title: Importance of cough and M. tuberculosis strain type as risks for increased transmission within households.
abstract: BACKGROUND
  The degree to which tuberculosis (TB) is transmitted between persons is variable. Identifying the factors that contribute to transmission could provide new opportunities for TB control. Transmission is influenced by host, bacterial and environmental factors. However, distinguishing their individual effects is problematic because measures of disease severity are tightly correlated, and assessing the virulence of Mycobacterium tuberculosis isolates is complicated by epidemiological and clinical confounders.
  
  
  OBJECTIVE
  To overcome these problems, we investigated factors potentially associated with TB transmission within households.
  
  
  METHODS
  We evaluated patients with smear-positive (≥2+), pulmonary TB and classified M. tuberculosis strains into single nucleotide polymorphism genetic cluster groups (SCG). We recorded index case, household contact, and environmental characteristics and tested contacts with tuberculin skin test (TST) and interferon-gamma release assay. Households were classified as high (≥70% of contacts with TST≥10 mm) and low (≤40%) transmission. We used logistic regression to determine independent predictors.
  
  
  RESULTS
  From March 2008 to June 2012, we screened 293 TB patients to enroll 124 index cases and their 731 contacts. There were 23 low and 73 high transmission households. Index case factors associated with high transmission were severity of cough as measured by a visual analog cough scale (VACS) and the Leicester Cough Questionnaire (LCQ), and cavitation on chest radiograph. SCG 3b strains tended to be more prevalent in low (27.3%) than in high (12.5%) transmission households (p = 0.11). In adjusted models, only VACS (p<0.001) remained significant. SCG was associated with bilateral disease on chest radiograph (p = 0.002) and marginally associated with LCQ sores (p = 0.058), with group 3b patients having weaker cough.
  
  
  CONCLUSIONS
  We found differential transmission among otherwise clinically similar patients with advanced TB disease. We propose that distinct strains may cause differing patterns of cough strength and cavitation in the host leading to diverging infectiousness. Larger studies are needed to verify this hypothesis.
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Boston Medical Center and Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Edward C
authors.initials: EC
authors.lastname: Jones-López
authors.affiliation: Department of Preventive Medicine and Community Health, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey, United States of America.
authors.forename: Soyeon
authors.initials: S
authors.lastname: Kim
authors.affiliation: Núcleo de Doenças Infecciosas (NDI), Universidade Federal do Espírito Santo (UFES), Vitória, Brazil.
authors.forename: Geisa
authors.initials: G
authors.lastname: Fregona
authors.affiliation: Núcleo de Doenças Infecciosas (NDI), Universidade Federal do Espírito Santo (UFES), Vitória, Brazil.
authors.forename: Patricia
authors.initials: P
authors.lastname: Marques-Rodrigues
authors.affiliation: Núcleo de Doenças Infecciosas (NDI), Universidade Federal do Espírito Santo (UFES), Vitória, Brazil.
authors.forename: David Jamil
authors.initials: DJ
authors.lastname: Hadad
authors.affiliation: Núcleo de Doenças Infecciosas (NDI), Universidade Federal do Espírito Santo (UFES), Vitória, Brazil.
authors.forename: Lucilia Pereira Dutra
authors.initials: LP
authors.lastname: Molina
authors.affiliation: Mycobacteriology Laboratory, Núcleo de Doenças Infecciosas, UFES, Vitória, Brazil.
authors.forename: Solange
authors.initials: S
authors.lastname: Vinhas
authors.affiliation: Division of Infectious Diseases, Department of Medicine, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey, United States of America.
authors.forename: Nancy
authors.initials: N
authors.lastname: Reilly
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Boston Medical Center and Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Moine
authors.affiliation: Division of Infectious Diseases, Department of Medicine, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey, United States of America.
authors.forename: Soumitesh
authors.initials: S
authors.lastname: Chakravorty
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Boston Medical Center and Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Mary
authors.initials: M
authors.lastname: Gaeddert
authors.affiliation: Cellular and Molecular Immunology Laboratory, Núcleo de Doenças Infecciosas, UFES, Vitória, Brazil.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Ribeiro-Rodrigues
authors.affiliation: Division of Infectious Diseases, Department of Medicine, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey, United States of America.
authors.forename: Padmini
authors.initials: P
authors.lastname: Salgame
authors.affiliation: Mycobacteriology Laboratory, Núcleo de Doenças Infecciosas, UFES, Vitória, Brazil.
authors.forename: Moises
authors.initials: M
authors.lastname: Palaci
authors.affiliation: Division of Infectious Diseases, Department of Medicine, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Alland
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Boston Medical Center and Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Jerrold J
authors.initials: JJ
authors.lastname: Ellner
authors.affiliation: Núcleo de Doenças Infecciosas (NDI), Universidade Federal do Espírito Santo (UFES), Vitória, Brazil.
authors.forename: Reynaldo
authors.initials: R
authors.lastname: Dietze
mesh_terms: D000328:Adult; D001938:Brazil / Q000453:epidemiology; D003371:Cough; D005191:Family Characteristics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009169:Mycobacterium tuberculosis; D012189:Retrospective Studies; D012307:Risk Factors; D014397:Tuberculosis, Pulmonary / Q000453:epidemiology* / Q000635:transmission*