[Complications of intravesical BCG therapy].

INTRODUCTION: BCG instillations are considered to be the standard of care therapy for superficial urothelial bladder carcinoma. Although serious adverse events are uncommon, the presence of high fever for at least two days in conjunction with systemic and/or local organ manifestations (except for urogenital symptoms), with the exclusion of other causes, suffice for the diagnosis of a disseminated BCG infection. Microbiologic detection of the pathogen is not necessary for diagnosis, as the detection of granuloma is more often successful and sufficient. Therapy for this infection includes oral Isoniazid, Rifampicin and Ethambutol for six months.

Clofazimine as a substitute for rifampicin improves efficacy of Mycobacterium avium pulmonary disease treatment in the hollow-fiber model.

Mycobacterium avium complex pulmonary disease is treated with an azithromycin, ethambutol, and rifampicin regimen, with limited efficacy. The role of rifampicin is controversial due to inactivity, adverse effects, and drug interactions. Here, we evaluated the efficacy of clofazimine as a substitute for rifampicin in an intracellular hollow-fiber infection model. THP-1 cells, which are monocytes isolated from peripheral blood from an acute monocytic leukemia patient, were infected with M. avium ATCC 700898 and exposed to a regimen of azithromycin and ethambutol with either rifampicin or clofazimine. Intrapulmonary pharmacokinetic profiles of azithromycin, ethambutol, and rifampicin were simulated. For clofazimine, a steady-state average concentration was targeted. Drug concentrations and bacterial densities were monitored over 21 days. Exposures to azithromycin and ethambutol were 20%-40% lower than targeted but within clinically observed ranges. Clofazimine exposures were 1.7 times higher than targeted. Until day 7, both regimens were able to maintain stasis. Thereafter, regrowth was observed for the rifampicin-containing regimen, while the clofazimine-containing regimen yielded a 2 Log10 colony forming unit (CFU) per mL decrease in bacterial load. The clofazimine regimen also successfully suppressed the emergence of macrolide tolerance. In summary, substitution of rifampicin with clofazimine in the hollow-fiber model improved the antimycobacterial activity of the regimen. Clofazimine-containing regimens merit investigation in clinical trials.

Efficacy and safety of rifampicin-based triple therapy for non-puerperal mastitis: A single-arm, open-label, prospective clinical trial.

OBJECTIVES: To assess the efficacy and safety of rifampicin-based triple therapy (rifampicin, isoniazid, and ethambutol) for treating NPM. METHODS: This single-center, single-arm, prospective clinical trial was conducted at the Second Hospital of Shandong University (Jinan, China). Patients with pathologically diagnosed granulomatous lobular mastitis and periductal mastitis received triple drugs, i.e., rifampicin (450 mg/day), isoniazid (300 mg/day), and ethambutol (15 mg/kg/day), until complete response or the investigator decided to discontinue treatment. The primary endpoint was the complete response rate (CRR) assessed by the investigator. The secondary endpoints included the overall remission rate (ORR), recurrence rate (RR), and safety. RESULTS: A total of 218 patients were enrolled in the study between January 1, 2013 and October 31, 2020. With a median follow-up time of 48 months, the CRR and the ORR were 78.44% and 94.04%, respectively. While 13 patients (5.96%) demonstrated no response and 19 relapsed (8.72%). Adverse events (AEs) were not common. The most common AEs during treatment were liver dysfunction (1.83%), gastrointestinal reactions (1.83%), fatigue (1.83%), erythema (1.38%), and menstrual disorders (0.92%). CONCLUSION: Rifampicin, isoniazid, and ethambutol demonstrated promising response rates with acceptable safety profiles in patients with NPM. Further confirmatory trial is warranted in the future. TRIAL REGISTRATION: The study was approved by the Ethics Committee of the Second Hospital of Shandong University and retrospectively registered at the China Clinical Trial Registration Center (registration number: ChiCTR2100049591).

Atypical Morphology of a Typical Mycobacterial Infection.

A-24-year-old woman reported with asymptomatic facial lesions present for 6 months. Examination revealed two closely located nodules which were firm, nontender, slightly erythematosus with crusting over the left cheek (Figure 1A). There was no regional lymphadenopathy, and the systemic examination was within normal limits. The differential diagnosis included cutaneous leishmaniasis, keratoacanthoma, and basal cell carcinoma. Tissue smear from nodules failed to reveal Leishmania donovan bodies. The histopathologic examination revealed nonca-seating epithelioid granulomas with lymphocyte cuffing in the dermis (Figures 2A and 2B). Special staining performed with Ziehl-Neelsen and Periodic acid-Schiff (PAS) stains was negative. Tissue cultures for bacteria, mycobacteria, and fungi were also negative; however Mantoux test (MT) performed for latent tuberculosis was strongly positive. Sputum for acid fast bacilli was negative, and serology for human immuno-deficiency virus (HIV)-1 and HIV-2 was nonreactive. A chest x-ray and ultrasound of the abdomen did not reveal any abnormality. Although the morphology of skin lesions did not favor classic lupus vulgaris (LV), considering the endemicity of tuberculosis in India, positive results of Mantoux test, and a dermal epithelioid granuloma, the patient was prescribed antitubercular therapy (ATT), comprising isoniazid, rifampicin, ethambutol, and pyrazinamide. Dramatic response was observed after 2 months, and complete healing with residual scarring took place in next 4 months (Figure 1B).

Visual change as the presenting symptom of a suspected metastatic brain lesion in esophageal cancer: A case report.

INTRODUCTION: Esophageal cancer is the seventh most common malignancy worldwide and the sixth leading cause of cancer mortality with an overall survival rate of <20%. Esophageal cancer frequently metastasizes to distant lymph nodes, lungs, liver, and bones. Cerebral metastases originating from esophageal cancer are rare and often carry a poor prognosis as do most all metastatic lesions in esophageal cancer. CASE PRESENTATION: In this report, we describe a 55-year-old patient with past history of esophageal carcinoma who presented with blurred vision after taking ethambutol for tuberculosis. Ethambutol-induced optic neuropathy was the lead diagnosis. Initial vision testing was normal so additional testing with visual field examination was warranted. The visual field examination revealed homonymous hemianopsia. Subsequent magnetic resonance imaging of his brain, demonstrated a focal lesion, consistent with but not diagnostic of a brain metastasis likely from his primary esophageal malignancy. CONCLUSION: We conclude that a careful review of the medical history and comprehensive assessment are essential in establishing an obscure clinical diagnosis especially in the event that an uncommon metastatic lesion is encountered.

Metagenomic next-generation sequencing identifying a rare case of Mycobacterium xenopi discitis.

Mycobacterium xenopi is a non-tuberculous mycobacterium (NTM) that sporadically causes infections in humans and can cause rare bone and joint infections in immunocompromised hosts with history of spinal surgery. This slow-growing mycobacterium takes 8-12 weeks to grow on culture. Metagenomic next-generation sequencing (MNGS) is a highly sensitive and specific plasma-based microbial cell-free DNA test that can detect M. xenopi weeks prior to culture growth. We present a case of M. xenopi lumbosacral discitis with presacral abscess in an immunocompromised woman without history of spinal surgery which was detected by MNGS 8 weeks prior to culture growth. The patient's discitis resolved with an M. xenopi-directed regimen of ethambutol, rifampin and azithromycin. This case illustrates the utility of next-generation sequencing tests in rapid diagnosis of rare and opportunistic infections, as compared with traditional diagnostic tests, with supporting contextual clinical and diagnostic findings.

Uncommon but Clinically Significant: Bacillus Calmette-Guerin (BCG) Infection of the Urinary Tract and its Impact on Quality of Life.

BACKGROUND The intravesical administration of bacillus Calmette-Guerin (BCG), an attenuated live strain of Mycobacterium bovis, is an immunotherapy given for superficial bladder cancer and is generally well tolerated and widely used. However, BCG sometimes causes local infections, such as cystitis and prostatitis or systemic infection. Because BCG infection is a rare complication of intravesical BCG instillation, the combination of an anti-tuberculous regimen and its duration of are unknown. CASE REPORT We describe 2 cases of BCG infection localized to the urinary tract. Case 1 was a 77-year-old man with BCG infection of the bladder and prostate. Combination therapy of anti-tuberculous agents with isoniazid, rifampicin, and ethambutol did not improve his symptoms, and his quality of life was significantly impaired from the symptoms of BCG infection; therefore, he underwent total resection of the bladder and prostate. Case 2 was an 84-year-old man with BCG infection of the bilateral ureter and bladder. It took 15 months for his symptoms to improve, but combination therapy with isoniazid, rifabutin, and ethambutol improved his condition completely. CONCLUSIONS Although BCG infection of the urinary tract is a rare complication, it is clinically important because it directly affects the quality of life of patients and requires a longer duration of treatment, depending on the symptoms. Tissue cultures are also difficult to culture, making a definitive diagnosis challenging. If the symptoms of BCG infection are not controlled, surgery can be necessary even if it is not a complication of a vital organ.

Effectiveness and Pharmacokinetic Exposures of First-Line Drugs Used to Treat Drug-Susceptible Tuberculosis in Children: A Systematic Review and Meta-Analysis.

BACKGROUND: Optimal doses of first-line drugs for treatment of drug-susceptible tuberculosis in children and young adolescents remain uncertain. We aimed to determine whether children treated using World Health Organization-recommended or higher doses of first-line drugs achieve successful outcomes and sufficient pharmacokinetic (PK) exposures. METHODS: Titles, abstracts, and full-text articles were screened. We searched PubMed, EMBASE, CENTRAL, and trial registries from 2010 to 2021. We included studies in children aged <18 years being treated for drug-susceptible tuberculosis with rifampicin (RIF), pyrazinamide, isoniazid, and ethambutol. Outcomes were treatment success rates and drug exposures. The protocol for the systematic review was preregistered in PROSPERO (no. CRD42021274222). RESULTS: Of 304 studies identified, 46 were eligible for full-text review, and 12 and 18 articles were included for the efficacy and PK analyses, respectively. Of 1830 children included in the efficacy analysis, 82% had favorable outcomes (range, 25%-95%). At World Health Organization-recommended doses, exposures to RIF, pyrazinamide, and ethambutol were lower in children than in adults. Children ≤6 years old have 35% lower areas under the concentration-time curve (AUCs) than older children (mean of 14.4 [95% CI 9.9-18.8] vs 22.0 [13.8-30.1] µg·h/mL) and children with human immunodeficiency virus (HIV) had 35% lower RIF AUCs than HIV-negative children (17.3 [11.4-23.2] vs 26.5 [21.3-31.7] µg·h/mL). Heterogeneity and small sample sizes were major limitations. CONCLUSIONS: There is large variability in outcomes, with an average of 82% favorable outcomes. Drug exposures are lower in children than in adults. Younger children and/or those with HIV are underexposed to RIF. Standardization of PK pediatric studies and individual patient data analysis with safety assessment are needed to inform optimal dosing.

Naringenin protects hepato-renal tissues against antituberculosis drugs induced toxic manifestations by modulating interleukin-6, insulin like growth factor-1, biochemical and ultra-structural integrity.

BACKGROUND: The antituberculosis drugs (ATDs), isoniazid, rifampicin, pyrazinamide and ethambutol prompt extreme hepatic and renal damage during treatment of tuberculosis. The present study aimed to investigate protective potential of naringenin against ATDs induced hepato-renal injury. METHODS: Rats were administered with ATDs (pyrazinamide; 210, ethambutol; 170, isoniazid; 85, rifampicin; 65 mg/kg b.wt) orally for 8 weeks (3 days/week) followed by naringenin at three different doses (10, 20 and 40 mg/kg b.wt) conjointly for 8 weeks (3 days/week alternately to ATDs administration) and silymarin (50 mg/kg b.wt) as positive control. RESULTS: Exposure to ATDs caused significant increase in interleukin-6 (IL-6), triglycerides, cholesterol, bilirubin whereas depletion in insulin like growth factor-1 (IGF-1), albumin and glucose in serum. Endogenous antioxidant enzymes glutathione reductase (GR), glutathione peroxidase (GPx) and glucose-6-phosphate-dehydrogenase (G-6-PDH) were diminished in liver and kidney tissues with parallel increase in triglycerides, cholesterol, microsomal LPO and aniline hydroxylase (CYP2E1 enzyme). Ultra-structural observations of liver and kidney showed marked deviation in plasma membranes of various cellular and sub-cellular organelles after 8 weeks of exposure to ATDs. CONCLUSIONS: Conjoint treatment of naringenin counteracted ATDs induced toxic manifestations by regulating IL-6, IGF-1, CYP2E1, biochemical and ultra-structural integrity in a dose dependent manner. Naringenin has excellent potential to protect ATDs induced hepato-renal injury by altering oxidative stress, modulation of antioxidant enzymes, serum cytokines and ultra-structural changes.

Immune disturbances in female genital tuberculosis and latent genital tuberculosis.

BACKGROUND: Female genital tuberculosis (FGTB), an important clinical sub-type of extra-pulmonary tuberculosis (EPTB) is responsible for about 10% cases of infertility in India. Both FGTB and latent genital tuberculosis (LGTB) can cause infertility through blockage of fallopian tubes and through altered uterine endometrial receptivity. AIMS: This review tries to elucidates the role of various immune factors in FGTB and LGTB. CONTENT: Various immune disturbances are observed in FGTB and LGTB like growth factors and cytokines which inhibit implantation and several inflammatory signaling pathways like mitogen activated protein kinase (MAPK), natural killer (NK) cells, nuclear factor kappa-B (NF-KB), tumor necrosis factor (TNF), and toll like receptors (TLR) signaling are dysregulated. These altered immune factors and pathways may be detected in the endometrial biopsies at the early stages of disease before permanent damage. Prompt and adequate treatment with the four anti-tubercular drugs (rifampicin [R], isoniazid [H], pyrazinamide [Z], and ethambutol [E]) can increase pregnancy rates in some of these women. Assisted reproduction especially in-vitro fertilization and embryo transfer may be required for some women. IMPLICATIONS: Inflammatory pathways identified from the gene profiling have enabled development of potential biomarkers for early diagnosis of FGTB. Immunomodulation and novel biotechniques like stem cell transplantation, nanoparticles and host directed therapies are being tried in selected patients of FGTB and LGTB with promising results.

The patterns and distribution of female genital tuberculosis among Togolese patients.

Tuberculosis is a real public health problem in developing countries. The aim of our article was to study the epidemiological, clinical, diagnostic characteristics of female genital tuberculosis in Togo. This was a descriptive and cross-sectional study on all cases concerning histologically diagnosed female genital tuberculosis in the department of pathological anatomy of Lomé in 1997-2018 (20 years). We collected 22 cases of women's Genital tuberculosis (GT), representing 2.2% (1008 cases) of extra-pulmonary tuberculosis. The mean age of the patients was 33.8 ± 0.2 years. Nine (9) patients had a history of treated GT. Depending on the location, the ovaries and fallopian tubes were the most affected (n=9 cases, 40.9%). Eighteen patients (81.8%) had at least one immunosuppression factor including HIV in 13 patients (72.2%). The reasons for consultation were metrorrhagia and pelvic pain with an associated mass in 7 women discovered on clinical examination and imaging. The macroscopic appearance of the specimens was suggestive of the diagnosis of genital tuberculosis in 12 cases (54.5%). Histology revealed caseous necrosis isolated in 3 patients (13.6%) and associated with gigantocellular epithelioid granulomas in 19 patients (86.4%). The patients received standard antibiotic treatment combining rifampicin, isoniazid, ethambutol and pyrazinamide. Genital tuberculosis is a rare extra-pulmonary location in Togo, often occurring in women with HIV, and the clinical polymorphism can lead to confusion with gynecological cancers.

[A clinical case of occupational cutaneous tuberculosis in the healthcare field].

Cutaneous tuberculosis is a rare extrapulmonary pre-sentation of tuberculosis, caused by mycobacterial species of the Mycobacterium tuberculosis complex. We describe a case of cutaneous tuberculosis in a 57-year-old technician from the microbiology laboratory in our hospital. She accidentally experienced a needlestick injury with a hollow needle while at work. Skin lesion developed shortly after on the punctured finger. A biopsy was performed, revealing necrotizing (caseating) granulomatous inflammation. Pharmacological treatment was initiated with four standard drugs: isoniazid, rifampicin, pyrazinamide, and ethambutol hydrochloride. Improvement was observed, but the initial treatment had to be suspended due to intolerance to some of the drugs and changed to a treatment with isoniazid, rifampicin, and levofloxacin. The long duration of the treatment may increase the risk of toxic effects, making it necessary to discard the drug causing these effects and change the treatment regimen.

A Mycobacterium tuberculosis-Infected Patient Who Could Not Tolerate Oral Intake Successfully Treated Using an Intravenous Tedizolid-Containing Regimen.

BACKGROUND Mycobacterium tuberculosis (M. tuberculosis) is usually treated by oral antimycobacterial agents, including rifampicin, ethambutol, and pyrazinamide, but the treatment regimen with intravenous and/or intramuscular antimycobacterial agents for patients who cannot take medications orally remains unclear. CASE REPORT A 77-year-old man with chronic renal failure had an esophageal-skin fistula after he had surgeries for removal of esophageal and gastric cancers and reconstruction using jejunum, and he showed a cavity, tree-in-bud formation, and pleural effusions in his left upper lung fields on his chest X-ray after treatment of cellulitis and bacteremia/candidemia by meropenem, teicoplanin, and micafungin. M. tuberculosis was isolated from his sputum and exudate fluid from the reconstructed esophageal-skin fistula. Although he could not take antimycobacterial agents orally, treatment was started with intravenous agents combining levofloxacin (LVFX) every other day, isoniazid (INH), and linezolid (LZD). However, his platelets were decreased 21 days after treatment started, and it was thought to be an adverse effect of LZD and/or INH. After changing LZD to tedizolid (TZD), in addition to changing from INH to intramuscular streptomycin twice per week, his platelet counts increased. Intravenous TZD could be continued, and it maintained his condition without exacerbations of thrombocytopenia and renal failure. The M. tuberculosis disappeared, and the abnormal chest X-ray shadows were improved 2 months after the start of treatment. CONCLUSIONS Administration of intravenous TZD, in addition to intravenous LVFX and intramuscular SM in combination, might be a candidate regimen for M. tuberculosis patients who cannot take oral medications.

Factors influencing treatment outcomes in patients with isoniazid-resistant pulmonary TB.

INTRODUCTION: Patients with isoniazid (H, INH) resistant pulmonary TB but undetected rifampicin (R, RIF) resistance are treated with a 6-month regimen of levofloxacin-RIF-ethambutol-pyrazinamide (6LvxREZ) under India´s National TB Elimination Programme (NTEP).OBJECTIVE: To describe the profile of and treatment outcomes in patients with pulmonary INH-resistant (INHR) TB initiated on TB treatment, and identify factors associated with unfavourable treatment outcomes (died, failed, treatment changed, lost to follow-up).METHODS: This was a retrospective analysis of NTEP database (Ni-kshay) on pulmonary INHR TB patients initiated on treatment with "H mono/poly regimen" (6LvxREZ) between July 2019 and June 2020 with documented treatment outcomes. Proportions with 95% confidence interval (CI) was calculated and logistic regression analysis was performed.RESULTS: Of the 11,519 patients with pulmonary INHR TB, 9,440 (82%) had treatment success (55.1% cured, 26.9% treatment completed). Unfavourable treatment outcome was observed in 1,901 (16.5%). Male sex, tobacco and alcohol use, HIV reactive status were associated with unfavourable treatment outcome. Patients with katG mutations and resistance to fluoroquinolones were likely to have poor treatment outcomes.CONCLUSION: A levofloxacin-based regimen offers a treatment success rate of 82% in patients with pulmonary INHR TB. Sex-specific strategies, interventions to address smoking and alcohol use, focus on HIV-reactive patients and optimising treatment regimens based on drug susceptibility should be considered for improving treatment outcomes.

[An atypical presentation of tuberculosis]. / Een atypische presentatie van tuberculose.

BACKGROUND: In 2020 there were 623 known TB infections in the Netherlands according to the Dutch ministry of health (RIVM). About 4% were located in bones and joints. The incidence of Multi Drug Resistant (MDR) TB in The Netherlands is about 1%. CASE: We describe the case of a 46-year-old female with a painful and swelling of the mid phalangeal bone of the fourth left digit. Quantiferon was positive and PCR of the biopsy for Mycobacterium tuberculosis complex (MTC) in Ziehl-Neelsen staining confirmed tuberculous osteomyelitis. The strain was resistant for rifampicin, isoniazid, ethambutol and pyrazinamid classifying it as MDR. Treatment in a specialized center with second line drugs was indicated due to rare resistance. CONCLUSION: Tuberculosis may manifest anywhere throughout the body, also as an (atypical) swelling of the hand. The golden diagnostic standard for bone and joint TB is biopsy with Ziehl-Neelsen staining.

Pyrazinamide related prolonged drug-induced liver injury: A case report.

RATIONALE: Drug induced liver injury (DILI) is a common side effect causing treatment discontinuation during tuberculosis (TB) treatment, and pyrazinamide (PZA) usually leads to a delayed and prolonged abnormal liver function of the 4 standard anti-tuberculosis regimens. However, a prolonged hepatitis lasting more than 4 months is rarely reported. PATIENT CONCERNS: A 78-year-old man presented with general weakness and poor appetite on his seventh week of anti-TB treatment for tuberculosis lymphadenitis. DIAGNOSIS: Drug induced liver injury, PZA-related. NAT2 slow acetylator phenotype was accidentally found during workup of DILI. INTERVENTION: A liver biopsy was performed and PZA-related DILI was suspected. All anti-TB medications were therefore discontinued. OUTCOME: After withholding all anti-TB medications for 4 months, the elevations of aminotransferases and hyperbilirubinemia completely resolved. Anti-TB therapy was switched to ethambutol and levofloxacin for 15 months without adverse events. Long-term ultrasound follow-up was performed and cervical lymphadenopathy completely resolved. CONCLUSION: Our patient presents with PZA related prolonged DILI resolved after drug discontinuation for 4 months. NAT2 slow acetylator phenotype may be related to this condition through unknown mechanisms.

[Action Mechanism of Ethambutol Tablets on Pulmonary Tuberculosis Rat Model Based on Janus Kinase/Signal Transducer and Activator of Transcription Signaling Pathway].

Objective To explore the therapeutic effect of ethambutol tablets (EMB) on pulmonary tuberculosis (PTB) in rats and whether the action mechanism of EMB is related to Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway. Methods Sixty SD rats were assigned into a control group,a PTB group,a PTB+EMB group (30 mg/kg),and a PTB+EMB+Colivelin (JAK/STAT pathway activator) group (30 mg/kg+1 mg/kg) via the random number table method,with 15 rats in each group.The rats in other groups except the control group were injected with 0.2 ml of 5 mg/ml Mycobacterium tuberculosis suspension to establish the PTB model.After the modeling,the rats were administrated with corresponding drugs for 4 consecutive weeks (once a day).On days 1,14,and 28 of administration,the body weights of rats were measured and the Mycobacterium tuberculosis colonies were counted.Hematoxylin-eosin staining was carried out to detect the pathological changes in the lung tissue.Enzyme-linked immunosorbent assay was employed to measure the levels of interleukin(IL)-6,tumor necrosis factor-α (TNF-α),IL-1ß,and interferon-γ (IFN-γ) in the serum.Flow cytometry was used to determine the levels of T lymphocyte subsets CD3+,CD4+,CD8+,and CD4+/CD8+.The 16S rRNA sequencing was performed to detect the relative abundance of the intestinal microorganisms.Western blotting was employed to determine the expression of the proteins in the JAK/STAT pathway. Results Compared with the control group,the modeling of PTB reduced the rat body weight (on days 14 and 28),increased Mycobacterium tuberculosis colonies,caused severe pathological changes in the lung tissue,and elevated the levels of IL-6,TNF-α,and IL-1ß in serum and CD8+.Moreover,the modeling increased the relative abundance of Bacteroides,Peptococcus,Clostridium,Actinomyces,Lactobacillus,Verrucomicrobium,and Veillonella in the intestine,up-regulated the protein levels of phosphorylated JAK2 and phosphorylated STAT3 in the lung tissue,and lowered the levels of CD3+,CD4+,CD4+/CD8+,and IFN-γ levels (all P<0.001).Compared with the PTB group,PTB+EMB increased the rat body weight (on days 14 and 28),reduced Mycobacterium tuberculosis colonies,alleviated the pathological damage in lung tissue,lowered the levels of IL-6,TNF-α,and IL-1ß in serum and CD8+.Moreover,the treatment decreased the relative abundance of Bacteroides,Peptococcus,Clostridium,Actinomyces,Lactobacillus,Verrucomicrobium,Veillonella in the intestine,down-regulated the protein levels of phosphorylated JAK2 and phosphorylated STAT3 in the lung tissue,and elevated the levels of CD3+,CD4+,CD4+/CD8+,and IFN-γ (all P<0.001).Colivelin weakened the alleviation effect of EMB on PTB (all P<0.001). Conclusion EMB can inhibit the JAK/STAT signaling pathway to alleviate the PTB in rat.

The Effect of Citicoline on Ethambutol Optic Neuropathy: Histopathology and Immunohistochemistry Analysis of Retina Ganglion Cell Damage Level in Rat Model.

Purpose: Ethambutol therapy in certain doses and period can cause bilateral ocular intoxication. There is no definitive therapy that has been found to prevent damage to retina neuronal cells in ethambutol optic neuropathy (EON) cases. Citicoline is thought to have a potential effect to maintain retinal neuron cells. This study aimed to analyze the effect of citicoline on damaged rat ganglion cells in EON. Methods: An experimental study of 15 Wistar rats was divided into 3 groups: the nontreatment group (A), the ethambutol (35 mg/kg/day) group (B), and the ethambutol (35 mg/kg/day) and citicoline (1 g/kg/day) group (C). Groups B and C were given treatment orally for 30 days, then a histopathology examination was performed to analyze retinal ganglion cell (RGC) density, and immunohistochemistry to assess bcl-2 and caspase-3 expression. Results: RGC density of rat with ethambutol intoxication that received citicoline was higher than those who did not get citicoline (P < 0.001). The rat retina ganglion layer without citicoline administration is thicker than the one with citicoline, the increase in thickness is due to the formation of vacuoles in the cytoplasm of ganglion cells. Rat with citicoline obtained higher bcl-2 ganglion expression, and lower caspase-3 expression compared with rat without citicoline. Conclusions: The ganglion cells damage process caused by EON can be suppressed by citicoline administration. It was proven by analyzing RGC density, ganglion layer thickness, and expression level of bcl-2 and caspase-3 on rat model.

Paradoxical upgrading reaction following treatment of disseminated tuberculosis-associated haemophagocytic lymphohistiocytosis in an infant without HIV: a case report and review of the literature.

Tuberculosis-associated haemophagocytic lymphohistiocytosis (HLH) is rare in paediatrics and can be fatal if not recognised and treated on time. A 3-month-old infant with tuberculosis and HLH is described. He was successfully treated with anti-tuberculous therapy (ATT) which comprised isoniazid, rifampicin, pyrazinamide, ethambutol, streptomycin and dexamethasone (10 mg/m2/day). On Day 28 of therapy, he developed a paradoxical upgrading reaction to ATT for which he was again treated with (oral) corticosteroids for 4 weeks. He recovered successfully and is now completely well and asymptomatic. To the best of our knowledge, this is the first case of a child having a paradoxical upgrading reaction following treatment for TB-HLH.Abbreviations ATT: anti-tuberculous therapy; CB-NAAT: cartridge-based nucleic acid amplification test; CECT: contrast-enhanced computed tomography; HLH: haemophagocytic lymphohistiocytosis; NK: natural killer, PUR: paradoxical upgrading reaction; sHLH: secondary HLH.

Ethambutol-induced optic neuropathy: Functional and structural changes in the retina and optic nerve.

BACKGROUD: Ethambutol hydrochloride (EMB) is used in the treatment of tuberculosis and is used as first line modality in combination with other medications. Ethambutol optic neuropathy (EON) is a rare but well-recognised adverse ocular event in patients who receive ethambutol for the treatment of mycobacterial infections and may be potentially devastating with reversible to irreversible changes in visual acuity. KEY FINDINGS: Optical coherence tomography has been used to evaluate the thickness of retinal nerve fibre and ganglion cell layers to look for degenerative changes and early markers. Electrophysiological tests like multifocal electroretinogram, visual evoked potentials and visual fields have been used to understand the functional changes associated with established EON and also whether these can be used to detect subclinical EON and correlate them with the structural changes. In this review, we have summarised evidence published till December 2021 related to evaluation of structural and functional changes in the retina and optic nerve in eyes with EON.