Tuberculosis at post-mortem in inpatient adults at a tertiary referral centre in sub-Saharan Africa – A prospective descriptive autopsy study

Background: The World Health Organisation (WHO) estimates that 3 million cases of tuberculosis (TB) are missed every year. Identification and treatment of these are critical to achieving global TB control. Patients with sub-clinical TB, extra-pulmonary TB, and drug-resistant TB are difficult to diagnose and may be missed at all points of healthcare. An autopsy study was conducted to ascertain the burden of TB at post-mortem in adults who died in the inpatient general medical wards at a tertiary care referral center in Lusaka, Zambia. Methods: Complete whole body autopsies were performed on 125 adult inpatients. Pathological examination involved two stages: (1) Gross pathology was recorded, and samples were taken from all organs for histopathology and cryopreservation; and (2) Histopathological examination of tissue after appropriate staining. Specific pathology and diseases identified on examination were recorded. Lung tissues were processed using the GeneXpert MTB/RIF Assay. Primary outcome measures were specific diseases stratified by HIV status. Secondary outcomes were missed TB and drug-resistant TB cases. Findings: Of 125 adults, median age 35 years (IQR: 29-43), 80 (64%) were male and 101 (80.8%) were HIV-positive. Tuberculosis was the most common finding at autopsy with 78/125 cases (62.4%), of which 66/78 (84.6%) were HIV-infected. There were 35/78 cases (44.9%) with extra-pulmonary TB, the odds of which were higher among HIV-infected cases (aOR 5.14 (95% CI: 1.04–25.4), p = 0.045); 25.6% (20/78) of the TB cases were not diagnosed ante-mortem; and 13/78 (16.7%) of the TB cases had undiagnosed MDR-TB. Other autopsy findings included: pyogenic pneumonia 36.8% (46/125); bacterial meningitis 7.2% (9/125); cardiac failure 7.2% (9/125); and malignancies 8.8% (11/125). Prevalence of HIV did not differ between TB and non-TB cases (84.6% vs. 74.5%: p = 0.163). Interpretation: TB remains an important cause of death in adult inpatients. A substantial number of inpatients with TB and MDR-TB are not diagnosed by the current cascade of healthcare. Inpatient settings in high TB endemic countries should be included in WHO ‘high risk’ groups, and heightened clinical awareness and more proactive screening for TB and MDR-TB in all inpatients should be required

Burden of tuberculosis at post mortem in inpatients at a tertiary referral centre in sub-Saharan Africa: a prospective descriptive autopsy study

Background Patients with subclinical tuberculosis, smear-negative tuberculosis, extrapulmonary tuberculosis, multidrug-resistant tuberculosis, and asymptomatic tuberculosis are difficult to diagnose and may be missed at all points of health care. We did an autopsy study to ascertain the burden of tuberculosis at post mortem in medical inpatients at a tertiary care hospital in Lusaka, Zambia. Methods Between April 5, 2012, and May 22, 2013, we did whole-body autopsies on inpatients aged at least 16 years who died in the adult inpatient wards at University Teaching Hospital, Lusaka, Zambia. We did gross pathological and histopathological analysis and processed lung tissues from patients with tuberculosis through the GeneXpert MTB/RIF assay to identify patients with multidrug-resistant tuberculosis. The primary outcome measure was specific disease or diseases stratified by HIV status. Secondary outcomes were missed tuberculosis, multidrug-resistant tuberculosis, and comorbidities with tuberculosis. Data were analysed using Pearson chi(2), the Mann-Whitney U test, and binary logistic regression. Findings The median age of the 125 included patients was 35 years (IQR 29-43), 80 (64%) were men, and 101 (81%) were HIV positive. 78 (62%) patients had tuberculosis, of whom 66 (85%) were infected with HIV.35 (45%) of these 78 patients had extrapulmonary tuberculosis. The risk of extrapulmonary tuberculosis was higher among HIV-infected patients than among uninfected patients (adjusted odds ratio 5.14, 95% CI 1.04-24.5; p=0.045). 20 (26%) of 78 patients with tuberculosis were not diagnosed during their life and 13 (17%) had undiagnosed multidrug-resistant tuberculosis. Common comorbidities with tuberculosis were pyogenic pneumonia in 26 patients (33%) and anaemia in 15 (19%). Interpretation Increased clinical awareness and more proactive screening for tuberculosis and multidrug-resistant tuberculosis in inpatient settings is needed. Further autopsy studies are needed to ascertain the generalisability of the findings