‘Must Have Been The Devil’
Aedes aegypti mosquitoes can spread viruses causing dengue, Zika, chikungunga, and yellow fever.
Over 1.4 million dengue cases and over 400 dengue-related deaths have been reported worldwide since the beginning of 2025 [1], and a current dengue outbreak is reported in the United States [2]. Dengue is caused by a virus spread by mosquitoes; viruses spread like this are a global public health threat.
Living in the UK, I frequently have buckets and kids’ toys gathering rainwater outside my house, but if I lived in a mosquito-prone region, I’d be encouraged to remove them and clean birdbaths and ponds out weekly – or not have them at all – since mosquitoes lay their eggs in or near water.
Only the female Aedes aegypti, also called the yellow fever mosquito, bites humans, and when they do, they can pick up and spread viruses causing diseases including dengue, Zika, chikungunga, and yellow fever, from an infected human. The virus lives inside the female mosquito for the next few days, replicating in the cells lining the gut before spreading to other tissues, including the salivary glands, ready to be injected when the mosquito bites its next victim.
Dengue originated in Africa, yet Ae. aegypti eggs can remain dormant in dry conditions for many months and so began to spread around the world with the international movement of people and goods, particularly during the slave trade, with dengue outbreaks along the east coast of North America coinciding with the arrival of slave ships [3]. Our warming global climate has enabled the movement of mosquitoes into regions previously too cool, as tropical, subtropical and temperate regions in which mosquitoes thrive expand.
Four variations of the dengue virus means that the development of appropriate vaccines is challenging, and available treatments are limited. 80% of dengue cases have no symptoms, making the spread of the virus difficult to track. The best advice is to avoid being bitten in the first place. The use of insecticides can have an unpredictable effect on local biodiversity, and have generated insecticide-resistant mosquitoes [4]. So what other options are there?
Efforts have been made to control the Ae. aegypti population itself to limit virus spread, either by reducing its numbers, or by replacing it with a population of mosquitoes unable to spread the disease-causing virus. There are two main approaches to this, one being the use of genetically-modified male Ae. aegypti to suppress the local population of biting females, and the other introduces Wolbachia pipientis bacteria, which naturally lives inside Ae. aegypti [5], blocking viral replication.
In the genetically-modified approach, Ae. aegypti are engineered to carry two extra genes, one that stops female offspring surviving to adulthood (the self-limiting gene), and the other a fluorescent marker gene, DsRed2, that makes the engineered mosquitoes glow orange under a special yellow light so that engineered mosquitoes and their offspring can be monitored. Engineered males are released as eggs, which hatch and develop into mature mosquitoes to seek out and mate with wild females. Any female offspring from this pairing die due to the self-limiting gene, reducing the portion of biting females, so limiting disease-causing virus transmission.
I have been thinking a lot about containment recently; it’s one thing engineering cells in a lab under controlled conditions, but what happens when the engineered cells are destined for the outside world? How do you control them then? How do you monitor them? How do you recall them if something goes wrong?
Engineered mosquitoes are now being widely used to control the spread of dengue in Brazil [6]. Since the offspring of the engineered mosquitoes containing the two extra genes die, the population inevitably goes into decline as the engineered mosquitoes reproduce, thus limiting the spread of the engineered mosquitoes. By their nature, the engineered mosquitoes won’t persist in their environment and the native population will recover over time. It is beneficial that Ae. aegypti won’t be eradicated completely, which would substantially alter the ecosystem, leaving a gap for the possible emergence of a new pest. Biodiversity is preserved, but the engineered population will need to be replenished – bringing more financial cost – but this offers a point of recall if you like, enabling the mosquitoes or their release to be modified the next time if needed.
In contrast to the engineered mosquitoes, Ae. aegypti containing Wolbachia are touted as ‘natural’ and ‘environmentally-friendly.’ Once let loose in the environment, Ae. aegypti containing Wolbachia will persist and multiply, with infected females being favoured to ensure Wolbachia spread in the mosquito population. Since they are naturally-occurring, it is not possible to track or monitor them. It’s ‘natural’, but there are more unknowns. The mechanism by which Wolbachia suppresses virus replication in the mosquitoes is not completely understood. Having too many Wolbachia in a single mosquito, while imparting the greatest ability to suppress viral replication, can take their toll on mosquito fitness. There is also the possibility that the viruses and/or mosquitoes will find a way to adapt – to overcome the ability of Wolbachia to suppress virus replication [5]. Though it has been argued that ‘even if resistance were to develop in the future, a great reduction in disease burden may have been afforded to communities in the intervening period’ [10].
References
European Centre for Disease Prevention and Control (2025) Dengue worldwide overview Accessed April 30, 2025.
U. S. Centers for Disease Control and Prevention (2025) Current Dengue Outbreak CDC. Accessed April 29, 2025.
Gould, E., Pettersson, J., Higgs, S., Charrel, R., de Lamballerie, X. (2017) Emerging arboviruses: Why today? One Health 4:1-13.
Rasli, R., Cheong, Y. L., Che Ibrahim, M. K., Farahininajua Fikri, S. F., Norzali, R. N., Nazarudin, N. A., Hamdan, N. F., Muhamed, K. A., Hafisool, A. A., Azmi, R. A., Ismail, H. A., Ali, R., Ab Hamid, N., Taib, M. Z., Omar, T., Wasi Ahmad, N., Lee, H. L. (2021) Insecticide resistance in dengue vectors from hotspots in Selangor, Malaysia. PLoS Negl Trop Dis. 15(3):e0009205.
Yen PS, Failloux AB. (2020) A Review: Wolbachia-Based Population Replacement for Mosquito Control Shares Common Points with Genetically Modified Control Approaches Pathogens. 9(5):404.
Oxitec (2024) 2023: Delivering Impact at Scale Oxitec. Accessed April 30, 2025.
Flores, H. A., O'Neill, S. L. (2018) Controlling vector-borne diseases by releasing modified mosquitoes. Nat Rev Microbiol. 16(8):508-518.
About the Title
‘Must Have Been The Devil’ is a line from the song ‘Red Mosquito’ by American rock band Pearl Jam (1996). This song soundtracked my writing of this post.
About the Illustration
Aedes aegypti mosquito, feeding on human flesh. Watercolour and blue biro on paper.