title: Investigation of the high rates of extrapulmonary tuberculosis in Ethiopia reveals no single driving factor and minimal evidence for zoonotic transmission of Mycobacterium bovis infection.
abstract: BACKGROUND
  Ethiopia, a high tuberculosis (TB) burden country, reports one of the highest incidence rates of extra-pulmonary TB dominated by cervical lymphadenitis (TBLN). Infection with Mycobacterium bovis has previously been excluded as the main reason for the high rate of extrapulmonary TB in Ethiopia.
  
  
  METHODS
  Here we examined demographic and clinical characteristics of 953 pulmonary (PTB) and 1198 TBLN patients visiting 11 health facilities in distinct geographic areas of Ethiopia. Clinical characteristics were also correlated with genotypes of the causative agent, Mycobacterium tuberculosis.
  
  
  RESULTS
  No major patient or bacterial strain factor could be identified as being responsible for the high rate of TBLN, and there was no association with HIV infection. However, analysis of the demographic data of involved patients showed that having regular and direct contact with live animals was more associated with TBLN than with PTB, although no M. bovis was isolated from patients with TBLN. Among PTB patients, those infected with Lineage 4 reported "contact with other TB patient" more often than patients infected with Lineage 3 did (OR = 1.6, CI 95% 1.0-2.7; p = 0.064). High fever, in contrast to low and moderate fever, was significantly associated with Lineage 4 (OR = 2.3; p = 0.024). On the other hand, TBLN cases infected with Lineage 4 tended to get milder symptoms overall for the constitutional symptoms than those infected with Lineage 3.
  
  
  CONCLUSIONS
  The study suggests a complex role for multiple interacting factors in the epidemiology of extrapulmonary TB in Ethiopia, including factors that can only be derived from population-based studies, which may prove to be significant for TB control in Ethiopia.
authors.affiliation: Animal and Plant Health Agency, TB Research Group, New Haw, Addlestone, Surrey, KT15 3NB, UK. stefan.berg@apha.gsi.gov.uk.
authors.forename: Stefan
authors.initials: S
authors.lastname: Berg
authors.affiliation: Swiss Tropical and Public Health Institute, PO Box CH-4002, Basel, Switzerland. esther.schelling@unibas.ch.|University of Basel, Basel, Switzerland. esther.schelling@unibas.ch.
authors.forename: Esther
authors.initials: E
authors.lastname: Schelling
authors.affiliation: Armauer Hansen Research Institute, PO Box 1005, Addis Ababa, Ethiopia. elenahailu@yahoo.com.
authors.forename: Elena
authors.initials: E
authors.lastname: Hailu
authors.affiliation: Armauer Hansen Research Institute, PO Box 1005, Addis Ababa, Ethiopia. rebumab@yahoo.com.|University of Würzburg, Institute for Molecular Infection Biology, Würzburg, Germany. rebumab@yahoo.com.
authors.forename: Rebuma
authors.initials: R
authors.lastname: Firdessa
authors.affiliation: Armauer Hansen Research Institute, PO Box 1005, Addis Ababa, Ethiopia. balako.gumi@yahoo.com.
authors.forename: Balako
authors.initials: B
authors.lastname: Gumi
authors.affiliation: Armauer Hansen Research Institute, PO Box 1005, Addis Ababa, Ethiopia. girum1825@yahoo.com.
authors.forename: Girume
authors.initials: G
authors.lastname: Erenso
authors.affiliation: Armauer Hansen Research Institute, PO Box 1005, Addis Ababa, Ethiopia. gadisa.endalamaw@googlemail.com.
authors.forename: Endalamaw
authors.initials: E
authors.lastname: Gadisa
authors.affiliation: Armauer Hansen Research Institute, PO Box 1005, Addis Ababa, Ethiopia. armen.kassa@gmail.com.
authors.forename: Araya
authors.initials: A
authors.lastname: Mengistu
authors.affiliation: Armauer Hansen Research Institute, PO Box 1005, Addis Ababa, Ethiopia. mekonnen.meseret@gmail.com.
authors.forename: Meseret
authors.initials: M
authors.lastname: Habtamu
authors.affiliation: Armauer Hansen Research Institute, PO Box 1005, Addis Ababa, Ethiopia. jemaldr@yahoo.com.
authors.forename: Jemal
authors.initials: J
authors.lastname: Hussein
authors.affiliation: Armauer Hansen Research Institute, PO Box 1005, Addis Ababa, Ethiopia. kmengie@yahoo.com.
authors.forename: Teklu
authors.initials: T
authors.lastname: Kiros
authors.affiliation: Armauer Hansen Research Institute, PO Box 1005, Addis Ababa, Ethiopia. shiferawbekele92@yahoo.com.
authors.forename: Shiferaw
authors.initials: S
authors.lastname: Bekele
authors.affiliation: Armauer Hansen Research Institute, PO Box 1005, Addis Ababa, Ethiopia. hevewondale@yahoo.com.
authors.forename: Wondale
authors.initials: W
authors.lastname: Mekonnen
authors.affiliation: Armauer Hansen Research Institute, PO Box 1005, Addis Ababa, Ethiopia. yohannesderese@yahoo.com.
authors.forename: Yohannes
authors.initials: Y
authors.lastname: Derese
authors.affiliation: Swiss Tropical and Public Health Institute, PO Box CH-4002, Basel, Switzerland. jakob.zinsstag@unibas.ch.|University of Basel, Basel, Switzerland. jakob.zinsstag@unibas.ch.
authors.forename: Jakob
authors.initials: J
authors.lastname: Zinsstag
authors.affiliation: Aklilu Lemma Institute of Pathobiology, Addis Ababa University, PO Box 1176, Addis Ababa, Ethiopia. gobenachimdi2009@yahoo.co.uk.
authors.forename: Gobena
authors.initials: G
authors.lastname: Ameni
authors.affiliation: Swiss Tropical and Public Health Institute, PO Box CH-4002, Basel, Switzerland. sebastien.gagneux@unibas.ch.|University of Basel, Basel, Switzerland. sebastien.gagneux@unibas.ch.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Gagneux
authors.affiliation: Center for Molecular Bacteriology and Infection, Department of Medicine, Flowers building, South Kensington, Imperial College London, London, SW7 2AZ, UK. b.robertson@imperial.ac.uk.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Robertson
authors.affiliation: Swiss Tropical and Public Health Institute, PO Box CH-4002, Basel, Switzerland. rea.tschopp@unibas.ch.|Armauer Hansen Research Institute, PO Box 1005, Addis Ababa, Ethiopia. rea.tschopp@unibas.ch.|University of Basel, Basel, Switzerland. rea.tschopp@unibas.ch.
authors.forename: Rea
authors.initials: R
authors.lastname: Tschopp
authors.affiliation: Animal and Plant Health Agency, TB Research Group, New Haw, Addlestone, Surrey, KT15 3NB, UK. glyn.hewinson@apha.gsi.gov.uk.
authors.forename: Glyn
authors.initials: G
authors.lastname: Hewinson
authors.affiliation: Armauer Hansen Research Institute, PO Box 1005, Addis Ababa, Ethiopia. yamuahlk@ahrialert.org.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Yamuah
authors.affiliation: UCD Schools of Veterinary Medicine, Medicine and Medical Science, Biomolecular and Biomedical Science and UCD Conway Institute, University College Dublin, Dublin, Republic of Ireland. stephen.gordon@ucd.ie.
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Gordon
authors.affiliation: Armauer Hansen Research Institute, PO Box 1005, Addis Ababa, Ethiopia. aseffaa@gmail.com.
authors.forename: Abraham
authors.initials: A
authors.lastname: Aseffa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D005002:Ethiopia / Q000453:epidemiology; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000150:complications / Q000453:epidemiology; D006268:Health Facilities / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D008875:Middle Aged; D009163:Mycobacterium bovis / Q000302:isolation & purification; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification; D012307:Risk Factors; D014376:Tuberculosis / Q000453:epidemiology* / Q000635:transmission / Q000662:veterinary; D055815:Young Adult; D015047:Zoonoses / Q000453:epidemiology* / Q000635:transmission