Morbid Anatomy of Patients with Mycobacterial Infections, a Cross Sectional Autopsy Study at a Tertiary Hospital in a High Disease Burden Setting

Abstract

Background: Tuberculosis is a major cause of morbidity and mortality globally. Infections caused by different mycobacteria can be clinically indistinguishable but the differences in their pathological features and mortality are unclear. Methods: To evaluate the contribution of different mycobacterial pathogens to lethal mycobacterial disease and assess subsequent pathological features, we performed autopsies of 49 patients with suspected TB. Autopsy specimens were examined histologically and cultured for mycobacteria. We identified Mycobacterium tuberculosis ( Mtb ) isolates and non-tuberculous mycobacteria (NTM), and further genotyped the Mtb isolates. Results: Mtb isolates were found in 37 patients and NTM in 12 patients. All patients had signs of caseous pneumonia and 42 patients (86%) had disease involving more than half of the lungs. Two-thirds of the patients with TB or NTM had extrapulmonary engagement in addition to pulmonary pathology. Gross pathology and histopathology were similar in TB patients and patients with NTM, except that patients with NTM had a significantly reduced tendency to cause pleural effusions. Of the Mtb isolates 55% were of the Uganda genotype, which is the predominant Mtb genotype in Uganda. This genotype was significantly more frequent in the younger patients. Conclusion: In this autopsy study of patients with presumptive TB a majority of culture positive cases were caused by Mtb. In 25% of patients NTM were identified, and histopathology was similar in TB and NTM patients, although NTM patients had significantly less pleural effusions. These results suggest that NTM contribute to mortality, and that their identification is important because of the special clinical and therapeutic implications associated with NTM infections. Funding Statement: The study was supported by funds from the Swedish International Development Cooperation Agency through Makerere University-Karolinska Institutet Research collaboration, and the Swedish Heart-Lung Foundation. Declaration of Interest: The authors declare that they have no competing interests. Ethical Approval Statement: The study was approved by the Internal Review Board (IRB) of the Makerere University School of Medicine. Final approval was granted by the Uganda National Council of Science and Technology. (HS 1364).