Full Text Review
Screening for Chlamydial Infection
Prepared by H. Dele Davies, MD, MSc, FRCPC, Assistant Professor of Microbiology,
of Infectious Diseases and of Pediatrics, University of Calgary, Alberta
These recommendations were finalized by the Task Force in October 1992
Contents
Overview
In 1984,
the Canadian Task Force on the Periodic Health Examination found that there
was fair evidence to support exclusion of routine screening of the general
population for chlamydial infections (D Recommendation), poor evidence
to support inclusion or exclusion of screening for high risk groups (C
Recommendation), and fair evidence to support screening of pregnant women
(B Recommendation).< 1>
After review of the literature published subsequently, the Task Force now
recommends screening for both high-risk groups and pregnant women (B Recommendations)
but not for the general population (D Recommendation). The basis of these
recommendations includes:
-
The burden of illness caused by asymptomatic chlamydial
infections and their sequelae is high;
-
Currently available screening tests are accurate, reliable
and cost effective for high-risk groups;
-
Effective treatment is available; and
-
Earlier detection leads to improved health outcome,
consisting of prevention of symptomatic disease in high risk non-pregnant
women and men and improved outcome of pregnancy.
Burden
of Suffering
Infection with Chlamydia trachomatis is the most common
sexually transmitted disease (STD) in North America, causing two to five
times more infections than Neisseria gonorrhea. In Canada, the incidence
is 216 per
100,000
population.<2> Most infections in females (60-80%) are asymptomatic,
but the disease spectrum includes mucopurulent cervicitis (MPC), endometritis,
salpingitis, the urethral syndrome, proctitis, post-abortal pelvic sepsis
and perihepatitis. In numerous case-control and cohort studies chlamydial
infection has been associated with the long-term complications of pelvic
inflammatory disease (PID), infertility and ectopic pregnancy. Serologic
studies suggest that 64% or more of tubal infertility and 42% of ectopic
pregnancies are attributable to chlamydial infection. Screening in different
female populations in Canada have shown carrier rates of 1%
to 25%. In Canada the women at highest risk for chlamydial infection are
those who are sexually active and aged 15-19
years, followed by 20-25 years.<2> Other factors associated with increased
risk of infection include: intercourse with 2 or more partners per year
or a new partner in the preceding year, low socioeconomic class, use of
non barrier contraception, intermenstrual bleeding, cervical friability
and purulent discharge on examination. Infection rates in pregnant women
range from 5% to 25%. In prospective cohort studies, 11%
to 44% of infants born to mothers infected with chlamydia developed conjunctivitis
and 11-20%
developed pneumonia<3-6> during the first year of life.
In males, the spectrum of disease due to C. trachomatis
includes urethritis, epididymitis, prostatitis and occasionally proctitis
or proctocolitis via homosexual transmission. Up to 50% of reported cases
of non-gonococcal urethritis and 31%
of cases of acute epididymitis are due to C. trachomatis. One percent to
21% of all
men may be asymptomatic carriers and act as a reservoir for spread. Younger
age, multiple sexual partners in the preceding year, and a history of gonorrhea
in the past year are associated with increased likelihood of chlamydial
infections in males.
Maneuver
There is no simple, inexpensive laboratory test for
diagnosing C. trachomatis infections, and different anatomical sites require
different screening tests. In adult females, examination with a speculum
and endocervical swabs are the appropriate methods. In prepubertal females,
the immature vagina is the genital site of infection with C. trachomatis
and N. gonorrhea. Thus, a speculum examination to obtain a cervical specimen
is both unnecessary and potentially traumatic.
Cervical swab for chlamydial culture has an estimated
sensitivity of 75% to 90%, and a specificity of 100%
but test time is 2-3 days. Cotton tipped aluminum and rayon tipped plastic
swabs are superior to calcium alginate or cotton tipped wooden swabs for
maximum yield of culture. This mode of diagnosis of C. trachomatis is expensive
and time consuming, and requires technical expertise unavailable to most
clinical laboratories. Cytologic testing using Giemsa or other methods
is 95-100%
sensitive for detecting conjunctivitis, but has low sensitivity for diagnosis
of genital infections. Direct fluorescent antibody (DFA) testing using
fluorescein-conjugated monoclonal antibodies and enzyme-linked immuno-assays
(EIA) are the most widely used non-culture techniques for diagnosing cervical
infections in clinical practice. DFA test time ranges from 15
minutes to 1 hour
while EIA requires from 3-5 hours. They are not recommended for use on
throat and rectal specimens from sexually abused children because chlamydia
may cross react with bacterial flora giving false positive results. DFA
sensitivity is 70-100%
and specificity is 85-98% when compared to culture of cervical and urethral
specimens in women.<7-9> The sensitivity and positive predictive value
of DFA decrease significantly as the prevalence of chlamydia in the population
decreases. EIA has a sensitivity of 67-98% for cervical infections and
specificity can be increased from 85% to almost 100%
by the use of confirmatory blocking antibody assays.<10>
In men, C. trachomatis infections have traditionally
been diagnosed by culture, DFA or EIA on urethral swabs. However, in contrast
to women, testing of first void urine (FVU) specimens gives a yield that
approaches that of urethral swabs. This represents a non-invasive alternative
for chlamydial screening.<11,12>
Polymerase chain reaction (PCR) testing of cervical
specimens in women and FVU specimens in men is 95–100%
sensitive and almost 100%
specific and its use may become more widespread with the availability of
commercial kits.<13,14>
Nucleic acid probes are about 95% sensitive and 98–100%
specific when compared to culture, are available in 2-4 hours, and like
EIA can be used for large volumes of samples, but are currently limited
by high cost.
Effectiveness
of Screening and Treatment
Although effective treatment is available for chlamydial
infections, no controlled studies have demonstrated that screening of non-pregnant
men or women leads to reduction in complications.
Treatment of
C. Trachomatis
Tetracyclines are the drugs of choice for treatment
of C. trachomatis infections in non-pregnant females and in males.<15,16>
The recommended dosage is 500 mg by mouth, four times a day for 7 days
or doxycycline 100
mg by mouth, two times a day for 7 days.
Traditionally, erythromycin 500 mg by mouth, four
times a day for 7 days has been recommended for pregnant women and for
those in whom tetracycline is contraindicated. Erythromycin is curative
in 90% or more of patients who are able to take it.<17>
The major drawback of the 2 g dose is the high incidence of gastrointestinal
side effects. Amoxicillin 500 mg by mouth, three times a day for 7 days
was shown in a recent double-blind randomized trial to be equal in efficacy
to erythromycin, but with fewer dropouts due to side effects.
More recently, introduction of azithromycin has raised
the prospect of single dose therapy. In prospective studies,<18-21>
a single 1 g
dose of oral azithromycin was as effective as 100
mg of doxycycline given twice a day for 7 days in eradicating uncomplicated
urogenital C. trachomatis infections in men and women. Side-effects (mainly
gastrointestinal) were mild and of equal frequency in both treatment groups.
Azithromycin is licensed in the United States but is not currently available
in Canada. Ofloxacin 300 mg twice a day for 7 days is also efficacious
for treatment of uncomplicated infections in non-pregnant women,<22>
but is expensive for first line usage.
Studies of Screening
for Chlamydia in Pregnancy and Outcome
Five published studies have assessed the outcome in
screened pregnant women.<23-27> The first study<23> was retrospective
cohort in nature with a 5.8% incidence of chlamydial infection among 5,875
pregnant women screened with DFA during their first prenatal visits and
then every 2 to 3 months. Infected patients who were successfully treated
with erythromycin had significantly lower rates of premature delivery (2.87%)
compared to those who failed therapy (13.92%)
and those who were negative for chlamydia (11.89%).
There were also significantly lower rates of premature rupture of membranes
(PROM), premature contractions, and small for gestational age (SGA) infants
in those successfully treated compared with those who failed treatment.
Similarly, in a prospective cohort study<24> involving 11,554
women screened with culture at their first prenatal visit, 1,110
were treated with erythromycin, 1,323
were left untreated and 9,111 were
not infected. PROM and SGA babies were twice as common in the untreated
group compared with the treated and uninfected groups. There was also a
four-fold improvement in perinatal mortality in the treated compared to
the untreated group.
The third study<27> provided weak evidence of
improved outcome of screening. During their third trimester, 1,082
women were cultured for C. trachomatis. Eighty five (7.8%) were positive
for chlamydia, and erythromycin therapy (500 mg twice a day for 10
days) was prescribed for 38 of these women. There were no complications
in the treated women compared with complications in 5 of 47 untreated women
(chorioamnionitis, endometritis, post partum fever, and a growth retarded
infant). Only 37 infants from the original 85 (41%)
were available for follow-up. In all these positive studies, the main value
of screening may have been due to other effects of erythromycin and not
necessarily the eradication of chlamydia. Erythromycin in the 3rd trimester
for women infected with Ureaplasma urealyticum and Mycoplasma hominis also
reduced the incidence of low birth weight infants and increased mean birth
weights.<28>
A fourth study<25> of poorer quality found no
difference in incidence of infant pneumonia and conjunctivitis in treated
and untreated women screened for chlamydia from a high prevalence (26%)
population. This study was limited by small sample size (199
women) and by the possibility of other confounding factors in untreated
women. A final prospective cohort study<26> involved 184
pregnant women screened for chlamydia by culture at their first prenatal
visit and treated with erythromycin at 36 weeks gestation. Seventy-seven
women (42%) were lost from the study; only 83 infants had complete follow-up.
Using chlamydial disease as end point, 2 treated infants had pneumonia
and 1 had
conjunctivitis (3/59 or 5% total complication rate), compared with infants
of 4 untreated women with pneumonia and 1
with
conjunctivitis (5/24 or 21%
total complication rate).
Thus, three cohort studies<23,24,27> have provided
fair (Level II) evidence for screening and intervention leading to better
outcome for some perinatal complications. Of the remaining two smaller
studies,<25,26> one supported, but the other did not support screening.
Contact Tracing
Contact tracing is an integral part of attempts at chlamydia
control. In most studies, men are more efficient in transmitting C. trachomatis
to their female partners with spread 40-64% of the time, whereas women
transmit the infection to their male partner 21-35%
of the time.<29-33> However, given the efficiency of transmission, and
despite difficulties in tracing partners, treatment of contacts may be
more cost effective than screening.
Costs and Economic
Evaluations
Chlamydial infections are estimated to cost over U.S.
$2.2 billion a year in the U.S.<34> Infections in women account for
over 79% of this cost.
Economic evaluations support chlamydial screening
of asymptomatic persons under specific conditions. Phillips et al<35>
used decision analysis to estimate the clinical and economic implications
of testing for cervical infection caused by C. trachomatis in asymptomatic
women during routine gynecologic visits. A strategy of no routine testing
was compared with one involving routine cultures or use of non-culture
tests (DFA or EIA). They concluded that the use of the non-culture tests
would reduce overall costs if the prevalence of infection was 7% or greater,
and routine cultures if the prevalence was 14%
or more.
In Canada, Estany et al<36> calculated that screening
with DFA or EIA in women would be cost effective if the prevalences of
chlamydial infection by each method exceeded 6% and 7% respectively. The
mean cost of DFA and EIA was estimated at $11.
Sensitivity analysis showed that the two most important factors in cost
savings were the probability of developing PID and the cost of the test.
Sellors et al<37> recently determined that selective screening of sexually
active young women with EIA is an effective and efficient strategy for
detecting chlamydia. Their model was based on average cost of $8.66 for
culture and $9.33 for EIA. Nettleman et al<38> estimated that DFA testing
of all pregnant women would be cost effective if the test cost less than
U.S. $6.30 or the prevalence of infection exceeded 6%.
Recommendations
of Others
In 1989
the U.S. Preventive Services Task Force<39> recommended routine screening
for asymptomatic persons at high risk of infection, and at the first prenatal
visit for pregnant women in high-risk categories. These recommendations
are currently being reviewed. The Canadian Expert Interdisciplinary Advisory
Committee on Sexually Transmitted Diseases in Children and Youths<15>
suggested more extensive screening, but many of their screening recommendations
were intended for detection of STDs other than chlamydia. Children recommended
for screening by this committee included sexual contacts of people with
proven or suspected urethritis or other STDs, sexual contacts of high-risk
adults, pregnant adolescents, male and female prostitutes, street youth,
users of illicit drugs, young women undergoing therapeutic abortion, those
with a history of previous STDs, children and siblings of children who
have been sexually abused, and neonates with one or both parents known
to have urethritis, cervicitis, PID, epidydimitis or other STDs.
More recently, the Centers for Disease Control have
suggested screening women with MPC, sexually active women <20 years
of age, women 20-24 years of age who are inconsistent in their use of barrier
contraceptives or having new or more than one sex partner during the last
3 months.<40>
Conclusions
and Recommendations
Although there is sufficient evidence linking chlamydial
infections to many complications, there is currently insufficient evidence
in males and non-pregnant females to show that screening is effective in
preventing these complications. Thus routine screening is not recommended
in the general population (D
Recommendation). However, the high burden of illness caused by chlamydia
and favourable economic evaluation studies suggest that screening of certain
populations at high risk for asymptomatic chlamydial infection may be useful
to try and prevent symptoms and to reduce overall cost of infection (B
Recommendation). These high risk groups are – sexually active females
less than 25 years old, new partner or two partners in preceding year,
cervical friability, use of non-barrier contraception and women symptomatic
with mucopurulent discharge or intermenstrual bleeding. Although the benefits
may be related to treatment with erythromycin, there is fair evidence (Level
II-2) that screening of pregnant women leads to improvements in pregnancy
outcome (B Recommendation).
Unanswered
Questions (Research Agenda)
A prospective, well designed randomized community trial
of screening for chlamydial infections in two similar asymptomatic populations
for development of complications is warranted.
Evidence
The literature was identified with a MEDLINE search
conducted by exploding the major MESH heading Chlamydial trachomatis with
the subheadings complications, diagnosis, drug therapy, economics, epidemiology,
etiology, history, microbiology, mortality, prevention and control, therapy,
and transmission, for the years 1983
through 1993.
This review was initiated in June 1992
and the recommendations finalized by the task force in October 1992.
Acknowledgements
The Task Force would like to acknowledge the help of
Robert C. Brunham, MD, FRCPC, Professor and Head, Department of Medical
Microbiology, University of Manitoba, Winnipeg, Manitoba, John W. Sellors,
MSc(DME), MD, CCFP, FCFP, Associate Clinical Professor, McMaster University,
Hamilton, Ontario and Paul R. Gully, MB, ChB, FFCM, FRCPC, Chief, Division
of STD control, Health Protection Branch, Health Canada, Ottawa, Ontario
for very useful comments on the technical report.
Full Citation
Link to Structured Abstract of
this review
Link to Summary Table of this
review
Link to Selected References list of
this review
Link to 1996 update: Screening for chlamydial
infections
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