# Presentation: 653160

## Chlamydia

*Chlamydia trachomatis*

## Learning Objectives

- Upon completion of this content, the learner will be able to:
- Describe the epidemiology of* *chlamydial infection in the U.S.
- Describe the pathogenesis of *Chlamydia trachomatis*.
- Describe the clinical manifestations of chlamydial infection.
- Identify common methods used in the diagnosis of chlamydial infection.
- List CDC-recommended treatment regimens for chlamydial infection.
- Summarize appropriate prevention counseling messages for patients with chlamydial infection.
- Describe public health measures for the prevention of* *chlamydial infection.

## Lessons

- Epidemiology: Disease in the U.S.
- Pathogenesis
- Clinical manifestations
- Diagnosis
- Patient management
- Prevention

## Lesson I: Epidemiology: Disease in the U.S.

## Incidence

- Estimated 3 million cases in U.S. annually
- Most frequently reported STD in U.S.
- Reported rates 3 times higher in females than in males

- Epidemiology

## Chlamydia — Rates by state: United States and outlying areas, 2003

*Source*: CDC/NCHSTP 2003 STD Surveillance Report

- Epidemiology

- Note: The total rate of chlamydia for the United States and outlying areas (Guam, Puerto Rico and Virgin Islands) was 301.3 per 100,000 population.

## Chlamydia — Rates by sex: United States, 1984–2003

*Source*: CDC/NCHSTP 2003 STD Surveillance Report

- Epidemiology

## Chlamydia — Age- and sex-specific rates: United States, 2003

*Source*: CDC/NCHSTP 2003 STD Surveillance Report

- Epidemiology

## Prevalence

- Prevalence (approximate) in selected populations:
- Family planning clinics, 3%-15%
- Indian Health Service, 7%-9%
- Youth detention facilities, 6%-28%
- National job training recruits, 4%-16%

- Epidemiology

## Risk Factors

- Adolescence
- New or multiple sex partners
- History of STD infection
- Presence of another STD
- Oral contraceptive user
- Lack of barrier contraception

- Epidemiology

## Transmission

- Transmission is **sexual** or **vertical**
- Highly transmissible
- Incubation period 7-21 days
- Significant asymptomatic reservoir exists in the population
- Re-infection is common
- Perinatal transmission results in neonatal conjunctivitis in 30%-50% of exposed babies

- Epidemiology

## Lesson II: Pathogenesis

## Microbiology

- Obligatory intracellular bacteria
- Infect columnar epithelial cells
- Survive by replication that results in the death of the cell
- Takes on two forms in its life cycle:
- Elementary body (EB)
- Reticulate body (RB)

- Pathology

## Pathology

*Source*: California STD/HIV Prevention Training Center

## Chlamydiaceae Family(species that cause disease in humans)

- Pathology

| Species (genus) |  | Disease |
| --- | --- | --- |
| C. trachomatis
2 biovars, non-LGV
                        LGV |  | Trachoma, NGU, MPC, PID, conjunctivitis,
Infant pneumonia,
LGV |
| C. pneumoniae |  | Pharyngitis, bronchitis, pneumonia |
| C. psittaci |  | Psittacosis |

## Lesson III: Clinical Manifestations

## Clinical Syndromes Caused by C. trachomatis

| Local Infection | Complication | Sequelae |
| --- | --- | --- |
| Conjunctivitis
Urethritis
Prostatitis | Reiter’s syndrome
Epididymitis | Chronic arthritis (rare)
Infertility (rare) |
| Conjunctivitis
Urethritis
Cervicitis
Proctitis | Endometritis
Salpingitis
Perihepatitis
Reiter’s syndrome | Infertility
Ectopic pregnancy
Chronic pelvic pain
Chronic arthritis (rare) |
| Conjunctivitis
Pneumonitis
Pharyngitis
Rhinitis | Chronic lung disease? | Rare, if any |

- Clinical Manifestations

## C. trachomatis Infection in Men

- Urethritis–One cause of non-gonococcal urethritis (NGU)
- Majority (>50%) asymptomatic
- Symptoms/signs if present: mucoid or clear urethral discharge, dysuria
- Incubation period unknown (probably 5-10 days in symptomatic infection)

- Clinical Manifestations

## Non-Gonococcal Urethritis: Mucoid Discharge

*Source*: Seattle STD/HIV Prevention Training Center at the University of Washington/UW HSCER Slide Bank

- Clinical Manifestations

## C. trachomatis Complications in Men

- Epididymitis
- Reiter’s Syndrome
- Rarely occurs in women

- Clinical Manifestations

## Swollen or tender testicles (epididymitis)

- Clinical Manifestations

*Source*:  Seattle STD/HIV Prevention Training Center at the University of Washington

## C. trachomatis Infections in Women

- Cervicitis
- Majority (70%-80%) are asymptomatic
- Local signs of infection, when present, include:
- Mucopurulent endocervical discharge
- Edematous cervical ectopy with erythema and friability
- Urethritis
- Usually asymptomatic
- Signs/symptoms, when present, include dysuria, frequency, pyuria

- Clinical Manifestations

## Normal Cervix

- Clinical Manifestations

*Source*: STD/HIV Prevention Training Center at the University of Washington/Claire E. Stevens

## Chlamydial Cervicitis

- Clinical Manifestations

*Source*: STD/HIV Prevention Training Center at the University of Washington/Connie Celum and Walter Stamm

## Cervicitis

- Clinical Manifestations

*Source*: St. Louis STD/HIV Prevention Training Center

## C. trachomatis Complications in Women

- Pelvic Inflammatory Disease (PID)
- Salpingitis
- Endometritis
- Perihepatitis (Fitz-Hugh-Curtis Syndrome)
- Reiter’s Syndrome

- Clinical Manifestations

## Normal Human Fallopian Tube Tissue

- Clinical Manifestations

*Source*: Patton, D.L. University of Washington, Seattle, Washington

## C. trachomatis Infection (PID)

- Clinical Manifestations

*Source*: Patton, D.L. University of Washington, Seattle, Washington

## Acute Salpingitis

- Clinical Manifestations

*Source*: Cincinnati STD/HIV Prevention Training Center

## C. trachomatis Syndromes Seen in Men or Women

- Non-LGV serovars
- Conjunctivitis
- Proctitis
- Reiter’s Syndrome
- LGV serovars
- Lymphogranuloma venereum

- Clinical Manifestations

## LGV Lymphadenopathy

- Clinical Manifestations

*Source*:  CDC Division of STD Prevention Clinical Slides

## C. trachomatis Infections in Infants

- Perinatal clinical manifestations:
- Inclusion conjunctivitis
- Pneumonia

- Clinical Manifestations

## C. trachomatis Infections in Children

- Pre-adolescent males and females:
- Urogenital infections
- Usually asymptomatic
- Vertical transmission
- Sexual abuse

- Clinical Manifestations

## Lesson IV: Diagnosis

## Testing Technologies

- Culture
- Non-culture tests
- Nucleic Acid Amplification Tests (NAATs)
- Non-Nucleic Acid Amplification Tests (Non-NAATs)
- Serology

- Diagnosis

## Culture

- Historically the “gold standard”
- Variable sensitivity (50%-80%)
- High specificity
- Use in legal investigations
- Not suitable for widespread screening

- Diagnosis

## NAATs

- NAATs amplify and detect organism-specific genomic or plasmid DNA or rRNA
- FDA cleared for urethral swabs from men/women, cervical swabs from women, and urine from both

- Diagnosis

## NAATs

- Commercially available NAATs include:
- Becton Dickinson *BDProbeTec**®*
- Gen-Probe *AmpCT, Aptima**®*
- Roche *Amplicor**®*
- Significantly more sensitive than other tests

- Diagnosis

**Notes:**

Most FDA- not all test are cleared for every specimen site

## Non-NAATs

- Direct fluorescent antibody (DFA)
- Detects intact bacteria with a fluorescent antibody
- Variety of specimen sites
- Can be used to determine quality of endocervical specimens
- Enzyme immunoassay (EIA)
- Detects bacterial antigens with an enzyme-labeled antibody
- Nucleic acid hybridization (NA probe)
- Detects specific DNA or RNA sequences of *C. trachomatis* and *N. gonorrhoeae*

- Diagnosis

## Serology

- Rarely used for uncomplicated infections (results difficult to interpret)
- Criteria used in LGV diagnosis
- Complement fixation titers >1:64 suggestive
- Complement fixation titers > 1:256 diagnostic
- Complement fixation titers <  1:32 rule out

- Diagnosis

## Lesson V: Patient Management

## Treatment of Uncomplicated Genital Chlamydial Infections 

**CDC-recommended regimens**
- Azithromycin 1 g orally in a single dose, OR
- Doxycycline 100 mg orally twice daily for 7 days
**Alternative regimens**
- Erythromycin base 500 mg orally 4 times a day for 7 days, OR
- Erythromycin ethylsuccinate 800 mg orally 4 times a day for 7 days, OR
- Ofloxacin 300 mg orally twice a day for 7 days, OR
- Levofloxacin 500 mg orally once a day for 7 days

- Management

## Treatment of Chlamydial Infection in Pregnant Women

**CDC-recommended regimens**
- Erythromycin base 500 mg orally 4 times a day for 7 days, OR
- Amoxicillin 500 mg orally 3 times a day for 7 days
**Alternative regimens**
- Erythromycin base 250 mg orally 4 times a day for 14 days, OR
- Erythromycin ethylsuccinate 800 mg orally 4 times a day for 7 days, OR
- Erythromycin ethylsuccinate 400 mg orally 4 times a day for 14 days, OR
- Azithromycin 1 g orally (single dose)

- Management

## Treatment of Neonatal Conjunctivitis and/or Pneumonia

**CDC-recommended regimen**
- Erythromycin base or ethylsuccinate 50 mg/kg/day orally divided into 4 doses daily for 14 days

- Management

## Treatment of Chlamydial Infection in Children

**Children who weigh <45 kg**:
- Erythromycin base or ethylsuccinate 50 mg/kg/day orally divided into 4 doses daily for 14 days
**Children who weigh ****≥****45 kg, but are <8 years of age**:
- Azithromycin 1 g orally in a single dose
**Children ****≥****8 years of age**:
- Azithromycin 1 g orally in a single dose, OR
- Doxycycline 100 mg orally twice a day for 7 days

- Management

## Treatment of Lymphogranuloma Venereum (LGV)

**CDC-recommended regimen**
- Doxycycline 100 mg orally twice a day for 21 days
**Alternative regimen**
- Erythromycin base 500 mg orally 4 times a day for 21 days

- Management

## Repeat Testing after Treatment

- Pregnant women
- Repeat testing, preferably by culture, 3 weeks after completion of recommended therapy
- Non-pregnant women
- Screen 3-4 months after treatment, especially adolescents
- Screen at next health care visit
- Consider test of cure 3 weeks after completion of therapy for anyone treated with erythromycin

- Management

## Lesson VI: Prevention

## Why Screen for Chlamydia?

- Screening can reduce the incidence of PID by more than 50%.
- Most infections are asymptomatic.
- Screening decreases the prevalence of infection in the population and reduces the transmission of disease.

- Prevention

## Screening Recommendations: Non-pregnant Women

- Sexually active women age 25 years and under should be screened annually.
- Women >25 years old should be screened if risk factors are present.
- Repeat screening of women 3-4 months after treatment for *C. trachomatis* infection, especially adolescents.
- Repeat screening of all women treated for *C. trachomatis* when they next present for care.

- Prevention

## Screening Recommendations:Pregnant Women

- Screen all pregnant women at the first prenatal visit.
- Pregnant women aged <25 years and those at increased risk for chlamydia should be screened again in the third trimester.

- Prevention

## Partner Management

- Sex partners should be evaluated, tested, and treated if they had sexual contact with the patient during the 60 days preceding the onset of symptoms or diagnosis of chlamydia.
- The most recent sex partner should be evaluated and treated even if the time of the last sexual contact was >60 days before symptom onset or diagnosis.

- Prevention

## Reporting

- Chlamydia is a reportable STD in all states.
- Report cases to the local or state STD program.

- Prevention

## Prevention Counseling

- Nature of the infection
- Chlamydia is commonly asymptomatic in men and women.
- In women, there is an increased risk of upper reproductive tract damage with re-infection.
- Transmission issues
- Effective treatment of chlamydia may reduce HIV transmission and acquisition.
- Abstain from sexual intercourse until partners are treated and for 7 days after a single dose of azithromycin or until completion of a 7-day regimen.

- Prevention

## Prevention Counseling (continued)

- Risk reduction
- 	The clinician should:
- Assess the patient’s behavior-change potential.
- Discuss prevention strategies (abstinence, monogamy, condoms, limit number of sex partners, etc.). Latex condoms, when used consistently and correctly, can reduce the risk of transmission of chlamydia.
- Develop individualized risk-reduction plans.

- Prevention

## Case Study

## History

- Suzy Jones:  17-year-old college student who presents to the Student Health Center seeking advice about contraception
- Shy talking about her sexual practices
- Has never had a pelvic exam
- Has had 2 sex partners in past 6 months
- Does not use condoms or any other contraceptives
- Her periods have been regular, but she has recently noted some spotting between periods. Last menstrual period was 4 weeks ago.
- Denies vaginal discharge, dyspareunia, genital lesions, or sores

- Case Study

## Physical Exam

- Vital signs: blood pressure 118/68, pulse 74, respiration 18, temperature 37.1° C
- Breast, thyroid, and abdominal exam within normal limits
- Genital exam reveals normal vulva and vagina
- The cervix appears inflamed, bleeds easily, with a purulent discharge coming from the cervical os.
- Bimanual exam is normal without cervical motion pain, uterine or adnexal tenderness.

- Case Study

## Questions

- What is the initial clinical diagnosis?
- What are the *possible* etiologic agents associated with the clinical findings?
- What is the most *likely* microbiologic diagnosis?
- Which laboratory tests should be ordered or performed?

- Case Study

## Laboratory Results

- NAAT for *Chlamydia trachomatis*:  positive
- NAAT for *Neisseria gonorrhoeae*:  negative
- RPR: negative
- Wet mount:  pH 4.2, no clue cells or trichomonads but numerous WBCs
- KOH preparation:  negative for “whiff test”
- HIV antibody test: negative
- Pap smear: ASC-US
- Pregnancy test: negative

- Case Study

## Questions

- 5.  What is the final diagnosis?
- What is the appropriate treatment at the initial visit?
- What are the appropriate prevention and counseling messages for Suzy?
- Who is responsible for reporting this case to the local health department?

- Case Study

## Partner Management

- Suzy’s sex partners from the past year:
- John – Last sexual exposure 5 weeks ago
- Tom – Last sexual exposure 7 months ago
- Michael – Last sexual exposure 2 weeks ago
- 9.  Which sex partners should be evaluated, tested, and treated?

- Case Study

## Follow-Up

- Suzy returned for a follow-up visit at 4 months.
- Her repeat Pap test came back normal.
- Her repeat chlamydia test returned positive.
- Suzy stated that her partner, Michael, went to get tested, but the test result was negative so he was not treated.
- 10.  What is the appropriate treatment at the 4-month follow-up visit?

- Case Study