Rapid expansion of lymphogranuloma venereum infections with fast diversification and spread of Chlamydia trachomatis L genovariants

Abstract

Invasive genotypes of Chlamydia trachomatis (L1–L3) are responsible for lymphogranuloma venereum (LGV), which, in industrialized countries, is prevalent among men who have sex with men. Our aim was to analyze the changing trends and diversification of LGV genovariants detected in Madrid, Spain. The study was launched at a public community healthcare center that has specialized in sexually transmitted infections (STIs) for 10 years (STI1). Screening rates have improved at this center, but LGV diagnoses have drastically increased, especially since 2016. We therefore extended the LGV diagnosis to another public community healthcare center that specializes in STIs (STI2), as well as to two general tertiary hospitals in Madrid from 2017 to 2019. Overall, between 2010 and 2019, 10,833 cases of C. trachomatis infection were detected among 121,955 screened samples with 1,253 LGV cases. The molecular characterization of L genotypes identified two main genovariants (ompA-L2 and ompA-L2b) in 2010–2014. However, three new successful genovariants (ompA-L2bV1, ompA-L2bV4, and ompA-L2bV7) emerged in 2016–2019. In recent years, 3.9% (31/803) of recombinant forms of ompA were detected between ompA-L2 and ompA-D. From the clinical and epidemiological standpoints, the patients infected by the ompA-L2 and ompA-L2bV1 genovariants were more frequently associated with asymptomatic infections and HIV ( P = 0.001), while ompA-L2b and ompA-L2bV4 were more frequently associated with concomitant ( P < 0.02) and previous ( P = 0.003) STI infections, suggesting distinct sexual networks. These findings suggest a growing trend toward higher transmission rates in the population along with an increasingly complex epidemiological scenario due to the selection of LGV genovariants through mutation and recombination. IMPORTANCE Numerous international organizations, including the World Health Organization, have been drawing attention to the global increase in sexually transmitted infections. Twenty years ago, lymphogranuloma venereum (LGV) was mainly considered a tropical disease; in recent decades, however, LGV has been increasingly present in high-income countries. This increase has been linked to men who have sex with men who participate in highly interconnected sexual networks, leading to a rapid spread of LGV. This study focuses on the spread of LGV, presenting the largest time series of LGV prevalence in Spain, which includes more than a thousand diagnosed cases in one large city. The number of LGV cases diagnosed was analyzed over time, and a selection of strains was subjected to molecular genotyping. The results indicate that the LGV epidemic is gradually evolving toward an increasingly complex diversification due to the selection of successful genovariants that have emerged by mutation and recombination events, suggesting that we are moving toward an unpredictable scenario.