LINKTBPORTO – Understanding the tuberculosis transmission chains in Porto to improve control strategies.

The effective control of tuberculosis (TB) requires targeted efforts to break transmission. The lack of obvious symptoms for long periods after infection delays diagnosis, facilitating transmission. Public Health authorities in Porto have been performing a meritorious effort to identify individuals at higher risk of having contact with TB cases and of developing the disease. The approaches include a routine epidemiological investigation after a new case of TB is notified, where close contacts are identified and specific screening strategies are implemented for recognized individuals that are more vulnerable. However, recent results from the team, based on genetic analysis of Mycobacterium tuberculosis (Mtb) strains from 2014-15, revealed that the ongoing strategies are insufficient. In fact, a longer follow-up is necessary for a comprehensive definition of the transmission chains. In order to do this, 4 years of longitudinal analysis of Mtb strains in Porto will be added to the previous analysis. The Mtb isolates from all confirmed laboratory cases will be genotyped in-house using a certified platform and this genetic characterisation will be complemented with whole genome sequencing for particularly relevant strains. Making use of a novel analytic method, developed by team members, the cases will be integrated in an evolutionary network highlighting characteristics of the cases, such as risk factors. To further improve TB screening strategies a fast and simple diagnostic method will be developed based on mass spectrometry with a portable apparatus to detect TB using urine. To ameliorate the identification of individuals that are at higher risk, and that should follow specific screening programs, immunological markers of increased vulnerability will be investigated using mass cytometry in close collaboration with the Karolinska Institutet (KI), Sweden. This work will be conducted by a multidisciplinary team and aims to generate data on three pivotal aspects to improve current TB control strategies in Porto: 1) complete understanding of TB transmission chains; 2) determination of the exact role of the more vulnerable groups in active transmission and 3) improved diagnostic methods and susceptibility markers for early TB diagnosis and screening. The genetic (ICVS members) and the epidemiologic data (ISPUP) will be combined, using the bioinformatic platform developed by team members (ICVS) to dissect the transmission chains and the role of the more vulnerable groups. This will be complemented with the advances on the diagnostic method (CBQF member) and immunologic markers of increased susceptibility (ICVS and KI). Public health specialists (ISPUP members) will integrate all this information to suggest tuned strategies for TB control in Porto and potentially in other cities in Portugal and other urban areas in Europe.

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S. Queirós, “Right ventricular segmentation in multi-view cardiac MRI using a unified U-net model”, in E. Puyol Antón et al. (eds) Statistical Atlases and Computational Models of the Heart. Multi-Disease, Multi-View, and Multi-Center Right Ventricular Segmentation in Cardiac MRI Challenge. STACOM 2021. Lecture Notes in Computer Science, vol 13131, pp. 287-295, Springer, Cham, 2022.

“Best Paper Award in the M&Ms-2 Challenge”, by M&Ms2 Challenge organizers and the Medical Image Computing and Computer Assisted Intervention (MICCAI) Society.

Main Project Outcomes

Intra-urban variation in tuberculosis and community socioeconomic deprivation in Lisbon metropolitan area: a Bayesian approach. Oliveira O, Ribeiro AI, Duarte R, Correia-Neves M, Rito T. Infect Dis Poverty. 2022 Mar 24;11(1):24. doi: 10.1186/s40249-022-00949-1. PMID: 35321758

Evaluation of drug-resistant tuberculosis treatment outcome in Portugal, 2000-2016. Oliveira O, Gaio R, Correia-Neves M, Rito T, Duarte R. PLoS One. 2021 Apr 20;16(4):e0250028. doi: 10.1371/journal.pone.0250028. eCollection 2021. PMID: 33878119

Using Bayesian spatial models to map and to identify geographical hotspots of multidrug-resistant tuberculosis in Portugal between 2000 and 2016. Oliveira O, Ribeiro AI, Krainski ET, Rito T, Duarte R, Correia-Neves M. Sci Rep. 2020 Oct 6;10(1):16646. doi: 10.1038/s41598-020-73759-w. PMID: 33024245

A nationwide study of multidrug-resistant tuberculosis in Portugal 2014-2017 using epidemiological and molecular clustering analyses. Oliveira O, Gaio R, Carvalho C, Correia-Neves M, Duarte R, Rito T. BMC Infect Dis. 2019 Jul 1;19(1):567. doi: 10.1186/s12879-019-4189-7. PMID: 31262256