Causes, Timings and Clinical Features of Tuberculosis-Associated Deaths in A Lowincidence Country

Abstract

Introduction Low-incidence countries make a small but steady contribution to global TB deaths despite wide availability of rapid diagnostics and effective treatment. Previous studies have often been limited by difficulty identifying which deaths resulted from TB directly, and which were coincident with treatment, but caused by other pathology. Here we describe the causes and timings of deaths occurring during TB treatment or following a diagnosis of TB, and clinical features including severity and complications over a 10-year period (2010-2020) across seven London hospitals. Methods London TB register (LTBR) and UK Health Security Agency records were used to identify all deaths on TB treatment, or with newly diagnosed tuberculosis where anti-tuberculosis therapy (ATT) was not initiated, or the diagnosis was made post-mortem. Laboratory, radiological and clinical records were used to categorise deaths as a) TB-associated, where TB or ATT-complications were the main cause, or TB contributed but was not primary cause, and b) non-TB Results From a total of 9334 people notified during this period, 313 deaths were identified (3.4%). In 71 deaths, TB was not a significant factor. Cancer was the commonest cause (25, 35.0%), frequently haematological or lung. Other important causes were infection, cardiovascular, dementia and cirrhosis. This group had significantly higher Charleson Comorbidity Indices (CCI), and deaths occurred throughout treatment. Tuberculosis caused 131 deaths (41.9%) and contributed to 102 deaths (32.6%). ATT-associated hepatic or renal failure caused 9 deaths (2.9%). TB-associated deaths occurred earlier in treatment than non-TB deaths: post-mortem diagnoses were more common, and more people received minimal or no treatment. The most common complications were neurological, pulmonary (haemorrhage, embolus, pneumothorax) and abdominal perforation or obstruction. Complications of bronchoscopy or surgery caused 3 deaths. Discussion Correctly attributing the cause of deaths, and the contribution to mortality from comorbidities and complications, is key to understanding tuberculosis mortality in lowincidence countries. More than 50% of TB-associated deaths occurred during the first month of treatment indicating the need for close monitoring of high-risk patients during this stage. Reducing the cases diagnosed peri- or post-mortem by encouraging earlier use of TB-diagnostics, or empirical treatment, may also impact mortality.