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Background: Saudi Arabia annually reports a relatively higher proportion (28–32%) of extrapulmonary tuberculosis (EPTB) cases in comparison to other global regions. However, there were few studies conducted so far to determine the sociodemographic factors and clinical manifestations associated with EPTB at a nationwide level. Methodology: A retrospective analysis on culture positive EPTB isolates collected from all the provinces of the country were conducted for a period of 12 months to determine the spectrum of diversity in EPTB infection sites and the confounding factors. A detailed clinical and demographical data analysis was carried out along with first line drug susceptibility testing. Principal Findings: Intra-thoracic and extra-thoracic lymph nodes (44.6%) were the most common sites of infection followed by gastrointestinal (17.3%) and central nervous systems (11.8%). Male patients were mostly infected (58.8%), in contrary to the global trend. Any drug resistance was observed in 23.1% isolates with a 2.1% of multi-drug resistance. HIV reactivity was found only in 2.2% cases. A higher proportion of Saudi nationals (58.8%) were infected compared to the immigrants, descending mostly from South Asia (34.4%) and South East Asia (31.2%). The Saudi population predominated with all forms of EPTB while immigrants showed no significant variations. Conclusions: Saudi Arabia faces a serious threat from EPTB, particularly to the central nervous system and gastrointestinal systems. More effective diagnostic strategies and control measures must be implemented to reduce the high rate of EPTB in the country. In addition, these findings warrant further detailed research to explore all related comorbid conditions of EPTB development, particularly the host-related factors. [ABSTRACT FROM AUTHOR]

Background: Bacillus Calmette Guerin (BCG) is the only available vaccine for tuberculosis (TB). Low grade complications in healthy recipients and disseminated vaccine associated complications among immuno-suppressed individuals were noticed globally after administration. Recently a series of clinically suspected BCG associated suppurative and non-suppurative lymphadenitis cases were reported from different regions of Saudi Arabia. However a molecular confirmative analysis was lacking to prove these claims. Methodology: During 2009–2010, 42 Mycobacterium bovis BCG suspected clinical isolates from children diagnosed with suppurative lymphadenitis from different provinces of the country were collected and subjected to 24 loci based MIRU-VNTR typing, spoligotyping and first line anti-TB drugs susceptibility testing. Principal Findings: Of the total 42 cases, 41 (97.6%) were Saudi nationals and particularly male (64.3%). Majority of the cases were aged below 6 months (83.3%) with a median of age 4 months. All the enrolled subjects showed left axillary mass which suppurated in a median of 4 months after vaccination. Among the study subjects, 1 (2.4%) case was reactive to HIV antigen and 2 (4.8%) case had severe combined immunodeficiency. Genotyping results showed that, 41 (97.6%) isolates were identical to the vaccine strain Danish 1331 and one to Tokyo 172-1. Phylogenetic analysis revealed all the Danish 1331 isolates in a single cluster. Conclusion: Elevated proportion of suppurative lymphadenitis caused by M. bovis BCG reported in the country recently is majorly related to the vaccine strain Danish 1331. However lack of nationwide data on real magnitude of BCG related adverse events warrants population centric, long term future studies. [ABSTRACT FROM AUTHOR]

Background: Non-Tuberculous Mycobacteria (NTM) are emerging around the world due to a higher prevalence of immunosuppressive illness and therapy. Saudi Arabia is not an exception as there have been novel mycobacterial species also identified. In addition, several published case reports from different parts of the country suggest a growing pathogenic potential of NTM. As the first nationwide study, we sought to gain an insight into the species diversity of NTM clinical isolates. Methodology/Principal findings: During June 2009–July 2010, 95 clinical isolates were collected from tuberculosis reference laboratories in major provinces within Saudi Arabia and subjected to standard line probe assay techniques to identify their species. Diagnostic guidelines of the American Thoracic Society were applied to determine the clinical relevance of respiratory isolates. Species diversity (13 species) was very high and dominated (61.0%) by rapid growing NTM. The major species obtained were Mycobacterium abscessus, M. fortuitum, M. intracellulare followed by M. kansassi, M. gordanae and M. avium. Interestingly this study reports for the first time the clinical relevance of M. celatum, M. xenopi, M. scrofulceum, M. lentiflavum, M. asiaticum and M. simiae in Saudi Arabia. Of the total, 67.1% were clinically relevant respiratory cases, 23.2% were non-respiratory cases and 9.7% were respiratory colonizers. Coexisting illness was reported in 53.7% of the studied cases. The major risk factors observed among the patients were previous history of tuberculosis, chronic obstructive pulmonary disorder and human immunodeficiency virus infection. Conclusion/Significance: The high rates of clinically confirmed respiratory cases suggest that NTM infections are indeed a new challenge to health authorities. The current findings show an opposite picture of the Western world where M. avium complex and particularly slow growing NTM are the most predominant respiratory pathogens. The complexity of species demands an immediate strengthening of the current diagnostic facilities. Author Summary: Non-Tuberculous Mycobacteria (NTM) are opportunistic human pathogens. Global reports show an emergence of various NTM diseases among immuno-suppressed as well as immuno-competent individuals. In Saudi Arabia, data are scarce on the prevalence of NTM and their genetic diversity. Currently, NTM infections are neglected in the country and the real magnitude of problems is still masked. As the first study of its type to be conducted in Saudi Arabia, we sought to explore the species spectrum of NTM by utilizing a nationwide collection of clinical isolates. The NTM species diversity is large and shows a different trend compared to Western countries as rapidly growing mycobacterial species are the most prevalent to cause diseases in the country. A large number of clinically relevant pulmonary cases show high pathogenic potential of NTM. Indeed, timely identification of mycobacterial species will lead to adapting an appropriate therapy and supports the implementation of control policies which is urgently needed in the country. [ABSTRACT FROM AUTHOR]

Background:Eastern province of Saudi Arabia is an industrial zone with large immigrant population and high level of tuberculosis case notification among immigrants. The impact of immigration and current trends of tuberculosis transmission among immigrants and autochthonous population in the region had not been investigated so far using molecular tools. Methodology:During 2009- 2011, a total of 524 Mycobacterium tuberculosis isolates were collected from the central tuberculosis reference laboratory, representing an estimated 79.2% of the culture-positive tuberculosis cases over the study period in the province. These isolates were genotyped by using 24 locus-based MIRU-VNTR typing and spoligotyping followed by first line drug susceptibility testing. The molecular clustering profiles and phylogenetic diversity of isolates were determined and compared to the geographical origins of the patients. Principle Findings:Genotyping showed an overall predominance of Delhi/CAS (29.4%), EAI (23.8%) and Ghana (13.3%) lineages, with slightly higher proportions of Delhi/CAS among autochthonous population (33.3 %) and EAI (30.9%) among immigrants. Rate of any drug resistance was 20.2% with 2.5% of multi-drug resistance. Strain cluster analysis indicated 42 clusters comprising 210 isolates, resulting in a calculated recent transmission index of 32.1%. Overall shared cluster ratio was 78.6% while 75.8% were shared between autochthonous population and immigrant population with a predominance of immigrants from South east Asia (40.7%). In contrast, cross national transmission within the immigrant population was limited (24.2%). Younger age (15-30- p value-0.043, 16-45, p value 0.030), Saudi nationality (p value-0.004) and South East Asian origin (p value-0.011) were identified as significant predisposing factors for molecular strain clustering. Conclusions:The high proportion of molecular clusters shared among the autochthonous and immigrant populations suggests a high permeability of tuberculosis transmission between both populations in the province. These results prompt for the need to strengthen the current tuberculosis control strategies and surveillance programs. [ABSTRACT FROM AUTHOR]