZCS) necessitate rapid development of a safe, efficacious vaccine. Preclinical studies of ZIKV vaccine candidates need to continue in parallel with human trials, informing their design and the evolving target product profile (TPP), including dose level and schedule, delivery method, and primary vaccine population. Though live or other replicating virus vaccine platforms would probably be less acceptable in emergencies, they might offer advantages for routine immunization, such as long-term protective immunity with minimal dosing. This starting age would align with WHO recommendations and with the precedent set by human papillomavirus vaccines (target group, girls 9 to 13 years old).⁴²

Safety and immunogenicity of anti-zikavaccine:

No serious adverse events were reported. The most frequently reported events were injection-site pain (any level), redness, swelling, and itching, which occurred in approximately 50% of the participants. Systemic adverse events were uncommon and included headache, myalgias, upper respiratory infection, fatigue, and nausea. Except, injection site pain 58% of the adverse events were unrelated to vaccine administration. Transient laboratory abnormalities included one case of grade 4 hyperkalemia, one case of grade 3 hypoglycemia, two cases of grade 1 neutropenia, and one case of grade 1 anemia, which totaled five events in four participants.⁴³

Lessons learned after pandemic:

The public health community was unprepared for the emergence of ZIKV and the dramatic and unexpected consequences of ZIKV infections during pregnancy. Pandemic increased positive awareness about critical social justice issues, such as stigma toward and isolation of families of infants with congenital Zika syndrome, the reproductive rights of women, and access to safe abortion and contraception in womens. The experience of the pandemic highlights important deficiencies in our understanding of ZIKV and the barriers to translating evidence into implementable guidelines, especially in low- and middle-income countries. The pandemic is illustrative of the universal failure of vector-control programs in regions where rapid urbanization and interconnectivity promote epidemic spread.

LITERATURE REVIEW:

· Michael S. Diamond: The 2019 Stanley J. Korsmeyeraward, was given by the American Society for Clinical Investigation (ASCI), honors Michael S. Diamond of the Washington University School of Medicine for his work uncovering the molecular basis of disease caused by globally emerging RNA viruses.Dr. Diamond has made seminal contributions to our understanding of the pathogenesis of several emerging viruses, including the Dengue, West Nile, Chikungunya, and Zika viruses, as well as the host immune system responses to infection.He worked on a lot of different viruses — some of them have not emerged, but He still work on them, and some of them do emerge. That said, Zika was relatively unique in circumstance, and it traces back to an NIH meeting in 2015 on Chikungunya virus.

·Theodore C. Pierson: While training there, Dr. Pierson initiated a new research program to study the cell biology of the envelope proteins of flaviviruses, with a focus on West Nile virus and dengue viruses. In 2005, Dr. Pierson was recruited to initiate the Viral Pathogenesis Section of the Laboratory of Viral Diseases and to continue his work on flaviviruses.

·Miller FG: His study shows that published cases with ZIKV-related GBS generally have both sensory and motor symptoms, facial palsy, demyelination on electrophysiological examination, and a severe disease course that often necessitates ICU admittance. Outbreaks of ZIKV and GBS may appear in the future and his study could help clinicians in diagnosing and managing GBS patients in ZIKV endemic areas, and increased our understanding of the neuropathology of ZIKV.

·Waqar Ali: Waqar Ali worked on origin, treatment, transmission of zika virus and he wrote many of books and articles about how zika originated, transmitted, treatments, preventions and all other information of zika. His study shows that information to peoples to avoid zika infection.

·McNeil: McNeil’s book is thorough in its timeline and excellent at describing the political history of public health management for Zika. This history includes the blaming of an insecticide for the initial cases of Guillain-Barré syndrome in French Polynesia in 2013, the US Centers for Disease Control and Prevention’s initial handling of evidence of a sexual transmission route for Zika virus, McNeil presented convincing arguments at the end of the book for why the recommendations to delay pregnancy should have been stronger, clearer.

MATERIALS AND METHODS:

For that project we take the information from review articles, journals, research papers, newspaper articles and the websites like pub med

Materials:

www.pubmed.com

research papers on goggle

review articles available from google

Methods:

First we go to the google and type research articles of zika virus then we download the articles of zika virus. Then we point out the parameters related to zika virus and then search each and every parameter on a PubMed. For that go to the google and type pub med and click on that website which comes at a first on a screen. Then type parameter which means to search and then we get more no of abstracts then select the appropriate informatation about the zika virus. For eg we want the information about the History of Zika Virus then type that in a search box of pub med and we get more no of articles and their abstracts then take the novel information from that. Collect all the information from the research papers, articles, Newspaper articles, Review articles, Journals and websites and then type that novel information in MS Word and make the word file of that information. We include that what we know about the Zika virus from many more information and write references of the articles, journals and copy the cite from pub med articles. AS per above steps we make the review project on Zika virus.

CONCLUSION:

ZIKV is a mosquito-borne flavivirus that has been quietly circulating in a number of countries in equatorial Africa and Asia for the past half-century. It did, however, migrate eastward from those endemic places in 2007, to the Pacific Islands, and then to the Americas in 2015. ZIKV has been circulating in these newly infected locations since then. In humans, ZIKV infection is largely asymptomatic, with only a tiny percentage of infected people experiencing mild fever symptoms. However, in recent years, ZIKV has been identified as an unknown cause of serious neurological illnesses such Guillain-Barré syndrome and microcephaly. ZIKV was first isolated in Uganda in 1947, and it is transmitted to humans mostly by the bite of infected Aedes species mosquitoes (e.g., Aedes aegypti and Aedes albopictus), as well as non-vector mechanisms (i.e., vertical transmission, sexual transmission, and blood transfusion).

ZIKV infection has a particular pathogenesis, as do the disorders it produces. Future research is needed to establish the similarities and differences between ZIKV and other flaviviruses in terms of replication, pathophysiology, and transmission, with the objective of improving diagnosis and generating possible treatments and vaccines for ZIKV.

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Received on 16.02.2022 Modified on 18.08.2022

Res. J. Pharmacology and Pharmacodynamics.2023;15(1):24-30.

DOI: 10.52711/2321-5836.2023.00006