You would have had to have been binge watching all eight seasons of “Breaking Bad” not to have seen the alarm about the emergence of a new, potentially significant outbreak/epidemic of the Zika virus.  There are a couple of key differences that make this both more and less worrisome than the Ebola outbreak that so many fought bravely last year.  A little scientific background on the virus: belongs to the Flaviviridae and the genus Flavivirus, and thus related to dengue, yellow fever, Japanese encephalitis, and West Nile viruses.

 

 

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First, the good.

  • Zika doesn’t kill rapidly (ie non haemorrhagic) and in most infected patients, causes a mild illness that resolves rapidly
  • The infection doesn’t result in symptoms (ie bleeding, vomiting, diarrhea) that increase the spread of the virus

Now, the bad.

  • In some cases, like other viruses in the family, it can cause serious illness
  • It is being linked to an increase in Guillain–Barré syndrome and other neurological conditions, based on a recent epidemic in French Polynesia and a rise in incident concomitant with the outbreak.
  • Of greater concern is the explosive Brazilian epidemic of microcephaly, manifested by an apparent 20-fold increase from 2014-2015.
  • Based on this observation, there are other concerns that viral infection could be teratogenic in other ways that may not be readily observable.
  • Transmission can occur both by bodily fluids (ie semen) and (this is the most scary), aerial transmission via mosquito vector

What are the options?

Well, first health authorities and scientists need to either confirm or rule out whether Zika viral infection is teratogenic and this is a challenging task.  Unfortunately, the fact that dengue and chikungunya, which result in similar clinical pictures, have both
been epidemic in the Americas confounds clinical diagnoses of Zika infection. Specific
tests for dengue and chikungunya are not always available, and commercial tests for Zika have not yet been developed. Moreover, because Zika is closely related to dengue, serologic samples may cross-react in tests for either virus. Gene-detection tests such
as the polymerase-chain-reaction assay can reliably distinguish the three viruses, but Zika-specific tests are not yet widely available ensuring that making a definitive diagnosis of Zika infection and confirming or denying the link to birth abnomalities will be a challenging effort.

Genekam announced Jan. 27 that it had developed a “highly sensitive” DNA test to detect the virus. One of the areas of the biotech company’s slim focus is diagnostics tests specifically for mosquito-borne diseases; for 12 years the company has worked on tests and therapies for flaviviruses, the family that includes Zika. In order to use the kit, labs need a machine known as a real-time PCR thermocycler, plus a centrifuge and other items like microtubes and pipettes, but it produces results within two and a half hours and requires skilled lab technicians making the test insufficient for epidemiological studies and too costly and complex for widespread use in developing economies.

For the purposes of surveillance this test may be ok, but it doesn’t really solve the issue of performing mass screening at low costs where patient treatment and differential diagnosis needs to occur.  A secondary need for differential diagnosis has emerged with the news that the virus may be transmitted sexually.  The need to halt the spread of the virus requires management and mitigation of all transmission vectors, including humans and diagnosing a primary infection correctly and using safe sex practices until the virus is cleared from the body is an important need.  Given this, a golden opportunity exists for POC diagnostics companies to develop a rapid, low-cost Zika virus diagnostic that can be used by front-line medical personnel.

Vaccine development is occurring but I really don’t see this as filling a near term gap. An excellent review of this can be found at Forbes by Bruce Lee.   Even if researchers, including stellar groups like the effort led by Tony Fauci, and other efforts such as the vaccine developed by a joint venture involving Inovio Pharmaceuticals, Inc., Laval University, Canada’s National Microbiology Laboratory, the University of Pennsylvania and South Korea’s GeneOne Life Science, Inc are successful, commercial vaccine will not be available for quite some time. Developers of this vaccine candidate have suggested that their vaccine may be available for human testing by the end 2016, which I doubt and human testing will take some time, especially if this is to be administered to pregnant women to prevent infection during gestation.

Vector control seems to be an intriguing option, however, heavy use of insecticides over the last 50 years has allowed resistance to emerge so that insecticidal sprays are not only not that desirable, they are also not that effective.  The WHO reports that a total of 60 countries have reported resistance to at least one class of insecticide, with a total of 49 of those countries reporting resistance to two or more classes.  An intriguing new method for controlling mosquito population involves genetically engineering male mosquitoes so that they produce offspring that die at the larval stage.  Using a method called “Gene Drive” or CRISPR/CAS9, British biotechnology company Oxitec has altered the reproduction mechanism so that a female mosquito (the biters) that makes her once-per-lifetime mating with an Oxitec male produces no descendants. The company is awaiting approval from federal regulators to release millions of sterile males in the Florida Keys to reduce Aedes populations as a way of combating dengue fever and has conducted field tests in Brazil, Panama, and the Cayman Islands, reducing Aedes populations by some 90 percent.

An excellent review of the topic and the ramifications of wiping out the mosquito population was well covered by the great folks over at Radiolab, which you can listen to here.

What are we doing?  Well, first getting the facts, and then secondly looking for investment opportunities.  Thankfully, we already have a company in the portfolio that could develop a rapid POC test for Zika, called Xagenic.  We will be working with the company over the coming months to assess the market opportunity and understand the development path more fully.

Stay tuned and in the meantime, put on the insect repellent

 

 

 

 

 

 

Dion Madsen

Those that know me well, know that my favorite words are “Super”, “Great” and “Awesome”. The geek part of me is energized solving the complexity of biology and improving the delivery of care.  I learned patience, hard work and entrepreneurship growing up on a farm in Saskatchewan and teamwork in the rinks and ballfields of my hometown.  After working in Europe and then dealing with bare-knuckle politics in Saskatchewan, I migrated west to Alberta where I began to hang out with some crazy guys doing something called “the Internet” which led to me being the CFO of a publicly-traded company.  After selling the company, I crossed over to the VC side and during a meeting with a vaccine company I had the epiphany of “I can make money and help people at the same time? Awesome!” and I have been working for or financing healthcare companies ever since.

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