Paralysis. Pregnancy complications. Possible sexual transmission. These are just some of the headlines surrounding the Zika virus. While not commonly associated with death, the World Health Organization (W.H.O.) declared the mosquito-borne illness an “international public health emergency” this month due to a surge in neurological disorders associated with viral infection. The W.H.O. predicts nearly four million people worldwide will contract Zika by the end of 2016; Brazil, the hardest-hit nation so far, currently harbors more than one million cases. Here is everything you should know about this rapidly evolving health crisis and the global response.
An escalating illness
Zika is a single-stranded RNA flavivirus first identified in rhesus monkeys in Uganda in 1947. Human transmission was documented five years later with only 14 cases diagnosed worldwide until 2007 (Campos, NIAID, Ramzy).
Like its flavivirus cousin’s yellow fever and dengue virus, Zika is transmitted by Aedes mosquitoes yet its symptoms are much milder. One in five people infected will develop a fever, rash, join pain, or red eyes. Such symptoms typically resolve in a week and rarely require hospitalization, leading health officials to originally dismiss the infection as a sporadic, “light dengue” that simply required observation (McNeil).
Zika’s classification as a “benign disease” ended last year (McNeil). An outbreak of the virus in Latin America and Caribbean countries correlates with a dramatic increase in diagnosis of microcephaly, or abnormally small heads and brains, in babies as well as adult Guillain-Barré syndrome (GBS), an autoimmune disorder characterized by temporary paralysis in the hands and feet (W.H.O., C.D.C.).
Microcephaly can cause seizures, feeding difficulties, and developmental delays in newborns. GBS paralysis can be fatal if it progresses to the lungs.
Six countries with confirmed Zika epidemics report increased incidence of microcephaly and Guillain-Barré syndrome (McNeil, W.H.O.-February 19th). Brazil reported more than 20x its annual rate of microcephaly cases in the past few months with nearly 4,000 newborns diagnosed (Vogel). The country, in addition with Colombia, Suriname, and El Salvador, is also experiencing a 2-4 fold increase in GBS diagnosis.
“Doctors, pediatricians, neurologists, they started finding this thing we never had seen,” said Dr. Celina M. Turchi, an infectious disease researcher at the Oswaldo Cruz Foundation in Brazil (McNeil). “Children with normal faces up to the eyebrows…no foreheads and very strange heads.”
Nikos Vasilakis, a virologist at the University of Texas on assignment in Salvador, told Science the surge in cases microcephaly cases “would break anyone’ heart.”
“I have witnessed expressions of love but also rejection of the babies,” he said (Vogel).
So far, circumstantial evidence links the Zika virus to microcephaly or GBS. The Brazilian Ministry of Health, Pan American Health Organization (P.A.H.O.) and U.S Centers for Disease Control and Prevention (C.D.C) confirmed the presence of viral RNA in 23 recent newborns, stillborns, and miscarriages with microcephaly as well as the placenta and amniotic fluid of four pregnant women whose fetuses were diagnosed with microcephaly (C.D.C, P.A.H.O., Schuler-Faccini). All cases tested were negative for infection with more common tropical viruses such as dengue, parvovirus, and yellow fever.
Retrospective data from a 2013 Zika outbreak in French Polynesia indicated a 4-9 fold increase in microcephaly incidence and a 20 fold increase in GBS cases (Oehler, P.A.H.O., W.H.O.). All GBS individuals tested positive for Zika antibodies and 88% reported “illness compatible with Zika infection” (P.A.H.O., Ramzy).
Dr. Albert Ko, an infectious disease physician and epidemiologist at the Yale School of Public Health working in collaboration with the Brazilian health ministry, strongly suspects Zika is responsible for the current surge in microcephaly incidence (WPost-interview).
“We still don’t have firm evidence… [but] we strongly believe that the cases of microcephaly we are identifying during this outbreak are due to Zika virus,” he told The Washington Post (Sun-February 9th).
A rapid response
The World Health Organization (W.H.O.), a branch of the United Nations, classified Zika as an “international public health emergency” on February 1st and is mobilizing global efforts to stall the epidemic.
“The level of alarm is extremely high, as is the level of uncertainty,” said Dr. Margaret Chan, head of the W.H.O., in an interview with CNN and The New York Times (Botelho, Sun-January 29th, Tavernise). “We need to get some answers quickly. We need a coordinated international response.”
Zika is the first mosquito-borne illness to receive health emergency status. Such a designation elevates the W.H.O. to “the position of global coordinator,” “gives its decisions the force of international law” and will help standardize and increase surveillance of new cases across countries (Tavernise, W.H.O-February 1st).
Dr. David L. Heymann, chairman of the W.H.O. emergency committee researching the virus, said their current focus is “clarifying the link between Zika and babies born with small heads and brains” (Bichell).
“The research needs to be pulled together instead of different groups doing different things in their own countries,” he said (Tavernise).
Dr. William Schaffner, an infectious disease specialist at Vanderbilt University, applauds the W.H.O.’s necessary attention to the Zika epidemic.
“If there is a ministry of health anywhere that hasn’t awakened to the problem, this will do that,” he told The New York Times (Tavernise).
Response to the Zika outbreak has also been swift in the United States. The C.D.C issued a travel advisory for pregnant women in January. President Obama submitted a Congressional on February 8th for $1.8 million in federal funding for virus surveillance, basic research, international aide, vector control and vaccine development.
Dr. Anne Schuchat, deputy director of the C.D.C., says the agency has placed its Zika emergency operations center, with a staff of 300 “on the highest level of activation” (Bichel, Murfson). She and Fauci believe that well-established mosquito prevention methods will limit the spread of the virus in the United States.
“We aren’t expecting large-scale amounts of serious Zika infections [however] we do think it’s likely we’ll have limited local transmission in some of the Southern states,” she told reporters (Rampton, Landler).
22 states and two territories in the US have reported cases of Zika virus infection for a total of 85 cases to date according to the C.D.C. All current cases except for one are travel-associated and were contracted from travel in foreign country experiencing Zika outbreaks. Most cases are in Texas and Florida where Aedes mosquitoes are endemic, however, no cases of transmission from local mosquitoes have been observed. A Hawaiian case of microcephaly and one case of Guillain-Barré syndrome are currently under investigation for a link to Zika infection (C.D.C., Sun-February 11th).
Florida declared a public health emergency in four counties with confirmed Zika virus cases to mobilize resources for the warm summer months.
“We know we must be prepared for the worst even as we hope for the best,” Governor Rick Scott told The Washington Post (Cha).
Researchers on the ground in Brazil agree believe any prevention or research efforts are critical to combat an epidemic of neurological defects that caught them by surprise.
Dr. Bruno Andrade, an immunologist at Fiocruz research institute in Bahia, Brazil described the situation to Nature as being “in the middle of this nightmare” while Dr. Laura C. Rodrigues, an epidemiologist at the London School of Hygiene and Tropical Medicine on contract to the Pan American Health Organization, was astonished by the new ferocity of the Zika virus (Check Hayden).
“There had never been a congenital malformation by mosquito before, not ever” she told The New York Times (McNeil). “It was totally outside our experience.”
Dr. Michael Diamond, an infectious disease specialist at Washington University in St. Louis, agrees with the sense of urgency.
“There really hadn’t been any work done in about 40 years on Zika virus in animals,” he said (Bichel). “We need vaccines, we need therapies, we need diagnostics. We need to know how this virus works.”
Seeking a cause and the cure
The primary focus of current research efforts is confirming if and how Zika causes neurological damage. Other viruses such as rubella and cytomegalovirus have already been established as causing birth-related or congenital defects including microcephaly. Many believe that examining the cellular mechanism by which these viruses work could provide a window into Zika’s effects.
“I think we’ll discover a lot of parallels [to Zika],” said Dr. Mark R. Schleiss, director of pediatric infectious diseases and immunology at the University of Minnesota Medical School in an interview with The New York Times (Zimmer).
Direct and indirect mechanisms of virus induced fetal damage have been demonstrated. Cytomegalovirus rapidly replicates insides the neural stem cells of the fetus, causing significant disruption to developing neurons while the immune system isn’t fully developed (Zimmer).
Dr. Gil G. Mor, the director of reproductive sciences at Yale University, demonstrated an indirect approach of “bystander damage” in pregnant mice infected with herpes like viruses, showing the difference between an STD that simply goes away and one that doesn’t. The virus never directly entered the fetus but activated an immune response in the placenta causing inflammation-triggering particles to be absorbed by the fetus. Uncontrolled swelling then killed off or severely damaged fetal brain tissue.
Either approach may occur during Zika infection and will require several years of testing and appropriate modeling to tease out. Dr. Koen Van Rompay, a virologist at the University of California Davis, will study the neurological effects of Zika in newborn monkeys whose pregnant mothers were infected with the virus (Zimmer).
Dr. Ko and Dr. Lavinia Schuler-Faccini of the Brazilian Medical Genetics Society-Zika Embryopathy Task Force are independently comparing brain damage between current Zika-associated cases of microcephaly and infection with other congenital viruses (Zimmer, Sun-February 9th). She and Ko have both observed an unusually smooth brain surface in Zika microcephaly cases in comparison to rubella or cytomegalovirus microcephaly cases.
Knowing how Zika works could also provide insight into possible treatments.
“If we understand how the virus infects cells, we can come up with ways to suppress it,” said Dr. Lenore Pereira, the UCSF virologist responsible for infection studies of cytomegalovirus (Zimmer).
Injecting an expectant mother to with antibodies to Zika, for example, could protect her fetus from infection.
The U.S. National Institute of Allergy and Infectious Diseases (NIAID) is developing a Zika-specific drug screening method based on its “existing antiviral drug screening program for other flaviviruses” such as dengue, yellow fever, and West Nile.
“The goal is to develop a broad-spectrum antiviral drug that could be used to treat a variety of flaviviruses,” the organization said in a February statement (NIAID).
Prior research into West Nile virus and Ebola are also rapidly mobilizing vaccination efforts. According to NIAID director Dr. Anthony Fauci, preliminary trials of an “investigational Zika vaccine” could be completed as early as this summer in animals with human trials beginning in the fall (NIAID, Vogel).
Twelve other research organizations in Brazil, Europe, and the United States are also developing a Zika virus vaccine, often in collaboration with pharmaceutical companies (Cohen, Reuter).
Dr. Nicholas Jackson heads the Zika research effort at Sanofi-Pasteur, the French pharmaceutical company currently producing the three existing flavivirus vaccines to yellow fever, Japanese encephalitis, and dengue.
“A typical vaccine takes about 10 years to develop,” he told CNN. “We have a jump start here because we have experts in-house, technologies in-house; we have an infrastructure that we put in place around dengue vaccine that we can tap into very quickly which will hopefully take [time] off the typical timeline.”
Still, experts warn it could be years before the necessary large-scale clinical trials, efficacy experiments, or basic research on the Zika virus are complete and available (Cohen). The results of case-control studies comparing the pregnancy outcomes of women infected the virus to those without as well as the C.D.C’s development of a more sensitive diagnostic test for Zika are also anticipated (Butler, Hayden).
Jackson acknowledges the challenges “are considerable.”
“We know very little about the biology of this virus,” he said (Christensen).
Transmission and Timelines
Another question confounding researchers is how a virus originally from Africa crossed the Pacific Ocean. 50 people experienced symptoms nearly 8,000 miles away in Yap Island, west of the Philippines, during the first significant outbreak in 2007. Six years later, the virus appeared in French Polynesia with several thousand cases diagnosed (Ramzy, W.H.O.).
Epidemiologists currently blame travel to international sporting events for Zika’s arrival in the America’s. The beginning of the Brazilian outbreak coincides with the time and location of festivities for the 2014 World Cup soccer championship and Va’a World Sprint Polynesian canoe race in Rio and the town of Natal (Landler, McNeil). An infected individual, most likely from French Polynesia where a 2013 Zika outbreak occurred, attended either event and was bitten by an uninfected female Aedes mosquito. The virus became active in the mosquitoes system after a 10-day incubation period and was transmitted to another unsuspecting host when she took her next blood meal. The current Zika virus is 99% genetic identical to the French Polynesian virus, supporting this hypothesis (Murthy, McNeil).
Epidemiologists are concerned that, like the Ebola outbreak in 2014, Zika’s explosion in urban centers could represent a severe setback in combating the virus. Aedes aegypti mosquitoes, the established vector for the disease, thrive in man-made environments where access to potential blood meals and stagnant water are plentiful. Durland Fish, a professor of microbial disease at Yale University, describes “tires and cans and plastic containers and rain barrels” as the ideal “artificially human-made habitats.”
“Aedes doesn’t live in the ground, or in swamps, or any other kinds of places where you would normally find mosquitoes,” he told The Washington Post (Mooney). “So human have created an environment it for it to proliferate, by having all of these water containing containers around, and the mosquito has adapted so well…it’s really kind of a human parasite.”
An El Niño associated increase in global temperatures this year will only enhance Aedes influence by increasing individual survival, reproduction and biting rates, and by prolonging the Brazilian drought causing many mosquitoes to seek the shelter of urban water oasis.
The developing aggression of the Zika virus also worries the health community. Prior to 2007, only 14 cases of Zika viral infection in humans had been reported worldwide with none requiring hospitalization (McNeil, Ramzy). The 2013 French Polynesian outbreak affected 10% of the population but only produced a handful of neurological cases. A genetic change in Zika as it spread across the Pacific may be responsible for its enhanced ability to cause neurological damage (McNeil, Vogel). Prior infection with more common flaviviruses such as dengue could also dampen the host’s immune response (Vogel).
Human to human transmission of Zika is a developing possibility. The Brazilian Ministry of Health reported two cases of viral transmission through blood transfusions in January. Live Zika virus was also detected in the urine and saliva of two additional patients on February 5th (Sreeharsha, P.A.H.O.).
In addition, two cases of viral transmission by sexual contact have been confirmed in the U.S. and French Polynesia. The most recent case occurred in January when a man returning from Venezuela had sex with his female partner in Dallas, Texas. The woman developed flu-like symptoms a few days later and tested positive for the Zika virus after going to the doctor. This is the only current confirmed case of person to person transmission in the United States.
“Now that we know that Zika virus can be transmitted through sex, this increases our awareness campaign in educating the public about protecting themselves,” said Dallas County’s health director, Zachary Thompson (Sun-February 3rd). “Next to abstinence, condoms are the best prevention method against any sexually transmitted infections.”
The C.D.C and W.H.O. issued detailed recommendations on February 12th for preventing sexual transmission of the virus (Oster). The virus remains in the blood stream for up to 10 days after infection so all individuals traveling to Zika-affected countries are encouraged to use condoms or abstain from sexual activity for at least 28 days upon their return. The C.D.C also advises male travelers to abstain from sex with their female partners for the remainder of their pregnancy.
Brazil, Colombia, El Salvador, Ecuador and Jamaica advise women in Zika-affected areas to postpone pregnancy for at least two years or until the epidemic has subsided (Bichell, Sun-January 29th). The Pope also recently supported the limited use of contraceptives for Catholic women living in areas experiencing epidemics (BBC News, Romero).
With few cases of human to human transmission and no direct evidence for Zika causing congenital disorders, experts are concerned that such strong advisories may generate unnecessary concern and confusion among the general public.
Dr. Peter J. Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine, questions the significance of the Brazilian studies detecting viral particles in the urine and saliva of Zika patients.
“It still seems highly likely that the overwhelming numbers of cases of Zika are transmitted through mosquito bites,” he stated in an interview with The New York Times (Sreeharsha). “We know for example that dengue is only transmitted via Aedes mosquito bites, and yet we can find the dengue genome in urine and saliva. More research would need to be done to determine if Zika can be transmitted through kissing.”
Kalina de Andrade, a 28-year-old cashier living in Rio and five months pregnant, expressed worry over the conflicting information.
“The government needs to get better at explaining to the population what this means,” she said in response to the saliva cases (Sreeharsha). “I’m trying to remain calm, but this really is some troubling news.”
Final thoughts and future efforts
Health officials warn that, with no current vaccine or disease treatment, anyone is at risk for contracting the Zika virus. The W.H.O. and C.D.C advise those living in or visiting regions where an outbreak has occurred to avoid mosquito bites. This includes wearing long clothing and EPA approved insect-repellant when outdoors, and removing stagnant water sources where mosquitoes could breed.
The W.H.O. also encourages its member nations to curb endemic mosquito populations. The Brazilian government said on Friday it has already inspected over 40% of its properties (27 million households) for Aedes, treating standing water with insecticides against mosquito larvae and fumigating densely populated urban areas (Brazilian Ministry of Health-Aedes Fighting). Experts believe water treatment is especially critical in Latin America where poor infrastructure often leaves families dependant on rain tanks for their water supply (Mooney).
Brazil and the United States may also add genetically modified Aedes mosquitoes to their prevention efforts. Brazil’s National Biosafety Committee and the Florida Keys Mosquito Control District recently partnered with Oxitec, a British company originally based at Oxford University, to trial their self-limiting Aedes aegypti mosquitoes (Kim, Harvey). Each male mosquito contains a self-destructive gene that stalls cellular survival in the absence of an antibiotic antidote. GMO males mate with females in the wild, causing their offspring to die because they inherit the gene. Eliminating future populations of the only confirmed vector for the Zika virus should drastically decrease spread of the disease as well as its flavivirus cousins.
Oxitec says former field trials in the Cayman Islands, Brazil and Panama reduced Aedes aegypti populations by nearly 99% (Kim).
“It’s going in with a scalpel and taking away Aedes aegypti, leaving everything else untouched,” said Derric Nimmo, Oxitec’s Product Development Manager (Kim).
Brazil is the first country to approve the widespread use of GMO mosquitoes (Harvey). Beth Ranson, spokeswoman for Florida Keys Mosquito Control District, says results of the Florida trial, an environmental assessment, and public hearings would be necessary for the U.S. Food and Drug Administration to implement similar country wide-approval (Sun-January 28th).
Critics warn such proactive efforts may be ineffective without appropriate international travel restrictions (Bogoch). A single infected person or mosquito could transfer the virus from one country to another or among local populations.
Hope Solo, a world-renown goalie for the U.S. women’s national soccer team, said she may not attend the 2016 Olympic Games in Rio due to Zika’s suspected link to birth defects. While Solo isn’t currently pregnant, she believes nobody should “risk the health of their unborn child for a gold medal.”
“If I had to make the choice today, I wouldn’t go,” she told Sports Illustrated. “I personally reserve my right to have a healthy baby. No athlete competing in Rio should be faced with this dilemma.”
Christophe Dubi, executive director of the International Olympic Committee (IOC), said coordinating prevention efforts with the W.H.O should enable the games to go ahead as planned.
“What will be really important is following what is recommended by the national health organizations, which is then relayed to the general public,” Dubi told ESPN (). “We want to make sure that any information that is out there can be made available.”
Britain, Australia, and New Zealand issued travel advisories warning all athletes, especially women wishing to get pregnant in the future, to consider not attending the games (Bases).
Donald Anthony, president and board chairman of USA Fencing, said the United States Olympic Committee issued similar informal recommendations during a conference call with U.S. sports federation officials on January 29th.
“They said no one who has reasons to be concerned should feel obliged to go,” he told Reuters (Bases). “[Officials] are taking the right approach from a standpoint of, let’s be cautious [and] not to do anything that is going to put anybody, our staff or our athletes in danger.”
With so many questions unanswered, and the viral landscape changing every day, experts agree that a, coordinated, concerted and proactive international approach is necessary to understand and eliminate the ever-changing Zika menace.
“There’s a lot of work and research that we need to do,” said NIAID director Dr. Fauci (McNeil, Hayden). “With Zika, we’re seeing new twists and turns every week. This epidemic is an unfolding story.”
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