Delineating the evolutionary pathway to multidrug-resistant outbreaks of a Mycobacterium tuberculosis L4.1.2.1/Haarlem sublineage.

Objectives: We sought to capture the evolutionary itinerary of the Mycobacterium tuberculosis L4.1.2.

On the onset and dispersal of a major MDR TB clone among HIV-negative patients, Tunisia.

Background: To carry out a whole genome sequencing (WGS)-based investigation on the emergence and spread of the largest multidrug-resistant tuberculosis (MDR TB) outbreak that has been thriving among HIV-negative patients, Tunisia, since the early 2000s.

Methods: We performed phylogeographic analyses and molecular dating based on a WGS dataset representing 68 unique Mycobacterium tuberculosis isolates, covering almost the entire MDR TB outbreak for the time period 2001-2016.

Results: The data indicate that the ancestor of the MDR TB outbreak emerged in the region of Bizerte, as early as 1974 (95% CI 1951-1985), from where it spread to other regions by 1992 (95% CI 1980-1996).

PHINDaccess Hackathons for COVID-19 and Host-Pathogen Interaction: Lessons Learned and Recommendations for Low- and Middle-Income Countries.

Hackathons are collaborative events that bring together diverse groups to solve predefined challenges. The COVID-19 pandemic caused by SARS-CoV-2 has emphasized the need for portable and reproducible genomics analysis pipelines to study the genetic susceptibility of the human host and investigate human-SARS-CoV-2 protein interactions. To build and strengthen institutional capacities in OMICS data analysis applied to host-pathogen interaction (HPI), the PHINDaccess project organized two hackathons in 2020 and 2021.

Genomic changes underpinning the emergence of a successful Latin American and Mediterranean clonal complex.

Introduction: The Latin American and Mediterranean sublineage (L4.3/LAM) is the most common generalist sublineage of lineage 4 (L4), yet certain L4.3/LAM genotypes appear to be confined to particular geographic regions.

Evolutionary history and spread of the Mycobacterium tuberculosis Latin American and Mediterranean (L4.3/LAM) sublineage, Tunisia.

Background: To infer the origin and spread of the Mycobacterium tuberculosis Latin American and Mediterranean (L4.3/LAM) sublineage in a Mediterranean country, Tunisia, where it predominates.

Methods: We combined Bayesian (STRUCTURE) and maximum likelihood (MIGRAINE) estimation approaches based on a global 24-loci mycobacterial interspersed repetitive units-variable numbers of tandem repeats (MIRU-VNTR24) genotyping dataset consisting of 1573 L4.

Successful expansion of Mycobacterium tuberculosis Latin American and Mediterranean sublineage (L4.3/LAM) in Tunisia mainly driven by a single, long-established clonal complex.

Objectives: To explore the evolutionary history of Mycobacterium tuberculosis Latin American and Mediterranean (L4.3/LAM) sublineage in Tunisia, where it predominates.

Methods: High-resolution genotyping of 252 L4.

Automated IS6110-based fingerprinting of Mycobacterium tuberculosis: Reaching unprecedented discriminatory power and versatility.

Background: Several technical hurdles and limitations have restricted the use of IS6110 restriction fragment length polymorphism (IS6110 RFLP), the most effective typing method for detecting recent tuberculosis (TB) transmission events. This has prompted us to conceive an alternative modality, IS6110-5'3'FP, a plasmid-based cloning approach coupled to a single PCR amplification of differentially labeled 5' and 3' IS6110 polymorphic ends and their automated fractionation on a capillary sequencer. The potential of IS6110-5'3'FP to be used as an alternative to IS6110 RFLP has been previously demonstrated, yet further technical improvements are still required for optimal discriminatory power and versatility.

MDR-TB Outbreak among HIV-Negative Tunisian Patients followed during 11 Years.

Background: Multidrug-resistant tuberculosis (MDR-TB) outbreaks that evolve, from the outset, in a context strictly negative for HIV infection deserve special consideration since they reflect the true intrinsic epidemic potential of the causative strain. To our knowledge, the long-term evolution of such exceptional outbreaks and the treatment outcomes for the involved patients has never been reported hitherto. Here we provide a thorough description, over an 11-year period, of an MDR-TB outbreak that emerged and expanded in an HIV-negative context, Northern Tunisia.