BackgroundWith high short-term mortality and substantial excess morbidity among survivors, tuberculous meningitis (TBM) is the most severe manifestation of extra-pulmonary tuberculosis (TB). The objective of this study was to assess the long-term mortality and causes of death in a TBM patient population compared to the background population.MethodsA nationwide cohort study was conducted enrolling patients notified with TBM in Denmark from 1972–2008 and alive one year after TBM diagnosis. Data was extracted from national registries. From the background population we identified a control cohort of individuals matched on gender and date of birth. Kaplan-Meier survival curves and Cox regression analysis were used to estimate mortality rate ratios (MRR) and analyse causes of death.FindingsA total of 55 TBM patients and 550 individuals from the background population were included in the study. Eighteen patients (32.7%) and 107 population controls (19.5%) died during the observation period. The overall MRR was 1.79 (95%CI: 1.09–2.95) for TBM patients compared to the population control cohort. TBM patients in the age group 31–60 years at time of diagnosis had the highest relative risk of death (MRR 2.68; 95%CI 1.34–5.34). The TBM patients had a higher risk of death due to infectious disease, but not from other causes of death.ConclusionAdult TBM patients have an almost two-fold increased long-term mortality and the excess mortality stems from infectious disease related causes of death.

BackgroundLong-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.MethodsA 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.ResultsOverall, 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).ConclusionWe 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.