|Year : 2015 | Volume
| Issue : 1 | Page : 7-17
Nontuberculous mycobacteria in Middle East: Current situation and future challenges
Ali Akbar Velayati1, Sanaz Rahideh1, Zahra Derakhshani Nezhad1, Parissa Farnia1, Mehdi Mirsaeidi2
1 Mycobacteriology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
2 Division of Pulmonary, Critical Care, Sleep and Allergy, University of Illinois at Chicago, USA
|Date of Web Publication||21-Feb-2017|
Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine M/C 719, University of Illinois at Chicago, 840 S. Wood St., Chicago, IL 60612-7323
Source of Support: None, Conflict of Interest: None
Nontuberculous mycobacteria (NTM) are a diverse group of bacterial species that are distributed in the environment. Many of these environmental bacteria can cause disease in humans. The identification of NTM in environmental sources is important for both clinical and epidemiological purposes. In this study, the distribution of NTM species from environmental and clinical samples in the Middle East was reviewed. In order to provide an overview of NTM, as well as recent epidemiological trends, all studies addressing NTM in the Middle East from 1984 to 2014 were reviewed.
A total of 96 articles were found, in which 1751 NTM strains were isolated and 1084 of which were obtained from clinical samples, 619 from environmental samples and 48 were cited by case reports.
Mycobacterium fortuitum was the most common rapid growing mycobacteria (RGM) isolated from both clinical (269 out of 447 RGM; 60.1%) and environmental (135 out of 289 RGM; 46.7%) samples. Mycobacterium avium complex (MAC) was the most common slow growing mycobacteria (SGM) isolated from clinical samples (140 out of 637 SGM; 21.9%). An increasing trend in NTM isolation from the Middle East was noted over the last 5 years. This review demonstrates the increasing concern regarding NTM disease in the Middle East, emphasizing the need for regional collaboration and coordination in order to respond appropriately.
Keywords: Nontuberculous mycobacteria (NTM), Middle East, Environmental samples, Clinical samples
|How to cite this article:|
Velayati AA, Rahideh S, Nezhad ZD, Farnia P, Mirsaeidi M. Nontuberculous mycobacteria in Middle East: Current situation and future challenges. Int J Mycobacteriol 2015;4:7-17
|How to cite this URL:|
Velayati AA, Rahideh S, Nezhad ZD, Farnia P, Mirsaeidi M. Nontuberculous mycobacteria in Middle East: Current situation and future challenges. Int J Mycobacteriol [serial online] 2015 [cited 2020 Aug 14];4:7-17. Available from: http://www.ijmyco.org/text.asp?2015/4/1/7/200593
| Introduction|| |
Nontuberculous mycobacteria (NTM) have been recognized as a diverse group of organisms that are ubiquitous in environmental sources . In most regions of the world, NTM are not reportable public health diseases, so epidemiological data are not easily available . However, data in published studies note increasing trends in the rate of NTM isolation from different geographic regions in the world. Increasing NTM isolation may have important public health implications . Exposure to these organisms can cause serious infections in both immunocompetent and immunocompromised individuals . According to the latest report released by WHO, about 35.3 million people in the world are living with HIV/AIDS, which represents one of the most vulnerable populations to NTM infection, as well as a higher risk for complications and poor disease outcomes . Those receiving immunosuppressive therapy secondary to organ transplantation, cancer, autoimmune disease and those with diabetes mellitus may also be more susceptible to NTM as compared with the general population, as well as suffer more severe diseases. The incidence of NTM infections is growing all over the world. Although countries in the Middle East have increasingly reported NTM diseases , no comprehensive study of NTM distribution has been conducted in this region. The purpose of this review is to piece together clinical and environmental NTM data reported in peer-reviewed published literature in Middle Eastern countries over the last 30 years.
| Methods|| |
Literature search strategy
This study was conducted by reviewing published literature from the Middle East using PubMed and Scopus for NTM during the study period 1984–2014 using search terms “atypical mycobacteria” [MeSH] AND “Middle East” [MeSH] OR “nontuberculous mycobacteria” [MeSH] AND “Middle East” [MeSH] OR “environmental mycobacteria” [MeSH] AND “Middle East” [MeSH].
Inclusion and exclusion criteria
Original articles that presented cross-sectional or cohort studies and reported the incidence of NTM in the Middle East were considered. Congress abstracts and studies using non-standard methods were excluded.
Data extraction and definitions
For all studies, the following data were extracted: year of publication, study setting, studies enroll time, and number of patients investigated. Inconsistencies between the reviewers were discussed to obtain consensus.
The present study search strategy aimed to identify all available published studies that reported data on the incidence of NTM in the Middle East. A total of 379 articles were identified.
Although 298 irrelevant subjects were excluded, after full text evaluation, 96 papers (original and case report articles) describing the incidence of NTM in the Middle East countries were selected for analysis.
Countries included in the study
Countries were divided in two groups: Middle East countries and Eastern neighbors of Iran (Afghanistan, Pakistan). Data were provided from 11 countries, including Iran (34 articles) ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, Turkey (21 articles) ,,,,,,,,,,,,,,,,,,,,, Saudi Arabia (18 articles) ,,,,,,,,,,,,,,,,,, Lebanon (5 articles) ,,,, Qatar (4 articles) ,,, Pakistan (4 articles) ,,, Iraq (3 articles) ,, Egypt (2 articles) ,, Bahrain (2 articles) ,, Kuwait (2 article) ,, and Oman (1 article) . No NTM data was reported in the remaining Middle Eastern countries, including Jordan, the United Arab Emirates, Syria, Yemen and Afghanistan.
| Results|| |
Out of the 96 articles identified in the search, 48 were original articles and the remaining were case reports. From 48 original articles, 20 studies were conducted in Iran and 13 in Turkey. The remaining reports were obtained from Pakistan (3), Lebanon (3), Saudi Arabia (3), Iraq (3), Egypt (1), Kuwait (1) and Oman (1).
In total, 1751 NTM strains were isolated from the original studies and case reports during the study period. Among the 1751 NTM isolates, 1084 were obtained from clinical samples, 619 from environmental samples and 48 were cited by case reports. The majority of NTM strains were isolated from respiratory specimens, followed by skin lesions, urogenital and cerebrospinal fluid. According to included studies, identification of NTM by conventional techniques were the most frequently used methods.
NTM in clinical samples
Out of the 1084 isolated strains from the clinical original studies, 434 (40.0%) were reported from Iran, 280 (25.8%) from Turkey, 137 (12.6%) from Saudi Arabia, 116 (10.7%) from Pakistan, 47 (4.3%) from Egypt, 43 (3.9%) from Lebanon, 14 (1.2%) from Kuwait and 13 (1.1%) from Oman ([Table 1]). Among the 1084 NTM isolates from clinical samples, 637 (58.7%) were categorized as slow growing Mycobacterium (SGM) and 447 (41.2%) were rapidly growing Mycobacterium (RGM). The most common SGM in clinical samples was Mycobacterium avium complex (MAC) (140 out of 637; 21.9%). The SGM were found in 245 (56.4%) out of 434 NTM isolates of clinical samples from Iran, 177 (63.2%) out of 280 NTM isolates from Turkey, 47 (34.3%) out of 137 NTM isolates from Saudi Arabia and 69 (59.4%) out of 116 NTM isolates from Pakistan.
|Table 1: Species distribution of clinical NTM isolated in articles reported from the Middle East.|
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The most common RGM isolated from clinical samples was Mycobacterium fortuitum (269 out of 447 RGM; 60.1%). M. fortuitum was found in 136 (71.9%) out of 189 RGM isolates from Iran, 49 (54.4%) out of 90 from Saudi Arabia, 48 (46.6%) out of 103 from Turkey, and 23 (48.9%) out of 47 from Pakistan. The species of the most common NTM isolates, the source of isolation and the country of origin are shown in [Table 2].
|Table 2: The most frequently clinical NTM species in articles of the Middle East.|
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NTM in environmental samples
A total of 619 environmental NTM isolates were reported from studies from the Middle East in the last 30 years. Of these isolates, 330 (53.3%) NTM species were SGM and 289 (46.6%) were RGM. Out of 619, 271 (43.7%) isolates were reported from Iran, 271 (43.7%) from Iraq, 62 (10.0%) from Turkey and 15 (2.4%) from Saudi Arabia ([Table 3]).
|Table 3: Species distribution of environmental NTM in articles reported from the Middle East.|
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The most common SGM by country was as follows: Mycobacterium flavescens in Iran (44 out of 271 SGM; 16.2%), Mycobacterium lentiflavum in Turkey (20 out of 62 SGM; 32.2%) and MAC in Iraq (40 out of 271 SGM; 14.7%) ([Table 3]).
A total of 289 NTM isolates were considered belonging to RGM. The most common RGM isolated from environmental samples was M. fortuitum (135; 46.7%), followed by Mycobacterium chelonae (91; 31.4%) and Mycobacterium abscessus (39; 13.4%).
As shown in [Table 4], the most common NTM isolated from soil and water samples was M. fortuitum. [Table 5] shows the frequency of the most RGM and SGM in different countries. There was no information available regarding environmental NTM from Israel, Pakistan, Egypt and Lebanon.
A total of 48 case reports of NTM were published from Middle Eastern countries, including 15 (31.2%) from Saudi Arabia, 14 (29.1%) from Iran, 8 (16.6%) from Turkey, 4 (8.3%) from Qatar, and the remaining from Lebanon, Bahrain, Pakistan, Kuwait and Egypt ([Table 6]). The case reports were published during the study period beginning in the year 2000 through 2014. The isolated NTM species and infected organs in the case report articles are shown in [Table 6].
Trends of NTM isolates
Together, 1751 NTM isolates were reported in the Middle East, including 1084 isolates from clinical samples, 619 from environmental samples and 48 from the case reports. The highest number of NTM was isolated from Iran and Turkey. The distribution of published clinical and environmental data is shown in [Figure 1]. Also, according to this study, there was an increasing trend in the number of NTM from clinical samples. Before 2000, less than 100 NTM isolates were reported from the Middle East countries. In the following years, the total number of NTM isolates increased rapidly in this region, showing a rise in the number of NTM reports.
|Figure 1: Distribution of published clinical and environmental data from the Middle East countries.|
Click here to view
| Discussion|| |
NTM infections are an increasing public health problem in many countries in the world. These environmental bacteria are capable of causing serious illnesses in both immunocompetent and immunocompromised individuals . The relatively few studies addressing this growing public health problem in the Middle Eastern countries is also a concern. Lack of awareness among physicians and microbiologists, limited laboratory facilities and the already overwhelmed health systems from other endemic diseases are possible explanations for the lack of NTM data in the Middle East. The absence of information regarding the distribution of NTM poses significant challenges for infection control strategies . Therefore, understanding the trends and true prevalence of NTM is one of the major priorities to optimize infection control programs and resources.
This study is the first review from the Middle Eastern countries describing the identification of NTM species from clinical and environmental samples. The increasing trends of NTM prevalence are notable in this study, which has important public health, healthcare system and policy implications in the region. For example, the similar clinical presentation of NTM to the well-established tuberculosis (TB) presents unique challenges in diagnosis and management. NTM can be easily misdiagnosed as TB and multidrug-resistant TB, resulting in inappropriate management. Misdiagnosis and delay in diagnosis of NTM can lead to serious morbidity and mortality ,.
Different methods were used for the identification of NTM in many countries. Most laboratories use conventional methods. In more recent reports, improved molecular methods resulted in the ability to identify more NTM species . National laboratories still need to standardize NTM protocols for diagnostic methods and management in most Middle Eastern countries.
Among the 1,084 NTM isolates from clinical samples in the Middle East, 58.7% were SGM and 41.2% were RGM. MAC and M. fortuitum were the most SGM and RGM, respectively. M. fortuitum is widely distributed in soil and water ,. This organism was first identified by Da Costa Cruz isolated from a skin abscess in 1938 . The clinical presentation of M. fortuitum includes various clinical manifestations, including most commonly skin and soft-tissue infections . The clinical diagnosis of RGM is difficult due to the absence of biochemical features . The prevalence of M. fortuitum in European countries has been reported previously 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%) ,. M. fortuitum was the most common RGM found in Iran and Turkey . According to this analysis, M. fortuitum was the most common species among the clinical isolates in the Middle East countries, including Iran.
SGM contain highly pathogenic species. MAC is a pathogen that may cause pulmonary disease, particularly in elderly women . Disseminated MAC disease may occur in immunocompromised patients, particularly HIV-infected persons. It is estimated that more than 500,000 people living in the Middle East are infected with HIV . Therefore, it could be speculated that MAC infection could increase in the Middle East in the near future. Studies suggest that the prevalence of MAC has increased in the United States, Europe and South Korea . Mycobacterium simiae is another SGM that lives in the environment; tap water is thought to be the main source of this Mycobacterium . M. simiae has been identified in various countries, such as France, Germany and Thailand, but most isolates have come from the Southern United States, Cuba and Israel ,,.
Based on this review, M. simiae was the second most prevalent SGM in clinical samples ([Table 1]). The majority of M. simiae strains were reported from Iran. Baghaei et al. recently reviewed 26 Persian patients with pulmonary M. simiae infection from a national referral TB hospital.
The third most common SGM in clinical isolates in the Middle East was Mycobacterium kansasii. Clinical and antigenic characteristics of M. kansasii make it the most similar bacteria to MTB. The geographic areas with the highest reported cases of M. kansasii are the central and southern states of the United States, England, Wales and mining areas from Continental Europe, mainly in the Czech Republic . In Spain, the most frequent NTM pulmonary disease is caused by M. kansasii. .
Mycobacterium gordonae was isolated from 9.4% of clinical samples ([Table 1]). The isolation of M. gordonae from environmental samples suggests that it may cause colonization and contamination of clinical samples ,. True infections with M. gordonae rarely occurs.
Mycobacterium xenopi belongs to a group of SGM that is widely distributed in various regions of Europe and Canada, but it is an uncommon pathogen of pulmonary disease in Asia ,,,. Identification of M. xenopi has increased globally during a 20-year period . In the present study, M. xenopi was the most frequently isolated SGM from clinical samples from Pakistan.
The present review indicates that the NTM incidence is rising in most geographical areas in the Middle East. The increasing number of NTM infections in Iraq, Saudi Arabia, Turkey and Iran may be caused by the increasing awareness of NTM and improvements in diagnosis methods . It is also possible that people in these countries are more susceptible to NTM infection.
Regarding environmental NTM, this review revealed that M. fortuitum (21.8%), M. chelonae (14.7%) and MAC (7.9%) were the most common species. The rapidly growing organisms, such as M. chelonae and M. fortuitum, are common in the environment and in hospital settings ,,. RGM are extremely resistant to antibiotics, antiseptics and disinfectants and, consequently, are significant nosocomial pathogens. Surgical procedures, accidental trauma or injections are also considered as risk factors for infections involving these organisms .
Similar to clinical samples, M. fortuitum was the most common species among RGM species obtained from environmental samples ([Table 3]). This finding strengthens the hypothesis that M. fortuitum is transmitted from nature to humans. Consequently, the probability of NTM transmission from person to person should be questioned. Among SGM isolates, MAC was the most common and M. flavescens placed second in environmental samples.
| Conclusion|| |
The number of NTM isolates has significantly increased in the Middle East. There is an increasing concern about NTM disease in the Middle East, and regional collaboration and coordination is needed to respond to it appropriately.
| Conflict of interests|| |
The authors have no conflicts of interests to declare related to this manuscript.
| Acknowledgements|| |
This study was supported by the Mycobacteriology Research Center of Masih Daneshvari Hospital. The authors would like to send their appreciation to Dr. Marybeth Allen for her great editorial comments. Mehdi Mirsaeidi MD is supported by NIH grant 5 T32 HL 82547-7. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]
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