ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Epidemiology of nontuberculous mycobacterial infections

Epidemiology of nontuberculous mycobacterial infections
Literature review current through: Jan 2024.
This topic last updated: Jun 23, 2021.

INTRODUCTION — Mycobacteria other than Mycobacterium tuberculosis and Mycobacterium leprae are generally free-living organisms that are ubiquitous in the environment (table 1). They have been recovered from surface water, tap water, soil, domestic and wild animals, milk, and food products [1-4]. These organisms can also inhabit body surfaces or secretions without causing disease. Thus, occasional isolates of nontuberculous mycobacteria (NTM) were largely considered contaminants or colonizers until the second half of this century. However, as tuberculosis declined and modern microbiological methods were developed, the importance of NTM in human disease became increasingly evident.

In broad terms, NTM cause four distinct clinical syndromes [5,6]:

Progressive pulmonary disease caused primarily (in the United States) by Mycobacterium avium complex (MAC), M. abscessus complex, and M. kansasii

Superficial lymphadenitis, especially cervical lymphadenitis, in children caused mostly by MAC, M. scrofulaceum, and, in northern Europe, M. malmoense and M. haemophilum; the most common cause in adults, however, is M. tuberculosis

Disseminated disease in severely immunocompromised patients

Skin and soft tissue infection usually as a consequence of direct inoculation

The epidemiology of NTM will be reviewed here. An overview of NTM in HIV-negative and HIV-positive patients, as well as the pathogenesis, microbiology, diagnosis, and treatment of NTM infections are presented separately. Rapidly growing NTM infections in HIV-negative patients, M. avium complex infections in HIV-infected patients, and NTM infections in solid organ transplant candidates and recipients are also discussed elsewhere. (See "Overview of nontuberculous mycobacterial infections" and "Overview of nontuberculous mycobacteria (excluding MAC) in patients with HIV" and "Pathogenesis of nontuberculous mycobacterial infections" and "Microbiology of nontuberculous mycobacteria" and "Diagnosis of nontuberculous mycobacterial infections of the lungs" and "Treatment of Mycobacterium avium complex pulmonary infection in adults" and "Rapidly growing mycobacterial infections: Mycobacteria abscessus, chelonae, and fortuitum" and "Mycobacterium avium complex (MAC) infections in persons with HIV" and "Nontuberculous mycobacterial infections in solid organ transplant candidates and recipients".)

COMMON PATHOGENIC SPECIES — The most common nontuberculous species causing human disease in the United States are the slowly growing species of the M. avium complex (MAC) and M. kansasii and the rapidly growing M. abscessus complex. Less common human pathogens include the slowly growing species M. marinum, M. xenopi, M. simiae, M. malmoense, and M. ulcerans, and the rapidly growing species M. abscessus subspecies massiliense and bolletii, M. fortuitum, and M. chelonae.

Among children, the predominant NTM disease in children is cervical lymphadenitis due to MAC and M. scrofulaceum and cutaneous disease due to M. marinum and M. ulcerans [7]. Rare cases of disseminated disease have been reported in children [8,9].

FREQUENCY OF DISEASE

Challenges in estimating incidence/prevalence — The precise frequency of disease due to the different species of NTM is unknown. Determining the incidence and prevalence of NTM lung disease is difficult because disease reporting is not mandatory in the United States and many other countries. Additionally, mere isolation of NTM does not necessarily indicate disease, and studies that use the frequency of NTM isolates as a surrogate for disease prevalence may overestimate it.

The best option for evaluating NTM lung disease epidemiology may be use of diagnostic codes in databases from large health care delivery systems, managed care providers, and health care insurers. However, there are potential limitations with this approach that can result in both underdiagnosis (lack of disease recognition by the clinician) and overdiagnosis (inappropriate diagnosis for patients who do not meet diagnostic criteria), since the accuracy of diagnostic codes depends on the clinical acumen of the clinician assigning them.

Clinical diagnosis of NTM lung disease is based on three criteria: symptoms, microbiology, and radiographic findings. Although some studies suggest that using the microbiologic criterion alone may be an acceptable proxy for disease for epidemiologic purposes in specific populations, it is unclear whether these are generalizable to larger and more diverse patient populations [10,11]. As an example, in a study of 367 patients on tumor necrosis factor alpha inhibitor therapy for rheumatoid arthritis, who had either a culture positive for NTM or had a diagnostic code for NTM, meeting microbiologic criteria (ie, one positive culture from a bronchoscopic specimen or two sputum cultures positive for the same species) a positive predictive value for NTM lung disease according to full criteria of 78 to 100 percent, depending on the center [11].

Increasing burden of disease — Despite methodologic differences, studies show a remarkably consistent trend of increasing NTM disease (particularly lung disease) prevalence, especially in older and female patients. Reasons for this observation are not immediately clear. Some increase may be due to better awareness of NTM lung disease, better diagnostic tools, and changing coding practices for NTM lung disease. It is also possible there is a true increase in NTM lung disease prevalence due to more extensive environmental NTM exposure or host susceptibility factors, such as increased incidence of bronchiectasis and/or chronic obstructive pulmonary disease (COPD) or use of immunosuppressive agents, including inhaled corticosteroids [12].

Global trends — Based upon the available data, the burden of NTM appears to be increasing worldwide. One comprehensive review of available information about global NTM disease prevalence emphasized the heterogeneity of isolates and disease burden worldwide but concluded that available population-based data suggested that NTM pulmonary disease was increasing in North America, Europe, Asia, and Australia [13].

NTM lung disease is especially prevalent in parts of Asia. One study from Japan analyzed data from NTM lung disease health insurance claims between 2009 and 2014 [14]. In this study, NTM lung disease was identified by at least one claim associated with an NTM diagnostic code and at least one claim for combinations of antimycobacterial medications. The prevalence in 2011 was 29 per 100,000 persons and was higher among females than males in most age groups. The most common comorbidities were bronchiectasis for women and COPD for men. Another study using a different method estimated a prevalence of 25 per 100,000 persons in Japan in 2019 [15]. In South Korea, a report found that prevalence of NTM lung disease between 2007 and 2016 increased from 6.7 cases to 39.6 cases per 100,000 persons [16]. Overall prevalence for the study was higher in older adults and in females.

In Ontario, Canada, prevalence of patients meeting ATS microbiologic criteria for NTM lung disease also increased 10 percent per year from 2003 to 2008 [17]. In a study of pulmonary NTM cases in Queensland, Australia, where NTM disease is a notifiable condition, the incidence of cases rose from 2.2 to 3.2 per 100,000 population between 1999 and 2005 [18].

Trends in the United States — Trends in NTM disease in the United States are similar to those worldwide, with increasing prevalence, particularly among females in older age groups.

One study reviewed annual medical claims with diagnostic codes for NTM disease within a national managed care database that represented a geographically diverse population of approximately 27,000,000 members [19]. A case of NTM lung disease was defined as having at least two medical claims with an NTM diagnostic code dated at least 30 days apart. From 2008 to 2015, the annual incidence of NTM lung disease increased from 3.1 to 4.7 per 100,000 person-years, and the annual prevalence increased from 6.8 to 11.7 per 100,000 persons. The average annual increases in incidence and prevalence were 5.2 and 7.5 percent, respectively. For women, the annual incidence increased from 4.2 to 6.7 per 100,000 person-years, and the annual prevalence increased from 9.6 to 16.8 per 100,000 persons. For individuals age 65 years or older, the annual incidence increased from 12.7 to 18.4 per 100,000 person-years, and the annual prevalence increased from 30.3 to 47.5 per 100,000 persons. The incidence and prevalence of NTM lung disease increased in most states as well as at the national level.

Earlier studies had also suggested a trend towards increased incidence and prevalence over the prior two decades [20-22].

Patients with cystic fibrosis — NTM strains are commonly isolated from sputum in patients with cystic fibrosis and may be clinically significant. In a study of more than 16,000 persons with cystic fibrosis, 20 percent had a pathogenic NTM species isolated at least once over a five-year period [23]. Most (61 percent) had MAC and 39 percent had M. abscessus complex isolated. Patients with either MAC or M. abscessus complex were significantly more likely to have been diagnosed with cystic fibrosis at an older age, have a lower body mass index, and have fewer years of chronic macrolide therapy. The incidence appeared to increase over time. (See "Cystic fibrosis: Antibiotic therapy for chronic pulmonary infection", section on 'Nontuberculous mycobacteria'.)

HOST SUSCEPTIBILITY — Many risk factors for NTM diseases are specific to the clinical syndrome or the species. However, a number of inherited and acquired defects in the host immune response, particularly those that affect the Th1 cell and macrophage pathway, have been associated with increased susceptibility to NTM infections in general. Many of these host immune defects are associated especially with disseminated infection. (See "Pathogenesis of nontuberculous mycobacterial infections", section on 'Mycobacterium avium complex'.)

These defects are discussed in further detail elsewhere and include the following:

Interferon gamma receptor deficiencies (see "Mendelian susceptibility to mycobacterial diseases: Specific defects", section on 'IFN-gamma receptor deficiencies')

Signal transducer and activator of transcription 1 (STAT1) deficiency (see "Mendelian susceptibility to mycobacterial diseases: Specific defects", section on 'STAT1 defects')

Auto-antibodies to interferon gamma (see "Mendelian susceptibility to mycobacterial diseases: An overview", section on 'Differential diagnosis')

CD4 lymphopenia due to HIV or other causes (see "Mycobacterium avium complex (MAC) infections in persons with HIV" and "Overview of nontuberculous mycobacteria (excluding MAC) in patients with HIV" and "Idiopathic CD4+ lymphocytopenia", section on 'Mycobacteria')

Use of TNF-alpha inhibitors, particularly infliximab and adalimumab (see "Risk of mycobacterial infection associated with biologic agents and JAK inhibitors", section on 'Nontuberculous mycobacterial disease')

HOST PROTECTION — Few patient characteristics that are protective of infection with NTM have been described. Epidemiologic studies from Sweden and Finland have suggested that childhood immunization with Bacillus Calmette-Guerin (BCG) vaccine is associated with a reduced risk of childhood cervical lymphadenitis due to NTM [24,25].

MYCOBACTERIUM AVIUM COMPLEX — The members of the M. avium complex (MAC) are ubiquitous, free-living organisms readily recovered from natural reservoirs including soil and water, domestic and wild animals, and foodstuffs [26]. Environmental MAC isolates and clinical isolates belong to different serovars [27]. However, mycobacteria can become aerosolized from aqueous sources, and the more easily aerosolized strains are often phenotypically the same as those that cause pulmonary infections [28,29]. Isolates similar or identical to clinical isolates have also been recovered from naturally occurring surface water, hot tubs, and piped hot water systems [27,30-32]. Prolonged exposure to soil has also been identified as a risk factor for MAC infection in the United States [33]. Studies using gene sequence analyses have demonstrated that NTM are enriched to high levels in many showerhead biofilms, supporting previous theories that showers may represent another potential source of MAC infection in humans [34,35].

Unlike M. tuberculosis, there are no convincing data demonstrating human-to-human transmission of infection. Thus, the concept prevails that these organisms are acquired from the environment. Furthermore, environmental exposure to these organisms must be common because data from several countries showed that a substantial fraction of children have delayed cutaneous hypersensitivity responses to MAC antigens, a fraction that increases with age [36-38].

A smaller survey of skin test reactivity to M. intracellulare antigen was reported from the National Health and Nutrition Examination Surveys (NHANES) comparing results from 1971 to 1972 with 1999 to 2000 [39]. Between these two time periods, the prevalence of M. intracellulare sensitization increased from 11.2 to 16.6 percent. The authors concluded that from 1999 to 2000, an estimated one in six persons in the US demonstrated M. intracellulare sensitization, up from one in nine persons from 1971 to 1972. They felt that the observed rising prevalence of sensitization was consistent with observed increases in rates of pulmonary NTM isolates in the United States (US) [40]. (See 'Frequency of disease' above.)

The geographic distribution of skin test reactivity to MAC is not uniform. A survey of skin test reactivity to a MAC antigen among 275,000 naval recruits who had lived their entire lives in a single county showed skin test reactivity to be most frequent among recruits from the southeastern and gulf coast states (figure 1) [41]. In these areas, more than 70 percent of individuals had been exposed to or infected with MAC or an antigenically similar organism.

More recent dual skin test studies have been conducted among healthy individuals in the United States using M. avium sensitin, a reagent that has been shown to be both sensitive and specific in distinguishing past disease due to M. avium from past disease due to M. tuberculosis [42]. Among 784 subjects from the northern and southern US, 40 percent of US-born subjects had M. avium-dominant reactions consistent with prior infection with M. avium or other NTM; M. avium-dominant reactions were found in 46 percent of subjects from southern sites and 33 percent from northern sites. Cross reactions due to NTM were found to be responsible for the majority of tuberculin skin test reactions in the 5 to 14 mm range [43].

Pulmonary disease — Since MAC is not a reportable disease, precise prevalence and incidence data are not available.

Although rigorous data are lacking, there is widespread impression that the frequency of MAC lung disease may be increasing, as discussed in detail above. (See 'Frequency of disease' above.)

Two major clinical syndromes of MAC lung disease are recognized:

Disease in those with known underlying lung disease, primarily white, middle-aged or older males, often with alcohol abuse and/or smokers with underlying chronic obstructive pulmonary disease. MAC lung disease has also been described in adolescents or adults with cystic fibrosis. (See "Overview of nontuberculous mycobacterial infections", section on 'Clinical manifestations'.)

Disease in those without known underlying lung disease, predominantly in nonsmoking women over age 60 years who have nodules and reticular changes on chest radiography. For reasons that are unclear, this is the form of MAC lung disease most likely encountered by clinicians in the US and Canada. (See "Overview of nontuberculous mycobacterial infections", section on 'Clinical manifestations'.)

Two other less common forms of MAC lung disease have been described:

A hypersensitivity pneumonitis syndrome most frequently reported in association with hot tub use ("hot tub lung"). (See "Overview of nontuberculous mycobacterial infections", section on 'Clinical manifestations'.)

One report noted an unexpectedly high frequency (78 of 244 patients) of MAC pulmonary infections presenting as solitary pulmonary nodules, which resembled lung cancer [44]. Another smaller study showed similar findings [45]. (See "Overview of nontuberculous mycobacterial infections", section on 'Clinical manifestations'.)

Disseminated disease — Disseminated NTM (particularly MAC) disease primarily occurs in severely immunocompromised patients, such as those with AIDS. It is thought to arise from infection of a mucosal surface (gut or lung), followed by local multiplication and entry into the bloodstream with seeding of other organs and tissues. (See "Pathogenesis of nontuberculous mycobacterial infections".)

Prior to the widespread use of potent antiretroviral therapy and mycobacterial antibiotic prophylaxis, disseminated MAC was very common among patients with advanced AIDS in developed countries but rare to nonexistent among patients with advanced AIDS in resource-limited countries where tuberculosis was endemic [46]. This was observed despite studies showing that isolation rates of MAC from the environment and rates of skin test reactivity to MAC in healthy persons were comparable in resource-rich and resource-limited countries [47,48]. This led to the hypothesis that patients in resource-limited countries had relative immunologic protection against MAC conferred by prior BCG and/or latent infection with M. tuberculosis [46].

The incidence of disseminated MAC has decreased dramatically since the introduction of potent antiretroviral therapy and effective MAC prophylaxis. This is discussed in detail separately. (See "Mycobacterium avium complex (MAC) infections in persons with HIV".)

MYCOBACTERIUM KANSASII — Because large scale testing of skin test reactivity to M. kansasii antigens has not been performed, the geography of M. kansasii is less well known than that of MAC. Based upon reports of clinical disease, the organism seems to predominate along the southeastern and southern coastal states and the central plains states [49]. The Centers for Disease Control and Prevention (CDC) surveys noted previously found that M. kansasii was the second most common respiratory NTM isolate in state laboratories in the United States, but more recently, M. abscessus complex has overtaken M. kansasii as the second most common respiratory NTM pathogen [5,6].

Unlike other NTM, M. kansasii has never been found in soil or natural water supplies but has been recovered consistently from tap water in cities where M. kansasii is endemic. Studies in Texas show that M. kansasii disease is concentrated in urban areas, supporting a possible association between clinical disease and potable water supplies [50].

Incidence — The incidence of M. kansasii infection was studied in a population-based laboratory survey from 1992 to 1996 in three counties of northern California and was surprisingly, found to be 2.4 cases per 100,000 adults annually [51]. Of the 270 cases identified, 187 were HIV positive, 33 HIV negative, and 50 with HIV status unknown. Patients without HIV tended to be older (median age 61 versus 39) and White (62 versus 49 percent); 40 percent of these patients did not have an identifiable underlying condition. Isolation of M. kansasii from respiratory specimens was associated with symptomatic illness in both HIV positive and negative patients. Homelessness and lower socioeconomic status were also important associated findings. The increased frequency reported appeared to track with HIV status (0.75 per 100,000 for HIV negative individuals compared to 115 per 100,000 for HIV positive and 647 per 100,000 for patients with AIDS).

Risk factors — M. kansasii causes pulmonary disease resembling tuberculosis. The major predisposing factor to lung infection is chronic obstructive pulmonary disease (COPD), which is present in over two-thirds of cases; other underlying conditions may include malignancy, immunosuppressive drugs, alcohol abuse, pneumoconiosis, and HIV infection [52-55]. Affected patients tend to be in their fifth decade or older, with an approximate 3:1 male predominance. Certain occupational groups are at increased risk, including miners, welders, sandblasters, and painters [52]. Some patients, however, have no risk factor other than their geographic area of residence.

A survey of 56 adults with M. kansasii pulmonary infection in Israel diagnosed in the time period 1999 to 2004 noted the following findings [56]:

Mean age 58±18 years

64 percent of cases occurred in males

59 percent had underlying lung disease

15 percent were receiving immunosuppressive medications

HIV-related — In addition to causing pulmonary disease resembling tuberculosis, M. kansasii also causes disseminated disease, particularly in HIV-infected individuals. This is discussed in detail elsewhere. (See "Overview of nontuberculous mycobacteria (excluding MAC) in patients with HIV", section on 'Mycobacterium kansasii'.)

RAPIDLY GROWING MYCOBACTERIA — Rapidly growing mycobacteria include three clinically relevant species M. abscessus complex, M. chelonae, and M. fortuitum (table 1). The most common of this group of organisms encountered in clinical practice or in the clinical microbiology laboratory is M. fortuitum, however, the most important human pathogen is M abscessus complex. M. fortuitum is rarely a significant respiratory pathogen in the absence of significant aspiration [57].

These, and other rapidly growing mycobacterial species, are hardy environmental saprophytes widely distributed in nature and able to withstand extremes of temperature and nutritionally-spartan environments. They have been isolated from soil, dust, water, terrestrial and aquatic animals, hospital environments (including hospital tap water), and contaminated reagents and pharmaceuticals [26,49,58]. An example of nosocomial transmission involves an outbreak of surgical wound infections caused by a novel species of rapidly growing mycobacteria involving 15 females who underwent breast implant insertion at a single medical center [59]. A single surgeon who performed all the surgical operations was identified as the source for the organism.

Direct or indirect person-to-person transmission of certain strains of M. abscessus has also been suggested. In a study of 168 separate isolates from 30 cystic fibrosis patients infected with M. abscessus complex, whole-genome sequencing demonstrated two clusters of drug resistant M. massiliense, in which isolates from different patients were highly related to each other, and epidemiological investigation suggested cross-infection between patients within the hospital [60]. Similar clustering across patients was not seen with M. abscessus complex isolates.

The clinical manifestations, diagnosis, and management of disease caused by rapidly growing mycobacteria are discussed in detail separately. (See "Rapidly growing mycobacterial infections: Mycobacteria abscessus, chelonae, and fortuitum".)

OTHER NONTUBERCULOUS MYCOBACTERIA

Mycobacterium marinum — Although infection with M. marinum is uncommon, the epidemiology of M. marinum disease is distinctive from the species described above. The natural habitat of M. marinum is aquatic, as the name suggests. It is found in fresh and salt water, including marine organisms, swimming pools, and fish tanks.

M. marinum causes cutaneous disease as a consequence of exposure to water, usually in the context of a minor abrasion, laceration, puncture wound, or bite wound. Skin infections can occur from putting one's hand into a contaminated fish tank, resulting in the condition called fish tank granuloma [61]. In a series of 63 cases from France, 84 percent were linked to fish tank exposure [62]. A similar epidemiologic pattern has been found in the United States, along with the recognition that M. marinum may cause a positive tuberculin skin test [63].

A 50-year epidemic of chronic progressive skin disease among residents of Satowan, in the Federated States of Micronesia, began after World War II [64]. In a case-control study, risk factors for disease were taro farming, which is done in standing water that reaches ankle height, and contact with water-filled World War II-era bomb craters. Histopathology of nine skin lesions demonstrated suppurative granulomatous inflammation and nontuberculous mycobacteria DNA was detected by polymerase chain reaction in seven of nine specimens. The two samples that were able to be sequenced had 95 and 87 percent identity to M. marinum.

Mycobacterium xenopi — M. xenopi is a slow-growing nontuberculous mycobacterium that is an opportunistic and nosocomial pathogen. It is an uncommon pathogen that most frequently causes pulmonary infection.

Its survival in water systems and resistance to common disinfectants enable M. xenopi to contaminate laboratory samples and medical devices such as bronchoscopes, thus causing healthcare-acquired pseudoinfections and laboratory contamination. In a retrospective review of 136 cases of M. xenopi infection seen over a 20 year period in France, three types of pulmonary disease were observed that varied with the host: acute infiltrates in immunocompromised hosts, solitary nodular disease in immunocompetent hosts, and cavitary disease in patients with preexisting lung disease [65]. A report from the Netherlands suggests a predominance of M. xenopi infections in males with preexisting lung disease [66]. A study from Great Britain suggests an unusually high mortality rate in such patients for unclear reasons [67].

The most common extrapulmonary sites are bone and joints. Fifty-eight cases of nosocomial spinal infection occurred in healthy patients following percutaneous nucleotomy for lower back pain or sciatica [68,69]. The outbreak stemmed from the practice of rinsing the surgical instruments with tap water. There were also seven cases of M. xenopi arthritis following invasive surgical procedures [70].

Mycobacterium haemophilum — M. haemophilum is slow-growing nontuberculous mycobacterium that is thought to live in water [71]. It has a predilection for causing skin and soft tissue infections, particularly in immunocompromised hosts because it grows at 30°C [72]. It is the second most common cause of cervical lymphadenitis in children [73], and has been reported rarely to cause lymphadenitis in immunocompetent adults [74].

M. haemophilum was identified as the cause of an outbreak of skin and soft tissue infection and cervical lymphadenitis in 12 immunocompetent individuals, which occurred in the setting of application of permanent makeup to the eyebrows performed by a single makeup artist in Switzerland [75].

M. haemophilum is difficult to isolate because it requires special media and conditions (incubation at 30°C) for growth. (See "Microbiology of nontuberculous mycobacteria", section on 'Infrequent or difficult to culture NTM'.)

Mycobacterium simiae — M. simiae has been isolated in the southwestern United States and in other areas of the world such as Israel, Cuba, and western Europe [5,76]. Only a minority of M. simiae respiratory isolates obtained from immune competent hosts are clinically relevant, making interpretation of the clinical significance of M. simiae isolates difficult [76]. Interpreting the clinical significance of M. simiae isolates is especially important due to the extreme difficulty effectively treating true M. simiae lung disease.

Mycobacterium szulgai — M. szulgai has been recovered from environmental sources and isolation is usually associated with preexisting pulmonary conditions such as chronic obstructive lung disease or healed tuberculosis [77]. The isolation of M. szulgai is also usually associated with significant disease.

SUMMARY

Mycobacteria other than Mycobacterium tuberculosis and Mycobacterium leprae are generally free-living organisms that are ubiquitous in the environment (table 1). They have been recovered from surface water, tap water, soil, domestic and wild animals, milk, and food products. These organisms can also inhabit body surfaces or secretions without causing disease. (See 'Introduction' above.)

The most common nontuberculous species causing human disease in the United States are the slowly growing species of the M. avium complex (MAC) and M. kansasii and the rapidly growing M. abscessus complex. Less common human pathogens include the slowly growing species M. marinum, M. xenopi, M. simiae, M. malmoense, and M. ulcerans. (See 'Common pathogenic species' above and 'Mycobacterium avium complex' above and 'Mycobacterium kansasii' above and 'Rapidly growing mycobacteria' above and 'Other nontuberculous mycobacteria' above.)

Although precise estimates of incidence and prevalence of nontuberculous mycobacterial (NTM) disease are difficult to determine, the burden of NTM disease, particularly lung disease, appears to be increasing worldwide. (See 'Frequency of disease' above.)

NTM cause four distinct clinical syndromes:

Progressive pulmonary disease (especially in older persons) caused primarily by MAC, M. abscessus complex, and M. kansasii. M. fortuitum and M. chelonae rarely causing lung disease.

Superficial lymphadenitis, especially cervical lymphadenitis, in children caused mostly by MAC, M. scrofulaceum, and, in northern Europe, M. malmoense and M. haemophilum; the most common cause in adults, however, is M. tuberculosis.

Disseminated disease in severely immunocompromised patients (eg, disseminated MAC in patients with AIDS). (See 'Disseminated disease' above.)

Skin and soft tissue infection usually as a consequence of direct inoculation. (See 'Introduction' above.)

Unlike other NTM, M. kansasii has never been found in soil or natural water supplies but has been recovered consistently from tap water in cities where M. kansasii is endemic. M. kansasii causes pulmonary disease resembling tuberculosis. The major predisposing factor to lung infection is chronic obstructive pulmonary disease (COPD), which is present in over two-thirds of cases; other underlying conditions may include malignancy, immunosuppressive drugs, alcohol abuse, pneumoconiosis, and HIV infection. (See 'Mycobacterium kansasii' above.)

Rapidly growing mycobacteria include three clinically relevant species: M. abscessus, M. chelonae, and M. fortuitum (table 1). Among these, the most important human pathogen is M. abscessus complex. Rapidly growing mycobacterial species are hardy environmental saprophytes widely distributed in nature and able to withstand extremes of temperature and nutritionally spartan environments. (See 'Rapidly growing mycobacteria' above and "Rapidly growing mycobacterial infections: Mycobacteria abscessus, chelonae, and fortuitum".)

  1. Wolinsky E, Rynearson TK. Mycobacteria in soil and their relation to disease-associated strains. Am Rev Respir Dis 1968; 97:1032.
  2. Chapman JS. The ecology of the atypicalmycobacteria. Arch Environ Health 1971; 22:41.
  3. Goslee S, Wolinsky E. Water as a source of potentially pathogenic mycobacteria. Am Rev Respir Dis 1976; 113:287.
  4. Gruft H, Falkinham JO 3rd, Parker BC. Recent experience in the epidemiology of disease caused by atypical mycobacteria. Rev Infect Dis 1981; 3:990.
  5. Griffith DE, Aksamit T, Brown-Elliott BA, et al. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med 2007; 175:367.
  6. Daley CL, Iaccarino JM, Lange C, et al. Treatment of Nontuberculous Mycobacterial Pulmonary Disease: An Official ATS/ERS/ESCMID/IDSA Clinical Practice Guideline. Clin Infect Dis 2020; 71:e1.
  7. Lincoln EM, Gilbert LA. Disease in children due to mycobacteria other than Mycobacterium tuberculosis. Am Rev Respir Dis 1972; 105:683.
  8. Vesterhus P, Holland SM, Abrahamsen TG, Bjerknes R. Familial disseminated infection due to atypical mycobacteria with childhood onset. Clin Infect Dis 1998; 27:822.
  9. Herlin T, Thelle T, Kragballe K, et al. Sustained depression of monocyte cytotoxicity in a boy with disseminated nontuberculous mycobacteriosis. J Pediatr 1981; 99:264.
  10. Winthrop KL, McNelley E, Kendall B, et al. Pulmonary nontuberculous mycobacterial disease prevalence and clinical features: an emerging public health disease. Am J Respir Crit Care Med 2010; 182:977.
  11. Winthrop KL, Baxter R, Liu L, et al. The reliability of diagnostic coding and laboratory data to identify tuberculosis and nontuberculous mycobacterial disease among rheumatoid arthritis patients using anti-tumor necrosis factor therapy. Pharmacoepidemiol Drug Saf 2011; 20:229.
  12. Griffith DE, Aksamit TR. Managing Mycobacterium avium Complex Lung Disease With a Little Help From My Friend. Chest 2021; 159:1372.
  13. Wagner D, Lipman M, Cooray S, et al. Nontuberculous Mycobacterial Disease: A Comprehensive Approach to Diagnosis and Management, Griffith DE (Ed), Humana Press, Switzerland 2019.
  14. Izumi K, Morimoto K, Hasegawa N, et al. Epidemiology of Adults and Children Treated for Nontuberculous Mycobacterial Pulmonary Disease in Japan. Ann Am Thorac Soc 2019; 16:341.
  15. Schildkraut JA, Gallagher J, Morimoto K, et al. Epidemiology of nontuberculous mycobacterial pulmonary disease in Europe and Japan by Delphi estimation. Respir Med 2020; 173:106164.
  16. Lee H, Myung W, Koh WJ, et al. Epidemiology of Nontuberculous Mycobacterial Infection, South Korea, 2007-2016. Emerg Infect Dis 2019; 25:569.
  17. Al-Houqani M, Jamieson F, Mehta M, et al. Aging, COPD, and other risk factors do not explain the increased prevalence of pulmonary Mycobacterium avium complex in Ontario. Chest 2012; 141:190.
  18. Thomson RM, NTM working group at Queensland TB Control Centre and Queensland Mycobacterial Reference Laboratory. Changing epidemiology of pulmonary nontuberculous mycobacteria infections. Emerg Infect Dis 2010; 16:1576.
  19. Winthrop KL, Marras TK, Adjemian J, et al. Incidence and Prevalence of Nontuberculous Mycobacterial Lung Disease in a Large U.S. Managed Care Health Plan, 2008-2015. Ann Am Thorac Soc 2020; 17:178.
  20. Prevots DR, Shaw PA, Strickland D, et al. Nontuberculous mycobacterial lung disease prevalence at four integrated health care delivery systems. Am J Respir Crit Care Med 2010; 182:970.
  21. Adjemian J, Olivier KN, Seitz AE, et al. Prevalence of nontuberculous mycobacterial lung disease in U.S. Medicare beneficiaries. Am J Respir Crit Care Med 2012; 185:881.
  22. Henkle E, Hedberg K, Schafer S, et al. Population-based Incidence of Pulmonary Nontuberculous Mycobacterial Disease in Oregon 2007 to 2012. Ann Am Thorac Soc 2015; 12:642.
  23. Adjemian J, Olivier KN, Prevots DR. Epidemiology of Pulmonary Nontuberculous Mycobacterial Sputum Positivity in Patients with Cystic Fibrosis in the United States, 2010-2014. Ann Am Thorac Soc 2018; 15:817.
  24. Katila ML, Brander E, Backman A. Neonatal BCG vaccination and mycobacterial cervical adenitis in childhood. Tubercle 1987; 68:291.
  25. Romanus V, Hallander HO, Wåhlén P, et al. Atypical mycobacteria in extrapulmonary disease among children. Incidence in Sweden from 1969 to 1990, related to changing BCG-vaccination coverage. Tuber Lung Dis 1995; 76:300.
  26. Wolinsky E. Nontuberculous mycobacteria and associated diseases. Am Rev Respir Dis 1979; 119:107.
  27. Horsburgh RC Jr. Epidemiology of Mycobacterium avium complex. In: Mycobacterium Avium Complex Infection, Korvick JA, Benson CA (Eds), Marcel Dekker, Inc, New York 1996. p.1.
  28. Meissner G, Anz W. Sources of Mycobacterium avium complex infection resulting in human diseases. Am Rev Respir Dis 1977; 116:1057.
  29. Meissner PS, Falkinham JO 3rd. Plasmid DNA profiles as epidemiological markers for clinical and environmental isolates of Mycobacterium avium, Mycobacterium intracellulare, and Mycobacterium scrofulaceum. J Infect Dis 1986; 153:325.
  30. von Reyn CF, Maslow JN, Barber TW, et al. Persistent colonisation of potable water as a source of Mycobacterium avium infection in AIDS. Lancet 1994; 343:1137.
  31. du Moulin GC, Stottmeier KD, Pelletier PA, et al. Concentration of Mycobacterium avium by hospital hot water systems. JAMA 1988; 260:1599.
  32. Marras TK, Wallace RJ Jr, Koth LL, et al. Hypersensitivity pneumonitis reaction to Mycobacterium avium in household water. Chest 2005; 127:664.
  33. Reed C, von Reyn CF, Chamblee S, et al. Environmental risk factors for infection with Mycobacterium avium complex. Am J Epidemiol 2006; 164:32.
  34. Feazel LM, Baumgartner LK, Peterson KL, et al. Opportunistic pathogens enriched in showerhead biofilms. Proc Natl Acad Sci U S A 2009; 106:16393.
  35. Gebert MJ, Delgado-Baquerizo M, Oliverio AM, et al. Ecological Analyses of Mycobacteria in Showerhead Biofilms and Their Relevance to Human Health. mBio 2018; 9.
  36. Edwards LB. Community-wide tuberculin testing study in Pamlico county, North Carolina. Am Rev Respir Dis 1965; 92:43.
  37. Lind A, Larsson LO, Bentzon MW, et al. Sensitivity to sensitins and tuberculin in Swedish children. I. A study of schoolchildren in an urban area. Tubercle 1991; 72:29.
  38. Osman AA, Hakim JG, Lüneborg-Nielsen M, et al. Comparative skin testing with PPD tuberculin, Mycobacterium avium and M. scrofulaceum sensitin in schoolchildren in Saudi Arabia. Tuber Lung Dis 1994; 75:38.
  39. Khan K, Wang J, Marras TK. Nontuberculous mycobacterial sensitization in the United States: national trends over three decades. Am J Respir Crit Care Med 2007; 176:306.
  40. Marras TK, Chedore P, Ying AM, Jamieson F. Isolation prevalence of pulmonary non-tuberculous mycobacteria in Ontario, 1997 2003. Thorax 2007; 62:661.
  41. Edwards LB, Acquaviva FA, Livesay VT, et al. An atlas of sensitivity to tuberculin, PPD-B, and histoplasmin in the United States. Am Rev Respir Dis 1969; 99:Suppl:1.
  42. von Reyn CF, Williams DE, Horsburgh CR Jr, et al. Dual skin testing with Mycobacterium avium sensitin and purified protein derivative to discriminate pulmonary disease due to M. avium complex from pulmonary disease due to Mycobacterium tuberculosis. J Infect Dis 1998; 177:730.
  43. von Reyn CF, Horsburgh CR, Olivier KN, et al. Skin test reactions to Mycobacterium tuberculosis purified protein derivative and Mycobacterium avium sensitin among health care workers and medical students in the United States. Int J Tuberc Lung Dis 2001; 5:1122.
  44. Teirstein AS, Damsker B, Kirschner PA, et al. Pulmonary infection with Mycobacterium avium-intracellulare: diagnosis, clinical patterns, treatment. Mt Sinai J Med 1990; 57:209.
  45. Lim J, Lyu J, Choi CM, et al. Non-tuberculous mycobacterial diseases presenting as solitary pulmonary nodules. Int J Tuberc Lung Dis 2010; 14:1635.
  46. Fordham von Reyn C, Arbeit RD, Tosteson AN, et al. The international epidemiology of disseminated Mycobacterium avium complex infection in AIDS. International MAC Study Group. AIDS 1996; 10:1025.
  47. von Reyn CF, Waddell RD, Eaton T, et al. Isolation of Mycobacterium avium complex from water in the United States, Finland, Zaire, and Kenya. J Clin Microbiol 1993; 31:3227.
  48. von Reyn CF, Barber TW, Arbeit RD, et al. Evidence of previous infection with Mycobacterium avium-Mycobacterium intracellulare complex among healthy subjects: an international study of dominant mycobacterial skin test reactions. J Infect Dis 1993; 168:1553.
  49. Chapman J. The Atypical Mycobacteria, Plenum Publishing, New York 1977.
  50. Steadham JE. High-catalase strains of Mycobacterium kansasii isolated from water in Texas. J Clin Microbiol 1980; 11:496.
  51. Bloch KC, Zwerling L, Pletcher MJ, et al. Incidence and clinical implications of isolation of Mycobacterium kansasii: results of a 5-year, population-based study. Ann Intern Med 1998; 129:698.
  52. Marks J. "Opportunist" mycobacteria in England and Wales. Tubercle 1969; 50:Suppl:78.
  53. Johanson WG Jr, Nicholson DP. Pulmonary disease due to Mycobacterium Kansasii. An analysis of some factors affecting prognosis. Am Rev Respir Dis 1969; 99:73.
  54. Lillo M, Orengo S, Cernoch P, Harris RL. Pulmonary and disseminated infection due to Mycobacterium kansasii: a decade of experience. Rev Infect Dis 1990; 12:760.
  55. Bamberger DM, Driks MR, Gupta MR, et al. Mycobacterium kansasii among patients infected with human immunodeficiency virus in Kansas City. Kansas City AIDS Research Consortium. Clin Infect Dis 1994; 18:395.
  56. Shitrit D, Baum GL, Priess R, et al. Pulmonary Mycobacterium kansasii infection in Israel, 1999-2004: clinical features, drug susceptibility, and outcome. Chest 2006; 129:771.
  57. Park S, Suh GY, Chung MP, et al. Clinical significance of Mycobacterium fortuitum isolated from respiratory specimens. Respir Med 2008; 102:437.
  58. Baker AW, Lewis SS, Alexander BD, et al. Two-Phase Hospital-Associated Outbreak of Mycobacterium abscessus: Investigation and Mitigation. Clin Infect Dis 2017; 64:902.
  59. Rahav G, Pitlik S, Amitai Z, et al. An outbreak of Mycobacterium jacuzzii infection following insertion of breast implants. Clin Infect Dis 2006; 43:823.
  60. Bryant JM, Grogono DM, Greaves D, et al. Whole-genome sequencing to identify transmission of Mycobacterium abscessus between patients with cystic fibrosis: a retrospective cohort study. Lancet 2013; 381:1551.
  61. Wayne LG, Sramek HA. Agents of newly recognized or infrequently encountered mycobacterial diseases. Clin Microbiol Rev 1992; 5:1.
  62. Aubry A, Chosidow O, Caumes E, et al. Sixty-three cases of Mycobacterium marinum infection: clinical features, treatment, and antibiotic susceptibility of causative isolates. Arch Intern Med 2002; 162:1746.
  63. Lewis FM, Marsh BJ, von Reyn CF. Fish tank exposure and cutaneous infections due to Mycobacterium marinum: tuberculin skin testing, treatment, and prevention. Clin Infect Dis 2003; 37:390.
  64. Lillis JV, Ansdell VE, Ruben K, et al. Sequelae of World War II: an outbreak of chronic cutaneous nontuberculous mycobacterial infection among Satowanese islanders. Clin Infect Dis 2009; 48:1541.
  65. Andréjak C, Lescure FX, Pukenyte E, et al. Mycobacterium xenopi pulmonary infections: a multicentric retrospective study of 136 cases in north-east France. Thorax 2009; 64:291.
  66. van Ingen J, Boeree MJ, de Lange WC, et al. Mycobacterium xenopi clinical relevance and determinants, the Netherlands. Emerg Infect Dis 2008; 14:385.
  67. Jenkins PA, Campbell IA, Research Committee of The British Thoracic Society. Pulmonary disease caused by Mycobacterium xenopi in HIV-negative patients: five year follow-up of patients receiving standardised treatment. Respir Med 2003; 97:439.
  68. Astagneau P, Desplaces N, Vincent V, et al. Mycobacterium xenopi spinal infections after discovertebral surgery: investigation and screening of a large outbreak. Lancet 2001; 358:747.
  69. Ziza JM. [Lessons in medicine: apropos of a modern epidemic of Mycobacterium xenopi spondylodiscitis]. Rev Med Interne 1997; 18:845.
  70. Salliot C, Desplaces N, Boisrenoult P, et al. Arthritis due to Mycobacterium xenopi: a retrospective study of 7 cases in France. Clin Infect Dis 2006; 43:987.
  71. Falkinham JO 3rd, Norton CD, LeChevallier MW. Factors influencing numbers of Mycobacterium avium, Mycobacterium intracellulare, and other Mycobacteria in drinking water distribution systems. Appl Environ Microbiol 2001; 67:1225.
  72. Saubolle MA, Kiehn TE, White MH, et al. Mycobacterium haemophilum: microbiology and expanding clinical and geographic spectra of disease in humans. Clin Microbiol Rev 1996; 9:435.
  73. Cohen YH, Amir J, Ashkenazi S, et al. Mycobacterium haemophilum and lymphadenitis in immunocompetent children, Israel. Emerg Infect Dis 2008; 14:1437.
  74. Minani TJ, Saubolle MA, Yu E, Sussland Z. Mycobacterium haemophilum as a novel etiology of cervical lymphadenitis in an otherwise healthy adult patient. J Clin Microbiol 2010; 48:2636.
  75. Giulieri S, Morisod B, Edney T, et al. Outbreak of Mycobacterium haemophilum infections after permanent makeup of the eyebrows. Clin Infect Dis 2011; 52:488.
  76. van Ingen J, Boeree MJ, Dekhuijzen PN, van Soolingen D. Clinical relevance of Mycobacterium simiae in pulmonary samples. Eur Respir J 2008; 31:106.
  77. van Ingen J, Boeree MJ, de Lange WC, et al. Clinical relevance of Mycobacterium szulgai in The Netherlands. Clin Infect Dis 2008; 46:1200.
Topic 5344 Version 22.0

References

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟