D. Sunitha1*, K. Hemalatha2, M. Nandha Kishora Chary1, Rahamat Unissa1
1Department of Pharmaceutical Chemistry, Malla Reddy College of Pharmacy, Maisammaguda, Secunderabad, Telangana, India
2Department of Pharmaceutical Chemistry, Acharya and B M Reddy College of Pharmacy, Bangalore, Karnataka, India.
*Corresponding Author E-mail: basasunitha@gmail.com
ABSTRACT:
The Zika virus is a mosquito-transmitted infection common in Africa and Asia, it did not begin spreading widely in the Western Hemisphere, when an outbreak occurred in Brazil. Few people with less immunity, showed rapidly spreading with infection. Millions of people in tropical regions of the Americas now have been infected. The infection causes no symptoms and leads to no lasting harm. Scientific concern is focused on women who become infected while pregnant and those who develop a temporary form of paralysis after exposure to the virus.
The World Health Organization has declared the Zika virus an international public health emergency, that it causes birth defects. As many as four million people could be infected by the end of the year.
Officials at the Centers for Disease Control and Prevention have urged pregnant women against travel to more than thirty countries, mostly in the Caribbean and Latin America, where the outbreak is growing. Some pregnant women who have been to these regions should be tested for the infection.
The infection appears to be linked to the development of unusually small heads and brain damage in newborns – called microcephaly – as well as other neurological defects. In adults, the virus is linked to a form of temporary paralysis. The vast majority of Zika infections are transmitted by mosquitoes, sexually transmitted in only few cases (around dozen).
Recently Bharat Biotech, a Hyderabad-based vaccines and bio-therapeutic manufacturer, developed a vaccine to fight against the dreaded mosquito-borne Zika virus.
This review gives an idea about the recent advances or developments available for treating Zika infection.
KEY WORDS: Zika virus, Aedes aegypti mosquito, birth defects, microcephaly, paralysis.
INTRODUCTION:
Zika virus is a member of the genus Flavivirus belonging to family Flaviviridae. This virus is transmitted through Aedes mosquitoes like A. aegypti and A. albopictus, which are active at day times1,2. Aedes aegypti mosquito bite transmits the disease which is same as the one that transmits dengue, yellow fever (both flaviruses) and chikungunya (a togavirus).
Fig. No. 1 Zika virus
Fig. No. 2 Aedes aegypti mosquito
The Zika virus (ZIKV) was first identified in Uganda in 1947. Around 3,893 microcephaly cases were suspected in Brazil in 2015. 1st case of Zika virus was reported by Centers for Disease Control and Prevention (CDC) in a South Korean 43-year-old man, who travelled to Brazil. Zika infections have been reported in Asian countries. The World Health Organization considers as a global emergency. Zika virus had been known to infect humans from the results of serological surveys in Uganda and Nigeria. It was not until 1954 that the successful isolation of Zika virus from a human was published 3,4.
The first case of the Zika virus was reportedly confirmed in Texas, USA in January 2016 in a traveller returning from Latin America. The health officials in the US have been alarmed about a possible link between the virus and a birth defect called microcephaly that causes babies to be born with abnormally small heads and potential developmental problems.
Structure of Zika virus:
Zika virus is enveloped and icosahedral and has a nonsegmented, single-stranded, positive-sense RNA genome. It is most closely related to the Spondweni virus1,2. The Zika virus is a positive sense single-stranded RNA molecule 10794 bases long 2 with two non-coding regions flanking regions known as the 5' NCR and the 3' NCR. The open reading frame of the Zika virus reads as follows: 5′-C-prM-E-NS1-NS2A-NS2B-NS3-NS4A-NS4B-NS5-3′ and codes for a polyprotein that is subsequently cleaved into capsid (C), precursor membrane (prM), envelope (E), and non-structural proteins (NS) 4. The E protein composes the majority of the virion surface and is involved with aspects of replication such as host cell binding and membrane fusion 2. NS1, NS3, and NS5 are large, highly-conserved proteins while the NS2A, NS2B, NS4A, and NS4B proteins are smaller, hydrophobic proteins. Located in the 3' NCR are 428 nucleotides that may play a part in translation, RNA packaging, cyclization, genome stabilization, and recognition. The 3' NCR forms a loop structure and the 5' NCR allows translation via a methylated nucleotide cap or a genome-linked protein 5.
The structure of ZIKV follows that of other flaviviruses. It contains a nucleocapsid approximately 25-30 nm in diameter surrounded by a host-membrane derived lipid bilayer that contains envelope proteins E and M. The virion is approximately 40 nm in diameter with surface projections that measure roughly 5-10 nm 4. The surface proteins are arranged in an icosohedral-like symmetry 5.
Steps of Zika Virus transmission:
Mosquito transmit Zika. The virus moves from its gut to its salivary glands. Only female mosquitoes bite people: they need blood to lay eggs. They pick up the virus in the blood. It travels from their gut through their circulatory system to their salivary glands and is injected into its next human victim. Mosquito saliva contains proteins that keeps blood from clotting. When a mosquito bites, it first injects saliva so its prey’s blood does not clog its strawlike proboscis.
1. Mosquito feeds on virus-infected blood.
2. Infected blood travels to the midgut.
3. Virus enters the circulatory system.
4. Virus travels to the salivary glands.
5. Mosquito bites again, injecting virus-infected saliva into victim before feeding.
Symptoms
· Most people infected with Zika virus won’t even know they have the disease because they won’t have symptoms. The most common symptoms of Zika are fever, rash, joint pain, or conjunctivitis (red eyes). Other common symptoms include muscle pain and headache. The incubation period (the time from exposure to symptoms) for Zika virus disease is not known, but is likely to be a few days to a week.
· The illness is usually mild with symptoms lasting for several days to a week after being bitten by an infected mosquito.
· People usually don’t get sick enough to go to the hospital, and they very rarely die of Zika. For this reason, many people might not realize they have been infected.
· Zika virus usually remains in the blood of an infected person for about a week but it can be found longer in some people.
· Once a person has been infected, he or she is likely to be protected from future infections.
ZIKV leads to:
1. Microcephaly: a birth defect leading to a small head and underdeveloped brain.
2. Guillain-Barre: a condition in which progressive paralysis sets in.
· The symptoms of Zika are similar to those of dengue and chikungunya, diseases spread through the same mosquitoes that transmit Zika.
· If recently traveled, in Zika infected areas, must go for blood tests for Zika or other similar viruses like dengue or chikungunya.
· Zika virus diagnosis can only be confirmed by laboratory testing for the presence of Zika virus RNA in the blood or other body fluids, such as urine or saliva.
Transmission
· Zika virus is transmitted to people through the bite of an infected mosquito from the Aedes genus, mainly Aedes aegypti in tropical regions. This is the same mosquito that transmits dengue, chikungunya and yellow fever. However, sexual transmission of Zika virus has been described in 2 cases, and the presence of the Zika virus in semen in 1 additional case. 14 new sexually transmitted cases of Zika Virus are reported by CDC.
· WHO has issued the Pre-qualification of Medicines Programme (PQP) certification to Chennai-based Green Signal Bio Pharma.
· The pharmaceutical company got the certification to manufacture a Bacillus Calmette-Guerin (BCG) vaccine, with which, it became the only Indian company to get PQP certification from WHO.
· WHO recently declared an international public health emergency over the explosive spread of the Zika virus. This is the fourth time that the organisation has made such a declaration, the previous one being for Ebola.
Prevention
· Mosquitoes and their breeding sites pose a significant risk factor for Zika virus infection. Prevention and control relies on reducing mosquitoes through source reduction (removal and modification of breeding sites) and reducing contact between mosquitoes and people.
· This can be done by using insect repellent regularly; wearing clothes (preferably light-coloured) that cover as much of the body as possible; using physical barriers such as window screens, closed doors and windows; and if needed, additional personal protection, such as sleeping under mosquito nets during the day. It is extremely important to empty, clean or cover containers regularly that can store water, such as buckets, drums, pots etc. Other mosquito breeding sites should be cleaned or removed including flower pots, used tyres and roof gutters.
· Repellents should contain DEET (N, N-diethyl-3-methylbenzamide), IR3535 (3-[N-acetyl-N-butyl]-aminopropionic acid ethyl ester) or icaridin (1-piperidinecarboxylic acid, 2-(2-hydroxyethyl)-1-methylpropylester). Product label instructions should be strictly followed. Special attention and help should be given to those who may not be able to protect themselves adequately, such as young children, the sick or elderly.
· Travellers should take the basic precautions described above to protect themselves from mosquito bites.
Treatment:
· Treat the symptoms:
o Get plenty of rest.
o Drink fluids to prevent dehydration.
o Take medicine such as acetaminophen or paracetamol to reduce fever and pain.
o Do not take aspirin and other non-steroidal anti-inflammatory drugs (NSAIDS) until dengue can be ruled out to reduce the risk of bleeding.
o If you are taking medicine for another medical condition, suggestion of healthcare provider is taken before taking additional medication.
· If infected already with Zika, prevent mosquito bites for the first week of illness.
o During the first week of infection, Zika virus can be found in the blood and passed from an infected person to a mosquito through mosquito bites.
o An infected mosquito can then spread the virus to other people.
Research:6-8
Researchers also have linked
Zika to stillbirths, miscarriages, eye problems and other complications, with
complications not only in the first trimester but throughout pregnancy. Recently,
Brazilian researchers reported that Zika preferentially targets developing
brain cells. They used stem cells to study embryonic brain development in lab
dish, and reported in the journal Science that virus taken from a Brazilian
patient destroyed the growing neural cells in a few days.
There is also evidence that some adults occasionally suffering from serious
effects of Zika. Researchers already were studying whether Guillain-Barre
syndrome, a nerve condition that can cause paralysis, is linked to Zika.
Two Zika patients were
suffering from another problem, a brain inflammation that damages the coating
of nerve cells in a way similar to multiple sclerosis.
The CDC has warned women who are pregnant or attempting to conceive to avoid travel to Zika-affected areas. Because Zika sometimes spreads through sexual intercourse, the CDC also says men who've traveled to Zika-affected areas either should use condoms with their pregnant partners or avoid sex until the baby's born.
Recent Developments:
World's First Zika Virus Vaccine Made in India, claim scientists: Using a live Zika virus imported officially, the Hyderabad Company has now developed two candidate vaccines
Highlights
1. Hyderabad lab claims to have developed world's first Zika Virus vaccine
2. If approved, the lab says it can make up to 1 million doses in 4 months
3. WHO has declared the Zika Virus a Global Health Emergency.
In an important "Make in India" moment, scientists at a Hyderabad lab said they have developed the world's first vaccine against the ZIKV. They said, that they have two types of vaccine:
WHO has declared Zika and its suspected link to birth defects a global
health emergency. More than 20 countries in Latin America have reported an
outbreak and a rare case of the Zika virus being transmitted through sex has
been reported in Texas, USA.
As the world searches for a vaccine and other global companies take first steps
on research, the Bharat Biotech International Limited in Hyderabad says it has
patented the ZIKV.
Using a live Zika virus imported officially, the Hyderabad company has
developed two candidate vaccines, but taking them through animal and human
trials could be a long haul. Dr Ella said, that he had sought the government's
support on this and the Indian Council of Medical Research (ICMR) has stepped
forward to help. Vaccine can help countries such as Brazil, a fellow
member of the BRICS (Brazil, Russia, India, China and South Africa) group, and
pave way for "vaccine diplomacy."
Bharat Biotech, a Hyderabad-based vaccines and bio-therapeutic manufacturer, claimed to have achieved a breakthrough in developing a vaccine to fight the dreaded mosquito-borne Zika virus.
The two candidate vaccines are in an advanced stage of development and could be ready soon after pre-clinical studies are concluded in the next five months.
1. The inactivated vaccine, which consists of the disease-causing microbe which is killed with chemicals, radiation or heat, is a more stable and safer vaccine compared to the vaccines using live microbes.
2. The other vaccine, known as Recombinant DNA vaccine, is based on the technology of using an attenuated virus or bacterium to introduce microbial DNA to the cells of the body.
As per a WHO report, Zika is now present in 23 countries and Brazil, the hardest-hit country, has reported around 3,530 cases of the devastating birth defect, called microcephaly in 2015, that are strongly suspected to be related to Zika.
WHO declares Zika virus outbreak as International Emergency9: After an emergency meeting by the WHO, headed by its Director-General Margaret Chan in Geneva, Switzerland, the organisation has declared an international public health emergency over the explosive spread of the mosquito-borne Zika virus.
Considering the underscoring seriousness of the outbreak, WHO has predicted that around four million people may be infected with Zika virus in the Americas (South and North America). The organisation has declared an international public health emergency for the fourth time. A once rare mosquito-borne virus called Zika was recently found to be spreading rapidly through the American continent.
Here are some important facts about the Zika virus and the fever 10:
· A member of the genus Flavivirus, Zika virus is responsible for causing Zika fever. The virus is transmitted by Aedes mosquitoes
· The illness is like a mild form of dengue fever 11,12 and usually lasts from four to seven days. The sickness is treated only with bed-rest and cannot be prevented by drugs or vaccines
· On January 15, 2016, CDC issued a travel alert advising pregnant women to consider postponing travel to the following countries and territories: Brazil, Colombia, El Salvador, French Guiana, Guatemala, Haiti, Honduras, Martinique, Mexico, Panama, Paraguay, Suriname, Venezuela and the Commonwealth of Puerto Rico, because of the 'growing evidence of a link between Zika and microcephaly'.
Sensing the emergency, the Government of India has issued detailed guidelines on how to tackle the outbreak of ZIKV. The guidelines were authorised by the Union Health Ministry. Although no cases of Zika attack has been reported from India, the guidelines have been issued as a precautionary measure.
The guidelines are as follows:
1. All citizens, especially pregnant women, must refrain from travelling to the affected countries.
2. All international airports and ports will display signage showing information on the disease. Quarantine facilities will also be set up at all major entry points to the country.
3. All travellers must report to the customs for medical checkup if they are returning from the affected countries and suffering from illness.
4. All travellers who are already in the affected countries should strictly follow protective measures, especially during the day to prevent mosquito bite.
5. Rapid Response Teams (RRT), comprising a microbiologist, an epidemiologist and a medical specialist, have been set up at central and state surveillance units.
6. The government-run Integrated Disease Surveillance Programme (IDSP) will track reports of acute febrile illness through its community and hospital-based data collection system. It will investigate such cases occurring to people who have recently been to the affected countries.
7. Delhi-based National Centre for Disease Control (NCDC) has been identified to be the nodal agency for investigation of Zika virus outbreak in the country.
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Received on 14.04.2016 Accepted on 15.05.2016
© Asian Pharma Press All Right Reserved
Asian J. Pharm. Res. 2016; 6(3): 183-187.
DOI: 10.5958/2231-5691.2016.00026.5