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.
Sobia Khan, S. Irfan, J. Ashraf et al.· International Journal of Inf...· 0 citations
Children typically experience milder SARS-CoV-2 infection than adults, yet a subset—especially those with immune compromise—develop persistent infection. This study examined clinical characteristics and intra-host viral evolution in pediatric patients with prolonged COVID-19, comparing immunocompetent and immunocompromised hosts.
Residual nasopharyngeal specimens from patients <20 years old with ≥3 samples ≤90 days apart underwent qRT-PCR confirmation and whole-genome sequencing using tiled amplicon Illumina methods. Demographic, clinical, and immune-status data were extracted through chart review. Viral load trajectories and longitudinal genomic changes were analyzed.
Sixteen patients met inclusion criteria: 5 immunocompetent and 11 immunocompromised children. Groups showed similar demographic distributions (mean ages 6 vs. 9.2 years; 60% vs. 64% male; 60% vs. 45% Hispanic). Vaccination was rare, with all immunocompetent and 82% of immunocompromised patients unvaccinated. COVID-19 treatment differed markedly: 1 immunocompetent (20%) versus 8 immunocompromised patients (73%) received therapies including monoclonal antibodies or remdesivir. Clinical severity varied, with immunocompetent children largely asymptomatic or managed as outpatients, whereas immunocompromised children more frequently required hospitalization (28%), ICU care (9%), or died (18%). Despite this, WHO severity scores were similar (2.4 vs. 2.2).
Sequencing yielded 15 isolates from immunocompetent and 35 isolates from immunocompromised patients. Viral loads generally declined over time, though several immunocompromised children demonstrated prolonged high viral loads. Longitudinal sequencing identified intra-host viral diversification in both groups, including nonsynonymous Spike mutations and minority variants associated with immune escape. Some immunocompromised patients accumulated mutations at positions linked to therapeutic resistance.
Pediatric persistent SARS-CoV-2 infection is associated with measurable intra-host viral evolution. Immunocompromised children demonstrated longer infection duration, more frequent treatment exposure, and extended viral shedding, creating conditions that may favor viral diversification. These findings highlight the need for continued genomic surveillance in vulnerable pediatric populations.
Charlie R. Boyle, Tien Doan, Estefany Rios-Guzman et al.· Journal of the Pediatric Inf...· 0 citations
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