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.

Dissecting the Latest Super Bug

The report of a highly resistant E.coli bacterium isolated from a urinary tract infection that occurred in a 49 year old Pennsylvania woman (in April of 2016) has temporarily stolen the headlines from Zika. This colistin-resistant E.coli was uncovered via a Department of Defense program in which bacteria that meet certain criteria are automatically forwarded on for further study. While there has been much written about this event and its implications, there are a lot of misconceptions in the headlines.

A few facts about this phenomenon:

1. Plasmid-mediated colistin resistance is a very bad development.

Colistin resistance has existed before, but usually is conferred through changes in the genes of the bacterial chromosome delimiting spread to other bacteria. Indeed, I've seen many colistin resistant bacteria. When resistance is present on a plasmid, which is a mobile piece of genetic information, it can more easily disseminate to neighboring bacteria. The mcr-1 plasmid is such a mechanism for transmission of resistance. Colistin, a drug well known to infectious disease physicians, was a drug put on the shelf decades ago because of toxicity concerns. Today, it is often a drug of last resort and taken off the shelf in special situations in which resistance makes its use necsessary. Losing it through the dissemination of plasmid-resistance, first described in China, would be very problematic. Of note, the woman, who recovered from her infection, had no travel in the 5 months prior to the infection and it will be important to investigate her close contacts (animal and human) to attempt to pinpoint how the strain was acquired.

2. This E.coli isolate was, thankfully not totally drug resistant.

Though this bacterium deserves the "superbug" moniker, given it was both colistin-resistant and harbored an extended-spectrum beta-lactamase (ESBL), it was not resistant to all antibiotics known to man -- something I have battled against twice (Klebsiella pneumonia, Pseudomonas aeruginosa) not too successfully. Cabapenem (it's not a CRE), aminoglycoside, and nitrofurantoin (!) susceptibility was present in the strain leaving the patient with options. 

3. The isolation of an E.coli bearing the mcr-1 plasmid in a pig intestine sample is highly significant.

The aspect of the story -- which hasn't garnered as much attention with the notable exception  Maryn McKenna, one of the best infectious disease journalists -- is a puzzling development as colistin is not an antibiotic used in agriculture. Tracing the origin of the pig intestine to the farm in which the pig it belonged to resided will be important as will sampling other animals -- and humans -- on the farm.

Antibiotic resistance is the norm--it is what bacteria do naturally to survive. The discovery of this strain in the US is not surprising in the least. This event, however, should serve to underscore the need to treat antibiotics as the precious resources they are and not squander them through injudicious use whether in the hospital, the pediatrician's office, or the urgent care center. Additionally, infectious disease medicine must meet these challenges with less reliance on broad-spectrum non-specific antimicrobials and more with targeted therapies such as monoclonal antibodies, bacteriophages, lysins, and virulence factor disruptors and sophisticated and fast companion diagnostics.

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.

Clandestine Diarrhea & Inadequate Chlorination: The Perfect Storm

Possibly lost amongst many other pressing infectious disease issues such as yellow fever, Zika, and antibiotic resistance was a report released by CDC assessing public swimming pools. The bombshell contained in the report is the finding that 80% of pools have been closed for safety violations. While I believe that many of these safety violations might be the result of bureaucratic intricacies and pose no danger, those that deal with diminished chlorine, for example, are likely serious as they potentially can allow dangerous microbes to pass from one swimmer to another. Rotavirus, E.coli O157, and cryptosporidium are pathogens that can find a poorly disinfected pool hospitable. 

While it is unequivocally important to highlight the appropriate disinfection procedures that must be followed for optimal safety, it is not a good state of affairs when people have to be warned not to swim in a public pool if they have diarrhea. A floating turd, which I have seen on multiple occasions (in fact it's how, as a child taking swimming lessons at the YMCA, I first learned what the word feces meant), is an identifiable hazard that can be easily seen, avoided, and remedied. Diarrhea, to unaware swimmers, to use threat analysis terms is an unknown unknown. 

Why people with diarrhea think it's OK to merge their "stream" with that of the pool's I will never know.

Will Dengue Unravel the Mystery of Zika?

One of the puzzles about Zika virus and its newly discovered penchant to cause fetal anomalies is understanding why these facts about Zika are being noticed now given relatively large outbreaks of the virus that occurred in Micronesia and French Polynesia. In those outbreaks, complications such as Guillain-Barre Syndrome were noted but not microcephaly was noted (French Polynesia recently reported 8 microcephaly cases from their outbreak).

One tantalizing hypothesis which is gaining evidence is the role of preexisting dengue antibodies. Dengue, a flavivirus like Zika, has the ability to cause severe disease by employing preexisting antibodies to one strain to enhance infection with another. This phenomenon is known as antibody-dependent enhancement and was discovered by Dr. Scott Halstead who, early on, thought this was playing a role with Zika.  

Now, evidence is beginning to be presented that shows that this may be more than a hypothesis. A pre-publication paper published by researchers at Florida Gulf Coast University illustrates that dengue monoclonal antibodies and immune sera both have the potential to enhance Zika infection in a cell culture model. 

These preliminary findings were pathbreaking in their own right but yesterday at the Cura Zika symposium at the University of Pittsburgh's School of Public Health a leading Zika researcher at the institute presenting some extremely important data on this phenomenon that deserve a wide audience.

Dr. Ernesto Marquez, working out of Recife, presented data illustrating that in Brazil -- as opposed to Southeast Asia and other other areas in which dengue and Zika co-circulate --monotypic infection is much more common. What this means is that Recife women are more likely to have been infected with just 1 (out of 4 strains) of dengue than in Thailand where multi-typic infection is the norm. DENV-3 is the 

What Marquez noted in his data was the almost unique association of DENV-3 to enhance infection. There is much more to this presentation and much nuance to how these antibodies work (for example, their quantity) so I suggest watching it online. It is a great example of how scientific analysis proceeds. 

The obvious policy question that comes to mind is how would the dengue vaccine, approved for use in Brazil, Mexico, and the Philippines, interact with Zika? Would it foster antibody dependent enhancement? Or would it be protective? Other questions to answer would involve looking at case-control data between dengue-naive and non-naive pregnant women who are infected and assessing how their clinical courses may differ. 

Nonetheless, science is advancing quite rapidly on this fascinating virus.