Zika Virus- And Its Emerging Impact On Global Health

The World Health Organization (WHO) declared a public health emergency of international concern (PHEIC) on February 1, 2016, as there were more than 4,000 microcephaly cases and neurological disorders in some areas affected by the Zika virus (ZIKV).

Authors: Dr. Muhammad Akram, Dr. Muhammad Ali Tahir, Dr. Ali Hussain, Dr. Muhammad Waqas Raza, and Dr. Muhammad Muneeb

Zika Virus

Also called Zika fever, Zika disease, Zika virus disease. an illness caused by a chiefly mosquito-borne virus of the genus Flavivirus, typically characterized by mild fever, rash, and joint pain. The data were gathered after searching for relevant articles published in, the World Health Organization’s (WHO) website, Centers for Disease Control and Prevention’s (CDC) website, and some other related websites on the Internet

Introduction

The World Health Organization (WHO) declared a public health emergency of international concern (PHEIC) on February 1, 2016, as there were more than 4,000 microcephaly cases and neurological disorders in some areas affected by the Zika virus (ZIKV). Due to the rapid emergence of ZIKV infection, it is naturally becoming a concern all over the world. The single-stranded RNA arbovirus of the Flavivirus genus was first identified in the Zika forest of Uganda and named accordingly. In May 2015, it was first reported from Brazil. Since then, it has rapidly become a significant problem in the medical field. In 1968, it was reported from Nigeria. In April 2007, there was an outbreak of ZIKV on Yap Island in the Federated States of Micronesia. In 2013, another outbreak was reported in French Polynesia. From 2012 to 2014 in Thailand, some cases were identified to be affected by ZIKV. The introduction of ZIKV in Easter Island in 2014 has been suggested to originate from French Polynesia in the literature.

zika virus

Similarities were found between the strains isolated from Thailand and the Pacific regions. It was postulated that might be a similar type of ZIKV prevalent among a large portion of the globe. In the USA, most cases are related to travel and the first case of microcephaly was reported from Hawaii in January 2016.

Transmission

ZIKV has been transmitted mainly by the bite of female Aedes mosquitoes. Favorable environmental factors for these vectors may play a role in the rapid emergence of the infection in countries in the Americas. At the time of drought, local people usually store water in the container, which is the ideal environment to help in the breeding of Aedes mosquitoes. But the infection can be spread through sexual intercourse, blood transfusion, and perinatal transmission. A blood transfusion may be a potential way of transmitting the disease.

zika virus

Pathogenesis

The detailed pathogenesis is still unknown. Emerging evidence suggests that ZIKV after being injected through the skin, gains access initially to immature dendritic cells, dermal fibroblast, and epidermal keratinocytes. Adhesion factors such as DC-SIGN, AXL, Tyro3, and TIM-1 help entry in these cells. with the help of envelope protein (E-protein), the virion attaches to the targeted cells. Then by the process of endocytosis with assistance from clathrin-coated pits, the virion enters the cytoplasm of the cells. Replication occurs primarily in the cellular cytoplasm through ZIKV RNA has been isolated from the nucleus. Then the cells undergo apoptosis and autophagy causing the release of virus particles, which ultimately spread to the lymphatics and bloodstream leading to the florid manifestation of the disease. The host innate immune system produces type 1 and types 2 interferons to which ZIKV is susceptible.

zika virus

Clinical feature

The incubation period of ZIKV infection is not known precisely. Most of the cases occur 3-12 days after mosquito bites. A majority of ZIKV infections are asymptomatic. Mild fever, skin rashes, conjunctivitis (nonpurulent), muscle pain and joint pain (small joints of hands and feet), back pain, malaise, or a headache lasting for 2-7 days are seen only in 20% of infected individuals. It is indistinguishable from the symptoms of other arboviral diseases such as dengue and chikungunya. Patients rarely become sick enough to get hospitalized, and mortality is rare.

zika viruszika virus

Diagnosis of ZIKV

At present, there is no commercial test to diagnose ZIKV. Viral RNA can be detected by reverse transcription-polymerase chain reaction (RT-PCR), and the antiviral antibodies can be detected by either immunoglobulin M (IgM) enzyme-linked immunosorbent assay (ELISA) or plaque reduction neutralization test (PRNT). IgM antibody appears in the blood toward the end of the first week of illness. Cross reaction with another Flavivirus is common. This cross-reaction effect can be attenuated by using PRNT.

Samples collection from different cells and Organs

Serum from the umbilical cord or the infant within 2 days of birth is used for RT-PCR testing. Cerebrospinal fluid (CSF), placental tissue, and amniotic fluid can also be used for RT-PCR. ZIKV has been isolated from the saliva but did not help to extend the period of detection of the virus. On the other hand, RNA can be isolated from urine even up to 3 weeks after the onset of symptoms, which is extremely advantageous in a practical scenario. RT-PCR is positive only for 3-7 days.  

Potential Complications

Recently, ZIKV infection has become a well-discussed topic for not only its rapidity of spread but also its effect on the neurological system that has been documented. Guillain–Barré syndrome (is a rare but serious autoimmune disorder in which the immune system attacks healthy nerve cells in your peripheral nervous system (PNS). This leads to weakness, numbness, and tingling, and can eventually cause paralysis) is associated with ZIKV infection. This infection in the first trimester of pregnancy leads to more microcephaly development in the fetus Apart from these, ophthalmological involvement is a less discussed topic regarding ZIKV. Infants from Brazil were found to have macular pigment mottling and loss of a foveal reflex. One of them manifested well-defined macular atrophy as well.

Treatment

There is no particular treatment for ZIKV infection.

  1. Supportive management is the only way.
  2. Taking rest, maintaining adequate hydration, and appropriate nutrition may help patients in early recovery. But patients must be kept under observation, and any signs of multiorgan involvement should be monitored
  3. Acetaminophen may be used for relieving fever
  4. Nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin should be used cautiously and after dengue infection (to avoid hemorrhagic complications) and pregnancy are ruled out.

Prevention

The Pan American Health Organization (PAHO) has pointed out reasons for the rapid spread of the virus. The population of the Americas had no previous exposure to ZIKV and they have to lack immunity, and Aedes mosquitoes — The principle vector for ZIKV transmission — Are present in all of the region’s countries except Canada and continental Chile.

Its recommendations are as follows:

  1. Necessary reduction of the mosquito population.
  2. Removal of potential breeding sites of mosquitoes.
  3. Use of necessary personal protection.
  4. People who live in or are going to visit susceptible areas have to use insect repellents and wear clothes covering the maximum body surface are preferred.

CDC recommendation for a pregnant lady for ZIKV infection

All pregnant women who visit the ZIKV-affected regions should consult their doctors for further suggestions. All symptomatic women including those who develop symptoms within 2 weeks of their travel in a ZIKV-endemic zone should positively consult the health care provider. ZIKV remains in the blood of an infected person for 1 week and in the semen for 2 weeks. There is currently no evidence of birth defects in babies conceived after the clearance of the virus from the blood or semen. Infants with congenital anomaly should be tested for ZIKV and reported accordingly.

To reduce sexual transmission, the following have been recommended:

  1. Men who live in or have to visit a ZIKV-infected area should use condoms during sex with their pregnant partners.
  2. Both the partners should discuss the possibility of transmission of the infection, and they should consult experts when needed.
  3. ZIKV can be detected in the semen when viremia is not present in the blood even after 2 weeks. So it is important to make more conclusive guidelines and provide sexual safety to people at risk.
  4. Travelers returning from an area with ZIKV infection should be kept under surveillance for ZIKV infection

Ongoing Researches on Zika

The National Institute of Allergy and Infectious Diseases is trying to find out antiviral drugs with actions against ZIKV. It is also working on the Zika virus vaccine. A DNA-based vaccine with the same principle used for the West Nile virus, a live attenuated ZIKV vaccine, and a genetically engineered vesicular stomatitis virus vaccine is being researched on. Animal models may be helpful for more information about the disease’s course as well as the treatment of ZIKV infection. As the preventive methods such as removing the breeding areas and insecticide use are now proving insufficient, new approaches of genetically engineered mosquitoes are gaining importance

Current scenario regarding Zika in the Pakistan #

Although no clinical cases of Zika virus disease have been notified in Pakistan, the first serological traces of infection date back to 1983. A seroepidemiological survey for certain arboviruses (Togaviridae) in Pakistan.Nov 1, 2016.Some areas of Pakistan are extremely dangerous whereas others are safe for tourists. It’s important to do some proper research beforehand and, if you go to a sensitive area like Peshawar or the Swat Valley, just travel with caution.

Conclusion

Though there are several unknown facts about the pathogenesis, transmission, complications, and treatment of ZIKV, physicians should guide patients regarding the prevention of the disease as much as possible. Particular care should be taken of pregnant women. The disease is asymptomatic in a majority of cases. Affected patients should be kept under close observation. They should be counseled about the use of condoms and the risk of blood donations. Mosquito control measures should also be implemented stringently. Proper preventive methods will break the chain of transmission. Countries, where other Aedes mosquito-borne diseases are endemic, should be extremely cautious and have thorough surveillance. If the current guidelines are followed properly, this infection can be combated successfully.

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