High-resolution mapping of tuberculosis transmission: Whole genome sequencing and phylogenetic modelling of a cohort from Valencia Region, Spain
| Autor: | Nieves Gonzalo-Jimenez, Montserrat Bosque, Javier Colomina, Yuanwei Xu, Rafael Borrás, Josep M. Prat, José Luis López-Hontangas, Elvira Pérez, Herme Vanaclocha, Bárbara Gomila-Sard, Nieves Orta, María Borrás-Máñez, Rosario Moreno-Muñoz, J.J. Camarena, Oscar Esparcia-Rodríguez, Ester Colomer-Roig, Juan Carlos Rodríguez, Adelina Gimeno-Gascón, Damiana González-Granda, Manuela Torres-Puente, María Remedio Guna-Serrano, Coral Martín-González, Ana Gil-Brusola, Iñaki Comas, Maria Navarro, Isabel Escribano, Concepción Gimeno, Irving Cancino-Muñoz, David Navarro, Luis M Villamayor, Caroline Colijn, María Montserrat Ruiz-García |
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| Přispěvatelé: | European Research Council, Ministerio de Economía y Competitividad (España), Engineering and Physical Sciences Research Council (UK), Comas, Iñaki, Torres-Puente, Manuela, Comas, Iñaki [0000-0001-5504-9408], Torres-Puente, Manuela [0000-0002-8352-180X] |
| Rok vydání: | 2019 |
| Předmět: |
Male
Bacterial Diseases Epidemiology Gene Identification and Analysis Genetic Networks 030204 cardiovascular system & hematology law.invention 0302 clinical medicine Risk Factors law HIV Seropositivity Medicine and Health Sciences 030212 general & internal medicine Phylogeny Data Management education.field_of_study Incidence Incidence (epidemiology) Phylogenetic Analysis Genomics General Medicine Middle Aged 3. Good health Phylogenetics Treatment Outcome Infectious Diseases Transmission (mechanics) Medicine Tuberculosis Diagnosis and Management Population study Female Network Analysis Research Article Adult Computer and Information Sciences medicine.medical_specialty Tuberculosis Adolescent Infectious Disease Control Population Polymorphism Single Nucleotide Infectious Disease Epidemiology Young Adult 03 medical and health sciences Diagnostic Medicine Genetics medicine Humans Evolutionary Systematics Risk factor education Tuberculosis Pulmonary Aged Taxonomy Evolutionary Biology Whole Genome Sequencing business.industry Biology and Life Sciences Bayes Theorem Mycobacterium tuberculosis Odds ratio Tropical Diseases medicine.disease Spain Medical Risk Factors Contact Tracing business Biomarkers Genome Bacterial Demography |
| Zdroj: | PLOS MEDICINE r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA instname r-IIS La Fe. Repositorio Institucional de Producción Científica del Instituto de Investigación Sanitaria La Fe PLoS Medicine PLOS Medicine Digital.CSIC. Repositorio Institucional del CSIC r-FISABIO: Repositorio Institucional de Producción Científica Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO) r-FISABIO. Repositorio Institucional de Producción Científica PLoS Medicine, Vol 16, Iss 10, p e1002961 (2019) r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante |
| ISSN: | 1549-1277 |
| Popis: | Artículo con 20 páginas, 5 figuras, 1 tabla. All the sequence data are deposited in the European Nucleotide Archive under the Bioproject number PRJEB29604 (https://www.ebi.ac.uk/ena/data/view/PRJEB29604) and the accession numbers ERR2099780 (https://www.ebi.ac.uk/ena/data/search?query=ERR2099780) and ERR2099784 (https://www.ebi.ac.uk/ena/data/search?query=ERR2099784). BACKGROUND: Whole genome sequencing provides better delineation of transmission clusters in Mycobacterium tuberculosis than traditional methods. However, its ability to reveal individual transmission links within clusters is limited. Here, we used a 2-step approach based on Bayesian transmission reconstruction to (1) identify likely index and missing cases, (2) determine risk factors associated with transmitters, and (3) estimate when transmission happened. METHODS AND FINDINGS: We developed our transmission reconstruction method using genomic and epidemiological data from a population-based study from Valencia Region, Spain. Tuberculosis (TB) incidence during the study period was 8.4 cases per 100,000 people. While the study is ongoing, the sampling frame for this work includes notified TB cases between 1 January 2014 and 31 December 2016. We identified a total of 21 transmission clusters that fulfilled the criteria for analysis. These contained a total of 117 individuals diagnosed with active TB (109 with epidemiological data). Demographic characteristics of the study population were as follows: 80/109 (73%) individuals were Spanish-born, 76/109 (70%) individuals were men, and the mean age was 42.51 years (SD 18.46). We found that 66/109 (61%) TB patients were sputum positive at diagnosis, and 10/109 (9%) were HIV positive. We used the data to reveal individual transmission links, and to identify index cases, missing cases, likely transmitters, and associated transmission risk factors. Our Bayesian inference approach suggests that at least 60% of index cases are likely misidentified by local public health. Our data also suggest that factors associated with likely transmitters are different to those of simply being in a transmission cluster, highlighting the importance of differentiating between these 2 phenomena. Our data suggest that type 2 diabetes mellitus is a risk factor associated with being a transmitter (odds ratio 0.19 [95% CI 0.02-1.10], p < 0.003). Finally, we used the most likely timing for transmission events to study when TB transmission occurred; we identified that 5/14 (35.7%) cases likely transmitted TB well before symptom onset, and these were largely sputum negative at diagnosis. Limited within-cluster diversity does not allow us to extrapolate our findings to the whole TB population in Valencia Region. CONCLUSIONS: In this study, we found that index cases are often misidentified, with downstream consequences for epidemiological investigations because likely transmitters can be missed. Our findings regarding inferred transmission timing suggest that TB transmission can occur before patient symptom onset, suggesting also that TB transmits during sub-clinical disease. This result has direct implications for diagnosing TB and reducing transmission. Overall, we show that a transition to individual-based genomic epidemiology will likely close some of the knowledge gaps in TB transmission and may redirect efforts towards cost-effective contact investigations for improved TB control. IC was supported by European Research Council (638553-TB-ACCELERATE), the Ministerio de Economía y Competitividad (SAF2016-77346-R). CC and YX were supported by the Engineering and Physical Sciences Research Council of the UK (EPSRC EP/K026003/1 (CC) and EPSRC EP/N014529/1 (CC and YX). |
| Databáze: | OpenAIRE |
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