Chlamydia Trachomatis Genital Infection Clinical Trial
Official title:
Are Rectal and Genital Chlamydia Trachomatis Infections in Women Related to Anal Sex, Autoinoculation / Contamination
Chlamydia trachomatis is the most common cause of sexually transmitted bacterial infection in
Sweden, an infection that is notifiable according to the Communicable Diseases Act and the
Communicable Diseases Ordinance.
Women account for 57 % of all cases detected since 1993. Recently published studies describe
a high proportion of positive rectal chlamydia tests in women and in half of the cases there
is no history of anal sex. In almost 20 % of cases, chlamydia has only been found rectally.
Samples in these studies were self-collected and although the sensitivity of modern NAATs
(Nucleic Acid Amplification Tests) is very high, there is even high risk of contamination of
the sample due to the short anatomical distance between the vagina and the anus. Furthermore
the vaginal sample has been taken prior to the rectal sample in the largest study from the
Netherlands, something that further increases the risk of contamination of the rectal sample.
There are experimental animal models which support the theory that chlamydia can be
transferred along the gastrointestinal tract! This is a possible explanation for the
occurrence of rectal chlamydia in women who have not had anal intercourse, but it is
necessary to minimize the risk of contamination.
The study will take part in three STD-clinics (2 counties) where two clinics are in the
county of Östergötland (Norrköping and Linköping with totally 300 000 inhabitants) and one in
the county of Jönköping (120 000 inhabitants).
The risk of contamination of the rectal samples is minimized as the rectal sample is taken
first and with the use of a pediatric proctoscope (a proctoscope that is designed to examine
children) which is first inserted in the anus to allow sample collection from the rectal
mucosa above the pectinate line, while avoiding contact of the collecting swab with the
perineal skin. Then vaginal speculum examination is performed and samples are taken from
endocervix and vagina for C.trachomatis N.gonorrhoeae and M.genitalium tests. Extra samples
from the anus and the vagina will be collected and immediately frozen to minus 80 degrees to
allow further testing with vPCR (viability Polymerase Chain Reaction). Positive chlamydia
samples will be further analyzed with a high resolution method (Multi Locus Sequence Typing,
or MLST and if necessary Multi-Locus Variable number tandem repeat Analysis or MLVA) to make
the discrimination of various chlamydia types possible.
In the county of Östergötland.
Both STD (Sexually Transmitted Diseases) outpatient clinics in Östergötland belong to the
Department of Dermatology and Venereology in Region Östergötland. The attendee has two
options: either makes an appointment to a physician if the attendee has symptoms or wishes a
gynecological exam because of other reasons, or make an appointment to a nurse for
self-collecting tests.
All attendees answer a questionnaire including experience of receptive anal sex and fellatio
(and condom use) during the last 12 months. In the study questionnaire there is an additional
question regarding fellatio and whether it happened that a male partner ejaculated in her
oral cavity.
At the visit by the physician:
The exam starts with an Abbot multi-collect swab taken from the anal verge, at the opening of
the anal canal, where the inverstigators think the most self-taken samples come from. This
sample will be immediately frozen for later analysis.
A pediatric proctoscope (a proctoscope designed and manufactured to examine children) is used
for sampling the rectal specimens using an Abbot multi-collect swab and a standard Sigma swab
of Sigma virocult, followed by vaginal speculum examination. Firstly samples from the lateral
fornix for wet smear are collected, secondly a swab for methylene-blue staining from the
endocervical orifice followed by two Abbot multi-collect swabs for chlamydia/gonorrhoea and
M.genitalium respectively from the orifice, the portio and the vaginal wall and one standard
Sigma swab of Sigma virocult from the same areas. Lastly a sample is collected from the
distal urethra and stained with methylene blue.
Samples collected with standard Sigma swab of Sigma virocult will be immediately frozen in
minus 80 grades.
Microscopic examination using a modern Zeiss microscope (Axio Lab A1) is performed. All the
tubes for the chlamydia samples and the virocult samples have an extra label for the study.
All women tested with a pediatric proctoscope will answer a questionnaire about their opinion
regarding this examination procedure.
At the visit by the nurse:
The participant collects the rectal sample for chlamydia/gonorrhea with an Abbot
multi-collect swab first and is instructed to try not to touch the perianal/perineal areas
with the swab. Then the vaginal samples for chlamydia/gonorrhoea and Mycoplasma genitalium
are collected by the patient using the same type of swab.
Attendees initially not treated but turned out to have chlamydia will be asked to be tested
once more to take new samples with the pediatric proctoscope before treatment is given.
Some women attend because of a verified chlamydia infection of their current partner and
those are offered treatment with doxycycline. In these cases the nurse will collect first an
Abbot multi-collect swab taken from the anal verge, at the opening of the anal Canal and then
the rectal samples (one Abbot multi-collect swab and one standard Sigma swab of Sigma
virocult) by using the pediatric proctoscope prior to the vaginal swabs which will be
self-collected (one Abbot multi-collect and one standard Sigma swab of Sigma virocult).
There is another group of women who have been tested positive for chlamydia by self-collected
vaginal swab which is sent to the patient by mail. Those are requested to attend the
STD-clinic for partner tracing and are offered antibiotic treatment with doxycycline as
standard treatment. Those accepting to participate in the study will be tested again and a
nurse will collect first an Abbot multi-collect swab taken from the anal verge, at the
opening of the anal canal that will be immediately frozen for later analysis and then the
rectal swabs by using a pediatric proctoscope (one Abbot multi-collect and one standard Sigma
swab of Sigma virocult) and the participant will collect a new vaginal sample for
chlamydia/gonorrhea and one for M.genitalium (two Abbot multi-collect swabs) The first sample
from the anal verge and all samples collected with standard Sigma swab of Sigma virocult will
immediately be frozen to minus 80 grades for later analysis.
All samples have an extra label for the study. All women tested with a pediatric proctoscope
will answer a questionnaire about their opinion regarding this examination procedure.
In the county of Jönköping:
The STD clinic of the County of Jönköping has another policy to trace and treat chlamydia
trachomatis infections and the group of patients that is suitable for the study is women
attending the STD clinic because of a verified chlamydia infection of their current partner.
This group of patients is examined and tested by a nurse or doctor before doxycycline
treatment is offered.
Those accepting to participate in the study answer the questions about the experience of
receptive anal sex and fellatio (and condom use) during the last 12 months and even an
additional question regarding fellatio and whether it happened that a male partner ejaculated
in her oral cavity.
The exam starts with an Abbot multi-collect swab taken from the anal verge, at the opening of
the anal canal. This sample will be immediately frozen for later analysis.Then the
participant is tested with a pediatric proctoscope and two rectal samples are collected (one
Abbot multi-collect and one standard Sigma swab of Sigma virocult) and even vaginal samples
are collected at the same time (one Abbot multi-collect and one standard Sigma swab of Sigma
virocult) The Abbot multi-collect swabs will be sent to Linköping for analysis. The first
sample collected with Abbot multi-collect swab from the anal verge and all samples collected
with standard Sigma swab of Sigma virocult will immediately be frozen to minus 80 grades for
later analysis.
All samples have an extra label for the study. All women tested with a pediatric proctoscope
will answer a questionnaire about their opinion regarding this procedure.
Positive chlamydia samples will be further analyzed with a high resolution method (Multi
Locus Sequence Typing, or MLST and if necessary Multi-Locus Variable number tandem repeat
Analysis or MLVA) to make the discrimination of various chlamydia types possible.
Discordance between chlamydial types in vagina and anus will favor the hypothesis of a
currently unknown chlamydia reservoir in the anal region or a possible orogastrointestinal
way of infection due to unprotected oral sex. Concordance will favor the autoinoculation of
chlamydia from vagina to anus or vice versa. Moreover vPCR testing of the frozen samples will
allow discrimination of real chlamydial infections (presence of viable bacteria) from
contamination (presence of chlamydial DNA but not of viable bacteria). The history of oral
sex and the difference in the groups that during sexual intercourse have had and have not had
semen in the oral cavity may or may not strengthen the hypothesis of orogastrointestinal
transport of chlamydia. After the sample collection with the pediatric proctoscope a
questionnaire will be given to the attendees to investigate if the participants feel that
this is an acceptable way to obtain rectal samples.
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