TB common at post-mortem among medical inpatients in Zambia

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

Bates M, Mudenda V, Shibemba A, Kaluwaji J, Tembo J, Kabwe M, Chimoga C, Chilukutu L, Chilufya M, Kapata N, Hoelscher M, Maeurer M, Mwaba P, Zumla A. Lancet Infect Dis. 2015 Mar 9. pii: S1473-3099(15)70058-7. doi: 10.1016/S1473-3099(15)70058-7. [Epub ahead of print]

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 chi2, 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 are needed. Further autopsy studies are needed to ascertain the generalisability of the findings.

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Editor’s notes: This paper adds to the growing body of literature documenting a very high burden of tuberculosis (TB) in young adults, the majority of whom are HIV-positive, dying in hospitals in sub-Saharan Africa. Accurate knowledge of causes of death among people living with HIV is critical to developing strategies to reduce mortality. Although autopsies are the gold standard for identifying specific causes of death, autopsy data are sparse. In this study the authors undertook whole-body autopsies in medical inpatient deaths to describe the burden of TB. The GeneXpert MTB/RIF assay was used to assess the prevalence of multidrug-resistant tuberculosis.

The study achieved only 9% coverage of all deaths during the study period, similar to most other studies attempting full autopsy, which has poor acceptability to families. Among 125 included inpatients, the median time from admission to death was seven days. The majority of included people were HIV-positive, all diagnosed before death. The authors report a substantial burden of TB at autopsy, of which 26% (20/78) was only diagnosed after death and 17% (13/78) had undiagnosed multidrug-resistant (MDR) TB. None of the people with MDR-TB was on appropriate treatment. Bacterial pneumonia, found in over one-third of autopsies, was the next most common autopsy finding after TB.

The high burden of undiagnosed TB and MDR-TB at autopsy reported in this study highlights the need for routine screening for TB and MDR-TB among inpatients in TB endemic settings, and for measures to prevent in-hospital TB transmission. Rapid point-of-care diagnostics are necessary to enable early initiation of appropriate treatment. The study also highlights the key role of autopsy in identifying TB at death. This is consistently underestimated by physicians. Less invasive autopsy techniques based on multiple tissue biopsies are more acceptable to families and could have an important role in surveillance for TB as a cause of death. 

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