Evaluating the burden of respiratory tract infections among mortality cases in Karachi, Pakistan: a post-pandemic surveillance analysis.

Background: Respiratory tract infections (RTIs) significantly impact global health, but particularly affect low- and middle-income countries. They contribute to morbidity and mortality, especially among vulnerable populations. We evaluated the burden of RTIs in mortality cases in an urban slum of Karachi, Pakistan, during the post-COVID-19 pandemic period. Methods: We conducted a prospective observational study from September 2022 to October 2023 in Ali Akbar Shah, Karachi. We collected 350 nasal swabs from deceased individuals and tested them for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other respiratory pathogens using reverse transcription polymerase chain reaction (RT-PCR) and the TaqMan Array Card (TAC) assay. Additionally, we performed verbal autopsies to determine the cause of death. Results: Most deaths occurred at home (n/N = 234/350, 66.8%). Hospital-based deaths were more common among children under five years of age (n/N = 81/132, 61.3%), while individuals over five were more likely to die at home (n/N = 180/211, 85.3%). In the post-pandemic period, 6% (n/N = 21/350) of deceased individuals tested positive for COVID-19. The TAC assay analysis found Klebsiella pneumoniae (n/N = 150/350, 42.8%), Staphylococcus aureus (n/N = 141/350, 40.3%), and Streptococcus pneumoniae (n/N = 106/350, 30.3%) to be the most common pathogens. Co-infections were common, with 90.4% of COVID-19-positive cases also harbouring other respiratory pathogens. Conclusions: We observed a high burden of RTIs in Karachi, with Klebsiella pneumoniae playing a major role in overall mortality across all age groups. Co-infections with multiple respiratory pathogens were common, underscoring the need for better diagnostic and treatment strategies. Improved surveillance and potential vaccine development for Klebsiella pneumoniae and other notable pathogens could reduce mortality in similar settings. However, limitations such as post-mortem colonisation, contamination, and the absence of histopathologic confirmation necessitate cautious interpretation of pathogen-related mortality.