International Journal of Mycobacteriology最新文献

Background: Mycobacterium abscessus complex (MABC) is an important cause of opportunistic infections in the respiratory tracts. Data on antimicrobial resistance of MABC in Vietnam were still lacking.

Methods: From December 2021 to July 2022, mycobacteria growth indicator tube (MGIT) culture and hsp65 gene sequencing were conducted to identify nontuberculous mycobacteria (NTM) from patients with respiratory infections at National Hospital 74, Vietnam. Finally, 123 NTM trains were retrieved. Out of them, 40 MABC were identified and tested for susceptibility to isoniazid, rifampicin, streptomycin, ethambutol, amikacin (AK), moxifloxacin, clarithromycin (CLR), and linezolid (LZD). DNA sequencing of erm (41), rrl, and rrs genes was performed on all CLR-resistant strains and one CLR-susceptible strain (as control).

Results: All 40 MABC strains, including 23 M. abscessus subsp. massiliense (M. massiliense), 16 subsp. abscessus (M. abscessus), and one subsp. bolletii (M. bolletii) were resistant to first-line antituberculosis drugs. Susceptibility was 40/40 in AK and 38/40 in LZD. For CLR, 24/40 strains were susceptible (23 M. massiliense, one M. abscessus). Of 16/40 strains that resisted with CLR, one M. bolletii and 14 M. abscessus exhibited inducible resistance and one M. abscessus had acquired resistance. All 16 CLR-resistant strains carried erm (41) T28 genotype, and the CLR-susceptible M. abscessus strain had T28C. No mutations associated with AK and CLR resistance were found in rrs and rrl genes.

Conclusions: Inducible CLR resistance was predominant, associated with erm (41) T28 genotype. AK and LZD appear to be promising for the treatment of MABC. CLR remains effective against M. massiliense but is less suitable for treating M. abscessus.

Abdominal tuberculosis (TB) can present with the involvement of the peritoneum, stomach, intestinal tract, hepatobiliary tree, pancreas, perianal area, or lymph nodes. Peritoneal TB is one of the most challenging forms to diagnose and usually occurs through reactivation of latent TB infection or through hematogeneous spread in the setting of active pulmonary TB. A 25-year-old male from Guinea-Bissau, with multiple visits to the emergency department in the last month due to several daily soft stools and generalized abdominal pain. He returned with an abdominal computed tomography (CT) revealing irregular ascites and suspected peritoneal carcinomatosis. He was admitted for an etiological study, and an abdominal CT scan was repeated, which showed diffuse thickening of the stomach wall. Erythrocyte sedimentation rate of 14 mm/1 h and C-reactive protein of 1.24 mg/dL. Interferon-gamma release assay was positive. Acid-fast bacilli smear in sputum and blood and urine cultures in Loewenstein-Jensen medium were negative. Upper gastrointestinal endoscopy revealed Helicobacter Pylori infection and colonoscopy was normal. Positron emission tomography-CT confirmed the abdominal CT findings. Diagnostic laparoscopy was performed to clarify the etiology, and pathological anatomy revealed findings compatible with tuberculosis. Treatment with isoniazid, rifampicin, pyrazinamide, and ethambutolepyridoxine was started. Although abdominal TB continues to be a significant health problem in the developing world, recently, there has been an increase in the number of patients diagnosed with abdominal TB in parts of the world where TB generally was rare. This is partly a result of increasing travel and migration and also of the rising number of HIV patients who are susceptible to opportunistic infections.

Background: This study aims to identify the signatures of natural selection in the pyrazinamidase (pncA) gene to see if genetic adaptations by Darwinian natural selection have shaped genetic composition of Mycobacterium tuberculosis (Mtb).

Methods: The present analyses were based on 209 DNA sequences (561 bp) of the pncA gene of the bacterial pathogen, Mtb from seven different counties (Peru, Pakistan, South Africa, Mexico, India, China, and Kuwait) endemic to tuberculosis (TB). Before conducting tests for Darwinian natural selection in the pncA gene, we conducted several tests for neutrality in all the available DNA sequences after retrieval from public domains. Several statistical analyses under different algorithms were conducted and biological/evolutionary inferences were drawn.

Results: The 209 sequences of the pncA gene in Mtb belonging to seven different countries were found to be perfectly aligned with the reference sequence. Data analyses under different population genetic models revealed the highest genetic diversity in India, followed by Peru; the lowest was in China. Interestingly, four populations; Peru, Pakistan, India, and Kuwait were found to be deviated from neutral model of evolution based on Tajima'D (TD) values; two populations (India and Peru) based on Fu and Li's D and F (FLD and FLF) test values and five populations (India, Peru, Pakistan, South Africa, and Kuwait) based on Fay and Wu's H (FWH) test. Moreover, based on the statistically significant results of neutrality tests, evidence for positive selection in three populations (Peru [P < 0.02945], Pakistan [P < 0.01767], and Kuwait [P < 0.00301]) at P < 0.05 level of significance] was found.

Conclusion: The present evolutionary genetic analysis of the pncA gene indicates different levels of genetic diversity in seven different country populations. As almost all the global populations showed deviation from neutral model and three populations showed signatures of natural selection, with no specific hotspot region identified for PZA resistance, this gene needs to be studied with larger population size covering countries with TB incidences to study the evolution of drug resistance in Mtb. This will help in the management of drug resistance and TB elimination plan.

Background: The M72/AS01E tuberculosis vaccine candidate, currently on trial in Indonesia, includes PPE18 (Rv1196) and PepA (Rv0125) as key antigens. Genetic variation in these proteins may affect immune recognition and vaccine efficacy. This study aims to analyse the genetic diversity of Rv1196 and Rv0125 in Mycobacterium tuberculosis clinical isolates from Indonesia and assess the structural and immunological implications using in silico methods.

Methods: Rv1196 and Rv0125 genes from clinical isolates were sequenced and analysed for polymorphisms. PPE18 variants were modelled using I-TASSER (Iterative Threading ASSEmbly Refinement), and structural stability and HLA (Human Leukocyte Antigen) binding predictions (HLA-I and HLA-II) were performed using IEDB (Immune Epitope Database) tools. Molecular docking with TLR2 (Toll-like Receptor 2) was conducted to evaluate receptor interactions.

Results: A novel non-synonymous mutation (T22G, Ser8Ala) was identified in Rv0125, which was otherwise conserved. Rv1196 showed high variability with 58 polymorphic sites, including 38 non-synonymous mutations, a frequent Arg287Gln substitution, and a ΔThr163-Ala164 deletion. Structural modelling indicated preserved PPE18 fold but altered epitope binding in an allele-specific manner. Docking showed stronger TLR2 interactions for variants 6S31 and 6S32, suggesting enhanced IL-10 induction and a Th2-skewed immune response.

Conclusions: PPE18 genetic variation may influence immune recognition and the effectiveness of M72/AS01E. Ongoing antigenic surveillance in endemic areas is essential to guide vaccine design and diagnostics.

Background: Tuberculosis (TB) remains a leading cause of mortality among people living with HIV/AIDS, who face a tenfold higher risk of Mycobacterium tuberculosis (MTB) infection. TB-HIV coinfection complicates disease management due to drug interactions, overlapping toxicities, immune reconstitution inflammatory syndrome, and high treatment burdens, potentially driving drug resistance. The emergence of resistant MTB further exacerbates this challenge. This study evaluated the drug resistance profile of MTB in TB-confirmed samples from HIV-positive patients.

Methods: An analytical cross-sectional study was conducted on 216 sputum samples from HIV patients on antiretroviral therapy at Jamot Hospital, Yaoundé, Cameroon (June-September 2022). Two consecutive samples per patient underwent fluorescent microscopy (Auramine-Rhodamine stain) and TB-Loop-Mediated Isothermal Amplification. DNA was extracted using the GenoLyse® kit (Hain Lifescience, Germany), and drug resistance profiles were assessed via GenoType® MTBDRplus and MTBDRsl line probe assays.

Results: TB was confirmed in 12.04% (26/216) of participants. Rifampicin (RIF) and isoniazid (INH) resistance were each detected in 50% (13/26) of cases, with 23% (6/26) exhibiting multidrug-resistance (MDR). Predominant mutations included rpoB MUT2B (15.38%) for RIF and inhA MUT2A (23.06%) for INH. Second-line resistance analysis revealed 61.54% (8/13) resistance to kanamycin (KAN)/amikacin (AMK)/viomycin, 7.69% (1/13) to AMK/capreomycin/viomycin, and 7.69% (1/13) to KAN. Notably, 61.54% (8/13) lacked the rrs wild-type probe, indicating resistance to injectable TB drugs.

Conclusion: High MDR-TB prevalence was observed among HIV-TB coinfected patients, underscoring the urgent need for enhanced resistance surveillance and optimized treatment strategies in TB/HIV-endemic regions like Cameroon. Further research is warranted to elucidate HIV's role in driving TB drug resistance.

Tuberculosis and its pathogen, Mycobacterium tuberculosis complex, are a major health challenge. The causative agent of tuberculosis is M. tuberculosis complex and is transmitted through airborne droplets. Tumor necrosis factor-alpha (TNF-α) is one of the cytokines that mediate a major role in the cellular immune response to tuberculosis and is essential for pathogen clearance, control of mycobacterial growth, and facilitation of apoptosis of infected cells. Susceptibility to tuberculosis and disease progression are influenced by environmental factors and the host's genetic predisposition. TNF polymorphisms affect disease susceptibility and patient response to drugs and treatment. Various studies have been conducted to associate TNF polymorphisms with susceptibility to tuberculosis. This activity aims to review the role of TNF-α cytokine and the impact of its polymorphisms on the occurrence of tuberculosis and compiles recent mechanistic and epidemiological findings.

Background: Studies on the role of mannose-binding lectin 2 (MBL2) in individuals infected with tuberculosis (TB) remain limited. This study aimed to compare MBL2 gene expression and protein concentration between active and latent TB cases and to assess the influence of sex on these differences.

Methods: This cross-sectional study involved 39 newly diagnosed active pulmonary TB patients and 25 individuals with latent TB who were household contacts. MBL2 gene expression was evaluated using a relative quantitative polymerase chain reaction method. MBL protein levels were measured using the enzyme-linked immunosorbent assay.

Results: Among female participants, MBL2 gene expression was significantly lower in those with active TB compared to those with latent TB (P = 0.02). In male participants, no significant difference was observed (P = 0.333). Similarly, MBL protein levels tended to be lower in females with active TB than in those with latent TB, though this difference was not statistically significant (median [range]: 124.78 [65.62-499.79] vs. 208.49 [99.85-498.65] ng/mL, P = 0.099). In males, no significant difference in MBL protein levels was detected between the active TB and latent TB groups (206.86 [59.11-526.77] vs. 143.55 [65.85-290.7] ng/mL, P = 0.285).

Conclusion: This study highlights the influence of sex on the expression of the MBL2 gene and plasma protein levels in TB patients. A lower expression of the MBL2 gene in active TB cases compared to latent TB cases was observed exclusively in women.

Background: Tuberculosis (TB) remains a leading global cause of infectious disease-related mortality. This study aimed to investigate the clinical characteristics, outcomes, and prognostic factors in patients diagnosed with tuberculous arachnoiditis, a serious complication of TB affecting the spinal cord and nerve roots.

Methods: This is a retrospective analysis of adult patients admitted with tuberculous arachnoiditis to a tertiary care center between July 2011 and November 2021. A total of 119 patients were included. Data collected included demographics, clinical presentation, cerebrospinal fluid (CSF) analysis, treatment regimens, and outcomes assessed using the Modified Rankin Scale at presentation and follow-up. Predictors of outcomes, including mortality, were analyzed using SPSS software.

Results: The median age of patients was 34 years (standard deviation ± 14.13), with a male-to-female ratio of 53:47. Common presenting features included lower-limb weakness (67% with power ≤3/5) and bowel/bladder dysfunction (61%). Higher CSF leukocyte counts and human immunodeficiency virus (HIV) co-infection were significantly associated with worse outcomes; 63.6% of HIV-positive patients died before review. Elevated CSF protein levels were directly correlated with mortality. Longer duration of antitubercular therapy (ATT) was associated with improved outcomes. Statistical analysis identified HIV status and CSF protein count as independent predictors of mortality in TB arachnoiditis.

Conclusion: In this cohort of patients with tuberculous arachnoiditis, lower-limb weakness and bowel/bladder incontinence were the predominant clinical features. HIV seropositivity, elevated CSF protein levels, and duration of ATT significantly influenced patient outcomes. These findings underscore the importance of early diagnosis, prompt initiation of ATT, and management of associated factors like HIV in improving outcomes for patients with TB arachnoiditis.

Background: In early April 2024, three Nepalese students (Pt1-Pt3) in the morning classes of a Japanese language school in Western Japan were diagnosed with sputum smear-positive pulmonary tuberculosis (TB). The smear status of Pt1 and Pt3 was 3+, whereas Pt2 was scanty positive. This study aims at describing cases with active TB as well as latent TB infection (LTBI) in this outbreak.

Methods: The outbreak cases are epidemiologically described in terms of time, place, and person.

Results: An intensive contact investigation using chest X-rays found 13 cases with active TB as of January 2025. Ten cases, including Pt1 and Pt2, were found in Classroom A, whereas one case each was found in the morning classes of Classrooms B (Pt3) and C and in Classroom D (afternoon class). In addition, 10 other cases of LTBI were found in Classroom A. Whole-genome sequencing (WGS) revealed that Pt3 and another case in Classroom A had genetically distinct Mycobacterium tuberculosis strains, with 1072 and 466 single nucleotide variants, respectively, indicating they were unrelated to the outbreak. On the other hand, the case of Classroom C shared the outbreak strain, and the person had frequently visited the apartment of Pt1 and Pt2. The case of Classroom D did not have close contact with those of Classroom A and was eventually excluded from the outbreak cases.

Conclusion: WGS is useful in distinguishing outbreak-related cases from coincidentally found ones in TB outbreak investigations.

Background: Even with early antituberculosis (TB) treatment, some patients with pulmonary TB (PTB) may experience progression of chest computed tomography (CT) lesions. However, there is limited information on the causes and management of this progression during treatment. This study was undertaken to improve clinical understanding of the various causes and management strategies for the worsening of chest CT lesions in patients with PTB.

Methods: A retrospective analysis was performed on the medical records of 61 PTB patients. We evaluated the radiological features, clinical characteristics, laboratory findings, causes, and management of chest CT lesions progression in PTB during anti-TB treatment and compared the characteristics of patients in the paradoxical response (PR) group and the non-PR group.

Results: The most common cause of the chest CT progression lesions was PR, accounting for 50.8% (n = 31) of the cases. Other important causes included insufficient anti-TB treatment (21.3%, n = 13), drug-resistant TB (8.2%, n = 5), and comorbidities such as bacterial infections (8.2%, n = 5), fungal infections (6.6%, n = 4), and lung cancer (4.9%, n = 3). Patients with PR were primarily treated by continuing their anti-TB management, whereas those with non-PR due to other causes received treatment targeting the underlying etiology. PR patients were younger (Mann-Whitney U-test, P < 0.001; 95% confidence interval [CI]: 15.8-32.2)., had more asymptomatic cases (74.2% vs. 4.0%; χ2 test, P < 0.001; odds ratio [OR]: 64.3, 95% CI: 12.5-330.2), showed higher Mycobacterium TB culture positivity (64.5% vs. 30.0%; χ2 test, P = 0.015; OR: 4.2, 95% CI: 1.4-12.6), and had quicker lesion progression than the non-PR group (P = 0.004; 95% CI: 1.0-3.0).

Conclusion: PR is the major cause of chest CT lesion progression in PTB during anti-TB. Continuation of anti-TB therapy can promote the absorption of lesions. Differences between PR and non-PR patients can help clinicians in diagnosing and guiding treatment strategies.