Zika is not new—why has it struck now?

There’s no doubt now that the Zika virus has reached far beyond the places where it exists in the wild. Several dozen cases have now been reported in the UK, all of them in people who have travelled in Zika-infected areas, where the virus is transmitted by mosquitoes. (It may also be sexually transmitted.) For most people the risks are minimal: some never see any symptoms at all, while others experience only a rash, mild fever, and headaches before the virus is cleared from the body. But for pregnant mothers the dangers are very real: the virus seems to cause cranial shrinkage and associated neurological disorders, called microcephaly, in babies born from mothers infected with the disease. The pandemic began in 2007, when several cases were reported in Gabon and in Micronesia—at first attributed to dengue fever, the symptoms of which are similar. In 2013 the virus had reached the islands of French Polynesia, where it is estimated to have affected about 11 per cent of the population. Then around 2013 it crossed the Pacific and entered Brazil, from where it has spread to Colombia, El Salvador, Suriname and Venezuela. There was no great international alarm, however, until the link with microcephaly started to look secure in late 2015. In rare cases, Zika can also cause the condition called Guillain-Barré syndrome, in which neural damage can cause paralysis and death. The explosive global spread of Zika is now considered by the World Health Organisation to be a public health emergency. Its emergence in Brazil for a time seemed to threaten the 2016 Olympics, and some countries in Central America are now advising women to delay pregnancy. But within all the alarm is a puzzle. The virus has been known since 1947, when it was reported in Uganda. So why has it only now become a worldwide problem? The spread of previously unrecognised infectious diseases by travellers who bring them back home is nothing new. That was long thought to be the origin of syphilis, which spread from Naples around 1494 to become a scourge for the next four centuries. It was thought that Spanish sailors had carried it back from the New World—from where the expensive (and largely ineffectual) cure, a concoction of wood called guaiac, was also soon imported. But there’s another theory of the origin of syphilis, which says that it was a disease always present but long dormant in the Old World, until it developed into a particularly virulent form in the late fifteenth century. Such a transformation might explain the outbreak of Zika in the past decade too. In other words, what we might be seeing here is evolution at work. The Zika virus ZIKV is a member of a family called flaviviruses, which includes the well-studied dengue and West Nile viruses. While there are still disturbingly large gaps in our knowledge of ZIKV, some of the understanding of these other pathogens is likely to carry over to Zika. It is spread via several species of mosquito native to Africa, south Asia, Polynesia and South and Central America, which infect humans when they bite. One of the possibilities for the sudden outbreak around 2007, then, is that ZIKV underwent some evolutionary change that made it easier for the virus to hitch a ride on mosquitoes. It sounds as though this is a classic case of Darwinian adaptation: a random mutation creating a “fitter” virus more able to spread and reproduce. Maybe so, although it’s also possible that the mutation might have been part of the non-adaptive “genetic drift” that also constantly takes place and can drive evolutionary change, especially in small populations. Or the virus might have evolved some way of thriving in the human bloodstream, so that even transmission of a tiny amount of virus from a mosquito bite could enable Zika infection to take hold. Alternatively, it’s conceivable that human activity alone might have created the conditions for the outbreak—the 2014 World Cup and other sporting events brought travellers from the South Pacific to Brazil around the time Zika arrived there. We just don’t know yet which of these hypotheses, if any, is correct. Scott Weaver, a specialist in infectious human disease at the University of Texas at Galveston, suspects that the pandemic signals some change to the virus itself—but if so, we don’t know what that is. There are some clues, however. For example, last March a team at the University of Hong Kong reported a comparison of the genomes of pre-epidemic strains of ZIKV since 1947 and those of recent strains found in South and Central America in 2014-15. (Like many viruses, flaviviruses have genes encoded in RNA, not DNA.) They found that the epidemic strains have some consistent differences in specific parts of the genome and in the proteins made from them. The trouble is, we’re not too sure what these proteins do. So it’s too early to know if what has been spotted here are the telltale genetic changes that unleashed Zika as a global hazard. If they are, that information might help in the development of a vaccine. None yet exists, but human trials are imminent, and some researchers hope to see vaccination happen by 2018. These efforts are building on experience with dengue and related viruses, but it would surely be helpful to know if, and how, ZIKV has somehow found a better way either to ride on mosquitoes or hijack human cells. There’s plenty more still to be figured out, not least a confirmation that Zika really is the cause of microcephaly and, if so, how that happens. In the meantime, the best defence is old-fashioned, low-tech mosquito control: repellents, clothing, and insecticides. Underpinning it all is the question that virologists and epidemiologists must now constantly ask: what will the next global pandemic be?