Genomics-informed surveillance for elimination of rabies in the Philippines

Bautista, Criselda T. (2025) Genomics-informed surveillance for elimination of rabies in the Philippines. PhD thesis, University of Glasgow.

Abstract

Surveillance comprises the collection, analysis and dissemination of health-related data to support planning, implementation and evaluation of public health response. Genomic surveillance involves incorporating genomic sequencing to understand transmission dynamics and the spread of outbreaks, thereby complementing traditional surveillance. The utility of genomic sequencing for supporting rabies elimination is demonstrated by its capacity to track viral sources, investigate host shifts, and identify cross-border incursions. However, despite its potential, genomic surveillance remains underutilised and its integration into public health interventions has been limited, particularly in countries where rabies is endemic.

In the Philippines, rabies remains a significant public health threat, with hundreds of human deaths annually and widespread canine rabies transmission across all island groups. While national programs have made progress in dog vaccination and awareness campaigns, surveillance continues to rely heavily on traditional epidemiological data, with limited integration of molecular or genomic approaches. Prior to this thesis, the application of whole genome sequencing to rabies virus surveillance in the Philippines was minimal, and no standardized genomic framework existed to support outbreak investigations or inform control strategies.

This thesis explores the integration of genomic data into epidemiological surveillance in rabies control efforts in the Philippines, with the ultimate goal of contributing to the global “Zero by 30” campaign to eliminate human deaths from dog-mediated rabies. Using nanopore sequencing technology, I tested and validated a cost-effective whole genome sequencing workflow from sample-to-sequence-to-interpretation. The workflow was tailored to meet the demands of Low- and Middle-Income Countries (LMIC) settings, providing a scalable model for genomic surveillance. Using this approach, I generated whole genome sequences from rabies samples collected across different regions of the Philippines.For phylogenetic inference, I used BEAST and auxiliary programs (Beauti, Tracer, LogCombiner, TreeAnnotator), and accounted for sampling bias by employing for Bayesian Tip Association Statistics Testing to assess strength of association. In addition, using epidemiological data and samples from an outbreak in Romblon, I reconstructed the likely source and timing of viral incursion(s).

Phylogenetic analysis of the generated sequences, alongside publicly available genomes, revealed the presence of four major rabies virus clades in the Philippines, corresponding to the three main island groups Luzon, Visayas and Mindanao and an older lineage within Luzon, estimated to have emerged around 1970. This lineage, predominantly found in Calabarzon, aligns with previous studies showing the region as the source of the most recent common ancestor (MRCA) of circulating strains. A strong geographic association of rabies virus (RABV) was evident at the island and regional levels, though less pronounced at finer geographic scales. Luzon exhibited the highest genetic diversity, likely due to better sampling coverage. In contrast, the Visayas had fewer samples, contributing to reduced statistical support in this region.

By combining genomic data and epidemiological data, this thesis established a practical approach for enhanced rabies outbreak detection and response. These findings highlight how genomic surveillance can support region-specific strategies and improve rabies control across diverse epidemiological settings. The development of a rapid, cost-effective sequencing workflow contributes to overcoming existing barriers related to cost, infrastructure, and expertise.

My findings have significant implications for rabies elimination and reinforce the importance of integrating genomics into the national surveillance systems. They also underscore the need for a One Health approach through intersectoral Bite Case Management (IBCM). Future research directions should focus on expanding genomic databases, performing finer-scale phylogeographic analyses, and addressing socio-cultural factors affecting control efforts. Ultimately, the tools and insights from this thesis can advance not only rabies control but also the broader application of genomic surveillance for other zoonotic and infectious diseases in the region.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Subjects: Q Science > QR Microbiology; Q Science > QR Microbiology > QR355 Virology
• Colleges/Schools: College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
• Funder's Name: DOST, British Council
• Supervisor's Name: Hampson, Professor Katie and Brunker, Dr. Kirstyn
• Date of Award: 2025
• Depositing User: Theses Team
• Unique ID: glathesis:2025-85273
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 30 Jun 2025 15:32
• Last Modified: 30 Jun 2025 15:34
• Thesis DOI: 10.5525/gla.thesis.85273
• URI: https://theses.gla.ac.uk/id/eprint/85273

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