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.
How this study connects
Role on claims
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Isoniazid resistance is common, comes first, and is invisible to a rifampicin-only test.
Tuberculosis resistance arises repeatedly and in a consistent order. Genome dating of an extensively drug-resistant clone placed founding katG S315T resistance around 1957, and in that collection multidrug resistance emerged 56 separate times with isoniazid resistance preceding rifampicin resistance 46 times to 2. Global surveillance of 211,753 patients found isoniazid-resistant, rifampicin-susceptible TB in 7.4% of new and 11.4% of previously treated patients, with katG 315 mutations in 78.6% of isoniazid-resistant isolates.
Evidence for the claim as stated.
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.
Inspect source passages
How old is KwaZulu-Natal’s XDR tuberculosis outbreak strain?
These passages occur verbatim in the stored paper text. They support the points listed below; they do not verify every statement in the explanation.
337 clinical isolates (2008–2013) plus three historical isolates were sequenced.
We performed whole genome sequencing and drug susceptibility testing on 337 clinical isolates of Mycobacterium tuberculosis collected in KwaZulu-Natal from 2008 to 2013, in addition to three historical isolates
INH/SM mutations in the clone dated to 1957 (HPD 1937–1971).
mutations conferring isoniazid and streptomycin resistance in this clone were acquired 50 y prior to the Tugela Ferry outbreak ( katG S315T [isoniazid]; gidB 130 bp deletion [streptomycin]; 1957 [95% highest posterior density (HPD): 1937–1971])
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.
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