Xpert Ultra Nasopharyngeal Swab Assessed for Identification of Tuberculosis Deaths

Post-mortem studies have confirmed a high prevalence of tuberculosis (TB) at autopsy in sub-Saharan Africa (sSA), in up to 43% in HIV-positive adults, and more than 30% of adults dying at home with unknown cause of death.

Identifying missed TB deaths is important for accurate measurement of disease burden, especially in endemic settings with limited clinical resources. Enhanced case detection by post-mortem testing would improve mortality assessments.

Image: Xpert MTB/RIF Ultra has the potential to reduce the number of missed smear-negative TB patients and may lead to a decrease in total costs of patient care due to the detection of MTB in patient specimens and RIF-resistance in a single test (Photo courtesy of Cepheid)

An international team of Infectious Diseases scientists led by Duke University (Durham, NC, USA) enrolled pediatric and adult medical deaths to a prospective autopsy study at two referral hospitals in northern Tanzania from October 2016 through May 2019. Of 205 decedents, 78 (38.0%) were female and median age was 45 years. The team swabbed the posterior nasopharynx prior to autopsy and at autopsy they collected lung, liver, and, when possible, cerebrospinal fluid for mycobacterial culture and histopathology.

The team assessed the diagnostic performance of Xpert MTB/RIF Ultra (Ultra; Cepheid, Sunnyvale, CA, USA) on nasopharyngeal specimens collected post-mortem. Confirmed tuberculosis was defined as Mycobacterium tuberculosis complex (MTBc) recovery by culture with consistent tissue histopathology findings; decedents with only histopathology findings, including acid-fast staining or immunohistochemistry were defined as probable tuberculosis.

The investigators reported that TB was identified at autopsy in 27 (13.2%) decedents, of which 22 (81.5%) were confirmed and five (18.5%) were probable. Six (22.2%) decedents with TB were diagnosed by minimally invasive tissue sampling (MITS), all confirmed by MTBc culture. Nineteen (70.4%) of 27 decedents with confirmed or probable TB had MTBc detected by Ultra nasopharyngeal swab. The median (range) time interval from death to collection of nasopharyngeal swab for those with Ultra MTBc detection was 18 (7, 47) hours and 22 (4, 74) hours for all Ultra undetected, without significant difference. No rifampicin resistance was detected. The post-mortem Ultra approach showed sensitivity of 81.8% and specificity of 98.4% for confirmed TB diagnosis, with separate calculations for confirmed or probable TB diagnoses.

The authors concluded that the Ultra assay by nasopharyngeal swab collected post-mortem showed moderate sensitivity and high specificity for the diagnosis of fatal TB. For both in-hospital deaths and deaths in the community, the nasopharyngeal Ultra may provide an accessible tool for critical assessment of TB-associated mortality missed during clinical evaluation. Enhanced case detection using this approach would likely benefit national TB prevention efforts in high-burden settings. The study was published on March 27, 2022 in the journal Clinical Microbiology and Infection.

Related Links:
Duke University
Cepheid