Mycobacterium Avium Research Articles

Genomic Epidemiology of Extrapulmonary Nontuberculous Mycobacteria Isolates at Emerging Infections Program Sites - United States, 2019-2020.

Nontuberculous mycobacteria (NTM) cause pulmonary and extrapulmonary infections. Although isolation of NTM from clinical specimens has increased nationally, few studies delineated the molecular characteristics of extrapulmonary NTM. Extrapulmonary isolates were collected by four Emerging Infections Program sites from October 2019 to March 2020 and underwent laboratory characterization, including matrix-assisted laser desorption ionization-time of flight mass spectrometry, Sanger DNA sequencing, and whole genome sequencing. Bioinformatics analyses were employed to identify species, sequence types (STs), antimicrobial resistance (AR), and virulence genes; isolates were further characterized by phylogenetic analyses. Among 45 isolates, the predominant species were Mycobacterium avium (n=20, 44%), Mycobacterium chelonae (n=7, 16%), and Mycobacterium fortuitum (n=6, 13%). The collection represented 31 STs across 10 species; the most common ST was ST11 (M. avium, n=7). Mycobacterium fortuitum and Mycobacterium abscessus isolates harbored multiple genes conferring resistance to aminoglycosides, beta-lactams, and macrolides. No known AR mutations were detected in rpoB, 16S, or 23S rRNAs. Slow-growing NTM species harbored multiple virulence genes including type-VII secretion components, adhesion factors, and phospholipase C. Continued active laboratory- and population-based surveillance will further inform the prevalence of NTM species and STs, monitor emerging clones, and allow AR characterization.

7660 Navigating Hypercalcemia: MAC Treatment Hurdles and the Unforeseen Impact of Vitamin D Supplementation

Abstract Disclosure: S. Noguchi: None. S. Lai: None. A. Rajpal: None. Introduction: Hypercalcemia is a recognized complication in granulomatous disorders such as sarcoidosis and tuberculosis, resulting from increased 1 alpha-hydroxylase activity in macrophages leading to excessive conversion to 1,25(OH)2 vitamin D (calcitriol). Mycobacterium avium complex (MAC) is an infectious granulomatous disease often suspected in immunocompromised individuals, including those with human immunodeficiency virus (HIV). Additionally, vitamin D deficiency is prevalent in the general population, prompting supplementation. We hereby present a patient with advanced HIV and disseminated MAC who developed severe calcitriol-induced hypercalcemia in the setting of high dose vitamin D supplementation. Case description: A 48-year-old male with advanced HIV (CD4 count <20 cells/mm^3) presented for evaluation of abdominal pain and constipation, and was found to have severe hypercalcemia of 14.8 mg/dL. Five months prior, he had restarted anti-retroviral therapy (ART) after having been out of care for over a year and was diagnosed with disseminated MAC for which he was on azithromycin and ethambutol. Cultures drawn during this admission were negative for MAC. Hypercalcemia was possibly due to paradoxical immune reconstitution inflammatory syndrome (IRIS) and with appropriate management his calcium level rapidly normalized to 9.7 mg/dL and remained stable until the recent admission. He represented one year later with a calcium level of 13.8 mg/dL with suppressed parathyroid hormone levels, which was refractory to bisphosphonate therapy, therefore was empirically initiated on dexamethasone. By day 4, his calcium levels improved significantly and was discharged on a taper regimen. Cultures collected this admission later revealed ongoing MAC infection, which raised concern for treatment failure and calcitriol-induced hypercalcemia. Calcitriol levels were elevated at 105 pg/mL, which further supported this hypothesis. Additionally, prior to admission he had been prescribed ergocalciferol 50,000 units weekly for 8 weeks, after which he was transitioned to 2,000 units daily. This likely exacerbated the calcitriol-induced hypercalcemia by providing sudden availability of substrate, 25-OH vitamin D, for the activated macrophages. Conclusion: ART has reduced the incidence of opportunistic infections such as MAC, however mortality remains high. Vigilant monitoring for complications, particularly life-threatening calcitriol-induced hypercalcemia and timely use of corticosteroids, is crucial. This case also highlights the need for careful oversight in high-dose vitamin D supplementation for individuals with granulomatous disease and vitamin D dysregulation. Presentation: 6/2/2024

Amikacin Liposomal Inhalation Suspension for Non-Tuberculous Mycobacteria Lung Infection: A Greek Observational Study.

Background and Objectives: Intravenous amikacin, recommended for severe or recurrent M. avium complex (MAC) infections and as initial treatment for M. abscessus lung disease, is often limited by serious adverse effects such as renal and auditory toxicities. Inhaled Amikacin Liposome Inhalation Suspension (ALIS) enhances pulmonary drug deposition while minimizing systemic adverse effects, and it has recently been introduced as an add-on therapy for refractory MAC infections or when other standard treatments are inadequate. This study aims to retrospectively describe the outcomes of Greek patients with difficult-to-treat non-tuberculous mycobacterial (NTM) lung disease following the addition of ALIS to guideline-based therapy. Materials and Methods: Seventeen consecutive patients (median age: 66 years) treated with ALIS as an add-on therapy to a standard regimen at "Sotiria" General Hospital of Chest Diseases (Athens, Greece) from 2020 to 2023 were enrolled in this study. These patients had recurrent or refractory NTM lung disease and/or limited treatment options due to prior treatment-related adverse effects. Clinical, radiological, and microbiological data on treatment response and overall outcomes after ALIS initiation were recorded for each patient. Results: By the end of 2023, 14 out of 17 patients had either successfully completed or were continuing their ALIS therapy. At 6 months, 85.7% (12/14) showed clinical, microbiological, and radiological improvement. However, 25% (3/12) of treated patients, primarily those with monomicrobial or combined M. abscessus lung disease, experienced disease relapse after therapy completion. The most frequent adverse effects related to ALIS were mild and localized to the respiratory tract, with only one patient discontinuing therapy due to hypersensitivity pneumonitis. Conclusions: Adding ALIS to standard regimens was effective and safe in a small group of Greek patients with refractory or recurrent NTM lung disease, particularly those who had discontinued intravenous aminoglycosides due to significant adverse effects, with notable responses observed in MAC lung disease. Further research is needed to validate these findings in clinical practice and to investigate ALIS's role in NTM lung disease caused by other species.

Multicenter study of the performance of NTM Elite agar for the detection of nontuberculous mycobacteria from patients with cystic fibrosis.

The performance of a novel selective agar was evaluated against the performance of conventional mycobacterial cultures, i.e., a combination of the mycobacterial growth indicator tube (MGIT) with Löwenstein-Jensen (LJ), for the detection of nontuberculous mycobacteria (NTM) in sputum samples from people with cystic fibrosis (pwCF). Two hundred eighty-three sputum samples (231 fresh sputum and 52 spiked sputum) from 143 pwCF were collected. They were inoculated without prior decontamination on NTM Elite agar (30°C ± 2°C for 28 days) and inoculated on both MGIT and LJ (35°C-37°C for 6-8 weeks) after N-acetyl-L-cysteine-2% sodium hydroxide decontamination. NTM were identified by Matrix-Assisted Laser Desorption Ionization/Time of Flight Mass Spectrometry and/or PCR, and whole-genome sequencing. A total of 67 NTM were recovered overall by the combination of all culture media. NTM Elite agar allowed the recovery of 65 NTM (97%), compared to 22 for the conventional MGIT and LJ media combination (32.8%), including 22 NTM for MGIT (32.8%) and 3 NTM with the LJ medium (4.5%). For Mycobacterium abscessus complex, the sensitivity of NTM Elite agar was 95% compared with a sensitivity of 30% for the conventional MGIT and LJ media combination. Overall, 17.3% of cultures on NTM Elite agar were contaminated with other micro-organisms vs 46.3% on MGIT and 77% on LJ. This study shows that the novel selective agar (NTM Elite agar) significantly outperforms the conventional MGIT and LJ media combination in terms of sensitivity, selectivity, and ease of culture, without the requirement of an L3 laboratory.IMPORTANCENontuberculous mycobacteria (NTM) are significant pulmonary pathogens in patients with pre-existing structural lung conditions such as cystic fibrosis, bronchiectasis, or chronic obstructive pulmonary disease. Mycobacterium avium complex and Mycobacterium abscessus complex (MABSC) are the most frequently isolated organisms. Compared to the recommended culture method for NTM, which combines solid and liquid culture media, NTM Elite agar enables a faster/easier diagnosis and speeds up identification and susceptibility testing as the final reading is at 28 days instead of 6-8 weeks for the conventional mycobacterial cultures. In addition, for the NTM Elite agar, no decontamination stage before inoculation is necessary, unlike the conventional mycobacterial cultures. NTM Elite agar is derived from a formulation of medium adapted to rapidly growing mycobacteria (RGM). The medium enables the growth of RGM while suppressing other flora. It is supported with published clinical data showing the benefits of this medium.

Genome-scale analysis of Mycobacterium avium complex isolates from Portugal reveals extensive genetic diversity

Opportunist infections caused by nontuberculous mycobacteria (NTM) have emerged as a significant public health problem. Among these, species of the Mycobacterium avium complex (MAC) are the main responsible for the increase in the number of human disease cases. In order to address the current needs in the detection and surveillance of MAC disease cases, we evaluated different species classification methodologies (BLASTn-based marker-gene approach, Kraken v2, rMLST and MLST databases) and their congruence with a core-SNP phylogenetic approach, based on whole genome sequencing (WGS) data. For this purpose, we used a collection of 142 MAC isolates from Portuguese patients diagnosed between 2014 and 2022. The marker-gene approach (based on the rpoB, hsp65 and groEL genes), showed the best results, allowing the identification of the 142 MAC isolates to the species/subspecies level (M. avium subsp. hominissuis, M. intracellulare, M. intracellulare subsp. chimaera, M. intracellulare subsp. yongonense, M. marseillence and M. colombiense). Additionally, we performed drug susceptibility testing that confirmed clarithromycin efficacy as a first-line treatment for MAC disease, as 93 % of the Portuguese isolates were susceptible. Using a core-SNP approach we also performed an in-depth phylogenetic analysis within each identified species group, and despite the high genetic diversity within the MAC species, we were able to clearly distinguish all the species/subspecies and identify genetic clusters with epidemiological potential.We highlight not only the need for the standardization of an appropriate genotyping approach for species identification and management of MAC disease, but also a more robust large-scale WGS data analysis, in a One Health perspective, in order to identify potential routes of transmission.

S4743 Constricting the Gut: Ileocecal Granulomatous Obstruction Induced by Mycobacterium avium Complex

S4743 Constricting the Gut: Ileocecal Granulomatous Obstruction Induced by Mycobacterium avium Complex

Isolation of genetically distinct strains within the same species during treatment of MAC pulmonary disease

Research on isolating genetically different strains within the same species in patients undergoing treatment for Mycobacterium avium complex (MAC) pulmonary disease (PD) is limited. We investigated the frequency of genetically distinct strains identified within the same species among on-treatment isolates compared with pre-treatment isolates throughout the course of MAC-PD treatment. What is the frequency of genetically distinct strains identified within the same species among pre- and on-treatment isolates in patients with MAC-PD? We serially collected pre- and on-treatment clinical isolates from patients with MAC-PD treated for over one month from November 2019 to October 2022 at a tertiary hospital in South Korea. We utilized multilocus sequence typing (MLST) genotypic analysis to determine whether the on-treatment isolate was a genetically different strain compared with the pre-treatment isolate. Among 327 enrolled patients, we identified the on-treatment isolates of 198 patients as the same species as the pre-treatment isolates. The median treatment duration for the 198 patients was 14.4 months (interquartile range, 12.1-16.9 months). Of these patients, MLST analysis revealed the presence of a genetically different strain among the on-treatment isolates at least once in 24.7% (49/198) of patients (95% confidence interval, 18.9-31.4) compared to the pre-treatment isolate. There were variations in the timing, frequency, and number of distinct strains in these 49 patients. We identified a genetically distinct strain within the same species at least once in approximately 25% of patients in whom the same species was isolated after the initiation of anti-MAC-PD therapy. These findings may affect the determination of treatment outcomes and corresponding MAC-PD treatment strategies.

Total syntheses of mavintramycin A and its structural analog, cytosaminomycin C, and evaluation of their antibacterial activities against Mycobacterium avium and Mycobacterium intracellulare

Mavintramycin A is a new aminohexopyranose nucleoside antibiotic with potent anti-Mycobacterium avium complex (MAC) activity against M. avium and M. intracellulare. Herein, we report the total syntheses of mavintramycin A and its structural analog cytosaminomycin C, which is a known anticoccidial antibiotic. Furthermore, the anti-MAC activities of mavintramycin A, cytosaminomycin C, and their corresponding p-methoxybenzyl-protected analogs were evaluated. Notably, the developed synthetic route enables ready access to various analogs of mavintramycin A for structure-activity relationship studies.

More Than Just Stool: Hypereosinophilic Syndrome Presenting as Persistent Diarrhea in a Patient With Ulcerative Colitis

We highlight a case of non-infectious diarrhea that progressed despite supportive care, prompting further workup. A 50-year-old man presented with 1 week of voluminous diarrhea, nausea, emesis, and abdominal pain. His history included ulcerative colitis, primary sclerosing cholangitis, Clostridioides difficile treated via total colectomy with ileoanal pouch, treated disseminated Mycobacterium avium complex, and international travel. On physical exam he had normal vital signs, diffuse abdominal tenderness without peritoneal signs, and a rash. Lab work revealed leukocytosis with eosinophilia, hyponatremia, and elevated creatinine. Lactate, inflammatory markers, stool studies, and computed tomography of his abdomen were normal. Tissue biopsies of the duodenum, ileum, and rectal pouch collected during colonoscopy and push enteroscopy revealed prominent mucosal eosinophilia, confirming the diagnosis of hypereosinophilic syndrome (HES). Treatment with steroids led to significant improvement in all symptoms and blood eosinophilia. This case highlights the importance of aggressive workup of diarrhea with peripheral eosinophilia, especially in patients with ulcerative colitis: waiting 6 months to confirm the diagnosis via blood work would delay treatment. Notably, infection with Strongyloides stercoralis was ruled out in this case prior to treatment. This is an important step in the workup and management of HES to prevent progression of Strongyloidiasis.

S4413 Hepatic Lesions Secondary to Disseminated Mycobacterium avium Complex: A Diagnostic Challenge in a Patient With Advanced HIV Complicated by Kaposi Sarcoma Inflammatory Cytokine Syndrome

S4413 Hepatic Lesions Secondary to Disseminated Mycobacterium avium Complex: A Diagnostic Challenge in a Patient With Advanced HIV Complicated by Kaposi Sarcoma Inflammatory Cytokine Syndrome

Emergence of Mycobacterium gordonae in heater–cooler units: a five-year prospective surveillance of devices frequently subjected to chloramine-T booster disinfection

Worldwide, the detection of Mycobacterium chimaera in LivaNova heater-cooler units (HCUs) has led to their replacement with other HCUs, although non-tuberculous mycobacteria (NTM) have been reported also for HCUs produced by other manufacturers. In almost all hospitals of our region, LivaNova HCUs have been replaced with Maquet HCU40s, regularly disinfected with chloramine-T. To report the results of the surveillance over a 63-month operation period of the Maquet devices, and to provide a trend in NTM positivity over time. Twenty-nine Maquet devices (HCU40 and HU35) were monitored by two culture methods and PMA-PCR method. The trend in NTM positivity rate was evaluated through the Locally Estimated Scatterplot Smoothing regression and then modelled over time through segmented logistic regression. The data acquired during the study period demonstrate a remarkable increase in the positivity rate, especially after their third year (maximum slope change at 1280 days). Non-tuberculous mycobacteria were isolated in 150 water samples (37.2%); 100% and 62% of HCU40 and HU35 devices respectively were colonized with non-tuberculous mycobacteria. The most frequently detected species were Mycobacterium gordonae (73%) followed by Mycobacterium chelonae (41%) and Mycobacterium paragordonae (11%). Preventive strategies by disinfection with chloramine-T did not effectively reduce non-tuberculous mycobacteria colonization of Maquet devices. Although, to date, no cases of post-operative invasive infections linked to Maquet devices have been reported, our microbiological results emphasize the need for 1) designing changes to increase safety of devices and 2) researching and developing new disinfection protocols including alternative molecules.

Efficacy of mefloquine and its enantiomers in a murine model of Mycobacterium avium infection.

The treatment of Mycobacterium avium infections is still long, complex, and often poorly tolerated, besides emergence of resistances. New active molecules that are more effective and better tolerated are deeply needed. Mefloquine and its enantiomers ((+) Erythro-mefloquine ((+)-EMQ) and (-)-Erythro-mefloquine ((-)-EMQ)) have shown efficacy in both in vitro and in vivo, in a mouse model of M. avium intraveinous infection. However, no study reports aerosol model of infection or combination with gold standard treatment. That was the aim of our study. In an aerosol model of M. avium infection in BALB/c mice, we used five treatment groups as followed: Clarithromycin-Ethambutol-Rifampicin (CLR-EMB-RIF, standard of care, n = 15), CLR-EMB-MFQ (n = 15), CLR-EMB-(+)-EMQ (n = 15), CLR-EMB-(-)-EMQ (n = 15) and an untreated group (n = 25). To evaluate drug efficacy, we sacrificed each month over 3 months, 5 mice from each group. Lung homogenates were diluted and plated for colony forming unit count (CFU) expressed in Log10. At each time point, we found a significant difference between the untreated group and each of the treatment groups (p<0.005). The (+)-EMQ-CLR-EMB group was the group with the lowest CFU count at each time point but never reached statistical significance. The results of each group 3 months after treatment are: (+)-EMQ-CLR-EMB (4.43 ± 0.26), RIF-CLR-EMB (4.83 ± 0.37), (-)-EMQ-CLR-EMB (4.82 ± 0.18), MFQ-CLR-EMB (4.70 ± 0.21). In conclusion, MFQ and its enantiomers appear to be as effective as rifampicin in combination therapy. Further studies are needed to evaluate the ability of these drugs to prevent selection of clarithromycin resistant strains and potential for lung sterilization.

Relationship between chronic diseases, hair cortisol concentration and welfare of housed dairy goats

The aim of this study was to evaluate the relationship between seroprevalence of chronic diseases, hair cortisol concentration (HCC), and welfare of dairy goats housed throughout a productive cycle. Sixty multiparous dairy goats, over four years old, were selected. An animal welfare assessment was conducted using health indicators for goats, according to the AWIN protocol. Blood samples were also collected for haematology and determination of seroprevalence of chronic diseases, hair samples for determination of HCC, milk samples for chemical composition and somatic cell counts, and faecal samples for parasite load. Small Ruminant Lentivirus (SRLv) had a prevalence of 71.66%, Mycobacterium avium subspecies paratuberculosis (MAP) of 5%, Leptospira interrogans of 40% and Ovine Gammaherpesvirus type 2 (OvHV-2) of 50%. The percentages of goats that tested positive for one, two or three diseases were 31.67%, 50% and 11.66%respectively. Haematological alterations included hyperproteinaemia (84.94 ± 1.58 g/L) and hyperfibrinogenaemia (6.11± 0.65 g/L) for those with one or two diseases, with significant differences being found (P &lt; 0.05). The welfare indicatorsrelated to health and the number of diseases were poor body condition, poor coat, poor udder conformation, andmucosal lesions (P &lt; 0.05). However, no significant differences were observed between HCC and the number of chronicdiseases in dairy goats (P &gt; 0.05). Higher concentrations of cortisol in hair were found at 150 days of lactation (16.65 ± 1.39pg/mg) compared to the mating season (9.55 ± 0.04 pg/mg) (P &lt; 0.05). No associations were found (P &gt; 0.05) betweenthe production, composition, and somatic cell counts in milk and cortisol concentrations and diseases. It was concludedthat the presence of chronic diseases in goats did not influence hair cortisol concentrations, possibly due to an effect ofadaptive tolerance to diseases, as occurs in other domestic species; however, there was an effect of the productive stage.

Microbiological and genetic typing of atypical mycobacteria identified in the Novosibirsk region

219 samples of biological material from animals and 54 samples of environmental objects from farms in the Novosibirsk region, which are free from bovine tuberculosis, were examined for isolation of the tuberculosis pathogen, microbiological and genetic typing of isolated cultures of atypical mycobacteria. Microbiologic diagnosis included culture method, biochemical tests and biological assay. During the treatment of animal biomaterial 50 cultures were isolated, and 20 cultures were isolated from the environmental objects. The isolated cultures were classified as mycobacteria on the basis of their culture and morphological properties and bacterioscopy. According to biochemical characteristics, out of 70 cultures studied, 27 isolates (38.6%) belonged to atypical mycobacteria of different species. Of these, 26 cultures (96.3%) were categorized as Group III and 1 culture (3.7%) as Group IV according to Runyon's classification. Next, a biological assay was performed by infecting nonlinear white mice with suspensions of 27 identified cultures of atypical mycobacteria. At autopsy and pathological-anatomical study of laboratory animals, changes in internal organs characteristic for tuberculosis were not found, which confirms that the cultures under study belong to atypical mycobacteria. Molecular systematization of the isolated cultures revealed the presence of Mycobacterium avium (20 cultures, 74%), M. nonchromogenicum (5 cultures, 18.5%), M. intracellulare (1 culture, 3.7%) and M. fortuitum (1 culture, 3.7%). Thus, based on the results of a comprehensive study of 70 cultures of atypical mycobacteria isolated from animal biomaterial and environmental objects from the territory of farms in the Novosibirsk region, free from bovine tuberculosis, 27 isolates belonging to atypical mycobacteria of groups III and IV were identified according to Runyon’s classification. On the basis of typing, it was found that the leading role among the identified pathogens is occupied by atypical mycobacteria of group III, in particular M. avium. The etiology of nonspecific tuberculin reactions in tuberculosis-free herds of cattle can be explained by the isolation of atypical Mycobacterium tuberculosis groups III and IV according to Runyon classification from environmental objects and their persistence in the organism of healthy animals.

Response of Mycobacterium avium subsp. paratuberculosis isolates to reactive oxygen stress generated by treatment with copper ions

Copper (Cu) ions have been recognized for their efficacy in inactivating bacteria, including Mycobacterium avium subsp. paratuberculosis (MAP), the causative agent of Johne’s disease (JD) known for its resilience to unfavorable conditions. However, the response of MAP isolates isolated from cows to Cu exposure remains inadequately understood, as their responses may differ from those of laboratory-adapted reference strains. In this study, we examined the response of MAP isolates obtained from MAP-infected and affected cows to Cu ion treatment, comparing that with the response of the reference strain ATCC 19698 to the same treatment. Three MAP field isolates and the MAP reference strain were exposed to Cu ions, and their viability, protein/lipid damage, ROS production, and gene expression were evaluated in triplicate. Survival differed among isolates, with an isolate from a cow with clinical JD exhibiting increased tolerance to Cu exposure. While Cu treatment induced lipid peroxidation and ROS production across all isolates, genes associated with Cu detoxification and virulence were upregulated, particularly in the reference strain. Whole genome sequencing analysis revealed that, despite genomic similarities between field isolates and the reference strain ATCC 19698, there were differences regarding the presence/absence of genes related with certain virulence factors. Further research on Cu exposure with larger numbers of MAP isolates is needed to explain the stress-induced responses that influence MAP survival during natural infections and in challenging environments.

Case report: granulomatous hepatitis due to Mycobacterium avium in an Atlantic yellow-nosed albatross (Thalassarche chlororhynchos) from Southern Brazilian coast.

This study reports a granulomatous hepatitis caused by Mycobacterium avium in an Atlantic yellow-nosed albatross (Thalassarche chlororhynchos) found dead on Brazil southern coast. At necropsy, the albatross was cachectic and the liver was severely enlarged with multifocal to coalescing white nodules. Histopathological evaluation revealed multifocal to coalescing granulomas with caseous necrosis, surrounded by an infiltrate of macrophages and multinucleated giant cells, and a thin capsule of fibrous connective tissue. The Fite-Faraco staining technique revealed multiple acid-fast bacilli (AFB) stained in magenta, predominantly in the areas of necrosis. Bacterial culture and polymerase chain reaction (PCR) analysis confirmed the presence of Mycobacterium avium in liver samples. This case underscores the importance of wildlife surveillance in coastal regions. Pelagic birds like the Atlantic yellow-nosed albatross can harbor pathogenic agents that represent a threat to wildlife and domestic animals. Enhanced monitoring and research are essential to understand the epidemiology and potential risks associated with such infections in coastal ecosystems.

Mycobacterium chimaera: a case report from Italy.

Mycobacterium chimaera is an environmental non-tuberculous mycobacterium belonging to Mycobacterium avium complex (MAC). It has been widely known to be associated with disseminated infection after cardiac surgery, related to heater-cooler units used during these procedures. Although M. chimaera seems to be a less virulent species compared to M. avium and M. intracellulare among MAC, several cases of M. Chimaera lung infections have been reported in settings of chronic obstructive pulmonary disease (COPD), cystic fibrosis, bronchiectasis, malignancy, or immunosuppression. Here, we present an Italian case report in association with newly diagnosed COPD.

Mycobacterium paratuberculosis: A HERV Turn-On for Autoimmunity, Neurodegeneration, and Cancer?

Human endogenous retroviruses (HERVs) are remnants of ancient retroviral infections that, over millions of years, became integrated into the human genome. While normally inactive, environmental stimuli such as infections have contributed to the transcriptional reactivation of HERV-promoting pathological conditions, including the development of autoimmunity, neurodegenerative disease and cancer. What infections trigger HERV activation? Mycobacterium avium subspecies paratuberculosis (MAP) is a pluripotent driver of human disease. Aside from granulomatous diseases, Crohn's disease, sarcoidosis and Blau syndrome, MAP is associated with autoimmune disease: type one diabetes (T1D), multiple sclerosis (MS), rheumatoid arthritis (RA) and autoimmune thyroiditis. MAP is also associated with Alzheimer's disease (AD) and Parkinson's disease (PD). Autoimmune diabetes, MS and RA are the diseases with the strongest MAP/HERV association. There are several other diseases associated with HERV activation, including diseases whose epidemiology and/or pathology would prompt speculation for a causal role of MAP. These include non-solar uveal melanoma, colon cancer, glioblastoma and amyotrophic lateral sclerosis (ALS). This article further points to MAP infection as a contributor to autoimmunity, neurodegenerative disease and cancer via the un-silencing of HERV. We examine the link between the ever-increasing number of MAP-associated diseases and the MAP/HERV intersection with these diverse medical conditions, and propose treatment opportunities based upon this association.

The Spread of Mycobacterium chimaera from Heater-Cooler Units and Infection Risk in Heart Surgery: Lessons from the Global Outbreak?

Mycobacterium chimaera (MC), a member of the Mycobacterium avium complex, can cause infections in patients after open-heart surgery due to contaminated heater-cooler units (HCUs). The transmission route of HCU-related MC infection is non-inhalational, and infection can occur in patients without previously known immune deficiency. Patients may develop endocarditis of the prosthetic valve, infection of the vascular graft, and/or manifestations of disseminated mycobacterial infection (splenomegaly, arthritis, hepatitis, nephritis, myocarditis, etc.). MC infections have serious outcomes (30-50% recurrence rate, 20-67% mortality rate). In 2015, an international outbreak of M. chimaera infections among patients undergoing cardiothoracic surgeries was associated with exposure to contaminated LivaNova 3T HCUs (formerly Stöckert 3T heater-cooler system, London, United Kingdom). In response to the global outbreak, many international agencies have issued directives and recommendations in order to reduce the risk of MC infection in cardiac surgery. Whole-genome sequencing (WGS) technology can be used to describe the global spread and dynamics of MC infections, to characterize local outbreaks, and also to identify sources of infection in hospital settings. In order to minimize the risk of contamination of HCUs and reduce the risk of patient infection, it is imperative that healthcare facilities establish a program of regular cleaning and disinfection maintenance procedures as well as monitoring of the water used and the air in the operating room, in accordance with the manufacturer's procedure.

Significance of changes in cavity after treatment in Mycobacterium avium complex pulmonary disease

Cavities are characteristic radiological features related to increased mycobacterial burden and poor prognosis in Mycobacterium avium complex pulmonary disease (MAC-PD). However, cavity changes following treatment and their clinical implications remain unknown. We aimed to elucidate whether cavity obliteration or reduction in cavity size or wall thickness correlates with microbiological cure. In total, 136 adult patients with cavitary MAC-PD treated for ≥ 6 months between January 1st, 2009, and December 31st, 2021, in a tertiary referral centre in South Korea were enrolled. The cavity with the largest diameter at treatment initiation was tracked for size and thickness changes. Following median treatment of 20.0 months, 74 (54.4%) patients achieved microbiological cure. Cavity obliteration, achieved in 58 (42.6%) patients at treatment completion, was independently associated with microbiological cure. In patients with persistent cavities, size reduction of ≥ 10% was significantly associated with microbiological cure, whereas thickness reduction was not. Five-year mortality rates in patients with cavity obliteration, persistent but reduced cavity, and persistent cavity without shrinkage were 95.6%, 72.1%, and 65.3%, respectively (P < 0.001). In conclusion, cavity obliteration or shrinkage at treatment completion is associated with microbiological cure and reduced mortality in MAC-PD, suggesting that cavity changes could serve as a proxy indicator for treatment response.