While You Were Watching Zika, Chikungunya came to Texas

Though chikungunya, last year's infectious disease fashion, slipped from headlines it is nonetheless a significant virus that is in the midst of its first ever foray into the Western Hemisphere. Spread by the now all too familiar, Aedes mosquitoes this virus has the penchant for causing severe disease characterized by debilitating arthritis. There is no vaccine and no treatment for chikungunya. 

There have been millions of cases since this outbreak began in the Caribbean and even about a dozen cases of local spread in Florida -- a hotspot for Aedes transmitted diseases.

Yesterday, however, local spread was reported in Cameron County, Texas. Cameron County is a Mexico-bordering county and is an area that is a national leader when it comes to another Aedes-related infection: dengue. The close proximity to Mexico confers a continual dengue-risk. When my colleagues and I conducted a research project on dengue response in the US, Cameron County public health authorities were near the top of those we wanted to speak with. 

It will be interesting to see how Texas ramps up anti-Aedes activities which are already enhanced due to the threat of Zika. Perhaps this is another area in which GMO mosquitoes should be considered? I suspect that the local populace, more attuned to the risk of dengue, would be more receptive to the idea than other locales.

It is unfortunate that chikungunya has slipped from the headlines because local spread in Texas is a significant event that merits more attention -- maybe we need another celebrity to become infected.

GMO Mosquitoes: Will Zika Change the Equation?

As the Zika virus outbreak continues and mosquito season in this hemisphere approaches, there will be a ramp up in vector control activities. These activities are aimed at reducing mosquito populations and are practiced for several types of mosquitoes, most notably those that spread West Nile Fever. However, even prior to the Zika outbreak, because of the threat of dengue and chikungunya, aggressive campaigns against Aedes mosquitoes had taken place in certain areas such as Texas, Hawaii, and Florida.

Florida, which has had several instances of local transmission of both dengue and chikungunya, has been a national leader in mosquito control as exemplified by the Key West Mosquito Control District. Over the past years, faced with a continual threat of dengue, the use of Oxitec's sterile male genetically modified mosquitoes to reduce Aedes aegypti populations has been contemplated as a means to augment ordinary mosquito control operations. 

However, in today's context, "genetically modified" evokes an unjustified Frankenstein/Jurassic Park horror in many people and has stalled release of these mosquitoes in the US (they have been part of trial releases in the Cayman Islands, Panama, and Brazil).

Given this context, pre-Zika, my colleagues and I sought to understand how the public conceives of GMO mosquitoes and what their support or opposition is influenced on. To meet this aim we fielded surveys to residents of a Florida community in which the release of these mosquitoes is being contemplated. PLoS Currents Outbreaks just published the results of that work.

There were several findings that we found particularly striking:

• Being a female was significantly associated with being opposed to the use of GMO mosquitoes
• Having never known anyone with chikungunya or dengue was significantly associated with opposition to use of GMO mosquitoes

The 2nd finding is what I deem the most important, as it reflects the role of risk assessment on an individual level and will likely change as people's threat assessment changes. A headline-grabbing virus like Zika may be just the threat that will cause people to think differently about GMO mosquitoes -- something that is already happening.

We hope to follow this paper with a follow-up post-Zika study of the same area as well as explore the mechanics and public health communication strategies used in the Cayman Islands, Panama, and Brazil. Additionally, it will be important to put GMO mosquitoes firmly in the tradition of such endeavors as the eradication of the agricultural screwworm pest, irradiated sterile mosquitoes, and Wolbachia-infected mosquitoes.

It is the role of public health authorities and physicians to help calibrate the general public's analysis and our hope is that this paper can help move the discussion of GMO mosquitoes further forward.

Chikungunya Gets Its Green Card

It comes as no surprise that autochthonous chikungunya has occurred in Florida. The simple maxim that must be kept in mind with respect to vector borne diseases is: if a competent vector exists in areas in which imported cases are occurring, it is only a matter of time before local vector populations contract the pathogen.

Florida is an area hospitable to Aedes mosquito and has been plagued with locally-transmitted dengue for several years. As chikungunya shares many of the same characteristics of dengue, it is no surprise that it has found welcome in Florida. 

Intensified efforts to control the vector, which is already ongoing for dengue, will likely occur. However, it may be exceedingly difficult to eradicate chikungunya if it has thoroughly settled in local Aedes population.

For a great overview of these issues see this recent NEJM piece by Fauci and Morens. 

GMO Mosquitoes: The 21st Century Bug Zapper

There are several mosquito-borne diseases that merit a lot of attention in the US. These include dengue, chikungunya, and West Nile Fever. The key to the control of these infections--none of which  are vaccine-preventable--is controlling the mosquito which serves as the vector for human infection. 

Vector-control is a challenging task. Prior to the sermons of fellow Pittsburgher Rachel Carson, which led to bans on DDT use and the collapse of the malaria eradication efforts in the 1960s, mosquito control was achieved using this highly efficacious insecticide. Current vector-control activities employ other compounds targeting mosquito larvae as well as adults. Often, simple efforts such as removing standing water from tires and other household items are highly effective measures. 

A new 21st century approach to vector control that I find very promising is the use of genetically modified mosquitoes. In this approach, pioneered by Oxitec, male mosquitoes are genetically engineered to produce offspring that cannot live outside the laboratory because they require the presence of the antibiotic tetracycline to live. In the wild, when a female mosquito mates with one of these engineered male mosquitoes, the offspring produced will die. Such an activity can substantially reduce vector populations and, therefore, render infection with mosquito-borne viruses less likely. Thus far this approach has been used against Aedes mosquitoes (the vector for chikungunya, dengue, and yellow fever).

Already, this approach has been employed in Malaysia, Brazil, and Panama with great success. Even Florida, recently plagued with dengue, has used this approach.

What I can't seem to fathom is why this measure, which could literally change the landscape in the realm of vector control, is met with derision and fear over tampering with the "fragile ecosystem." Such a reaction completely drops the context. All types of vector control, from bug zappers to DDT to a fly swatter, represent attempts to "tamper" with the ecosystem and are laudable attempts to tame mosquito-borne diseases. Mosquito lives aren't as important as human lives, unless one holds a wickedly egalitarian and nihilistic standard. 

I wonder if these individuals would have counseled against smallpox eradication because of the ecological niche once played by the virus. 

A favorite quote of mine, from Francis Bacon, is applicable here: "Nature, to be commanded, must be obeyed." Viewing nature as a realm able to be shaped and reconfigured by man's mind, while respecting the rules of reality, is what is sorely missing in the minds of those who reflexively oppose the use of these mosquitoes. It is reminiscent of Mary Shelley's panic over the progress of science, which inspired her Frankenstein.

Getting to the Brain by Hijacking miRNA: The EEE story

The mechanism by which Eastern Equine Encephalitis (EEE), a deadly mosquito-borne viral disease with a 50% mortality rate, causes its characteristic illness is the subject of a pathbreaking article in Nature by authors from Pitt's Center for Vaccine Research. 

The paper is focused on the role of miRNAs and their interaction with viral RNA. miRNAs are small pieces of RNA that cells use to regulate the expression of genes. miRNAs have not been thought to have a role in controlling viral genes. In the case of EEE, however, William Klimstra and colleagues found an miRNA that binds to the virus, blunting its ability to infect specific cells of the immune system and, consequently, stops the triggering of an immune response.

This suppression of host immune defenses by exploiting--or hijacking, as the authors put it--host miRNAs allows the virus to reek havoc in the central nervous system causing the signs and symptoms of encephalitis.

Furthermore, the viral sequences that bind the miRNA serve a dual purpose, enhancing replication in the mosquito vector.

The elegance and ingenuity of this viral mechanism is truly fascinating and it will be important to determine if other viruses use similar mechanisms.