Tuberculosis Outbreak in an Educational Institution in Norway

Norheim, Gunnstein; Seterelv, Siri; Arnesen, Trude Margrete; Mengshoel, Anne Torunn; Tønjum, Tone; Rønning, Janne O.; Eldholm, Vegard

doi:10.1128/jcm.01152-16

Cited by 26 publications

(20 citation statements)

References 14 publications

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“…Additionally, we found complex evolutionary patterns within an otherwise identical MIRU cluster and identified the interplay of host and epidemiological factors contributing to transmission potential of a cluster. The higher resolution gained by WGS is consistent with prior reports 2,3,36–38 , but the maximum genetic distance we find between the clustered isolates is larger than previously seen and we further estimate the group of LAM-4.3.3 sequenced isolates to have been circulating for over 8 decades in our study community. Previous studies performing WGS of MIRU-VNTR clusters in low prevalence settings have noted shorter genetic distance between isolates, 2,3,13 and in one case the distances were insufficient to reliably and consistently inform contact tracing interventions.…”

Section: Discussionsupporting

confidence: 92%

Genotypic clustering does not imply recent tuberculosis transmission in a high prevalence setting: A genomic epidemiology study in Lima, Peru

Dixit

Freschi

Vargas

et al. 2018

Preprint

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BackgroundWhole genome sequencing (WGS) can elucidate Mycobacterium tuberculosis (Mtb) transmission patterns but more data is needed to guide its use in high-burden settings. In a household-based transmissibility study of 4,000 TB patients in Lima, Peru, we identified a large MIRU-VNTR Mtb cluster with a range of resistance phenotypes and studied host and bacterial factors contributing to its spread.MethodsWGS was performed on 61 of 148 isolates in the cluster. We compared transmission link inference using epidemiological or genomic data with and without the inclusion of controversial variants, and estimated the dates of emergence of the cluster and antimicrobial drug resistance acquisition events by generating a time-calibrated phylogeny. We validated our findings in genomic data from an outbreak of 325 TB cases in London. Using a larger set of 12,032 public Mtb genomes, we determined bacterial factors characterizing this cluster and under positive selection in other Mtb lineages.FindingsFour isolates were distantly related and the remaining 57 isolates diverged ca. 1968 (95% HPD: 1945-1985). Isoniazid resistance arose once, whereas rifampicin resistance emerged subsequently at least three times. Amplification of other drug resistance occurred as recently as within the last year of sampling. High quality PE/PPE variants and indels added information for transmission inference. We identified five cluster-defining SNPs, including esxV S23L to be potentially contributing to transmissibility.InterpretationClusters defined by MIRU-VNTR typing, could be circulating for decades in a high-burden setting. WGS allows for an improved understanding of transmission, as well as bacterial resistance and fitness factors.FundingThe study was funded by the National Institutes of Health (Peru Epi study U19-AI076217 and K01-ES026835 to MRF). The funding sources had no role in any aspect of the study, manuscript or decision to submit it for publication.Research in contextEvidence before this studyUse of whole genome sequencing (WGS) to study tuberculosis (TB) transmission has proven to have higher resolution that traditional typing methods in low-burden settings. The implications of its use in high-burden settings are not well understood.Added value of this studyUsing WGS, we found that TB clusters defined by traditional typing methods may be circulating for several decades. Genomic regions typically excluded from WGS analysis contain large amount of genetic variation that may affect interpretation of transmission events. We also identified five bacterial mutations that may contribute to transmission fitness.Implications of all the available evidenceAdded value of WGS for understanding TB transmission may be even higher in high-burden vs. low-burden settings. Methods integrating variants found in polymorphic sites and insertions and deletions are likely to have higher resolution. Several host and bacterial factors may be responsible for higher transmissibility that can be targets of intervention to interrupt TB transmission in communities.

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Section: Discussionsupporting

confidence: 92%

Genotypic clustering does not imply recent tuberculosis transmission in a high prevalence setting: A genomic epidemiology study in Lima, Peru

Dixit

Freschi

Vargas

et al. 2018

Preprint

View full text Add to dashboard Cite

show abstract

“…The higher resolution gained by WGS is consistent with prior reports 2,3,[53][54][55] , but the maximum genetic distance we find between the clustered isolates is larger than previously seen and we further estimate the group of LAM-4.3.3 sequenced isolates to have been circulating for over 8 decades in our study community. Previous studies performing WGS of MIRU-VNTR clusters in low prevalence settings have noted shorter genetic distance between isolates 2,3,13 , and in one case the distances were insufficient to reliably and consistently inform contact tracing interventions 13 .…”

Section: Discussionsupporting

confidence: 92%

Genotypic Clustering Does Not Imply Recent Tuberculosis Transmission in a High Prevalence Setting: A Genomic Epidemiology Study in Lima, Peru

et al. 2018

View full text Add to dashboard Cite

Whole genome sequencing (WGS) can elucidate Mycobacterium tuberculosis (Mtb) transmission patterns but more data is needed to guide its use in high-burden settings. In a household-based TB transmissibility study in Peru, we identified a large MIRU-VNTR Mtb cluster (148 isolates) with a range of resistance phenotypes, and studied host and bacterial factors contributing to its spread. WGS was performed on 61 of the 148 isolates. We compared transmission link inference using epidemiological or genomic data and estimated the dates of emergence of the cluster and antimicrobial drug resistance (DR) acquisition events by generating a time-calibrated phylogeny. Using a set of 12,032 public Mtb genomes, we determined bacterial factors characterizing this cluster and under positive selection in other Mtb lineages. Four of the 61 isolates were distantly related and the remaining 57 isolates diverged ca. 1968 (95%HPD: 1945-1985). Isoniazid resistance arose once and rifampin resistance emerged subsequently at least three times. Emergence of other DR types occurred as recently as within the last year of sampling. We identified five cluster-defining SNPs potentially contributing to transmissibility. In conclusion, clusters (as defined by MIRU-VNTR typing) may be circulating for decades in a high-burden setting. WGS allows for an enhanced understanding of transmission, drug resistance, and bacterial fitness factors.

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“…Norheim et al . conducted a study on tuberculosis outbreaks in an educational institution in Norway [10]. They performed MIRU-VNTR genotyping on the strains of the confirmed patients, and 22 of the 24 patients had the same VNTR site, confirming that it was a homologous outbreak.…”

Section: Discussionmentioning

confidence: 99%

“…Compared to other school settings, boarding schools are subject to a higher risk of tuberculosis outbreaks, where adolescents often cluster under relatively overcrowded conditions [8, 9]. In developed countries with a low-tuberculosis burden, clustered tuberculosis outbreaks often occur in schools [10, 11]. In China, a large amount of work has been carried out on tuberculosis prevention and control in schools in recent years.…”

Section: Introductionmentioning

confidence: 99%

A tuberculosis school outbreak in China, 2018: reaching an often overlooked adolescent population

You

Zhu

et al. 2019

Epidemiol. Infect.

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Adolescents have been largely neglected from tuberculosis control efforts. In low- to medium burden settings much of the tuberculosis burden in this age group occurs from school outbreaks. We report on a large tuberculosis outbreak in adolescents from a boarding high school in Jiangsu Province, China. From March to June 2018, a tuberculosis outbreak occurred in a boarding high school. We conducted an outbreak investigation involving clinical diagnostic tests and molecular analysis to determine the outbreak origin. Cases were detected through symptom screening, tuberculin skin testing (TST), chest radiography, sputum smear, solid sputum culture and GeneXpert MTB/RIF. Mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) genotyping and spoligotyping methods were performed on Mycobacterium tuberculosis (M. tuberculosis) isolates to identify the outbreak origin. A total of 845 students and 131 teachers/staff attended a TST screening for tuberculosis infection. The prevalence of elevated tuberculin reactions at ≥5, ≥10 and ≥15 mm was 12.19% (119/976), 6.35% (62/976) and 3.28% (32/976), respectively. Radiographic abnormalities were present in 5.73% (56 of 976) individuals, 40 students and 16 teachers/staff. Of these, 12 students were diagnosed with confirmed tuberculosis. In total, 14 students (two index cases and 12 confirmed cases) were diagnosed and reported in the tuberculosis outbreak, an attack rate of 1.7% (14/847) among students (two index cases and 845 screened students). Results from MIRU-VNTR typing and spoligotyping analyses demonstrated that three M. tuberculosis strains belong to the Beijing family with corresponding MIRU-VNTR alleles. This school-based tuberculosis outbreak among adolescents demonstrates that transmission among individuals in this age group is common and must be prioritised. It suggests that identifying and timely diagnosis of smear-positive cases, especially in the early phase of outbreaks, is the key to preventing further spread among close contacts.

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Tuberculosis Outbreak in an Educational Institution in Norway

Cited by 26 publications

References 14 publications

Genotypic clustering does not imply recent tuberculosis transmission in a high prevalence setting: A genomic epidemiology study in Lima, Peru

Genotypic clustering does not imply recent tuberculosis transmission in a high prevalence setting: A genomic epidemiology study in Lima, Peru

Genotypic Clustering Does Not Imply Recent Tuberculosis Transmission in a High Prevalence Setting: A Genomic Epidemiology Study in Lima, Peru

A tuberculosis school outbreak in China, 2018: reaching an often overlooked adolescent population

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