Autopsy studies have demonstrated that the prevalence of extra-pulmonary TB is high in HIV-associated adult deaths in sub-Saharan Africa. Diagnostic infrastructure for EPTB is chronically weak across the continent, resulting in many untreated infections causing prolonged morbidity and mortality. We have identified two high-mortality patient groups for whom EPTB is a candidate cause, but is not currently included in routine screening.
Intestinal perforations are a common cause of generalized peritonitis, with the resultant faecal contamination and overwhelming sepsis lead to high mortality and morbidity. Known etiologies include both non-communicable and communicable diseases. Primary infectious causes include tuberculosis and typhoid, both of which are highly prevalent in our setting.
Reticulocytopenia is defined as a peripheral blood recticulocyte proportion less than 2%. The apparent failure of the marrow to respond appropriately to anemic or hypoxic conditions may be due to a number of factors, including opportunistic infections, drug therapy, immune mechanisms and possibly direct insult by HIV. Possible infectious causes include tuberculosis, and a range of neurotropic viral infections.
We will conduct cross-sectional aetiology studies in both patient groups, screening for EPTB by mycobacterial culture from either tissue or bone marrow specimens collected for routine investigations. Samples will also be screened with the Xpert MTB/RIF assay, to evaluate it's accuracy for diagnosing EPTB using biopsy specimens in these patient groups. We will also screen each patient group for an array of other candidate pathogens, based on the available literature, with particular weight being given to relevant data from high HIV-burden settings.
The results of these studies will inform on diagnostic algorithms for EPTB, and priorities for diagnostic service development at both our centre, and other similar tertiary referral centres across the region.