Identificación de especies micobacterianas ambientales u oportunistas en pacientes sintomáticos y con VIH/sida / Identification of environmental or opportunistic mycobacterial species in symptomatic symptomatic and HIV/AIDS patients

El aumento de las infecciones por micobacterias ambientales u oportunistas (MAO) coincide mundialmente con el declive de la infección tuberculosa e incremento de la infección por el virus de inmunodeficiencia humana (VIH). El presente trabajo es un estudio retrospectivo realizado en el Laboratorio Nacional de Referencia-Investigaciones de Tuberculosis/Micobacterias/Lepra (LNRI-TB/Lepra/Micobacterias), del Instituto de Medicina Tropical Pedro Kourí (IPK), La Habana, Cuba, durante el período enero 2014-diciembre 2018. El objetivo de nuestro estudio fue conocer la variabilidad de especies aisladas para establecer un referente actualizado sobre las infecciones causadas por estas. En este trabajo se clasificaron-identificaron 413 cepas procedentes de pacientes sintomáticos; 162 (39.22%) eran aislamientos de pacientes con VIH/sida atendidos en nuestro Hospital Nacional de Referencia a Atención al paciente VIH/sida (IPK), y el resto (n = 251 [60.77%]), procedentes de pacientes inmunocompetentes, incluyendo aislamientos recibidos de los Centros Provinciales de Higiene, Epidemiología, y Microbiología (CPHEM). Las muestras fueron analizadas con las técnicas convencionales establecidas: las pulmonares fueron descontaminadas por el método de Petroff modificado; las extrapulmonares, por el método del ácido sulfúrico al 4%; el cultivo se realizó en medio de Löwenstein-Jensen modificado. Posteriormente se realizó la clasificación-identificación de especies según el esquema fenotípico-bioquímico establecido. Las especies con mayor porcentaje de aislamiento pertenecieron a los Grupos III y IV, complejo Mycobacterium avium-intracellulare (34.14%) y complejo M. fortuitum (20.82%), respectivamente. Estos resultados permitirán conocer la prevalencia de estas especies en nuestro país, reafirmando la importancia diagnóstica de estos microorganismos para aplicar tratamiento específico, sobre todo en pacientes con factores de riesgo, en quienes es más probable la diseminación de la infección.

The increase in infections by environmental or opportunistic mycobacteria (MAO) coincides worldwide with the decline in tuberculosis infection and an increase in infection by the human immunodeficiency virus (HIV). The present work is a retrospective study carried out at the National Reference Laboratory-Tuberculosis/Mycobacterial/Leprosy Research (LNRI-TB / Leprosy / Mycobacteria), of the Pedro Kourí Institute of Tropical Medicine (IPK), La Habana, Cuba, during the period January 2014-December 2018. The objective of our study was to know the variability of isolated species to establish an updated reference on the infections caused by MAO. In this study, 413 strains from symptomatic patients were classified and identified; 162 (39.22%) were isolates from patients with HIV/AIDS treated at our National Hospital of Reference for Attention to HIV/AIDS patients (IPK), and the remaining (n=251 [60.77%]), from immunocompetent patients, including isolates received from the Provincial Centers of Hygiene, Epidemiology, and Microbiology (CPHEM). The samples were analyzed with the established conventional techniques: the lung samples were decontaminated by the modified Petroff method; the extrapulmonary, by the 4% sulfuric acid method; the culture was carried out in modified Löwenstein-Jensen medium. Subsequently, the classification-identification of species was carried out according to the established phenotypic-biochemical scheme. The species with the highest percentage of isolation belonged to Groups III and IV, Mycobacterium avium-intracellulare complex (34.14%), and M. fortuitum complex (20.82%), respectively. These results will allow us to know the prevalence of these species in our country, emphasizing the diagnostic importance of these microorganisms and thus apply a specific treatment, especially in patients with risk factors, in whom the spread of the infection is more likely

Treatment Outcomes after Discontinuation of Ethambutol due to Adverse Events in Mycobacterium avium Complex Lung Disease

BACKGROUND: Long-term administration of ethambutol (EMB) for Mycobacterium avium complex lung disease (MAC-LD) sometimes leads to permanent discontinuation of EMB due to various adverse events. This study aimed to investigate treatment outcomes after discontinuation of EMB.METHODS: Among patients diagnosed with MAC-LD between January 2001 and December 2014, 508 patients whose treatment was initiated with standard regimen until May 2018 were enrolled at a tertiary referral center in Korea. Of these 508 patients, 60 (11.8%) discontinued EMB due to various adverse effects. Among these 60 patients, treatment outcomes were analyzed for 44 patients by comparing their outcomes with those of matched subjects who received the standard treatment regimen without EMB discontinuation.RESULTS: The mean age of the 60 patients who discontinued EMB was 64.4 years. Ocular toxicity was the most common cause of discontinuation of EMB (75.0%, 45/60). The mean duration of EMB administration before its discontinuation was 7.0 ± 4.6 months. The treatment failure rate of the 44 patients with EMB discontinuation analyzed for treatment outcome was 29.6%, which was higher than that of the matched patients who received the standard regimen (18.3%), although the difference was not significant (P = 0.095). Of these 44 patients, EMB was substituted with later-generation fluoroquinolone in 23 patients, and the treatment failure rate of these 23 patients was significantly higher than that of the matched patients who received the standard regimen (39.1% vs. 19.3%, P = 0.045).CONCLUSION: These findings suggest that treatment outcomes are unsatisfactory in patients with MAC-LD who discontinue EMB owing to adverse events. Notably, there was a statistically significant high failure rate in patients who were prescribed fluoroquinolone to replace EMB.

Prevalence of Opportunistic Pathogens and Diversity of Microbial Communities in the Water System of a Pulmonary Hospital / 生物医学与环境科学（英文）

Objective@#Our objective was to investigate the occurrence of opportunistic pathogens and characterize the bacterial community structures in the water system of a pulmonary hospital.@*Methods@#The water samples were collected from automatic and manual faucets in the consulting room, treatment room, dressing room, respiratory ward, and other non-medical rooms in three buildings of the hospital. Quantitative polymerase chain reaction was used to quantify the load of several waterborne opportunistic pathogens and related microorganisms, including spp., spp., and . Illumina sequencing targeting 16S rRNA genes was performed to profile bacterial communities.@*Results@#The occurrence rates of spp., spp., and were 100%, 100%, and 76%, respectively in all samples. Higher occurrence rates of were observed in the outpatient service building (building 1, 91.7%) and respiration department and wards (building 2, 80%) than in the office building (building 3), where no was found. were more abundant in automatic faucets (average 2.21 × 10 gene copies/L) than in manual faucets (average 1.03 × 10 gene copies/mL) ( < 0.01). , , , , , and were the dominant bacterial phyla. Disinfectant residuals, nitrate, and temperature were found to be the key environmental factors driving microbial community structure shifts in water systems.@*Conclusion@#This study revealed a high level of colonization of water faucets by opportunistic pathogens and provided insight into the characteristics of microbial communities in a hospital water system and approaches to reduce risks of microbial contamination.

Nontuberculous mycobacteria in patients with suspected tuberculosis and the genetic diversity of Mycobacterium avium in the extreme south of Brazil / Micobactérias não tuberculosas em pacientes com suspeita de tuberculose e a diversidade genética de Mycobacterium avium no extremo sul do Brasil

ABSTRACT Objective: Nontuberculous mycobacteria (NTM) are a heterogeneous group of bacteria that are widely distributed in nature and associated with opportunistic infections in humans. The aims of this study were to identify NTM in patients with suspected tuberculosis who presented positive cultures and to evaluate the genetic diversity of strains identified as Mycobacterium avium. Methods: We studied pulmonary and extrapulmonary samples obtained from 1,248 patients. The samples that tested positive on culture and negative for the M. tuberculosis complex by molecular identification techniques were evaluated by detection of the hsp65 and rpoB genes and sequencing of conserved fragments of these genes. All strains identified as M. avium were genotyped using the eight-locus mycobacterial interspersed repetitive unit-variable-number tandem-repeat method. Results: We found that NTM accounted for 25 (7.5%) of the 332 mycobacteria isolated. Of those 25, 18 (72%) were M. avium, 5 (20%) were M. abscessus, 1 (4%) was M. gastri, and 1 (4%) was M. kansasii. The 18 M. avium strains showed high diversity, only two strains being genetically related. Conclusions: These results highlight the need to consider the investigation of NTM in patients with suspected active tuberculosis who present with positive cultures, as well as to evaluate the genetic diversity of M. avium strains.

RESUMO Objetivo: As micobactérias não tuberculosas (MNT) são um grupo heterogêneo de bactérias amplamente distribuídas na natureza e relacionadas com infecções oportunistas em seres humanos. Os objetivos deste estudo foram identificar MNT em pacientes com suspeita de tuberculose e culturas positivas e avaliar a diversidade genética de cepas identificadas como Mycobacterium avium. Métodos: Foram estudadas amostras pulmonares e extrapulmonares provenientes de 1.248 pacientes. As amostras que apresentaram resultado positivo em cultura e negativo para o complexo M. tuberculosis na identificação molecular foram avaliadas por meio da detecção dos genes hsp65 e rpoB e de sequenciamento de fragmentos conservados desses genes. Todas as cepas identificadas como M. avium foram genotipadas pelo método mycobacterial interspersed repetitive unit-variable-number tandem-repeat com oito loci. Resultados: Das 332 micobactérias isoladas, 25 (7,5%) eram MNT. Dessas 25, 18 (72%) eram M. avium, 5 (20%) eram M. abscessus, 1 (4%) era M. gastri e 1 (4%) era M. kansasii. As 18 cepas de M. avium apresentaram alta diversidade, e apenas duas eram geneticamente relacionadas. Conclusões: Esses resultados mostram a necessidade de considerar a investigação de MNT em pacientes com suspeita de tuberculose ativa e culturas positivas e de avaliar a diversidade genética de cepas de M. avium.

Brazilian Green Propolis: Chemical Composition of Essential Oil and Their In Vitro Antioxidant, Antibacterial and Antiproliferative Activities

Abstract Propolis is a resinous substance collected and processed by Apis mellifera from parts of plants, buds and exudates. In Minas Gerais (MG) state, Brazil, green propolis is produced from the collection of resinous substance found in shoot apices of Baccharis dracunculifolia. This paper aims to investigate the chemical composition and in vitro antioxidant, anti-Helicobacter pylori, antimycobacterial and antiproliferative activities of essential oil (EO) from Brazilian green propolis (BGP-EO). The oil showed high antibacterial activity against H. pylori (MIC = 6.25 µg/mL), Mycobacterium avium (MIC = 62.5 µg/mL) and M. tuberculosis (MIC = 64 µg/mL). Its antioxidant activity was evaluated in vitro by both DPPH (IC50 = 23.48 µg/mL) and ABTS (IC50 = 32.18 µg/mL) methods. The antiproliferative activity in normal (GM07492A, lung fibroblasts) and tumor cell lines (MCF-7, HeLa and M059J) was analyzed by the XTT assay. BGP-EO showed inhibition of normal cell growth at 68.93 ± 2.56 µg/mL. Antiproliferative activity was observed against human tumor cell lines, whose IC50 values were 56.17, 66.43 and -65.83 µg/mL for MCF-7, HeLa and M059J cells, respectively. Its major constituents, which were determined by GC-FID and GC-MS, were carvacrol (20.7 %), acetophenone (13.5 %), spathulenol (11.0 %), (E)-nerolidol (9.7 %) and β-caryophyllene (6.2 %). These results showed the effectiveness of BGP-EO as a natural product which has promising biological activities.

Identificación y estudio de susceptibilidad antimicrobiana en cepas de mycobacterium spp. aisladas en un hospital de alta complejidad / Identification and study of antimicrobial susceptibility of isolated mycobacterium spp. strains in a hospital of high complexity

El género Mycobacterium se encuentra asociado a una cantidad importante de patologías, donde la tuberculosis destaca dentro de los principales problemas de salud pública a nivel mundial y nacional. Esta se agudiza con el incremento en la resistencia antimicrobiana y, por ello, la pesquisa de micobacterias contempla un pilar fundamental en el diagnóstico de patologías infecciosas de importancia clínica. Por lo tanto, el objetivo fue describir las principales especies de micobacterias aisladas y su patrón de susceptibilidad a partir de muestras clínicas procesadas en el Hospital Dr. Hernán Henríquez Aravena durante el año 2012. Se realizó un estudio descriptivo retrospectivo, en donde se utilizaron los resultados de 7023 baciloscopías procesadas en el Laboratorio Clínico del Hospital Dr. Hernán Henríquez Aravena de Temuco el año 2012. Todas las baciloscopías fueron analizadas y solicitadas según criterios establecidos por el Instituto de Salud Pública de Chile, comprendiendo muestras de expectoración y no expectoración. De las 7023 baciloscopías realizadas, 100 resultaron ser positivas para Mycobacterium. De 21 cepas enviadas al Instituto de Salud Pública de Chile para identificación, 19 cepas corresponden al complejo Mycobacterium tuberculosis y dos a Mycobacterium avium intracelular. En el estudio de sensibilidad, se encontró resistencia a estreptomicina e isoniazida en 13,3 % de las expectoraciones. De acuerdo a lo establecido por la literatura, más del 90 % pertenecen a Mycobacterium tuberculosis, mientras que, de las micobacterias no tuberculosas sólo se aislaron Mycobacterium avium intracelular. Los antimicrobianos con mayores niveles de resistencia son estreptomicina e isoniazida.

The genus Mycobacterium is associated with a significant number of pathologies, where tuberculosis stands out among the main public health problems worldwide and nationally. This is exacerbated by the increase in antimicrobial resistance and, therefore, the research of mycobacteria contemplates a fundamental pillar in the diagnosis of infectious pathologies of clinical importance. Therefore, the aim was to describe the main species of isolated mycobacteria and their susceptibility pattern from clinical samples processed at the Dr. Hernán Henríquez Aravena Hospital during 2012. A retrospective descriptive study was carried out, where the results of 7023 sputum microscopy processed in the Clinical Laboratory of the Dr. Hernán Henríquez Aravena Hospital in Temuco in 2012. All sputum microscopy was analyzed and requested according to criteria established by the Instituto de Salud Pública of Chile, including expectoration and non-sputum samples. Of the 7023-sputum microscopy performed, 100 were positive for Mycobacterium. Of 21 strains sent to the Instituto de Salud Pública of Chile for identification, 19 strains correspond to the Mycobacterium tuberculosis complex and two to intracellular Mycobacterium avium. In the sensitivity study, resistance to streptomycin and isoniazid was found in 13.3 % of the expectorations. According to what is established by the literature, more than 90 % belong to Mycobacterium tuberculosis, while only intracellular Mycobacterium avium was isolated from non-tuberculous mycobacteria. Antimicrobials with higher levels of resistance are streptomycin and isoniazid.

Treatment of Mycobacterium avium Complex Pulmonary Disease / 결핵및호흡기질환

The pathogen Mycobacterium avium complex (MAC) is the most common cause of nontuberculous mycobacterial pulmonary disease worldwide. The decision to initiate long-term antibiotic treatment is difficult for the physician due to inconsistent disease progression and adverse effects associated with the antibiotic treatment. The prognostic factors for the progression of MAC pulmonary disease are low body mass index, poor nutritional status, presence of cavitary lesion(s), extensive disease, and a positive acid-fast bacilli smear. A regimen consisting of macrolides (clarithromycin or azithromycin) with rifampin and ethambutol has been recommended; this regimen significantly improves the treatment of MAC pulmonary disease and should be maintained for at least 12 months after negative sputum culture conversion. However, the rates of default and disease recurrence after treatment completion are still high. Moreover, treatment failure or macrolide resistance can occur, although in some refractory cases, surgical lung resection can improve treatment outcomes. However, surgical resection should be carefully performed in a well-equipped center and be based on a rigorous risk-benefit analysis in a multidisciplinary setting. New therapies, including clofazimine, inhaled amikacin, and bedaquiline, have shown promising results for the treatment of MAC pulmonary disease, especially in patients with treatment failure or macrolide-resistant MAC pulmonary disease. However, further evidence of the efficacy and safety of these new treatment regimens is needed. Also, a new consensus is needed for treatment outcome definitions as widespread use of these definitions could increase the quality of evidence for the treatment of MAC pulmonary disease.

Treatment of Mycobacterium Abscessus Pulmonary Disease / 대한내과학회지

Mycobacterium abscessus is the second most important pathogen in pulmonary disease caused by nontuberculous mycobacteria (NTM), following Mycobacterium avium. Mycobacterium abscessus is classified into three subspecies: M. abscessus subsp. abscessus, M. abscessus subsp. massiliense, and M. abscessus subsp. bolletii. Mycobacterium abscessus is the most difficult to treat NTM due to its resistance to many antibiotics. Treatment should include an initial regimen of 2–3 injectable and oral antibiotics for several weeks or months, followed by inhaled amikacin and 1–3 oral antibiotics, depending on the subspecies and drug susceptibility patterns, including macrolide susceptibility. The continuation phase should be continued for a minimum of 12 months after culture conversion. Suitable injectable antibiotics include amikacin, imipenem, cefoxitin, and tigecycline, while oral antibiotics include macrolides (azithromycin or clarithromycin), clofazimine, linezolid, and moxifloxacin. Surgery can be a useful adjunctive therapy for some patients with refractory disease. However, the overall treatment prognosis is still unsatisfactory. Therefore, novel and more effective interventions are required for the treatment of M. abscessus pulmonary disease.

Gene Expression Profiles of Th1-type Chemokines in Whole Blood of Mycobacterium avium subsp. paratuberculosis-Infected Cattle

Johne's disease (JD) is a chronic, debilitating disease of ruminants including cows, and is caused by Mycobacterium avium subsp. paratuberculosis (MAP). MAP is not only important in animal husbandry, but also in public health as it is associated with the onset of Crohn's disease, a chronic inflammatory bowel disease in humans. JD, like other mycobacterial diseases including tuberculosis, is classified into different stages based on the progression of infection. In addition, development of diagnostic assays that can distinguish between subclinical and clinical stages of JD is essential to control mycobacterial infection by providing an effective treatment. For the development of novel diagnostic methods of JD, it is important to investigate and understand the mRNA expression of the various immune markers in individuals at each stage of infection. In this study, we measured the levels of Th1-type chemokines, CXCR3, CCL4, CCL5, CXCL9, CXCL10, and CXCL11 in MAP-infected bovine blood by interferon (IFN)-γ release assay (IGRA) using IFN-γ as an alternative biomarker. The association of mRNA expression patterns of these chemokines with the MAP infection stages was analyzed and IFN-γ, CCL5, and CXCL10 were found to be significantly upregulated compared to IFN-γ, the biomarker used in IGRA. Our results further indicate that IFN-γ levels significantly increased in individuals with MAP-specific antibody, and CCL5 and CXCL10 levels significantly increased in those with MAP DNA. In particular, CCL5 was significantly upregulated in individuals, in which both MAP-specific antibody and MAP DNA were detected, but the expression of CXCL10 was specifically elevated in MAP DNA-detected individuals without MAP-specific antibody.

Mycobacterium avium Complex Infection-Related Immune Reconstitution Inflammatory Syndrome Mimicking Lymphoma in an Human Immunodeficiency Virus-Infected Patient

In acquired immunodeficiency syndrome (AIDS) patients, immune reconstitution inflammatory syndrome (IRIS) due to Mycobacterium avium complex (MAC) infection is one of the most difficult IRIS types to manage. We report an unusual case of MAC-associated IRIS. At first the patient was diagnosed human immunodeficiency virus (HIV) infection after he was admitted with pneumocystis pneumonia. After starting antiretroviral therapy he presented unmasked IRIS with MAC infection. Next, he was hospitalized with continuous loose stools and new-onset fever. Investigation included computed tomography (CT), which showed homogeneous enhancement and enlargement of the lymph nodes (LN), elevation of ferritin (>1,650 ng/mL) and lactate dehydrogenase (306 IU/L) levels, and F- fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) scan, which showed increased FDG uptake. These findings were highly indicative of lymphoma. We performed laparoscopic biopsy of the mesenteric LN, and the biopsy culture grew MAC. So we made a diagnosis of MAC-associated. Therefore, IRIS must be considered as a possible diagnosis when AIDS patients develop new symptoms or exhibit exacerbations of existing symptoms. Furthermore the biopsies should be conducted.

Mycobacterium avium Complex Infection-Related Immune Reconstitution Inflammatory Syndrome Mimicking Lymphoma in an Human Immunodeficiency Virus-Infected Patient

In acquired immunodeficiency syndrome (AIDS) patients, immune reconstitution inflammatory syndrome (IRIS) due to Mycobacterium avium complex (MAC) infection is one of the most difficult IRIS types to manage. We report an unusual case of MAC-associated IRIS. At first the patient was diagnosed human immunodeficiency virus (HIV) infection after he was admitted with pneumocystis pneumonia. After starting antiretroviral therapy he presented unmasked IRIS with MAC infection. Next, he was hospitalized with continuous loose stools and new-onset fever. Investigation included computed tomography (CT), which showed homogeneous enhancement and enlargement of the lymph nodes (LN), elevation of ferritin (>1,650 ng/mL) and lactate dehydrogenase (306 IU/L) levels, and F- fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) scan, which showed increased FDG uptake. These findings were highly indicative of lymphoma. We performed laparoscopic biopsy of the mesenteric LN, and the biopsy culture grew MAC. So we made a diagnosis of MAC-associated. Therefore, IRIS must be considered as a possible diagnosis when AIDS patients develop new symptoms or exhibit exacerbations of existing symptoms. Furthermore the biopsies should be conducted.

Genetic diversity of bovine Mycobacterium avium subsp. paratuberculosis discriminated by IS1311 PCR-REA, MIRU-VNTR, and MLSSR genotyping

The aim of this study was to describe the genetic diversity of Mycobacterium avium subsp. paratuberculosis (MAP) obtained from individual cows in Korea. Twelve MAP-positive fecal DNA samples and 19 MAP isolates were obtained from 10 cattle herds located in 5 provinces in Korea. In addition, 5 MAP isolates obtained from the Czech Republic and Slovakia and 3 isolates from Australia were genotyped for comparison with the domestic isolates. The most prevalent strains in Korea were of the “bison-type” genotype (23 of 31 fecal DNA/isolates) and were distributed nationwide. The remaining MAP isolates (8) and all of the foreign isolates were identified as “cattle-type”. The bison-type strains which were discriminated only as INMV 68 in variable-number tandem repeats of mycobacterial interspersed repetitive units (MIRU-VNTR) typing. Multilocus short sequence repeat (MLSSR) typing differentiated the bison-type strains into 3 different subtypes. The cattle-type strains were divided into 3 subtypes by MIRU-VNTR and 8 subtypes by MLSSR. The allelic diversities in the MIRU-VNTR and MLSSR results were calculated as 0.567 and 0.866, respectively. These results suggest that MIRU-VNTR typing cannot provide a sufficient description of the epidemiological situation of MAP. Therefore, an alternative method, such as MLSSR, is needed for typing of MAP strains to elucidate the molecular epidemiology of MAP infections. Overall, this study is the first epidemiological survey report in Korea using both MIRU-VNTR and MLSSR typing methods, and it has provided basic data necessary to elucidate the characteristics of MAP infections in Korea.

Rapid visual detection of Mycobacterium avium subsp. paratuberculosis by recombinase polymerase amplification combined with a lateral flow dipstick

Paratuberculosis (Johne's disease) is a chronic debilitating disease of domestic and wild ruminants. However, widespread point-of-care testing is infrequent due to the lack of a robust method. The isothermal recombinase polymerase amplification (RPA) technique has applied for rapid diagnosis. Herein, RPA combined with a lateral flow dipstick (LFD) assay was developed to estimate DNA from Mycobacterium avium subsp. paratuberculosis. First, analytical specificity and sensitivity of the RPA-nfo primer and probe sets were assessed. The assay successfully detected M. paratuberculosis DNA in 30 min at 39℃ with a detection limit of up to eight copies per reaction, which was equivalent to that of the real-time quantitative polymerase chain reaction (qPCR) assay. The assay was specific, as it did not amplify genomes from five other Mycobacterium spp. or five pathogenic enteric bacteria. Six hundred-twelve clinical samples (320 fecal and 292 serum) were assessed by RPA-LFD, qPCR, and enzyme-linked immunosorbent assay, respectively. The RPA-LFD assay yielded 100% sensitivity, 97.63% specificity, and 98.44% concordance rate with the qPCR results. This is the first report utilizing an RPA-LFD assay to visualize and rapidly detect M. paratuberculosis. Our results show this assay should be a useful method for the diagnosis of paratuberculosis in resource-constrained settings.

Adamantinoma de la tibia / Adamantinome du tibia / Adamantinoma of the tibia

El adamantinoma es un tumor maligno de origen epitelial con una frecuencia de aparición escasa. Con este artículo se pretende describir la conducta y evolución de un paciente portador de adamantinoma de la tibia asociado a infección pulmonar y ósea por Mycobacterium avium. Se presenta un paciente masculino de 43 años de edad con el diagnóstico de adamantinoma, localizado en el tercio medio-inferior de la tibia derecha. Los hallazgos clínicos, imaginológicos e histopatológicos permiten llegar al diagnóstico de un adamantinoma del esqueleto apendicular. Se realizó la exéresis de la tumoración y relleno con cemento quirúrgico. Doce meses después del tratamiento aparecieron signos clínicos y radiográficos de recidiva tumoral y fue necesaria la amputación infratuberositaria de la pierna derecha. Además, se observaron lesiones fibroquísticas en el vértice del pulmón izquierdo relacionadas con Mycobacterium avium. Luego de un seguimiento por dos años, se observaron múltiples nódulos metastásicos en ambos campos pulmonares(AU)

Adamantinoma is an epithelial-origin malignant tumor with uncommon frequency of appearance. This article aims to describe the behavior and evolution of a patient with adamantinoma of the tibia associated with pulmonary and bone infection by Mycobacterium avium. We present a 43 years old male patient with the diagnosis of adamantinoma. This adamantinoma was located in the middle-lower third of the right tibia. The clinical, imaging and histopathological findings allowed to reach the diagnosis of adamantinoma of the appendicular skeleton. The excision of the tumor and filling with surgical cement was performed. Twelve months after the treatment, clinical and radiographic signs showed tumor recurrence. The infratuberosal amputation of the right leg was necessary. In addition, fibrocystic lesions were observed at the apex of the left lung related to Mycobacterium avium. After a two-year follow up, multiple metastatic nodules were observed in both lung fields(AU)

L'adamantinome est une tumeur maligne assez rare d'origine épithéliale. Le but de cet article est de décrire le comportement et l'évolution d'un patient atteint d'un adamantinome au niveau du tibia, associé à une infection pulmonaire et osseuse par Mycobacterium avium. Le cas d'un patient âgé de 43 ans, diagnostiqué d'un adamantinome localisé dans le tiers moyen inférieur du tibia droit, est présenté. Les observations cliniques, histopathologiques et d'imagerie ont permis de confirmer le diagnostic d'un adamantinome du squelette appendiculaire. On a effectué l'exérèse de la tumeur et le remplissage à ciment chirurgical. Douze mois après ce traitement, des signes cliniques et radiographiques d'une récidive tumorale ont apparu, et une amputation infratubérositaire de la jambe droite a été nécessaire. On a aussi trouvé des lésions fibrokystiques sur l'apex du poumon gauche, associées à Mycobacterium avium. Après un suivi de deux ans, on a rencontré plusieurs nodules métastatiques dans tous les deux côtés de la région pulmonaire(AU)

Paratuberculosis: new histopathological findings in red deer (Cervus elaphus) and fallow deer (Dama dama) in Chile / Paratuberculosis: novos achados histopatológicos em Veado Vermelho (Cervus elaphus) e Gamo (Dama dama) no Chile

Paratuberculosis is a disease caused by Mycobacterium avium subsp. paratuberculosis (MAP) that affects domestic and wild ruminants. The most common gross lesions are emaciation and corrugation and thickening of the mucosa of the small intestine. Mesenteric lymph nodes might be enlarged. For the present study, 14 red deer and 9 fallow deer from game reserves or venison farms were analyzed. The lesions found correspond to those found by other authors in other geographic locations, except for some differences in histopathological examinations. Among these differences, stands out that intestinal lesions were concentrated mostly in the ileum and granulomas were shown to be more frequent in this section of the intestine than in the corresponding lymph node. Furthermore, in multibacillary lesions the inflammatory infiltrate in the lymph nodes was mainly composed of macrophages. These differences may be due to individual variations of the animals, the stage of disease or a different strain of the pathogen. This study allowed to obtain basic information about the disease and to describe patterns of lesions found in red deer and fallow deer with prediagnosis of clinical paratuberculosis which were not described in the literature before.(AU)

Paratuberculosis é uma doença causada por Mycobacterium avium subsp. paratuberculosis (MAP) que afecta ruminantes selvagens e domésticos. As lesões macroscópicas mais comuns são ondulação e espessamento da mucosa do intestino delgado. Os linfonodos mesentéricos podem aparecer com volume aumentado. Para este estudo, foram analisados 14 veados vermelhos e 9 veados gamo de reservas de caça e fazendas de carne. As lesões encontradas correspondem à encontrada por outros autores em outras localizações geográficas, com exceção de algumas diferenças no exame histopatológico. Entre essas diferenças, sobressai que as lesões intestinais se concentraram principalmente no íleo, os granulomas ocorreram com maior frequência nesta seção do intestino que no seu correspondente linfonodo. Além disso, nas lesões bacterianas, o infiltrado inflamatório linfonodos linfáticos era composta principalmente por macrófagos. Estas diferenças podem ser devidas a variações individuais dos animais, o estádio da doença ou de uma estirpe diferente do agente patogénico. Este estudo permitiu obter informação básica sobre a doença e descrever padrões de lesões encontradas em veados e em gamos com pré-diagnóstico, de paratuberculosis clínica nunca antes descritas na literatura.(AU)

Recovery Rates of Non-Tuberculous Mycobacteria from Clinical Specimens Are Increasing in Korean Tertiary-Care Hospitals

Non-tuberculous mycobacteria (NTM) are being recognized increasingly as the causative agents of opportunistic infections in humans. This study investigated the epidemiologic trends of NTM recovery from various clinical specimens in 2 Korean tertiary-care hospitals. We reviewed the laboratory records of patient samples cultured for mycobacteria between 2009 and 2015 at 2 tertiary-care hospitals in Korea. The medical records for patients with positive NTM samples were also reviewed. During the study period, 144,540 specimens were cultured for mycobacteria. The proportion of NTM-positive samples increased from 23.3% in 2009 to 48.2% in 2015. The 2 most frequently isolated NTM were Mycobacterium intracellulare (38.3%) and M. avium (23.1%). The number of clinically significant diseases caused by NTM in inpatients and outpatients increased from 6.8 to 12.9 per 100,000 patients over the same period. The rates of recovery of NTM from clinical specimens and the number of patients with NTM infections increased significantly (P < 0.001, testing for trend) between 2009 and 2015.

Simultaneous Diagnosis of Pneumococcal Sepsis and Disseminated Mycobacterium avium Complex Infection in a Patient with Acquired Immunodeficiency Syndrome / 대한내과학회지

The incidence of bacteremia in human immunodeficiency virus (HIV)-infected patients is significantly decreased by highly active antiretroviral therapy (HAART). However, bacteremia remains a major cause of morbidity and mortality in HIV-infected patients. A 43-year-old male who had fever and cough for 1 week presented to the emergency room. He was diagnosed with acquired immunodeficiency syndrome combined with atypical pneumonia and started on antibiotics plus HAART. After 3 days, Streptococcus pneumoniae was grown in blood cultures. Three weeks later, acid-fast bacilli cultures of blood and bronchoalveolar lavage fluid grew Mycobacterium avium complex (MAC); hence, the patient was treated with antimycobacterial drugs. HIV-infected patients with persistent fever despite administration of appropriate antibiotics should be examined for simultaneous infection by other organisms, such as nontuberculous mycobacteria. We report a case of simultaneous detection of MAC and S. pneumoniae in the blood of a treatment-naïve HIV-infected patient.

Multiple Cavitary Pulmonary Nodules Caused by Mycobacterium intracellulare / 가정의학회지

Nontuberculous mycobacteria (NTM) have been increasingly recognized as an important cause of chronic pulmonary infections. The Mycobacterium avium complex (MAC), which is composed of two species, Mycobacterium avium and Mycobacterium intracelluare, is the most commonly encountered pathogen associated with NTM lung disease. MAC pulmonary infection typically presents in a fibrocavitary form or a nodular bronchiectatic form. However, there have been atypical presentations of MAC pulmonary infections, including solitary pulmonary nodules (SPN). There have been several previous reports of SPN due to MAC infection in the United States, Japan, and Korea. In 2009, Sekine and colleagues reported a case of MAC pulmonary infection presenting with multiple nodules. To date, however, there have been no cases of NTM lung infection with multiple cavitary pulmonary nodules, and neither a fibrotic change nor nodular bronchiectasis. The present case showed a multiple cavitating nodular lung infection due to MAC, which is very rare and different from the typical presentation of MAC pulmonary infections. We also showed that percutaneous transthoracic needle aspiration can be a useful diagnostic tool to evaluate a case of multiple cavitary nodules.

Development of vaccines to Mycobacterium avium subsp. paratuberculosis infection

Johne's disease or paratuberculosis is a chronic debilitating disease in ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). The disease causes significant economic losses in livestock industries worldwide. There are no effective control measures to eradicate the disease because there are no appropriate diagnostic methods to detect subclinically infected animals. Therefore, it is very difficult to control the disease using only test and cull strategies. Vaccination against paratuberculosis has been considered as an alternative strategy to control the disease when combined with management interventions. Understanding host-pathogen interactions is extremely important to development of vaccines. It has long been known that Th1-mediated cellular immune responses are play a crucial role in protection against MAP infection. However, recent studies suggested that innate immune responses are more closely related to protective effects than adaptive immunity. Based on this understanding, several attempts have been made to develop vaccines against paratuberculosis. A variety of ideas for designing novel vaccines have emerged, and the tests of the efficacy of these vaccines are conducted constantly. However, no effective vaccines are commercially available. In this study, studies of the development of vaccines for MAP were reviewed and summarized.