anti-TB Chemotherapy Research Articles

Efficacy Analysis of Anti-Tuberculosis Chemotherapy Combined with Arthroplasty or Joint Replacement for Tuberculous of the Elbow Joint: A Retrospective Study of 40 Patients.

Tuberculous arthritis of the elbow joint (TAEJ) is a relatively rare infectious bone and joint disease. Misdiagnosed owing to inconspicuous early symptoms, often the elbow joint has suffered serious damage at the time of treatment. This study retrospectively investigated the clinical manifestations, population characteristics, clinical diagnosis, surgical treatment, and functional recovery of elbow joint tuberculosis (TB). A retrospective study of 40 patients was conducted. These patients were diagnosed with tuberculous arthritis of the elbow from June 2007 to August 2021 and were diagnosed with TAEJ by fine-needle aspiration biopsy or biopsy of surgically excised lesions. All patients underwent surgery after taking regular anti-TB drugs and chemotherapy for 2 weeks. Visual analogue scale score, Mayo elbow performance score, and hospital for special surgery assessment scale score were used to evaluate postoperative functional recovery. Imaging tests were used to evaluate patients' postoperative recovery. Forty patients were followed up for an average of 12.5 ±0.5 months. Erythrocyte sedimentation rate and C-reactive protein values returned to normal after anti-TB drug chemotherapy combined with surgical removal of infected lesion tissue; only one patient relapsed 16 months after surgery. Tuberculous arthritis of the elbow joint should be diagnosed in an early stage based on clinical manifestations, laboratory tests, and histopathological examinations. Complete surgical removal of the lesions should be performed after chemotherapy with anti-TB drugs for 2 weeks. The corresponding operation should be selected according to the damage in the elbow joint.

A Systematic Review and Qualitative Analysis of Studies Performing Total Knee Arthroplasty (TKA) in Tuberculosis (TB) of the Knee.

Tuberculosis (TB) is a widespread global disease that significantly impacts daily life. Skeletal TB comprises about 10-35% of all TB cases. Significant research on the spine and hip exists, but due to the rarity of cases, the management of TB is less explored. Furthermore, exercising the option of total knee arthroplasty (TKA) in TB knees is still in its initial stages. This systematic review aims to identify and comprehend the difficulties associated with diagnosing TB-affected knees, their treatment outcomes, and complications related to TKA. A systematic review of existing English literature retrieved from PubMed, Google Scholar, and Web of Science databases was performed using the PRISMA guidelines. A case series of arthroplasty performed on TB knees included a description of the diagnostic approach, clinical outcome, and complication rates. Moreover, studies involving case series with follow-up functional outcomes were included. The Coleman Methodology was used to assess the quality of the studies. A total of six studies (75 knees) were systematically reviewed in this study. The diagnosis of TB knee is multimodal, with MRI being a reliable tool. Administering anti-TB chemotherapy is essential during the perioperative period. Regarding recurrence, a two-stage TKA has a lower risk of recurrence. It is plausible to state that anti-TB chemotherapy needs to be initiated in the perioperative period to prevent the chances of recurrences. Two-stage TKA is reserved for patients who require soft tissue debridement despite adequate chemotherapy.

In vitro evaluation of the binding activity of novel mouse IgG1 opsonic monoclonal antibodies to Mycobacterium tuberculosis and other selected mycobacterial species

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.

Aerosolization of viable Mycobacterium tuberculosis bacilli by tuberculosis clinic attendees independent of sputum-Xpert Ultra status

Potential Mycobacterium tuberculosis (Mtb) transmission during different pulmonary tuberculosis (TB) disease states is poorly understood. We quantified viable aerosolized Mtb from TB clinic attendees following diagnosis and through six months' follow-up thereafter. Presumptive TB patients (n=102) were classified by laboratory, radiological, and clinical features into Group A: Sputum-Xpert Ultra-positive TB (n=52), Group B: Sputum-Xpert Ultra-negative TB (n=20), or Group C: TB undiagnosed (n=30). All groups were assessed for Mtb bioaerosol release at baseline, and subsequently at 2 wk, 2 mo, and 6 mo. Groups A and B were notified to the national TB program and received standard anti-TB chemotherapy; Mtb was isolated from 92% and 90% at presentation, 87% and 74% at 2 wk, 54% and 44% at 2 mo and 32% and 20% at 6 mo, respectively. Surprisingly, similar numbers were detected in Group C not initiating TB treatment: 93%, 70%, 48% and 22% at the same timepoints. A temporal association was observed between Mtb bioaerosol release and TB symptoms in all three groups. Persistence of Mtb bioaerosol positivity was observed in ~30% of participants irrespective of TB chemotherapy. Captured Mtb bacilli were predominantly acid-fast stain-negative and poorly culturable; however, three bioaerosol samples yielded sufficient biomass following culture for whole-genome sequencing, revealing two different Mtb lineages. Detection of viable aerosolized Mtb in clinic attendees, independent of TB diagnosis, suggests that unidentified Mtb transmitters might contribute a significant attributable proportion of community exposure. Additional longitudinal studies with sputum culture-positive and -negative control participants are required to investigate this possibility.

IP-10 for the Diagnosis and Treatment Monitoring of Tuberculosis in Children.

To determine the utility of interferon-gamma-inducible protein 10 (IP-10) for identifying active tuberculosis (TB) and TB infection (TBI) in children in BCG-vaccinated populations, establish its diagnostic performance characteristics, and evaluate changes in IP-10 level during anti-TB chemotherapy. Concentrations of IP-10 and IFN-γ were measured in QuantiFERON-TB Gold (QFT) supernatants in children with suspected TB or due to recent TB contact. A total of 225 children were investigated: 33 with active TB, 48 with TBI, 83 TB contacts, 20 with suspected TB but other final diagnoses, and 41 controls. In 60 children, cytokine responses were evaluated at a follow-up visit after 2 months of anti-TB treatment. IP-10 expression was significantly higher in infected children (active TB and TBI cases) than in uninfected individuals. IP-10 proved effective in identifying TB infection at its optimal cut-off (>1084.5 pg/mL) but was incapable of differentiating between children with active TB and TBI. Combining IP-10 and IFN-γ increased the QFT sensitivity. IP-10 but not IFN-γ decreased significantly during anti-TB treatment in children with active TB (p = 0.003). IP-10 identifies TB infection and declines during anti-TB chemotherapy in children. Incorporating IP-10 into new immunodiagnostic assays could improve TB diagnosis and allow for treatment monitoring.

Long term management of people with post-tuberculosis lung disease.

Post-tuberculosis lung disease (PTLD) is emerging as a significant area of global interest. As the number of patients surviving tuberculosis (TB) increases, the subsequent long-term repercussions have drawn increased attention due to their profound clinical and socioeconomic impacts. A primary obstacle to its comprehensive study has been its marked heterogeneity. The disease presents a spectrum of clinical manifestations which encompass tracheobronchial stenosis, bronchiectasis, granulomas with fibrosis, cavitation with associated aspergillosis, chronic pleural diseases, and small airway diseases-all persistent consequences of PTLD. The spectrum of symptoms a patient may experience varies based on the severity of the initial infection and the efficacy of the treatment received. As a result, the long-term management of PTLD necessitates a detailed and specific approach, addressing each manifestation individually-a tailored strategy. In the immediate aftermath (0-12 months after anti-TB chemotherapy), there should be an emphasis on monitoring for relapse, tracheobronchial stenosis, and smoking cessation. Subsequent management should focus on addressing hemoptysis, managing infection including aspergillosis, and TB-associated chronic obstructive pulmonary disease or restrictive lung function. There remains a vast expanse of knowledge to be discovered in PTLD. This review emphasizes the pressing need for comprehensive, consolidated guidelines for management of patients with PTLD.

Latent tuberculosis infection in myasthenia gravis patients on immunosuppressive therapy: high incidence yet moderate reactivation rate

Background Immunosuppressive therapies (ISTs) are mainstays for management of myasthenia gravis (MG). Meanwhile, latent tuberculosis infection (LTBI) is common in the setting of high-burden countries. However, the prevalence of LTBI among MG patients and whether receiving ISTs for MG would aggravate LTBI reactivation remain unknown. Methods We retrospectively analyzed the frequency of LTBI via interferon-gamma release assay (IGRA) positivity among hospitalized MG patients from both rural and urban areas in a tertiary hospital, and those receiving ISTs were followed up to investigate the reactivation risk of LTBI. Results A total of 300 MG patients with determinate IGRA results were enrolled, where the frequency of LTBI was 35.0%. Male (OR = 1.910, 95% CI: 1.181–3.089, p = .008) and elderly (OR = 1.044, 95% CI: 1.027–1.061, p < .001) patients were prone to LTBI. Of those with LTBI, 78 individuals on ISTs were successfully followed up for a median duration of 18.3 (8.5–24.0) months, of which 25 (32.1%) received anti-tuberculosis (TB) treatments. The rate of various degrees of adverse events was 82.1% over the course of the follow-up, but was not different between individuals with and without therapies against TB (χ 2 < 0.001, p > .999). Only 1 patient eventually reported lymph node and intestinal TB, with the incidence rate of LTBI reactivation preliminarily estimated to be 0.81 per 100 person years. Conclusion The frequency of LTBI is high in our MG cohort, especially among those with advanced age and males. However, receiving immunosuppressives seems not to increase the risk of LTBI reactivation. LTBI screening is strongly recommended for all MG patients ready to receive ISTs, while preventive anti-TB chemotherapy should be prescribed after weighing potential benefits against the risk of side effects in those with LTBI. In-depth investigation is still entailed to further verify these findings due to the limitation of the retrospective single-center design of our study.

Adverse Drug Reaction Patterns of First-line Anti-tubercular Drugs among Saharia Tuberculosis Patients: An Observational Study in Particularly Vulnerable Tribal Group of Madhya Pradesh, India.

The Saharia tribe of Madhya Pradesh has a very high tuberculosis (TB) burden. However, there is no report of adverse drug reaction (ADR) available in patients receiving anti-TB chemotherapy in the community. Reporting and monitoring of ADRs among TB patients is still rare in marginalized communities. An observational prospective study was performed from November 2019 to June 2020 to assess the patterns of ADRs in 250 Saharia TB patients, who were prescribed Category-I daily DOTS (HRZE) by the physician. Both male and female participants equally experienced ADR during the treatment, but relatively more females (92.6%) than males (88.6%) reported ADR during Phase I. Out of 250 patients, 224 patients (89.6%) experienced one or more ADRs in Phase I. The central nervous system-related (75.6%) ADR was mostly reported followed by any gastrointestinal (74.4%), cardiovascular (49.2%) and any dermatological related (44.4%) ADRs. It is paramount to timely monitor and proactively manages ADRs pertaining to anti-TB drug treatment with minimal alteration in the treatment course.

Port site tuberculosis: is an epidemic on shore?

Background: Bangladesh has to carry an extensive burden of tuberculosis in varied form of presentation. In the era of minimally invasive surgery (MIS) port site tuberculosis is usually a rare incidence. Among all the infections it has been identified as a prolong burden for both patients and surgeons. This study was done to notify such rare complication of MIS and tried to find out is there really an upsurge of this infection in Bangladesh. Methods: This retrospective study was done an urban area of Bangladesh during September 2020 to June 2021. 483 laparoscopic surgeries were done by six different surgeons in 5 different hospitals during September 2020 to January 2021. All surgeons have minimum five years experiences in laparoscopic surgery. 20 minutes emersion of the laparoscopic instruments into activated glutaraldehyde solution 2% (CIDEX) was used as method of chemical sterilization. Other surgical instruments were sterilized by conventional autoclave method. Results: Among them 87 patients developed port infections. 66 (75.86%) patients of this 87 developed non-healing ulcer. Biopsy from the ulcer showed granulomatous tissue in 56 patients and the other 10 was nonspecific inflammation. CAT I anti-TB chemotherapy was initiated to all the patients and all improved by this therapy. Use of 3.54% glutaraldehyde instead of 2% or immersion of instruments for a longer period (more than 20 minutes) could be tried in larger scale to prove its efficacy. Conclusions: National tuberculosis control program (NTP) should give more emphasis on cutaneous tuberculosis as the morbidity of this disease is high. Surgeons of Bangladesh should admit and report such incidences as, if it is documented in other areas of the country, it may need to develop a national guideline to prevent and treat port site tuberculosis.

A Rare Case Report of an Extra Pulmonary Tuberculosis: Testicular Tuberculosis

Testicular tuberculosis (TB) is a rare form of genitourinary TB. It presents as a painless or slightly painful scrotal swelling and so it is difficult to differentiate from typical epididymo-orchitis or other conditions such as tumor or infraction. Middle aged males, especially of 20–40 years of age are most commonly affected, and presented with painful or painless scrotal swelling with or without discharging sinus. Epididymal involvement is usually seen in testicular TB. Ultrasound (USG) and USG-guided fine needle aspiration cytology of testicular swelling for the diagnosis was done, CBNAAT of aspirated fluid of testicular swelling confirm the diagnosis. Anti-TB chemotherapy is the mainstay of treatment to ensure the complete resolution of the lesion. However, in very few cases, surgical removal is required for both diagnosis and treatment. Here, we report a very rare case of left sided isolated testicular TB in a 60-year-old male who was completely cured with 6 months regimen of anti-TB chemotherapy.

Inhibition of indoleamine dioxygenase leads to better control of tuberculosis adjunctive to chemotherapy.

The expression of indoleamine 2,3-dioxygenase (IDO), a robust immunosuppressant, is significantly induced in macaque tuberculosis (TB) granulomas, where it is expressed on IFN-responsive macrophages and myeloid-derived suppressor cells. IDO expression is also highly induced in human TB granulomas, and products of its activity are detected in patients with TB. In vivo blockade of IDO activity resulted in the reorganization of the granuloma with substantially greater T cells being recruited to the core of the lesions. This correlated with better immune control of TB and reduced lung M. tuberculosis burdens. To study if the IDO blockade strategy can be translated to a bona fide host-directed therapy in the clinical setting of TB, we studied the effect of IDO inhibitor 1-methyl-d-tryptophan adjunctive to suboptimal anti-TB chemotherapy. While two-thirds of controls and one-third of chemotherapy-treated animals progressed to active TB, inhibition of IDO adjunctive to the same therapy protected macaques from TB, as measured by clinical, radiological, and microbiological attributes. Although chemotherapy improved proliferative T cell responses, adjunctive inhibition of IDO further enhanced the recruitment of effector T cells to the lung. These results strongly suggest the possibility that IDO inhibition can be attempted adjunctive to anti-TB chemotherapy in clinical trials.

Allergic adverse reactions in children following tuberculosis chemotherapy

Introduction. Tolerability of anti-TB chemotherapy in children is an urgent problem. The study is devoted to the characteristics of adverse reactions (AR) of an aller-gic type (allergic and toxic-allergic) and the factors con-tributing to their occurrence. Materials and methods. The retrospective study included 146 children aged 0 to 14 years with respiratory TB who received TB chemo-therapy, including 22 children with multidrug-resistant agent contact (MDR-TB). The spectrum of clinical and laboratory manifestations of АRs, frequency, risk factors were studied. Results. ARswith an allergic component were observed in 54 (37.0%) children, among them allergic in 32 (21.9%) and toxic-allergic in 22 (15.1%). The most common allergic reaction was asymptomatic eosinophilia (81.2%), in other cases, a combination of eosinophilia with dermatitis or only skin manifestations. A mild degree of eosinophilia prevailed, but in 3 patients it was severe (more than 20% of eosinophils in the leuk-ogram). In toxic-allergic reactions, signs of allergy were combined with an increase in liver enzymes in 59.0% of children, less often with other disorders. It was found that the early age of children, complicated course of TB, MDR-TB regimen, hyperergic skin tests do not increase the chance of developing allergic ARs. A burdened aller-gic history increases the chance of allergic АR to anti-TB drugs 2.8 times, and the presence of a primary affect in the lung 3.1 times. Temporary discontinuation or re-placement of drugs was required much more often in toxic-allergic reactions — 40.9% than in allergic ones — 18.7% (р &lt;0.05). Allergic and toxic-allergic reactions were reversible. Conclusion. In the development of АRs to anti-TB drugs in children, the allergic factor is of sig-nificant importance. The creation of laboratory methods for diagnosing allergic reactions to anti-TB drugs would be useful

Clinical Features and Outcomes of Spinal Tuberculosis in Central China.

The appropriate management of spinal tuberculosis (TB) is challenging for clinicians and the key to treat spinal TB. Surgery and long course anti-TB chemotherapy may not be necessary to all situations. This study aimed to characterize the clinical features and factors affecting treatment outcomes. A retrospective study of patients with spinal TB over a 5-year period at a teaching hospital in central China was conducted. Features of patients with spinal TB who received different treatment modalities and factors associated with patient outcomes at the end of chemotherapy were analyzed. Forty-five patients (21 men and 24 women) with spinal TB were available for analysis. The mean age was 55.39 ± 14.94 years. The most common vertebral area involved was the lumbar (42.2%). The mean number of vertebrae involved was 2.20 ± 0.59. 27 patients (60.0%) received surgical treatment, of which 21 (77.8%) received radical surgical treatment. Thirty-five patients (77.8%) had achieved a favorable status. Statistically, there was no significant correlation between favorable status and surgery, but among 27 surgical patients with spinal tuberculosis, patients receiving radical surgery tended to achieve good prognosis (P = 0.010; odds ratio = 0.053; 95% confidence interval 0.006-0.493). Moreover, there was no significant difference between long course and short course of anti-TB chemotherapy in prognosis in different treatment modalities. Although the patients with spinal TB who needed surgical treatment often got a better prognosis when they had radical surgery, surgery was not actually a factor for the favorable outcomes of patients with spinal TB. In different treatment modalities, there was no additional benefit in longer anti-TB chemotherapy periods.

Incidental Tuberculosis Epididymitis/Epididymo-orchitis: A Retrospective Analysis at a Tertiary Center in Taiwan

ObjectivesTo determine the earliest noticeable manifestation and diagnosis in patients diagnosed with tuberculosis (TB) epididymitis/epididymo-orchitis incidentally and to analyze their responses to surgical and medical treatment. MethodsPatients who underwent surgery for the preliminary impression of chronic epididymitis/epididymo-orchitis or epididymal/testicular tumor from 2000 to 2019 were included in the study. The clinical presentations, laboratory data, radiological examinations, and operative findings were analyzed retrospectively. The outcomes were assessed by the responses to anti-TB chemotherapy and post treatment radiographic evaluations. ResultsAll of our 25 patients with a mean age of 60.6 years were diagnosed incidentally with TB epididymitis (48.0%) and TB epididymo-orchitis (52.0%) according to the histopathological findings from their surgeries. The presence of a palpable scrotal mass (76.0%), was the major presentation. Nineteen (76.0%) patients had undergone complete chemotherapy after the surgery and 15 (78.9%) patients showed complete recovery. Four (21.1%) patients had unfavorable outcomes, 3 had TB autonephrectomies and 1 required re-surgery years after complete chemotherapy. Of the 3 (12.0%) patients who did not receive chemotherapy after their surgeries, 1 had a TB relapse in the spine and lung and 1 developed bladder cancer years later. ConclusionTuberculosis epididymitis/epididymo-orchitis is difficult to diagnose. However, some clinical clues can assist including aged patients, extragenital TB histories, poor responses to antibiotic treatment and scrotal skin lesion. Complete anti-TB chemotherapy is mandatory even after the total removal of TB lesion. Supplemental surgical interventions can be considered when the symptoms are not relieved after chemotherapy. Lifespan follow-up is recommended due to high relapse rate.

Risk factors associated with tuberculosis recurrence in South Korea determined using a nationwide cohort study.

ObjectivePrevention of tuberculosis (TB) recurrence is an important issue in TB control. South Korea, a country with a high average income, has been challenged with an intermediate burden of TB. We aimed to estimate the TB recurrence rate after successful completion of the first anti-TB chemotherapy, and to identify the risk factors for the TB recurrence by focusing on co-morbidities and behavioral factors.MethodsThis is a population-based cohort study using data from the National Health Insurance (NHI) database between 2002 and 2013. Newly diagnosed TB patients were identified using the classification of disease codes and prescription records. Final analytical subjects included people who successfully completed the first anti-TB chemotherapy. The primary outcome measure was recurrent TB 6-month after the first treatment completion. A set of associated risk factors, including demographic characteristics, co-morbidities, and health behavior factors were analyzed using Cox regression analysis.ResultsAmong 5,446 TB patients, 2,226 (40.1%) completed the first anti-TB treatment. During the follow-up period, 150 (6.7%) patients had TB recurrence, and the crude recurrent rate was 22.6 per 1000 person-years. The majority of recurrence cases (89%) occurred within the first 2-year period. The major findings show that participants who are male (adjusted HR (aHR) = 1.81, at a 95% CI, range: 1.11–2.94), older in age (aHR = 1.07, at a 95% CI, range: 1.00–1.14), have a lower income (aHR = 1.96, at a 95% CI, range: 1.10–3.48) and who are underweight (aHR = 1.92, at a 95% CI, range 1.15–3.20) were at higher risks for TB recurrence.ConclusionPeople who have risk factors for recurrent TB need to improve treatment compliance through more effective TB management, and follow-up observation for one or two years after the treatment completion.

Gene-Based Diagnosis of Tuberculosis from Oral Swabs with a New Generation Pathogen Enrichment Technique.

ABSTRACTA rapid and sensitive diagnosis is crucial for the management of tuberculosis (TB). A simple and label-free approach via homobifunctional imidoesters with a microfluidic platform (SLIM) assay showed a higher sensitivity than the Xpert MTB/RIF assay in the diagnosis of pulmonary TB (PTB). Here, we evaluated the efficacy of the SLIM assay for oral swab samples from cases of suspected PTB. Patients with clinically suspected PTB were prospectively enrolled and oral swab samples were processed using the SLIM assay and the attending physicians were blinded to the results of the SLIM assay. TB cases were defined as those treated with anti-TB chemotherapy for at least 6 months at the discretion of the specialists based on their clinical features and conventional laboratory results, including the Xpert assay. A total of 272 patients (with TB, n = 128 [47.1%]; without TB, n = 144 [52.9%]; mean age, 59.8 years) were enrolled. Overall, the sensitivity of the oral swab-based SLIM assay (65.6%) was higher than that of the sputum-based Xpert assay (43.4%; P = 0.001). Specifically, the SLIM oral swab assay showed a notably higher sensitivity in culture-negative TB cases compared with the Xpert assay (69.0% [95% CI: 49.2 to 84.7%] versus 7.4% [95% CI: 0.9 to 24.3%]; P = 0.001). The specificity of the SLIM and the Xpert assays was 86.1% (95% CI: 79.3 to 91.3%) and 100% (95% CI: 97.2 to 100%), respectively. When only culture-confirmed cases were analyzed, the SLIM oral swab was comparable to sputum Xpert in sensitivity (64.7% versus 54.3%, P = 0.26). The oral swab-based SLIM assay showed a superior sensitivity for TB diagnosis over the sputum-based Xpert assay, especially for culture-negative cases.IMPORTANCE The development of a rapid, accessible, and highly sensitive diagnostic tool is a major challenge in the control and management of tuberculosis. Gene-based diagnostics is recommended for the rapid diagnosis of pulmonary tuberculosis (PTB), but its sensitivity, such as Xpert MTB/RIF assay (Xpert), drops in cases with a low bacterial load. It can only be applied to sputum samples, and it is quite difficult for some patients to produce an adequate amount of sputum. We evaluated the clinical validity of an oral swab-based microfluidic system, i.e., the SLIM assay. The SLIM assay showed a significantly higher sensitivity than the Xpert assay, especially in smear-negative TB cases. This non-sputum-based SLIM assay can be a useful diagnostic test by overcoming the limitations of conventional sputum-based tests in pulmonary TB.

Efficacy of anterior debridement and bone grafting with fusion using internal fixation combined with anti-tuberculosis chemotherapy in the treatment of subaxial cervical tuberculosis

BackgroundTo evaluate the efficacy of anterior debridement and bone grafting with fusion using internal fixation (BFIF) combined with anti-tuberculosis chemotherapy in the treatment of subaxial cervical spine tuberculosis (SCS-TB).MethodsClinical and radiographic data of patients with SCS-TB treated by anterior debridement and BFIF at our hospital from January 2010 to December 2017 were analyzed retrospectively. The SCS sagittal parameters at the preoperative, postoperative, and final follow-up were documented and compared, including the Occiput-C2 angle, C2–C7 Cobb angle, local Cobb angle, spinal canal angle (SCA), C2–C7 sagittal vertical axis (C2–C7 SVA), the center of gravity of the head-C7 sagittal vertical axis (CGH-C7 SVA), T1 slope (T1S), neck tilt (NT), and thoracic inlet angle (TIA). The ASIA grade, NDI index, JOA score, and VAS score were utilized to assess the postoperative function recovery, and the complications were recorded.ResultsA total of 23 patients were included in the study with a mean age of 46.74 ± 15.43 years, including 8 males and 15 females. All patients with SCS-TB were treated with anterior debridement and BFIF, with a mean postoperative follow-up time of 37.17 ± 12.26 months. The poisoning symptoms of TB were relieved in all patients, and ESR (42.09 ± 9.53 vs 8.04 ± 5.41, P < 0.05) and CRP (30.37 ± 16.02 vs 7.4 ± 2.68, P < 0.05) were decreased at the 3 postoperative months in the comparison of the preoperative. The C0–C2 Cobb angle, C2–C7 Cobb angle, local Cobb angle, SCA, TIS, C2–C7 SVA, and CGH-C7 SVA were corrected remarkably after surgery (P < 0.05). Further, there was a significant improvement in the JOA, VAS, and NDI with the comparison of the preoperative (P < 0.05).ConclusionsAnterior debridement and BFIF combined with anti-TB chemotherapy was a practical tool for the treatment of SCS-TB with the help of SCS sagittal parameters, which can remove the lesion completely, decompress the spinal cord compression, and correct the kyphotic deformity to restore the spine sagittal balance.

Clostridium, Bacteroides and Prevotella associates with increased fecal metabolites Trans-4-Hydroxy-L-proline and Genistein in active pulmonary tuberculosis patients during anti-tuberculosis chemotherapy with isoniazid-rifampin-pyrazinamide-ethambutol (HRZE)

PurposeTo investigated the changes of gut microbiome and fecal metabolome during anti-tuberculosis chemotherapy with isoniazid (H)-rifampin (R)-pyrazinamide (Z)-ethambutol (E).Patients and methods(1) In this study, we recruited 168 stool specimens from 49 healthy volunteers without M. tuberculosis (Mtb), 30 healthy volunteers with latently infected by Mtb, 41 patients with active tuberculosis (ATB), 28 patients with 2-month HRZE treatment and 20 patients with 2-month HRZE followed by 4-month HR treatment. (2) We used 16S rRNA sequencing and an untargeted Liquid Chromatograph Mass Spectrometer-based metabolomics to investigate the changes of gut microbiome and the alteration of fecal metabolome, respectively, during anti-TB chemotherapy.ResultsMtb infection can reduce the diversity of intestinal flora of ATB patients and change their taxonomic composition, while the diversity of intestinal flora of ATB patients were restored during anti-TB chemotherapy. Especially, family Veillonellacea and Bateroidaceae and their genera Veillonella and Bacteroides significantly increased in the gut microbiota during anti-TB chemotherapy. Additionally, Mtb infection dynamically regulates fecal metabolism in ATB patients during anti-TB chemotherapy. Interestingly, the altered abundance of fecal metabolites correlated with the altered gut microbiota, especially the change of gut Clostridium, Bacteroides and Prevotella was closely related to the change of fecal metabolites such as Trans-4-Hydroxy-L-proline and Genistein caused by Mtb infection or anti-TB chemotherapy.ConclusionAnti-TB chemotherapy with HRZE can disrupt both gut microbiotas and metabolome in ATB patients. Some specific genera and metabolites are depleted or enriched during anti-TB chemotherapy. Therefore, revealing potential relevance between gut microbiota and anti-TB chemotherapy will provide potential biomarkers for evaluating the therapeutic efficacy in ATB patients.

Autologous Cytokine-Induced Killer Cell Immunotherapy Enhances Chemotherapy Efficacy against Multidrug-Resistant Tuberculosis.

Objective Multidrug-resistant tuberculosis (MDR-TB) causes persistent infection and challenges tuberculosis control worldwide. T cell-mediated immunity plays a critical role in controlling Mycobacterium tuberculosis (Mtb) infection, and therefore, enhancing Mtb-specific T cell immune responses represents a promising therapeutic strategy against TB. Cytokine-induced killer (CIK) immunotherapy is based on autologous infusion of in vitro expanded bulk T cells, which include both pathogen-specific and nonspecific T cells from patient peripheral blood mononuclear cells (PBMC) into TB patients. Preclinical mouse studies have shown that the adoptive T cell therapy inhibited Mtb infection. However, the efficacy of CIK immunotherapy in the treatment of MDR-TB infection has not been evaluated in clinical trials. Methods We performed a retrospective study of MDR-TB patients who received CIK immunotherapy in combination with anti-TB chemotherapy and those who had standard chemotherapy. Results Our results showed that CIK immunotherapy in combination with anti-TB chemotherapy treatment increased the conversion rate of sputum smear and Mtb culture, alleviated symptoms, improved lesion absorption, and increased recovery. The kinetics of serology and immunology index monitoring data showed good safety profiles for the CIK treatment. Conclusion Our study has provided strong evidence that CIK immunotherapy in combination with anti-TB chemotherapy is beneficial for MDR-TB patients. A multicenter clinical trial is warranted to evaluate CIK as a new immune therapy for MDR-TB.

Diagnosis and Management of Occult Cervical Tuberculous Lymphadenopathy.

Objective: Some cervical tuberculous lymphadenopathy (CTL) presents no evidence of tuberculosis (TB), even after thorough examination of a fine-needle aspiration (FNA) specimen. After the examination of excisional specimens, when the polymerase chain reaction (PCR) analysis identifies the nucleic acid of Mycobacterium tuberculosis (Mtb) or the culture results are positive, then the diagnosis of CTL is established. We refer to this condition as occult CTL (OCTL). Patient and Methods: The present work is a retrospective review of a consecutive series of OCTL cases that were treated at the Department of Otolaryngology-Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, between June 2015 and September 2020. When the diagnosis of OCTL was established, the patients received the standard anti-TB chemotherapy. Results: Fourteen cases of OCTL, including 9 female and 5 male patients, aged 24 to 71years (median age 42years), were included in the present study. The most commonly observed levels of lymph node involvement were level V and level II. Each level of the involved lymph nodes was removed entirely through en bloc surgical resection. An evaluation of the excisional specimens led to positive PCR results in all 14 cases, with 2 cases presenting positive culture and 3 cases exhibiting positive acid-fast bacilli (AFB) staining. Recovery was uneventful, and the anti-TB chemotherapy was completed in all cases. The median duration of follow-up was 29months, during which no case of TB relapse was observed. Conclusions: Wide surgical excision is crucial for the diagnosis and management of OCTL, and when used in combination with anti-TB chemotherapy, it results in satisfactory patient outcomes.