Laurie Garrett :
With an estimated 3 to 4 million people having come down with Zika virus ailments since infected mosquitoes reached the Americas some nine months ago, 23 countries and territories have reported cases, and there are some 4,000 babies that have been born with the skull-misshaping microcephaly, according to the World Health Organization.
“Last year, the virus was detected in the Americas, where it is now spreading explosively,” WHO Director-General Margaret Chan said in a speech Thursday to the organization’s Executive Board. “The level of alarm is extremely high.”
The race is on to stop the epidemic. On Feb. 1, health experts will meet in Geneva to decide whether the WHO should formally declare a “public health emergency of international concern,” under the agency’s International Health Regulations. Such a declaration (which the WHO delayed executing for the first nine months of the 2014 Ebola epidemic) would trigger urgent mobilization of resources, scientific research, and vaccine development.
But Marcelo Castro, the minister of health from the country hardest hit by the virus, Brazil, warns that Zika has already gone from being an epidemic to an endemic disease in his country, meaning Zika may now be a permanent feature of the nation’s ecology.
If Zika becomes endemic in the Western Hemisphere, it will follow three other mosquito-carried viral diseases introduced to the region from other continents: yellow fever, dengue, and chikungunya, each of which have made permanent homes in ecologies ranging from the Amazon rainforest to posh Caribbean resorts to Andean villages to Mexico City.
The prospect of a disease never previously seen in the Western Hemisphere taking hold permanently, and endangering thousands of babies every year, is chilling. Control efforts, like spraying insecticides and covering standing water, would be of no value inside tropical rainforests like the Amazon or swamplands such as the Louisiana bayous. Aggressive urban mosquito abatement programs would help reduce human infections, but the virus would keep coming back year after year, popping out of its remote hiding places. And in the end, the only hope for eliminating human disease would rest with the invention of an effective vaccine and mass, routine vaccination of hundreds of millions of people across the Western Hemisphere.
Could it happen?
During the late summer of 1999, a handful of individuals in New York City came down with a strange neurological disease that caused encephalitis, seizures, and some deaths. W. Ian Lipkin, a researcher who was then located in California but is now a professor and lab director at Columbia University, made the stunning discovery that the cause was West Nile virus, a mosquito-carried microbe previously found in the Middle East and Great Lakes region of Africa. Even more startling, the virus was easily spread by North American mosquitoes, and it obliterated highly susceptible populations of Western Hemisphere birds, such as crows and many songbird species. Further, West Nile virus turned out to be lethal for horses – another animal not native to Africa and, like the birds, lacking natural immunity to the new virus. By 2000, when West Nile virus returned to New York and other parts of the United States, veterinarians and wildlife experts realized that the African virus was readily passed to birds by mosquitoes that fed on nested chicks during the spring, then horses and humans during the hot summer months, creating an entirely new biological cycle for the virus and the disease.
Sixteen-and-a-half years later, West Nile virus causes infections in people all over North America, the Caribbean, and into Central America – it is endemic. Despite the best efforts of health departments and vaccine scientists, nobody has figured out how to stop West Nile’s annual spring and summer spread across the region because it has a sylvatic cycle, meaning it now circulates in wild animals and birds.
How likely is it that the Zika virus will take hold and find nonhuman hosts and targets from Tierra del Fuego to Nova Scotia? Remarkably little is known about the biology of Zika, though it was discovered in Uganda in 1947 by scientists from the Rockefeller Foundation, who stumbled on the virus when they experimentally injected Asian lab monkeys and American research mice with it – the mice proved vulnerable to mild forms of the disease.
New World monkeys, such as South America’s tamarin, howler monkey, and squirrel monkey, are rarely used in routine biology research experiments, and their susceptibility to African viruses isn’t well known. In some cases, such as the African monkey forms of the AIDS virus, American primates have proved invulnerable, and the viruses could not infect their cells. As a result, humans are the only carriers of HIV and the monkey SIV viruses in the Western Hemisphere. Similarly, scientists have not been able to experimentally cause dengue fever in New World monkeys, though the high costs of the research animals have severely limited the number of experimental attempts. New World monkeys are susceptible to the Asian chikungunya virus and Africa’s yellow fever, both of which are from other continents. Both viruses have sylvatic cycles in the Americas, especially across the Amazon rainforest region. Here is how a 2010 study illustrated the cycles for yellow fever and chikungunya viruses. (You can view the graphic here.)
When I looked at the graphic, I was stunned to see that the sylvatic cycle pictured hypothetically in Africa involved monkeys and chimps infected by the Aedes africanus mosquito – the same species that has for millennia carried Zika in African equatorial areas. Further, the urban cycle that it depicts shows people acquiring infection from two other Aedes mosquito species – aegypti and albopictus – which are now spreading Zika all over South America.
In the summer of 2014, chikungunya was almost exclusively found in equatorial Africa, Southeast Asia, and China, but by the summer of 2015, the U.S. Centers for Disease Control and Prevention identified human cases of the mosquito-carried disease all over the Americas. Almost overnight – in the span of less than two years – chikungunya has gone from an obscure tropical disease to a global phenomenon, infecting new animals, mosquitoes, and human beings on vulnerable continents.
The geographic and human spread of Zika has been even faster than was seen with chikungunya, with most of the identified cases in 23 countries and territories of the Americas occurring since late November. Researchers at Fiocruz, Brazil’s top biomedical institute, have managed to experimentally infect a genus of mosquito that is native to the Americas, Culex. Unlike the Aedes insects that originated in Africa, Culex is an Americas mosquito with a complex cycle of blood-feeding across multiple species – including human beings – all over North and South America. Odds are that those itchy bites you’ve scratched in the summertime were the result of a little brown Culex sucking your blood, as they are ubiquitous in warm, wet areas from Alaska to southern Argentina. (West Nile virus is spread in North America by Culex pipiens.) A 1993 Chinese study showed that Culex mosquitoes could spread dengue viruses. Researchers in Senegal have captured 13 mosquito species in West Africa, finding Zika viruses in 10 of them, including African forms of Aedes and Culex. The insects were snared from rainforest areas, where they were blood-feeding on wild animals, particularly monkeys. And further work in Senegal shows that a long list of viruses – including the current scourges of dengue, yellow fever, Zika, and chikungunya – readily infect a large range of African apes and monkeys, as well as multiple species of mosquitoes, shifting from one sylvatic cycle to another seasonally.
Last year, an unfortunate 27-year-old adventure-seeker on holiday from Australia was bitten by an Indonesian monkey while outside of Bali and came down with Zika. That showed that the African virus had managed to go sylvatic in Southeast Asian monkeys; in 2001, scientists published research showing Zika in wild orangutans in Borneo. But analysis shows some minor genetic differences in Zika strains found in wild areas of Asia versus Africa that might (though nobody really knows) affect which species of mosquito or animal cells the viruses can infect.
(To be continued)
Virus hunter Edward Hayes of the Barcelona Centre for International Health Research writes that, “There is to date no solid evidence of nonprimate reservoirs of [Zika],” though rodents can be infected experimentally. He concludes that any sylvatic cycle would have to involve monkeys and apes – which are plentiful in places like the vast Amazon, but rarely seen in the large urban centers of the Americas. Nikos Vasilakis of the University of Texas Medical Branch in Galveston has shown through his work that dengue and yellow fever – both viruses native to the Old World – have established firm sylvatic cycles in South America, infecting monkeys and a range of wild mosquito species, and occasionally spilling over into urban areas to infect and sicken people.
So, given evidence that other mosquito-carried viral diseases that are new to the Americas have found permanent homes there, including in New World animals and birds, how likely is it that Zika will become a permanent feature of the public health landscape and ecologies of the Western Hemisphere? I polled several prominent arbovirus experts in the United States, Canada, Brazil, and Mexico, and asked them how likely a sylvatic scenario might be for Zika.
Maurício Lacerda Nogueira of the São José do Rio Preto medical school in Brazil told me that virtually zero funding is available for the study of disease ecology in Latin America, and none of the research that is urgently needed is supported by the region’s governments. Nogueira’s U.S. colleagues say the funding situation is equally bad in the country, and funding cycles are so distant that scientists would have to wait until 2017 to get money to chase mosquitoes and animals in the Everglades, or capture and test wild mosquitoes all over the country.
The Zika blood test is quite poor, researchers bemoan, and even when using sophisticated laboratory technology it is extremely difficult to find the virus in infected people, much less insects, birds, and animals. Lyle Peterson and his team at the CDC have developed an improved RT-PCR test – nerd-speak for a DNA-based screening method – but even within the United States only a handful of public health labs know how to use it, he told a special Jan. 28 Zika meeting at the WHO.
There are enormous gaps in our understanding of Zika, the scientists tell me, and it is unlikely funding will materialize before the virus has taken up residence all over the hemisphere. Virtually nothing definitive is known about the interactions between Zika and New World animals. Scott Weaver of the University of Texas Medical Branch, in a lengthy correspondence over email, told me he thinks it’s highly unlikely Zika will be spread by Culex and notes that the Aedes mosquitoes are so efficient in spreading the virus that the Culex issue may not be very important. Kansas State University expert Stephen Higgs says that it is very difficult to predict what will happen when a new virus enters a complex insect and animal ecology or to know which mosquito species will play a role in transmission: There have been surprises. He notes that in 2007 Zika was spread by albopictus, or “tiger mosquitoes,” in Gabon, which was a complete surprise at the time. West Nile virus has now been found in some 60 different mosquito species in North America, he says – also a complete surprise.
When G.W.A. Dick of the National Institute for Medical Research in London discovered Zika in 1947 in Uganda, he used captive rhesus monkeys to see if the yellow fever virus infected primates, tying the animals to trees and waiting for them to be bit by mosquitoes. The animals were bit, but the virus inserted by the mosquitoes into their blood was something never previously seen. Dick named it “Zika” after the local forest area. Today, despite startling advances in metagenomics research and virus analysis, Dick’s 1947 experimental method is not much improved. It is difficult to hunt down infected animals, snare wild forest mosquitoes, and analyze them in a laboratory.
At the U.S. National Institutes of Health, David Morens is leading new Zika research initiatives. He tells me that Zika has found new life cycles in each new ecology it has entered and will likely do so across the Western Hemisphere. “But what would they be? We can only speculate at this point,” he said. In the spirit of speculation, Morens added, “Regarding birds, while it can’t be ruled out, the Western Hemisphere is a new area for this virus, with different species and ecologic niches. It wouldn’t be my greatest fear, but it has to be considered a possibility.”
Overall, the scientists I was in touch with who work in this field told me two things: First, not enough is known about Zika (especially in the New World) to definitively answer the question; and second, other similar viruses (dengue, yellow fever, and chikungunya) have become endemic and sylvatic in the Americas, so, why not Zika, too?
I asked Claudio Maierovitch, the director of Communicable Diseases Surveillance for Brazil’s Ministry of Health, at a WHO press conference Thursday about the possibility. “Most things about the Zika virus are not known yet, and that is a big question,” Maierovitch said, noting that most of Brazil’s work is at the cellular level, infecting insect and human cells. Bruce Aylward, who runs the WHO’s epidemic response unit, added, “It would be a mistake to say [that what is now known about Zika] explains what we see now,” in the Americas.
There are many uncertainties about Zika, including whether it is directly responsible for the misshapen skulls of babies born to infected mothers. For example, there are four types of dengue virus, and the severity of infection can range from mild aches and pains all the way to an Ebola-like hemorrhagic death. For years, scientists tried to pinpoint which strain caused which symptoms, but it is now known that the worst outcomes arise when an individual is infected sequentially with different strains, triggering his immune system into a massive overreaction. With this, and other complicated examples of mosquito-carried viral diseases in mind, the WHO is very cautiously referring to an “association” between microcephaly and Zika – not yet cause and effect. Seriously complicating matters is the Zika blood test: It can only detect viruses in human blood during the first five days of infection, but average Zika incubation time is four to five days, meaning that by the time individuals seek medical help the virus is already undetectable with current diagnostics. A longer-term assay, which tests for the presence of antibodies to Zika, is so weak that it cross-reacts with dengue and chikungunya, rendering it useless in the context of concurrent spread of all three viruses.
But Zika has been circulating in South America since last April or May, and explosive spread in Brazil has been underway since October. The correlation (if not causation) between Zika, pregnancy, and microcephaly has been noted by Brazilian health authorities since November, as have a worrying number of cases of paralytic Guillain-Barré syndrome. Yet the WHO has done little publicly throughout November and December, save releasing a few press statements. This week, the New York Times and Newsweek, among others, asked whether the WHO was asleep at the wheel.
My conclusion is that public health leaders and politicians had better brace for a very long haul on Zika. The virus will hide, infecting a range of insects, perhaps monkeys, even birds. And it will return in seasonal cycles, as have other mosquito-carried viruses, such as yellow fever, West Nile virus, chikungunya, and dengue. Because so many “foreign” viruses carried by mosquitoes are now spreading across the Western Hemisphere at the same time, there will be misdiagnosis, mystery, and perhaps acute illnesses due to co-infections. Until we have an effective vaccine and have executed mammoth immunization campaigns in all of the nations of the Americas, Zika will haunt us, sicken some of us, and endanger our babies.
(Laurie Garrett is senior fellow for global health at the Council on Foreign Relations and a Pulitzer Prize winning science writer).
