High-resolution mapping of tuberculosis transmission: Whole genome sequencing and phylogenetic modelling of a cohort from Valencia Region, Spain

• DOI: 10.1371/journal.pmed.1002961
• Publication Date: 2019-10-31T17:45:40Z
• Authors: Yuanwei Xu; Irving Cancino-Muñoz; Manuela Torres-Pu...; Luis M. Villamayor; Rafael Borrás; María Borrás-Máñez; Montserrat Bosque; Juan J. Camarena; Ester Colomer-Roig; Javier Colomina; Isabel Escribano; Oscar Esparcia-Ro...; Ana Gil-Brusola; Concepción Gimeno; Adelina Gimeno-Ga...; Bárbara Gomila-Sard; Damiana González-...; Nieves Gonzalo-Ji...; María Remedio Gun...; José Luis López-H...; Coral Martín-Gonz...; Rosario Moreno-Muñoz; David Navarro; María Navarro; Nieves Orta; Elvira Pérez; Josep Prat; Juan Carlos Rodrí...; María Montserrat ...; Herme Vanaclocha; Caroline Colijn; Iñaki Comas
• Keywords: Adult; Male; 0301 basic medicine; Adolescent; Polymorphism, Single Nucleotide; 03 medical and health sciences; Risk Factors; HIV Seropositivity; Humans; Phylogeny; Aged; Incidence; R; Bayes Theorem; Genomics; Mycobacterium tuberculosis; Middle Aged; 3. Good health; Treatment Outcome; Spain; Medicine; Female; Contact Tracing; Biomarkers; Genome, Bacterial; Research Article

Background Whole genome sequencing provides better delineation of transmission clusters in Mycobacterium tuberculosis than traditional methods. However, its ability to reveal individual links within is limited. Here, we used a 2-step approach based on Bayesian reconstruction (1) identify likely index and missing cases, (2) determine risk factors associated with transmitters, (3) estimate when happened. Methods findings We developed our method using genomic epidemiological data from population-based study Valencia Region, Spain. Tuberculosis (TB) incidence during the period was 8.4 cases per 100,000 people. While ongoing, sampling frame for this work includes notified TB between 1 January 2014 31 December 2016. identified total 21 that fulfilled criteria analysis. These contained 117 individuals diagnosed active (109 data). Demographic characteristics population were as follows: 80/109 (73%) Spanish-born, 76/109 (70%) men, mean age 42.51 years (SD 18.46). found 66/109 (61%) patients sputum positive at diagnosis, 10/109 (9%) HIV positive. links, factors. Our inference suggests least 60% are misidentified by local public health. also suggest transmitters different those simply being cluster, highlighting importance differentiating these 2 phenomena. type diabetes mellitus factor transmitter (odds ratio 0.19 [95% CI 0.02–1.10], p < 0.003). Finally, most timing events occurred; 5/14 (35.7%) transmitted well before symptom onset, largely negative diagnosis. Limited within-cluster diversity does not allow us extrapolate whole Region. Conclusions In study, often misidentified, downstream consequences investigations because can be missed. regarding inferred occur patient suggesting transmits sub-clinical disease. This result has direct implications diagnosing reducing transmission. Overall, show transition individual-based epidemiology will close some knowledge gaps may redirect efforts towards cost-effective contact improved control.