WHO catalogue 2nd edition

[jodyphelan]

WHO catalogue

On the 15th of November 2023 the WHO released the second edition of their drug resistance catalogue (available here).

Using it with tb-profiler

I've got a few requests to ask if it is already available to use with tb-profiler and the answer is that it will be very soon! We're currently working on it and I hope to have it ready in early February.

Firstly, we are waiting for the data to be released with a minor change to make it easier to parse. Secondly, the new catalogue contains mutations as before but also includes expert rules that account interaction between mutations such as the epistatic effect between loss of function mutations mmpR5 (Rv0678) and mmpL5/mmpS5 for bedaquiline resistance. To enable this feature required a major overhaul of pathogen-profiler, the library that tb-profiler relies on.

In addition to adding this functionality we're also using the opportunity to improve documentation and code standard of tb-profiler and hope this will make it easier to implement and for developers to contribute to.

A note on Pretomanid

You might have noticed that resistance to pretomanid is not predicted. This is because the WHO has not yet set a critical concentration for pretomanid and was not included in their analysis. Specifically, the WHO states that:

WHO has not yet set a CC for PMD because of the different intrinsic susceptibility of different MTBC lineages; however, the issue should be settled in 2023 (17,18). Standard analysis for PMD was therefore not possible for the second edition. Irrespective of whether lineage 1 isolates (which have intrinsically higher PMD MICs than lineages 2, 3, 4 and 7) should be considered susceptible or not (17), there was sufficient evidence from several laboratories that LoF mutations in ddn, fbiA, fbiB, fbiC, fgd1 and Rv2983 confer cross-resistance to DLM and PMD and should, therefore, be interpreted as Group 2 interim resistance mutations for both DLM and PMD (Table 1) (84–87).

With pretomanid being an essential component of the BPaL regimen we will release an additional version of the catalogue that includes pretomanid resistance predictions using all the mechanisms described for delamanid.