The first Saudi Arabian national inventory study revealed the upcoming challenges of highly diverse non-tuberculous mycobacterial diseases

Abstract

BackgroundIncidences of nontuberculous mycobacteria (NTM) causing pulmonary and extrapulmonary diseases are reportedly increasing globally and the current epidemiologic situation in Saudi Arabia remains unclear. To study such trend, we carried out a nationwide systematic epidemiological study focusing on NTM diseases for the first time in the country.Methods/Principle findingsA nationwide collection of NTM isolates with clinical and demographical data was conducted for a period of 24 months. Primary species identification was carried out by line probe assays followed by sequencing of 16S rRNA, 16S-23S ITS region, rpoB and hsp65 genes. The laboratory findings were comprehensively analysed against demographical and clinical data. A total of 527 isolates were enrolled with a higher proportion of Saudi citizens (76.5%), elderly (>60 years) patients (34.2%), and male gender (65.3%) respectively. Overall, 75.1% isolates were pulmonary origin with a proven clinical significance of 44.7%. In total, 34 NTM species including 17 rare species were identified, in addition to 8 ‘undefined’ isolates. M.simiae (22.6%), M.fortuitum (18.1%) and M.abscessus (17.8%) were predominant species. Interestingly, 27 new cases of clinically relevant M.riyadhense were also noticed (Primary data on emergence of rare NTM species and M.riyadhense has been recently reported). Results showed, rare clinical events such as mycobacteremia, cecum abscess, peritonitis and ascites caused by M.wolinskyi, M.holsaticum, M.duvalii and M.monacence respectively. Diabetes mellitus (P value-0.04) and previous history of tuberculosis (P value- 0.001) were identified as independent risk factors associated with NTM diseases.Conclusions/SignificanceNTM disease spectrum and pathogen diversity is an emerging challenge to any nation, including Saudi Arabia. Therefore, more priorities will be given to NTM’s with an immediate initiative to develop diagnostic infrastructures and disease management plans.

Diversity of Nontuberculous Mycobacteria in Kuwait: Rapid Identification and Differentiation of <b><i>Mycobacterium</i></b> Species by Multiplex PCR, INNO-LiPA Mycobacteria v2 Assay and PCR Sequencing of rDNA

“…The distribution of NTM species is not uniform either, as marked geographic variability has been noted both with regard to the prevalence of NTM lung disease and with regard to the NTM species causing these infections [2, 5, 12, 20]. The susceptibility of NTM to anti-TB drugs and other antibiotics varies markedly even among members belonging to the same species/species complex which necessitates different treatment strategies for NTM infections and in vitro susceptibility does not always correlate with effective in vivo response to antibiotics [2, 5, 20].…”

“…Altogether 11 previously reported and 2 novel species were identified among 53 NTM isolates in Kuwait with M. fortuitum ( n = 12), M. kansasii ( n = 10), M. abscessus ( n = 7), M. intracellulare ( n = 7), and M. avium ( n = 4) being the most frequently isolated species. While M. avium and M. intracellulare are the most commonly isolated NTM in several countries [5, 10, 20, 25, 26], M. fortuitum was also the most common or second most common NTM species in Iran and Saudi Arabia [10, 12, 27]. Interestingly, M. simiae , another common NTM in Saudi Arabia [12], was not detected in Kuwait.…”

“…While M. avium and M. intracellulare are the most commonly isolated NTM in several countries [5, 10, 20, 25, 26], M. fortuitum was also the most common or second most common NTM species in Iran and Saudi Arabia [10, 12, 27]. Interestingly, M. simiae , another common NTM in Saudi Arabia [12], was not detected in Kuwait. The high recovery of M. fortuitum from pulmonary specimens ( n = 8) could be attributed to the use of liquid culture (MGIT) applied for cultivation as it has been shown to enhance the diagnosis of patients with an even milder form of NTM lung disease [26].…”

“…The second (M. kansasii) and third (M. abscessus) most commonly isolated NTM in Kuwait are also among the most frequently isolated pulmonary NTM pathogens from several countries including USA, several European countries, Saudi Arabia, South Korea, and China [6, 7, 10, 12, 25, 26]. Interestingly, M. kansasii and M. abscessus are among the relatively more virulent species of NTM which are frequently associated with pulmonary infections, particularly when they are isolated repeatedly from patients with symptoms of pneumonia [6, 7, 20, 28].…”

“…Most epidemiological studies of NTM have been performed in developed countries including Japan, Australia, and countries in North America and Europe [4-7, 9]. The epidemiology of NTM infections from Saudi Arabia has recently shown highly diverse diseases involving common and rare species of NTM [10-12]; however, only scant information is available from Kuwait and other Arabian Gulf countries [13, 14]. In Kuwait, nearly 800 mycobacterial infections are diagnosed every year [15, E. Mokaddas, unpublished data].…”