Epidemiologic Characteristics of 1.4 Million Multiplex PCR Tests for 12 Urogenital and Sexually Transmitted Infection Pathogens in Korea (2021–2024)

Sexually transmitted infections (STIs) remain a global health concern, but large-scale multiplex PCR surveillance data are limited. This study aimed to characterize sex- and age-specific distributions, temporal patterns, and co-infection dynamics of 12 urogenital and sexually transmitted infection (STI) pathogens in Korea. We retrospectively analyzed 1,399,431 multiplex PCR test records (902,713 females, 496,718 males) collected nationwide between 2021 and 2024. Positivity rates were stratified by sex, age, month, season, and year. Co-infection coverage and inter-pathogen correlations were assessed; <i>φ</i> coefficients ≥0.20 were considered relevant. Overall, 67.23% of tests were positive for at least one pathogen. Annually, positivity rates for most pathogens, including the six traditional STIs (<i>N. gonorrhoeae</i>, <i>C. trachomatis</i>, <i>M. genitalium</i>, <i>T. vaginalis</i>, <i>T. pallidum</i>, and HSV II), showed a significant decline over the four-year period (<i>p</i> < 0.0001). Females had higher positivity than males (77.73% vs. 48.14%, <i>p</i> < 0.0001), largely driven by <i>G. vaginalis</i> (64.70%), <i>U. parvum</i> (41.37%), and <i>C. albicans</i> (18.07%), whereas traditional STIs, except <i>T. vaginalis</i> and HSV II, were more frequent in males (<i>p</i> < 0.0001). Adolescents and young adults carried the highest burden of traditional STIs such as <i>C. trachomatis</i> and <i>N. gonorrhoeae</i> (<i>p</i> < 0.0001). In females, <i>C. albicans</i> decreased with age (32.17% in 10s to 6.45% in 80s) but increased annually (<i>p</i> = 0.0058), while HSV II positivity significantly declined in males over time (<i>p</i> = 0.0038). No seasonal variation was observed (<i>p</i> > 0.90). Co-infections were predominantly commensal-driven, with <i>U. parvum</i>/<i>G. vaginalis</i> being the most frequent pair in females, and <i>U. urealyticum</i>/<i>G. vaginalis</i> being frequent in males (8.24% in 10s, 10.48% in 20s). Traditional STI co-infections were rare but concentrated in adolescents, with <i>C. trachomatis</i>/<i>N. gonorrhoeae</i> reaching 4.25% in males. Correlation analysis confirmed strong associations among commensals (<i>φ</i> = 0.24-0.35) and moderate correlations involving <i>C. trachomatis</i> in youth (<i>φ</i> = 0.25-0.28), with <i>G. vaginalis</i> consistently identified as the central hub organism across all age groups. This nationwide four-year analysis highlights declining prevalence of traditional STIs, sex-specific STI patterns, distinct age-specific distributions, and commensal-driven co-infection patterns. The findings underscore the need for age- and sex-tailored screening strategies, particularly in adolescents, young adults, and women of reproductive age, and highlight the value of multiplex PCR for STI surveillance.