We are Going to Need More Itch Ointment

Why the current Zika virus outbreak is the least of our worries

By Jamie Schmid

It could be lurking inside your bloodstream for days or weeks. Thanks to a small needle prick from nature’s bloodsucker: the mosquito. Once its thin feeding tube, called a proboscis, punctures the skin, there is no escaping. Slowly the crimson blood travels upward towards the insect’s body. Slowly the Zika virus travels downward into the warm human host.

But, contact with the virus does not result in sudden death. It can live comfortably in the bloodstream for a number of weeks without symptoms. If symptoms do show up, they are mild, maybe a fever, joint pain, a rash, or maybe, a plain old headache. Even the great Sherlock Holmes would have trouble detecting a Zika-infected person. Yet, he would have no trouble detecting a Zika-infected infant.

The problem: Zika produces birth abnormalities, and it’s spreading through the population rapidly.

On Feb. 1, 2016, the World Health Organization declared Zika a “Public Health Emergency of International Concern.” In a press release, the Director-General stated the need for an “international response” to the virus, including the “control of mosquito populations” and the development of “diagnostic tests and vaccines.”

Sounds simple. But different experts tackle the virus from all different directions. Here are six ways scientists recommend overcoming this world health crisis.

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Solution One: Meet mosquito 2.0

In an October 2015 article published by the Proceedings of the National Academy of Sciences, researchers created a mosquito that is resistant to the parasite Plasmodium falciparum. This parasite causes malaria in humans. Essentially, the lead researcher, Anthony James, and his team created an anti-malaria mosquito.

They used a genome-editing procedure called CRISPR/Cas 9. If you ignore the complicated name, basically they cut out a portion of the mosquito’s genetic sequence.

Now its genome is like a giant puzzle with one missing piece. In order to complete the puzzle and make the mosquito whole again, researchers put a new puzzle piece that codes for the production of anti-malaria antibodies. These antibodies allow the mosquito to fight off the malaria virus before passing it on to a human host.

Using this same technology, perhaps the University of California-Irvine team could implant an anti-Zika gene into a mosquito’s genome. But, this would not happen without hiccups along the way.

“If we genetically modify the mosquito to not be able to transmit malaria, dengue fever or Zika, the challenges are that the mosquito will evolve and actually bypass the genetic modification,” said Dr. José Esparza, the president of the Global Virus Network. The GVN is an institution with centers in more than 25 countries staffed with experts in all human disease-causing viruses.

When malaria became prevalent in the 1950s, the insecticide, DDT, and the antimalarial medication, cholorquine, were used to combat the surge in the virus. However, soon the insects built resistance to both the DDT and the cholorquine.

Despite the possibility that mosquitos will evolve around a genetic change, other experts see potential in a genetically modified approach.

“Are you going to crash the ecosystem and so forth? I think that is totally misplaced. The western hemisphere did quite well without the Aedes aegypti [the mosquito that transmits Zika]. It was an invasive species that came 300 years ago. I think the ecosystem will do very well without it,” said Kenneth Olson, Ph.D., a professor of virology and the former director of the Arthropod-borne and Infectious Disease Laboratory at Colorado State University.

Olson said that the key to solving a mosquito-borne virus like Zika is to take a vector approach. Vectors are tools used by molecular biologists to input genetic information into the cells of certain animals. Hence, his support and interest in re-engineering the insect.

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Solution Two: Good old vaccines

To the public, vaccines are held as the “cure” to all the globes health crises. We scream: Ebola! And then ask: Is there a cure? Malaria! Is there a cure? Are these cures too good to be true?

“I am all in favor for the research on genetically modified vectors, but I will not hold my breath thinking that this will be the solution. We have to fight with as many weapons as we have, and I believe vaccines are the best weapons we have,” said Dr. Esparza.

Surprisingly, developing a vaccine in a laboratory is relatively easy, he said. Vaccine making, at its core, is all about molecular biology. Dr. Esparza said we have the expertise and knowledge to make these cures. It’s the human trials and testing of the vaccines in the field that takes decades.

In the third phase of human trials, thousands of people receive the vaccine or a placebo. Researchers then follow these people for up to two years in order to monitor the efficacy, effectiveness, and safety of the vaccine. Sounds complicated? Well, it is.

But, even with a lengthy time delay between the outbreak of an epidemic and the development of a vaccine, experts still agree that a Zika vaccine should be in the works.

“If I had to give priority to a vaccine, and the choice between Ebola and Zika, there is no doubt that we should put the money in a Zika vaccine,” said Peter Palese, Ph.D., a professor and chair of microbiology at the Icahn School of Medicine at Mount Sinai Hospital.

Not only does Zika affect more people, compared to Ebola it is more difficult to control. Given these factors, Palese said that a vaccine is extremely important in the fight against Zika.

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Solution Three: It’s all about the diagnostics

Ebola first appeared in the Democratic Republic of the Congo in 1976. Sporadic outbreaks continued throughout the African continent, yet the United States did not jump into crisis mode until almost 40 years later. On Sept. 30, 2014, the CDC confirmed the first case of Ebola in Dallas, Texas. This patient zero for Ebola in the United States carried the virus from Liberia. He was asymptomatic, meaning the man produced no symptoms of Ebola, allowing him to travel freely.

Rhoel Dinglasan, Ph.D., an assistant professor at Johns Hopkins Bloomberg School of Public Health, argues that we would have been able to track the man earlier if we had the diagnostic tests for Ebola. Resources need to be funneled into preventive measures not extravagant molecular biology such as genetic modification.

The moment the man got off the plane from Liberia, said Dinglasan, there should have been a diagnostic test to detect Ebola in his saliva. Putting weird mutated mosquitoes and vaccines aside for a moment, Dinglasan sees the lack of diagnostic tests as the major issue facing global viral outbreaks.

“Essentially, if we have 164 individuals come off of an airplane and we have 164 diagnostics that can be read within 30 minutes. The person could still be in the airport, waiting for their bags and we could tag them,” said Dinglasan.

Would Americans allow their saliva to be swabbed and tested? Given the HIPAA Privacy Rule, trying to test a passenger at the airport runs into all sorts of confidentiality barriers. Additionally, the cost of implementing such a large infrastructure of diagnostics would be costly and require global cooperation. But, Dinglasan rationalizes the testing this way.

“Which is better: You are dead tomorrow or we inconvenienced you for 30 minutes,” he said. In the end, if authorities can catch Zika-carrying people before they enter the country that would be a large piece of the solution to the epidemic.

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Solution Four: Who you gonna call? Mosquito-busters!

            The United States banned DDT in 1972 when it was shown to build up in the fatty tissue of animals, allowing it to travel up and linger in many food chains. Today, DDT is thought to be a probable human carcinogen. Yet, DDT successfully eradicated a great deal of malaria-causing mosquitos before being banned.

“To be honest, if I could eliminate malaria, the Zika virus, chikungunya, dengue, etcetera, etcetera, with DDT, and I would lose one or two bird species: I still think this would be an advance,” said Palese.

Maybe, it is time to look at the bigger picture. Birds can take one for the team. Should we equip municipalities with DDT-carrying “mosquito busters?”

The United States contains almost 1,100 mosquito control entities that are operated out of state municipalities. Joseph Conlon, a retired US Navy entomologist, said that these entities have no capacity for surveying mosquito populations and species.

“If they did catch mosquitos they would have no idea where to send them to get them tested for virus,” said Conlon, who now works for the American Mosquito Control Association (yes, such a thing exists). Its mission is to provide “leadership, information, and education” that leads to the “suppression of mosquitos and other vector-transmitted diseases.”

Environmental risks of DDT-like substances aside, the United States lacks the infrastructure to carry out a full-scale DDT assault. Workers do not have the capacity for identifying mosquitos, let alone planning a widespread wipeout.

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Solution Five: Mosquito vs. mosquito

Zika-carrying mosquitos like the Aedes aegypti thrive in artificial containers. These containers can be anything from a barrel, to a tire, and even a cup. Any water-holding container that is man-made. Aedes aegypti only survive where humans provide a habitat for their larvae, hence the artificial containers.

In the mid 1980s, the Asian tiger mosquito or Aedes albopictus landed in the United States, flourished in these artificial containers, and began to displace the A. aegypti from most of its habitat.

“In principal, we have learned from nature that one Aedes species can displace another Aedes species. This happened. So why isn’t anyone looking into the mosquito being replaced by another species,” said Durland Fish, Ph.D., a professor emeritus of microbial diseases and a professor of forestry and environmental studies at the Yale School of Public Health.

Fish argues for an ecological approach to the Zika problem. He recognizes the need to study the ecology of the mosquito in order to find methods of reducing their ability to transmit diseases. In so many words, more fieldwork and less molecular biology laboratory work.

Of the more than 3,500 mosquito species, there must be other species that can replace other disease-carrying species. So, why isn’t research being done on this solution?

“All this genetic manipulation of mosquitos is funded because you can patent that and make money. To release something into the environment that would solve this problem - like competitors that would displace the mosquito or some enemy that would kill the mosquito - you can’t patent that. So who is going to fund the research? So that’s why it hasn’t been done,” Fish said.

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Solution Six: There is no “I” in team

Maybe it is simply naïve to think there is just one-way to approach the Zika virus. In fact, that might just be the problem: a failure to look at these outbreaks in an all-encompassing, global and objective manner. We tend to respond to epidemics when they reach the United States, even though they have been circulating in Africa or South America for decades.

For 18 years, Dr. Esparza worked with the World Health Organization and the Joint United Nations Program on HIV/AIDS and saw this inability to address global crises.

The HIV virus jumped from chimpanzees to the human population in West Africa all the way back in the 1920s, said Dr. Esparza. The disease AIDs was only discovered 60 years later when it started appearing in Europeans and Americans.

“So for 60 years, HIV was circulating in Africa without anyone knowing it. Now know we look back and start finding cases of AIDS in Africa long before they were discovered in Europe and the United States,” he said. “I think that in the future to protect the world from these pandemics we have to go to the places where those viruses are emerging,” said Dr. Esparza.

It is 2016. We can’t keep gasping in awe and shaking our heads when another outbreak reaches the status of a “Public Health Emergency of International Concern.” Instead, all the experts can agree on the need to approach Zika from multiple directions, whether through a biological, ecological or internal infrastructure lens.

Combative measures aside, its time we stop putting the Europe and the United States first. No longer can we wait 60 years to address a virus like HIV/AIDS. Zika will not be the last global epidemic, but maybe it will teach the world the most.

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