Evidence map›Paper›PMID 41391587›Full record

ArticleJournal of global antimicrobial resistance2026

Undetected rifampicin-resistant tuberculosis associated with rpoB I491F and V170F mutations in Botswana: Diagnostic implications.

Tuelo Mogashoa, Justice T Ngom, Johannes Loubser, Kedumetse Seru, Tuduetso Molefi, One Stephen, Rosemary M Musonda, Simani Gaseitsiwe, Robin M Warren, Anzaan Dippenaar and 2 more

Abstract read
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In one paragraph

Article in Journal of global antimicrobial resistance, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Tuelo MogashoaResearch Laboratory, Botswana Harvard Health Partnership, Gaborone, Botswana; South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa. Electronic address: tuelomogashoa@me.com.
Justice T NgomSouth African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Johannes LoubserSouth African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Kedumetse SeruResearch Laboratory, Botswana Harvard Health Partnership, Gaborone, Botswana.
Tuduetso MolefiMinistry of Health, Botswana National Tuberculosis Program, Gaborone, Botswana.
One StephenBotswana National Tuberculosis Reference Laboratory, Gaborone, Botswana.
Rosemary M MusondaResearch Laboratory, Botswana Harvard Health Partnership, Gaborone, Botswana.
Simani GaseitsiweResearch Laboratory, Botswana Harvard Health Partnership, Gaborone, Botswana.
Robin M WarrenSouth African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Anzaan DippenaarUniversity of Antwerp, Family Medicine and Population Health, Antwerp, Belgium.
Elizabeth M StreicherSouth African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Sikhulile MoyoResearch Laboratory, Botswana Harvard Health Partnership, Gaborone, Botswana; University of Botswana, Department of Medical Sciences, Gaborone, Botswana; Department of Pathology, Division of Medical Virology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; School of Health Systems and Public Health, University of Pretoria, Pretoria, South Africa; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Funding

Viral Diversity an Innovative Biomarker for Refining Estimates of HIV IncidenceK43TW012350 · FIC · THE BOTSWANA HARVARD HEALTH PARTNERSHIP · PI Sikhulile Moyo · 2022 to 2026
$682k
FIC NIH HHS K43 TW012350
6 · The paper itself

Abstract

backgroundUndetected rifampicin resistance is a threat to global tuberculosis (TB) control efforts by delaying effective treatment. In different studies, non-canonical rpoB mutations outside the rifampicin resistance-determining region have been reported at varying prevalences by country. Here, we report cases of rifampicin resistance in Botswana that were missed by the routine molecular diagnostic assays.

methodsIndividuals were tested under routine programme conditions, in accordance with national guidelines, at four designated drug-resistant TB clinics from 2017 to 2022. Initial testing at the facilities included GeneXpert MTB/RIF ultra and later phenotypic drug susceptibility testing (pDST), as well as the Hain MTBDRsl line probe assay, at the National Tuberculosis Reference Laboratory. A total of nine isolates were subsequently sequenced on the Illumina NextSeq 2000 instrument.

resultsAt the point of care, routine molecular tests classified all nine individuals as susceptible to rifampicin. Subsequent culture and phenotypic drug susceptibility testing confirmed rifampicin resistance. Whole-genome sequencing identified non-canonical rpoB mutations outside the rifampicin resistance-determining region I49F and V170F, which are associated with low-level rifampicin resistance. Of the nine isolates sequenced, 4 (44%) harboured the rpoB V170F mutation, while 5 (56%) harboured the rpoB I491F mutation.

conclusionsThese results highlight a diagnostic gap within the current algorithms and show the value of sequencing-based approaches for accurately detecting drug resistance. Incorporating sequencing into routine clinical practice could help guide the selection of TB treatment and improve treatment outcomes in patients who do not respond to first-line therapy.

Indexed as

Antitubercular AgentsBacterial ProteinsDNA-Directed RNA PolymerasesDrug Resistance, BacterialMycobacterium tuberculosisRifampinTuberculosis, Multidrug-ResistantAdultAntibiotics, AntitubercularBotswanaFemaleHumansMaleMicrobial Sensitivity TestsMiddle AgedMutationAntibiotics, AntitubercularAntitubercular AgentsBacterial ProteinsDNA-Directed RNA PolymerasesRifampinrpoB protein, Mycobacterium tuberculosisBotswanaMycobacterium tuberculosisrifampicin-resistancerpoBI491FrpoBV170Fwhole-genome sequencing

Identifiers

PMID41391587
PMCPMC13329411

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.