Abstract
BackgroundTuberculosis remains common in Singapore, increasing in incidence since 2008. We attempted to determine the molecular epidemiology of Mycobacterium tuberculosis complex (MTC) isolates locally, identifying major circulating genotypes and obtaining a glimpse of transmission dynamics.MethodologyNon-duplicate MTC isolates archived between 2006 and 2012 at the larger clinical tuberculosis laboratory in Singapore were sampled for spoligotyping and MIRU-VNTR typing, with case data obtained from the Singapore Tuberculosis Elimination Program registry database. Isolates between 2008 and 2012 were selected because of either multidrug-resistance or potential epidemiological linkage, whereas earlier isolates were randomly selected. Separate analyses were performed for the early (2006-2007) and later (2008-2012) study phases in view of potential selection bias.Principal FindingsA total of 1,612 MTC isolates were typed, constituting 13.1% of all culture-positive tuberculosis cases during this period. Multidrug-resistance was present in 91 (5.6%) isolates – higher than the national prevalence in view of selection bias. The majority of isolates belonged to the Beijing (45.8%) and EAI (22.8%) lineages. There were 347 (30.7%) and 133 (27.5%) cases clustered by combined spoligotyping and MIRU-VNTR typing from the earlier and later phases respectively. Patients within these clusters tended to be of Chinese ethnicity, Singapore resident, and have isolates belonging to the Beijing lineage. A review of prior contact investigation results for all patients with clustered isolates failed to reveal epidemiological links for the majority, suggesting either unknown transmission networks or inadequate specificity of the molecular typing methods in a country with a moderate incidence of tuberculosis.ConclusionOur work demonstrates that Singapore has a large and heterogeneous distribution of MTC strains, and with possible cross-transmission over the past few years based on our molecular typing results. A universal MTC typing program coupled with enhanced contact investigations may be useful in further understanding the transmission dynamics of tuberculosis locally.
Highlights
Tuberculosis remains an infectious disease of global public health importance, causing significant morbidity and mortality even in developed countries
Genotyping using spoligotyping [4] and 15- to 24loci MIRU-VNTR [5] have been shown to be a useful proxy for demonstrating transmission of tuberculosis [6,7], they have considerably lower discriminatory power compared to whole genome sequencing and may not define the actual transmission chains of each Mycobacterium tuberculosis complex (MTC) clone [8]
During the earlier (2006-2007) and later (2008-2012) phases, there were a total of 3,987 (3,268 culture-positive) and 13,908 (9,068 culture-positive) non-duplicate tuberculosis cases notified to Singapore Tuberculosis Elimination Programme (STEP). It is routine practice for the microbiology laboratories in Singapore to perform drug susceptibility testing on at least one MTC isolate cultured from each patient, and there were 39 and 127 MDR-TB cases reported to STEP – comprising 1.2% and 1.4% of all culture-positive cases – during the earlier and later phases
Summary
Tuberculosis remains an infectious disease of global public health importance, causing significant morbidity and mortality even in developed countries. We attempted to determine the molecular epidemiology of Mycobacterium tuberculosis complex (MTC) isolates locally, identifying major circulating genotypes and obtaining a glimpse of transmission dynamics. There were 347 (30.7%) and 133 (27.5%) cases clustered by combined spoligotyping and MIRU-VNTR typing from the earlier and later phases respectively. Patients within these clusters tended to be of Chinese ethnicity, Singapore resident, and have isolates belonging to the Beijing lineage. A review of prior contact investigation results for all patients with clustered isolates failed to reveal epidemiological links for the majority, suggesting either unknown transmission networks or inadequate specificity of the molecular typing methods in a country with a moderate incidence of tuberculosis. A universal MTC typing program coupled with enhanced contact investigations may be useful in further understanding the transmission dynamics of tuberculosis locally
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