Zika Virus
Zika belongs to the flavivirus group that is spread by arthropods: Yellow Fever virus [YFV], Japanese Encephalitis Virus [JEV], Tick-borne encaphalitis virus [TBEV] Dengue [DEN] and West Nile Virus [WNV].
Each of these viruses has a wide and growing distribution, due to international travel and climate change favouring spread of infected people and mosquitoes:
Why is Zika virus vaccine taking so long?
1. Because Zika virus seemed to be harmless
Zika was isolated from Rhesus macaque monkeys in Zika Forest, Uganda in 1947. When human infections with Zika were detected in the 1950's, the symptoms were mild: flu-like transient fever, headache and muscle pains.However since then two changes have occurred. Transmission of the virus by mosquitoes and the development of Pacific strain associated with microcephaly and Guillain Barre Syndrome [GBS: a neuropathy, or nerve disease].
Spread of the virus has been aided by international travel and climate change favouring the spread of Aedes aegypti, the main mosquito vector. Other mosquito species such as Aedes albopictus are capable of harbouring Zika which would be a serious development.
2. Because most Zika infections go unnoticed
Zika infections usually have no symptoms. In any case flu-like symptoms are so common they are rarely investigated. However older people are at higher risk of GBS after Zika infection and the dangers to unborn children are extremely severe, especially in the first three months of pregnancy.Japanese encephalitis virus is similar to Zika. Most JEV infections go unnoticed but one case in a thousand progresses to brain infection. A mouse brain derived vaccine is available with 80-95% efficacy and vaccination in affected countries has led to a fall in incidence since 1960. A cell-grown strain appears to be safer and more effective. A two dose regime is suggested to match the conversion rate of other vaccines.
3. Because Zika virus is constantly changing
Viruses are the fastest evolving organisms on earth. They exist in multiple forms so that drug resistant strains are already present before the drugs are even developed. Viruses exchange genetic material and switch genetic code frequently leading to multiple mutant strains, some of which survive and come to dominate the population. This is illustrated by the current change in Zika to become much more invasive and adapted to life in a mosquito.
The RNA of flaviviruses can be read backwards or start from a different base pair and still produce viable organisms. They are the masters of improvisation.
Like most viruses, JEV has shown changes in the dominant strain from genotype 3 to genotype 1 however immunisation with one strain has been shown to protect humans from all strains.
4. Because Zika virus rapidly enters human cells
Zika's ability to penetrate human cells is the key to its success. Once inside the cell the virus is protected from the body's defences. Zika deconstructs itself and the RNA component hijacks the cell into making more viruses, ultimately leading to cell death and release of mature virus particles.
Survival inside the cell means that viral infections such as Herpes can persist for long periods. A vaccine needs to target the immediate entry of viruses in the blood stream before they enter human cells.
5. Because Zika virus survives in other animals
YFV cannot be eradicated because a reservoir exists in non-human primates, and tropical birds and mammals 'the sylvatic cycle', in towns YFV is spread from person to person by Aedes aegypti the 'urban cycle'. In addition some mosquitoes target humans and non-human primates 'the intermediate cycle'.
Despite the wide availablity of vaccine, outbreaks still occur. So far YFV has not become endemic in Asia but a current outbreak in Angola [April 2016] increases the risk via migrant workers returning to Asia.
6. Because of the danger of brain complications from the vaccine
The first YFV vaccine was made in the 1930's and substrains of the YFV-17D vaccine, are used nowadays to protect against infection. >98% of people have an immune response to a single dose and because antibodies are detectable 30 years later, a follow-up at ten years is no longer recommended.
However the early vaccine was complicated by brain and spine complications and the current vaccine has an adverse rate is 38/100,000. Some people are allergic to gelatin or chicken egg protein,however 1/100,000 reactions are dangerous: encephalitis or multiple organ failure.
These complications can't be detected until the vaccine is tested in a large human population. Scientists are understandably cautious about introducing the vaccine until they are sure that the vaccine is effective and safe.
7. Because detecting Zika is difficult
Host response to the Zika virus, antibodies, are only detectable in the blood of infected people briefly. Antibodies are detected in the urine for longer. However immunity to YFV may interact with the result, complicating the issue.
The most sensitive test is to isolate the Zika virus itself by RT-PCR but this requires deep refridgeration at -80C to preserve the virus, which isn't widely available.
8. Despite years of study, there is no vaccine to Dengue virus
Like Zika, closely related Dengue is spread by mosquitoes and as the map shows, it's the most widespread and the most dangerous flavivirus, causing 50m infections and 20,000 deaths a year. Antibody-dependent enhancement [ADE] explains Dengue's resistance to vaccines. The body's response to infection creates an army of monocytes and macrophages that ultimately spread the infection.This may explain why second infections in an individual can provoke dangerous Dengue Haemorrhagic Fever [DHF]
Dengue has four subtypes, so a vaccine must protect against all four otherwise it might be associated with DHF. Conversion rates of 40% against all 4 serotypes are reported and 70% after two immunisations, however the risk of DHF has halted some testing.
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