How old is KwaZulu-Natal’s XDR tuberculosis outbreak strain?
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.
Source
Evolution of Extensively Drug-Resistant Tuberculosis over Four Decades: Whole Genome Sequencing and Dating Analysis of Mycobacterium tuberculosis Isolates from KwaZulu-Natal
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.
Structured fields used in claim comparison tables when every cited study has a complete layer.
What they did
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.
What they found
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.
The limits
What it doesn't show
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.
Key terms
- XDR-TB
- Extensively drug-resistant tuberculosis: MDR plus resistance to a fluoroquinolone and a second-line injectable.
- Tugela Ferry outbreak
- Largest described XDR-TB outbreak, identified in KwaZulu-Natal in 2005.
- LAM4
- Spoligotype lineage of the Tugela Ferry XDR clone sequenced here.
- katG S315T
- Canonical isoniazid-resistance mutation dated to ~1957 in this clone.
- RIF-only rapid diagnostics
- Tests that detect rifampicin resistance only and would miss earlier isoniazid resistance.
Flashcards
Research intelligence for this paper
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Quiz yourself
Clinical isolates sequenced (2008–2013) numbered:
Common questions
How many genomes?
337 clinical isolates plus three historical isolates.
When did INH/SM resistance arise in the outbreak clone?
About 1957 (50 years before Tugela Ferry).
How often did INH precede RIF?
46 times vs twice the reverse.
Why does order matter for diagnosis?
South African rapid tests that only call rifampicin would miss the usual first INH step.
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