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:
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
Davies H.D. Screening for chlamydial infection.
In: Canadian Task Force on the Periodic Health Examination. Canadian
Guide to Clinical Preventive Health Care. Ottawa: Health Canada,
1994; 732-42.