Journal of Clinical Tuberculosis and Other Mycobacterial Diseases最新文献

Background

Analyzing the epidemiology and clinical manifestations of pediatric tuberculosis in endemic regions is crucial to meet the goal of ending tuberculosis. The objective was to assess the various clinical scenarios of tuberculosis in a large pediatric cohort in Mexico.

Methods

This retrospective study from a pediatric referral center in Mexico included patients diagnosed with tuberculosis from 2012 to 2021. We analyzed clinical data and diagnostic study results, including demographic characteristics, underlying medical conditions, BCG vaccination, clinical presentation, imaging findings, microbiologic data, treatment, and clinical outcomes. Basic descriptive statistics and Chi-squared analysis were performed to summarize the metadata of pediatric patients with different clinical presentations of tuberculosis and evaluate their association with mortality, respectively.

Results

A total of 100 patients were included with a mean age of 7.76 years ± 1.49 years. The most prevalent clinical presentation was pulmonary tuberculosis (n = 51). Only 51 patients were immunized with Bacillus Calmette–Guérin vaccine. The most commons symptoms were fever, cough and weight loss. Among patients with meningeal tuberculosis (n = 14), the most common clinical signs were seizures, fever, and vomiting. Cure was achieved in 52 patients, 12 patients died, and 36 continue in treatment. Clinical presentation of tuberculosis (p-value = 0.009) and immunodeficiency (p-value = 0.015) were significantly associated with mortality.

Conclusions

Increasing the visibility of tuberculosis is imperative to end this disease. We report relevant clinical data of a large pediatric tuberculosis cohort, stratified by the different forms of disease. A high index of suspicion of tuberculosis is required for a timely diagnosis and treatment initiation, particularly among immunocompromised individuals, in whom mortality is higher.

The USPSTF has updated Latent TB Infection (LTBI) screening and treatment recommendations in 2023; describing treatment courses, side effects and benefits associated with each regimen. Overall, rifampin-containing shortened regimens are the preferred modality for LTBI treatment. A recent study in 2023 evaluated adherence and tolerance of the isoniazid(INH) + rifapentine(RPT), or “3HP” regimen and identified patient groups that may be at higher risk for non-completion of this regimen. It emphasized the need for targeted education at the beginning of treatment, to avoid early discontinuation. Our experience in New Orleans demonstrated that the 3HP is well-tolerated, with higher completion rates than other LTBI regimens. Utilizing a retrospective chart review model, we reviewed 756 patients who were treated for LTBI over a two-year period from 1/2021––12/2022. The three possible treatment regimens included isoniazid (INH) alone, rifampin (RIF) alone, or INH + RPT (3HP). Of these regimens, the highest completion rate was in the 3HP group, despite literature suggesting this regimen is difficult to tolerate. Our experience suggests that this may still be an efficacious regimen that is well-tolerated if there is good access to clinicians to discuss mitigating side effects. More data is needed to determine factors that led to the success or failure for each regimen. Our clinic does have increased availability of nursing and medical staff to discuss side effects and answer questions, which may have contributed to our relatively higher success rate. In addition, we applied the review recommendations to our patient population, and would recommend the consideration of diabetes, heavy alcohol use, and tobacco use as risk factors for patients that would benefit from LTBI screening and treatment.

Nontuberculous mycobacteria are a rare but still emerging cause of difficult-to-treat prosthetic joint infection. To our knowledge only 17 cases of M. abscessus complex prosthetic joint infection are reported in literature, of which only 1 is by M. abscessus subps. abscessus. No guidelines are available for this clinical scenario.

We describe a 68-years-old female patient with an early-onset M. abscessus subsp. abscessus prosthetic joint infection, successfully treated with a tailored medical-surgical strategy, and present an overview of cases currently available in the literature to assist physicians in the management of these uncommon infections.

Introduction

Intraocular tuberculosis (IOTB) is a common site of extrapulmonary tuberculosis and a main cause of infectious uveitis. It can result in severe visual morbidity if not recognized and treated properly. The clinical manifestations of IOTB are varied, and the duration of treatment is unclear. This study describes the clinical characteristics and outcomes of patients with IOTB and compares the duration of antituberculosis therapy (ATT) and steroid use.

Method

An 8-year retrospective study of IOTB patients in an endemic area of a tertiary hospital in Thailand. All patients had a complete treatment of ATT at least for 6 months.

Results

Forty-three patients with 57 eyes and a mean age of 43.72 years were included. Panuveitis (38.6 %), retinal phlebitis (31.6 %), and posterior uveitis (15.8 %) were common clinical characteristics. A significant difference between initial and final best corrected visual acuity (BCVA) after ATT in 6 months for therapy and at least 9 months for therapy was observed (p = 0.004, 0.003, respectively). Ninety point nine percent of patients who received ATT for 9 months achieved a successful treatment outcome, while 66.7 % of patients who received ATT for 6 months did (p = 0.056). Patients who received systemic and/or regional corticosteroids therapy during treatment had a higher rate of treatment failure (p < 0.001).

Conclusion

IOTB had a variety of clinical manifestations, including nongranulomatous inflammation. Patients who completed treatment with ATT for at least 6 months improved their final BCVA. There was no difference in treatment outcomes regarding the duration of treatment. Combined treatment with systemic and/or regional corticosteroids was significantly associated with failed treatment outcomes.

Mycobacterium bovis bacille Calmette-Guérin (BCG) is the most effective intravesical immunotherapy for non-muscle invasive bladder cancer (NMIBC), administered after its transurethral resection. Although its instillation is generally well tolerated, BCG-related infectious complications may occur in up to 5% of patients. Clinical manifestations may arise in conjunction with initial BCG instillation or develop months or years after the last BCG instillation. The range of presentations and potential severity pose an imminent challenge for clinicians. We present a case of an isolated subcutaneous chest wall abscess in an immunocompetent 52-year-old patient nearly two years after intravesical BCG instillation for NMIBC, an absolute rarity. As the enlarging chest wall tumor may be misinterpreted as malignancy, its expedient diagnosis and prompt treatment are of critical importance.

Background

The increasing number of patients with miliary tuberculosis (MTB) is a concern in an aging society because of its high mortality rate. Several prognostic biomarkers for MTB have been identified; however, the predictive ability of monocytes as biomarkers remains unknown. This study demonstrates the usefulness of monocytes as prognostic biomarkers for MTB.

Materials and methods

We retrospectively compared the clinical findings of 52 patients with MTB hospitalized between April 2013 and October 2021. The predictive ability of biomarkers for 3-month prognosis and their cutoff values were calculated. Survival times and longitudinal changes in monocytes after initiating treatment were compared.

Results

A smaller number of monocytes (#M), higher lymphocyte-monocyte ratio (LMR), higher neutrophil-monocyte ratio, and poorer performance status were associated with death within 3 months. #M was an independent prognostic factor. #M and LMR exhibited the highest predictive performance compared to others using receiver operating characteristic curve analysis (area under the curve = 0.86 and 0.85, respectively). Survival time was shorter in patients with #M ≤ 200 cells/μL and LMR > 2.5. Rapidly increasing #M after treatment was related to better prognosis in patients with #M ≤ 200 cells/μL at diagnosis.

Conclusions

#M at diagnosis and longitudinal changes in monocytes are related to MTB prognosis.

There are different tuberculosis diagnostic tools available that detect an antigen-specific immune response. The present study aims to evaluate the potential of cross-reactive responses of a CFP-10 and ESAT-6 antigen-based TB test using bioinformatics tools. The study found that the presence of the sequences coding for the CFP-10 and ESAT-6 antigens in mycobacterial genomes is not associated with their pathogenicity, and not even consistent within a single species among its strains, which can lead to either false positive or false negative test results. The data that was analyzed included genome assemblies of all available mycobacterial strains obtained from the NCBI Genome database, while the standalone BLAST and tblastn programs were utilized to detect the presence of the CFP-10 and ESAT-6 sequences. The findings revealed that a number of non-pathogenic mycobacteria contained the aforementioned sequences, while some pathogenic mycobacteria did not, indicating that a standard tuberculin skin test should be more preferable for detecting various pathogenic mycobacteria compared to antigen-specific tests. In the Mycobacterium tuberculosis complex (MTBC), the proportion of positive strains varied within individual species, indicating a complex relationship. Among non-tuberculous mycobacteria (NTMB), more than half of the analyzed species did not contain these sequences which is consistent with their non-pathogenicity. Further research is necessary to fully comprehend the relationship between MTBC pathogenicity and the CFP-10 and ESAT-6 sequences. This could lead to a conclusion that a standard tuberculin skin test, although non-specific due to the undefined antigen content, may be able to detect various pathogenic mycobacteria in a more reliable manner than antigen-specific tests.

In this study, we jointly modeled longitudinal CD4 count data and survival outcome (time-to-first occurrence of composite outcome of death, cardiac tamponade or constriction) in other to investigate the effects of Mycobacterium indicus pranii immunotherapy and the CD4 count measurements on the hazard of the composite outcome among patients with HIV and tuberculous (TB) pericarditis. In this joint modeling framework, the models for longitudinal and the survival data are linked by an association structure. The association structure represents the hazard of the event for 1-unit increase in the longitudinal measurement. Models fitting and parameter estimation were carried out using R version 4.2.3. The association structure that represents the strength of the association between the hazard for an event at time point j and the area under the longitudinal trajectory up to the same time j provides the best fit. We found that 1-unit increase in CD4 count results in 2 % significant reduction in the hazard of the composite outcome. Among HIV and TB pericarditis individuals, the hazard of the composite outcome does not differ between of M.indicus pranii versus placebo. Application of joint models to investigate the effect of M.indicus pranii on the hazard of the composite outcome is limited. Hence, this study provides information on the effect of M.indicus pranii on the hazard of the composite outcome among HIV and TB pericarditis patients.

Antimicrobial resistance alongside other challenges in tuberculosis (TB) therapeutics have stirred renewed interest in host-directed interventions, including the role of antibodies as adjunct therapeutic agents. This study assessed the binding efficacy of two novel IgG1 opsonic monoclonal antibodies (MABs; GG9 & JG7) at 5, 10, and 25 µg/mL to live cultures of Mycobacterium tuberculosis, M. avium, M. bovis, M. fortuitum, M. intracellulare, and M. smegmatis American Type Culture Collection laboratory reference strains, as well as clinical susceptible, multi-drug resistant, and extensively drug resistant M. tuberculosis strains using indirect enzyme-linked immunosorbent assays. These three MAB concentrations were selected from a range of concentrations used in previous optimization (binding and functional) assays. Both MABs bound to all mycobacterial species and sub-types tested, albeit to varying degrees. Statistically significant differences in MAB binding activity were observed when comparing the highest and lowest MAB concentrations (p < 0.05) for both MABs GG9 and JG7, irrespective of the M. tuberculosis resistance profile. Binding affinity increased with an increase in MAB concentration, and optimal binding was observed at 25 µg/mL. JG7 showed better binding activity than GG9. Both MABs also bound to five MOTT species, albeit at varied levels. This non-selective binding to different mycobacterial species suggests a potential role for GG9 and JG7 as adjunctive agents in anti-TB chemotherapy with the aim to enhance bacterial killing.

Background

World Health Organization suggests concurrent bedaquiline-delamanid (BDQ-DLM) as part of individualised regimens for eligible patients with pulmonary drug-resistant tuberculosis (DR-TB); however, data for patients with drug-resistant extrapulmonary tuberculosis (EPTB) is extremely limited. This study documents the treatment outcomes and adverse events associated with concurrent BDQ-DLM-based regimens in patients with drug-resistant EPTB at a Médecins Sans Frontières clinic in Mumbai, India.

Methods

Retrospective cohort study based on routinely collected programmatic data. Individualised regimens were based on drug-susceptibility testing and previous drug exposure. Drug-resistant EPTB patients initiated on regimens containing concurrent BDQ and DLM from April 2016 to October 2019 were included. Patients who completed treatment were followed up at 12 months.

Results

Of 17 patients, median age was 23 years (IQR = 21–30 years) and 12/17 (71 %) were female. Pre-extensively drug-resistant tuberculosis and extensively drug-resistant TB was reported in 13/17 (76.4 %) and 2/17 (11.7 %) patients respectively. Microbiological reports were unavailable for two patients with central nervous system TB. Lymph node TB was the commonest form of EPTB in 9/17 (53 %) of patients. Median duration of treatment was 18.9 months. At least one grade three or four severe adverse event (SAE) was reported by 13/17 (76.4 %) patients. Thirteen (76.4 %) patients had favourable outcomes. None of the patients relapsed or died in the one-year period of post-treatment follow-up.

Conclusion

Concurrent BDQ-DLM-based regimens in drug-resistant EPTB were effective and associated with manageable adverse events.