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[This document kindly provided by Dr Stary, European President of the IUSTI, and republished here with minor editing for the web. This is a preliminary draft of the recommendations which were finally published in the October issue of the International Journal of STD and AIDS (2001) 12, Suppl 3, 30 - 33.]

1.2.1 Clinical features:
1.2.1.1 In women:
1.2.1.2 In men:
1.2.1.3 In both:
1.2.2 Indications for testing:
1.2.3 Laboratory Diagnosis
1.2.3.1 Cell culture:
1.2.3.2 Direct fluorescent antibody assays (DFA):
1.2.3.3 Enzyme immunoassays:
1.2.3.4 RNA-DNA hybridisation:
1.2.3.5 Nucleic acid amplification (NAA), e.g. PCR or LCR.

1.3.1 General principles.
1.3.2 Indications for therapy.
1.3.3 Recommended antibiotic regimens.
1.3.3.1 Alternative regimens (equivalent).
1.3.4 Special considerations.
1.3.5 Management of chlamydial infections in pregnant women
1.3.5.1 Recommended regimens for pregnant women.
1.3.5.2 Alternative regimens for pregnant women.
1.3.5.3 Special considerations for therapy during pregnancy.
1.3.6 Management of chlamydial infections in HIV-infected persons.
1.3.7 Management of sex partners.

1.4.1 Possible indications for follow up examination:
1.4.2 Timing of test of cure:

2.2.1 Clinical
2.2.2 Indications for testing
2.2.2.1 Laboratory testing:

2.3.1 General principles.
2.3.2 Recommended regimen for neonatal conjunctivitis and pneumonia.
2.3.3 Follow-up.

3.2.1 Laboratory diagnosis.

3.3.1 Recommended Regimen
3.3.2 Follow-up.

References.

1. Urogenital infections among adults

Urogenital infection with C. trachomatis serovars D - K is the most common bacterial sexually transmitted infection in both men and women in European countries. Asymptomatic infection is common especially in women (up to 80%) and often unrecognized, leading to infection in sexual partners and to long term sequela.

1.2.1 Clinical features:

1.2.1.1 In women:

Urogenital infection is symptomatic in ±30% cases:

• Mucopurulent cervicitis

• Purulent vaginal discharge

• Lower abdominal pain

• Postcoital or intermenstrual bleeding

• Dysuria

• Signs of pelvic inflammatory disease (PID) including chronic pelvic pain.

1.2.1.2 In men:

Urogenital infection is symptomatic in ±75% cases:

• Urethral discharge

• Dysuria

• Signs of epididymitis and prostatitis

1.2.1.3 In both:

• Symptoms of rectal, pharyngeal or conjunctival infections; reactive arthritis

• Anorectal discharge or discomfort

• Conjunctivitis

• Arthralgia

1.2.2 Indications for testing:

• Patients with symptoms due to lower genital tract infection caused by C. trachomatis.

• Patients with complications (PID, sexually acquired reactive arthiritis, chronic pelvic pain, tubal sterility, epididymo-orchitis, adult conjunctivitis), which may be caused by C. trachomatis.

• Contact tracing and partner control

• Screening of young adult women <25 years of age

• Screening of men and women who have new or multiple partners

• Screening of men and women who do not consistently use barrier contraceptives

• Screening of women during pregnancy

• Exclusion of infection before medical intervention (termination of pregnancy, IUD insertion, insemination).

1.2.3 Laboratory Diagnosis

Chlamydial diagnosis has rapidly developed during the last few years. The ideal diagnostic test sensitivity is >90% with specificity >99%. Nucleic acid amplifying assays most closely approach these demands. For screening programmes, those techniques which are suitable for non-invasive samples (e.g. urine or introital samples) are preferred.

1.2.3.1 Cell culture:

• Highly specific and therefore still essential for medico-legal diagnosis.

• Sensitivity ranges: 40 to 85% when using genital specimens (cervical, urethral)

• Needs expertise; only for a small number of samples and invasive (cervical, urethral) samples are most appropriate.

1.2.3.2 Direct fluorescent antibody assays (DFA):

• Sensitivity (50-90%) but highly dependent on expertise (considerable learning curve involved) and the number of elementary bodies in the specimen.

• Unsuitable for large numbers of specimens. Useful in experienced hands for a small number of symptomatic patients.

• Suitable for invasive and noninvasive samples (but urine samples are time consuming!).

1.2.3.3 Enzyme immunoassays:

• Sensitivity low in the range 20 to 85%, dependent on the kind of assay.

• High specificity if positive results are confirmed.

• Rapid, machine read so automatable; inexpensive. Thus testing of large numbers of samples is possible, but only really suitable for invasive samples.

1.2.3.4 RNA-DNA hybridisation:

• Sensitivity good, range 70-85%.

• Rapid and machine readable so suitable for automated testing of large numbers of samples.

• Only suitable for invasive samples.

1.2.3.5 Nucleic acid amplification (NAA), e.g. PCR or LCR.

• Highest sensitivity range (70-95%) hence particular care is required to prevent inadvertent contamination in during processing.

• Highest specificity (97-99%) other than cell culture.

• Testing of large numbers of urogenital samples, either invasive (cervical, urethral) or non-invasive (urine and vulvo-vaginal) is possible, but expensive.

• Inhibitors may be a problem, especially for urine samples.

1.3.1 General principles.

Treatment of infected patients must prevent the important sequelae resulting from C. trachomatis infection. It must also prevent transmission of infection to sexual partners or, in pregnancy, to the newborn.

Treatment should be effective (cure rate >95%), with an easy treatment schedule, low side effects and thus high compliance.

Patients with chlamydial infection should be screened for gonorrhoea and other genital tract infections.

1.3.2 Indications for therapy.

• Confirmed oculo-genital C. trachomatis infection

• Infection with C. trachomatis in the partner

• Where laboratory tests for C. trachomatis are not available in a patient with a confirmed N. gonorrhoeae infection

• Where laboratory tests for C. trachomatis are not available in a patient with clinical signs of a chlamydial infection.

The following recommended treatment regimens, or the alternatives, generally cure infection and relieve symptoms.

1.3.3 Recommended antibiotic regimens.

• Azithromycin 1 g orally in a single dose, or

• Doxycycline 100 mg orally twice a day for 7 days.

1.3.3.1 Alternative regimens (equivalent).

• Erythromycin base 500 mg orally 4 times a day for 7 days,

• Erythromycin ethyl-succinate 1000 mg twice a day orally for 7 days;

• Ofloxacin 200 mg orally twice a day for 7 days

• Roxithromycin 150mg orally twice a day for 7 days

• Clarithromycin 250mg orally twice a day for 7 days.

1.3.4 Special considerations.

Abstinence from sexual intercourse for 7 days after single dose therapy or until completion of a 7 day regimen of antibiotic and until all of the partners are cured.

Azithromycin has shown approximately equal efficacy to doxycycline in studies to date. It is preferable when non-compliance with treatment is suspected. For men azithromycin will generally be preferred. It is also effective for non-specific urethritis. It is not known whether doxycycline is more effective than azithromycin for women with an asymptomatic ("silent") PID. Symptomatic PID should be excluded before recommending treatment for a woman.

Doxycycline has a longer history of extensive use, and the advantage of low cost.

Erythromycin is less efficacious than azithromycin or doxycycline, and gastrointestinal side effects frequently discourage patients from complying with this regimen.

Roxithromycin and Clarithromycin are alternative macrolide antibiotics with high tissue concentrations and better toleration by patients, having a lower profile of side effects.

Ofloxacin is similar in efficacy to doxycycline and azithromycin, but is more expensive and offers no advantage in dosing. Other quinolones are not reliably effective against chlamydial infection.

Compliance with therapy: is related to providing information about mode of transmission of chlamydiae, sequelae, importance for the partner, the diagnosis and treatment schedule, side effects.

1.3.5 Management of chlamydial infections in pregnant women

1.3.5.1 Recommended regimens for pregnant women.

• Erythromycin base 500 mg orally 4 times daily for 7 days,

• Amoxicillin 500 mg orally 3 times daily for 7 days.

• Josamycin 750mg orally twice daily for 7 days

1.3.5.2 Alternative regimens for pregnant women.

• Erythromycin base 250 mg orally 4 times daily for 14 days,

• Erythromycin ethylsuccinate 800 mg orally 4 times daily for 7 days,

• Erythromycin ethylsuccinate 400 mg orally 4 times daily for 14 days,

• Azithromycin 1 gm orally, single dose.

1.3.5.3 Special considerations for therapy during pregnancy.

Doxycycline and ofloxacin are contraindicated in pregnant women .

Erythromycin estolate is contraindicated during pregnancy because of drug-related hepato-toxicity.

Preliminary data suggests that azithromycin may be safe and effective. However, there are insufficient data presently to recommend its routine use in pregnant women.

Repeat laboratory testing 3 weeks after completion of  therapy is recommended for all regimens because none are highly efficacious and the frequent side effects of erythromycin (in particular) may discourage patient compliance.

1.3.6 Management of chlamydial infections in HIV-infected persons.

Persons with HIV infection plus chlamydial infection should receive the same treatment as chlamydial-infected patients without HIV.

1.3.7 Management of sex partners.

• Treatment of sex partners will help to prevent re-infection of the index patient or infection of their partners.

• Patients should be instructed to refer their sex partners for evaluation, testing and treatment.

• Sex partners whose last sexual contact with the index patient was within 60 days of onset of the index patient's symptoms or diagnosis, should be evaluated, tested, and treated.

• Partners at risk should be informed and invited to attend for evaluation and epidemiological treatment, even if tests are negative.

• Patients should be instructed to abstain from sexual intercourse until both patient and partner(s) have completed treatment (7-days after a single dose regimen or after completion of a 7-day regimen).

• Epidemiological treatment of partner(s): azithromycin 1 g orally in a single dose.

1.4.1 Possible indications for follow up examination:

• Reassurance of the patient (emotional reasons)

• Asymptomatic C. trachomatis infection

• Persistence of symptoms

• Suspected non-compliance of the patient

• Possibility of re-infection

• After therapy with erythromycin (higher risk of treatment failure).

Microbiological follow-up is not strictly necessary after treatment with doxycycline or azithromycin, but may be useful for health education, follow-up partner notification, and for providing reassurance to the patient.

1.4.2 Timing of test of cure:

• Culture, EIA/ELISA and DNA hybridisation tests: 2 weeks after the end of therapy.

• DNA amplification methods (PCR/LCR/TMA tests): 2 - 4 weeks after the end of therapy.

• Re-screening women several months following treatment may be an effective strategy for detecting further morbidity in some populations, such as adolescents.

2. Chlamydial infections among infants.

C. trachomatis infection of neonates results from perinatal exposure to the mother's infected cervix. Infants born to mothers with untreated chlamydiae are at high risk of infection, and should be followed for development of infection and treated appropriately.

Pre-natal screening of pregnant women can prevent chlamydial infection among neonates.

2.2.1 Clinical

• Initial C. trachomatis perinatal infection involves mucous membranes of the eye, oro-pharynx, urogenital tract, and rectum.

• C. trachomatis infection among neonates can most often be recognised because of conjunctivitis developing 5-12 days after birth.

• C. trachomatis is a common cause of subacute, afebrile pneumonia with onset from 1 to 3 months of age (Beem and Saxon syndrome).

• Characteristic signs of chlamydial pneumonia among infants include a repetitive staccato cough with tachypnea, and hyperinflation and bilateral diffuse infiltrates on a chest X-ray.

• Asymptomatic infections of the oropharynx, genital tract, and rectum among neonates also occur.

2.2.2 Indications for testing:

• Clinical symptoms of conjunctivitis.

• Clinical symptoms of pneumonia.

Neonatal ocular prophylaxis with silver nitrate solution or antibiotic ointments is ineffective in preventing perinatal transmission of chlamydial infection from mother to infant. However, ocular prophylaxis with these agents does prevent gonoccocal ophthalmia neonatorum.

2.2.2.1 Laboratory testing:

Conjunctivitis: Specimens for culture isolation and nonculture tests should be obtained from the everted eyelid using a Dacron-tipped swab or the swab specified by the manufacturer's test kit.

Pneumonia: Specimens should be collected from the nasopharynx for chlamydial testing. Tissue culture remains the definitive standard for chlamydial pneumonia; Tracheal aspirates and lung biopsy specimens should be tested if available.

The micro-immunofluorescence test for C. trachomatis antibody is useful for diagnosis of chlamydial pneumonia in neonates but not widely available. An acute IgM antibody titer 1:32 or more is strongly suggestive of C. trachomatis pneumonia.

2.3.1 General principles.

Ocular exudate from infants being evaluated for chlamydial conjunctivitis should also be tested for N. gonorrhoeae. A specific diagnosis of C. trachomatis infection confirms the need for chlamydial treatment not only for the neonate, but also for the mother and her sex partner(s).

2.3.2 Recommended regimen for neonatal conjunctivitis and pneumonia:

• Erythromycin 50 mg/kg/day orally divided into 4 doses for 10-14 days.

Topical antibiotic therapy alone is inadequate for treatment of chlamydial infection and is unnecessary when systemic treatment is administered.

2.3.3 Follow-up.

Follow-up of infants to determine resolution of symptoms and infection is recommended. The efficacy of erythromycin treatment is approximately 80%; a second course of therapy may be required. The possibility of concomitant chlamydial pneumonia should be considered.

3. Chlamydial infections among children.

3. 1 Introduction.

Sexual abuse must be considered a cause of chlamydial infection among preadolescent children, although perinatally transmitted C. trachomatis infection of the nasopharynx, urogenital tract and rectum may persist beyond 1 year.

3. 2 Diagnosis

3.2.1 Laboratory diagnosis.

Because of the potential for a criminal investigation and legal proceedings for sexual abuse, diagnosis of C. trachomatis among pre-adolescent children requires the unambiguous specificity of isolation in cell culture. The cultures should be confirmed by microscopic identification of the characteristic chlamydial inclusions, preferably with fluorescein-conjugated monoclonal antibodies specific for C. trachomatis.

3.3 Management

3.3.1 Recommended Regimen

Children who weigh <45 kg:

• Erythromycin 50 mg/kg/day divided into four doses for 10-14 days.

Note: The effectiveness of erythromycin treatment is approximately 80%; a second course of therapy may be required.

Children who are 8 years of age or who weigh 45 kg but who are <8 years of age:

Use the same treatment regimens for these children as the adult regimens of azithromycin.

3.3.2 Follow-up

Follow-up cultures are necessary to ensure that treatment has been effective.

[AS] Aug 2001

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