Neither outcome had a significant annual difference or linear trend across the study period. The study, published in BMC Infectious Diseases , examined laboratory records generated from January 2020 through December 2024. The investigators used descriptive statistics and logistic regression to assess MTB detection, rifampicin resistance and associated factors.

Chi-square tests evaluated annual proportions, while continuous-year logistic regression assessed whether calendar year was associated with either outcome. A case-mix-adjusted sensitivity analysis examined temporal changes in MTB detection after accounting for age, sex, previous TB treatment, specimen type and referring facility. Firth-penalized logistic regression was used to assess the robustness of associations with rifampicin resistance in the presence of sparse resistant cases.

The records represented a hospital testing population rather than a population-based sample, so the results describe facility-level testing patterns and cannot directly establish trends in community TB incidence or drug resistance. Calendar year was not significantly associated with MTB detection in the continuous-year model. The estimated odds ratio was 1.007 per year, with a 95% confidence interval of 0.946 to 1.071.

Year was likewise not significantly associated with rifampicin resistance, for which the odds ratio was 1.089 and the 95% confidence interval was 0.848 to 1.399. Adjustment for the measured case-mix factors did not change the finding for MTB detection: the adjusted odds ratio per year was 1.025, with a 95% confidence interval of 0.957 to 1.097 and a p value of 0.481. The lack of a statistically detectable trend does not demonstrate that the underlying burden or resistance level remained constant.

Previous TB treatment had strong associations with both outcomes in the adjusted analyses. Compared with people without a reported history of prior TB treatment, those previously treated had an adjusted odds ratio of 13.99 for MTB detection, with a 95% confidence interval of 7.85 to 24.95. For rifampicin resistance, the corresponding adjusted odds ratio was 49.72, with a 95% confidence interval of 18.60 to 132.90.

These retrospective estimates represent associations among the tested records rather than causal effects or direct measures of individual risk. Male sex was also associated with rifampicin resistance, with an adjusted odds ratio of 4.59 and a 95% confidence interval of 1.32 to 16.00. HIV positivity was associated with MTB detection in univariable analysis, yielding a crude odds ratio of 7.03 and a 95% confidence interval of 1.99 to 24.77, but extensive missing HIV data constrained the interpretation of that result.

Only 28 rifampicin-resistance events were identified, contributing to wide confidence intervals, particularly for the association between previous TB treatment and resistance. The findings are also limited to one hospital, its recorded testing population and the five-year period from 2020 through 2024. A null temporal association in these records does not establish the absence of trends in other settings or at other times.

Overall, the analysis identified MTB in approximately one in nine tested records and rifampicin resistance in 5.6% of MTB-detected records with determinate results. Previous TB treatment was the factor most strongly associated with both outcomes, while the study detected no significant year-to-year shift in either MTB detection or Xpert-detected rifampicin resistance during the study period.

Subject of Research: Temporal patterns in tuberculosis detection and rifampicin resistance among Xpert-tested records at a northeastern Ethiopian hospital

Article Title: Trends in Mycobacterium tuberculosis detection and rifampicin resistance using Xpert MTB/RIF assay at Woldia comprehensive specialized hospital, Northeastern Ethiopia: a 5-year retrospective study

Article References: Tamrat, E., Kassanew, B., Mollaw, N. G., Girma, T., Asfaw, T., Habtamu, T., Jemal, A., Gashaw, M., Bazezew, A., Damtie, A. A., Gedfie, S., Gashaw, Y., Asmare, Z., Biset, S., & Reta, M. A. (2026). Trends in Mycobacterium tuberculosis detection and rifampicin resistance using Xpert MTB/RIF assay at Woldia comprehensive specialized hospital, Northeastern Ethiopia: a 5-year retrospective study. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14670-z

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14670-z

Keywords: tuberculosis, rifampicin resistance, Xpert MTB/RIF, Ethiopia, retrospective study, hospital records, Mycobacterium tuberculosis, diagnostic testing, Trends, Mycobacterium, detection, rifampicin

The research team, led by João Paulo Cola and Thiago Nascimento do Prado and spanning institutions including the State Department of Health of Espírito Santo, the Federal University of Espírito Santo, the Federal University of Rio de Janeiro, and the Oswaldo Cruz Institute, analyzed notifications recorded in Brazil’s national tuberculosis database between 2018 and 2023. Their focus was a cohort of children and young adolescents aged 0 to 15 years who had been prescribed tuberculosis preventive treatment, commonly abbreviated TPT. Out of 31,121 notified cases, 24,903 carried complete outcome information — a substantial analytical sample that allowed the investigators to model completion patterns with statistical rigor using a robust variance Poisson regression approach, reporting relative risks with 95 percent confidence intervals.

The headline finding is both encouraging and sobering. Completion rates were modestly higher among children aged 5 to 9 years, with a relative risk of 1.02 (95 percent CI 1.01–1.04), and among adolescents aged 10 to 15, with a relative risk of 1.03 (95 percent CI 1.02–1.05). Children of white skin color showed slightly higher completion (RR 1.02; 95 percent CI 1.01–1.03), as did those vaccinated with BCG (RR 1.05; 95 percent CI 1.02–1.08) and those using immunosuppressive therapy (RR 1.07; 95 percent CI 1.03–1.19). But the strongest signals belonged to the treatment regimens themselves: shorter courses of four months of rifampicin (RR 1.10; 95 percent CI 1.08–1.12) and three months of isoniazid plus rifapentine (RR 1.13; 95 percent CI 1.12–1.15) were associated with meaningfully better completion than the traditional long-course alternatives.

To appreciate why these numbers matter, it helps to understand the pharmacological landscape of preventive therapy. For decades, the global standard for treating latent tuberculosis infection has been six to nine months of daily isoniazid — regimens designated 6H and 9H in the study’s nomenclature, involving 180 to 270 doses taken over six to twelve months. Adherence to such prolonged schedules is notoriously difficult for anyone, let alone a toddler or a teenager juggling school, family dynamics, and the general impatience of youth. Each additional month of daily pills multiplies the opportunities for missed doses, side effects, caregiver fatigue, and eventual dropout. The alternative regimens examined in this study flip that equation: 4R consists of 120 doses of rifampicin taken over four to six months, while 3HP — the regimen combining rifapentine with isoniazid — requires only 12 weekly doses administered over 12 to 15 weeks. The 3HP scheme, in particular, represents a paradigm shift, compressing what was once nearly a year of daily compliance into roughly three months of weekly visits.

The Brazilian health system context amplifies the significance of these findings. Brazil’s Unified Health System, known locally as SUS, provides tuberculosis care free of charge across a vast and geographically diverse country, and the national surveillance infrastructure — including the Information System for Notification of People on Tuberculosis Preventive Treatment, or IL-TB — captures granular data on who is prescribed preventive therapy and how their courses conclude. This study leveraged that infrastructure to assemble one of the most comprehensive pictures to date of pediatric preventive treatment in a high-burden, middle-income setting. The cohort period, 2018 to 2023, also straddles an important policy transition: the gradual introduction of shorter regimens, including 3HP, into Brazilian clinical practice following World Health Organization recommendations.

Notably, the association between 3HP and completion held even after the researchers adjusted for demographic and clinical confounders in their multivariate model. A relative risk of 1.13 may sound incremental, but when applied across tens of thousands of treatment courses, it translates into thousands of additional children who finish therapy and thereby gain durable protection against future active disease. The 4-month rifampicin regimen showed a similar magnitude of benefit at RR 1.10. These effect sizes are consistent with the broader international literature, which has repeatedly demonstrated that shorter preventive regimens outperform longer ones on adherence, though direct comparisons across health systems are complicated by differences in drug availability, cost, and clinical guidelines.

One of the more intriguing findings concerns the youngest children. Those under 5 years of age did not show the modest completion advantage observed in older age bands — and this matters enormously from a public health standpoint, because children under 5 who are household contacts of infectious tuberculosis cases face the highest risks of rapid progression from infection to severe, disseminated disease such as tuberculous meningitis. Pediatric guidelines therefore prioritize this age group for preventive treatment, often without requiring confirmation of infection through a tuberculin skin test or interferon gamma release assay. Yet the very factors that make young children a priority — their dependence on caregivers for every dose, the challenges of administering medications formulated for adults, and the frequency of intercurrent childhood illnesses that interrupt treatment — also make them the most vulnerable to incomplete courses. The study’s authors conclude that targeted strategies to improve adherence among children younger than 5 years may be essential to enhancing overall completion in Brazil.

The associations with BCG vaccination status and skin color deserve careful interpretation. The finding that BCG-vaccinated children showed higher completion (RR 1.05) likely reflects underlying differences in healthcare access and surveillance rather than any direct pharmacological effect of the vaccine on adherence. Similarly, the modest completion advantage among children recorded as having white skin color (RR 1.02) echoes well-documented patterns of health inequity in Brazil, where structural factors — including socioeconomic status, geographic proximity to clinics, and the quality of patient-provider interactions — shape treatment trajectories long before a prescription is written. The researchers were careful to characterize these associations as modest, and the confidence intervals, while statistically significant, indicate effects that are real but small in absolute terms. The clinical and policy implications therefore hinge less on any single demographic factor and more on the systemic levers — regimen choice above all — that can be pulled at scale.

The finding that children on immunosuppressive therapy showed higher completion (RR 1.07; 95 percent CI 1.03–1.19) is also worth unpacking. These are children whose underlying conditions — perhaps autoimmune diseases, oncologic diagnoses, or pre-transplant preparation — require medications that dampen the immune system, dramatically raising the stakes of untreated latent tuberculosis infection, which can reactivate catastrophically under immunosuppression. In such cases, families and clinicians alike have powerful, immediate motivations to see preventive therapy through to completion, and the data suggest that this heightened vigilance translates into measurable adherence gains. It is a reminder that perceived risk is one of the strongest drivers of health behavior, and that communicating the seriousness of latent infection to families of otherwise healthy children remains an ongoing challenge.

As the world pursues the End TB Strategy’s goals of drastic reductions in tuberculosis incidence and mortality, the study’s message is clear: the tools to prevent disease in children already exist, and the frontier now lies in delivery. Shorter regimens like 3HP and 4-month rifampicin offer a pharmacological shortcut to adherence, but their impact will be realized only if health systems can reliably identify eligible children, initiate treatment promptly after exposure, and support families through the full course. Brazil’s experience, documented across more than 31,000 pediatric notifications over six years, provides both a warning — that the youngest and most vulnerable remain the hardest to reach with complete preventive courses — and a roadmap, showing that regimen simplification is among the most effective levers available. For a disease that has coexisted with humanity for millennia, the quiet arithmetic of pill counts and completed courses may prove as consequential as any laboratory breakthrough.

Subject of Research: Completion of tuberculosis preventive treatment among children and adolescents aged 0 to 15 years in Brazil

Article Title: Completion of tuberculosis preventive treatment in children and adolescents aged 0 to 15 in Brazil: analysis of a retrospective cohort

Article References: Cola, J. P., da Conceição Costa, L., de Souza, F. M., Caetano, C. L., dos Santos, G. S., Sales, C. M. M., Carvalho, A. C. C., Maciel, E. L. N., & do Prado, T. N. (2026). Completion of tuberculosis preventive treatment in children and adolescents aged 0 to 15 in Brazil: analysis of a retrospective cohort. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14204-7

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14204-7

Keywords: tuberculosis, preventive treatment, children, adolescents, Brazil, 3HP regimen, isoniazid, rifapentine, rifampicin, treatment adherence, public health, BMC Infectious Diseases

The finding matters because the diagnostic backbone of tuberculosis control in high-burden countries is built around rifampicin. Rapid molecular tests such as Xpert MTB/RIF detect mutations in the rpoB gene that confer rifampicin resistance, and a rifampicin-susceptible result is generally treated as a green light for standard first-line therapy. When isoniazid resistance flies under that radar, patients may receive regimens that are partially ineffective, promoting treatment failure, relapse, and the further accumulation of resistance mutations. The study’s authors argue that the predominance of Hr-TB in western Kenya means rifampicin-based diagnostics risk systematically under-detecting a substantial share of drug-resistant disease.

To look beneath the surface of routine testing, the team selected an enriched subset of 316 isolates for whole-genome sequencing, of which 290 yielded high-quality genomes. The sequencing workflow was technically thorough: genomic DNA was extracted with a modified cetyltrimethylammonium bromide method optimized for the tough mycobacterial cell wall, libraries were prepared with the NEBNext Ultra II FS kit, and paired-end 2 by 150 base pair reads were generated on the Element AVITI platform. Bioinformatic processing used the DuffyNGS pipeline, aligning reads to the H37Rv reference genome with Bowtie2 and calling variants with Samtools and BCFtools, while TBProfiler annotated resistance determinants against the World Health Organization mutation catalogue, version 2.

The genomic data confirmed the classical resistance mechanisms. Rifampicin resistance was driven mainly by the rpoB S450L substitution, the canonical mutation in the RNA polymerase gene that most molecular assays are designed to catch. Isoniazid resistance was dominated by katG S315T, which disables the catalase-peroxidase that activates the drug, together with mutations in the inhA promoter, including the -15 C>T and -8 T>A variants, which alter expression of the enzyme targeted by both isoniazid and ethionamide. Pyrazinamide resistance mapped largely to pncA mutations such as L172P, ethambutol resistance to embB M306V, streptomycin resistance to rpsL K43R, and fluoroquinolone resistance to gyrA mutations. Notably, no resistance-conferring mutations were found for newer or repurposed agents such as bedaquiline and clofazimine, and all isolates were genotypically susceptible to the injectables amikacin and kanamycin.

Among the 290 sequenced isolates, whole-genome sequencing identified resistance-associated mutations in 43 cases, or 14.8 percent. Within this enriched subset, Hr-TB was again the most frequent resistance class at 16 isolates, followed by rifampicin-resistant tuberculosis at 11 and multidrug-resistant tuberculosis at 9, with three isolates classified as pre-extensively drug-resistant based on fluoroquinolone resistance mutations layered onto multidrug resistance. The sequenced population skewed male, at 72 percent, with a median age of 34 years, and 36 percent of patients were living with HIV, reflecting the heavy HIV-TB co-infection burden of the region.

Geographically, the study revealed striking heterogeneity. Resistant isolates clustered heavily in the Lake Victoria basin, with the highest counts in Kisii, Homa Bay, Migori, and Siaya counties, while Bomet and Bungoma contributed none. Kisii alone accounted for 12 of the 43 WGS-detected resistant isolates, or 27.9 percent. The authors suggest this concentration points to localized transmission or shared epidemiologic drivers within the basin, and they emphasize that such county-level variation argues for granular, local genomic surveillance rather than reliance on national averages that can mask hotspots.

The genetic population structure of the isolates was diverse. Susceptible isolates were spread across Lineage 4, the globally distributed Euro-American lineage, at about 40 percent, Lineage 3, common in East Africa and South Asia, at about 38 percent, and Lineage 2 at about 21 percent, with a single Mycobacterium bovis isolate also identified, a reminder of potential zoonotic transmission through cattle or unpasteurized dairy. Among resistant isolates, Lineage 4 and Lineage 3 predominated, though no statistically significant association between lineage and resistance emerged, suggesting that drug resistance is arising across multiple co-circulating strain populations rather than within one dominant clone. Resistance appeared particularly prominent within sub-lineages 4.3.3 and 4.6.1.2, although the authors caution that small sample sizes make some sub-lineage estimates unstable.

The most consequential result, however, was the discordance between routine testing and sequencing. Routine methods, either line probe assays or phenotypic drug susceptibility testing in liquid culture, flagged 56 isolates as resistant, while WGS called only 43 resistant. Concordant resistance was seen in 35 isolates, but 21 isolates were resistant by routine testing yet genomically susceptible, and 8 were resistant by WGS yet susceptible or untested by routine methods. A McNemar’s test with continuity correction confirmed the difference was statistically significant, with p equal to 0.026. Critically, re-evaluation against the WHO catalogue showed that 18 of the 21 routine-positive, WGS-negative cases carried mutations classified as being of uncertain significance, meaning the global reference database simply cannot yet interpret them confidently.

This discordance cuts both ways and exposes the limits of each method. For drugs such as pyrazinamide and ethambutol, resistance mechanisms are incompletely defined, and phenotypic testing itself suffers from technical variability in critical concentrations and pH sensitivity. Biological factors such as heteroresistance, transient efflux pump activity, and altered cell wall permeability can produce phenotypic resistance without any detectable resistance mutation, and culture-based sequencing may itself select subpopulations that do not represent the full within-host diversity. Conversely, the eight WGS-positive, routine-negative isolates included genuine discordant cases involving rifampicin, isoniazid, fluoroquinolones, and capreomycin, plus two streptomycin resistance mutations that routine testing had never evaluated, showing that sequencing can also catch resistance that conventional workflows miss.

The authors conclude that whole-genome sequencing and phenotypic testing should operate as complementary tools rather than competitors, with sequencing providing genome-wide, high-resolution mutation detection while phenotypic assays confirm resistance where genomic interpretation remains uncertain. Their recommendations are concrete: integrate WGS into Kenya’s national tuberculosis surveillance, beginning at central reference laboratories, and prioritize better detection of isoniazid resistance given the prominence of Hr-TB. They also stress that continued generation of local genomic and phenotypic data from high-burden settings is essential for refining the global mutation catalogues on which genomic resistance prediction depends. The study’s limitations, including its retrospective design, referral-laboratory sampling that enriches for resistant cases, and the absence of SNP-based transmission clustering, mean the proportions reported describe the study population rather than true regional prevalence. Even so, the message is clear: in western Kenya, a hidden epidemic of isoniazid resistance is circulating beneath a rifampicin-focused diagnostic screen, and closing that gap will require both wider sequencing capacity and a more complete global map of what tuberculosis resistance mutations actually mean.

Subject of Research: Genomic surveillance of drug-resistant Mycobacterium tuberculosis in western Kenya

Article Title: Genomic characterization of drug-resistant Mycobacterium tuberculosis complex in western Kenya reveals predominance of isoniazid resistance and discordance with routine susceptibility testing

Article References: Musau, S., Odera, S., Musyoki, V. M., Lamont, E. I., Onyango, N., Morrison, B., Murithi, W., Wandiga, S., Nduba, V., Sherman, D., & Mureithi, M. W. (2026). Genomic characterization of drug-resistant Mycobacterium tuberculosis complex in western Kenya reveals predominance of isoniazid resistance and discordance with routine susceptibility testing. Frontiers in Tuberculosis, 4, Article 1855780. https://doi.org/10.3389/ftubr.2026.1855780

Image Credits: AI Generated

DOI: 10.3389/ftubr.2026.1855780

Keywords: tuberculosis, whole-genome sequencing, drug resistance, isoniazid, rifampicin, Mycobacterium tuberculosis, Kenya, Hr-TB, diagnostics, WHO mutation catalogue, genomic surveillance, line probe assay

The scale of the problem is considerable. Globally, an estimated 13 percent of deaths attributed to antimicrobial resistance are due to drug-resistant tuberculosis, much of which remains undetected. In 2024, roughly 390,000 people were estimated to have developed rifampicin-resistant or multidrug-resistant TB, defined as resistance to both rifampicin and isoniazid, the two most critical first-line anti-TB drugs. Missed or erroneous detection of resistance creates gaps in surveillance and can lead to mismanagement of treatment, perpetuating transmission and driving the epidemic.

For decades, culture-based phenotypic drug susceptibility testing has been considered the gold standard for detecting resistance, but the method has known limitations, including inaccuracy in detecting particular cases of resistance to rifampicin. Genotypic tests, such as the Xpert MTB/RIF assay and line probe assays, have accelerated the turnaround time for confirming drug-resistant TB, but they interrogate only narrow regions within a limited number of resistance-associated genes. Sequencing-based detection offers a more comprehensive approach and is included in global guidance for programmatic implementation, yet practical barriers related to cost, laboratory infrastructure, and technical expertise have hindered adoption in many high-burden countries.

Nigeria, a high HIV/TB and multidrug-resistant TB burden country, prioritized addressing DR-TB in its National Strategic Plan for 2021 to 2025. Under the leadership of the National Tuberculosis and Leprosy Control Programme, and with support from the U.S. Centers for Disease Control and Prevention, the country established its first sequencing model for DR-TB surveillance in 2022. The approach deliberately leveraged sequencing laboratories previously established for HIV drug-resistance monitoring, integrating services for these pathogens for the first time and demonstrating how limited resources can be stretched through a multi-disease platform.

The technical workflow began at zonal and national TB reference laboratories, where clinical sputum specimens from health facilities across the country are routinely subjected to genotypic tests. Drug-resistant isolates are then referred for phenotypic testing using the automated BACTEC MGIT 960 system. For the sequencing pilot, 49 Mycobacterium tuberculosis isolates previously identified as resistant to rifampicin and/or isoniazid were selected proportionately across all six geopolitical zones. Mycobacterial cultures were inactivated using heat at 95 degrees Celsius for 20 minutes and ultrasonication for 15 minutes, and genomic DNA was extracted on site before being shipped through a courier-based referral pathway to sequencing laboratories, where quality and quantity were assessed using spectrophotometry and fluorometry.

Rather than sequencing whole genomes, the team designed a targeted Sanger sequencing algorithm covering eight genomic regions associated with resistance to six anti-TB drugs, a strategy intended to maximize programmatic value while keeping costs manageable. The rpoB gene, linked to rifampicin resistance, was sequenced for all isolates to confirm results or identify resistance missed by other tests. Rv0678 and atpE, associated with resistance to the newer drugs bedaquiline and clofazimine, were also sequenced for all isolates. Genes including gyrA, gyrB, katG, the inhA promoter, and rrs were sequenced conditionally, only for isolates determined to be susceptible to the corresponding drug classes, in order to detect mutations not targeted by line probe assays. Identified mutations were cross-referenced with the World Health Organization’s global catalogue of resistance-associated mutations.

Implementation proceeded in four phases over two years: planning, validation of the new method, rollout, and data analysis for programmatic use. Laboratory staff received training, standard operating procedures were developed, and sequencing-specific quality control measures and performance indicators were established. Validation was successful at all participating laboratories, which exceeded established acceptance criteria. Of the 49 isolates selected, genomic DNA suitable for sequencing was extracted from 96 percent, adherence to the sequencing algorithm reached 100 percent, and high-quality results were obtained for 623 of 642 sequencing reactions, or 97 percent.

The results demonstrated the added value of sequencing in striking terms. While sequencing largely confirmed resistance reported by routine tests, it identified additional rifampicin resistance in 5 of 47 isolates, or 11 percent, and additional isoniazid resistance in 1 isolate, or 2 percent, that had been missed by phenotypic or genotypic testing. Discordance between the two routine methods was also notable, observed for rifampicin in 9 percent of isolates, isoniazid in 15 percent, fluoroquinolones in 9 percent, and second-line injectables in 6 percent. In several cases, sequencing settled these disagreements, confirming rpoB mutations that one method had detected and the other had not.

Particularly significant were nine borderline mutations in rpoB associated with low-level rifampicin resistance, identified in isolates from all geopolitical zones. Phenotypic testing can fail to detect these clinically relevant variants, which may fuel transmission of resistance if left undiagnosed. The study found that phenotypic testing missed rifampicin resistance in two isolates with confirmed borderline mutations, L452P and L430P, findings consistent with comparative studies from other high-burden settings. The analysis also revealed the limits of automated bioinformatics software: one potential instance of rifampicin heteroresistance, indicated by a double chromatogram peak, and a unique insertion mutation in rpoB were missed by automated tools, which are often restricted to a database of defined mutations.

Not every result favored sequencing. No additional resistance was detected in genes associated with fluoroquinolone or second-line injectable resistance among isolates deemed susceptible by routine tests, and no mutations were found in Rv0678 or atpE even among the small number of isolates phenotypically resistant to bedaquiline or clofazimine, underscoring that phenotypic testing remains essential for newer drugs whose resistance mechanisms are not yet fully understood. The authors also acknowledge limitations, including the small sample size and algorithm constraints that restrict generalizability, and the inability to repeat phenotypic testing due to resource restrictions.

Following the analysis, the National Tuberculosis and Leprosy Control Programme convened a stakeholder meeting to review lessons learned and chart the path forward. Leveraging existing laboratory infrastructure and workforce expertise, along with the targeted algorithm design, supported cost-effective implementation. Building on the pilot’s success, the program is now transitioning from Sanger sequencing at HIV laboratories to targeted next-generation sequencing at the Nigeria Centre for Disease Control and Prevention’s multi-disease testing laboratory. Next-generation sequencing offers higher throughput and improved sensitivity for detecting heteroresistance at lower frequencies, and commercially available end-to-end solutions with automated bioinformatic pipelines may expand uptake. The work demonstrates feasibility and provides a practical model for operationalizing DR-TB sequencing in a national program setting, offering an example for other high-burden countries seeking to strengthen genomic surveillance, improve drug selection and treatment for TB patients, and guide testing policies as new treatment regimens are scaled up.

Subject of Research: Implementation of DNA sequencing-based surveillance for drug-resistant tuberculosis in Nigeria

Article Title: Implementation of sequencing-based surveillance for drug-resistant tuberculosis in Nigeria

Article References: McLaughlin, H. P., Audu, I., Tola, M., Onwuamah, C. K., Ogwu, J., Atoe, K., Kunle-Ope, C. N., Ahmadu, I., Gowon, J., Meshak, D. B., Iwakun, M., Ude, C. E., Abiona, M., Momoh, A. E., Ore, T., Ogbu, C. A., Abiodun, T. A., Dawson, J., Hall-Eidson, P., … Chukwuma, A. (2026). Implementation of sequencing-based surveillance for drug-resistant tuberculosis in Nigeria. Frontiers in Tuberculosis, 4, Article 1855903. https://doi.org/10.3389/ftubr.2026.1855903

Image Credits: AI Generated

DOI: 10.3389/ftubr.2026.1855903

Keywords: tuberculosis, drug resistance, genomic surveillance, Sanger sequencing, Nigeria, Mycobacterium tuberculosis, rifampicin, isoniazid, drug susceptibility testing, next-generation sequencing, public health, antimicrobial resistance

The trial, known as SHARP, was an open-label, individually randomized controlled study in which participants with PCR-confirmed Buruli ulcer were assigned in equal proportions to one of two oral regimens. The experimental arm received rifampicin at 20 milligrams per kilogram of body weight together with clarithromycin at 15 milligrams per kilogram for four weeks, while the control arm received the conventional rifampicin dose of 10 milligrams per kilogram with the same clarithromycin dose for eight weeks. All participants, regardless of assignment, had their wounds managed with dressings coated with dialkylcarbamoyl chloride, a synthetic material designed to bind and remove bacteria and debris from the wound bed, ensuring that any differences in outcome could be attributed to the antibiotic regimens rather than wound care.

The primary endpoint was deliberately microbiological rather than purely clinical: the time until viable M. ulcerans could no longer be detected, assessed using quantitative PCR targeting the 16S ribosomal RNA gene, with sampling continuing up to week 20. This choice reflects a key challenge in Buruli ulcer research. Because M. ulcerans grows extremely slowly in culture, conventional culture-based confirmation of clearance can take months, whereas molecular assays provide a faster and more standardized readout of bacterial burden. The researchers reasoned that if a shorter high-dose regimen could sterilize lesions as quickly as, or faster than, the standard course, it would open the door to a fundamentally more practical treatment.

Between late November 2021 and the end of July 2024, the team randomized 42 participants, 23 to the high-dose short-course arm and 19 to the standard arm. That number fell well short of the 112 participants the trial had been designed to enroll, a shortfall that shaped the statistical power of the study and, ultimately, the confidence that can be placed in its conclusions. Recruitment difficulties in trials of neglected tropical diseases are common, driven by factors ranging from seasonal patterns of disease presentation to the logistical burdens of follow-up in rural communities, and the SHARP investigators were transparent about the implications of their smaller-than-planned sample.

On the primary outcome, the mean time to clearance of viable M. ulcerans was 4.9 weeks in the high-dose arm, compared with 7.0 weeks in the standard-dose arm. At first glance, that difference of roughly two weeks appears meaningful, suggesting that the more intensive regimen was pushing the bacteria toward elimination faster. But when the investigators adjusted their analysis, the estimated mean difference shrank to just 0.5 weeks in favor of the short course, with a 95 percent confidence interval stretching from 5.0 weeks faster to 4.1 weeks slower and a p-value of 0.835. In plain terms, the data were entirely compatible with there being no real difference in microbiological clearance time between the two strategies.

Yet the trial was not without signals of potential advantage for the shorter regimen. Paradoxical reactions, a well-recognized phenomenon in Buruli ulcer in which lesions paradoxically enlarge or new inflammatory lesions emerge after treatment begins, even as the bacteria themselves are killed, occurred in none of the 21 participants assessed in the high-dose arm, compared with 5 of 15 in the standard-dose arm. The adjusted odds ratio of 0.19, with a confidence interval that included the null value and a p-value of 0.102, means this difference could plausibly have arisen by chance, particularly given the small numbers involved. Still, the complete absence of paradoxical reactions in the intensive arm is an intriguing observation that deserves scrutiny in larger studies, because such reactions can prolong morbidity, complicate wound management and sometimes require corticosteroid treatment.

Safety and tolerability emerged as reassuring themes. The high-dose rifampicin regimen was well tolerated in this population, with rates of secondary wound infection similar between the two groups. This matters because rifampicin dosing at 20 milligrams per kilogram, double the conventional dose, raises theoretical concerns about hepatotoxicity and other adverse effects, and the trial provides early human evidence that short-course intensive dosing is feasible in a Buruli ulcer population. No recurrences of disease were observed in either arm during follow-up, an important finding given that relapse, though uncommon, is the feared late failure mode of antibiotic therapy for this infection.

The authors’ conclusion was measured: the trial did not find evidence of a significantly shorter time to microbiological clearance or healing with the high-dose short-course approach, and larger trials are needed to determine its efficacy and safety. That caution is scientifically appropriate. With only 42 randomized participants, the study was underpowered to detect the kind of modest differences that could still be clinically important. A two-week reduction in clearance time, if real, could translate into meaningful savings in clinic visits and reduced disruption for patients, but the confidence interval in this trial cannot rule out either a substantial benefit or a modest disadvantage for the shorter regimen.

The broader context makes the question urgent. Buruli ulcer, one of the WHO-listed neglected tropical diseases, predominantly affects children in rural West and Central Africa, where M. ulcerans is thought to be transmitted through contact with contaminated aquatic environments, although the exact mode of transmission remains debated. Since the shift from surgical excision to antibiotic therapy in the mid-2000s, the standard regimen has been eight weeks of daily rifampicin and streptomycin, later adapted in many settings to fully oral combinations such as rifampicin with clarithromycin to avoid the injections and associated complications of aminoglycosides. Eight weeks of daily medication, wound dressings and clinic attendance imposes a heavy burden on families who may travel long distances and sacrifice income and schooling, so every week that can safely be removed from the regimen carries real economic and social value.

The SHARP trial thus functions as an important proof-of-concept step rather than a practice-changing result. It demonstrates that a four-week, high-dose, fully oral regimen can be delivered safely in the field, that molecular monitoring of bacterial clearance is a workable trial endpoint, and that the question of shortening Buruli ulcer therapy can be rigorously tested. It also highlights the persistent challenge of trial recruitment for neglected diseases, which often forces studies to report underpowered comparisons and underscores the need for sustained funding and multi-site collaboration. For now, patients should continue to receive the standard eight-week regimen, which remains supported by the weight of existing evidence. But the complete absence of paradoxical reactions, the absence of recurrences, and the tolerability of double-dose rifampicin give researchers concrete reasons to design the larger, adequately powered trials that will determine whether Buruli ulcer treatment can one day be halved without compromising cure.

Subject of Research: A randomized controlled trial comparing short-course high-dose versus standard-dose antibiotic therapy for Buruli ulcer in Ghana

Article Title: High-dose rifampicin and clarithromycin for 4 weeks versus standard-dose rifampicin and clarithromycin for 8 weeks to treat Buruli ulcer: An open-label, individually randomized, controlled trial in Ghana

Article References: Agbanyo, A., Amoako, Y. A., Opondo, C., Oppong, M. N., Asante-Poku, A., Novignon, J., Tuffour, J., Mintah, I. S., Tuwor, R. D., Ahiatrogah, D. K., Akuffo, R. A., Gborglah, M., Mosweu, I., Pitt, C., Allen, E., Walker, S. L., Yeboah-Manu, D., Marks, M., Phillips, R. O., & SHARP Collaboration (2026). High-dose rifampicin and clarithromycin for 4 weeks versus standard-dose rifampicin and clarithromycin for 8 weeks to treat Buruli ulcer: An open-label, individually randomized, controlled trial in Ghana. PLOS Neglected Tropical Diseases, 20(9), e0014783. https://doi.org/10.1371/journal.pntd.0014783

Image Credits: AI Generated

DOI: 10.1371/journal.pntd.0014783

Keywords: Buruli ulcer, Mycobacterium ulcerans, rifampicin, clarithromycin, randomized controlled trial, Ghana, neglected tropical diseases, antibiotic therapy, paradoxical reactions, microbiological clearance, PLOS Neglected Tropical Diseases, clinical trial

The research team, led by scientists at the Ocean University of China working with collaborators at the BYHEALTH Institute of Nutrition and Health and other Chinese institutions, set out to investigate whether chronic, low-level antibiotic exposure could trigger adaptive responses in this non-spore-forming bacterium. Unlike spore-forming species such as Bacillus, which can build tough, desiccated spores to ride out hostile conditions, Lactobacillus species have long been considered relatively fragile outside their comfortable niches. Bacterial dormancy offers an alternative strategy: a metabolically suppressed but fully reversible state that allows non-spore-forming bacteria to withstand adverse conditions without constructing specialized survival structures. The researchers exposed the sp1.1 strain of L. delbrueckii subsp. bulgaricus to concentrations of rifampicin that stressed but did not kill the cells, then tracked what happened to their physiology, their stress resistance, and their behavior in living animals.

The results were striking. Rifampicin-treated cells entered a state the authors characterize as dormancy, marked by sharply reduced ATP levels, the cellular energy currency, and impaired cell division. The bacteria essentially throttled themselves down, halting growth and conserving resources. Crucially, the state was reversible: when the antibiotic stress was removed, colonies recovered and normal growth resumed. This reversibility distinguishes dormancy from death and from irreversible injury, and it suggests a programmed, controlled response rather than simple damage. In the food industry, where starter cultures routinely face freezing, drying, acidification, and thermal processing steps that whittle down viable cell counts, a reversible dormant state that confers cross-tolerance to multiple stressors at once would be an enormously valuable property.

And cross-tolerance is exactly what the team observed. Dormant cells tolerated acid, alkali, and heat stress significantly better than untreated controls, meaning a single trigger, sublethal rifampicin exposure, produced broad-spectrum resistance rather than protection against just one threat. The functional consequences extended beyond the laboratory bench. When the researchers administered the treated bacteria to mice, the dormant cells persisted longer in the intestinal tract than normal cells, a property known as prolonged intestinal retention. They also exerted a greater impact on the structure of the gut microbial community, indicating that the dormant state changes not just survival but ecological behavior once the bacteria reach the gut. For probiotic formulations, where the central challenge is delivering enough live cells through gastric acid and bile to produce a benefit, these findings point to a potentially powerful new lever.

The mechanism behind this transformation turned out to be one of the most intriguing aspects of the study. When the researchers disrupted the protein aggregates that formed in the dormant cells, either by adjusting pH or by treating the cells with 1,6-hexanediol, a chemical that dissolves certain types of protein condensates, the enhanced tolerance vanished entirely. That causal experiment established that the aggregates are not a byproduct of dormancy but its functional engine. Rifampicin, which targets RNA polymerase and inhibits transcription, triggered a metabolic shift toward transcriptional and translational inhibition, and as protein synthesis slowed, proteins began to clump together into aggregates within the cells. What could have been cellular garbage, however, turned out to be something far more purposeful.

Proteomic analysis of the aggregates revealed a striking selectivity. Rather than capturing random cellular proteins, the aggregates were enriched for proteins involved in translation, RNA metabolism, and DNA repair, precisely the functions a cell would need to restart growth once conditions improve. The authors propose a model in which these aggregates function as molecular safe houses, sequestering and protecting key proteins from degradation or damage during the dormant period. By concentrating translation and DNA repair machinery in one protected location, the aggregates may locally enhance the efficiency of those processes when the cell revives, while also serving as a protein reservoir that allows rapid recovery of growth. In this view, the aggregate is less like a junk pile and more like a sealed emergency kit, packed with the tools needed for reconstruction.

Two intrinsically disordered proteins, identified in the study as Gene1622 and Gene1909, emerged as likely architects of this process. Disordered proteins lack a fixed three-dimensional structure and are known drivers of biomolecular condensate formation in many organisms. In the rifampicin-treated bacteria, both proteins were upregulated in whole-cell measurements and were enriched within the aggregates, suggesting they help nucleate or organize the condensates. The involvement of disordered proteins links this bacterial phenomenon to a broader and rapidly growing body of research on biomolecular condensates, membrane-less compartments that cells across all domains of life use to organize their biochemistry. That a food bacterium uses condensate biology to survive antibiotic stress adds a new ecological dimension to what has largely been studied in model organisms and human cells.

The study also uncovered hidden diversity within the bacterial population. Using single-cell RNA sequencing, the researchers identified a subpopulation of cells that sustained expression of alaS and gatA, genes involved in translation, even while global protein synthesis was being suppressed. These genes were downregulated in bulk RNA sequencing, which averages signals across the whole population, but single-cell analysis revealed that a distinct cluster of cells kept them active. This population heterogeneity means that not all cells respond identically to antibiotic stress; some appear to hedge their bets, maintaining critical functions while their neighbors go fully dormant. Such bet-hedging strategies are well known in microbial ecology, and this study demonstrates them at single-cell resolution in a commercially important probiotic, showing how a population can prepare for recovery even while most of its members are shut down.

The implications cut in two directions. On the constructive side, the findings provide a theoretical basis for engineering more robust starter cultures and probiotics. If manufacturers can deliberately induce and control this reversible dormant state, perhaps through stress conditioning rather than antibiotic exposure, they could produce cultures that survive processing better, retain viability longer on the shelf, and persist more effectively in the gut. The authors note that the work was supported by the National Natural Science Foundation of China and the BYHEALTH Nutrition and Health Research Foundation, reflecting industry interest in exactly these applications. On the cautionary side, the study raises ecological questions about stress-induced adaptation in the food chain. Antibiotic residues at sublethal levels are a known feature of some food production environments, and this research shows that such exposure can make food bacteria hardier and more persistent in the gut, where they exert stronger effects on microbial community structure. Whether that enhanced persistence is beneficial or disruptive to gut microbial homeostasis remains an open question, and one the authors flag explicitly. As the boundaries between food microbiology, antibiotic stewardship, and gut ecology continue to blur, this study suggests that the microbes in our yogurt may be far more adaptable, and far more responsive to their chemical environment, than anyone assumed.

Subject of Research: Sublethal antibiotic-induced dormancy and protein aggregation in Lactobacillus delbrueckii subsp. bulgaricus

Article Title: Sublethal rifampicin enhances the tolerance of Lactobacillus delbrueckii subsp. bulgaricus to food processing and intestinal retention through protein aggregation

Article References: Liu, L., Li, Z., Di, C., Ma, C., Huang, Y., Hao, X., Fu, Z., Yi, H., Zhang, Z., Li, P., Li, L., Ze, X., He, R., Zhang, L., & Gong, P. (2026). Sublethal rifampicin enhances the tolerance of Lactobacillus delbrueckii subsp. bulgaricus to food processing and intestinal retention through protein aggregation. Microbiome. https://doi.org/10.1186/s40168-026-02517-3

Image Credits: AI Generated

DOI: 10.1186/s40168-026-02517-3

Keywords: Lactobacillus delbrueckii subsp. bulgaricus, rifampicin, bacterial dormancy, protein aggregates, probiotics, starter cultures, gut microbiome, stress tolerance, single-cell RNA sequencing, intrinsically disordered proteins, food fermentation, intestinal retention

The assay under scrutiny is Deeplex Myc-TB, a targeted next-generation sequencing test developed to detect mutations in the tuberculosis genome that are associated with resistance to a broad range of first- and second-line anti-TB drugs. Unlike conventional rapid molecular tests, which typically interrogate only a handful of genetic regions, targeted sequencing approaches can survey dozens of genes and intergenic regions in a single run. This breadth matters enormously in clinical practice, because treatment decisions for multidrug-resistant and extensively drug-resistant tuberculosis depend on knowing, quickly and reliably, which drugs are likely to fail and which are likely to work.

To evaluate the assay, the researchers turned to an unusual but powerful resource: isolates distributed through the World Health Organization global Tuberculosis Drug-Susceptibility Testing Proficiency Testing Program, organized and administered by the TB Supranational Reference Laboratory in Antwerp, Belgium. A total of 41 isolates were included in the study. These samples are particularly valuable for verification work because they have been exhaustively characterized by reference laboratories using multiple independent methods. In this study, phenotypic drug susceptibility testing performed on Löwenstein-Jensen medium and in mycobacteria growth indicator tube culture, together with whole-genome sequencing, served as the reference standards against which the Deeplex assay was judged.

The analytical workflow was straightforward in concept. Remnant DNA extracted from the proficiency testing isolates was subjected to targeted next-generation sequencing using the Deeplex Myc-TB assay. The resulting sequence data were interpreted using the manufacturer’s Deeplex web application, and, in parallel, with TBProfiler, an open-source tool for predicting drug resistance from mycobacterial sequence data, applying a composite interpretation rule. Concordance, sensitivity, and specificity were then calculated for each drug class, providing a detailed picture of where the assay excels and where it falls short.

The headline result is striking: the Deeplex Myc-TB assay achieved 100 percent specificity across all drug targets examined. In diagnostic terms, this means that whenever the assay reported a resistance mutation, the isolate genuinely carried a mutation associated with resistance. False positives, which can lead clinicians to withhold effective drugs unnecessarily, were entirely absent from the dataset. For several drugs, the assay’s sensitivity was equally impressive. It correctly identified resistance in every tested isolate for rifampicin, detecting 17 of 17 resistant strains; for pyrazinamide, 7 of 7; for fluoroquinolones, 13 of 13; and for linezolid, 6 of 6. For isoniazid, sensitivity was 94.1 percent, with 16 of 17 resistant isolates correctly flagged.

The single isoniazid miss is instructive rather than alarming. The one false-susceptible result traced back to a specific insertion mutation in the katG gene, designated katG c.45_46insA, which fell outside the region targeted by the assay. This illustrates a fundamental property of targeted sequencing: its performance is bounded by the mutations it is designed to detect. When a resistance-conferring variant lies outside the panel’s target regions, even a technically flawless assay will report susceptibility. The finding underscores why laboratories adopting such assays must understand the local epidemiology of resistance mutations in the strains they encounter.

Performance was more mixed for the newer and repurposed drugs that have become central to modern regimens for drug-resistant tuberculosis. For clofazimine, the assay detected resistance in 4 of 5 phenotypically resistant isolates, a sensitivity of 80 percent. For bedaquiline, sensitivity dropped to 44.4 percent, with only 4 of 9 resistant strains correctly identified. In five cases, isolates that were resistant by phenotypic testing carried no resistance variants detected by the assay. The authors traced much of this gap to the biology of resistance to these drugs. Mutations in the mmpR5 gene, also known as Rv0678, a major regulator of efflux pump expression, were largely detected by the assay, but resistance mediated through the atpE gene was not identified, because that gene is not adequately covered by the assay’s target panel.

Overall concordance between the Deeplex assay and the reference standards ranged from 87.5 percent for bedaquiline to a perfect 100 percent for rifampicin, pyrazinamide, fluoroquinolones, and linezolid. Notably, the assay consistently detected several recurrent mutations associated with resistance to the different drugs, reinforcing the idea that for the common, well-established resistance mechanisms, targeted sequencing performs at or near the level of whole-genome sequencing while being faster and cheaper to deploy in routine laboratory settings. For a disease where every week of delayed or inappropriate treatment increases the risk of transmission, disease progression, and death, that speed advantage carries real clinical weight.

The implications of this verification study extend well beyond one laboratory in Uganda. Proficiency testing panels offer a rare opportunity to benchmark a diagnostic assay against isolates whose resistance profiles are known with high confidence, free from the uncertainties that complicate evaluations using routine clinical samples. By demonstrating near-perfect specificity and strong sensitivity for the cornerstone drugs of tuberculosis therapy, the study provides laboratories considering adoption of targeted next-generation sequencing with concrete, independently grounded performance data. At the same time, the documented gaps for bedaquiline and clofazimine serve as a caution against treating any single assay as a complete solution. The authors emphasize that understanding local resistance mutation patterns is essential when implementing sequencing-based resistance detection, because an assay that misses the mutations circulating in a given region will systematically underreport resistance there.

The broader context makes these findings timely. Drug-resistant tuberculosis kills thousands of people each year, and the introduction of bedaquiline, linezolid, and other newer agents has transformed outcomes for patients with resistant disease, but only when those drugs are deployed appropriately. Molecular diagnostics that can rapidly and accurately profile resistance across the full range of current and repurposed drugs are a critical link in that chain. This study shows that targeted sequencing platforms have matured to the point where they can match reference standards for the most important drugs, while also mapping precisely where the remaining blind spots lie. For laboratory directors, national tuberculosis programs, and diagnostic developers alike, the message is twofold: the technology is ready for prime time in the core of TB drug resistance testing, but careful attention to target coverage, and to the mutation landscape of the populations being served, remains indispensable.

Subject of Research: Analytical performance verification of a targeted next-generation sequencing assay for detecting drug-resistant Mycobacterium tuberculosis

Article Title: Analytical performance verification of the Deeplex Myc-TB assay using well-characterized Mycobacterium tuberculosis proficiency testing isolates

Article References: Kabahita, J. M., Lunkuse, J. M., Batte, D. N., Nakato, H. S., Namutebi, J., Kabugo, J., Adam, I., Kanyerezi, S., Makoha, C., Nsubuga, M. L., Oundo, H. R., Wenka, G. T., Sseruyange, J., Murungi, M., Kasule, G. W., Lutaaya, P., Kyokushaba, J., Byabajungu, H., Ademun, P., … Joloba, M. L. (2026). Analytical performance verification of the Deeplex Myc-TB assay using well-characterized Mycobacterium tuberculosis proficiency testing isolates. BMC Genomics. https://doi.org/10.1186/s12864-026-13336-z

Image Credits: AI Generated

DOI: 10.1186/s12864-026-13336-z

Keywords: tuberculosis, drug resistance, Deeplex Myc-TB, targeted next-generation sequencing, whole-genome sequencing, diagnostics, bedaquiline, clofazimine, isoniazid, rifampicin, proficiency testing, Uganda

The first patient was a four-year-old neutered male Savannah cat from Inverness, Scotland, who was presented to his general practice veterinarian with an intermittent cough and mild weight loss lasting three weeks. The cat was strictly indoor-only and had been fed a commercially available raw meat-based diet containing poultry and supplemental beef offal. Initial treatment with the anti-inflammatory drug meloxicam produced no response, and over the following two weeks the cough became more persistent while the cat grew increasingly lethargic with a reduced appetite.

Thoracic radiographs revealed a marked broncho-interstitial lung pattern, and a blind bronchoalveolar lavage performed under anaesthesia showed moderate neutrophilic inflammation but was negative on routine bacterial culture. An empirical course of the antibiotic marbofloxacin also failed to help. By the time the cat was referred to a specialist institution, he had lost 30 percent of his body weight. A computed tomography scan showed severe, diffuse nodular to confluent soft tissue lesions affecting all lung lobes, together with enlarged mediastinal lymph nodes. Fine-needle aspirates of consolidated lung tissue revealed severe pyogranulomatous inflammation, and Ziehl-Neelsen staining identified small numbers of acid-fast bacilli with the slender, curved morphology typical of mycobacteria. Culture subsequently confirmed Mycobacterium caprae.

Treatment began with a triple antibiotic protocol comprising pradofloxacin at 5 mg/kg, rifampicin at 10 mg/kg and azithromycin at 15 mg/kg, each given orally once daily in liquid formulations. An oesophagostomy tube was placed to help the owners administer the prolonged medication with minimal stress. The cat was hospitalised in isolation for eight days with strict infection control precautions, including personal protective equipment for staff. Public health officials were notified once the diagnosis was confirmed, but no further testing of in-contact people was deemed necessary. Clinically, the cat improved rapidly, gaining weight within a month and coughing far less frequently. Although repeat radiographs at three-monthly intervals showed only mild improvement, treatment was stopped after eleven months when lung changes had remained static for more than two months. The cat remains clinically normal a year after therapy ended.

The second patient was a three-year-old neutered female British Shorthair from Hampshire, England, who was fed the same raw meat-based diet product and presented with a one-month history of cough, weight loss and fever. Radiographs revealed a cavitating mass in the caudal left lung field, a large nodule in the left cranial lung and multifocal areas of dense consolidation throughout the remaining lung fields. Cytology of a bronchoalveolar lavage sample showed marked neutrophilic and macrophagic inflammation with epithelioid macrophages containing non-staining ghost bacilli, and Ziehl-Neelsen staining again revealed intracellular acid-fast organisms. Polymerase chain reaction testing at a mycobacterial reference laboratory detected DNA of the Mycobacterium tuberculosis complex, and sequencing confirmed M. caprae.

The same triple antibiotic regimen was prescribed, again using liquid formulations to support long-term daily compliance. The cat improved rapidly, gaining weight within a month, with coughing notably reduced by four months of therapy. Radiographs after five months showed significant improvement without complete normalisation, and after a further three months the findings were unchanged. Given the patient was clinically well and had completed nine months of treatment, therapy was discontinued. She remains clinically normal ten months after cessation.

The clinical significance of these cases extends beyond the rarity of the pathogen. In the United Kingdom, feline infections with the M. tuberculosis complex are usually caused by Mycobacterium bovis or Mycobacterium microti, and M. caprae has only recently been identified in domestic cats, previously documented in detail in a single post-mortem case. The treatment protocol used in both cats was adapted from human tuberculosis guidelines and consists of rifampicin, a fluoroquinolone and a macrolide continued for at least three months and for two months beyond resolution of clinical signs. Earlier retrospective work found that only 42 percent of treated cats achieved complete remission, often despite inappropriate therapy, whereas the updated multidrug approach has produced remission rates of approximately 80 percent.

Notably, neither cat achieved radiographic resolution despite extended therapy, yet both remained free of relapse. The authors draw an analogy with post-tuberculosis lung disease in humans, an increasingly recognised spectrum of structural and functional pulmonary abnormalities that persists after successful anti-mycobacterial therapy in 18 to 80 percent of treated patients. They suggest that stable radiographic changes could serve as a reasonable therapeutic endpoint in feline mycobacterial infections where initial lung damage is too severe to be expected to normalise.

The report also underscores the practical demands of treatment. Both cats required prolonged daily multidrug therapy with frequent follow-up visits, demanding substantial financial and emotional investment from their owners alongside excellent patient compliance. The authors caution that where such commitment is not feasible, euthanasia should be considered for severely affected animals, both for welfare reasons and to reduce the risk of antimicrobial resistance developing from inconsistent dosing. They further note that empirical treatment choices early in the diagnostic process, such as anti-inflammatory drugs, can complicate or worsen the clinical course and should be weighed carefully with owners.

Zoonotic considerations shaped the management of both cases. Transmission of M. bovis from cats to humans has been documented previously, although the risk is considered very low, and M. caprae transmission to humans has only been identified in proximity to infected goats, its reservoir host, never from cats. Because no in-contact humans had risk factors for zoonotic transmission, treatment of both cats was judged reasonable. The authors hope that raising awareness of this first reported successful treatment of M. caprae infection in UK domestic cats will aid patient management while mitigating zoonotic risks, and they highlight the oesophagostomy tube used in the first case as a practical aid that reduces stress and supports the owner-caregiver relationship throughout months of therapy.

Subject of Research: Successful treatment of Mycobacterium caprae tuberculosis infection in two domestic cats in the United Kingdom

Article Title: Successful Treatment of Mycobacterium caprae Infection in Two UK Cats

Article References: Clark, E., Gunn‐Moore, D., & O'Halloran, C. (2026). Successful Treatment of Mycobacterium caprae Infection in Two UK Cats. Veterinary Medicine and Science, 12(5), Article e71180. https://doi.org/10.1002/vms3.71180

Image Credits: AI Generated

DOI: 10.1002/vms3.71180

Keywords: Mycobacterium caprae, feline tuberculosis, zoonotic disease, veterinary medicine, triple antibiotic therapy, rifampicin, pradofloxacin, azithromycin, raw meat-based diet, post-tuberculosis lung disease, Mycobacterium tuberculosis complex, UK cats