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



Objective
To make recommendations about screening for chlamydial infection (Chlamydia trachomatis) among general, high risk and pregnant populations in Canada. This updates a 1984 report.

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. Screening in different female populations in Canada have shown carrier rates of 1% to 25%, while 1% to 21% of all men may be asymptomatic carriers.  Risk factors for women include sexual activity during adolescence, intercourse with 2 or more partners per year or new a partner in the preceding year, low socioeconomic class, use of non barrier contraception, intermenstrual bleeding, cervical friability and purulent discharge on examination.  Risk factors for men include younger age, multiple sexual partners in the preceding year, and a history of gonorrhea in the past year.
 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. In males, the spectrum of disease due to C. trachomatis includes urethritis, epididymitis, prostatitis and occasionally proctitis or proctocolitis via homosexual transmission.

Options
Primary screening tests for adult women included speculum examination and endocervical swab; cytologic testing using Giemsa or other methods; direct fluorescent antibody (DFA) test using fluorescein-conjugated monoclonal antibodies; and enzyme linked immuno-assays (EIA). Screening options for men were culture, DFA or EIA on urethral swabs, and testing of first void urine. Other options included polymerase chain reaction testing of cervical specimens in women, first void volume in men, and nucleic acid probes.

Pharmacologic therapy included tetracyclines, erythromycin, azithromycin, and ofloxacin.

Outcomes
Sensitivity, specificity, test time and costs. Health outcomes for pregnant women included premature delivery, premature rupture of membranes (PROM), premature contractions, and pregnancy complications. Outcomes for their infants included small for gestational age (SGA) infants, perinatal mortality, pneumonia, conjunctivitis, and total complication rate. Overall costs and cost-effectiveness were discussed.

Evidence
MEDLINE was searched for 1983 to 1993 using the exploded MeSH heading "Chlamydial trachomatis" with subheadings "complications", "diagnosis", "drug therapy", "economics", "epidemiology", "etiology", "history", "microbiology", "mortality", "prevention and control", "therapy" and "transmission". Study results were synthesized in table or graphic format only.

Values
The 13-member Task Force of experts in family medicine, geriatric medicine, pediatrics, psychiatry and epidemiology used an evidence-based method for evaluating the effectiveness of preventive health care interventions. Recommendations were not based on cost-effectiveness of options. Patient preferences were not discussed.

Background papers providing critical appraisal of the evidence and tentative recommendations prepared by the chapter author were pre-circulated to the members. Evidence for this topic was presented and deliberated upon in 1- to 2-day meetings from October 1993 to March 1994. Consensus was reached on final recommendations.

Benefits, Harms, and Costs
Cervical swab for culture has a sensitivity of 75% to 90% and a specificity of 100%, but the test is expensive, takes 2 to 3 days and requires specific technical expertise. Cytologic testing is 95% to 100% sensitive for conjunctivitis, but has low sensitivity for genital infections. DFA sensitivity and specificity are 70% to 100% and 85% to 95%, respectively; test time is 15 minutes to 1 hour. EIA takes 3 to 5 hours, has a sensitivity of 37% to 98%, and a specificity of 85% for cervical infections. Polymerase chain reaction testing of cervical specimens and first void urine specimens from men is 95% to 100% sensitive and almost 100% specific. Nucleic acid probes are 95% sensitive and 98% to 100% specific, are available in 2 to 4 hours, but are costly.

3 cohort studies provide evidence of improved pregnancy-related outcomes with screening and erythromycin therapy. Of 2 smaller studies, one found no difference in infant complications (pneumonia, conjunctivitis) in treated and untreated groups, while the other reported that 3/59 (5%) infants of treated women had complications compared with 5/24 (21%) infants of untreated women.

No controlled studies have shown that screening of men or non-pregnant women leads to decreased infection-associated complications.

Economic evaluations support screening under certain conditions. One decision analysis reported that non-culture or culture tests of asymptomatic persons could reduce overall costs if disease prevalence was 7% or 14% respectively. A Canadian study estimated that DFA or EIA screening of women would be cost effective if the disease prevalence was >6% or 7% respectively. Mean cost of DFA and EIA was $11. Sensitivity analysis showed that probability of developing PID and test cost were most important to cost savings. Another study estimated that DFA testing of pregnant women would be cost effective if disease prevalence >6% and test cost was <US $6.30.

Recommendations
Recommendation grade [A, B, C, D, E]  and level of evidence [I, II-1, II-2, II-3, III] are indicated after each recommendation. Citations in support of individual recommendations are identified in the guideline text.

Validation
This report was externally peer-reviewed. The Canadian Expert Interdisciplinary Advisory Committee on Sexually Transmitted Diseases in Children and Youths recommended more extensive screening, primarily aimed at diseases other than chlamydia. The US Centers for Disease Control and Prevention recommend screening women with mucopurulent cervicitis, sexually active women <20 years, and women who are inconsistent users of barrier contraceptives or who have new or >1 new partners in past 3 months.

Sponsors
The Canadian Task Force on the Periodic Health Examination developed this guideline with funding from Health Canada.

Selected References

Source Document

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.

Other
Canadian Task Force on the Periodic Health Examination. The periodic health examination. Can Med Assoc J. 1984;130:1278-85.