New cases of Dengue per year in India (Lakhs, 2000-2020). Source: Institute for Health Metrics and Evaluation, Data Visualization Tool of the Global Burden of Disease Project, Accessed July 28, 2024
Fumigation is one way to curb mosquito breeding.
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Dengue, a familiar threat in India, imposes a tremendous burden on the economy, estimated at around ₹28,300 crore in direct costs per year and 5.68 lakh years of young life lost annually. Existing vector control strategies, including insecticides and community education, have achieved only modest success. Clinical trials have yet to define the safety and efficacy of India’s two dengue vaccine candidates and unearth effective antiviral agents. Given that a female Aedes mosquito transmits dengue, chikungunya, and Zika, biological vector control methods (e.g., sterile insect techniques) appear cost-effective, but mixed results limit their use.
In this context, innovative vector control methods have been studied globally since 2009. This method employs a naturally occurring bacterium (Wolbachia) in fruit flies (Drosophila melanogaster) — many insect species in the wild host Wolbachia, but not the Aedes mosquito.
Wolbachia: An unlikely hero
Wolbachia exhibits two facets of a symbiotic relationship (mutualism and parasitism) with the host insect. Scientists observed that Wolbachia provides resistance to viral infections in the fruit fly (mutualism) but can also impose a parasitic cost by shortening its life span and skewing insect populations toward a female majority. Resistance to viral infections could be due to direct competition between the virus and Wolbachia for the host cell’s resources. This observation laid the foundation for studying Wolbachia-infected mosquitoes at the University of Queensland. In 2009, McMeniman used the wMelPop strain to reduce the lifespan of Aedes by half. In 2011, Walker and Johnson successfully used the wMel strain to promote viral resistance without reducing the mosquito’s life span. The near-normal life span of the wMel mosquito allowed for more mating opportunities, rapidly establishing the bacterium in the study’s mosquitoes. It soon became a promising candidate for blocking dengue transmission. The stage was set for field trials and clinical studies, first in Australia and then across Oceania, Latin America, and Southeast Asia under the aegis of the World Mosquito Program.
Using wMel to combat dengue
Laboratory personnel mechanically transfer wMel to the cytoplasm (embryos/adult mosquitoes), termed transinfection, and, after establishing successful lines, release them into urban areas. Countries have successfully used two strategies: population suppression and population replacement.
Singapore releases infected male mosquitoes (males don’t bite humans) into its communities, covering 35% of households. When these males mate with uninfected females, they produce non-viable eggs (“cytoplasmic instability”), drastically reducing the Aedes population by 90%. Singapore estimated that people in the release areas are 77% less likely to have dengue infection.
Australia pioneered the population replacement strategy, releasing infected mosquitoes over many population centres over 1-6 months. Mating between infected males and females, or uninfected males and infected females, produced viable wMel carrying offspring via maternal transmission. The wMel-Aedes mosquitoes soon became dominant in the wild, with no new releases needed since 2017. Studies performed seven years after the initial releases show a stable wMel genome — a pre-requisite for continued success. Since then, Australia has reported successful outcomes in dengue control, nearing dengue elimination.
Scientists found a bacteria tricked a wasp to get rid of its males
In 2021, a multi-national effort resulted in a pathbreaking randomised controlled trial (RCT) in Indonesia. RCTs are considered the gold standard for testing interventions. In this trial, investigators released wMel mosquitoes in 12 geographic regions, with 12 similar no-release areas. At the end of 3 years, people living in the mosquito deployment areas were approximately 77% less likely to contract dengue and 86% less likely to need hospitalisation.
The long-term impact of wMel releases into the ecosystem is unknown. However, Wolbachia naturally occurs within 60% of insect species and doesn’t infect humans and vertebrate animals. Importantly, Aedes mosquitoes are a recent import into non-African ecosystems initiated by the slave trade and, in the last 50 years, accelerated by the combination of global trade, travel, and rapid urbanisation. Scientists do not classify wMel transinfection as genetic engineering because the process does not involve integrating the bacterium’s genome into the host’s genome.
wMel Programs in India
India currently does not have an active wMel mosquito release programme. On July 5, 2022, the Indian Council of Medical Research — Vector Control Research Center (ICMR-VCRC) provided an update about developing two colonies of Puducherry wMel Aedes strains. The update mentioned successful studies since 2018 and pending government approvals. However, the ICMR-VCRC has not issued significant public updates since then. ICMR has recently reported that Wolbachia was found naturally in Aedes in NE India, though its immediate significance is unknown.
The magnitude of results in field trials and the Indonesian trial highlight important implications for India. The wMel strategy could be highly cost-effective given its potential to reduce the burden of other emerging infections like Zika, Japanese encephalitis and chikungunya. wMel strategy also gains importance because we must rely on more than insecticides due to resistance, safety concerns, and their limited effectiveness. Ensuring appropriate public messaging about planned mosquito releases is essential in the era of social media and disinformation. We can also learn valuable lessons from the experiences of mosquito releases in cities across 14 different countries. During the monsoon, the surge in similar febrile illnesses overwhelms our healthcare systems. Reducing mosquito-borne illnesses through proven interventions has an immense potential to reduce the burden on our health systems and productivity. Exploring all possible interventions to ensure a healthy, productive young population and realising our demographic dividend is crucial. We must resurrect and fund innovative vector control programs across India to combat the Aedes-borne triple epidemic of Dengue, Chikungunya, and Zika.
(Dr. Mummadi is with the Division of Pulmonary & Critical Care Medicine, The Metro Health System, Cleveland, OH, USA. m.srinivasreddy@gmail.com; Dr. Scaria is Senior Consultant, Genome Informatics and Computational Biology, Vishwanath Cancer Care Foundation and Adjunct Professor – Indian Institute of Technology, Kanpur. drvinod@gmail.com)
