title: Variation and risk factors of drug resistant tuberculosis in sub-Saharan Africa: a systematic review and meta-analysis.
abstract: BACKGROUND
  Prevalence of multidrug resistant tuberculosis (MDR-TB), defined as in vitro resistance to both rifampicin and isoniazid with or without resistance to other TB drugs, in sub-Saharan Africa (SSA) is reportedly low compared to other regions. These estimates are based on data reported to the World Health Organization (WHO) on drug resistance surveys, which may suffer from a reporting bias. We set out to evaluate the variation in prevalence of drug resistant tuberculosis (DR-TB) and its determinants across SSA countries among new and previously treated TB patients.
  
  
  METHODS
  The aim was to perform a systematic review and meta-analysis of DR-TB prevalence and associated risk factors in SSA. PubMed, EMBASE, Cochrane and bibliographies of DR-TB studies were searched. Surveys at national or sub-national level, with reported DR-TB prevalence (or sufficient data to calculate a prevalence) to isoniazid (INH), rifampicin (RMP), ethambutol (EMB), and streptomycin (SM) conducted in SSA excluding the Republic of South Africa, published between 2003 and 2013 with no language restriction were considered. Two authors searched and reviewed the studies for eligibility and extracted the data in pre-defined forms. Forest plots of all prevalence estimates by resistance outcome were performed. Summary estimates were calculated using random effects models, when appropriate. Associations between any DR-TB and MDR-TB with potential risk factors were examined through subgroup analyses stratified by new and previously treated patients.
  
  
  RESULTS
  A total of 726 studies were identified, of which 27 articles fulfilled the inclusion criteria. Studies reported drug susceptibility testing (DST) results for a total of 13,465 new and 1,776 previously treated TB patients. Pooled estimate of any DR-TB prevalence among the new cases was 12.6% (95% CI 10.6-15.0) while for MDR-TB this was 1.5% (95% CI 1.0-2.3). Among previously treated patients, these were 27.2% (95% CI 21.4-33.8) and 10.3% (95% CI 5.8-17.4%), respectively. DR-TB (any and MDR-TB) did not vary significantly with respect to study characteristics.
  
  
  CONCLUSIONS
  The reported prevalence of DR-TB in SSA is low compared to WHO estimates. MDR-TB in this region does not seem to be driven by the high HIV prevalence rates.
authors.affiliation: National Tuberculosis and Leprosy Program, Kampala, Uganda. deuslukoye@gmail.com.|Management Sciences for Health (MSH), 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, Kampala, Uganda. willyssengooba@gmail.com.|Academic Medical Center, Department of Global Health and Amsterdam Institute for Global Heath and Development, Pietersbergweg 17, 1105 BM, Amsterdam, The Netherlands. willyssengooba@gmail.com.
authors.forename: Willy
authors.initials: W
authors.lastname: Ssengooba
authors.affiliation: National TB Reference Laboratory, Kampala, Uganda. kenmusisi@yahoo.co.uk.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Musisi
authors.affiliation: National Tuberculosis and Leprosy Program, Kampala, Uganda. kasulegw@gmail.com.|National TB Reference Laboratory, Kampala, Uganda. kasulegw@gmail.com.
authors.forename: George W
authors.initials: GW
authors.lastname: Kasule
authors.affiliation: Academic Medical Center, Department of Global Health and Amsterdam Institute for Global Heath and Development, Pietersbergweg 17, 1105 BM, Amsterdam, The Netherlands. f.cobelens@aighd.org.|KNCV Tuberculosis Foundation, The Hague, Hague, The Netherlands. f.cobelens@aighd.org.
authors.forename: Frank G J
authors.initials: FG
authors.lastname: Cobelens
authors.affiliation: National Tuberculosis and Leprosy Program, Kampala, Uganda. m.joloba@gmail.com.|Department of Medical Microbiology, Makerere University College of Health Sciences Kampala, Kampala, Uganda. m.joloba@gmail.com.|National TB Reference Laboratory, Kampala, Uganda. m.joloba@gmail.com.
authors.forename: Moses
authors.initials: M
authors.lastname: Joloba
authors.affiliation: Academic Medical Center, Department of Global Health and Amsterdam Institute for Global Heath and Development, Pietersbergweg 17, 1105 BM, Amsterdam, The Netherlands. g.gomez@aighd.org.|London School of Hygiene and Tropical Medicine, Department of Global Health and Development, London, UK. g.gomez@aighd.org.
authors.forename: Gabriela B
authors.initials: GB
authors.lastname: Gomez
mesh_terms: D017954:Africa South of the Sahara / Q000453:epidemiology; D000995:Antitubercular Agents / Q000627:therapeutic use; D001431:Bacteriological Techniques; D004977:Ethambutol / Q000627:therapeutic use; D006801:Humans; D007538:Isoniazid / Q000627:therapeutic use; D015995:Prevalence; D012293:Rifampin / Q000627:therapeutic use; D012307:Risk Factors; D013307:Streptomycin / Q000627:therapeutic use; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy / Q000453:epidemiology*; D014944:World Health Organization
chemical_list: D000995:Antitubercular Agents; D004977:Ethambutol; D007538:Isoniazid; D012293:Rifampin; D013307:Streptomycin