# Unexpected increase in ompA-genotype L1 variants responsible for anorectal lymphogranuloma venereum in France.

Arabella Touati, Cécile Laurier-Nadalié, Cécile Bébéar, Olivia Peuchant

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Arabella Touati, Cécile Laurier-Nadalié, Cécile Bébéar, Olivia Peuchant. Unexpected increase in ompA-genotype L1 variants responsible for anorectal lymphogranuloma venereum in France.. The Lancet Microbe, In press, pp.101097. 10.1016/j.lanmic.2025.101097. hal-04984177

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Submitted on 10 Mar 2025

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Distributed under a Creative Commons Attribution 4.0 International License
Unexpected increase in
*ompA-genotype L1*
variants responsible
for anorectal
lymphogranuloma
venereum in France

Investigations into circulating *Chlamydia trachomatis* genotypes are useful to elucidate the dynamics and evolution of lymphogranuloma venereum. *ompA*-genotype L2b was the causative agent of the first cases of rectal lymphogranuloma venereum in Europe in 2003, which then spread globally.¹ Since 2013, the evolution of the ongoing lymphogranuloma venereum epidemic has been marked by a shift to *ompA*-genotype L2 and emergence of *ompA*-genotype L2 and L2b variants.²

In France, the diversity of ompA-
genotypes responsible for lymphogra-
nuloma venereum is monitored by
sequencing the ompA gene from all
lymphogranuloma venereum-positive
rectal samples collected as part of
a 3-month prospective nationwide
survey with universal lymphogranu-
loma venereum screening.³ This sur-
veillance was initiated in 2020 and
has been conducted every year by
the National Reference Center for Bac-
terial Sexually Transmitted Infections,
Bordeaux, France.

Collection and analysis of 652 anorectal lymphogranuloma venereum-positive specimens between 2020 and 2024 indicated a significant decrease in the *ompA*-genotype L2 (p<0.0001) and disappearance of the *ompA*-genotype L2b variant (appendix p 1). In contrast, the proportions of the *ompA*-genotype L1 variants increased markedly: two (1.5%) of 137 in 2020, two (1.6%) of 128 in 2021, 12 (8.9%) of 135 in 2022, 15 (15.3%) of 98 in 2023, and 40 (26%) of 154 in 2024.

We identified three ompA-genotype L1
variants that differed from the L1/440
reference strain. The first, GenBank
accession number MN563611.1, differed

by ten mutations and was the most fre-
quent (58 [81.7%] of 71 samples). The
first variant was identified in two
samples in 2020 and 2021 each,
12 samples in 2022, 14 samples in
2023, and 28 samples in 2024. The
second, PQ151388, differed by 11 muta-
tions and was detected in one sample
in 2023 and 11 samples in 2024.
The third, PQ1656811, differed by
12 mutations and was identified in
one sample in 2024. All the ompA-
genotype L1 variants identified in our
study had the characteristic nine-bp
insertion in the pmpH gene of variant
L2b,² suggesting recombination between
the genomes of lymphogranuloma
venereum strains. The L1 variants were
not geographically clustered and were
distributed throughout France. No
associations were found between the
L1 variants and anorectal symptoms,
HIV status, or pre-exposure prophylaxis
use.

Lymphogranuloma venereum cases
with the ompA-genotype L1 variant
(GenBank GQ413956) were first described
in the 1980s among men who have sex
with men.⁴ This strain did not spread
further during the lymphogranuloma
venereum outbreak. *OmpA-genotype*
L1 variants were sporadically reported
in Europe since 2014.² Conversely,
*ompA-genotype L1* variants accounted
for 27 (31%) of 88 of the lymphogra-
nuloma venereum cases in Argentina
from 2017 to 2019.⁵

In conclusion, our results highlight the
unique genotype distribution of lym-
phogranuloma venereum in France in
2024, which is characterised by the
presence of ompA-genotype L1 variants
in about a quarter of the cases. The
occurrence of ompA-genotype L1 variants
is unprecedented among lymphogra-
nuloma venereum cases in Europe and
reflects changes in the operating sexual
networks of men who have sex with
men and distinct migration or travel
patterns.

We declare no competing interests. This work did not
receive any funding. CB and OP designed the study.
CL-N collected the demographic, clinical, and
biological data. AT sequenced the ompA and pmpH

genes. CL-N, AT, and OP analysed the data. AT and
OP prepared the first draft of the manuscript. All
authors reviewed and approved the final version of
the manuscript. We would like to thank all clinicians
and biologists who participated in the
lymphogranuloma venereum surveillance network.
The French national sentinel surveillance for
anorectal *Chlamydia trachomatis* infections was
approved by the French Data Protection Authority,
Commission Nationale de l'Informatique et des
Libertés (approval number 10.362), and data were
collected after written informed consent was
obtained from the affected patients.

Copyright © 2025 The Author(s). Published by
Elsevier Ltd. This is an open access article under the
CC BY-NC-ND license (http://creativecommons.org/
licenses/by-nc-nd/4.0/).

Arabella Touati, Cécile Laurier-Nadalié,
Cécile Bébéar, *Olivia Peuchant
olivia.peuchant@u-bordeaux.fr

Centre Hospitalier Universitaire de Bordeaux,
Department of Bacteriology, National Reference
Centre for Bacterial Sexually Transmitted Infections,
Bordeaux 33000, France (AT, CL-N, CB, OP); University
of Bordeaux, UMR 5334 CNRS Microbiologie
Fondamentale et Pathogénité, Antimicrobial
Resistance in Mycoplasmal and gram-NEGative
bacteria (ARMYNE), Bordeaux, France (CB, OP)

1. Harris SR, Clarke IN, Seth-Smith HM, et al. Whole-genome analysis of diverse *Chlamydia trachomatis* strains identifies phylogenetic relationships masked by current clinical typing. *Nat Genet* 2012; **44**: 413-19.

2 Seth-Smith HMB, Bénard A, Bruisten SM, et al. Ongoing evolution of *Chlamydia trachomatis* lymphogranuloma venereum: exploring the genomic diversity of circulating strains. *Microb Genom* 2021; **7**: 000599.

3 Peuchant O, Laurier-Nadalié C, Albucher L, et al. Anorectal lymphogranuloma venereum among men who have sex with men: a 3-year nationwide survey, France, 2020 to 2022. *Euro Surveill* 2024; **29**: 2300520.

4 Christerson L, de Vries HJ, de Barbeyrac B, et al. Typing of lymphogranuloma venereum *Chlamydia trachomatis* strains. *Emerg Infect Dis* 2010; **16**: 1777-79.

5 Büttner KA, Entrocassi AC, Gallo Vaulet ML, et al. ompA sequencing and multilocus sequence typing of lymphogranuloma venereum cases in Buenos Aires reveal new *Chlamydia trachomatis* genotypes. *Microorganisms* 2024; **12**: 587.

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Lancet Microbe 2025

Published Online
https://doi.org/10.1016/
j.lanmic.2025.101097

See online for appendix