Mycobacterium kansasaii and Mycobacterium scrofulaceum dual pulmonary infection in an immunocompetent male: first report from India.

A 57-year-old farmer presented with chronic cough and recurrent hemoptysis, previously treated for sputum positive pulmonary tuberculosis. Referred to us for evaluation of drug resistant tuberculosis as his sputum was persistently positive for acid fast bacilli along with radiological worsening even after 6 months of antitubercular treatment. Bronchoalveolar lavage was done and he was diagnosed with a rare mixed non-tuberculous mycobacyteria (NTM) pulmonary infection despite no immune dysfunction. He was successfully treated with multidrug regimen of rifampicin, isoniazid, ethambutol and clarithromycin.

Rare manifestation of ocular immune reconstitution inflammatory syndrome from mycobacterium scrofulaceum infection in a patient with AIDS.

Immune reconstitution inflammatory syndrome (IRIS) is a common complication following the initiation of antiretroviral therapy (ART). The most commonly associated pathogens include Mycobacterium tuberculosis and Cryptococcus spp.[1] IRIS following nontuberculosis mycobacteria (NTM) infection is uncommon, particularly, IRIS following NTM conjunctivitis.[2] Herein, we present a case of Mycobacterium scrofulaceum conjunctivitis with peripheral ulcerative keratitis and orbital cellulitis in a 45-year-old patient with AIDS who developed IRIS 1 month after starting ART therapy. A combination of both systemic and topical antibiotics together with corticosteroids were used and resulted in a satisfactory outcome with no early recurrence. This case demonstrated a rare ocular IRIS manifestation involving both the external eye and orbit and to the author's knowledge is the first case in the literature in which M. scrofulaceum has been found to be involved in the eye.

Disseminated Mycobacterium scrofulaceum Infection in a Patient with Anti-Interferon-γ Autoantibodies: A Case Report and Review of the Literature.

Mycobacterium scrofulaceum is an environmental mycobacterial species rarely reported to cause disseminated infection in adults. We report the case of a disseminated M. scrofulaceum infection in a 55-year-old nonhuman immunodeficiency virus-infected Thai man with anti-interferon-γ autoantibodies. The clinical signs of the infection improved after the induction regimen with amikacin, rifampicin, ethambutol, and clarithromycin, followed by the consolidation regimen with ethambutol, clarithromycin, and trimethoprim/sulfamethoxazole. Our review of previous reported cases of this infection indicates its association with immune deficiency, complex treatment, and a high rate of unfavorable outcomes.

Infección diseminada por Mycobacterium scrofulaceum en paciente en tratamiento con golimumab / Disseminated Mycobacterium scrofulaceum infection in a patient in treatment with golimumab

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Mycobacterium scrofulaceum disease: experience from a tertiary medical centre and review of the literature.

Introduction:Mycobacterium scrofulaceum infection has been identified in cases of paediatric cervical lymphadenitis but is less well defined in adults. To further characterize manifestations of M. scrofulaceum disease and treatment approaches, we reviewed our medical centre's experience and other published reports. Methods: We performed a retrospective chart review of patients at our medical centre with a positive M. scrofulaceum culture over a 15-year period. We compare our findings with those published in the literature to identify commonalities in disease presentations and treatment outcomes. Results: We identified 17 patients in our centre with positive M. scrofulaceum cultures, 10 of whom were diagnosed with clinical infection. The types of disease encountered included pulmonary and pleural infection (4), bone and joint infections with a foreign body (2), skin and soft tissue infection (2), brain abscess (1) and paediatric cervical adenitis (1). Structural lung disease was a common finding in cases of pulmonary infection. All adult patients except those with bone and joint infections had some type of immunomodulatory condition and/or structural lung disease. In seven patients, M. scrofulaceum was isolated in urinary or respiratory cultures without signs of clinical disease. Conclusion:M. scrofulaceum is a rare cause of non-tuberculosis mycobacterial infection in humans but can infect any tissue. Adults with pulmonary disease often have underlying structural lung disease, and those with extrapulmonary disease commonly have immunosuppressive conditions or foreign body-associated infections. Treatment outcomes are generally favourable; however, in patients with pulmonary M. scrofulaceum disease prognosis is more guarded.

[Mycobacterium scrofulaceum infection in a pediatric patient from the Galapagos Islands - Ecuador]. / Infección por Mycobacterium scrofulaceum en un niño de las Islas Galápagos - Ecuador.

Mycobacterium scrofulaceum is a slow-growing atypical mycobacteria with a reservoir in the environmen, and occasionally it causes disease in humans. The case of a 10-year-old patient with fever of four months of evolution is presented. Symptoms include bilateral adenopathies of neck, thorax, abdomen and inguinal region, rash, abdominal pain and vomiting; in addition, a positive serology for EBV and a culture of the left inguinal ganglia with growth of M. scrofulaceum were evidenced. Thus, this is the first report of human infection caused by the aforementioned mycobacterium in Ecuador, which it was particularly manifested with an unusual pattern of resistance.

Infección por Mycobacterium scrofulaceum en un niño de las Islas Galápagos - Ecuador / Mycobacterium scrofulaceum infection in a pediatric patient from the Galapagos Islands - Ecuador

Resumen Mycobacterium scrofulaceum es una micobacteria atípica de crecimiento lento que tiene como reservorio el ambiente. De forma ocasional causa enfermedad en humanos. Se presenta el caso de un niño de 10 años de edad con fiebre de cuatro meses de evolución, adenopatías cervicales, torácicas, abdominales e inguinales bilaterales, exantema, dolor abdominal y vómitos; con evidencia concomitante de serología positiva para el VEB y cultivo de los ganglios inguinales izquierdos con crecimiento de M. scrofulaceum. Es la primera comunicación de una infección causada por esta micobacteria en Ecuador, y que particularmente se presentó con un patrón de resistencia inusual.

Mycobacterium scrofulaceum is a slow-growing atypical mycobacteria with a reservoir in the environmen, and occasionally it causes disease in humans. The case of a 10-year-old patient with fever of four months of evolution is presented. Symptoms include bilateral adenopathies of neck, thorax, abdomen and inguinal region, rash, abdominal pain and vomiting; in addition, a positive serology for EBV and a culture of the left inguinal ganglia with growth of M. scrofulaceum were evidenced. Thus, this is the first report of human infection caused by the aforementioned mycobacterium in Ecuador, which it was particularly manifested with an unusual pattern of resistance.

Disseminated Mycobacterium scrofulaceum Infection in an Immunocompetent Host.

A 56-year-old woman, without any immunocompromising diseases, was referred to our hospital because of a recurrence of pyogenic spondylitis. Computed tomography revealed multiple osteolytic changes in the whole body. Vertebral magnetic resonance imaging revealed osteomyelitis and spondylitis. Mycobacterium scrofulaceum was detected in sputum cultures, in abscesses from the right knee, and in a subcutaneous forehead abscess. Therefore, the patient was diagnosed with disseminated Mycobacterium scrofulaceum infection. The patient was treated with rifampicin, ethambutol, and clarithromycin, which resulted in symptomatic relief and radiological improvement. We herein report a rare case of disseminated Mycobacterium scrofulaceum infection in an immunocompetent host.

Clinical characteristics of pulmonary Mycobacterium scrofulaceum disease in 2001-2011: A case series and literature review.

BACKGROUND: Mycobacterium scrofulaceum is a well-known pathogen associated with cervical lymphadenitis in children. However, pulmonary M. scrofulaceum disease is a rare condition with unknown clinical features. The present study aimed to clarify the clinical features of pulmonary M. scrofulaceum disease described in recent cases and reports. METHODS: We reviewed the medical records of all adult patients with pulmonary M. scrofulaceum disease at Keio University Hospital and the National Center for Global Health and Medicine Center Hospital between 2001 and 2011. We also conducted a review of the PubMed database to identify additional cases of pulmonary M. scrofulaceum disease in adults. RESULTS: Our study identified 8 cases of pulmonary M. scrofulaceum disease at the 2 identified institutions during our study period. Most cases were diagnosed in middle-aged and elderly men with underlying pulmonary diseases such as chronic obstructive pulmonary disease and Mycobacterium avium complex lung disease, as well as those with a history of pulmonary tuberculosis. In contrast, most previously reported cases identified through our literature review had a history of dust inhalation or underlying silicosis. Three of 8 cases at our institutions and 20 of 23 cases from the literature were treated with combination therapies. CONCLUSIONS: We conclude that in the recent histories of our institutions, pulmonary M. scrofulaceum disease has mainly occurred in patients with chronic pulmonary diseases. We further conclude that combination therapies that include clarithromycin might yield better patient outcomes.

TLR4 and DC-SIGN receptors recognized Mycobacterium scrofulaceum promoting semi-activated phenotype on bone marrow dendritic cells.

Nontuberculous mycobacteria (NTM) are recognized as emerging pathogens and their immune regulatory mechanisms are not well described yet. From them, Mycobacterium avium is known to be a weak activator of dendritic cells (DCs) that impairs the response induced by BCG vaccine. However, whether other NTM such as Mycobacterium scrofulaceum may modulate the activation of DCs, has not been extensively studied. Here, we exposed bone marrow-derived DCs (BMDCs) to M. scrofulaceum and we analyzed the effect on the activation of DCs. We found that M. scrofulaceum has a comparable ability to induce a semi-mature DC phenotype, which was produced by its interaction with DC-SIGN and TLR4 receptors in a synergic effect. BMDCs exposed to M. scrofulaceum showed high expression of PD-L2 and production of IL-10, as well as low levels of co-stimulatory molecules and pro-inflammatory cytokines. In addition to immunophenotype induced on DCs, changes in morphology, re-organization of cytoskeleton and decreased migratory capacity are consistent with a semi-mature phenotype. However, unlike other pathogenic mycobacteria, the DC-semi-mature phenotype induced by M. scrofulaceum was reversed after re-exposure to BCG, suggesting that modulation mechanisms of DC-activation used by M. scrofulaceum are different to other known pathogenic mycobacteria. This is the first report about the immunophenotypic characterization of DC stimulated by M. scrofulaceum.

Lovastatin Analogues from the Soil-Derived Fungus Aspergillus sclerotiorum PSU-RSPG178.

Three new lovastatin analogues (1, 4, and 5) together with four known lovastatin derivatives, namely, lovastatin (2), α,ß-dehydrolovastatin (3), α,ß-dehydrodihydromonacolin K (6), and α,ß-dehydro-4a,5-dihydromonacolin L (7), were isolated from the soil-derived fungus Aspergillus sclerotiorum PSU-RSPG178. Their structures were established using spectroscopic evidence. Compound 5 exhibited the most potent activity against HMG-CoA reductase, with an IC50 value of 387 µM. In addition, the present study indicated the direct interaction of compound 5 with HMG-CoA reductase. Compound 5 was considered to be noncytotoxic against noncancerous Vero cells, with an IC50 value of 40.0 µM, whereas compound 2 displayed much stronger activity, with an IC50 value of 2.2 µM.

Microaerobic growth and anaerobic survival of Mycobacterium avium, Mycobacterium intracellulare and Mycobacterium scrofulaceum.

Representative strains of Mycobacterium avium, Mycobacterium intracellulare and Mycobacterium scrofulaceum (MAIS) grew at equal rates in laboratory medium at 21% (air) and 12% oxygen. Growth in 6% oxygen proceeded at a 1.4-1.8-fold lower rate. Colony formation was the same at 21% (air) and 6% oxygen. The MAIS strains survived rapid shifts from aerobic to anaerobic conditions as measured by two experimental approaches (Falkinham (1996) [1]). MAIS cells grown aerobically to log phase in broth were diluted, spread on agar medium, and incubated anaerobically for up to 20 days at 37°C. Although no colonies formed anaerobically, upon transfer to aerobic conditions, greater than 25% of the colony forming units (CFU) survived after 20 days of anaerobic incubation (Prince et al. (1989) [2]). MAIS cells grown in broth aerobically to log phase were sealed and vigorous agitation led to oxygen depletion (Wayne model). After 12 days anaerobic incubation, M. avium and M. scrofulaceum survival were high (>50%), while M. intracellulare survival was lower (22%). M. avium cells shifted to anaerobiosis in broth had increased levels of glycine dehydrogenase and isocitrate lyase. Growth of MAIS strains at low oxygen levels and their survival following a rapid shift to anaerobiosis is consistent with their presence in environments with fluctuating oxygen levels.

An atypical deep neck infection in a two-year-old child.

Non-tuberculous mycobacteria are one of the major causes of lymphadenitis in children and seldom of deep neck infections. We reported the case of an immunocompetent two-year-old girl with adenitis and retropharyngeal abscess caused by an atypical mycobacterium. She had a positive tuberculin skin test, whereas the Quantiferon TB Gold test was negative. The child underwent a complete nodal excision. The search for acid fast bacilli was positive and Mycobacterium scrofulaceum was isolated from the surgically removed material. The retropharyngeal abscess was treated only with antimicrobial therapy, which resulted in an appreciable size reduction of the abscess. After two months antimicrobial treatment was interrupted, and complete resolution was achieved after twelve months. No relapse of disease or possible long-term complications were observed. The surgical wound healed completely, with normal overlying skin and a good aesthetic result. The clinical management of atypical mycobacteria lymphadenitis and retropharyngeal abscess in children is discussed.

Characterization of Proinflammatory Responses and Innate Signaling Activation in Macrophages Infected with Mycobacterium scrofulaceum

Mycobacterium scrofulaceum is an environmental and slow-growing atypical mycobacterium. Emerging evidence suggests that M. scrofulaceum infection is associated with cervical lymphadenitis in children and pulmonary or systemic infections in immunocompromised adults. However, the nature of host innate immune responses to M. scrofulaceum remains unclear. In this study, we examined the innate immune responses in murine bone marrow-derived macrophages (BMDMs) infected with different M. scrofulaceum strains including ATCC type strains and two clinically isolated strains (rough and smooth types). All three strains resulted in the production of proinflammatory cytokines in BMDMs mediated through toll-like receptor-2 and the adaptor MyD88. Activation of MAPKs (extracellular signal-regulated kinase 1/2, and p38, and c-Jun N-terminal kinase) and nuclear receptor (NF)-kappaB together with intracellular reactive oxygen species generation were required for the expression of proinflammatory cytokines in BMDMs. In addition, the rough morphotypes of M. scrofulaceum clinical strains induced higher levels of proinflammatory cytokines, MAPK and NF-kappaB activation, and ROS production than other strains. When mice were infected with different M. scrofulaceum strains, those infected with the rough strain showed the greatest hepatosplenomegaly, granulomatous lesions, and immune cell infiltration in the lungs. Notably, the bacterial load was higher in mice infected with rough colonies than in mice infected with ATCC or smooth strains. Collectively, these data indicate that rough M. scrofulaceum induces higher inflammatory responses and virulence than ATCC or smooth strains.

Epithelioid histiocytic infiltrate caused by Mycobacterium scrofulaceum infection: a potential mimic of various neoplastic entities.

Mycobacterium scrofulaceum is a slow-growing atypical mycobacterium that is ubiquitous within our environment found in the water and soil. Most commonly, it manifests as the organism responsible for lymphadenitis in children. In adults, infection by this organism is rare and usually occurs in the setting of local or systemic host immunosuppression. We herein report a case of a 45-year-old woman who presented with a large subcutaneous nodule over her right upper arm. She had been on low dose oral prednisone for 17 years for systemic lupus erythematosus without complication. A biopsy of the nodule revealed a diffuse dermal infiltrate of epithelioid histiocytes laden with acid-fast bacilli mimicking a fibrohistiocytic neoplasm. Treatment with clarithromycin monotherapy resulted in clinical remission. Consideration of atypical mycobacterial infection is warranted in fibrohistiocytic proliferations of the skin especially within immunosuppressed patients.

Disseminated Mycobacterium scrofulaceum infection in a child with interferon-gamma receptor 1 deficiency.

Disseminated disease caused by non-tuberculous, environmental mycobacteria (EM) reflects impaired host immunity. Disseminated disease caused by Mycobacterium scrofulaceum has primarily been reported in patients with AIDS. Moreover, observing M. scrofulaceum as the agent of localized disease in childhood has become increasingly rare. We report the first case of disseminated disease caused by M. scrofulaceum in a child with inherited interferon-gamma receptor 1 (IFN-gammaR1) complete deficiency. As in this case, mycobacterial bone infections in IFN-gammaR1 deficiency can sometimes mimic the clinical picture of chronic recurrent multifocal osteomyelitis.

[A case of pulmonary Mycobacterium scrofulaceum infection and review of the tendency towards recent acid-fast bacilli infection].

A 47-year-old man presented to a local physician with a chief complaint of sputum and cough for 3 months. Chest X-ray showed bilateral consolidation in the upper lung fields, and the patient was suspected to have pulmonary tuberculosis: he was then referred to our hospital. Smear and culture of both sputum and gastric juice showed acid-fast bacilli, and we started administration of rifampicin, isoniazid, ethambutol, and pyrazinamide. Results of the culture and identification test showed the causative bacillus to be Mycobacterium scrofulaceum (M. scrofulaceum). We stopped pyrazinamide and added clarithromycin to the treatment regimen, which resulted in symptomatic relief and radiological improvement. The frequency of pulmonary nontuberculous mycobacteriosis is increasing: in contrast, pulmonary infection by M. scrofulaceum has been decreasing. Nevertheless, M. scrofulaceum infection should be considered in the differential diagnosis from tuberculosis when the results of radiological findings and sputum culture suggest pulmonary tuberculosis.