2024-03-29T12:42:07Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1939652021-12-27T16:14:46Zcom_10261_109com_10261_1col_10261_362
DIGITAL.CSIC
author
Xu, Yuanwei
author
Cancino-Muñoz, Irving
author
Torres-Puente, Manuela
author
Villamayor, Luis M.
author
Borrás, Rafael
author
Borrás-Máñez, María
author
Bosque, Montserrat
author
Camarena, Juan J.
author
Colomer-Roig, Ester
author
Colomina, Javier
author
Escribano, Isabel
author
Esparcia-Rodríguez, Oscar
author
Gil-Brusola, Ana
author
Gimeno, Concepción
author
Gimeno-Gascón, Adelina
author
Gomila-Sard, Bárbara
author
González-Granda, Damiana
author
Gonzalo-Jiménez, Nieves
author
Guna-Serrano, María Remedio
author
López-Hontangas, José Luis
author
Martín-González, Coral
author
Moreno-Muñoz, Rosario
author
Navarro, David
author
Navarro, María
author
Orta, Nieves
author
Pérez, Elvira
author
Prat, Josep
author
Rodríguez, Juan Carlos
author
Ruiz-García, María Montserrat
author
Vanaclocha, Herme
author
Colijn, Caroline
author
Comas, Iñaki
funder
European Research Council
funder
Ministerio de Economía y Competitividad (España)
funder
Engineering and Physical Sciences Research Council (UK)
orcid
Comas, Iñaki [0000-0001-5504-9408]
orcid
Torres-Puente, Manuela [0000-0002-8352-180X]
2019-11-05T07:42:34Z
2019-11-05T07:42:34Z
2019-10-31
PLoS Medicine 16(10):e1002961. (2019)
1549-1277
http://hdl.handle.net/10261/193965
10.1371/journal.pmed.1002961
1549-1676
http://dx.doi.org/10.13039/501100000266http://dx.doi.org/10.13039/501100000781http://dx.doi.org/10.13039/501100003329
31671150
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.
eng
openAccess
High-resolution mapping of tuberculosis transmission: Whole genome sequencing and phylogenetic modelling of a cohort from Valencia Region, Spain
artículo
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URL
https://digital.csic.es/bitstream/10261/193965/1/2019%20PLoS%20Med%2016-e1002961.pdf
File
MD5
b5dd553fe23628191706a5d655f4e192
2327549
application/pdf
2019 PLoS Med 16-e1002961.pdf