Sobia Muhammad Asad Khan, Seema Irfan, Javaria Ashraf, Hassan Ghayas, Najia Ghanchi, Joveria Farooqi, Kauser Jabeen, Noureen Saeed, Muhammad Naeem, Sadaf Zaka, Egon A Ozer, Rumina Hasan
Circulation of diverse C. diphtheriae strains with alarming antimicrobial resistance underscores the need for genomic surveillance to evaluate transmission trends. We further highlight Elek test limitations in detecting toxin production and the need for improved diagnostics in low- and middle-income countries.
BACKGROUND: Diphtheria remains endemic in Pakistan with cases increasing following the COVID-19 pandemic despite on-going vaccination programs. This study analyzes the genomic diversity, virulence and antimicrobial resistance patterns of pharyngeal diphtheria strains collected during the Karachi outbreak.
METHODS: C. diphtheriae isolates from a tertiary care hospital laboratory in Karachi (August 2023- October 2024) were included. Antimicrobial susceptibility testing and whole-genome sequencing of phenotypically confirmed isolates was performed. Phylogenetic and bioinformatics analysis was done using diphtOscan and AMRfinderPlus tools.
RESULTS: A total of 47 pharyngeal C. diphtheriae isolates were included. Median age of patients was 7 years and male to female ratio was 1.6:1. The tox gene was present in 89.4% of isolates, while only 29% (n=13/45) demonstrated toxin production. Genomic analysis identified ten sequence types; ST384 and ST698 were most prevalent. Phenotypically, 34% (n=16) were resistant to both erythromycin and penicillin and 49% (n=23) were multi-drug resistant. The most prevalent resistance genes were sul1 (100%), ermX (76.6%) and pbp2m (51.1%).
CONCLUSION: Circulation of diverse C. diphtheriae strains with alarming antimicrobial resistance underscores the need for genomic surveillance to evaluate transmission trends. We further highlight Elek test limitations in detecting toxin production and the need for improved diagnostics in low- and middle-income countries.