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Apremilast is a relatively new oral treatment for psoriasis, which reduces expression of pro‐inflammatory factors, including tumour necrosis factor‐α (TNFα), critical to the immune control of Mycobacterium tuberculosis infection. In randomised controlled trials (RCTs) for apremilast no new cases of active tuberculosis (TB) were identified, thus, screening for latent TB infection (LTBI) is not currently recommended prior to apremilast initiation. We describe a case of M.tuberculosis reactivation shortly after commencement of apremilast for psoriasis. We are recommending clinicians perform LTBI risk assessment in all patients, and appropriate LTBI screening in select populations prior to apremilast initiation. [ABSTRACT FROM AUTHOR]

Mendelian susceptibility to mycobacterial diseases (MSMD) is a rare clinical syndrome characterized by vulnerability to weakly virulent mycobacterial species, including Bacillus Calmette-Guérin (BCG) vaccines and environmental mycobacteria. We sought to perform a systematic review of the genetic, immunologic, and clinical findings for reported patients with MSMD. We searched PubMed, Web of Science, and Scopus databases for publications in English relating to MSMD. All full texts were evaluated for eligibility for inclusion. Two reviewers independently selected the publications, with a third reviewer consulted in cases of disagreement. A primary systematic search and searches of other resources identified 16,155 articles. In total, 158 articles from 63 countries were included in qualitative and quantitative analyses. In total, 830 patients—436 males (52.5%), 369 females (44.5%), and 25 patients of unknown sex (3.0%)—from 581 families were evaluated. A positive family history was reported in 347 patients (45.5%). The patients had a mean age of 10.41 ± 0.42 (SEM) years. The frequency of MSMD was highest in Iran, Turkey, and Saudi Arabia. Lymphadenopathy was the most common clinical manifestation of MSMD, reported in 378 (45.5%) cases and multifocal in 35.1%. Fever, organomegaly, and sepsis were the next most frequent findings, reported in 251 (30.2%), 206 (24.8%), and 171 (20.8%) cases, respectively. In total, 299 unique mutations in 21 genes known to be involved in MSMD were reported: 100 missense (34%), 80 indel-frameshift (insertion or deletion, 27%), 53 nonsense (18%), 35 splice site (12%), 10 indel-in frame (2.7%), 6 indel (2%), and 15 large deletion/duplication mutations. Finally, 61% of the reported patients with MSMD had mutations of IL12RB1 (41%) or IFNGR1 (20%). At the time of the report, 177 of the patients (21.3%) were dead and 597 (71.9%) were still alive. MSMD is associated with a high mortality rate, mostly due to impaired control of infection. Preexposure strategies, such as changes in vaccination policy in endemic areas, the establishment of a worldwide registry of patients with MSMD, and precise follow-up over generations in affected families, appear to be vital to decrease MSMD-related mortality. [ABSTRACT FROM AUTHOR]

Mycobacterial infection in Nile crocodile tissues sent from a private zoo was characterized pathomorphologically and immunohistochemically in this case. Macroscopically, multifocal, greyish-white areas ranging in size from 1 mm to 5 mm were seen in the lung, liver, and spleen. Histologically, a large number of well-demarcated necrotic areas were seen. These areas included nuclei debris locally. Inflammatory cells along with a couple of multinucleated giant cells surrounded the necrotic cores. Numerous acid-fast bacilli were detected by Ziehl-Neelsen staining method. Immunolabelling for both Mycobacterium bovis and anti-BCG antibodies was positive in each tissue. [ABSTRACT FROM AUTHOR]

Ocular tuberculosis (OTB) is a chronic eye infection caused by Mycobacterium tuberculosis. Some cases of myelitis are associated with Epstein-Barr virus (EBV), with 1-5% of EBV infections leading to neurologic complications. We describe a 34-year-old Iranian woman with OTB and EBV coinfection. Despite initial success with anti-TB agents, the disease progressed, necessitating enucleation. Mycobacterium tuberculosis was detected by a tuberculin coagulation test, and EBV was confirmed via polymerase chain reaction. MRI showed plaques in the spinal cord and brain. The patient was treated with anti-TB and antiretroviral agents. Recognizing TB in the differential diagnosis of EBV myelitis is crucial.

Abstract Background Mycobacterium abscessus, a fast-growing non-tuberculous mycobacterium, is an emerging opportunistic pathogen responsible for chronic bronchopulmonary infections in people with respiratory diseases such as cystic fibrosis (CF). Due to its intrinsic polyresistance to a wide range of antibiotics, most treatments for M. abscessus pulmonary infections are poorly effective. In this context, antimicrobial peptides (AMPs) active against bacterial strains and less prompt to cause resistance, represent a good alternative to conventional antibiotics. Herein, we evaluated the effect of three arenicin isoforms, possessing two or four Cysteines involved in one (Ar-1, Ar-2) or two disulfide bonds (Ar-3), on the in vitro growth of M. abscessus. Methods The respective disulfide-free AMPs, were built by replacing the Cysteines with alpha-amino-n-butyric acid (Abu) residue. We evaluated the efficiency of the eight arenicin derivatives through their antimicrobial activity against M. abscessus strains, their cytotoxicity towards human cell lines, and their hemolytic activity on human erythrocytes. The mechanism of action of the Ar-1 peptide was further investigated through membrane permeabilization assay, electron microscopy, lipid insertion assay via surface pressure measurement, and the induction of resistance assay. Results Our results demonstrated that Ar-1 was the safest peptide with no toxicity towards human cells and no hemolytic activity, and the most active against M. abscessus growth. Ar-1 acts by insertion into mycobacterial lipids, resulting in a rapid membranolytic effect that kills M. abscessus without induction of resistance. Conclusion Overall, the present study emphasized Ar-1 as a potential new alternative to conventional antibiotics in the treatment of CF-associated bacterial infection related to M. abscessus.

This article discusses a rare case of influenza and rapid progressive neurotuberculosis coinfection in a 22-year-old Indian woman living in Germany. The patient initially presented with high fever, joint pain, and headache, and was diagnosed with Influenza B. However, she was readmitted a few days later with worsening symptoms, including seizures and neurological deficits. Further testing revealed a Mycobacterium tuberculosis infection in the brain and spine. The article emphasizes the importance of interdisciplinary diagnostics, especially in migrants from low- and middle-income countries, and highlights the increasing prevalence of complex infections like tuberculosis in low-incidence countries. [Extracted from the article]

Background: Autosomal recessive interleukin (IL)-12p40 deficiency is a genetic etiology of Mendelian susceptibility to mycobacterial disease (MSMD). It has been described in ∼50 patients, usually with onset at childhood with Bacille Calmette-Guérin (BCG) and Salmonella infections. Case Presentation: A male patient born to consanguineous parents was diagnosed with presumed lymph node MSMD at the age of 13 years after ocular symptoms. A positive history of inborn error of immunity was present: BCG reaction, skin abscess, and recurrent oral candidiasis. Abnormal measurements of cytokine levels, IL-12p40 and interferon-gamma (IFN-γ), lead to the diagnosis of MSMD. Genetic analysis showed a mutation in exon 7 of the IL12B gene. Currently, the patient is alive under prophylactic antibiotics. Conclusion: We report a rare case of IL-12p40 deficiency in a Latin American patient. Medical history was crucial for immune defect suspicion, as confirmed by precision diagnostic medicine tools. [ABSTRACT FROM AUTHOR]

Augmentation mammoplasty is one of the most popular cosmetic surgeries, but there is a high reoperation rate (29.7%) commonly due to capsular contracture, implant malpositioning, infection, and unsatisfactory size. Although infection only accounts for 2% of cases, its management is very challenging, especially with nontuberculous mycobacteria (NTM) infection. Breast prosthetic NTM infection is a rare but is a disastrous condition with an incidence of approximately 0.013%. Immediate salvage reimplantation is usually not suggested, and most studies recommend a gap of 3 to 6 months after combination antibiotics therapy before reimplantation. However, delayed reimplantation often leads to great psychological stress and struggle between the doctor and patient. We present the case report of successful reimplantation in treating prosthetic NTM infections in a 28-year-old female. We discuss a novel technique “transaxillary capsulorrhaphy” to correct the bottoming-out deformity. One year after the combination of antibiotics and surgery, the follow-up computed tomography scan showed complete remission of NTM without recurrence. We discuss the surgical technique in detail. The 1-year follow-up assessment (photos and dynamic video) revealed good cosmesis and reliable correction using the new technique. This report is the first formal description and discussion of one-stage reimplantation following NTM infections. Transaxillary capsulorrhaphy allows for a successful salvage operation when an implant is displaced. This approach provides highly favorable result in eastern women undergoing revision augmentation mammoplasty. This study reflects level of evidence V, considering opinions of respected authorities based on clinical experience, descriptive studies, or reports of expert committees.

Summary: Case: A 36-year-old female healthcare worker with no past medical history, accidentally injected her flexed right middle finger with live attenuated Mycobacterium bovis bacillus Calmette-Guérin (BCG). Swelling and erythema around the injured area appeared two days after the needlestick injury. She was referred to the hospital and presented approximately nine days after self-inoculation. Surgical debridement was immediately performed. After 38 days, colonies were observed on cultures of the removed tissue on Ogawa's medium. This isolate was identified as M. bovis BCG by polymerase chain reaction (PCR) based on RD1 gene deletion. She had a history of BCG vaccination and her skin lesion appeared immediately after the accidental injection of M. bovis BCG. Therefore, in the differential diagnosis, the possibility that the lesion was an allergic reaction to BCG was considered. The subsequent culture results came back positive for M. bovis BCG and acute tenosynovitis caused by M. bovis BCG was diagnosed. The skin lesion was treated with anti-mycobacterial drugs and resolved. Discussion: The allergic reactions to BCG should be considered in the differential diagnosis of skin lesions following BCG vaccination. It is important to promptly submit a specimen for culture as delayed initiation of appropriate treatment can lead to a poor prognosis. In patients with accidental injection of M. bovis BCG, it is important to consider timely surgical excision and appropriate antimycobacterial therapy.

Background: The incidence of mycobacterial infections in patients with hematologic malignancies and hematopoietic stem cell transplant (HSCT) recipients is increasing, contributing to significant mortality and morbidity. This review explores the epidemiology, risk factors, clinical presentation, diagnosis, and treatment of nontuberculous mycobacteria (NTM) in this population. Methods: A literature search was performed using PubMed with keywords and MeSH terms pertaining to the topics of nontuberculous mycobacteria, hematologic malignancies, hematopoietic stem cell transplant, cellular therapies, chimeric antigen therapies, epidemiology, diagnosis, and treatment. Additionally, we examined the reference lists of the included articles to identify other pertinent studies. Results: Diagnosing mycobacterial disease among patients with hematologic disease and treatment‐associated immunosuppressive conditions is challenging due to the lack of distinctive clinical, radiographic, and laboratory markers, as well as the atypical manifestations compared to immunocompetent patients. Treatment involves using a combination of antibiotics for extended durations, coupled with strategies to achieve source control and reduce immunosuppression when feasible. This is complicated by the absence of clear data correlating in‐vitro drug susceptibility and clinical outcome for many antimicrobials use to treat NTM, adverse drug‐drug interactions, and the frequent challenges related to poor medication tolerability and toxicities. Conclusion: The rising incidence and corresponding clinical challenges of mycobacterial infections in this unique patient population necessitate a heightened awareness and familiarity of NTM disease by clinicians to achieve timely diagnosis and favorable treatment outcomes. [ABSTRACT FROM AUTHOR]

Augmentation mammoplasty is one of the most popular cosmetic surgeries, but there is a high reoperation rate (29.7%) commonly due to capsular contracture, implant malpositioning, infection, and unsatisfactory size. Although infection only accounts for 2% of cases, its management is very challenging, especially with nontuberculous mycobacteria (NTM) infection. Breast prosthetic NTM infection is a rare but is a disastrous condition with an incidence of approximately 0.013%. Immediate salvage reimplantation is usually not suggested, and most studies recommend a gap of 3 to 6 months after combination antibiotics therapy before reimplantation. However, delayed reimplantation often leads to great psychological stress and struggle between the doctor and patient. We present the case report of successful reimplantation in treating prosthetic NTM infections in a 28-year-old female. We discuss a novel technique "transaxillary capsulorrhaphy" to correct the bottoming-out deformity. One year after the combination of antibiotics and surgery, the follow-up computed tomography scan showed complete remission of NTM without recurrence. We discuss the surgical technique in detail. The 1-year follow-up assessment (photos and dynamic video) revealed good cosmesis and reliable correction using the new technique. This report is the first formal description and discussion of one-stage reimplantation following NTM infections. Transaxillary capsulorrhaphy allows for a successful salvage operation when an implant is displaced. This approach provides highly favorable result in eastern women undergoing revision augmentation mammoplasty. This study reflects level of evidence V, considering opinions of respected authorities based on clinical experience, descriptive studies, or reports of expert committees. [ABSTRACT FROM AUTHOR]

Copyright of Journal der Deutschen Dermatologischen Gesellschaft is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary: Mycobacterium haemophilum (MH) is a slow‐growing, non‐tuberculous Mycobacterium that most commonly causes infections in immunocompromised patients. The skin is the most prevalent site of infection and can be an isolated presentation or part of a disseminated disease. Herein, we reported a case of isolated MH infection of the hand and a case of disseminated MH infection with multiple skin lesions. In addition, other MH cases with cutaneous involvement over the last 10 years, from 2011–2022, were reviewed and analyzed. Among the 79 included cases, the common skin findings in MH infections included nodules, ulcers, abscesses, swelling, and pustules. Middle‐aged patients with iatrogenic immunosuppression from glucocorticoids, mycophenolate mofetil, cyclosporine, and cyclophosphamide are the most susceptible to MH infection, with a higher risk of dissemination to internal organs. Disseminated MH infections commonly present as tenosynovitis, arthritis/arthralgia, or osteomyelitis. There is a lack of strong evidence for treatment; however, triple therapy of quinolone, macrolides, and rifampicin is most often used in clinical practice. The overall prognosis is good. The presence of iatrogenic immunocompromised diseases, lesions involving the proximal limbs, and dissemination of MH infections are associated with worse clinical outcomes. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance is an increasing threat to human populations. The emergence of multidrug-resistant "superbugs" in mycobacterial infections has further complicated the processes of curing patients, thereby resulting in high morbidity and mortality. Early diagnosis and alternative treatment are important for improving the success and cure rates associated with mycobacterial infections and the use of mycobacteriophages is a potentially good option. Since each bacteriophage has its own host range, mycobacteriophages have the capacity to detect specific mycobacterial isolates. The bacteriolysis properties of mycobacteriophages make them more attractive when it comes to treating infectious diseases. In fact, they have been clinically applied in Eastern Europe for several decades. Therefore, mycobacteriophages can also treat mycobacteria infections. This review explores the potential clinical applications of mycobacteriophages, including phage-based diagnosis and phage therapy in mycobacterial infections. Furthermore, this review summarizes the current difficulties in phage therapy, providing insights into new treatment strategies against drug-resistant mycobacteria. [ABSTRACT FROM AUTHOR]

Local and systemic complications of Bacillus Calmette-Guérin therapy are important to recognize as they require prolonged antimicrobial therapy; molecular genomic testing may be key to diagnosis when culture data are inconclusive.

A 59-year-old woman with prior bilateral lower eyelid autologous fat transfer, subdermal micro-needling and fractional radiofrequency skin resurfacing presented with delayed left-sided preseptal cellulitis with small multinodular abscesses unresponsive to oral outpatient antibiotic regimens and inpatient intravenous antibiotics. Wound culture revealed Mycobacterium chelonae infection treated successfully with a 4-month regimen of clarithromycin and tedizolid without recurrence. This case highlights (1) the need for vigilance and a broad differential in delayed post-operative wound infections including non-tuberculous mycobacterial infections, (2) resolution of infection without recurrence on clarithromycin and novel tedizolid oral antibiotic therapy, and (3) that caution should be exercised when performing combination autologous fat transfers with subdermal micro-needling procedures as the breakdown in skin integrity may potentiate infection. [ABSTRACT FROM AUTHOR]

Summary: Bovine tuberculosis is a contagious and zoonotic disease of animals and humans. In Europe, the number of reported cases of tuberculosis has decreased. Equidae are relatively rarely infected even in endemic areas. The presented report describes a case of chronic Mycobacterium bovis tuberculosis in a 30‐year‐old female donkey. The donkey initially presented with persistent lymphadenopathy; however, as the disease progressed, weight loss became apparent. To the authors' knowledge, this is the second confirmed case of tuberculosis in a donkey in Europe. [ABSTRACT FROM AUTHOR]

Mycobacterium tuberculosis (M. tb) is one of the successful pathogens and claim millions of deaths across the globe. The emergence of drug resistance in M. tb has created new hurdles in the tuberculosis elimination programme worldwide. Hence, there is an unmet medical need for alternative therapy, which could be achieved by targeting the host's critical signalling pathways that are compromised during M. tb infection. In this review, we have summarized some of the findings involving the modulation of host GPCRs in the regulation of the mycobacterial infection. Understanding the role of these GPCRs not only unravels signalling pathways during infection but also provides clues for targeting critical signalling intermediates for the development of GPCR‐based host‐directive therapy. LINKED ARTICLES: This article is part of GPCR Review Series. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/toc/10.1111/(ISSN)1476‐5381.GPCRReviews [ABSTRACT FROM AUTHOR]

Copyright of Osmangazi Journal of Medicine / Osmangazi Tip Dergisi is the property of Eskisehir Osmangazi University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Bovine tuberculosis (bTB), caused by Mycobacterium bovis, remains a high-priority global pathogen of concern. The role of youngstock animals in the epidemiology of bTB has not been a focus of contemporary research. Here we have aimed to collate and summarize what is known about the susceptibility, diagnosis, transmission (infectiousness), and epidemiology to M. bovis in youngstock (up to 1-year of age). Youngstock are susceptible to M. bovis infection when exposed, with the capacity to develop typical bTB lesions. Calves can be exposed through similar routes as adults, via residual infection, contiguous neighborhood spread, wildlife spillback infection, and the buying-in of infected but undetected cattle. Dairy systems may lead to greater exposure risk to calves relative to other production systems, for example, via pooled milk. Given their young age, calves tend to have shorter bTB at-risk exposure periods than older cohorts. The detection of bTB varies with age when using a wide range of ante-mortem diagnostics, also with post-mortem examination and confirmation (histological and bacteriological) of infection. When recorded as positive by ante-mortem test, youngstock appear to have the highest probabilities of any age cohort for confirmation of infection post-mortem. They also appear to have the lowest false negative bTB detection risk. In some countries, many calves are moved to other herds for rearing, potentially increasing inter-herd transmission risk. Mathematical models suggest that calves may also experience lower force of infection (the rate that susceptible animals become infected). There are few modeling studies investigating the role of calves in the spread and maintenance of infection across herd networks. One study found that calves, without operating testing and control measures, can help to maintain infection and lengthen the time to outbreak eradication. Policies to reduce testing for youngstock could lead to infected calves remaining undetected and increasing onwards transmission. Further studies are required to assess the risk associated with changes to testing policy for youngstock in terms of the impact for within-herd disease control, and how this may affect the transmission and persistence of infection across a network of linked herds.

Abstract Background It is challenging to proceed thoracoscopic anatomic resection when encountering severe pleural adhesion or calcified peribronchial lymphadenopathy. Compared with multiple-port video-assisted thoracoscopic surgery (MP-VATS), how to overcome these challenges in single-port (SP-) VATS is still an intractable problem. In the present study, we reported the surgical results of chronic inflammatory lung disease and shared some useful SP-VATS techniques. Methods We retrospectively assessed the surgical results of chronic inflammatory lung disease, primarily bronchiectasis, and mycobacterial infection, at our institution between 2010 and 2018. The patients who underwent SP-VATS anatomic resection were compared with those who underwent MP-VATS procedures. We analyzed the baseline characteristics, perioperative data, and postoperative outcomes, and illustrated four special techniques depending on the situation: flexible hook electrocautery, hilum-first technique, application of Satinsky vascular clamp, and staged closure of bronchial stump method. Results We classified 170 consecutive patients undergoing thoracoscopic anatomic resection into SP and MP groups, which had significant between-group differences in operation time and overall complication rate (P = 0.037 and 0.018, respectively). Compared to the MP-VATS group, the operation time of SP-VATS was shorter, and the conversion rate of SP-VATS was relatively lower (3.1% vs. 10.5%, P = 0.135). The most common complication was prolonged air leakage (SP-VATS, 10.8%; MP-VATS, 2.9%, P = 0.045). Conclusions For chronic inflammatory lung disease, certain surgical techniques render SP-VATS anatomic resection feasible and safe with a lower conversion rate.

Abstract Background Sarcoidosis is pathologically characterized by the formation of non-necrotizing epithelioid cell granulomas. However, pathological findings of patients with sarcoidosis have rarely revealed necrosis. We report here on a patient with sarcoidosis which needed to be distinguished from infectious disease because of marked necrosis in the lymph nodes. Case presentation A 46-year-old Japanese woman was referred to our hospital due to a dry cough and appetite loss. A chest X-ray and computed tomography revealed markedly enlarged mediastinal and hilar lymph nodes and hepatosplenomegaly. Surgical biopsy of these lymph nodes was performed in order to make a diagnosis. Pathological findings revealed epithelioid cell granuloma with marked necrosis that suggested infectious etiology such as mycobacterial and fungal infections. In addition to the pathological findings, immunoglobulin A (IgA) antibody for Mycobacterium avium complex (MAC), enlargement of lymph nodes and hepatosplenomegaly indicated disseminated MAC, while sarcoidosis was considered as another important differential diagnosis according to elevated angiotensin-converting enzyme, soluble interleukin-2 receptor and uveitis. While waiting for the results of the cultures of acid-fast bacilli, the symptoms of cough and consumption had worsened, and initiation of therapy was required before the confirmed diagnosis. The therapy for MAC was initiated because it was feared that immunosuppressive therapy containing corticosteroid for sarcoidosis could worsen the patient’s condition if MAC infection was the main etiology. However, the treatment for MAC was not effective, and it was clarified that no acid-fast bacilli were cultured in the liquid culture medium, so the diagnosis was corrected to sarcoidosis after reconsideration of clinical and pathological findings. Prednisolone (30 mg/day) was administered orally, and the patient’s symptoms and radiological findings improved. Conclusion Sarcoidosis must be considered even if pathological findings reveal marked necrosis, because rare cases of sarcoidosis exhibit extensive necrosis in lymph nodes. It is extremely important to carefully examine the clinical and pathological findings through discussion with the examining pathologist to reach the correct diagnosis.

The role of the innate immune response and host resistance to Mycobacterium tuberculosis infection (TB) is reviewed. Based on our data and the abundant literature, an early type 1 immune response is critical for infection control, while ILC3 and Th17 cells seem to be dispensable. Indeed, in M. tuberculosis infected mice, transcriptomic levels of Il17, Il17ra, Il22 and Il23a were not significantly modified as compared to controls, suggesting a limited role of IL-17 and IL-22 pathways in TB infection control. Neutralization of IL-17A or IL-17F did not affect infection control either. Ongoing clinical studies with IL-17 neutralizing antibodies show high efficacy in patients with psoriasis without increased incidence of TB infection or reactivation. Therefore, both experimental studies in mice and clinical trials in human patients suggest no risk of TB infection or reactivation by therapeutic IL-17 antibodies, unlike by TNF.

The NOD-like receptors (NLRs) have been shown to be involved in infection and autoinflammatory disease. Previously, we identified a zebrafish NLR, nlrc3-like , required for macrophage homeostasis in the brain under physiological conditions. Here, we found that a deficiency of nlrc3-like leads to decreased bacterial burden at a very early stage of Mycobacterium marinum infection, along with increased production of pro-inflammatory cytokines, such as il-1β and tnf-α. Interestingly, myeloid-lineage specific overexpression of nlrc3-like achieved the opposite effects, suggesting that the impact of nlrc3-like on the host anti-mycobacterial response is mainly due to its expression in the innate immune system. Fluorescence-activated cell sorting (FACS) and subsequent gene expression analysis demonstrated that inflammasome activation-related genes were upregulated in the infected macrophages of nlrc3-like deficient embryos. By disrupting asc , encoding apoptosis-associated speck-like protein containing a CARD, a key component for inflammasome activation, the bacterial burden increased in asc and nlrc3-like double deficient embryos compared with nlrc3-like single deficient embryos, implying the involvement of inflammasome activation in infection control. We also found extensive neutrophil infiltration in the nlrc3-like deficient larvae during infection, which was associated with comparable bacterial burden but increased tissue damage and death at a later stage that could be alleviated by administration of dexamethasone. Our findings uncovered an important role of nlrc3-like in the negative regulation of macrophage inflammasome activation and neutrophil infiltration during mycobacterial infection. This highlights the importance of a balanced innate immune response during mycobacterial infection and provides a potential molecular basis to explain how anti-inflammatory drugs can improve treatment outcomes in TB patients whose infection is accompanied by a hyperinflammatory response. [ABSTRACT FROM AUTHOR]

Background: Tuberculous meningitis (TBM) is the most frequent, severe, and disabling form of central nervous system (CNS) tuberculosis (TB). TBM paradoxical manifestations are characterized by clinical or paraclinical worsening after 1 month of effective anti-TB treatment in patients who initially responded to treatment despite the use of adjunctive corticosteroids. Methods: Retrospective descriptive study of consecutive HIV-negative adult patients (≥ 18 years) with definitive TBM who developed a paradoxical manifestation following anti-TB in a tertiary-care hospital in Mexico from 2009 to 2019; we also conducted a literature review of published cases/series of paradoxical manifestations in HIV-negative patients from 1980 to 2020. Results: We detected 84 cases of definitive TBM; 55 (68.7%) HIV-negative patients and 29 (36.3%) HIV-infected patients. Among HIV-negative patients, four (7.3%), three female and one male (19–49 years old), developed a paradoxical manifestation within 4–14 weeks following treatment initiation despite receiving adequate corticosteroid doses; Mycobacterium bovis was isolated from the cerebrospinal fluid of three cases and Mycobacterium tuberculosis in one more. Two patients developed vasculopathy-related cerebral infarctions, one severe basilar meningitis, and hydrocephalus, one more a tuberculoma. Two were treated with intravenous cyclophosphamide, and two with steroids. One of the patients treated with steroids died; patients who received cyclophosphamide had a good clinical response. Conclusions: This case series illustrates the diverse clinical/radiologic paradoxical manifestations of TBM in HIV-negative patients. Cyclophosphamide may be safe and effective in treating TBM-associated paradoxical manifestations. Specific diagnostic and care protocols for these patients are needed. [ABSTRACT FROM AUTHOR]

The NOD-like receptors (NLRs) have been shown to be involved in infection and autoinflammatory disease. Previously, we identified a zebrafish NLR, nlrc3-like, required for macrophage homeostasis in the brain under physiological conditions. Here, we found that a deficiency of nlrc3-like leads to decreased bacterial burden at a very early stage of Mycobacterium marinum infection, along with increased production of pro-inflammatory cytokines, such as il-1β and tnf-α. Interestingly, myeloid-lineage specific overexpression of nlrc3-like achieved the opposite effects, suggesting that the impact of nlrc3-like on the host anti-mycobacterial response is mainly due to its expression in the innate immune system. Fluorescence-activated cell sorting (FACS) and subsequent gene expression analysis demonstrated that inflammasome activation-related genes were upregulated in the infected macrophages of nlrc3-like deficient embryos. By disrupting asc, encoding apoptosis-associated speck-like protein containing a CARD, a key component for inflammasome activation, the bacterial burden increased in asc and nlrc3-like double deficient embryos compared with nlrc3-like single deficient embryos, implying the involvement of inflammasome activation in infection control. We also found extensive neutrophil infiltration in the nlrc3-like deficient larvae during infection, which was associated with comparable bacterial burden but increased tissue damage and death at a later stage that could be alleviated by administration of dexamethasone. Our findings uncovered an important role of nlrc3-like in the negative regulation of macrophage inflammasome activation and neutrophil infiltration during mycobacterial infection. This highlights the importance of a balanced innate immune response during mycobacterial infection and provides a potential molecular basis to explain how anti-inflammatory drugs can improve treatment outcomes in TB patients whose infection is accompanied by a hyperinflammatory response.

Background: Resistance to anti-tuberculosis (TB) drugs is a major issue in TB control, and demands the discovery of new drugs targeting the virulence factor ESX-1.Methods: We first established a high-throughput screen (HTS) assay for the discovery of ESX-1 secretion inhibitors. The positive hits were then evaluated for the potency of diminishing the survival of virulent mycobacteria and reducing bacterial virulence. We further investigated the probability of inducing drug resistance and the underlying mechanism using mycobacterial protein fragment complementation.Results: A robust HTS assay was developed to identify small molecules that inhibit ESX-1 secretion without impairing bacterial growth in vitro. A hit named IMB-BZ specifically inhibits the secretion of CFP-10 and reduces virulence in an ESX-1-dependent manner, therefore resulting in significant reduction in intracellular and in vivo survival of mycobacteria. Blocking the CFP-10-EccCb1 interaction directly or indirectly underlies the inhibitory effect of IMB-BZ on the secretion of CFP-10. Importantly, our finding shows that the ESX-1 inhibitors pose low risk of drug resistance development by mycobacteria in vitro as compared with traditional anti-TB drugs, and exhibit high potency against chronic mycobacterial infection.Conclusions: Targeting ESX-1 may lead to the development of novel therapeutics for tuberculosis. IMB-BZ holds the potential for future development into a new anti-TB drug. [ABSTRACT FROM AUTHOR]

(C) Flow cytometric analysis in patient compared with healthy control, showing significantly reduced IFN- R1 expression and normal IFN- R2 expression. In a novel form of IFN-gamma receptor 1 deficiency, cell surface receptors fail to bind IFN-gamma. Keywords: HLH; IFNGR; interferon-gamma receptor deficiency; leishmaniasis; mycobacterial infection EN HLH IFNGR interferon-gamma receptor deficiency leishmaniasis mycobacterial infection 1 4 4 01/05/22 20220101 NES 220101 ACKNOWLEDGEMENT We would like to thank the patient and his family for participation in this research. IFN R1 deficiency presenting with visceral leishmaniasis and Mycobacterium Avium infections mimicking HLH. [Extracted from the article]

Summary: The two human pathogens Helicobacter pylori and Mycobacterium tuberculosis (Mtb) co-exist in many geographical areas of the world. Here, using a co-infection model of H. pylori and the Mtb relative M. bovis bacillus Calmette-Guérin (BCG), we show that both bacteria affect the colonization and immune control of the respective other pathogen. Co-occurring M. bovis boosts gastric Th1 responses and H. pylori control and aggravates gastric immunopathology. H. pylori in the stomach compromises immune control of M. bovis in the liver and spleen. Prior antibiotic H. pylori eradication or M. bovis-specific immunization reverses the effects of H. pylori. Mechanistically, the mutual effects can be attributed to the redirection of regulatory T cells (Treg cells) to sites of M. bovis infection. Reversal of Treg cell redirection by CXCR3 blockade restores M. bovis control. In conclusion, the simultaneous presence of both pathogens exacerbates the problems associated with each individual infection alone and should possibly be factored into treatment decisions.

Extracellular vesicles (EVs), such as exosomes, play a critical role in cell-to-cell communication and regulating cellular processes in recipient cells. Non-tuberculous mycobacteria (NTM), such as Mycobacterium abscessus, are a group of environmental bacteria that can cause severe lung infections in populations with pre-existing lung conditions, such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). There is limited knowledge of the engagement of EVs in the host-pathogen interactions in the context of NTM infections. In this study, we found that M. abscessus infection increased the release of a subpopulation of exosomes (CD9, CD63, and/or CD81 positive) by mouse macrophages in cell culture. Proteomic analysis of these vesicles demonstrated that M. abscessus infection affects the enrichment of host proteins in exosomes released by macrophages. When compared to exosomes from uninfected macrophages, exosomes released by M. abscessus-infected macrophages significantly improved M. abscessus growth and downregulated the intracellular level of glutamine in recipient macrophages in cell culture. Increasing glutamine concentration in the medium rescued intracellular glutamine levels and M. abscessus killing in recipient macrophages that were treated with exosomes from M. abscessus-infected macrophages. Taken together, our results indicate that exosomes may serve as extracellular glutamine eliminators that interfere with glutamine-dependent M. abscessus killing in recipient macrophages., (© 2024 Wiley‐VCH GmbH.)

Ocular tuberculosis (OTB) is a chronic eye infection caused by Mycobacterium tuberculosis . Some cases of myelitis are associated with Epstein-Barr virus (EBV), with 1-5% of EBV infections leading to neurologic complications. We describe a 34-year-old Iranian woman with OTB and EBV coinfection. Despite initial success with anti-TB agents, the disease progressed, necessitating enucleation. Mycobacterium tuberculosis was detected by a tuberculin coagulation test, and EBV was confirmed via polymerase chain reaction. MRI showed plaques in the spinal cord and brain. The patient was treated with anti-TB and antiretroviral agents. Recognizing TB in the differential diagnosis of EBV myelitis is crucial., (© 2024 The Author(s).)

A previously healthy 49-year-old Japanese woman presented with cervical lymph node swelling and tenderness. Lymph node biopsy revealed reactive lymphadenitis without granulomas. No malignant cells were found, and no acid-fast positive bacilli were identified by Ziehl–Neelsen staining. She was treated unsuccessfully with various antibiotics, and it was very challenging to reach a diagnosis. 18F-Fluorodeoxyglucose (18F-FDG) uptake in bones was evaluated using positron emission tomography-computed tomography (PET-CT), and disseminated mycobacterial infection was suspected. The interferon-gamma (IFN-γ) release assays QuantiFERON (QFT) and T-SPOT were used to diagnose tuberculosis infection. On testing, a difference in mitogen response was found between these assays. The response was low for QFT but adequate for T-SPOT, suggesting the presence of anti-IFN-γ antibodies. This difference depended on whether the patient's plasma (including anti-IFN-γ antibodies) was used within the assay system. Mycobacterium abscessus was isolated from lymph node cultures, and plasma anti-IFN-γ antibodies were confirmed. The patient was diagnosed with disseminated M. abscessus infection with underlying adult-onset immunodeficiency caused by anti-IFN-γ antibodies. Granulomas are a pathological hallmark of mycobacterial infection, but may not fully form in immunodeficient patients. Clinicians should be aware of the possibility of mycobacterial infection without granuloma formation due to anti-IFN-γ antibodies. [ABSTRACT FROM AUTHOR]

To compare the characteristics, presentation, investigations, and outcomes in tuberculous meningitis (TBM) patients with and without human immunodeficiency virus (HIV) coinfection. A retrospective cohort study was conducted on adult (age > 18 years) patients whose final diagnosis was TBM and who were treated at Vajira Hospital, Navamindradhiraj University, Thailand, between January 2005 and December 2016. A final total of 174 individuals were included in the study. Of these, 97 (55.75%) were HIV positive. Treatment was successful in 53 (30.5%) individuals. In HIV-infected TBM patients, there were higher proportions of patients who were younger in age (≤40 years), patients with a low body mass index, history of previous tuberculosis infection, or hepatitis C virus coinfection. A successful treatment outcome rate was lower in HIV-infected TBM patients than in HIV-uninfected TBM patients. Since HIV infection decreases the chance of successful treatment outcomes of TBM patients, future studies are needed to determine the clinical indicators for poorer survival outcomes in HIV-positive TBM patients. [ABSTRACT FROM AUTHOR]

Abstract Background One Health (OH) is an integrated approach, formed inclusive of using multiple disciplines to attain optimal health for humans, animals, and the environment. The increasing proximity between humans, livestock, and wildlife, and its role in the transmission dynamics of mycobacterial infections, necessitates an OH approach in the surveillance of zoonotic diseases. The challenge remains as humans, livestock, and wildlife share resources and interact at various interfaces. Therefore, this review explores the potential of the OH approach to understand the impact of mycobacterial infections in Tanzania in terms of lessons learnt and future perspectives. Materials and methods Available literature on OH and mycobacterial infections in Tanzania was searched in PubMed, Google Scholar, and Web of Science. Articles on mycobacterial infections in Tanzania, published between 1997 to 2017, were retrieved to explore the information on OH and mycobacterial infections. Main body The studies conducted in Tanzania had have reported a wide diversity of mycobacterial species in humans and animals, which necessitates an OH approach in surveillance of diseases for better control of infectious agents and to safeguard the health of humans and animals. The close proximity between humans and animals increases the chances of inter-specific transmission of infectious pathogens, including drug-resistant mycobacteria. In an era where HIV co-infection is also the case, opportunistic infection by environmental non-tuberculous mycobacteria (NTM), commonly known as mycobacteria other than tuberculosis (MOTT) may further exacerbate the impact of drug resistance. NTM from various sources have greatest potential for diverse strains among which are resistant strains due to continued evolutional changes. Conclusion A collaborative interdisciplinary approach among professionals could help in solving the threats posed by mycobacterial infections to public health, particularly by the spread of drug-resistant strains.

Key Clinical Message Local and systemic complications of Bacillus Calmette‐Guérin therapy are important to recognize as they require prolonged antimicrobial therapy; molecular genomic testing may be key to diagnosis when culture data are inconclusive.

Background: It is challenging to proceed thoracoscopic anatomic resection when encountering severe pleural adhesion or calcified peribronchial lymphadenopathy. Compared with multiple-port video-assisted thoracoscopic surgery (MP-VATS), how to overcome these challenges in single-port (SP-) VATS is still an intractable problem. In the present study, we reported the surgical results of chronic inflammatory lung disease and shared some useful SP-VATS techniques.Methods: We retrospectively assessed the surgical results of chronic inflammatory lung disease, primarily bronchiectasis, and mycobacterial infection, at our institution between 2010 and 2018. The patients who underwent SP-VATS anatomic resection were compared with those who underwent MP-VATS procedures. We analyzed the baseline characteristics, perioperative data, and postoperative outcomes, and illustrated four special techniques depending on the situation: flexible hook electrocautery, hilum-first technique, application of Satinsky vascular clamp, and staged closure of bronchial stump method.Results: We classified 170 consecutive patients undergoing thoracoscopic anatomic resection into SP and MP groups, which had significant between-group differences in operation time and overall complication rate (P = 0.037 and 0.018, respectively). Compared to the MP-VATS group, the operation time of SP-VATS was shorter, and the conversion rate of SP-VATS was relatively lower (3.1% vs. 10.5%, P = 0.135). The most common complication was prolonged air leakage (SP-VATS, 10.8%; MP-VATS, 2.9%, P = 0.045).Conclusions: For chronic inflammatory lung disease, certain surgical techniques render SP-VATS anatomic resection feasible and safe with a lower conversion rate. [ABSTRACT FROM AUTHOR]

Background: Sarcoidosis is pathologically characterized by the formation of non-necrotizing epithelioid cell granulomas. However, pathological findings of patients with sarcoidosis have rarely revealed necrosis. We report here on a patient with sarcoidosis which needed to be distinguished from infectious disease because of marked necrosis in the lymph nodes.Case Presentation: A 46-year-old Japanese woman was referred to our hospital due to a dry cough and appetite loss. A chest X-ray and computed tomography revealed markedly enlarged mediastinal and hilar lymph nodes and hepatosplenomegaly. Surgical biopsy of these lymph nodes was performed in order to make a diagnosis. Pathological findings revealed epithelioid cell granuloma with marked necrosis that suggested infectious etiology such as mycobacterial and fungal infections. In addition to the pathological findings, immunoglobulin A (IgA) antibody for Mycobacterium avium complex (MAC), enlargement of lymph nodes and hepatosplenomegaly indicated disseminated MAC, while sarcoidosis was considered as another important differential diagnosis according to elevated angiotensin-converting enzyme, soluble interleukin-2 receptor and uveitis. While waiting for the results of the cultures of acid-fast bacilli, the symptoms of cough and consumption had worsened, and initiation of therapy was required before the confirmed diagnosis. The therapy for MAC was initiated because it was feared that immunosuppressive therapy containing corticosteroid for sarcoidosis could worsen the patient's condition if MAC infection was the main etiology. However, the treatment for MAC was not effective, and it was clarified that no acid-fast bacilli were cultured in the liquid culture medium, so the diagnosis was corrected to sarcoidosis after reconsideration of clinical and pathological findings. Prednisolone (30 mg/day) was administered orally, and the patient's symptoms and radiological findings improved.Conclusion: Sarcoidosis must be considered even if pathological findings reveal marked necrosis, because rare cases of sarcoidosis exhibit extensive necrosis in lymph nodes. It is extremely important to carefully examine the clinical and pathological findings through discussion with the examining pathologist to reach the correct diagnosis. [ABSTRACT FROM AUTHOR]

Nontuberculous mycobacterial lymphadenitis often presents a diagnostic challenge. This study aimed to evaluate the role of fine-needle aspiration cytology in the diagnosis of nontuberculous mycobacterial lymphadenitis in children. We conducted a retrospective review of fine-needle aspiration cytology performed in patients < 17 year-old with subacute lymphadenitis from 2003 to 2016 in a tertiary hospital in Spain. Confirmed nontuberculous mycobacterial lymphadenitis (isolation of nontuberculous mycobacterial in culture from fine-needle aspiration cytology or biopsy samples) and probable nontuberculous mycobacterial lymphadenitis ("granulomatous inflammation" in cytopathologic examinations from fine-needle aspiration cytology or biopsy and clinical-epidemiological history compatible with nontuberculous mycobacterial) were selected. Forty-one patients with nontuberculous mycobacterial lymphadenitis were included: 14 confirmed and 27 probable. Fine-needle aspiration cytology was done in all of them. For 34 patients with excised lymphadenopathy, cytopathology from fine-needle aspiration cytology was concordant with biopsy in 100% cases. Culture results were available from 78.0% (32/41) of patients with fine-needle aspiration cytology and from 85.3% (29/34) with excisional biopsy. Among 22 patients with microbiological results from fine-needle aspiration cytology and biopsy, fine-needle aspiration cytology allowed advanced results in concordance with biopsy or with positive isolation not found in biopsy in 90.1% (20/22) of patients. Sensitivity of nontuberculous mycobacterial cultures obtained by fine-needle aspiration cytology compared to biopsy was 45.5% vs. 36.4% (p = 0.07). Two patients with previous skin alterations presented fistulas after fine-needle aspiration cytology (4.9%); no other complications were described. Conclusion: Fine-needle aspiration cytology provides quick cytopathologic information and is an accurate and safe technique for the diagnosis of nontuberculous mycobacterial lymphadenitis, especially in cases with challenging work-up. What is Known: • Nontuberculous mycobacterial (NTM) infection is an important cause of subacute lymphadenitis in children. • Fine-needle aspiration cytology (FNAC) is an available technique for the diagnosis of lymphadenitis of unknown etiology. What is New: • FNAC is an accurate and safe technique for the diagnosis of NTM lymphadenitis in children. • FNAC can provide reliable samples for cytopathological studies and even a better sensitivity for microbiological culture than excisional biopsy in the study of suspected NTM lymphadenitis. [ABSTRACT FROM AUTHOR]

Autophagy, an intracellular catabolic pathway featuring lysosomal degradation, is a central component of the host immune defense against various infections including Mycobacterium tuberculosis (Mtb), the pathogen that causes tuberculosis. Mtb can evade the autophagic defense and drive immunometabolic remodeling of host phagocytes. Co-regulation of the autophagic and metabolic pathways may play a pivotal role in shaping the innate immune defense and inflammation during Mtb infection. Two principal metabolic sensors, AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) kinase, function together to control the autophagy and immunometabolism that coordinate the anti-mycobacterial immune defense. Here, we discuss our current understanding of the interplay between autophagy and immunometabolism in terms of combating intracellular Mtb, and how AMPK-mTOR signaling regulates antibacterial autophagy in terms of Mtb infection. We describe several autophagy-targeting agents that promote host antimicrobial defenses by regulating the AMPK-mTOR axis. A better understanding of the crosstalk between immunometabolism and autophagy, both of which are involved in host defense, is crucial for the development of innovative targeted therapies for tuberculosis.

Objectives: Intravesical Bacillus Calmette-Guérin (BCG) treatment for superficial bladder cancer is interrupted in approximatively 8% of cases as a result of complications. The objective is to report the severe related complications of Bacillus Calmette-Guérin (BCG) following an intravesical instillation for bladder tumor encountered at our institution for the past 5 years. Methods: Medical records of a tertiary teaching hospital, located in Beirut, Lebanon, were retrospectively analyzed from June 2014 to June 2019 searching for severe related complications of BCG. A comprehensive review of articles on this subject was conducted. Results: The incidence of severe systemic adverse events related to BCG instillation was 1.5% (5 out of 332 patients). A total of five patients were found to have a severe BCG related complication, with fever, chills, and irritative urinary signs being the most frequent symptoms. All patients received antituberculosis therapy (Isoniazid, Rifampin and Ethambutol). Two were put on add-on corticosteroids. Three patients had a computed tomography scan image in favor of an infection. Two patients had a favorable outcome, three patients died. Conclusion: BCG severe adverse events were mostly seen in patients with a traumatic instillation. Treatment used at our institution was similar to most cases reported in the literature. A standardized diagnostic and treatment approach should be implemented to help physicians tackle these life-threatening complications.

Abstract Background Presence of Mycobacterium fortuitum in respiratory tracts usually indicates mere colonization or transient infection, whereas true pulmonary infection occurs in patients with gastroesophageal disease. However, little is known about the diagnostic indications for true M. fortuitum pulmonary infection and the natural history of the disease. Case presentation A 59-year-old man was referred to our hospital for treatment against M. fortuitum pulmonary infection. Fifteen years before the referral, he underwent total gastrectomy, after which he experienced esophageal reflux symptoms. After the referral, the patient was closely monitored without antimicrobial therapy because of mild symptoms and no pathological evidence of M. fortuitum pulmonary infection. During the observation, chest imaging showed migratory infiltrates. Two years after the referral, his lung biopsy specimen revealed foamy macrophages and multinucleated giant cells, indicating lipoid pneumonia. However, he was continually monitored without any treatment because there was no evidence of nontuberculous mycobacterial infection. Four years after the referral, he developed refractory pneumonia despite receiving adequate antibiotic therapy. After confirmation of granulomatous lesions, multiple antimicrobial therapy for M. fortuitum resulted in a remarkable improvement with no exacerbation for over 5 years. Random amplified polymorphic DNA polymerase chain reaction analysis revealed identical M. fortuitum strains in seven isolates from six sputum and one intestinal fluid specimens obtained during the course of the disease. Conclusions We have described a patient with M. fortuitum pulmonary infection who presented with migratory infiltrates. The pathological evidence and microbiological analysis suggested that M. fortuitum pulmonary infection was associated with lipoid pneumonia and chronic exposure to gastrointestinal fluid. Therefore, physicians should carefully monitor patients with M. fortuitum detected from lower respiratory tract specimens and consider antimicrobial therapy for M. fortuitum infection when the patient does not respond to adequate antibiotic therapy against common pneumonia pathogens.