title: Increased level of acute phase reactants in patients infected with modern Mycobacterium tuberculosis genotypes in Mwanza, Tanzania.
abstract: BACKGROUND
  There is increasing evidence to suggest that different Mycobacterium tuberculosis lineages cause variations in the clinical presentation of tuberculosis (TB). Certain M. tuberculosis genotypes/lineages have been shown to be more likely to cause active TB in human populations from a distinct genetic ancestry. This study describes the genetic biodiversity of M. tuberculosis genotypes in Mwanza city, Tanzania and the clinical presentation of the disease caused by isolates of different lineages.
  
  
  METHODS
  Two-hundred-fifty-two isolates from pulmonary TB patients in Mwanza, Tanzania were characterized by spoligotyping, and 45 isolates were further characterized by mycobacterium interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR). The patients' level of the acute phase reactants AGP, CRP and neutrophil counts, in addition to BMI, were measured and compared to the M. tuberculosis lineage of the infectious agent for each patient.
  
  
  RESULTS
  The most frequent genotype was ST59 (48 out of 248 [19.4%]), belonging to the Euro-American lineage LAM11_ZWE, followed by ST21 (CAS_KILI lineage [44 out of 248 [17.7%]). A low degree of diversity (15.7% [39 different ST's out of 248 isolates]) of genotypes, in addition to a high level of mixed M. tuberculosis sub-populations among isolates with an unreported spoligotype pattern (10 out of 20 isolates [50.0%]) and isolates belonging to the ST53 lineage (13 out of 25 [52%]) was observed. Isolates of the 'modern' (TbD1-) Euro-American lineage induced higher levels of α1-acid glycoprotein (β = 0.4, P = 0.02; 95% CI [0.06-0.66]) and neutrophil counts (β = 0.9, P = 0.02; 95% CI [0.12-1.64]) and had lower BMI score (β = -1.0, P = 0.04; 95% CI[-1.89 - (-0.03)]). LAM11_ZWE ('modern') isolates induced higher levels of CRP (β = 24.4, P = 0.05; 95% CI[0.24-48.63]) and neutrophil counts (β = 0.9, P = 0.03; 95% CI[0.09-1.70]).
  
  
  CONCLUSIONS
  The low diversity of genotypes may be explained by an evolutionary advantage of the most common lineages over other lineages combined with optimal conditions for transmission, such as overcrowding and inadequate ventilation. The induction of higher levels of acute phase reactants in patients infected by 'modern' lineage isolates compared to 'ancient' lineages may suggest increased virulence among 'modern' lineage isolates.
authors.affiliation: Department of Clinical Science, Infection, Faculty of Medicine and Dentristry, University of Bergen, Bergen, Norway. Ruth.Stavrum@gades.uib.no.
authors.forename: Ruth
authors.initials: R
authors.lastname: Stavrum
authors.forename: George
authors.initials: G
authors.lastname: PrayGod
authors.forename: Nyagosya
authors.initials: N
authors.lastname: Range
authors.forename: Daniel
authors.initials: D
authors.lastname: Faurholt-Jepsen
authors.forename: Kidola
authors.initials: K
authors.lastname: Jeremiah
authors.forename: Maria
authors.initials: M
authors.lastname: Faurholt-Jepsen
authors.forename: Henrik
authors.initials: H
authors.lastname: Krarup
authors.forename: Martine G
authors.initials: MG
authors.lastname: Aabye
authors.forename: John
authors.initials: J
authors.lastname: Changalucha
authors.forename: Henrik
authors.initials: H
authors.lastname: Friis
authors.forename: Aase B
authors.initials: AB
authors.lastname: Andersen
authors.forename: Harleen M S
authors.initials: HM
authors.lastname: Grewal
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D005838:Genotype; D006801:Humans; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000302:isolation & purification; D013636:Tanzania; D014397:Tuberculosis, Pulmonary / Q000097:blood / Q000175:diagnosis / Q000382:microbiology*; D055815:Young Adult
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers