Diagnostic accuracy
How old is KwaZulu-Natal’s XDR tuberculosis outbreak strain?
Open access · cc by · source: Europe PMC
WGS of 337 KZN isolates plus 3 historical genomes dated LAM4 XDR’s isoniazid/streptomycin mutations to ~1957 and found INH resistance evolved before rifampicin 46 times vs 2 the other way.
Study at a glance
- Design
- Computational / modelling — Whole-genome sequencing, phylogenetic dating, and resistance-mutation ordering of KwaZulu-Natal M. tuberculosis isolates.
- N
- N=340 · 337 clinical isolates (2008–2013) plus 3 historical isolates (1994 pansusceptible/MDR; 2005 Tugela Ferry XDR).
- Population
- Mycobacterium tuberculosis isolates from patients in KwaZulu-Natal, South Africa, including the LAM4 Tugela Ferry XDR lineage.
- Outcome
- Timing and order of resistance-mutation acquisition, independent MDR/XDR emergences, and implications for rifampicin-only rapid tests.
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Key findings
A 50-member XDR clone matched Tugela Ferry. katG S315T and a gidB deletion dated to 1957 (HPD 1937–1971); MDR ~1984; XDR ~1995—before the local HIV explosion. MDR arose 56 times and XDR 9 times. INH before RIF 46:2. RIF-only rapid tests would miss that first INH step.
Methodology
Sequenced and drug-susceptibility tested 337 2008–2013 clinical isolates plus 1994/1995/2005 historical isolates, then used phylogeny and molecular clock dating to order resistance mutations and count independent MDR and XDR origins, especially in LAM4.
Limitations
Dating and mutation order in this provincial collection may not be universal; HIV still shapes today’s transmission even if mutations pre-dated the HIV boom.
How this study connects
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