As the image above suggests, the Zika virus is of concern here in Puerto Rico, as it is in Brazil, other parts of South America, other Caribbean islands, and the US mainland. Zika’s rapid spread around the world represents an object lesson in globalization, and the complex interactions among environmental factors, disease vector(s), and humans. Still, by a fortunate series of events, the Zika virus is reasonably well understood, and two vaccines are now or soon will be in clinical trials.

The current Zika outbreak seems to have begun in the South Pacific. A woman and her husband returned to Australia after travel to a funeral in the Cook Islands. She went to the local hospital, outside of Melbourne, complaining of a fever, headaches, and an unusual rash. Australia has a particularly well developed system with regards to travel-related diseases. Nenad Acesic, a fellow in infectious diseases, took the call.

Acesic first considered the usual suspects, including dengue and chikungunya, both mosquito-borne viral diseases (and both present in the Caribbean now, as well). However, the patient’s symptoms were milder and spontaneously cleared within a day or two. Acesic’s forays into the medical literature caused him to suspect Zika. A blood test showed the presence of the virus.

Acesic learned that Zika had shown up in 2013 in a cluster of cases, perhaps as many as 32,000, in French Polynesia, again with typical symptoms similar to but milder than dengue and chikungunya. There were, however, some cases of Guillain-Barre syndrome, a debilitating but temporary paralysis, at the same time as the Zika outbreak, a bizarre premonition of more serious complications to come. What Acesic did not know was that the Tahiti soccer team had, in 2013, with many supporters, traveled to Brazil for the Confederate Cup tournament. It is possible, but cannot be proven, that Zika entered Brazil then.

Zika was first isolated in 1947 from a rhesus monkey in a forest in Uganda. Its name derives from that region. The monkey was infected as a part of a naturally occurring mosquito – monkey – mosquito cycle. At some point, the virus jumped to humans and became part of a mosquito – human – mosquito cycle. The map below, derived from serological data, shows the spread of Zika since the early 1950s.

Brazil is the epicenter of the Zika virus in the Western Hemisphere. In 2015, health workers noted an increase in Zika cases in the northeastern parts of Brazil. Again, the cases were mild and seemed self-clearing. Some weeks later, however, health workers noted an increase in children born with small heads, a tragic condition known as microcephaly. In the Brazilian state of Bahia, the background rate for microcephaly before Zika was about 0.02 percent. After Zika was introduced, the rate rose to between 0.88 and 13.2 percent of women who had been infected with Zika in the first trimester of their pregnancy. The incidence of patients with Guillain-Barre syndrome rose as well.

Mosquitos were implicated in the spread of the disease, and two invasive species, originally from Africa, Aedes aegypti and Aedes allopictus, seemed primarily responsible. Both species are sip-feeders, that is, they take a little bit of blood per bite from multiple victims. The mosquitos are unwitting carriers – they seem to derive no benefit from their hosting activities. After a sip of blood from an infected individual, the virus replicates and, over a 5 to 10 day span, moves to the salivary glands, where it can be injected into the next bite victim.

The ecological habits of A. aegypti and A. allopictus overlap such that one or the other species is around most of any day. Their habitat requirements are modest –they can breed in small pools of standing water such as bird feeders, gutters, flower vases, shower stalls, and toilet tanks, all close to or within houses. Females require blood meals for egg development; males do not feed on blood. (I am trying very hard here to not be anthropomorphic). They both have characteristic black and white bands on their legs.

The Zika virus is relatively simple, as viruses go. It is an RNA virus of the Flaviviridae family and the Flavivirus genus. It is related to the dengue, yellow fever, Japanese encephalitis, and West Nile viruses. There are two Zika lineages: African and Asian. The Zika responsible for the current outbreak in the Americas is most closely related to the Asian, the same lineage found in the French Polynesian outbreak.

The Zika virus congregates in the semen of infected men; transmission by sexual contact has been observed during the current outbreak. And that the virus can move from mother to fetus, with devastating results, is of great concern. While cases of Guillain-Barre syndrome have increased during Zika outbreaks, there is as yet no clear understanding as to how this occurs.

So there is the Zika Troika – susceptible human hosts, mosquito vectors well adapted to human habitats, and an agent whose clinical manifestation is sometimes benign, sometimes horrific. The possibility of sexual transmission, not of the classic host – agent – vector troika, adds complexity to the picture.

Public health responses to a disease outbreak focus on one of more components of the troika. In the case of Zika, one could hope for a readily available vaccine to prevent infection by the virus. Or, mosquito control efforts might reduce the population of infected mosquitos. Perhaps a genetically-modified virus released in the environment can, as it spreads, act as an inoculating agent and confer disease resistance. Of course, public health education efforts can reduce the incidence of Zika spread by sexual contact. Individual actions – use of effective insect repellent, vigilance in clearing suspected breeding areas – can help.

There are good reasons to hope a Zika vaccine will soon be available. Researchers quickly noted that the Zika viral strains were genetically similar. They also noted that the disease is often self-clearing, and that a previous Zika infection confers resistance to continued exposure. Several virology laboratories around the world were able to shift their focus to Zika research, using skills and methods derived during research into HIV, among other diseases. As I write this, it appears two Zika vaccines are ready for clinical trials starting some time in 2017, a remarkable feat made possible by the relative simplicity of the Zika virus, and the ability of labs around the world to shift their skills and attention to this new disease.

Mosquito control efforts for species as wide-spread as A. aegypti and A. allopictus have proven difficult. Chemical insecticide sprays may be effective in the short term, but are often met with opposition from the public. A more promising method involves mosquitos genetically modified to carry a self-limiting gene. Modified male mosquitos (remember, male mosquitos neither bite nor carry disease) are released in large numbers. They mate with females; the offspring inherit a gene that causes them to die before reaching maturity. Early trials showed a greater than 90% target species reduction. The modified mosquitos have been approved for use in Brazil, and the US Food and Drug Administration has, in 2016, approved their use in the US.

The genetically-modified insect technique can presumably be applied to other mosquito species – perhaps the Anopheles that spreads malaria.

In any case, I’ll be using insect repellent, just as I have all along. I think I am a poster boy for DEET. And, I’m sure I’ll be an early adopter of a Zika vaccine when it comes out. Perhaps, if we’re really lucky, the vaccine will also confer immunity to dengue and chikungunya. If so, the vaccine might be know as the CDZ vaccine.

In the meantime, I’m going to enjoy life here as I always have. Happy hour – time for a beer.

Notes and Sources

I relied on two general articles. First, Siddhartha Mukherjee, “The Race for a Zika Vaccine’, New Yorker, August 22, 2016. See that article for more details as to the development of a Zika vaccine. Mukherjee wrote The Emperor of All Maladies: A Biography of Cancer, which won a Pulitzer Prize in 2011 for General Non-Fiction. I am now reading his latest book The Gene: An Intimate History, which I am  enjoying immensely.

See also Robert L. Dorit: ”Zika Goes Viral”, American Scientist, September-October 2016. Dorit’s emphasizes public health considerations and writes of Zika as an example of an emerging epidemic.

See Wikipedia entries for Zika virus and Aedes aegyptii for general information.

The map showing Zika spread is from Wikimedia Commons. The complete attribution is: Faye O, Freire C, Iamarino A, Faye O, de Oliveira J, Diallo M, Zanotto P, Sall A (2014). “Molecular Evolution of Zika Virus during Its Emergence in the 20th Century“. PLOS Neglected Tropical Diseases. DOI:10.1371/journal.pntd.0002636. PMID 24421913. PMC: 3888466.

The image of the Aedes aegyptii mosquito is in the public domain, having originated at the US Center for Disease Control.

The image of the Zika virus from Wikimedia Commons. The full attribution is: David Goodwill (RCSB Molecule of the Month 197, June 2016) [CC BY 4.0 (http://creativecommons.org/licenses/by/4.0)], via Wikimedia Commons. See it at https://commons.wikimedia.org/wiki/File%3A197-Zika_Virus-ZikaVirus.tif

The modified male mosquitos, known as OX513A, were developed by Oxitec, an offshoot of Oxford University. This seems promising as A. aegypti is a vector of dengue and chikungunya as well as Zika – a three for one benefit. Google OX513A for more information.