Zika virus continues to make news.

There is an increasing body of evidence linking Zika virus infection to serious disease in humans, especially fetal abnormalities (microcephaly). While the mechanisms are not yet clear this link is now considered to be established. Cases of microcephaly have been detected predominantly in Brazil to date, with 4,863 cases (4,222 suspected and 641 confirmed) reported to March 2016. The occurrence of this condition is around twenty times higher than was seen in Brazil prior to the arrival of Zika virus. Additionally, Zika has been suggested as the cause of conditions ranging from paralysis to autoimmune disease, most notably Guillain-Barré syndrome.

In the period from its initial identification in Uganda in 1947 to its appearance in the Americas in 2015, Zika was restricted to a narrow equatorial band. During this period it was only associated with infrequent and mild infections, with symptoms including fever, rash, muscle pain and conjunctivitis, although when it spread to French Polynesia in 2013 there is some retrospective evidence suggesting more serious effects. One major reference work noted in 2007 that, while evidence of infection was widespread in Africa, “overt infections in humans have been few”. It is thought that only around 20% of people infected actually develop symptoms- such a ratio with only a minority of infections leading to apparent disease is seen with many virus infections.

Zika virus belongs to the family Flaviviridae and the genus Flavivirus. It has a single-stranded RNA genome and a lipid envelope, and is closely related to a range of viruses causing serious infections in humans, including yellow fever, dengue, and West Nile viruses. It is an arthropod-borne infection (an “arbovirus”) spread by mosquitoes of the Aedes genus. Arboviruses multiply in both their insect and vertebrate hosts, spreading and amplifying as they do so. Transfer from as yet unknown animal hosts to humans by mosquito bites is the main route of infection, though some transfer between humans via sexual contact does occur.

It is the distribution of Aedes mosquitoes which underlies much of the concern about the spread of the Zika virus. With around 20 countries in the Americas already affected (among more than 60 countries and territories worldwide) it is clear that many tropical (and some subtropical) areas around the world inhabited by over two billion people are likely to be able to support the infection. Estimates vary, but it is clear that at least some southern areas of the United States, notably Florida and Texas, may be included in this category. It should, however, be noted that in some island locations Zika appears to have come and gone, so that it may not become established (endemic) at least in smaller and more isolated areas.

The World Health Organisation has declared Zika infection to be a public health emergency, while the US Centers for Disease Control have issued warnings against pregnant women travelling to affected areas. However, such limitations are likely to be increasingly impractical if the range of the virus expands to cover much of the Americas.

It is far from clear why Zika, with a history as an infrequent cause of relatively mild human disease, has suddenly become such a major pathogen. There are a number of possible reasons, which may operate singly or together. Prevailing immunity to related viruses could be involved, as with Dengue virus where immunity to one strain results in more severe disease when infected by another. Human genetics could be involved, as with the different response of individuals bearing different types of cellular HLA surface antigens to hantaviruses. Or it could be a mutant form of the virus, as seen with the unexpectedly pathogenic 1921 swine influenza. Zika is already known to exist in multiple forms (African and Asian lineages) and this may be a natural variant. Certainly other types of viruses can show different pathology in the Americas and in Asia, notably the hantaviruses.

There is no vaccine against Zika virus, and no antiviral drugs are known to be active. Thus prevention of infection by limiting contact with mosquitoes is the main way to limit disease. This can involve reductions in the numbers of mosquitoes, via habitat controls (such as reduction in stagnant water to reduce the availability of suitable breeding grounds) or by spraying of insecticides (although control efforts for Zika need to be tailored to reflect the habits of the specific mosquitoes involved).  More personal approaches are also possible, such as the use of insecticide-impregnated bed nets, insect repellents, and minimising the exposure of the skin- or of course for those located outside the risk zones, simply not travelling to areas where the infection is active.

From a public health point of view, prevention and response efforts will need to include a longer-range view similar to efforts to protect against influenza.  That is, if Zika is here to stay – as appears likely in some areas – we will then need to use those techniques that provide for education, mitigation, and prevention alongside efforts to develop vaccines or antiviral drugs.

At the moment neither the cause of the more severe disease seen predominantly in the Americas nor even the precise role of Zika virus in causing it is known with any certainty. All that can be said is that, in the words of the CDC, Zika is “scarier than thought”.

 

Learn more about this story with eLS:


The GB Viruses: An Update of Their Biology, Molecular Virology and Significance
P Karayiannis
Published online: April 2013

Arthropodborne Viruses
Dana L Vanlandingham, Kate McElroy Horne
Published online: June 2014

Flavivirus Infections in Humans
John T Roehrig, Alan DT Barrett
Published online: June 2013

West Nile Virus Infection
Céline Bahuon, Sylvie Lecollinet, Cécile Beck
Published online: May 2015

 

Learn more on Zika virus:

WHO Fact sheet: http://www.who.int/mediacentre/factsheets/zika/en/

From the CDC: http://www.cdc.gov/zika

 

About the Authors

David Harper is eLS Editor for Virology. He collaborated on this article with Dr. James Logan, Department of Disease Control, London School of Hygiene and Tropical Medicine, London, UK and Dr. John Litaker, Managing Director, The Litaker Group, Austin, Texas, USA.