title: The Mycobacterium tuberculosis Uganda II family and resistance to first-line anti-tuberculosis drugs in Uganda.
abstract: BACKGROUND
  The global increase in the burden of multidrug-resistant tuberculosis (MDR-TB) underscores an urgent need for data on factors involved in generation and spread of TB drug resistance. We performed molecular analyses on a representative sample of Mycobacterium tuberculosis (MTB) isolates. Basing on findings of the molecular epidemiological study in Kampala, we hypothesized that the predominant MTB strain lineage in Uganda is negatively associated with anti-TB drug resistance and we set out to test this hypothesis.
  
  
  METHODS
  We extracted DNA from mycobacterial isolates collected from smear-positive TB patients in the national TB drug resistance survey and carried out IS6110-PCR. To identify MTB lineages/sub lineages RT-PCR SNP was performed using specific primers and hybridization probes and the 'melting curve' analysis was done to distinguish the Uganda II family from other MTB families. The primary outcome was the distribution of the Uganda II family and its associations with anti-TB drug resistance and HIV infection.
  
  
  RESULTS
  Out of the 1537 patients enrolled, MTB isolates for 1001 patients were available for SNP analysis for identification of Uganda II family, of which 973 (97%) had conclusive RT-PCR results. Of these 422 (43.4%) were of the Uganda II family, mostly distributed in the south west zone (55.0%; OR = 4.6 for comparison with other zones; 95% CI 2.83-7.57; p < 0.001) but occurred in each of the other seven geographic zones at varying levels. Compared to the Uganda II family, other genotypes as a group were more likely to be resistant to any anti-TB drug (OR(adj) =2.9; 95% CI 1.63-5.06; p = 0.001) or MDR (OR(adj) 4.9; 95% CI, 1.15-20.60; p = 0.032), even after adjusting for geographic zone, patient category, sex, residence and HIV status. It was commonest in the 25-34 year age group 159/330 (48.2%). No association was observed between Uganda II family and HIV infection.
  
  
  CONCLUSIONS
  The Uganda II family is a major cause of morbidity due to TB in all NTLP zones in Uganda. It is less likely to be resistant to anti-TB drugs than other MTB strain lineages.
authors.affiliation: National Tuberculosis and Leprosy Program, Kampala, Uganda. ezatinick@yahoo.co.uk.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Ezati
authors.affiliation: National Tuberculosis and Leprosy Program, Kampala, Uganda. deuslukoye@gmail.com.
authors.forename: Deus
authors.initials: D
authors.lastname: Lukoye
authors.affiliation: Department of Medical Microbiology, Makerere University College of Health Sciences, Kampala, Uganda. wamps@covab.mak.ac.ug.|Department of Bio-molecular Resources and Biolab Sciences, College of Veterinary Medicine, Animal Resources and Bio Security, Makerere University, Kampala, Uganda. wamps@covab.mak.ac.ug.
authors.forename: Eddie M
authors.initials: EM
authors.lastname: Wampande
authors.affiliation: National Tuberculosis Reference Laboratory (NTRL), Kampala, Uganda. kenmusisi@yahoo.co.uk.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Musisi
authors.affiliation: National Tuberculosis Reference Laboratory (NTRL), Kampala, Uganda. kasulegw@gmail.com.
authors.forename: George W
authors.initials: GW
authors.lastname: Kasule
authors.affiliation: Department of Global health and Amsterdam Institute for Global Heath and Development, Academic Medical Center, Amsterdam, The Netherlands KNCV Tuberculosis Foundation, The Hague, The Netherlands. f.cobelens@aighd.org.
authors.forename: Frank G J
authors.initials: FG
authors.lastname: Cobelens
authors.affiliation: Department of Medical Microbiology, Makerere University College of Health Sciences, Kampala, Uganda. davidkateete@gmail.com.
authors.forename: David P
authors.initials: DP
authors.lastname: Kateete
authors.affiliation: National Tuberculosis Reference Laboratory (NTRL), Kampala, Uganda. mlj10@case.edu.|Department of Medical Microbiology, Makerere University College of Health Sciences, Kampala, Uganda. mlj10@case.edu.
authors.forename: Moses L
authors.initials: ML
authors.lastname: Joloba
mesh_terms: D000293:Adolescent; D000328:Adult; D000995:Antitubercular Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics*; D060085:Coinfection; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000453:epidemiology*; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D017720:Molecular Epidemiology; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014376:Tuberculosis / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology; D014454:Uganda / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins