Prevalence Of Nontuberculous Mycobacteria Infections Research Articles

Nationwide Increasing Incidence of Nontuberculous Mycobacterial Diseases Among Adults in Denmark: Eighteen Years of Follow-Up

BackgroundThe epidemiology of nontuberculous mycobacteria (NTM) infections is not well described. In this study, we determined the incidence and prevalence of NTM infections and focused on social risk factors. Additionally, we described persons suffering from pulmonary and extrapulmonary NTM. Research questionWhat is the incidence and prevalence of NTM and what are the characteristics of the affected patients? MethodsThis is a nationwide retrospective register-based cohort study in Denmark. Adult patients with NTM diagnosis in the Danish national registers from 2000-2017 were classified as having either pulmonary or extrapulmonary NTM disease. ResultsWe identified 1,146 adults with an NTM diagnosis. 661 patients had pulmonary NTM of which 50.4% were male, while 485 had extrapulmonary NTM of which 59.6% were male. The median age (Interquartile range), was 66 years (18) and 57 years (32), respectively. The yearly incidence rate per 100,000 increased between 2000 and 2017 for both pulmonary (0.4 to 1.3) and extrapulmonary NTM (0.3 to 0.6). The annual prevalence per 100,000 increased from 0.4 to 3.5 for pulmonary and 0.3 to 1.0 for extrapulmonary NTM. The incidence rate increased with age. The incidence of pulmonary NTM was highest in 70+ year-olds (19.3 per 100,000). Compared to pulmonary NTM patients, extrapulmonary NTM patients were more likely to be employed and had a higher educational level. InterpretationThe prevalence of NTM disease in Denmark increased between 2000 and 2017. Pulmonary and extrapulmonary NTM patients are two distinct groups that differ in age, gender, education, and employment status. Increased suspicion of pulmonary NTM disease is warranted in the elderly after exclusion of more common lung infections.

Epidemiology of Nontuberculous Mycobacteria in Tuberculosis suspects, Southwest of China, 2017-2022.

This study summarizes the epidemiological characteristics, species distribution, and drug sensitivity of clinical nontuberculous mycobacteria (NTM) isolates at the Public Health Clinical Center of Chengdu, China, from January 2017 to December 2022. We retrospectively analyzed data from patients with clinically isolated NTM strains. Chi-square analysis assessed the rate of Mycobacterium strain isolation over 6 years. The number of samples tested for Mycobacterium tuberculosis (MTB) and/or NTM increased each year, while MTB detection decreased and NTM detection rose significantly each year (P=0.03). The average age of NTM patients was 51 ± 17.53 years, with a 14.1% HIV infection rate. The predominant isolates were Mycobacterium avium-intracellulare (MAC) and M. chelonae/M. abscessus, with 96.4% of cases being of Han ethnicity. Amikacin, moxifloxacin, and clarithromycin were effective against M. avium and M. intracellulare; linezolid, amikacin, and cefoxitin were effective against M. chelonae/M. abscessus. Over 90% of NTM cases originated from the respiratory tract. The NTM isolation rate in Southwest China has risen in recent years, primarily among elderly patients with a high HIV co-infection rate. The main NTM isolates were MAC and M. chelonae/M. abscessus. Amikacin, moxifloxacin, clarithromycin, and linezolid exhibited strong antibacterial activity against SGM, while amikacin and linezolid displayed relatively better antibacterial activity against RGM. The prevalence of NTM infection may be positively associated with regional economic development and health conditions.

The frequency and related factors of non-tuberculosis mycobacteria infections among patients with cystic fibrosis.

Non-tuberculous mycobacteria (NTM) can cause chronic lung infection particularly in patients who have structural lung disease such as cystic fibrosis (CF). We evaluated the incidence and management of NTM infections in patients with CF in our center. A retrospective cohort study was carried out on CF patients having at least one positive NTM isolate between 2012 and 2020. Ten patients (2.1%) had at least one positive NTM culture from respiratory samples. All of them were vaccinated with Bacille Calmette-Guérin (BCG) vaccine, which is in the national vaccination program in our country. Eight patients had the Mycobacterium abscessus complex, one had Mycobacterium avium, and one had Mycobacterium szulgai growth in their respiratory samples. Three patients had transient NTM infection, two had persistent, and five had active NTM infection (NTM pulmonary disease). Patients with NTM pulmonary disease received antibiogram-directed antimycobacterial therapy. In patients with NTM pulmonary disease, the median ppFEV1 and BMI decreased by 17% and 1%, respectively, at the time of the first NTM isolation when compared with the values one year before the first NTM isolation. Culture conversion was not seen in any patient infected with Mycobacteriunm abscessus complex. The NTM infection incidence is lower in our country than in those countries where the BCG vaccine is not routinely applied. The BCG vaccine may be a protective factor for NTM infection. Further studies are needed about the prevalence of NTM infections, facilitating and protective factors, and appropriate management of NTM infections in patients with CF.

Nontuberculous Mycobacteria, Macrophages, and Host Innate Immune Response.

Although nontuberculous mycobacteria (NTM) are considered opportunistic infections, incidence and prevalence of NTM infection are increasing worldwide becoming a major public health threat. Innate immunity plays an essential role in mediating the initial host response against these intracellular bacteria. Specifically, macrophages phagocytose and eliminate NTM and act as antigen-presenting cells, which trigger downstream activation of cellular and humoral adaptive immune responses. Identification of macrophage receptors, mycobacterial ligands, phagosome maturation, autophagy/necrosis, and escape mechanisms are important components of this immunity network. The role of the macrophage in mycobacterial disease has mainly been studied in tuberculosis (TB), but limited information exists on its role in NTM. In this review, we focus on NTM immunity, the role of macrophages, and host interaction in NTM infection.

General Overview of Nontuberculous Mycobacteria Opportunistic Pathogens: Mycobacterium avium and Mycobacterium abscessus.

Nontuberculous mycobacteria (NTM) are emerging human pathogens, causing a wide range of clinical diseases affecting individuals who are immunocompromised and who have underlying health conditions. NTM are ubiquitous in the environment, with certain species causing opportunistic infection in humans, including Mycobacterium avium and Mycobacterium abscessus. The incidence and prevalence of NTM infections are rising globally, especially in developed countries with declining incidence rates of M. tuberculosis infection. Mycobacterium avium, a slow-growing mycobacterium, is associated with Mycobacterium avium complex (MAC) infections that can cause chronic pulmonary disease, disseminated disease, as well as lymphadenitis. M. abscessus infections are considered one of the most antibiotic-resistant mycobacteria and are associated with pulmonary disease, especially cystic fibrosis, as well as contaminated traumatic skin wounds, postsurgical soft tissue infections, and healthcare-associated infections (HAI). Clinical manifestations of diseases depend on the interaction of the host’s immune response and the specific mycobacterial species. This review will give a general overview of the general characteristics, vulnerable populations most at risk, pathogenesis, treatment, and prevention for infections caused by Mycobacterium avium, in the context of MAC, and M. abscessus.

Clinical characteristics of non-tuberculous mycobacterial pulmonary infections in Bamako, Mali.

The global spread of non-tuberculous mycobacteria (NTM) may be due to HIV/AIDS and other environmental factors. The symptoms of NTM and tuberculosis (TB) disease are indistinguishable, but their treatments are different. Lack of research on the epidemiology of NTM infections has led to underestimation of its prevalence within TB endemic countries. This study was designed to determine the prevalence and clinical characteristics of pulmonary NTM in Bamako. A cross-sectional study which include 439 suspected cases of pulmonary TB. From 2006 to 2013 a total of 332 (76%) were confirmed to have sputum culture positive for mycobacteria. The prevalence of NTM infection was 9.3% of our study population and 12.3% of culture positive patients. The seroprevalence of HIV in NTM group was 17.1%. Patients who weighed <55 kg and had TB symptoms other than cough were also significantly more likely to have disease due to NTM as compared to those with TB disease who were significantly more likely to have cough and weigh more than 55 kg (OR 0.05 (CI 0.02-0.13) and OR 0.32 (CI 0.11-0.93) respectively). NTM disease burden in Bamako was substantial and diagnostic algorithms for pulmonary disease in TB endemic countries should consider the impact of NTM.

Prevalence of Nontuberculous Mycobacteria Infections in Patients Diagnosed with Pulmonary Tuberculosis in Ibadan

Prevalence of Nontuberculous Mycobacteria Infections in Patients Diagnosed with Pulmonary Tuberculosis in Ibadan

Nontuberculous mycobacteria immune reconstitution syndrome.

The prevalence of nontuberculous mycobacteria infection (NTM) in Sub-Saharan Africa is estimated to be less than 1%. NTM is often underdiagnosed or misdiagnosed as tuberculosis in patients who present with immune reconstitution syndrome (IRS) following initiation of antiretroviral treatment (ART). Immune reconstitution syndrome is common in patients who start ART with low CD4 counts and high HIV viral load. Furthermore, Mycobacterium avium complex (MAC) commonly infects those with CD4 counts less than 50 cells/mm3. Three patients, with low baseline CD4 counts, presenting with NTM following the initiation of antiretroviral treatment are described in this case series. The first patient presented with disseminated NTM two weeks after commencing antiretroviral treatment. Acid fast bacilli were found in the liver, duodenum, and bone marrow and were suggestive of MAC microscopically. The second developed cervical lymphadenitis following the initiation of ART. Lymph node aspirate culture grew NTM. The last patient developed pancytopenia after 3 months of ART. AFB was seen on bone marrow biopsy. Culture of the bone marrow aspirate was suggestive of NTM. All three patients improved on ethambutol, clarithromycin, and rifampicin. NTM may be underdiagnosed in areas with a high TB prevalence and should be actively excluded by culture.

Non-Tuberculous Mycobacteria in TB-Endemic Countries: Are We Neglecting the Danger?

There are more than 120 members of the genus Mycobacterium, which are diverse in pathogenicity, in vivo adaptation, virulence, response to drugs, and growth characteristics. Mycobacteria other than M. tuberculosis complex and M. leprosy are known as Non-Tuberculous Mycobacteria (NTM) and are known by various acronyms. They attracted abrupt attention only after the AIDS epidemic, but most of the reports were published from TB non-endemic countries [1] and only rarely from TB-endemic countries. This is probably because the chances of missing NTM species are higher in TB-endemic countries, which are poorly equipped and overburdened with other diseases (Box 1). The information regarding their true incidence and prevalence in these countries is scarce [2]. In the absence of such authentic information, the current dogma has been that the NTM are of the least consequence. However, we do not agree with this myth and wish to present our viewpoint on this important aspect and emphasize the need for a fresh look at this neglected aspect. Box 1. Possible Factors for Under-reporting of NTM from TB-Endemic Countries NTM infections are not reportable in any country. Awareness is lacking among treating physicians and microbiologists. Laboratory infrastructure is lacking for culture and identification of non-tuberculous mycobacteria. High burden of TB and HIV attracts the bulk of the attention of the health care system; governmental fiscal inputs toward the costs of these neglected infections continue to be neglected. Standardized or accepted criteria to define NTM respiratory disease are lacking. Prevalence of NTM Infections before and after the AIDS Epidemic We searched methodological search terms and phrases such as “non-tuberculous mycobacteria and AIDS” in Medline records and found that 3,020 articles were published between 1981 and 2009. Using the same phrase, only 59 articles were published between 1900 and 1981, indicating a clear upsurge of NTM disease in the post-AIDS era. However, most of these publications were from TB non-endemic countries [1]–[5], but not much significance could be adhered to these isolations [2]. The disseminated NTM infection is typically seen when the CD4+ T lymphocyte number falls below 50 µl. For this reason, it is argued that in TB-HIV co-endemic countries, AIDS patients usually die of tuberculosis or other infections before their CD4+ count falls low enough for NTM to cause a disease (Box 2). Nevertheless, we feel that besides this argument, in a majority of the patients, the diagnosis of NTM disease gets missed in these countries. Box 2. Facts about Non-tuberculous Mycobacterial Disease AIDS patients are significantly more vulnerable to NTM infections due to severe T cell immunodeficiency. Solid organ transplant patients, even though immunocompromised, are not at as high a risk as their HIV-positive counterparts. Although some genetic and anatomical factors predispose to NTM, no proven associations have been proven among geographical, occupational, or ethnic factors and NTM infections. Anatomical abnormalities and other co-morbidities such as chronic obstructive pulmonary disease (COPD), bronchiectasis, cystic fibrosis (CF), pneumoconiosis, past history of TB, pulmonary alveolar proteinosis, and esophageal motility disorders are well-established predisposing conditions. Disseminated NTM infections have been associated with specific genetic syndromes such as mutations in interferon (IFN)-γ, interleukin (IL)-12 synthesis, and in response pathways and the nuclear factor-κB essential modulator (NEMO). Conventional methods are not sufficiently sensitive to estimate prevalence and incidence of NTM infections. Monoplex TB-specific PCR needs to be replaced by multiplex PCR systems on relevant clinical samples along with blood and urine samples in tertiary-care settings. Multiplex PCR primers have been designed to amplify genus-specific regions, M. tuberculosis complex specific, M. avium complex specific, M fortuitum complex specific, and species-specific gene targets, that can be performed in a single tube. Geographical Distribution of NTM Some workers also consider that the low detection rate of NTM is due to diversity in the environmental and climatic conditions in the HIV-TB-endemic countries, but this argument is not supported by the literature [3]–[5]. In most of the surveys, the rate of human NTM infections is estimated by non-specific antibody assays or skin tests [6]. Hence, these findings may not be a reliable source of information. The International Union against Tuberculosis and Lung Diseases (IUATLD) reviewed data from 14 countries and found that the M. avium complex (MAC) was the most frequently isolated species in all these countries, which included China, India, and Korea. While M. fortuitum was the most frequently encountered species in Belgium (2.1%), the Czech Republic (17.5%), Denmark (5.3%), Finland (6.7%), France (6.5%), Germany (12.2%), Italy (2.5%), Portugal (16.5%), Spain (10.8%), Switzerland (17.5%), Turkey (33.9%), and the United Kingdom (6.0%), undoubtedly, environment is the main reservoir of NTM. There is no evidence of human-to-human or animal-to-human transmission [6]. Most infections are acquired either from the water (treated or untreated) or soil. MAC and M. fortuitum are frequently isolated from the drinking water distribution systems and swimming pools in both developing and developed countries.

Adult cystic fibrosis presenting with recurrent non-tuberculous mycobacterial infections

In November, 1997, a previously healthy 54-year-old white man presented with productive cough, low-grade fever, and chills resistant to outpatient treatment with clarithromycin and cefpodoxime proxetil. CT of the chest showed consolidation of the left lower lobe and lingula. Spirometry was normal, and HIV serology was negative. Sputum showed acid-fast bacilli (AFB) and cultures grew Mycobacterium avium intracellulare. The patient was treated with rifampicin, ethambutol hydrochloride, and clarithromycin for 2 years. In January, 2002, he presented to our clinic with recurrent symptoms. Chest CT showed only linear densities in the left lower lobe. AFB smears were again positive. Cultures grew Mycobacterium chelonae and the patient was treated with doxycycline, clarithromycin, and ciprofl oxacin. Several months later a repeat AFB smear was positive, with cultures growing Mycobacterium abcessus and M avium intracellulare. He was admitted to our unit, and highresolution chest CT showed mild bilateral central bronchiectasis. Barium swallow showed a normal swallowing mechanism without gastro-oesophageal refl ux and no laryngeal penetration. Tests for antinuclear antibody and rheumatoid factor were negative. α-1 antitrypsin and immuno globulin concentrations were normal. He was discharged 10 days after admission. Despite repeated attempts, the patient had fathered no children, therefore a sweat chloride test was done as an outpatient; the concentration was high at 96 mmol/L (normal 40–60 mmol/L). Cystic fi brosis (CF) genotyping showed that the patient was heterozygous for two diff erent CF trans membrane conductance regulator gene alleles: δF508 and R117C. The patient was treated with ciprofl axacin, clarithromycin, and ethambutol for 3 years. When last seen in March, 2006, the patient had negligible sputum production, and AFB smears have been negative since 2004. Non-tuberculous mycobacteria (NTM) are free-living organisms that are ubiquitous in the environment. Occasional isolates of NTM were generally thought to be contaminants or colonisers until the second half of the 20th century. As the prevalence of Mycobacterium tuberculosis declined in developed nations and modern microbiological methods were developed, the importance of NTM in human disease became increasingly evident. By the early 1990s, laboratories in the USA informally reported that about two-thirds of recovered mycobacteria species were NTM. Some of this increase is related to the high rate of disseminated M avium complex disease in patients with AIDS; however, there could also have been an increase in the rate of NTM infections in other groups of patients, such as those with CF. The classic description of NTM pulmonary infection is that of a patient with cavitary infi ltrates and underlying lung disease. We have seen two patients in their mid-50s, who developed recurrent NTM pulmonary infections and were sub sequently diagnosed with CF. Our second patient had congenital absence of the vas deferens and normal sweat chloride concentration; he was confi rmed to have CF by genotyping showing the δ508 and D1152H alleles. Among adults with CF, 63% are aged 18–29 years, 25% 30–39 years, 10% 40–49 years, and 2% over 50 years ; adults will represent >40% of the US cystic fi brosis population in 2005. Among the 22 301 patients in the 2000 CF Foundation registry, the diagnosis was established after the age of 17 years in only 831 (3·7%); sweat chloride tests were abnormal in 90% of cases. Although NTM infections in CF are well described, recurrent NTM infection as the initial presentation of CF has not been described. The reported prevalence of NTM in CF ranges from 3% to 30%. Contamination of mycobacterial cultures (especially by Pseudomonas aeruginosa) can lead to underestimation of the prevalence of NTM infection in CF. Controversy surrounds the distinction between NTM infection and simple colonisation in CF. Symptomatic patients with persistently positive AFB smears and new radiographic abnormalities are most likely to be truly infected. Patients with negative AFB smears but positive cultures with low numbers of colonyforming units are probably colonised. We believe our patients were actively infected and not just colonised because they were symptomatic and had repeatedly positive AFB smears, high colony-forming unit counts on culture, and new radiographic changes. Both also improved with appropriate anti-NTM therapy. Our patients were pancreatic suffi cient and their respiratory symptoms were mild and delayed in comparison to more severe CF phenotypes. They remain free of sputum colonisation by pseudomonas at age 60 years (case history presented in detail) and 57 years. We postulate that the benign course of their illness is related to the fact that they are heterozygous for two diff erent CF gene alleles, the usual δF508 and R117C/ D1152H—the latter two are associated with milder disease. We conclude that in patients with recurrent NTM infections and new radiographic abnormalities, a diagnosis of CF should be considered irrespective of the patient’s age.

157 Prevalence of nontuberculous mycobacteria infection in Cystic Fibrosis (CF) pediatric patients in Piedmont region of Italy

157 Prevalence of nontuberculous mycobacteria infection in Cystic Fibrosis (CF) pediatric patients in Piedmont region of Italy

Investigation into typical and atypical tuberculin sensitivity in the Royal Netherlands Army, resulting in a more rational indication for isoniazid prophylaxis

Setting: The Department of Military Health Services (DMGZ) vaccination clinic, Utrecht, The Netherlands. Objectives: To improve upon PPD skin testing procedure by introducing a double Mantoux test. Design: During the first part of the study, from 1986–1988, army recruits were double-tested simultaneously with PPD and Mycobacterium scrofulaceum sensitin. During the second part of the study, from 1989 to 1993, recruits reacting to PPD, with an induration in the range of 10–15 mm, underwent a second skin test with M. scrofulaceum sensitin. The total study population consisted of 237 692 non-BCG-vaccinated recruits. Results: From 1986–1993 an average of 0.45% persons reacted with indurations ≥ 10 nun to PPD. An average of 7.76% army recruits reacted with indurations ≥ 10 mm to M. scrofulaceum sensitin during the first part of the study. Using a modified ITSC (International Tuberculosis Surveillance Centre) model, 48% of the persons reacting to PPD with indurations in the range 10 mm and 15 mm were classified as false-positive. A total of 16% with indurations ≥ 10 mm to PPD were classified as false positive. False-positive persons were then excluded from INH chemoprophlaxis. Conclusions: In areas with a high prevalence of non-tuberculous mycobacteria infection the use of double skin testing might be useful in differentiating between indurations due to tubercle bacilli and those due to infection with non-tuberculous mycobacteria.