METHODS: We used the synthetic control method (SCM) under assumption of partial interference to evaluate the direct and spillover PEs of Wolbachia-mediated introgression in a long-running operational trial of the intervention in Malaysia. Synthetic controls (SCs), which comprise of a weighted sum of non-spillover controls, were constructed for each directly-treated and spillover site in the pre-intervention period to account for historical imbalances in dengue risk and risk trajectories. SCs were compared to directly/spillover-treated sites to estimate the impact of Wolbachia-introgression on dengue incidence across each site, calendar year and intervention time. Robustness checks, including visual inspections, root-mean-square error (RMSE) calculations, in-space and in-time placebo checks, and permutation tests, were used to inspect the model's ability in attributing dengue incidence reductions to the Wolbachia interventions.
FINDINGS: The direct and spillover PEs of Wolbachia on dengue incidence were expressed as a percentage reduction of dengue incidence, or the absolute case reductions, by comparing SCs to actual intervention/spillover sites. Findings indicate a direct reduction in dengue incidence by 64.35% (95% CI: 63.50-66.71, p mosquitoes as a sustainable, cost-effective strategy against dengue.
FUNDING: This research is hosted by CNRS@CREATE and supported by the National Research Foundation, Prime Minister's Office, Singapore, under its Campus for Research Excellence and Technological Enterprise (CREATE) program, and is funded by the Lee Kong Chian School of Medicine-Ministry of Education Start-Up Grant. The original Hoffmann et al. (2024) study was funded by the Wellcome Trust Awards 226166, 108508, 202888 and the Ministry of Health Malaysia NMRR-16-297-28898.
Methods: : Extensive surveys were carried out from November 2017 to January 2018 (post-monsoon season) randomly in the nine inhabited islands of Lakshadweep for conducting faunastic studies on mosquitoes and to know the basic binomics like breeding and resting preference of mosquitoes. The study islands included, Kavaratti, Agatti, Chetlat, Bitra, Amini, Kadmath, Andrott, Kalpeni and Kiltan. Both immature and adult collections were carried out by standard/appropriate sampling techniques. The obtained data were calculated and analysed in terms of different entomological indices.
Results: : A total of 3356 mosquitoes were collected during the study period which comprised of 16 species from nine genera. Out of the 16 species, six belonged to mosquito vectors. The collection included malaria vector, Anopheles stephensi; Japanese encephalitis vector, Culex tritaeniorhynchus; Bancroftian filariasis vector, Cx. quinquefasciatus; Brugian filariasis vector, Mansonia uniformis; and dengue and chikungunya vectors, Stegomya albopicta and St. aegypti. Stegomya albopicta was the most predominant species observed constituting 54% of the catch, followed by Cx. quinquefasciatus, An. stephensi, Cx. tritaeniorhynchus, and St. aegypti constituting 10.5, 6, 3 and 1.2%, respectively. Apart from vector species many non-vectors such as Heizmannia chandi, An. subpictus, An. varuna, Cx. sitiens, Cx. minutissimus, Cx. rubithoracis, Fredwardsius vittatus, Lutzia fuscana, Malaya genurostris and Armigeres subalbatus were also present in the study area. In Kavaratti Island, the capital of Lakshadweep, a non-vector species of sandfly, Sergentomyia (Parrotomyia) babu was observed during the indoor resting collection. The major breeding sites which supported various mosquito species included, discarded plastic containers, tree holes, open sintex tanks (water storage tanks), unused wells, discarded tyres, discarded iron pots, unused and damaged boats, cement tanks, pleated plastic sheets, coral holes, pits and irrigation canals, discarded washing machines, and Colocasia plant leaf axils. Breteau index ranged between 65.3 and 110, CI ranged between 63.64 and 72.41; and HI ranged between 38.46 and 70 among the various islands.
Interpretation & conclusion: : Entomological indices such as house index (HI), breteau index (BI) and pupal index (PI) were high in all the nine islands and exceeded the threshold levels specified by WHO, indicating high risk for dengue virus transmission in case of outbreaks. Occurrence of vector as well as non-vector species indicates that the global change in climate is causing notable changes in terms of breeding of vector and non-vector species in the islands. With the reported cases of VBDs and the presence of vectors species in Lakshadweep Islands, a stringent control measure needs to be implemented at the Lakshadweep Islands.