Tuberculosis Outbreak in an Educational Institution in Norway

Abstract

Within 1 week in April 2013, three cases of pulmonary tuberculosis (TB) were reported among students attending training sessions at an educational institution in Oslo, Norway. By the end of October 2013, a total of nine epidemiologically linked cases had been reported. The outbreak encompassed a total of 24 cases from 2009 to 2014, among which all of the 22 Mycobacterium tuberculosis isolates available had identical mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) profiles (MtbC15-9 code 10287-189) belonging to the Beijing lineage. Whole-genome sequencing (WGS) of the M. tuberculosis isolates revealed 20 variable nucleotide positions within the cluster, indicating a clonal outbreak. The most likely index case was identified and diagnosed in Norway in 2009 but was born in Asia. WGS analyses verified that all of the cases were indeed part of a single transmission chain. However, even when combining WGS and intensified contact tracing, we were unable to fully reconstruct the TB transmission events.

Keywords: Mycobacterium tuberculosis; Norway; genotyping; outbreak; whole-genome sequencing.

FIG 1

(A) Epidemiological curve for the 22 cases with an available isolate, identified as part of the cluster defined by MIRU-VNTR typing, and their respective subcluster association identified based on whole-genome sequencing. D (black bars), patients associated with the educational-institution outbreak; S (gray bars), patients with no verified epidemiological association with the educational-institution outbreak setting. (B) Proportion infected among identified contacts of case D1. In total, 8 active cases and 49 cases of latent TB were newly diagnosed among contacts of case D1. (Adapted from reference 5 with permission of the publisher.) Exposure data: >250 h, 14 infected plus 5 active TB out of 25 contacts (76%); 100 to 250 h, 6 infected plus 1 active TB out of 25 contacts (28%); 40 to 99 h, 24 infected plus 1 active TB out of 153 contacts (16%); 8 to 39 h, 4 infected plus 1 active TB out of 40 contacts; <8 h, 1 infected and no active TB out of 76 contacts.

FIG 2

(A) Single-nucleotide polymorphism (SNP) distances against time from first case of TB. Pink circles indicate cases associated with the educational institution. Stars denote repeated isolates from the same patient (D1-1, D1-2, D1-3). (B) Maximum-likelihood phylogeny of Mycobacterium tuberculosis (Mtb) outbreak isolates. Blue links indicate known epidemiological links outside the D cluster. (C) Minimum-spanning network of Mtb outbreak isolates. The Mtb isolates belonging to the educational-institution students and their known epidemiological links are highlighted in pink. Stars are used to indicate the serial isolates from the single patient that is the likely index case of the suboutbreak at the educational institution. In A and C, the index case of the whole outbreak is highlighted in yellow.