Keystone Virus Makes First Known Jump From Mosquitoes To Humans 
 
 Enlarge this image toggle caption Alan Diaz/AP Alan Diaz/AP 
 
 Updated at 10:45 a.m. ET Friday 
 
 Just in time for the hot, humid, bug-bite-riddled summer: Researchers from the University of Florida have confirmed the first known case of a human infected with the mosquito-borne Keystone virus. 
 
 A 16-year-old boy in North Central Florida went to an urgent care clinic after coming down with a fever and a severe rash in August 2016, during the Zika outbreak in Florida and the Caribbean. 
 
 Doctors couldn't figure out what made him sick. They tested for Zika and various other pathogens but hit a series of dead ends. 
 
 "We couldn't identify what was going on," J. Glenn Morris, director of the university's Emerging Pathogens Institute, told NPR member station WUSF. "We screened this with all the standard approaches and it literally took a year and a half of sort of dogged laboratory work to figure out what this virus was." 
 
 Researchers published their findings earlier this month in the journal Clinical Infectious Diseases. 
 
 The virus was first found in the U.S. in 1964, when researchers isolated it from mosquitoes in Keystone, Fla. Since then, it "has been found in animal populations along coastal regions stretching from Texas to the Chesapeake Bay," according to a statement from University of Florida Health. 
 
 But until now, there hasn't been a way to test humans for the Keystone virus, which is carried by the Aedes atlanticus mosquito, a cousin to the Zika-spreading Aedes aegypti. 
 
 The virus can cause a rash and mild fever in humans. The teenager did not show signs of encephalitis, or inflammation of the brain — but Keystone is part of a group of viruses "known to cause encephalitis in several species, including humans," said lead study author John Lednicky, a University of Florida research professor in the environmental and global health department of the College of Public Health and Health Professions. 
 
 Morris suspects many people might have the Keystone virus. 
 
 "Although the virus has never previously been found in humans, the infection may actually be fairly common in North Florida," he said in the statement. 
 
 "It's one of these instances where if you don't know to look for something, you don't find it." ||||| A mosquito-borne illness originally found in the Tampa Bay area has been confirmed in a human for the first time, according to University of Florida researchers. 
 
 The Keystone virus, named after the northwestern Hillsborough County area where it was initially identified in 1964, has been found in animal populations along coastal regions stretching from Texas to the Chesapeake Bay. 
 
 UF researchers have been sequencing the virus since August 2016, when a 16-year-old boy in North Central Florida showed up to a clinic with a rash and fever during the Zika virus epidemic in Florida and the Caribbean. The report was published June 9 in the journal Clinical Infectious Diseases. 
 
 Because of concerns about Zika, laboratory samples were collected from the patient, but studies were negative for Zika or related viruses. 
 
 But the researchers found Keystone virus when they did viral cultures from the patient samples. Although the teenager did not report symptoms of encephalitis, lab studies indicate that Keystone virus can infect brain cells, and may pose a risk for brain infections. 
 
 Dr. Glenn Morris, director of the university's Emerging Pathogens Institute, said until now, there hasn't been a way to test for the virus. 
 
 "We couldn't identify what was going on,” Morris said. “We screened this with all the standard approaches and it literally took a year and a half of sort of dogged laboratory work to figure out what this virus was.” 
 
 Morris said biotech companies are already reaching out to the institute to develop commercial tests that can be used in clinics and hospitals. 
 
 Keystone is spread by aedes atlanticus, a common Florida mosquito and cousin to the mosquito, aedes aegypti, that spreads Zika. 
 
 It’s part of a group of viruses that are known to cause encephalitis - inflammation of the brain - in several species, including humans. Morris said they’re not absolutely certain that Keystone can also cause encephalitis. 
 
 Morris said although the virus has never previously been found in humans, the infection may actually be fairly common in North Florida. A 1972 article in the American Journal of Tropical Medicine and Hygiene reported Keystone virus antibodies in 19 to 21 percent of the people tested in the Tampa Bay region. 
 
 “There’s a high likelihood that Keystone virus is continuing to circulate in Florida, as it has for at least 50 or 60 years, and as it may well have for hundreds of years,” Morrisa said. “This is one of our native Florida viruses.” 
 
 "It's likely there have continued to be a fair number of human infections. In most instances, it would appear to be asymptomatic or cause mild infection, fever and a rash." 
 
 Morris emphasized the need for additional research into the prevalence of vector-borne diseases in the United States, and stressed the importance of minimizing the risk of mosquito bites by using mosquito repellent. ||||| The explosive pandemic of Zika virus infection occurring throughout South America, Central America, and the Caribbean (see map Countries with Past or Current Evidence of Zika Virus Transmission (as of December 2015).For countries with serosurvey data only, evidence of Zika virus transmission is derived from studies that detected Zika virus antibodies in healthy people. Outlined areas, all with locally acquired cases or virus isolation, include Cape Verde, Cook Islands, Easter Island, Federated States of Micronesia, French Polynesia, Martinique, New Caledonia, Puerto Rico, Solomon Islands, and Vanuatu. Data are from the Centers for Disease Control and Prevention (http://www.cdc.gov/zika). ) and potentially threatening the United States is the most recent of four unexpected arrivals of important arthropod-borne viral diseases in the Western Hemisphere over the past 20 years. It follows dengue, which entered this hemisphere stealthily over decades and then more aggressively in the 1990s; West Nile virus, which emerged in 1999; and chikungunya, which emerged in 2013. Are the successive migrations of these viruses unrelated, or do they reflect important new patterns of disease emergence? Furthermore, are there secondary health consequences of this arbovirus pandemic that set it apart from others? 
 
 “Arbovirus” is a descriptive term applied to hundreds of predominantly RNA viruses that are transmitted by arthropods, notably mosquitoes and ticks. Arboviruses are often maintained in complex cycles involving vertebrates such as mammals or birds and blood-feeding vectors. Until recently, only a few arboviruses had caused clinically significant human diseases, including mosquito-borne alphaviruses such as chikungunya and flaviviruses such as dengue and West Nile. The most historically important of these is yellow fever virus, the first recognized viral cause of deadly epidemic hemorrhagic fever. 
 
 Zika, which was discovered incidentally in Uganda in 1947 in the course of mosquito and primate surveillance,1 had until now remained an obscure virus confined to a narrow equatorial belt running across Africa and into Asia. The virus circulated predominantly in wild primates and arboreal mosquitoes such as Aedes africanus and rarely caused recognized “spillover” infections in humans, even in highly enzootic areas.2 Its current explosive pandemic reemergence is therefore truly remarkable.3 Decades ago, African researchers noted that aedes-transmitted Zika epizootics inexplicably tended to follow aedes-transmitted chikungunya epizootics and epidemics. An analogous pattern began in 2013, when chikungunya spread pandemically from west to east, and Zika later followed. Zika has now circled the globe, arriving not only in the Americas but also, in September, in the country of Cape Verde in West Africa, near its presumed ancient ancestral home. 
 
 With the exception of West Nile virus, which is predominantly spread by culex-species mosquitoes, the arboviruses that recently reached the Western Hemisphere have been transmitted by aedes mosquitoes, especially the yellow fever vector mosquito A. aegypti. These viruses started to emerge millennia ago, when North African villagers began to store water in their dwellings. Arboreal A. aegypti then adapted to deposit their eggs in domestic water-containing vessels and to feed on humans, which led to adaptation of arboreal viruses to infect humans. The yellow fever, dengue, and chikungunya viruses evolved entirely new maintenance cycles of human–A. aegypti–human transmission.4 Now, 5000 years later, the worst effects of this evolutionary cascade are being seen in the repeated emergence of arboviruses into new ecosystems involving humans. Moreover, arboviruses transmitted by different mosquitoes have, in parallel, adapted to humans’ domestic animals, such as horses in the case of Venezuelan equine encephalitis and pigs in the case of Japanese encephalitis virus, or to vertebrate hosts and non-aedes mosquitoes found in areas of human habitation, as West Nile virus did. The possibility that Zika may yet adapt to transmission by A. albopictus, a much more widely distributed mosquito found in at least 32 states in the United States, is cause for concern. 
 
 Through early epidemiologic surveillance and human challenge studies, Zika was characterized as a mild or inapparent denguelike disease with fever, muscle aches, eye pain, prostration, and maculopapular rash. In more than 60 years of observation, Zika has not been noted to cause hemorrhagic fever or death. There is in vitro evidence that Zika virus mediates antibody-dependent enhancement of infection, a phenomenon observed in dengue hemorrhagic fever; however, the clinical significance of that finding is uncertain. 
 
 The ongoing pandemic confirms that Zika is predominantly a mild or asymptomatic denguelike disease. However, data from French Polynesia documented a concomitant epidemic of 73 cases of Guillain–Barré syndrome and other neurologic conditions in a population of approximately 270,000, which may represent complications of Zika. Of greater concern is the explosive Brazilian epidemic of microcephaly, manifested by an apparent 20-fold increase in incidence from 2014 to 2015, which some public health officials believe is caused by Zika virus infections in pregnant women. Although no other flavivirus is known to have teratogenic effects, the microcephaly epidemic has not yet been linked to any other cause, such as increased diagnosis or reporting, increased ultrasound examinations of pregnant women, or other infectious or environmental agents. Despite the lack of definitive proof of any causal relationship,5 some health authorities in afflicted regions are recommending that pregnant women take meticulous precautions to avoid mosquito bites and even to delay pregnancy. It is critically important to confirm or dispel a causal link between Zika infection of pregnant women and the occurrence of microcephaly by doing intensive investigative research, including careful case–control and other epidemiologic studies as well as attempts to duplicate this phenomenon in animal models. 
 
 In a “pure” Zika epidemic, a diagnosis can be made reliably on clinical grounds. Unfortunately, the fact that dengue and chikungunya, which result in similar clinical pictures, have both been epidemic in the Americas confounds clinical diagnoses. Specific tests for dengue and chikungunya are not always available, and commercial tests for Zika have not yet been developed. Moreover, because Zika is closely related to dengue, serologic samples may cross-react in tests for either virus. Gene-detection tests such as the polymerase-chain-reaction assay can reliably distinguish the three viruses, but Zika-specific tests are not yet widely available. 
 
 The mainstays of management are bed rest and supportive care. When multiple arboviruses are cocirculating, specific viral diagnosis, if available, can be important in anticipating, preventing, and managing complications. For example, in dengue, aspirin use should be avoided and patients should be monitored for a rising hematocrit predictive of impending hemorrhagic fever, so that potentially lifesaving treatment can be instituted promptly. Patients with chikungunya virus infection should be monitored and treated for acute arthralgias and postinfectious chronic arthritis. 
 
 There are no Zika vaccines in advanced development, although a number of existing flavivirus vaccine platforms could presumably be adapted, including flavivirus chimera or glycoprotein subunit technologies. Zika vaccines would, however, face the same problem as vaccines for chikungunya,4 West Nile, St. Louis encephalitis, and other arboviruses: since epidemics appear sporadically and unpredictably, preemptively vaccinating large populations in anticipation of outbreaks may be prohibitively expensive and not cost-effective, yet vaccine stockpiling followed by rapid deployment may be too slow to counter sudden explosive epidemics. Although yellow fever has historically been prevented entirely by aggressive mosquito control, in the modern era vector control has been problematic because of expense, logistics, public resistance, and problems posed by inner-city crowding and poor sanitation. Among the best preventive measures against Zika virus are house screens, air-conditioning, and removal of yard and household debris and containers that provide mosquito-breeding sites, luxuries often unavailable to impoverished residents of crowded urban locales where such epidemics hit hardest. 
 
 With its recent appearance in Puerto Rico, Zika virus forces us to confront a potential new disease-emergence phenomenon: pandemic expansion of multiple, heretofore relatively unimportant arboviruses previously restricted to remote ecologic niches. To respond, we urgently need research on these viruses and the ecologic, entomologic, and host determinants of viral maintenance and emergence. Also needed are better public health strategies to control arboviral spread, including vaccine platforms for flaviviruses, alphaviruses, and other arbovirus groups that can be quickly modified to express immunogenic antigens of newly emerging viruses. With respect to treatment, the arbovirus pandemics suggest that the one-bug–one-drug approach is inadequate; broad-spectrum antiviral drugs effective against whole classes of viruses are urgently needed. 
 
 As was realized more than 50 years ago, when enzootic Zika virus spread was linked to human activity, arboviruses continually evolve and adapt within ecologic niches that are increasingly being perturbed by humans. Zika is still a pandemic in progress, and many important questions about it, such as that of teratogenicity, remain to be answered. Yet it has already reinforced one important lesson: in our human-dominated world, urban crowding, constant international travel, and other human behaviors combined with human-caused microperturbations in ecologic balance can cause innumerable slumbering infectious agents to emerge unexpectedly. In response, we clearly need to up our game with broad and integrated research that expands understanding of the complex ecosystems in which agents of future pandemics are aggressively evolving. ||||| Two years ago, hardly anyone had heard of the Zika virus. A handful of specialists knew of it as a mostly benign mosquito-borne disease that jumped from Africa to a few Pacific islands and occasionally caused, at worst, mild fever, aches, or rash. Nothing to fret about. 
 
 Then everything changed. The virus arrived in Brazil in 2014, likely brought by a World Cup traveler, and spread rapidly throughout Latin America, carried by the pervasive Aedes aegypti mosquito and infecting millions. Suddenly, Zika appeared to be doing things no one thought it could do — like (possibly) causing microcephaly, a birth defect characterized by shrunken heads, in infants. 
 
 Scientists were caught completely flat-footed. Thomas Frieden, the director of the Centers for Disease Control and Prevention, pointed out today that the entire research literature on Zika could, when printed out, basically fit into a shoebox: 
 
 Entire world literature on Zika. 50 years of neglect. pic.twitter.com/iX7zbJSTC5 — Dr. Tom Frieden (@DrFriedenCDC) February 12, 2016 
 
 That's it. That's everything we know right now. A small stack of papers. 
 
 To put this in context, a search on the PubMed database reveals 14,000-plus hits for "dengue fever," another mosquito-borne disease afflicting the region. For "West Nile virus," you get 5,962 hits. For "Zika virus," just 146. 
 
 That's a big reason why this outbreak has unnerved so many people. The Zika virus has infected more than 1 million people in Brazil and South America and has been spreading "explosively," as the World Health Organization put it, to Central America, the Caribbean, and even the southern United States. Yet there are all sorts of basic things that scientists are still racing to figure out. Like: 
 
 1) What does Zika actually do to people? Scientists have long known that the vast majority of people who contract Zika don't get any symptoms at all. A small fraction (20 percent or so) develop mild fevers, aches, and rashes. 
 
 Yet that might not be the end of the story. Since the Brazil outbreak, evidence has surfaced that pregnant women who contract Zika may be able to pass it to their infants, causing microcephaly (shrunken heads and incomplete brain development). Unfortunately, scientists still don't know how that happens, how often it happens, or whether it's a major risk or minor one. Maybe something else is causing the apparent uptick of microcephaly cases in Brazil. It's unclear. 
 
 And in the absence of clarity, we're seeing lots of panic and calls for drastic measures — many Latin American countries are simply telling women to postpone pregnancy. 
 
 2) Can Zika really cause Guillain-Barré syndrome in adults? This is a neurological condition that can cause muscle weakness and even paralysis, lasting weeks, months, or even years. A link seems possible, but scientists are still trying to figure this one out. 
 
 3) How do you actually test for and track the virus? Again, about 80 percent of people who get Zika don't show any symptoms (but they can still spread the disease if they are bitten by a mosquito). That makes monitoring the outbreak much, much harder. The fact that Zika may be mutating and the fact that it's similar to other flaviviruses like dengue and yellow fever make testing even tougher. 
 
 4) How does Zika actually spread? Right now, scientists think the disease is mainly spread when Aedes aegypti mosquitoes, a species ubiquitous in Latin America and the southern United States, bites an infected person and then bites an uninfected person. 
 
 But that still leaves plenty of questions. It's unclear whether Aedes albopictus, a similar mosquito with a larger range throughout North America, might also help spread the virus. And scientists are investigating whether Culex mosquitoes, another common species, could be a carrier. 
 
 On top of that, scientists are learning that Zika can sometimes be spread through sexual contact (though it's unclear how long the virus stays in semen). And it's possible, though not certain, that Zika could be spread through saliva. Figuring this stuff out is crucial for halting the current outbreak. See Julia Belluz's great piece on this for more. 
 
 A related question is why Zika has spread with such alarming speed throughout South and Central America. Is it just because the disease is hitting a population with no natural defenses? Or has the virus mutated in some way that makes it easier to spread? 
 
 5) How do we make a Zika vaccine? Making a vaccine takes years, as Brian Resnick nicely explained. And it will take even longer because research on Zika is so primitive. "Nobody thought Zika was a high enough priority to warrant making a vaccine for it," Peter Hotez, a tropical disease expert, told Resnick. "It was always the last slide on a PowerPoint presentation about arboviruses." 
 
 The good news is that research is ramping up, particularly since the World Health Organization declared an emergency. Experts on viruses, on tropical disease outbreaks, on mosquito control — they're all starting to dig into these questions. Just this week a paper in the New England Journal of Medicine published the strongest evidence yet of a link between Zika and microcephaly. And the Obama administration recently asked Congress for $1.8 billion, with a big chunk of that aimed at bolstering the CDC's research and containment programs. 
 
 But there's no question the world has been caught by surprise, which means there is going to be a lot of uncertainty about Zika in the meanwhile. 
 
 Further reading:
– A coastal virus that can cause a rash and mild fever has officially infected a person for the first time, NPR reports. Scientists say it took 18 months to figure out that a Florida teen who got sick during the Zika outbreak of 2016 actually had the Keystone virus, which is carried by mosquitos. "We couldn't identify what was going on," J. Glenn Morris, head of the Emerging Pathogens Institute at the University of Florida, tells WUSF. "We screened this with all the standard approaches and it literally took a year and a half of sort of dogged laboratory work to figure out what this virus was." There wasn't even a test to detect Keystone virus in humans. The 16-year-old boy had a fever and a bad rash, but not the encephalitis (or brain inflammation) that a group of viruses including Keystone can cause in animals. First seen in America in 1964, Keystone is known to infect "animal populations along coastal regions stretching from Texas to the Chesapeake Bay," per a University of Florida Health statement. Scientists have long suspected there are human cases, but the new study in Clinical Infectious Diseases confirms it. "The infection may actually be fairly common in North Florida," says lead study author John Lednicky. "It's one of these instances where if you don't know to look for something, you don't find it."