The mosquito, the microbes, and the mission
Authors: None The Lancet Microbe
Journal: The Lancet Microbe (2022)

The latest report by the UN Intergovernmental Panel on Climate Change states that warming temperatures and extreme weather events will increase the range of Aedes aegypti mosquitoes in Asia, Europe, central and South America, and Africa. This habitat expansion could put an additional 1 billion people at risk of dengue fever by 2080. Already, dengue incidence is increasing. According to WHO, 504 430 cases were reported in 2000, compared with 5·2 million cases in 2019, and dengue transmission was detected in Afghanistan for the first time in the same year. The dramatic increase in cases can partly be attributed to improvements in recording and reporting systems, but the idea that dengue is entering new populations is alarming. The spread of Aedes spp mosquitoes, along with the existence of four distinct dengue virus serotypes, rising insecticide resistance, and a suboptimal vaccine, threatened the progress of dengue control, but this view changed thanks to one group of bacteria: wolbachia. Wolbachia species infect between 20% and 70% of all insects on the planet and have the potential to reverse the trend of rising dengue. A project pioneered by the World Mosquito Program, wolbachia-infected A aegypti can reduce the ability to transmit the dengue virus owing to wolbachia-mediated inhibition of viral replication and dissemination within the mosquito. In June, 2021, a major efficacy study was published showing that wolbachia had reduced the incidence of symptomatic dengue by 77% in Yogyakarta, Indonesia, supporting the results of previous smaller laboratory and field studies. The landmark trial in Indonesia provides hope for the future of controlling the diseases associated with an expanding Aedes spp population. The success of wolbachia-infected mosquitoes implies that this method of disease control could be scaled up in coming years, so a key question now is whether the dengue virus could eventually evolve resistance to or outcompete wolbachia within the mosquito. If, when, and how dengue overcomes wolbachia is unknown, but we do know that RNA viruses are particularly good at adapting to antiviral pressures, as exemplified by SARS-CoV-2 variants throughout the COVID-19 pandemic. For this reason, it is crucial that resistance surveillance is incorporated into future programmes that release wolbachia-infected mosquitoes. Monitoring for pathogen resistance to an antiviral microbe within a disease vector is unchartered territory, particularly on a large scale. What is clear is that the wolbachia trials have and will inspire an interest in using microbes to reduce pathogen survival within vectors. We have seen this already with the number of studies of tick microbiomes that have been published over the past 10 years. In 2019, the commensal bacterium Kosakonia cowanii Zambiae was found to inhibit the growth of Trypanosoma spp parasites within the midgut of the tsetse fly vector of African trypanosomiasis and, similarly, the bacteriome of the blackfly was characterised in 2021 in the hope that these bacteria could be studied as potential tools for onchocerciasis control. Using commensal microbes as a means of disease control is not the only innovation occurring in medical entomology. The sterile insect technique, which rears and releases large quantities of sterilised male mosquitoes into the environment, has been used in field trials to reduce mosquito populations in the USA, Caribbean, and Africa. In 2021, WHO published guidelines for the testing of genetically modified mosquitoes after several release trials—including wolbachia-based strategies—were published over the past decade. Unlike the genetic sterility approach, the wolbachia method does not affect the survival or reproduction of mosquitoes; therefore, this approach is unlikely to cause ecological damage. However, given the increase of studies on microbes within vectors, WHO should consider publishing a guidance document specifically for this novel approach to controlling vector-borne diseases. Guidelines, particularly those on monitoring and evaluation, will become increasingly important as programme managers scale up the release of wolbachia-infected mosquitoes. The efforts and success of the wolbachia project should be celebrated. It has brought much needed innovation to dengue control efforts and paved the way for future studies of other disease vectors. Research attention needs to focus on how these hybrid vectors can be monitored in the long term, particularly in our changing climate. As we have seen with antibiotics, it is easy to attract funding and political will when the treatment is working, but the same urgency is difficult to find when progress wanes and the hard work of reinforcing the intervention begins.