Zika virus crisis not over

A brain affected by Zika virus.
Saturday, December 3, 2016

The Zika virus, borne by the mosquito Aedes aegypti, was declared by the World Health Organization (WHO) on November 18 to no longer be a global emergency, to the dismay of many health workers around the world. This decision will minimise the amount of research and public vigilance against Zika infection.

The United States Centre for Disease Control and Prevention (CDC) warned that pregnant women should avoid travelling to areas where the virus was being transmitted. This means avoiding Texas, California, Florida and Puerto Rico, where outbreaks have already occurred, and probably the rest of the world. More than 50 countries have experienced an outbreak of Zika virus infections since 2015 and there have been almost 2200 cases of microcephaly — babies with small brain size — associated with Zika. The vast majority — 2033 cases — have occurred in Brazil, with 28 reported in the US.

Outbreaks

In August, Puerto Rico reported 10,690 cases of Zika infection, including 1035 pregnant women, but it is thought this is underestimated. Researchers estimate between 5900 and 10,300 pregnant women will ultimately be infected with Zika in Puerto Rico. They further project that 100-270 cases of microcephaly could result between mid-2016 and mid-2017 in the absence of effective interventions.

Scott Weaver, a virologist at the University of Texas Medical Branch in Galveston, who was among the first to warn that the virus threatened the Americas, said: “I think the worst is yet to come in southern Brazil, places like Sao Paulo. And some places in the Amazon haven’t seen the virus at all yet.”

Recent outbreaks and related birth defects have also been detected in Southeast Asia and the Pacific although scientists believe Zika has circulated there for decades. Although the virus is not killing or deforming as many babies as originally expected, Dr Lawrence Gostin, director of Georgetown University’s O’Neill Institute for National and Global Health Law, said: “The international response has been lethargic”.

WHO first declared a state of emergency on February 1. Zika usually causes a mild disease characterised by fever, rashes, conjunctivitis and joint pain, if it causes any disease. About 80% of infections cause no symptoms at all. Zika is a flavivirus, similar to dengue, yellow fever and chikungunya. In fact, for people infected with Zika, the infection is indistinguishable from dengue fever virus using classic antibody tests.

The full extent of the damage in Latin America is unknown because many infected babies are yet to be born. At the time, it was unknown whether Brazil’s surge in microcephalic babies was caused by Zika, which had been discovered in 1947 and had been considered a mild disease.

WHO officials decided that the risk was not sufficient to justify cancelling the Olympic Games in Rio de Janeiro in August, but was high enough to encourage pregnant women to avoid travelling to the area.

Little is known about Zika because it was not recognised as a serious threat until just over a year ago. It now joins rubella and cytomegalovirus as pathogens that cause only mild maternal illness but serious defects in offspring.

Morphology

Zika has been shown to infiltrate radial glial cells, the neural stem cells that give rise to the neurons and astrocytes that will form the foetal cerebral cortex. Recent studies suggest that the virus gains entry to these progenitor cells via the AXL protein receptors that dot their surface.

Once inside the cells, the virus inhibits their growth, proliferation and differentiation. AXL receptors are also present on the stem cells of the retina, which might explain visual problems sometimes encountered in Zika-infected newborns.

Equally troubling, while the virus generally clears the blood within seven days, in pregnant women it can be detected in the blood for at least 70 days. It appears that the virus, which seems to freely cross the placenta, travels from the mother to the foetus, which then sheds more virus that reinfects the mother in a feedback loop. Foetuses have also been killed by the virus and infected infants have been born blind, deaf, with clubbed feet and permanent limb rigidity.

Another worry to pregnant women is that the baby may show no signs at birth of the presence of the virus, but brain damage and mental illnesses become obvious as the child develops. While the foetus is most vulnerable during the first trimester — when the central nervous system is forming — it may be under attack by the virus for months afterward, when more subtle central nervous system assaults may occur.

Nearly a third of deliveries in mothers infected with Zika will involve severe birth complications, including microcephaly, foetal cerebral calcification and central nervous system alterations. But as evidence mounts that the virus’s strong affinity for neural stem cells may also cause subtler central nervous system damage, the medical community fears that the current tragedy may give way to an equally horrific second act as exposed children who seemed unscathed at birth exhibit serious neurological ills as they age. Expectations range from auditory and visual problems to cognitive delays and seizure disorders.

Zika seems capable of hiding from the host’s ability to mount an immune response. There are implications for these findings in the Zika vaccines under development and the future of dengue outbreaks. Developers of a Zika vaccine must ensure antibodies developed against the Zika vaccine will not result in antibody-dependent enhancement of dengue in the future. In a region where dengue is common, the recent Zika outbreak may result in more severe cases of dengue, including dengue haemorrhagic fever.

Zika is most commonly transmitted in humans as the result of a bite from an infected mosquito or from an infected human to another. The virus also can be transmitted via the environment if an individual is pricked with an infected needle or has an open cut and comes in contact with the live virus.

While there are no known cases of the general public being infected with Zika through the environment, there has been at least one documented case of laboratory-acquired Zika infection. Under certain conditions, Zika can live for several hours on hard non-porous surfaces and still be highly contagious, but some commonly used disinfectants are extremely effective in killing the virus.

Breakthrough

There is a chance that the virus can be stopped. In a breakthrough by scientists from Monash University, the Aedes aegyti mosquito has been infected with Wolbachia bacteria. Infection by Wolbachia prevents the mosquito from spreading Zika and other viruses. About 60% of insects are normally infected with Wolbachia, but not Aedes aegypti. This work was begun in 2005 by Scott O’Neill to prevent the spread of dengue fever, but has now accelerated due to the damage caused by Zika.

Mosquitoes in two large areas of Brazil and Colombia are to be infected with Aedes aegypti carrying Wolbachia. The infected mosquitoes will then breed with local mosquitoes and pass Wolbachia on to their offspring, so the project is self-sustaining. In areas where trials have been done so far — in Vietnam, Indonesia and Rockhampton — transmission of the viruses has stopped.

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