Introduction
An outbreak of rectal lymphogranuloma venereum (LGV) was detected among
men who have sex with men (MSM) in Rotterdam during the summer of 2003
[1]. LGV, a sexually transmitted infection (STI) caused by Chlamydia
trachomatis genotype L1, L2 or L3 is endemic in tropical countries
but remains rare in industrialized countries. The classical clinical
presentation of the infection is a genital ulcer with buboes. Rectal
presentations have also been described, especially in MSM [2].
After the Dutch alert, a retrospective investigation was conducted in France
which identified 21 cases of rectal LGV. Epidemiological information obtained
for 14 of these 21 cases showed that all the patients were MSM, 8 were
infected with HIV and 9 had also another sexually transmitted infection
(STI). The mean duration of symptoms before diagnosis was lengthy (50 days),
suggesting that clinicians were not aware of this STI [3].
In April 2004, as a public health response to these findings, a large-scale
information campaign aimed at microbiologists, clinicians and groups focusing
on MSM was begun, and a voluntary-based sentinel LGV surveillance system
was launched in France. The results of this surveillance are presented
in this paper.
Methods
Sentinel Surveillance design
In April 2004, six centres were recruited on a volunteer basis. They
included two STI clinics, a laboratory, an outpatient proctology clinic
and two microbiology laboratories, and all were located in Paris. The
national reference centre, which is located in Bordeaux, also participated.
In 2005, six additional laboratories located in other large cities were
recruited
All rectal swabs positive for C. trachomatis by PCR were sent to the
national reference centre, where genotyping was performed. Participating
clinicians and microbiologists were also asked to provide basic epidemiological
data such as age, HIV status, date of symptom onset, and date of sampling.
Anonymised microbiological and clinical data were sent to InVS for analysis.
Case definition
Only confirmed rectal cases were included in the LGV surveillance. A
confirmed rectal case was defined as a male patient with symptomatic
proctitis due to C. trachomatis diagnosed using polymerase chain reaction
(PCR) [Cobas Amplicor Roche Diagnostic System, Meylan, France] with
the C. trachomatis strain belonging to L1, L2 or L3 genotype.
C. trachomatis strain genotyping was performed at
the national reference centre for Chlamydia infection using
a nested omp1 PCR-restriction fragment length polymorphism
assay [4].
Since a new LGV C. trachomatis variant characterised by a single
mutation in the omp1 gene of the major outer membrane protein (MOMP)
and named L2b had recently been identified [5], the omp1 gene of a random
sample of L2 strains isolated in France during 2004-2005 was sequenced.
Results
From March 2004 to December 2005, 328 rectal C. trachomatis strains
were genotpyed.
Of these, 244 (74%) belonged to the L2 genotype, which confirmed the
diagnosis of rectal LGV. No C. trachomatis strain belonging
to the L1 or L3 genotype was found.
For 22 rectal LGV cases which occurred between April 2002 and December
2003, the diagnosis was made retrospectively in March 2004. For 2004,
104 rectal LGV cases (24 cases retrospectively from January to March
and 80 prospectively from April onwards) were reported to the LGV surveillance
system. For 2005, 118 rectal cases were recorded [FIGURE].
Of the 244 identified rectal LGV, 174 (72%) were sequenced, and all
these exhibited the omp1 gene mutation of the MOMP that characterises
the newly described L2b variant. The median age of patients with a rectal
LGV infection was 39 years (range: 34-44). HIV status was available for
96 patients, and 82 (85%) were known to be infected with HIV. Most of
the patients with rectal LGV lived in the Paris area (92%). Of the remaining
patients, 5% lived in Bordeaux and 3% were diagnosed in other cities,
including Tourcoing, Lille and Marseille.
Eighty five of the genotyped C. trachomatis rectal strains
(26%) did not belong to the LGV genotypes. For these 85 strains, the
genotypes were found to be mainly Da (10%) and G (9%). In 2004, the proportion
of non-LGV genotypes was 20%, in 2005 this proportion increased significantly
from 20% to 30% (chi2= 4.4, P=0.03). Patients with C. trachomatis proctitis
were younger than patients with LGV proctitis, with a median age of 34
years (range: 21-58), and were less likely to have an HIV infection (60%)
(chi2=8.1, P=0.004) than those with LGV proctitis.
Discussion
Since the French surveillance system includes only confirmed cases which
require strain genotyping, and there are only a small number of participating
centres, mainly located in Paris, the number of reported rectal LGV cases
is certainly underestimated for France. However, the number of reported
rectal LGV cases in 2004-2005 higher than in previous years. A study
in the late 1980s at a STI clinic in Paris found two rectal forms diagnosed
in MSM among a total of 27 LGV cases [6], and no further cases were reported
in France until the current epidemic.
The genotyping of C. trachomatis strains appears to be necessary
to confirm the diagnosis of LGV, because a quarter of C. trachomatis
strains isolated in men were not LGV strains.
The number of LGV cases in 2004 and 2005 are similar, but reports of
non-LGV C. trachomatis proctitis increased during this period,
almost certainly due to a surveillance bias (more participating centres).
LGV cases have been diagnosed in several Europeans countries [7] and
in some cities in the United States [8]. In all these countries, LGV
proctitis has only been seen in MSM, most of whom were HIV-infected.
A recent case-control study (LGV proctitis versus non-LGV C. trachomatis
proctitis) showed that HIV infection was strongly associated with LGV
[9]. This result is consistent with the French data in which patients
with LGV are more frequently HIV-infected than those with a non-LGV proctitis
(82% versus 60%). The new variant L2b recently described in the Netherlands
was found in all the sequenced L2 C. trachomatis stains in France
suggesting that this specific LGV strain has spread in the two countries.
The LGV emergence is a serious concern for gay men and in Europe. LGV
diagnosis should be prompt and appropriated treatment administered to
avoid serious sequels as rectal stricture (2) and to interrupt transmission.
Furthermore, rectal LGV characterised by deep mucosal lesions could facilitate
HIV transmission. Patients with rectal LGV are often infected with several
others pathogens such as herpes simplex virus or human papillomavirus.
Screening and treating STIs should be included in the clinical follow–up
of all HIV-infected MSM.
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