title: Study of Mycobacterium tuberculosis complex genotypic diversity in Malaysia reveals a predominance of ancestral East-African-Indian lineage with a Malaysia-specific signature.
abstract: BACKGROUND
  Tuberculosis (TB) still constitutes a major public health problem in Malaysia. The identification and genotyping based characterization of Mycobacterium tuberculosis complex (MTBC) isolates causing the disease is important to determine the effectiveness of the control and surveillance programs.
  
  
  OBJECTIVE
  This study intended a first assessment of spoligotyping-based MTBC genotypic diversity in Malaysia followed by a comparison of strains with those prevailing in neighboring countries by comparison with an international MTBC genotyping database.
  
  
  METHODS
  Spoligotyping was performed on a total of 220 M. tuberculosis clinical isolates collected in Kelantan and Kuala Lumpur. The results were compared with the SITVIT2 international database of the Pasteur Institute of Guadeloupe.
  
  
  RESULTS
  Spoligotyping revealed 77 different patterns: 22 corresponded to orphan patterns while 55 patterns containing 198 isolates were assigned a Spoligo International Type (SIT) designation in the database (the latter included 6 newly created SITs). The eight most common SITs grouped 141 isolates (5 to 56 strains per cluster) as follows: SIT1/Beijing, n = 56, 25.5%; SIT745/EAI1-SOM, n = 33, 15.0%; SIT591/EAI6-BGD1, n = 13, 5.9%; SIT256/EAI5, n = 12, 5.5%; SIT236/EAI5, n = 10, 4.6%; SIT19/EAI2-Manila, n = 9, 4.1%; SIT89/EAI2-Nonthaburi, n = 5, 2.3%; and SIT50/H3, n = 3, 1.4%. The association between city of isolation and lineages was statistically significant; Haarlem and T lineages being higher in Kuala Lumpur (p<0.01). However, no statistically significant differences were noted when comparing drug resistance vs. major lineages, nor between gender and clades.
  
  
  CONCLUSIONS
  The ancestral East-African-Indian (EAI) lineage was most predominant followed by the Beijing lineage. A comparison of strains with those prevailing in neighboring countries in South Asia, East Asia and South East Asia underlined the phylogeographical specificity of SIT745 for Malaysia, and its probable ongoing evolution with locally evolved strains sharing a specific signature characterized by absence of spacers 37, 38, and 40. Pending complementary genotyping confirmation, we propose that SIT745/EAI-SOM is tentatively reclassified as SIT745/EAI-MYS.
authors.affiliation: Department of Medical Microbiology & Parasitology, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Kelantan, Malaysia.
authors.forename: Fazli
authors.initials: F
authors.lastname: Ismail
authors.affiliation: WHO Supranational TB Reference Laboratory, Institut Pasteur de la Guadeloupe, Abymes, Guadeloupe, France.
authors.forename: David
authors.initials: D
authors.lastname: Couvin
authors.affiliation: Department of Medical Microbiology & Parasitology, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Kelantan, Malaysia.
authors.forename: Izzah
authors.initials: I
authors.lastname: Farakhin
authors.affiliation: Department of Medical Microbiology & Parasitology, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Kelantan, Malaysia.
authors.forename: Zaidah
authors.initials: Z
authors.lastname: Abdul Rahman
authors.affiliation: WHO Supranational TB Reference Laboratory, Institut Pasteur de la Guadeloupe, Abymes, Guadeloupe, France.
authors.forename: Nalin
authors.initials: N
authors.lastname: Rastogi
authors.affiliation: Department of Medical Microbiology & Parasitology, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Kelantan, Malaysia.
authors.forename: Siti
authors.initials: S
authors.lastname: Suraiya
mesh_terms: D001208:Asia; D015373:Bacterial Typing Techniques; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008296:Malaysia; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000472:pathogenicity; D058974:Phylogeography; D014376:Tuberculosis / Q000235:genetics* / Q000382:microbiology* / Q000473:pathology