The dynamics of drug resistance evolution and diagnosis in Mycobacterium tuberculosis : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy (PhD) in Genetics/Genomics, Massey University, Manawatu, New Zealand

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dc.confidentialEmbargo : No
dc.contributor.advisorLockhart, Peter
dc.contributor.authorFong, Yang (Richard)
dc.date.accessioned2025-09-01T22:54:43Z
dc.date.available2025-09-01T22:54:43Z
dc.date.issued2024-07-30
dc.description.abstractTuberculosis (TB) remains a critical global health challenge with over 10.4 million new cases annually, complicated by rising antimicrobial resistance (AMR) threatening to surpass cancer mortality by 2050. This PhD thesis establishes a systematic diagnostic framework addressing AMR challenges through progressive research from fundamental microbiome characterization to innovative diagnostic applications in resource-limited settings like Myanmar. The "Microbiome Dataset from the Upper Respiratory Tract of Patients Living with HIV, HIV/TB and TB from Myanmar" establishes the foundational understanding of microbial community structures in complex clinical presentations (n=309 isolates). This microbiome characterization reveals critical signatures that directly inform direct sequencing strategies for enhanced MTBC detection in polymicrobial environments, addressing a fundamental challenge in AMR detection. Next, the "Genomic Profiling of Mycobacterium tuberculosis Strains, Myanmar" validates and expands these microbiome-informed approaches through comprehensive whole genome sequencing surveillance, establishing genotype-phenotype correlations that achieve 97.8% concordance with phenotypic testing. This genomic profiling directly addresses AMR surveillance gaps by enabling rapid resistance prediction. Subsequently by "Unveiling Hr-TB in Myanmar: Comprehensive Genotypic and Phenotypic Insights for Improved TB Management" demonstrates targeted application of microbiome-informed diagnostic approaches to isoniazid mono-resistant TB, a clinically critical AMR variant frequently missed by conventional methods. The integrated microbiome-genomic approach enhances MTBC detection accuracy by 23% compared to standard methods, reducing diagnostic time from weeks to under one week. Future perspectives translate these discoveries into field-deployable MDA primer systems for point-of-care AMR detection using portable MinION sequencing technology. This systematic progression from microbiome foundation to diagnostic innovation establishes a replicable technological blueprint for next-generation TB AMR diagnostics, supporting Myanmar's National TB Control Program while providing a framework for global TB elimination efforts Keywords: Mycobacterium tuberculosis (MTB), Tuberculosis (TB), Antimicrobial Resistance (AMR), Isoniazid Mono-Resistant (Hr-TB), Drug-Resistant Tuberculosis (DR-TB), Whole-genome sequencing (WGS), Resistance associated Mutations, Epidemiology, Surveillance, Rapid Diagnosis, Microbiome, Yangon, Myanmar.
dc.identifier.urihttps://mro.massey.ac.nz/handle/10179/73462
dc.publisherMassey University
dc.rights© The Author
dc.subjectbiological science, biochemistry, microbiology, bioinformatics, medical diagnosis, epidemiology, public health, tuberculosis, antimicrobial resistance, whole-genome sequencing, next generation sequencing
dc.subjectMycobacterium tuberculosis
dc.subjectDrug resistance in microorganisms
dc.subjectTuberculosis
dc.subjectMyanmar
dc.subjectCase studies
dc.subjectMicrobiology
dc.subjectDiagnosis
dc.subject.anzsrc310509 Genomics
dc.subject.anzsrc310704 Microbial genetics
dc.titleThe dynamics of drug resistance evolution and diagnosis in Mycobacterium tuberculosis : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy (PhD) in Genetics/Genomics, Massey University, Manawatu, New Zealand
thesis.degree.disciplineGenetics
thesis.degree.nameDoctor of Philosophy (Ph.D.)
thesis.description.doctoral-citation-abridgedDr Yang Fong (Richard) is awarded the Doctor of Philosophy in Genetics and Genomics for research that strengthens global efforts to combat antimicrobial resistance in tuberculosis. He developed patented Multiple Displacement Amplification primers and field deployable nanopore workflows, bringing resistance profiling down from months to days and enabling de-centralized diagnostics in low resource settings. As a case study, whole genome analysis of 309 Myanmar isolates mapped Lineage 2 predominance and showed resistance arising repeatedly, informing surveillance and treatment strategies aligned with WHO End TB goals.
thesis.description.doctoral-citation-longDr Yang Fong is awarded the Doctor of Philosophy in Genetics and Genomics for research that strengthens global efforts to combat antimicrobial resistance in tuberculosis, aligning scientific innovation with the WHO End TB Strategy. He connected microbiome insights with whole genome sequencing to deliver rapid, field ready diagnostics and a practical pathway for decentralised testing in underserved settings. As a case study, whole genome analysis of 309 clinical isolates from Myanmar revealed Lineage 2 Beijing predominance and showed that drug resistance arises largely through repeated independent events rather than single transmission chains, informing surveillance and care. His workflow achieved over 97 percent agreement between genomic predictions and phenotypic testing and reduced diagnostic timelines from weeks to under one week. Building on this, Dr Fong designed and patented Multiple Displacement Amplification primers that enable sequencing from low bacillary samples and support point of care nanopore applications. Together, these advances offer a replicable blueprint for national programmes and contribute meaningfully to the global fight against antimicrobial resistance.
thesis.description.name-pronounciationYang Fong
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