Emerging Genomic Trends on Rabies Virus in Davao Region, Philippines, 2018-2021.

Rabies, caused by the rabies virus (RABV), remains a significant public health issue in the Philippines despite efforts to control it. To eliminate rabies by 2030, effective surveillance strategies are crucial. In this study, we examined RABV evolution and phylodynamics in the Davao Region using genome sequences from Davao City and nearby provinces. We adapted the RABV ARTIC Protocol for Oxford Nanopore High-Throughput Sequencing to optimize workflow efficiency under limited resources. Comparing new virus samples collected from June 2019 to June 2021 (n = 38) with baseline samples from June 2018 to May 2019 (n = 49), new sub-clades were observed in the phylogenetic tree, suggesting divergence from older variants that were previously undetected. Most of the new viruses belonged to the Asian SEA4_A1.1.1 lineage, but new (SEA4_B1 and SEA4_B1.1) and emerging (SEA4_B1.1_E1) lineages that have never been reported in the Philippines were also identified. The baseline study reported phylogeographic clustering of RABV isolates from the same areas. However, this pattern was disrupted in the current biosurveillance, with variants detected in areas outside the original cluster. Furthermore, our findings revealed significant transmission routes between Davao City and neighboring provinces, contrasting with the predominantly intra-city transmission observed in the baseline study. These results underscore the need for ongoing and timely genomic surveillance to monitor genetic diversity changes and the emergence of novel strains, as well as to track alterations in transmission pathways. Implementing cost-effective next-generation sequencing workflows will facilitate the integration of genomic surveillance into rabies control programs, particularly in resource-limited settings. Collaborations between different sectors can empower local laboratories and experts in genomic technologies and analysis.

Genome-based local dynamics of canine rabies virus epidemiology, transmission, and evolution in Davao City, Philippines, 2018-2019.

Rabies is a fatal zoonotic and neglected tropical disease caused by the rabies virus (RABV) and is associated with neuronal dysfunction and death, with dogs as the predominant carrier. The Philippines plans to eradicate rabies by 2022, but this is challenged with sub-optimal coverage of vaccination programs coupled with sustained transmission chains, making it unable to eradicate the disease. We investigated the dynamics of canine rabies in the highly urbanized Davao City of the Philippines and its neighboring localities by assessing genetic relationships, transmission patterns, selection pressure, and recombination events using the whole genome sequence of 49 RABV cases from June 2018 to May 2019, majority of which (46%) were from the district of Talomo, Davao City. Although phylogeographic clustering was observed, local variants also exhibited genetic sub-lineages. Phylogenetic and spatial transmission analysis provided evidence for intra- and inter-city transmission predominantly through the Talomo district of Davao City. Around 84% of the cases were owned dogs, but the genetic similiarity of RABVs from stray and owned dogs further alluded to the role of the former as transmission vectors. The high rate of improper vaccination among the affected dogs (80%) was also a likely contributor to transmission. The RABV population under Investigation is generally under strong purifying selection with no evidence of vaccine evasion due to the genetic homogeneity of viruses from vaccinated and improperly vaccinated dogs. However, some homologous recombination (HR) events were identified along the G and L genes, also predominantly associated with viruses from Talomo. The complementary findings on epidemiology, transmission, and recombination for Talomo suggest that high incidence areas can be seeds for virus dispersal and evolution. We recommend further Investigations on the possibility of HR in future large-scale genome studies. Finally, districts associated with these phenomena can be targeted for evidence-based local strategies that can help break RABV transmission chains and prevent emergence of novel strains in Davao City.