Immunogenicity of Whole / 生物医学与环境科学（英文）

Objectives@#To evaluate the immunogenicity of @*Methods@#Protein extracts from @*Results@#Immunization with @*Conclusion@#This is the advanced study to investigate the immunogenicity of

Effect of coexisting advanced extrapulmonary solid cancer on progression of Mycobacterium avium complex lung disease / Efeito da coexistência de câncer sólido extrapulmonar avançado na progressão da doença pulmonar por complexo Mycobacterium avium

ABSTRACT Objective: Although Mycobacterium avium complex (MAC) lung disease has been shown to be associated with lung cancer and hematologic malignancies, there have been few studies of its relationships with other types of cancer. The aim of this study was to assess the effect that coexisting advanced extrapulmonary solid tumors have on the progression of MAC lung disease. Methods: This was a retrospective study of patients diagnosed with MAC lung disease, on the basis of the American Thoracic Society (ATS) criteria, between October of 2005 and March of 2019. The patients were divided into three groups: those with advanced-stage cancer (A-SC group); those with early-stage cancer (E-SC group); and those without cancer (control group). Progression of MAC lung disease was defined as exacerbation seen on imaging. Patient characteristics and the time to progression were compared among the three groups. Results: A total of 286 patients met the ATS diagnostic criteria for MAC lung disease, and 128 of those were excluded. Of the remaining 158 patients, 20 (7.0%) were in the A-SC group, 36 (12.6%) were in the E-SC group, and 102 (35.7%) were in the control group. The median time to progression in the A-SC, E-SC, and control groups was 432, 3,595, and 2,829 days, respectively (p < 0.01). A proportional hazards model showed that the significant predictors of MAC lung disease progression were advanced-stage cancer (hazard ratio [HR] = 6.096; 95% CI: 2.688-13.826; p < 0.01), cavitary lesions (HR = 2.750; 95% CI: 1.306-5.791; p < 0.01), and a high Nodule-Infiltration-Cavity-Ectasis score (HR = 1.046; 95% CI: 1.004-1.091; p = 0.033). Conclusions: A coexisting advanced extrapulmonary solid tumor could hasten the progression of MAC lung disease.

RESUMO Objetivo: Embora tenha sido demonstrado que a doença pulmonar por Mycobacterium avium complex (MAC, complexo M. avium) está associada a câncer de pulmão e neoplasias hematológicas, há poucos estudos sobre sua relação com outros tipos de câncer. O objetivo deste estudo foi avaliar o efeito da coexistência de tumores sólidos extrapulmonares avançados na progressão da doença pulmonar por MAC. Métodos: Estudo retrospectivo de pacientes diagnosticados com doença pulmonar por MAC, segundo os critérios da American Thoracic Society (ATS), entre outubro de 2005 e março de 2019. Os pacientes foram divididos em três grupos: grupo câncer em estágio avançado (grupo CEA), grupo câncer em estágio inicial (grupo CEI) e grupo sem câncer (grupo controle). Progressão da doença pulmonar por MAC foi definida como exacerbação observada em exame de imagem. As características dos pacientes e o tempo para progressão foram comparados entre os três grupos. Resultados: Um total de 286 pacientes preencheu os critérios diagnósticos da ATS para doença pulmonar por MAC, sendo 128 deles excluídos. Dos 158 pacientes restantes, 20 (7,0%) eram do grupo CEA, 36 (12,6%), do grupo CEI e 102 (35,7%), do grupo controle. A mediana de tempo para progressão nos grupos CEA, CEI e controle foi de 432, 3.595 e 2.829 dias, respectivamente (p < 0,01). Um modelo de riscos proporcionais demonstrou que os preditores significativos de progressão da doença pulmonar por MAC foram câncer em estágio avançado (razão de risco [RR] = 6,096; 95%IC: 2,688-13,826; p < 0,01), lesões cavitárias (RR = 2,750; 95%IC: 1,306-5,791; p < 0,01) e pontuação alta no sistema Nódulo-Infiltração-Cavidade-Ectasia (RR = 1,046; 95%IC: 1,004-1,091; p = 0,033). Conclusões: A coexistência de tumor sólido extrapulmonar avançado poderia acelerar a progressão da doença pulmonar por MAC.

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

Enfermedad pulmonar por Mycobacterium intracellulare en una paciente inmunocompetente: reporte de un caso en el Perú / Pulmonary disease by mycobacterium intracellulare in an immunocompetent patient: Report of a case in Peru

RESUMEN Presentamos una paciente inmunocompetente cuya enfermedad comenzó a los 49 años con tos, seguida de esputo purulento y hemoptoico, por lo que se diagnosticó bronquiectasias. Tres años después, luego de hemoptisis, le practicaron segmentectomía medial del lóbulo medio y quedó asintomática por meses. Al encontrarse tuberculosis en el informe de patología fue tratada con 4HREZ2R2H2. Cinco años después su BK fue 2+ recibiendo un nuevo esquema de 4HREZ2R2H2, con lo que no logro negativizar declarándose el fracaso al tratamiento. Al hallar en la genotipificación de su cultivo Mycobacterium intracellulare, la paciente recibió azitromicina, moxifloxacina y etambutol, hubo mejoría, pero abandonó el tratamiento a los ocho meses; lo reinició 18 meses después, junto con tratamiento para la depresión y el reflujo gastroesofágico. Al mes la paciente estuvo asintomática, pero hizo reacción dérmica a la moxifloxacina y se la reemplazó por amikacina. Salió de alta y al año estuvo curada, a los 64 años de edad.

ABSTRACT We present the case of an immunocompetent patient whose illness began at age 49 with a cough, followed by purulent and hemoptoic sputum; bronchiectasis was diagnosed. Three years later, after hemoptysis, she underwent medial segmentectomy of the middle lobe and was asymptomatic for months. When tuberculosis was found in the pathology report, she was treated with 4HREZ2R2H2. Five years later her BK was 2+, thus receiving a new scheme of 4HREZ2R2H2, which did not succeed in obtaining negative results and the treatment was declared as a failure. After genotyping her Mycobacterium intracellulare culture, the patient received azithromycin, moxifloxacin and ethambutol. There was improvement, but she abandoned the treatment at 8 months; she restarted it 18 months later, along with treatment for depression and gastroesophageal reflux. After one month the patient was asymptomatic, but she had a dermal reaction to moxifloxacin which was replaced with amikacin. One year later, she was cured and discharged, at the age of 64.

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.

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.

Prevalence and Species Spectrum of Pulmonary Nontuberculous Mycobacteria Isolates at a Tertiary Care Center / 대한임상미생물학회지

BACKGROUND: Pulmonary infection with nontuberculous mycobacteria (NTM) is increasing in South Korea. Since treatment strategy differs by NTM species, accurate identification is necessary. In this study, using Mycobacterium pulmonary isolates recently recovered from a general hospital in Seoul, the prevalence of NTM isolates was investigated. METHODS: A total of 483 Mycobacterium pulmonary strains isolated between May and November 2018 from an 814-bed general hospital in South Korea were analyzed. Bacterial species were identified based on nucleotide sequences of the 16S–23S rDNA internal transcribed spacer and the rpoB gene. RESULTS: From a total of 1,209 pulmonary specimens from patients suspected to be infected with mycobacteria, 324 deduplicate strains were isolated, comprising 90 Mycobacterium tuberculosis and 229 NTM strains. Among the NTM isolates, 61.5% (n=144) were Mycobacterium avium complex (MAC), including 92 M. avium and 52 Mycobacterium intracellulare, while 8.1% (n=19) represented Mycobacterium abscessus, including 10 M. abscessus subsp. abscessus and 9 M. abscessus subsp. massiliense. In addition, 12 (5.1%) Mycobacterium lentiflavum, 12 (5.1%) Mycobacterium gordonae, 6 (2.6%) Mycobacterium kansasii, and 5 (2.1%) Mycobacterium fortuitum were identified. In addition, Mycobacterium mucogenicum (n=2), Mycobacterium septicum (n=1), Mycobacterium colombiens (n=1), Mycobacterium asiaticum (n=1), and Mycobacterium celatum (n=1) were identified. CONCLUSION: Among the recently recovered Mycobacterium pulmonary strains, more than half were identified as NTM, and MAC was the most prevalent NTM, followed by M. abcessuss.

Infectious Diseases of the Stomach in Immune-compromised Patients

The gastrointestinal tract is a vast reservoir for internal microbiota; it is exposed directly to various externally introduced microbes, including bacteria, viruses, parasites and others. In immune-compromised conditions, the gastrointestinal tract is frequently affected by infectious diseases that seldom manifest clinically in immune-competent hosts. Immune-compromised conditions result from a variety of reasons, including human immunodeficiency virus infection, anti-cancer chemo-radiotherapy, immune suppressive therapy for autoimmune diseases, and organ transplantations. The stomach is a relatively rare site for opportunistic infections in immune-compromised patients compared to the esophagus and colon, where esophagitis and colitis develop frequently and cause significant clinical consequences. Helicobacter pylori infection is majorly involved in gastric malfunctioning in immune-compromised patients, followed by cytomegalovirus infection. Infections by Cryptosporidium, Mycobacterium avium complex, histoplasmosis, leishmaniasis, aspergillosis, or treponema, have been reported; however, gastric involvement of these agents is extremely rare. This review discusses the general aspects and recent reports on gastric infection in immune-compromised patients.

Micobacterium avium complex en paciente inmunodeprimido: reporte de un caso / Mycobacterium avium complex in immunosuppressed patient: a case report

INTRODUCCIÓN: Dentro de las micobacterias atípicas destaca el Complejo Micobacterium Avium, cuyo nicho principal en humanos son los pacientes con inmunodeficencia. PRESENTACIÓN DEL CASO: Paciente masculino, 30 años, con antecedentes de infección por Virus de Inmonudeficiencia Humana en terapia antirretroviral y por virus Hepatitis B. Hospitalizado por cuadro de dolor abdominal asociado a síndrome consuntivo. Durante hospitalización se realizó Tomografía Computarizada que mostró múltiples adenopatías. Luego se realizó biopsia ganglionar que concluyó Tuberculosis ganglionar, comenzando con tratamiento antituberculoso. En el transcurso del tratamiento el paciente inició con sintomatología respiratoria y sus baciloscopías de esputo persistieron positivas, manteniéndose con dicho cuadro hasta confirmar la presencia de Micobacterium Avium en el cultivo, comenzando su tratamiento específico, con positivos resultados. DISCUSIÓN: El Complejo Micobacterium Avium corresponde a la causa más común de enfermedad por micobacteria no tuberculosa en inmunosuprimidos. Por lo tanto, es un patógeno que merece ser considerado al menos como diagnóstico diferencial en dicho tipo de pacientes. En el presente caso se evidencia tanto una sospecha como un diagnóstico tardío, lo que llevó a una demora en el inicio del tratamiento y a complicaciones sintomáticas del paciente. Es necesario para la pesquisa precoz, realizar cultivos tanto para M. tuberculosis como para micobacterias atípicas para mejorar pronóstico y a su vez disminuir el riesgo de complicaciones.

INTRODUCTION: Among the atypical mycobacteria, the Micobacterium Avium Complex stands out. Its main niche in humans is immunodeficient patients. CASE REPORT: 30 years old male patient, with a history of infection by Human Immunodeficiency Virus on antiretroviral therapy, and Hepatitis B virus. Hospitalized for abdominal pain associated with consumptive syndrome. During his hospitalization, a computerized tomography was performed, showing multiple adenopathies. Then, a lymph node biopsy was performed that concluded nodal tuberculosis, beginning with antituberculous treatment. During the course of this treatment, patient presented respiratory symptoms and sputum bacilloscopy persisted positive, maintaining this condition until the presence of Mycobacterium Avium was confirmed in the culture, beginning with specific treatment, with positive results. DISCUSSION: The Mycobacterium Avium Complex is the most common cause of nontuberculous mycobacterial disease in immunosuppressed patients. Therefore, its a pathogen that has to be considered at least as a differential diagnosis in such patients. In the present case, suspicion and a late diagnosis are evidenced, which lead to a delay in the initiation of treatment and complications for the patient. It is necessary for early screening, culture for both M. tuberculosis and atypical mycobacteria to improve prognosis and to reduce the risk of complications.

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

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 / 감염과화학요법

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.

Changing Epidemiology of Nontuberculous Mycobacterial Lung Diseases in a Tertiary Referral Hospital in Korea between 2001 and 2015

This study investigated the changes in the major etiologic organisms and clinical phenotypes of nontuberculous mycobacterial lung disease (NTM-LD) over a recent 15-year period in Korea. The increase of number of patients with NTM-LD was primarily due to an increase of Mycobacterium avium complex (MAC) lung disease (LD). Among MAC cases, the proportion of M. avium increased compared with M. intracellulare, whereas the incidence of M. abscessus complex and M. kansasii LD remained relatively stable. The proportion of cases of the nodular bronchiectatic form increased compared with the fibrocavitary form of NTM-LD.

Nasal swab real-time PCR is not suitable for in vivo diagnosis of bovine tuberculosis / A PCR em tempo real de swab nasal não é adequada para o diagnóstico in vivo de tuberculose bovina

Bovine tuberculosis (bTB) is a zoonosis causing economic losses and public health risks in many countries. The disease diagnosis in live animals is performed by intradermal tuberculin test, which is based on delayed hypersensitivity reactions. As tuberculosis has complex immune response, this test has limitations in sensitivity and specificity. This study sought to test an alternative approach for in vivo diagnosis of bovine tuberculosis, based on real-time polymerase chain reaction (PCR). DNA samples, extracted from nasal swabs of live cows, were used for SYBR® Green real-time PCR, which is able to differentiate between Mycobacterium tuberculosis and Mycobacterium avium complexes. Statistical analysis was performed to compare the results of tuberculin test, the in vivo gold standard bTB diagnosis method, with real-time PCR, thereby determining the specificity and sensitivity of molecular method. Cervical comparative test (CCT) was performed in 238 animals, of which 193 had suitable DNA from nasal swabs for molecular analysis, as indicated by amplification of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene, and were included in the study. In total, 25 (10.5%) of the animals were CCT reactive, of which none was positive in the molecular test. Of the 168 CCT negative animals, four were positive for M. tuberculosis complex at real time PCR from nasal swabs. The comparison of these results generated values of sensitivity and specificity of 0% and 97.6%, respectively; moreover, low coefficients of agreement and correlation (-0.029 and -0.049, respectively) between the results obtained with both tests were also observed. This study showed that real-time PCR from nasal swabs is not suitable for in vivo diagnosis of bovine tuberculosis; thus tuberculin skin test is still the best option for this purpose.(AU)

A tuberculose bovina (bTB) é uma zoonose que causa perdas econômicas e riscos à saúde pública em muitos países. O diagnóstico da doença em animais vivos é realizado pelo teste intradérmico da tuberculina, que é baseado em reações de hipersensibilidade tardia. Como a tuberculose tem resposta imunológica complexa, este teste tem limitações em termos de sensibilidade e especificidade. Este estudo procurou desenvolver uma abordagem alternativa para o diagnóstico in vivo da tuberculose bovina, com base na reação em cadeia da polimerase (PCR) em tempo real. As amostras de DNA, extraídas de suabes nasais de vacas vivas, foram usadas para PCR em tempo real com SYBR® Green, capaz de diferenciar os complexos Mycobacterium tuberculosis e Mycobacterium avium. A análise estatística foi realizada para comparar os resultados de teste de tuberculina, padrão ouro para o diagnóstico in vivo da bTB, com PCR em tempo real, determinando-se assim a especificidade e sensibilidade do método molecular. O teste cervical comparativo (TCC) foi realizado em 238 animais, dos quais 193 tiveram DNA dos suabes nasais adequados para análise molecular, como indicado pela amplificação do gene gliceraldeído-3-fosfato-desidrogenase (GAPDH), e foram incluídos no estudo. No total, 25 (10,5%) animais foram reativos no TCC, dos quais nenhum foi positivo no teste molecular. Dos 168 animais negativos no TCC, quatro foram positivos para o complexo M. tuberculosis na PCR em tempo real a partir dos suabes nasais. A comparação destes resultados gerou valores de sensibilidade e especificidade de 0% e 97,6%, respectivamente; além disso, baixos coeficientes de concordância e correlação (-0,029 e -0,049, respectivamente) entre os resultados obtidos com ambos os testes também foram observados. Este estudo mostrou que a PCR em tempo real a partir de suabes nasais não é adequada para o diagnóstico in vivo da tuberculose bovina; portanto, o teste da tuberculina ainda é a melhor opção para este fim.(AU)

Enfermedad pulmonar causada por complejo Mycobacterium avium y M. abscessus / Pulmonary disease caused by Mycobacterium avium complex and M. abscessus

Resumen Introducción: después del complejo Mycobacterium tuberculosis, las principales especies de micobacterias causando enfermedad pulmonar son el complejo Mycobacterium avium (MAC) y Mycobacterium abscessus, el tratamiento es prolongado, presentan un amplio perfil de resistencia y algunas veces es necesaria la resección quirúrgica del tejido, dificultando la curación de algunos casos. Objetivo: realizar un análisis de los casos a los que se les aisló de muestras pulmonares MAC y M. abscessus en el periodo de 2012-2014 en el Laboratorio Nacional de Referencia de Colombia. Material y métodos: se realizó un estudio de serie de casos de 42 personas a las que se les aisló de muestras pulmonares MAC y M. abscessus, los cuales fueron identificados mediante pruebas fenotípicas y genotípicas. La fuente de información fue el Formato Único de Vigilancia de las Micobacterias que se recibe con cada uno de los aislados que llegan al INS. Se analizaron las variables edad, sexo, tipo de muestra y presencia de factores de riesgo. Resultados: en 32 de los casos se identificó MAC y en 10 M. abscessus como agente etiológico causante de enfermedad pulmonar, 26 (61.9%) de los casos tenían entre 51 y 86 años. Los principales factores de riesgo fueron: antecedente de tratamiento antituberculosis 16 (38.1%) y persona con VIH 7 (16.7%) y sin factor de riesgo 9 (21.2%) casos. Discusión: este trabajo reporta como agente etiológico MAC y M. abscessus en personas mayores de 50 años sin factores de riesgo, con antecedentes de tuberculosis, indicando que se debe fortalecer la realización de cultivo e identificación de especie en éstas para que tengan un adecuado diagnóstico y tratamiento.

Abstract Introduction: after the Mycobacterium tuberculosis complex, the main species of mycobacteria causing lung disease are Mycobacterium avium complex and Mycobacterium abscessus. The treatment is prolonged; they present a broad resistance profile and sometimes the surgical resection of the tissue is necessary, making healing difficult in some cases. Objective: to perform an analysis of the cases to which MAC and M. abscessus were isolated from pulmonary samples in the period from 2012 to 2014 in the National Reference Laboratory of Colombia. Materials and Methods: a case series study of 42 individuals to whom Mac and M. abcessus were isolated from pulmonary samples that were identified by phenotypic and genotypic tests, was carried out. The source of information was the unique format of surveillance of mycobacteria that is received with each of the isolates that come to the National Health Institute. The variables age, sex, type of sample and presence of risk factors were analyzed. Results: in 32 patients MAC was identified as etiological agent causing pulmonary disease and in 10 cases, M. abscessus was the agent. 26 (61.9%) of the patients were between 51 and 86 years of age. The main risk factors were: antecedent of anti-tuberculosis treatment in16 (38.1%),7 with HIV (16.7%) and without risk factor 9 cases (21.2%).

Mycobacterium avium-intracellulare and the unpredictable course of hypercalcemia in an AIDS patient

Abstract A 37-year-old man with AIDS presented with altered mental status four weeks after stopping his medications for Mycobacterium avium-intracellulare (MAI). He had low CD4 cell count and severe hypercalcemia. Bone marrow biopsy revealed bone marrow infiltration by granulomas positive for acid-fast bacilli and cultures grew MAI. His hypercalcemia continued to worsen with the initiation of MAI therapy but we were able to treat it successfully with pamidronate and calcitonin.

Nontuberculous mycobacterial infection in rheumatoid arthritis patients: a single-center experience in South Korea

BACKGROUND/AIMS: Nontuberculous mycobacteria (NTM) infection has been increasing worldwide in both general population and immunocompromised patients, which has also been reported in rheumatoid arthritis (RA) patients. This study aimed to identify the incidence and clinical characteristics of NTM infection in RA patients living in tuberculosis (TB) infection endemic area. METHODS: We performed a retrospective analysis of NTM infection cases in our RA registry at a tertiary referral center from January 1995 to December 2013. The clinical features of them were compared to those of 52 TB infection patients from same registry. RESULTS: Among 1,397 patients with RA, NTM infection was newly developed in 26 patients and the incidence of NTM infection was 164.8 per 100,000 patient-years. The Mycobacterium avium complex was the most frequent isolate (76.9%). None of the NTM infections had extrapulmonary involvement, which was rather common in TB infection (26.9%). Patients with NTM infection were older, received higher cumulative steroid doses, and had higher rates of past TB infection history and concomitant interstitial lung disease (ILD) than cases with TB infection. CONCLUSIONS: In South Korea, NTM infection is not rare in RA patients, and infection rates are growing. Physicians should be cautious about NTM infection in patients with a history of TB infection or concomitant ILD, even living in TB endemic area.

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.

Comparing the Genotype and Drug Susceptibilities between Mycobacterium avium and Mycobacterium intracellulare in China / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>Mycobacterium avium (M. avium) and Mycobacterium intracellulare (M. intracellulare) are the major causative agents of nontuberculous mycobacteria (NTM)-related pulmonary infections. However, little is known about the differences in drug susceptibility profiles between these two species.</p><p><b>METHODS</b>A total of 393 NTM isolates were collected from Shanghai Pulmonary Disease Hospital. Sequencing of partial genes was performed to identify the strains at species level. The minimum inhibitory concentration (MIC) was used to evaluate the drug susceptibility against 20 antimicrobial agents. Variable number of tandem repeat (VNTR) typing was conducted to genotype these two species.</p><p><b>RESULTS</b>A total of 173 (44.0%) M. avium complex (MAC) isolates were identified, including 41 (10.4%) M. avium isolates and 132 (33.6%) M. intracellulare isolates. Clarithromycin and amikacin were the two most effective agents against MAC isolates. The Hunter-Gaston Discriminatory Index (HGDI) values for VNTR typing of M. avium and M. intracellulare isolates were 0.993 and 0.995, respectively. Levofloxacin resistance was more common among the unclustered strains than among the clustered strains of M. intracellulare.</p><p><b>CONCLUSION</b>M. intracellulare was the most common NTM species in China. Clarithromycin and amikacin had high antimicrobial activities against MAC. VNTR typing of MAC isolates revealed a high discriminatory power. Levofloxacin resistance was associated with unclustered strains of M. intracellulare.</p>

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.