title: Long-term mortality in patients with pulmonary and extrapulmonary tuberculosis: a Danish nationwide cohort study.
abstract: BACKGROUND
  Long-term mortality and causes of death in patients with pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) are poorly documented. In this study, long-term mortality and causes of death in PTB and EPTB patients were compared with the background population and it was investigated whether mortality was associated with family-related risk factors.
  
  
  METHODS
  A NATIONWIDE COHORT STUDY WAS CONDUCTED INCLUDING: all adult Danes notified with PTB or EPTB from 1977 to 2008 and alive 1 year after diagnosis; a randomly selected comparison cohort matched on birth date and sex; adult siblings of PTB patients; and population controls. Data were extracted from national registries. All-cause and cause-specific mortality rate ratios were calculated for patients and siblings and compared with their respective control cohorts. A total of 8,291 patients (6,402 PTB and 1,889 EPTB), 24,873 population controls, 1,990 siblings of PTB patients and 11,679 siblings of PTB population controls were included.
  
  
  RESULTS
  Overall, the mortality rate ratio was 1.86 (95% confidence interval [CI] 1.77-1.96) for PTB patients and 1.24 (95% CI 1.12-1.37) for EPTB patients. Both patient cohorts had significantly increased risk of death due to infectious diseases and diabetes. Further, the PTB patients had increased mortality due to cancers (mainly respiratory and gastrointestinal tract), liver and respiratory system diseases, and alcohol and drug abuse. The PTB patients had increased mortality compared with their siblings (mortality rate ratio 3.55; 95% CI 2.57-4.91) as did the siblings of the PTB patients compared with the siblings of population controls (mortality rate ratio 2.16; 95% CI 1.62-2.87).
  
  
  CONCLUSIONS
  We conclude that adult PTB patients have an almost two-fold increased long-term mortality whereas EPTB patients have a slightly increased long-term mortality compared with the background population. The increased long-term mortality in PTB patients stems from diseases associated with alcohol, tobacco, and drug abuse as well as immune suppression, and family-related factors.
authors.affiliation: Department of Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Anne-Sophie Halkjær
authors.initials: AS
authors.lastname: Christensen
authors.affiliation: Department of Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Casper
authors.initials: C
authors.lastname: Roed
authors.affiliation: Department of Infectious Disease Epidemiology, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Andersen
authors.affiliation: Department of Infectious Diseases, Odense University Hospital, Odense, Denmark.
authors.forename: Ase Bengård
authors.initials: AB
authors.lastname: Andersen
authors.affiliation: Department of Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Obel
keywords: causes of death; cohort study; extrapulmonary tuberculosis; mortality; pulmonary tuberculosis; siblings