Wolbachia: The Bacterium Helping Us Fight Dengue
What Is Wolbachia?
Wolbachia is a bacterium that grows and reproduces inside cells. This bacterium is not present in our cells, but it naturally occurs in around 60% of all insect species and some roundworms called nematodes. The featured image of this post depicts an insect cell containing Wolbachia (green) and DNA (blue). Wolbachia was first identified in 1924, but interest regarding its use in disease control was not sparked until the 1970s. This post will explore the effect of Wolbachia in insects, as the interactions and outcomes of this tiny bacterium in insects are completely different to that seen in nematodes, which will be explored in a future post.
How Is Wolbachia Spread?
Wolbachia is almost exclusively transmitted from mother to offspring via infected eggs, an explanation as to why such a large volume of insects are infected with it and why it is rapidly spreading throughout the insect population. Wolbachia infect predominantly the testes or ovaries of insects, leading to Wolbachia inhabitation in eggs, but surprisingly not sperm. This means that only females infected with Wolbachia can pass on the infection to their offspring, regardless of whether they have mated with a Wolbachia-infected or uninfected male. An infected male can only pass on Wolbachia to offspring if they have mated with an infected female. The same cannot be said if an infected male reproduces with an uninfected female. Ultimately, an infected female is always required for Wolbachia to be passed on to the offspring. This is an important consideration for dengue control specifically, which will be discussed further down, as research focus is on females. The fact that it is only the female mosquitoes that bite, thus only they have the ability to transmit disease, unlike males, is another consideration for female focus.
When we think of bacterial infections that humans are susceptible to such as Tuberculosis or Whooping cough, we know that they cause symptoms or further health problems and are sometimes transferred from person to person directly. However, we must think of the Wolbachia infection differently. Firstly, the term ‘infection’ could be classed differently for Wolbachia, as unlike the typical pathway of infection that we go down causing health implications, Wolbachia does not typically cause any negative effects for the hosts’ general fitness, except in a certain species of mosquito linked to dengue which will be discussed further down. You could think of it as quite a dormant, passive bacterium that is just spreading through the insect population but not causing much change to them. Additionally, Wolbachia is not easily spread directly from insect to insect, it is much more commonly transferred from mother to offspring.
How Is Wolbachia Being Used to Control Dengue?
So, how does all this information about a bacterium explain how it is used to control dengue? They seem to be independent topics, but this section will explain just how vital this little bacterium has been in controlling the devastating mosquito-borne disease, dengue. Firstly, we must understand a little bit more about dengue and how it is spread.
Dengue is transmitted by the Aedes aegypti mosquito, a mosquito that is instantly recognisable due to the white stripes on its legs, and lyre pattern on its thorax as seen in the photo below.
A female mosquito will bite an infected person and the virus will develop inside the mosquito for it soon to be transmitted to another victim when that mosquito takes her next blood meal. This species of mosquito is the main carrier and transmitter of other viruses such as Zika, chikungunya and yellow fever. Aedes aegypti mosquitoes are widespread, inhabiting tropical and subtropical regions of the world, meaning that there is potential for the diseases they carry to be spread around an increased geographical range. Dengue is spreading rapidly, it has observed a 30-fold increase in global incidence over the past 50 years according to the World Health Organization, in addition to estimates of half of the world’s population at risk of contracting it. A multitude of factors have contributed to this rapid increase, these include; climate change, as increases in temperature favour mosquito survival and disease development within them, human population growth and higher population densities can lead to increased disease outbreaks, urbanisation as Aedes aegypti have adapted to urban environments, increased travel and movement can contribute to the spread of disease, and the inadequate implementation of control measures such as insufficient and ineffective vaccinations. Additionally, no cure or treatment for dengue exists, thus the focus is on controlling the mosquito in order to control the disease. Typical mosquito control methods include using insecticides and bed-nets, however, the adoption of these methods for dengue is not very effective. The ever-increasing levels of insecticide resistance in mosquitoes means that the efficacy of insecticides are diminishing, thus their use must be carefully controlled so that they still have some effect whilst new control methods are being discovered and tested, before their ultimate failure means their use is completely redundant. Aedes mosquitoes, unlike the malaria mosquito species (Anopheles), are active in the day rather than at night, this means the use of bed-nets is pointless. People would have to remain in a bed-net all day for them to be effective against Aedes, which is completely impractical, and a good example of understanding mosquito behaviour and its effect on disease control.There is a desperate need for another method that targets the mosquito, and this is where we welcome Wolbachia.
Many mosquitoes carry Wolbachia, but Aedes aegypti; the mosquito predominantly responsible for transmitting dengue, does not. What would happen if you artificially inserted Wolbachia directly into Aedes aegypti mosquitoes? This is what researchers did, and the results showed that the Wolbachia was competing with the viruses within the mosquito. This meant that the Wolbachia was making it difficult for the viruses to reproduce inside the mosquito, thus was decreasing the mosquito’s ability to carry and transmit an infection. You could think of it as the Wolbachia immunising the mosquito against the virus. We do not fully understand the reasoning behind why the dengue virus has difficulty growing in Wolbachia-infected Aedes mosquitoes, but what is clear is that this discovery was a turning point in dengue control. However, this process may seem straight-forward, but it was laborious and time-consuming to infect the mosquitoes initially. Microscopic needles are used to transfer Wolbachia taken from another insect, commonly a fruit fly, into the miniscule eggs of a mosquito. Many of the eggs burst, thus thousands of eggs were used in experimentation to finally successfully transfer Wolbachia without destroying the eggs. The Word Mosquito Program breed Aedes aegypti mosquitoes that are infected with Wolbachia and then release them into dengue-affected areas in partnership with local communities. As the genetic material of the mosquito is not being altered, rather it is simply a case of infecting the mosquitoes with the bacterium, this method of control is not classed as genetic modification (GM). This method does not aim to kill mosquitoes, but rather suppress their ability to carry disease, thus when released into communities, it must be clear to the people that mosquitoes will still be present but they will no longer pose the threat of these types of viruses. This method is self-sustaining, as once the initial batch of mosquitoes have been infected with Wolbachia and later released, they transmit the bacterium through to their offspring, and thus it naturally spreads through the population and requires no additional interventions. There are different strains of Wolbachia, with some more commonly decreasing mosquito life than others. However, it is important that the Wolbachia used in dengue control does not cause this reduction in longevity, as it is critical for the sustainability of this method that the mosquito lives long enough to reproduce and pass on the Wolbachia to offspring. This method is closely monitored to ensure its continuous effectiveness. Monitoring, of the mosquito population and disease incidence, is conducted before and after releasing the Wolbachia-infected mosquitoes.
Is This Method of Control Accepted and Safe?
Before the Wolbachia-infected mosquitoes can be released into the wild, a lot of concerns within communities have to be addressed. As mentioned briefly in the previous section, the Wolbachia method does not cause a reduction in the number of mosquitoes, and as you can imagine, a method described as a control method that does not seem to be ‘controlling’ the mosquitoes may seem strange and misleading. This means that the focus is on education of the community, ensuring wide-spread understanding of this disease control method, rather than simply viewing it as a mosquito control method. Permissions of release always must be obtained, and this was a priority of this method.
Studies have shown that Wolbachia poses no threat to humans, nor can it be passed on to humans through the bite of a Wolbachia-infected mosquito. Other studies have showed that Wolbachia seem to only reside within the cells of insects or certain arthropods and cannot survive within the bloodstream of humans or other mammals.
Three independent risk assessments have been conducted on the Wolbachia method, all of which have concluded that there is negligible risk to people, animals or the environment following the Wolbachia-infected mosquito release. This is the lowest risk, as no method comes with zero risk, even insecticide-use poses risk to the environment and people, but it still has approval because it is about balancing the risk and the benefits of the outcome. The World Mosquito Program has approval from the governments of all the countries where the mosquitoes are released and must always obtain approval and support from the local community of that area.
Overall
Dengue and other diseases carried by the Aedes aegypti mosquito have a widespread incidence and devastating health implications, often targeting those already burdened with poverty or poor health. The reducing effectiveness of control methods such as insecticides, the absence of a cure, and the versatility of this species of mosquito to carry a multitude of diseases in both urban and rural areas highlights the need for a novel method to control dengue and prevent serious outbreaks. Wolbachia-based control has presented a method that does not kill mosquitoes, but it can reduce disease transmission in a self-sustaining manner that does not alter mosquito genetics. Ongoing trials in Australia, Vietnam, Indonesia and Brazil have shown continual success in reducing dengue transmission, and plans exist for expanding the range even further. This little bacterium, found by chance during a dissection many years ago, has proved to be ground-breaking in the control of dengue, and the potential for its use against other diseases in different animals is under-researched in comparison, but potential discoveries remain a mystery awaiting conclusion.
