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Summary Mycobacterial infections are rare in horses, donkeys and mules. Although there are a few reports in horses, mycobacterial disease is poorly documented in the donkey. Mycobacterial infection of equine species typically affects the alimentary tract, causing granulomatous enterocolitis resulting in diarrhoea and chronic weight loss, while lymph nodes and liver may also be affected. We now document recurrent oesophageal obstruction, secondary to cranial mediastinal lymphadenitis caused by Mycobacterium avium complex (MAC). To the best of our knowledge, this is the first report of MAC infection in a donkey in the UK.

The US Food and Drug Administration convened a workshop to discuss clinical trial design challenges and considerations related to the treatment of nontuberculous mycobacterial pulmonary disease, to include topics such as clinical trial end points, duration, and populations. The clinicians participating in the meeting provide here their interpretation of the discussion, which included US Food and Drug Administration and industry representatives. The treatment of nontuberculous mycobacterial pulmonary disease typically includes multiple antibiotics for a prolonged period and can be difficult to tolerate; there is a great need for new treatment options. Most individuals have a microbiologic response to therapy, but data correlating decreasing bacillary load with patient-reported outcomes or measured functional improvement are lacking. Accordingly, trial designs for new therapeutic agents should incorporate both microbiologic and clinical outcome measures and select appropriate study candidates with capacity for measurable change of such outcome measures. The need for shorter study designs, early primary end points, and placebo control arms was highlighted during the workshop.

The number of patients with pulmonary nontuberculous mycobacterial disease complicated by chronic pulmonary aspergillosis (CPA) has been increasing. Additionally, CPA is reportedly associated with mortality in patients with Mycobacterium avium complex lung disease (MAC-LD). In the present study, we aimed to identify risk factors for developing CPA and stratify the risk for CPA development in patients with MAC-LD.We retrospectively examined 361 patients newly diagnosed with MAC-LD. Risk factors for CPA development were examined using multivariate Cox proportional hazards regression analyses. A risk stratification system was established using the risk factors and receiver operating characteristic curve analyses.CPA developed in 20 (5.5%) of the 361 patients. Independent risk factors for CPA development included the presence of pulmonary emphysema, baseline steroid use, a serum albumin level3.5 g/dL, and the presence of MAC-LD cavities. A 4-point scoring system was established to stratify patients into low-risk (0-1 point) and high-risk (2-4 points) groups. The 5-year incidence rates of CPA were 2.2% and 31% in the low- and high-risk groups, respectively (P 0.001).We identified independent predictors of CPA development and established a simple risk stratification system for identifying patients with MAC-LD who were at a high risk of developing CPA.

Background An Expert Forum was held at the 2014 European Respiratory Society International Congress to address issues involved in the management of Pseudomonas aeruginosa infection in patients with non-cystic fibrosis bronchiectasis (NCFB). Multiple studies have found that chronic P. aeruginosa infection is associated with more severe disease and higher morbidity and mortality. Overview Participants discussed appropriate management of P. aeruginosa infection at three stages: 1) first isolation, including eradication protocols; 2) during exacerbations; and 3) during chronic infection, including long-term antibiotic therapy to reduce the severity of symptoms and frequency of exacerbations. Topics covered included frequency of sputum cultures, antibiotic treatment at first isolation and for exacerbations, optimal use of inhaled antibiotics, indications for long-term therapy, and treatment regimens that may reduce the frequency or severity of symptoms. Electronic polling and roundtable discussions followed by expert insights were used to address these topics. Significant diversity in management practices was reported among different countries and centres, and in many cases clinical management was at variance with published guidelines. Conclusions This Expert Forum identified standardised terminology, clinician training, additional research into management strategies, and the development of new drugs as areas requiring improvement for the optimal management of P. aeruginosa in NCFB.

Objective/background The prevalence of pulmonary nontuberculous mycobacterial (pNTM) disease, including Mycobacterium avium complex (MAC), varies widely according to geographic region. However, the factors that influence regional variations in pNTM disease prevalence remain unknown. This study was undertaken to examine whether environmental or occupational factors or host traits could influence regional variations in pNTM disease prevalence. Methods We collected laboratory data on pulmonary tuberculosis (pTB) and pNTM from two hospitals in the West Harima area of Japan and five hospitals in Kyoto City, Japan from 2012 to 2013. We estimated microbiological pNTM disease prevalence by multiplying all pTB cases in each area with the ratio of pNTM cases and pTB cases at the survey hospitals in each area. We administered a standardized questionnaire to 52 patients and 120 patients with pulmonary MAC (pMAC) disease at Ako City Hospital and Kyoto University Hospital, respectively. Results The estimated prevalence of microbiological pNTM disease in the West Harima area (85.4/100,000 population-years) was significantly higher than that observed in Kyoto City (23.6/100,000 population-years; p

Increased serum CA 19-9 levels in patients with nonmalignant diseases have been investigated in previous reports. This study evaluates the clinical significance of serum CA 19-9 elevation in pulmonary nontuberculous mycobacterial disease and pulmonary tuberculosis. The median CA 19-9 level was higher in patients with pulmonary nontuberculous mycobacterial disease than in patients with pulmonary tuberculosis (pulmonary nontuberculous mycobacterial disease: 13.80, tuberculosis: 5.85, p

The nontuberculous mycobacteria are opportunistic water- and soilborne pathogens that include over 150 species. Though slow growing, they are the hardiest of bacteria, able to grow in drinking water and resistant to disinfectants, antibiotics, and heat. They are natural inhabitants of drinking water distribution systems and plumbing in houses, hospitals, condominiums, and apartments, commonly known as premise plumbing. Thus, humans are surrounded and continually exposed. Nontuberculous mycobacteria cause pulmonary and dermal infections in adults, cervical lymphadenitis in young children, and bacteremia in immunocompromised individuals. The frequency of pulmonary infections is 10/100,000, with the highest rates in persons older than 60 years (100/100,000). In addition to community-acquired infections, hospital-acquired infections are becoming increasingly prevalent, usually associated with surgery or injection. Multiple mycobacterial species or clones are common in pulmonary patients, necessitating isolation of multiple mycobacterial-like colonies from patient samples, as isolates from a single patient may belong to different species with different antibiotic susceptibilities. The reemergence of nontuberculous mycobacterial disease following successful antibiotic therapy is common.

Buruli ulcer is a cutaneous mycobacterial disease caused by Mycobacterium ulcerans, whose incidence is increasing steadily, especially in West Africa. This study reports a first documented case of M. ulcerans infection which can be attributed to a water bug bite at the site of the primary lesion.

An urgent question that needs to be addressed rapidly by the mycobacteriology laboratory is whether Mycobacterium tuberculosis complex or NTM is involved. NAA assays are excellent tools for the purpose, and can be used directly on the clinical specimens of patients suspected of having mycobacterial disease, allowing same-day reporting of results. The CDC recommends using both liquid and solid media for growth detection of mycobacteria to decrease the time to detection and to increase the yield of growth detection. DNA sequencing of variable genomic regions offers a rapid, accurate, and relatively inexpensive method for the identification of mycobacteria.

Highlights • In Uruguay (Uy), bTB highly prevalent dairy herds have emerged. • Johne's disease (JD) control programs lack at the national level in Uy. • In high prevalence coinfected herds, bTB- and JD-diagnosis interact. • An integrated control program is needed for high prevalent coinfected dairies in Uy., The consolidation of the dairy industry, with increase in sizes, density and productivity of the herds, was associated to unprecedented bovine tuberculosis (bTB) prevalence levels in dairy herds in Uruguay, where Johne's disease (JD), another mycobacterial disease, is also prevalent. Here, we aimed to characterize the association between bTB- and JD-diagnostic results in two heavily bTB- and JD-coinfected dairy herds. Results from bTB-intradermal tests and JD-ELISA in 686 cows indicated a significantly (P

Over the last 30 years it has become increasingly clear that nontuberculous mycobacterial (NTM) lung infections and bronchiectasis are closely related disorders. Although incontrovertible proof is lacking, there is a growing consensus of opinion that NTM lung disease characterized by nodules and bronchiectasis (nodular/bronchiectatic NTM lung disease) may be a consequence of preexisting bronchiectasis that predisposes to NTM infection and disease. To use published diagnostic guidelines effectively, physicians must become familiar with the disease-causing potential of individual NTM species. Essentially all NTM patients have bronchiectasis, so optimal overall patient management requires successful therapeutic strategies for both NTM infection and bronchiectasis.

This paper examines skeletal and ancient DNA evidence in the study of suspected tuberculosis infection in the late pre-Hispanic and Colonial-era Lambayeque Valley Complex, north coast Peru (A.D. 900–1750). We integrate information on macroscopic lesion characteristics and distribution, radiographic and CT scan imagery, and analysis of Mycobacterium tuberculosis complex rpoB and IS6110 ancient DNA (aDNA) sequences. Destructive lesions were observed in the vertebral bodies of three precontact indigenous adult males, one colonial adolescent female, and in the cranium of a Colonial-period subadult. Assessment of lesion morphology and distribution led us to consider multiple diseases, but tuberculosis represents the most likely diagnostic option in all individuals. DNA was poorly preserved in all samples, but an IS6110 sequence was amplified in one precontact individual consistent with macroscopic diagnosis. These findings expand the geographic and temporal extent of tuberculosis to the late pre-Hispanic and Colonial north coast of Peru to highlight potential synergisms between diet, settlement patterns, and the evolution of Andean tuberculosis before and after European conquest. Moreover, this study helps focus several key questions in Andean tuberculosis research, including possible reassessment of the presence of the IS6110 sequence in the pre-Columbian Americas. Methodological considerations include differential diagnosis – especially with incomplete skeletons – and limitations of aDNA studies underscoring an approach integrating macroscopic, radiographic, and molecular lines of evidence in the paleopathological investigation of one of humankind’s most devastating and destabilizing diseases.

A decline in the prevalence of tuberculosis in the developed world over the past several years has been accompanied by an increase in the rate of mycobacterial disease caused by non-tuberculous mycobacteria. However, it is still unclear whether there is a real increase in prevalence or whether non-tuberculous mycobacterial disease is being recognised more frequently by clinicians in a variety of clinical settings, thus enhancing the competence of microbiologists to detect the more unusual and fastidious mycobacteria. The introduction of liquid media for isolation of mycobacteria coupled with more accurate methods for identification have allowed several new species associated with human disease to be recognised. Despite this progress, several issues related to non-tuberculous mycobacterial infections need to be addressed, including the timely and reliable identification of isolates, standardisation and clinical evaluation of susceptibility testing, and capability to distinguish disease-causing isolates from contaminant or saprophytic species. Treatment regimens for non-tuberculous mycobacterial disease are still largely undefined and outcome remains disappointing despite substantial upgrading in laboratory diagnosis and the availability of new antimicrobials. Treatment success is impaired by the long duration of regimens, side-effects, and drug interactions, which prevent patients from full compliance. We discuss the epidemiological features, clinical syndromes, and developments in the investigation, prevention, and treatment of pulmonary non-tuberculous mycobacterial infections.

Setting : Members of the Mycobacterium avium complex (MAC) are responsible for mycobacterial disease in children, the aged and in immunocompromised individuals. The complex consists of different species, serovars and morphologic forms that vary in virulence. One isolate of the MAC is currently being sequenced (MAC 104) and was chosen based on its derivation from an AIDS patient and the fact that it could be genetically manipulated. Objective : MAC 104 was therefore analyzed for virulence, colony morphotype and expression of the glycopeptidolipid (GPL) responsible for serotying differences and the rough to smooth morphological switch. Results : The isolate was found to be virulent in the murine model of low-dose aerosol infection in that it could colonize the lung, proliferate within the tissue and disseminate to other organs. MAC 104 expressed a variety of colony morphotypes, the most prevalent of which were smooth opaque, smooth transparent and rough. All three morphotypes could persist in the lung; however, the transparent and rough morphotypes grew more rapidly in vivo . The rough morphotype was unusual in that it expressed an atypical form of the GPL usually absent from rough morphotypes. Conclusion : This characterization complements the genome data and confirms that MAC 104 behaves similarly to other MAC isolates.

The epidemic of birth defects in Europe in the early 1960s attributed to thalidomide led to stringent and unprecedented drug safety requirements in many countries. No definitive mechanism of action has been determined for the biological activities associated with thalidomide. Food and Drug Administration and congressional concerns about the handling of clinical investigations of thalidomide led to sweeping new regulations for clinical trials. Thalidomide is currently being used clinically to treat such conditions as cachexia associated with HIV and cancer, mycobacterial disease, and autoimmune diseases.

Mycobacterial disease remains a major public health problem and there appears to be a genetic component underlying susceptibility. This paper describes a group of related children who appear to have a genetic predisposition to disseminated atypical mycobacterial infection. Identification of the defect in this group could lead to better understanding of the genetics of susceptibility to mycobacterial infection.

This study was conducted to determine the prevalence of mycobacterial disease in an adult cystic fibrosis (CF) population and to determine if there were any patients at higher risk for this disease within the group. Sixty-four patients (28 women, 36 men), ranging in age from 17 to 50 years were screened. One-step purified protein derivative skin testing with controls was performed and sputum was taken for examination. Eight of 64 had positive sputum culture for nontuberculous Mycobacterium. The CF patients with positive mycobacterial sputum cultures tended to be older and to have lower clinical scores than those who did not have Mycobacterium organisms in sputum. Guidelines to determine whether mycobacterial disease or colonization is present should be pursued for the CF population.

AIDS has been responsible for a significant increase in mycobacterial disease, which in this setting is often extrapulmonary. In contrast to HIV-associated Mycobacterium avium complex disease, HIV-associated tuberculosis is normally transmissible between humans by the aerosol route, occurs earlier than most AIDS-related infections, and is readily treatable and preventable with conventional drugs.

Non-BCG-vaccinated schoolchildren (8 or 9 years of age) were simultaneously tested on separate arms with 2 IU PPD RT23 and 0.1 microgram Mycobacterium avium sensitin RS10 or 0.1 microgram Mycobacterium scrofulaceum sensitin RS95. None of the 2819 analysed children had any known exposure to tuberculosis. A total of 3.4% reacted with an induration greater than or equal to 6 mm to PPD RT23. Half the number of children were tested with M. avium sensitin and 25.4% reacted while the remaining were tested with M. scrofulaceum sensitin and 32.4% reacted when the cut-off was 6 mm. For about 90% of the children the sensitin reaction was larger than or equal to the tuberculin (PPD RT23) reaction. Correlation analyses showed that moderate and high PPD RT23 values were combined with still higher sensitin values, indicating that the tuberculin reactions were mainly cross-reactions due to the antigenic similarity between tuberculin and sensitins. The presence of birds, dogs and cats in the homes was combined with an increased frequency of children reacting to the sensitins used. The children with reactions to PPD RT23 greater than or equal to 6 mm were examined and chest X-rays were performed. None of them showed any signs or symptoms of mycobacterial disease. In non-BCG-vaccinated Swedish schoolchildren without clinical signs of tuberculosis and without known contact with a contagious tuberculous person, indurations less than 12 to 14 mm on tuberculin testing are probably caused by atypical mycobacteria. In such cases sensitin tests should be performed to verify the suspicion.

We present the case of a 47-year-old immunocompetent patient with clinical evidence of pulmonary mycobacterial disease which was found to be due to Mycobacterium triplex. This novel organism is an uncommon, emerging, pathogen for which few reports of clinical infection exist in the medical literature.

Resume L'examen des resultats bacteriologiques montre a l'evidence que la tuberculose humaine a Mycobacterium tuberculosis demeure un probleme actuel, surtout pour les sujets a risque. Actuellement il n'est pas exceptionnel de diagnostiquer des meningites tuberculeuses ou des localisations urinaires lors d'examens systematiques. L'isolement de quelques souches polyresistantes est un phenomene nouveau dans notre region, le traitement standard sans antibiogramme risque de laisser longtemps contagieux des sujets apparemment en traitement suffisant. La tuberculose humaine a Mycobacterium bovis reste peu frequente, le taux se situe au niveau de la moyenne nationale. La tuberculose animale a M. bovis ne represente pas un probleme majeur par le nombre d'animaux malades; la surveillance doit cependant rester constante et les saisies sont encore nombreuses par souci de securite. Dans les regions d'elevage de caprins et d'ovins il serait peut-etre indique d'envisager la surveillance de ces animaux puisque quelques cas ont ete signales. L'infection des porcs et eventuellement des autres animaux, volailles en particulier, par Mycobacterium avium ne semble pas etre un probleme de sante veterinaire. Par contre elle intervient peut-etre dans les reactions faibles lors de la tuberculinisation du cheptel.

The purpose of this article is to review current knowledge about the mechanisms of pathogenicity of mycobacteria. The following aspects of the problem are discussed: chemically-defined compounds implicated in the mechanisms of pathogenicity; location in the cell wall of these compounds and their biological activities; mechanisms of intracellular survival of pathogenic mycobacteria as compared to intracellular killing of non-pathogenic mycobacteria; and pathogenesis of mycobacterial infection. The future prospects in the elucidation of the mechanisms of pathogenicity and their possible application for a better control of mycobacterial diseases are briefly discussed.

A retrospective study of 212 patients with mycobacterial infection was conducted to determine intradermal reactivity to five tuberculin units (TU) of purified protein derivative of Mycobacterium tuberculosis (PPD-S), and purified protein derivatives (PPDs) derived from non-tuberculous mycobacteria. PPDs B, Y, A, G, and F were used. The study included 138 patients with Mycobacterium tuberculosis infection, and 74 with proved nontuberculous mycobacterial infection. Eight possible patterns of skin test reactivity were discerned using PPD-S, PPD-B, and PPD-Y. In this population, selection of the largest skin test reaction within any one pattern correlated with the infecting organism in 87 per cent of the cases. Use of PPD-A, PPD-G, and PPD-F did not increase diagnostic capability. We conclude that differential skin testing with PPD-S, PPD-B and PPD-Y, is useful in the diagnosis of mycobacterial disease.

Mycobacterial disease is an increasingly common and serious problem in patients infected with the human immunodeficiency virus. Whereas Mycobacterium avium complex organisms are noncommunicable and extremely difficult to treat, Mycobacterium tuberculosis is transmissible to patients who do not have the acquired immunodeficiency syndrome, but is preventable and treatable.

During five years, 6,879 patients underwent bronchoscopic study at the Mayo Clinic. Mycobacterial cultures were obtained from 4,120 (60 percent). Mycobacterial organisms (typical or atypical) other than Mycobacterium gordonae were isolated in 70/4,120 (1.7 percent) patients. During the same period, 209 patients had culture-proved M tuberculosis from various sources. Bronchoscopy was performed on 34/209 (16 percent) patients. Washings or secretions from bronchoscopy grew M tuberculosis in 32/34 (94 percent) cases. Bronchoscopy and bronchoscopic cultures were important in the diagnosis of M tuberculosis in 16/34 (47 percent) patients. Atypical mycobacteria were cultured from various sources in 428 patients during the period of study. In 254 of these, M gordonae was isolated, but it was considered to be nonpathogenic in all. Of the remaining 174 patients with culture-proved atypical mycobacteriosis, 40 (23 percent) underwent bronchoscopic studies. Of these 40 patients, 24 had active disease and 11 had saprophytic colonization; in five, the disease activity was indeterminate. Bronchoscopic cultures of secretions or washings or both were positive for atypical organisms in 38/40 (95 percent) patients.

Summary Haematological changes associated with infectious diseases are relatively common but true aplastic anaemia secondary to infection is rare. We describe a patient with disseminated Mycobacterium avium-intracellulare infection and who had a histologically proven remission of his aplastic anaemia accompanying antimycobacterial therapy. We also review the literature on the haematological changes associated with mycobacterial infections and other infectious causes of aplastic anaemia.

In 11 patients with pulmonary disease due to Mycobacterium xenopi , definite aspergilloma subsequently developed in five and probable aspergilloma in a further three. Those patients with evidence of Aspergillus infection formed a much higher proportion (73 %) than in previous reports of patients with mycobacterial disease. Patients with both Mycobacterium xenopi infection and aspergilloma appear to have a poor prognosis.

Opportunist mycobacterial diseases of the lung are reviewed and the epidemiology of the infections discussed. The course of disease based on radiological changes is described in 27 patients. Seventeen patients (63 per cent) had distinctive radiographic changes; 5 showed very distinctive lesions consisting of groups of 1 cm homogeneous shadows around translucent zones with line shadows radiating from each lesion, while 12 had relatively small but thick-walled cavities. In 10 patients (37 per cent) the appearances were non-specific; 5 had large relatively thin-walled cavities in shrunken upper lobes (an appearance often considered pathognomonic of opportunist mycobacterial disease), and another 5 had shrunken upper lobes with only small cavities or dilated bronchi within them.

4,203 cases of notified mycobacterial disease were reviewed. The series comprised 3,758 pulmonary and 445 non-pulmonary cases. The population was made up of 2,976 males and 1,227 females; of these, 3,053 were Australian-born and 1,150 overseas-born. The annual number of notifications fell from 21.4 to 13.0/100,000 population for pulmonary disease, and varied between 1.4 and 2.5/100,000 for non-pulmonary disease. The age incidence rose steadily from childhood with increasing age, to over 100/100,000 in the male population, but among the females did not exceed 25/100,000 at any age. Thirteen percent of the non-pulmonary cases were accompanied by active, and 11 % by inactive pulmonary tuberculosis. Under the age of 10, lymph node disease was common (30% in all age groups). In adults, genito-urinary disease was the commonest (36%); its incidence was significantly higher in those born overseas. Sixty-one percent of the pulmonary cases were judged to be of moderate severity on discovery, 25% minimal and 11% advanced; 3% presented with pleural effusion. The response to tuberculin was recorded in 73% of the cases, being positive in 68%. BCG vaccine had been given to only 9 cases; no information was recorded in 81 %. Positive bacteriological findings (by microscopy or culture or both) were noted in approximately 60%; there was no record in about 0.3% of pulmonary and 6.3% of non-pulmonary cases. In 1968-9, 58% of the 841 isolates were examined for identity; of the strains so tested, 90% were Myco. hominis, and 10% anonymous. Over the 5 yr., 380 deaths were registered as being due to mycobacterial disease; the rates varied between 0.74 and 1.07/100,000. They fell for males, but not for females between 1965 and 1969. Seven deaths occurred under the age of 10, all in females; above the age of 10, the overall number of deaths for the whole of the period rose from 0/yr. in 10-19 age groups, to 145 in those aged 70 and over.