Sunday, June 19, 2016

Zika & Wolbachia II: Disease transmission

    I am back. I had some business to take care of, and then of course there was another visit to spend time with my nephew and fulfill my duties as a new aunt. But I am here and excited to resume our conversation about Zika.

    The first part of the Zika and Wolbachia story morphed into a biography of Wolbach, for whom Wolbachia was named. I provided a teaser about recent research that suggests Wolbachia can reduce Zika transmission by mosquitoes. But I didn’t actually talk about Zika at all, and even though it’s only been a short time (~4 weeks) several new Zika stories have come out. Lucky for us, scientists world-wide are ramping up their efforts to understand Zika, and continue research on other diseases like Ebola, which remain important even when not in the spotlight (ideally congress would agree).

Aedes aegypti (Image credit: James Gathany, Center for Disease Control and Prevention Public Health Image Library)

   In 2009, a group of 17 scientists from Australia and Brazil published a study showing that when the mosquito Aedes aegypti is infected with particular strains of Wolbachia, the mosquitoes were less competent disease vectors, and could reduce transmission of diseases such as dengue, chikungunya, and Plasmodium (malaria) (Moreira et al. 2009). Let's put this in perspective, 85 years after Wolbach and Hertig first discovered Wolbachia in a mosquito in Boston (Culex pipiens), and after decades of Wolbachia research resulting in hundreds of publications that have little to do with humans and disease transmission, scientists discovered that Wolbachia could reduce the number of humans contracting deadly viruses. If this is not a solid argument for exploratory research then go fishing. Listen in, and we will see how it works. But first, there are several pieces of information that will help you follow the story: 1) The three main players are mosquitoes, Wolbachia bacteria, and Drosophila fruit flies, 2) There are over 3500 species of mosquitoes and only a handful carry diseases (a.k.a disease vectors), 3) Some mosquito species carry one disease, some carry many diseases, most carry no diseases, 4) The main species of mosquito that carries dengue, chikungunya, and Zika is Aedes aegypti, which is not typically infected with Wolbachia in the wild, and 5) Wolbachia is a genus of bacteria comprising many different types/strains that infect a variety of different insects. The most well-studied strains of Wolbachia are from the model organism Drosophila melanogaster, a fruit fly we will inevitably revisit in future posts.

Drosophila melanogaster: Illustration by Katy Wiedemann (Wiedemann Illustrations)

    Moving on. Methods to reduce the number of humans contracting diseases carried by mosquitoes focus on prevention, either through the development of vaccines or use of bug spray to prevent mosquito bites. The other option is to try and get rid of mosquitoes. Methods of reducing mosquito populations include spraying copious amounts of DDT into houses with growing children, and introducing copepods that eat mosquito larvae.
     
    Between 2000 and 2008, data from several labs coalesced on a different kind of preventive method. By infecting A. aegypti mosquitoes with certain Wolbachia strains isolated from the fruit fly D. melanogaster, the life span of A. aegypti was reduced. From the perspective of limiting disease transmission, this is good because many mosquitoes die before they can transmit disease. At the same time, another group of scientists studying Wolbachia in D. melanogaster found that certain strains were beneficial to D. melanogaster individuals that had harmful insect viruses such as Drosophila C virus, Flock House virus, and Cricket paralysis virus.

    In 2009, Moreira and colleagues put these two things together and hypothesized that Wolbachia infected mosquitoes would be less effective disease vectors. The idea was to test whether A. aegypti mosquitoes infected with Wolbachia from D. melanogaster fruit flies would reduce disease transmission. The answer was yes. The authors showed that A. aegypti with Wolbachia are resistant to several diseases, which prevents the mosquito from being able to pass the diseases onto the next human they bite. The mechanism for how this works remains unclear. The authors suggest it has something to do with how the mosquito immune system reacts to the Wolbachia bacteria, but no direct link was found. The other possibility is that there is competition for resources between the disease and Wolbachia in the cells of the mosquito, and Wolbachia outcompetes the disease. But no conclusive evidence has been presented to support either hypothesis. Regardless of the mechanism, it is clear that Wolbachia infected mosquitoes offer a two-pronged approach for controlling disease transmission: they have a shorter life-span and they show resistance to several different diseases. As a result, non-profit groups such as Eliminate Dengue Program are using this approach to slow the spread of dengue (and other diseases) in multiple locations around the world.

Eliminate Dengue Program


    That was the status of things before the spread of Zika skyrocketed last year, and was declared a Public Heath Emergency of International Concern (PHEIC) on February 1st, 2016. Scientists were quick to react and on June 8th, 2016, six Brazilian researchers published the results of a study demonstrating the effectiveness of Wolbachia to block two Zika strains currently being transmitted by A. aegypti mosquitoes in Brazil (Dutra et al. 2016). The release of Wolbachia infected mosquito eggs and adults is currently underway in Brazil and scientists are optimistic about the spread of the Wolbachia in Brazilian A. aegypti populations. All of this is very recent but at present it appears to be good news for humans, science, and exploratory research.

   Exactly how Wolbachia spreads in insect populations is an intriguing topic we will investigate next time. It is based on decades of exploratory research covering many different Wolbachia strains in many different types of insects.

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