Complement C4 deficiency--a plausible risk factor for non-tuberculous mycobacteria (NTM) infection in apparently immunocompetent patients.

BACKGROUND: Non-tuberculous mycobacteria (NTM) are ubiquitous in the environment and they infect mainly persons with underlying pulmonary diseases but also previously healthy elderly women. Defects in host resistance that lead to pulmonary infections by NTM are relatively unknown. A few genetic defects have been associated with both pulmonary and disseminated mycobacterial infections. Rare disseminated NTM infections have been associated with genetic defects in T-cell mediated immunity and in cytokine signaling in families. We investigated whether there was an association between NTM infections and deficiencies of complement components C4A or C4B that are encoded by major histocompatibility complex (MHC). METHODS: 50 adult patients with a positive NTM culture with symptoms and findings of a NTM disease were recruited. Patients' clinical history was collected and symptoms and clinical findings were categorized according to 2007 diagnostic criteria of The American Thoracic Society (ATS). To investigate the deficiencies of complement, C4A and C4B gene copy numbers and phenotype frequencies of the C4 allotypes were analyzed. Unselected, healthy, 149 Finnish adults were used as controls. RESULTS: NTM patients had more often C4 deficiencies (C4A or C4B) than controls (36/50 [72%] vs 83/149 [56%], OR = 2.05, 95%CI = 1.019-4.105, p = 0.042). C4 deficiencies for female NTM patients were more common than for controls (29/36 [81%] vs 55/100 [55%], OR = 3.39, 95% CI = 1.358-8.460, p = 0.007). C4 deficiences seemed not to be related to any specific underlying disease or C4 phenotype. CONCLUSIONS: C4 deficiency may be a risk factor for NTM infection in especially elderly female patients.

[Tuberculosis is transmitted in hospital and autopsy room--an epidemic in healthcare personnel]. / Tuberkuloosi tarttuu sairaalassa ja ruumiinavaussalissa--terveydenhuollon henkilökunnan epidemia.

We describe an epidemic of tuberculosis of occupational origin in five healthcare workers, which originated from a patient with tuberculous peritonitis. The source of the infection was not revealed until one year after the patient's death. Over 300 workers were exposed to tuberculosis. Up-to-date microbiological molecular technology was applied to the investigation of the infection among the exposed workers. This was the first time that an electronic reporting system for biological exposures was utilized for the investigation of an epidemic. Within this epidemic it is assumed that another five workers will develop a symptomatic tuberculosis infection during their lifetime.

Prognostic value of American Thoracic Society criteria for non-tuberculous mycobacterial disease: a retrospective analysis of 120 cases with four years of follow-up.

BACKGROUND: Non-tuberculous mycobacteria (NTM) cause disease in healthy and immunocompromised patients. The American Thoracic Society (ATS) 2007 diagnostic criteria were devised to distinguish NTM disease from airway colonization. The aim of this study was to evaluate the prognostic value of the ATS criteria. METHODS: In a 4-y follow-up study that ended on 8 June 2006, we retrospectively analyzed the symptoms, underlying diseases, and mortality of 120 adult non-HIV patients with NTM culture findings obtained between 1990 and 1998. We categorized the patients according to the 2007 ATS NTM case definition into positive and negative groups. RESULTS: Only 61/120 patients (51%) fulfilled the ATS criteria for NTM disease. As compared to ATS-negative subjects, the ATS-positive group showed lower age, a higher proportion of females, and fewer fatal underlying diseases. Among ATS-negative subjects, 46/59 (78%) did not fulfil the microbiological criteria and 43/59 (73%) did not fulfil the radiological criteria. Mycobacterium avium complex (MAC) comprised 61% of isolations in the ATS-positive and 47% in the ATS-negative group (p = 0.15). No significant difference in median survival time was found between the groups: ATS-positive 7.4 y (95% confidence interval (CI) 0.2-14.6) and ATS-negative 5.3 y (95% CI 3.0-7.6). No significant difference was found in symptoms except fatigue, which was more common in the ATS-positive (56% vs 37%, p = 0.04). Symptoms lasted for less than a year in 48%, which suggests a more rapid disease progression than has previously been reported. CONCLUSIONS: The fulfillment of ATS criteria was poorly associated with any difference in prognosis, and based on our findings would be a poor prognostic marker.

Clinical symptoms and survival in non-smoking and smoking HIV-negative patients with non-tuberculous mycobacterial isolation.

BACKGROUND: Non-tuberculous mycobacteria (NTM) cause infections in patients with smoking-related chronic lung diseases and also in non-smoking healthy elderly women. We analyzed the clinical symptoms, underlying diseases and mortality in patients with NTM culture findings, with special emphasis on smoking status. METHODS: A total of 120 consecutive adult HIV-negative patients with NTM isolation were followed between 1990 and 1998 by retrieving data from their medical records for a period of at least 4 y, until 8 June 2006. Their clinical pictures and outcomes were analysed according to smoking status. RESULTS: In this study, 42% of the patients had never smoked. Females accounted for 72% of non-smokers, but only 30% of smokers (p < 0.001). Mycobacterium avium complex (MAC) accounted for 72% of all isolates in non-smokers and 41% in smokers (p = 0.001). Furthermore, 28% of non-smokers and 19% of smokers had no previous pulmonary diseases (p = 0.223). In nearly half of all patients (48%), symptoms of NTM infection started within a year prior to NTM isolation. Smokers had a higher risk of mortality compared to non-smokers (hazard ratio 1.64, p = 0.049), though this was not found after adjusting for underlying diseases. No fatal underlying diseases were found for 82% of non-smokers and 59% of smokers (p < 0.01). CONCLUSIONS: Non-smokers with NTM isolates had fewer previous lung diseases but had a higher incidence of MAC and bronchiectasis. Time from symptoms to NTM isolation was shorter than previously reported.