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Robert Tesh

Robert Tesh: Arbovirus hunter

Physician who traveled throughout Latin America, collecting pathogens transmitted by arthropods talks about Brazil’s performance during the Zika epidemic

João Moura Tesh: It’s not realistic to expect that some new technology will lead to eradication of the Aedes aegypti and the diseases it transmitsJoão Moura

Getting ahead of the great viral threats to public health is an extremely difficult task, even for someone like American physician and virologist Robert Tesh, who for over five decades has been studying the global diversity of arboviruses, the viruses transmitted by insects and other arthropods.  “There are always surprises,” says Tesh, who is a professor emeritus at the University of Texas Medical Branch (UTMB) in Galveston.  “Who would have ever thought 20 years ago that the Zika virus would be a threat?”

For decades, Tesh has headed up the World Health Organization’s World Reference Center for Emerging Viruses and Arboviruses (WRCEVA) housed at UTMB. It is a repository for samples of more than 7,000 viruses from all over the planet, available for study by researchers looking for clues to possible current and future epidemics and ways to fight them.  Tesh himself has taken part in collecting many of these pathogens, a task conducted mainly in Latin America.  Now 81, Tesh has lost count of how many times he has visited Brazil, where he has spent periods as visiting professor at the Evandro Chagas Institute in the state of Pará and at the Adolfo Lutz Institute in São Paulo.

Most recently, the virologist and his colleagues accompanied the slow and steady advance of the Zika virus through Asia and the Pacific islands before it arrived in Brazil and affected a large number of people.  To him, the confusion and panic that accompanied the epidemic would not have been much different had it occurred in the United States or in any other industrialized country.  He also thinks that it is not realistic to expect that some new technology will lead to eradication of the Aedes aegypti mosquito and the diseases it transmits because both the virus as well as the mosquito are versatile and can adapt to attempts of human interference.  “In short, we’re in for a long fight,” he says.

In early June, 2017, Tesh was in São José do Rio Preto, in inland São Paulo State, to take part in the FAPESP-sponsored São Paulo School of Advanced Science in Arbovirology. Shortly before leaving for a tour of the Pantanal wetland, he gave an interview to Pesquisa FAPESP about the history and future of arboviruses in the Americas and in the world.

How much do we know and what do we still need to learn about the diversity of arboviruses in Brazil and in the world? 
When we talk about arboviruses, we’re talking about viruses that are transmitted by blood-sucking arthropods such as ticks, European stilts and phlebotominae.  Of all arboviruses known, most come from South America [region of origin of nearly 150 of the more than 500 known species.]

Surpassing those that originated in Africa?
Yes, partly because the most labor-intensive work of identification was done in South America.

The fact that there is more known about arboviruses from South American stems from a sampling issue then?
It has to do with where the laboratories, especially those funded by the Rockefeller Foundation, went looking for these viruses.  Very few were known before the 1930s, such as those that cause of yellow fever, dengue and one or two types of encephalitis.  The Rockefeller Foundation established a program that set out to find new viruses, which really increased the discoveries of arboviruses.  But there are still a lot to be found. We’re beginning to understand that there is a huge number of viruses spread by mosquitos and other vectors that affect only insects and never vertebrates, although they are very closely related to arboviruses.

Why did they come back to be more threatening in recent decades?
Viruses have travelled very quickly with humanity’s increased mobility.  Today, you can get on an airplane and in less than 24 hours, get to Tokyo or China.  With this capacity to travel such distances in so little time, viruses such as Zika or chikungunya whose distribution was once limited, spread quickly after arriving in the New World.  Another example is the West Nile virus that arrived in North America in 1999.  It had been isolated in Africa during the 1930s and was also found in the Middle East, but suddenly it was in the New World.

Is it possible to say that we underestimated the Zika virus when it first appeared in Brazil?  Was it inevitable that it would become such a serious problem? 
We were not interested in Zika because it is an arbovirus.  In 2010, I isolated a strain obtained from a child in Cambodia.  We knew that Zika was present in Southeast Asia and Africa, but there were not many reported cases in humans, partly because Zika causes symptoms very similar to that of dengue and chikungunya fevers. Clinically, it is very hard to differentiate symptoms caused by one of the viruses from symptoms caused by the others, and there are also the asymptomatic cases.  It is possible that the Zika was actually diagnosed, but most laboratories did not try to identify the virus until it arrived on some of the Pacific islands such as French Polynesia and caused a huge outbreak.

Including cases of microcephaly, correct?
Yes, microcephaly and Guillain-Barre syndrome (the autoimmune reaction that can severely affect the nervous system of adults). After the virus spread throughout the Pacific and reached Easter Island, I thought: “Well, it could get to Chile.” But it showed up in Brazil, which was a surprise.  Experts were watching it, but did not expect it to cause the effects it did, nor did they expect it would spread so widely.  Looking at the situation from today’s perspective and considering that the Zika virus cycle is very similar to dengue and involves the Aedes aegypti mosquito perhaps it wasn’t such a surprise that it had spread so far and given rise to such a large number of cases, since it came in contact with a virgin population, one in which no one had been infected before.  Then, we all know what happened. From Brazil, it went to Colombia and from there to the Caribbean, Central America and Mexico, with a lot of cases in Puerto Rico, Haiti, the Dominican Republic and Honduras and a few cases in Florida and Cuba.

What is the current situation in those areas?
In Puerto Rico, cases have begun to diminish. There comes a point at which the proportion of people who have become immune [because they have already had the disease] is so large that what is called herd immunity occurs. Each virus is a unique case, but after 50% of the people have been infected, it becomes harder for the virus to circulate because there are fewer individuals who are susceptible.  During its short life, the infected mosquito needs to bite a non-infected person in order for the cycle to continue.  From now on, I don’t think Zika will disappear from Brazil or the Americas, but there will certainly be fewer cases.

Even when a new generation of children is born that has not yet had the disease?
At that point, the Zika infection will likely become like dengue.  There are four serotypes of dengue.  In some years, the virus of serotype 1 or 2 is on the rise, so people are infected and develop immunity to it.  A few years later, cases of type 3 or 4 dengue begin to increase.  The virus never really goes away, but it goes to other places and then is reintroduced into a region in which it had already circulated.

People are still trying to understand why the Zika virus had such severe effects during pregnancy.
That was the big surprise. There is a virus called akabane that occurs in Japan and Australia, causing malformations in sheep, similar to those caused by the Zika virus to limbs of children infected during pregnancy.  That virus can also lead to miscarriages.  But we knew no other arbovirus that behaved in that way.  The Zika virus appears to remain in the fetus for a long time.  In the case of infected humans, it remains for long periods in the testicles, something similar to what we determined in cases of Ebola.  Men who contracted the virus continued to be able to infect other people for months through sexual relations.

Has our ability to prevent this type of epidemic or stop it in its early stages improved?
If it is a new virus for which there is no vaccine and there are many transmitters, such as the Aedes aegypti, it’s very hard to control.

Personal archives The researcher in his former laboratory in the United StatesPersonal archives

At least in principle, would we be able to prevent this type of epidemic?
Mosquitos are very hard to control. It is something that people have been trying to do since they realized the connection between them and those diseases, but they have not been very successful.  We’ve made lots of progress in the case of yellow fever, but this is also related to the development of a vaccine.  We were able to eliminate the Aedes aegypti from urban environments for a time, but we did not eradicate wild yellow fever, which involves infection of monkeys.  A lot of people are now trying new techniques to control mosquitos without using insecticides.  There are strategies such as infecting mosquitos with bacteria of the genus Wolbachia or breeding transgenic mosquitos. I’m rather skeptical with regard to these approaches.  In the case of transgenics, they are introduced in male genes that render offspring infertile.  The next generation will die without leaving descendants, but then you have to introduce more genetically modified males into the population.  It’s not impossible that, through natural selection, the viruses or the mosquitos find ways of circumventing these strategies, much like the antibiotic resistance that is appearing among bacteria.  In short, we’re in for a long fight.

What is the most frightening virus you have ever faced? 
It’s not an arbovirus. I was involved in a research study on Venezuelan hemorrhagic fever, caused by an arenavirus known as Guanarito, in the same group as the Junin virus, which causes Argentine hemorrhagic fever, or the Machupo virus, found in the Beni region of Bolivia.  In the case of Venezuelan hemorrhagic fever, a scientist from that country isolated the virus and sent samples to me.  I also worked in Venezuela for five years, collecting rodents so I could understand the virus’ lifecycle.  Those viruses are very dangerous, with a mortality rate of around 25%.  There is still no treatment available for the infection they cause, although there is a vaccine for Junin [virus] that is being used in Argentina.

How are they transmitted?
By inhaling aerosolized droplets. Certain wild rodents serve as the natural reservoir of these diseases and carry them throughout their lives, much like what occurs with the hantaviruses.  Those animals release the virus in the environmental through urine or saliva.  There are no person-to-person transmissions although hospital staff can become infected by contact with patient blood.

Has Brazil done its homework with regard to emerging viruses and Zika virus?
Brazil was the first country to experience a Zika epidemic of such magnitude.  If the same situation had occurred in the United States, and in such an explosive a manner as here, some of the same things would have transpired.  Perhaps things are a little more organized in the United States and it would be a little easier to address the problem, but it is a kind of emergency that instills panic in people.  Honestly, I don’t know if we would have been able to do much better than Brazil.

Is there any connection between the disappearance of urban yellow fever in Brazil and the advance of the dengue virus?  Is the fact that the viruses are competing amongst themselves in the body of the mosquito what explains why yellow fever does not come back in full force?
For starters, mosquitos are not usually infected by two closely related viruses at the same time.  It is not possible to infect them with type 1 and type 4 dengue virus at the same time, for example, and I don’t think it’s possible to be infected with dengue and yellow fever simultaneously.  Now co-infection from chikungunya and dengue in a single insect can occur because the first is an alphavirus and the second is a flavivirus, which are very different.  The disappearance of urban yellow fever can be explained as an outcome of action by the Pan-American Health Organization (PAHO), which after World War II, decided to attempt to eradicate the Aedes aegypti mosquito from the Americas. PAHO established a program that, after 20 years of effort, became very successful.  Nearly all of South and Central America were free of the mosquito.  Venezuela, however, decided to vaccinate its population and pay less attention to mosquito eradication, which was not good for the other countries since insects are able to cross borders.  There was also no eradication in the Caribbean.  The United States tried for 10 years and gave up. Then in the 1970s, they decided to stop funding the program.  With the program discontinued, the mosquito began to spread, country by country, and now the situation has gotten to where it was before, or even worse.  At the same time, a vaccine was successfully developed and used in Brazil.  The combination of the use of vaccines and temporary eradication of mosquitos nearly wiped out urban yellow fever in Brazil.  Dengue did not disappear only because the Aedes aegypti mosquito returned and there wasn’t at the time, nor is there now, a vaccine to fight dengue.

Is there a chance that some viral epidemic will soon emerge to cause significant damage?
Experts always say that we need to concern ourselves with the influenza virus that causes the flu.  There is currently a strain of influenza in China that is quite virulent. If there were to occur a flu pandemic like we had in 1918, millions of people could die, especially the elderly who suffer from other respiratory or cardiovascular problems.

Although the 1918 Spanish Flu killed many young people. 
Yes, and that was why it was especially bad. A virus of that type, that can easily be transmitted from person to person, can reach any place on earth.  Other viruses people are studying closely are those that cause the Middle East Respiratory Syndrome, MERS, and the Severe Acute Respiratory Syndrome, SARS.  But surprises are always possible.  Who would have thought 20 years ago that Zika would be a threat? People think we can prevent what will happen in the coming years, but I tend to be a skeptic in that regard.