Nucleic Acid Amplification Testing (NAAT) for Neisseria Gonorrhoeae and Chlamydia Trachomatis
Indications
Second Generation Tests are Indicated to Detect Both Neisseria Gonorrhoeae and Chlamydia Trachomatis in Males/Females with or without Symptoms
Availability
Commercially Available from Multiple Manufacturers (Roche, etc)
Technique
PCR Amplification, Strand Displacement Amplification (SDA), or Transcription-Mediated Amplification (TMA) of Organism DNA/RNA in Sample
Technique Can Theoretically Detect as Little as One Organism Per Sample (In Contrast, the Detection Threshold of Culture is Approximately 1000 Organisms Per Sample)
Sensitivity of Various Amplification Methods Varies
Optimal Specimen Type
Preferred Sample for Male Patient is a First Void Urine Sample (i.e. During the Initial Part of the Urine Stream)
First Void Urine Sample Performs as Well or Better than Urethral Swab
Preferred Sample for Female Patient is a Vaginal Swab
Vaginal Swab Performs as Well as Cervical Swab (Although Cervical Swabs May Be Substituted in Cases When a Pelvic Exam is Performed)
Self-Collected Vaginal Swab is Equivalent in Sensitivity/Specificity to Clinician-Collected Vaginal Swabs
Use of Female Urine Specimens
Female Urine Specimens are 10% Less Effective than Vaginal Swabs for Detection of Neisseria Gonorrhoeae (Possibly Related to the Presence of Urine Inhibitory Substances Which May Interfere with NAAT)
Female “Clean Catch” Urine (if Being Performed at the Same Time) Requires External Cleansing of the Urethra, Which Will Impede Optimal NAAT Testing of Urine
Therefore, NAAT of Female Urine Should Be Performed Using First Void Urine Without External Cleansing Prior to Collection
Cost-Effectiveness
NAAT is Cost Effective in Preventing Sequelae of Neisseria Gonorrhoeae and Chlamydia Trachomatis Infections
Cross-Reactivity with Non-Gonococcal Neisseria Species: none
Advantages of NAAT Over Urethral Swab Culture
NAAT Has Faster Test Turnaround Time Than Urethral Swab Culture
NAAT Has Higher Sensitivity (100%) and Equal Specificity (99%) Than Urethral Swab Culture
Non-Invasive Collection Method: NAAT requires only urine to perform, rather than a urethral swab
Single Test Can Be Employed for Both Organisms
Advantages of NAAT Over Other Molecular Testing Methods
NAAT is Preferred Over Direct Fluorescence Antibody Testing/ELISA/Nucleic Acid Hybridization Tests, Due to Their Superior Sensitivity/Specificity
Disadvantages of NAAT
NAAT is Expensive
NAAT Does Not Enable Determination of Antibiotic Sensitivity for the Organism
Therefore, Cultures are Still Required in Cases Where Antibiotic Resistance is Suspected
NAAT Requires Processing in the Lab (Not Available at the Point of Care)
Use of NAAT with Non-Genital Body Specimens
NAAT has Higher Sensitivity than Culture to Detect Chlamydia Trachomatis in Oropharyngeal or Rectal Samples in Males Who Have Intercourse with Other Males
However, This Use is Not FDA-Approved and Needs to Be Validated in Terms of Performance at the Local Lab/Clinical Site
Urination within 2 hrs of exam should be avoided, as it may impair the ability to detect organisms
Criteria: >10 WBC per hpf on first void urine is consistent with urethritis
Criteria: positive leukocyte esterase (on dipstick) on first void urine is consistent with urethritis
Urethral Swab with Culture
Used historically to diagnose Neisseria Gonorrhoeae and Chlamydia Trachomatis infections: however, NAAT above is now the preferred diagnostic method to detect these organisms
Culture is currently the only means of detecting Mycoplasma Genitalium and Ureaplasma Urealyticum infections
DNA-based testing methods (with 97% sensitivity) for these organisms have been developed, but are not commercially available yet
Criteria: >5 neutrophils per hpf indicates presence of urethritis
Suspected Sexually-Transmitted Infection or Genital Ulcer: due to possibility of co-infection with syphilis
Screening
Recommended Screening for Sexually Transmitted Infections (STI) by Group (2010: CDC, IDSA, USPTF)
General Comments
There is No Current Recommendation to Screen for Herpes-Simplex Virus in Human Immunodeficiency Virus (HIV)-Negative Patients with Risk Factors for Sexually Transmitted Infections
Sexually Active Females <25 y/o
Screen Annually for Neisseria Gonorrhoeae/Chlamydia Trachomatis
Females 13-25 y/o
Screen at Least Once for HIV
Screen Annually for HIV (if High Risk)
Screen for Other Sexually Transmitted Infections Based on Risk Profile
Females 26-64 y/o
Screen at Least Once for HIV
Screen Annually for HIV (if High Risk)
Screen for Other Sexually Transmitted Infections Based on Risk Profile
Pregnant Females
Screen for Chlamydia Trachomatis/HIV/Hepatitis B/Syphilis in First Trimester
HIV-Positive Female
Screen Annually for Neisseria Gonorrhoeae/Chlamydia Trachomatis/Trichomoniasis
Screen for Hepatitis B/Hepatitis C/Syphilis/HSV2 at First Visit and Then Per Risk Profile
Heterosexual Men 13-64 y/o
Screen for HIV at Least Once
Screen Annually for HIV (if High Risk)
Screen for Other Sexually Transmitted Infections Based on Risk Profile
Males Who Have Sex with Males
Screen Annually for Neisseria Gonorrhoeae/Chlamydia Trachomatis/Syphilis/HIV, and More Frequently According to Risk
Screen for Hepatitis B at Least Once
HIV Positive Males
Screen annually for Neisseria Gonorrhoeae/Chlamydia Trachomatis/Syphilis
Screen for HSV-2/Hepatitis B at First Visit
Injectable Drug Users
Screen for Hepatitis A/Hepatitis B: if not immune, vaccination should be offered
Persons with History of Multiple Sexual Partners
Screen for Hepatitis A/Hepatitis B: if not immune, vaccination should be offered
Screening for Hepatitis C is of Uncertain Need in this Population (and in Those with other Sexually Transmitted Infections)
Adults Born Between 1945-1965: this age group accounts for approximately 27% of the population, but accounts for approximately 75% of all chronic Hepatitis C infections
Screen for Hepatitis C (CDC recommendation in 1/14)
Screening Interval
Patients with Prior Negative Screening: interval for repeat testing is based on risk factor profile
Previously Infected Females: rescreening at 3-4 months is recommended (due to high rates of reinfection)
Previously Infected with Neisseria Gonorrhoeae/Chlamydia Trachomatis: California Department of Public Health recommends rescreening at 3 months
Previously Infected Males: rescreening interval is unclear
Previously Infected with Neisseria Gonorrhoeae/Chlamydia Trachomatis: California Department of Public Health recommends rescreening at 3 months
Clinical Manifestations
Renal/Urologic Manifestations
General Comments
Presence of Symptoms in Males
Historically, Only 5-10% of Gonoccocal Urethritis were Believed to Be Asymptomatic
However, Some Studies Suggest that this Rate May Be Much Higher
Anywhere Between 40-90% of Chlamydia Trachomatis Cases are Asymptomatic
Mycoplasma Genitalium May Be More Likely to Be Symptomatic than Chlamydia Trachomatis Infection
Usefulness of Clinical Features to Distinguish Microbiologic Etiologies
Clinical Features Alone are Not Usually Adequate to Distinguish Gonococcal from Non-Gonococcal/Chlamydial Urethritis
Prevalence of Co-Infection
Approximately 25-30% of Male Gonococcal Urethritis Cases are Co-Infected with Chlamydia Trachomatis
Unclear if These infections Cause Long-Term Complications
Treatment
Antibiotics
General Comments
Patient and Partner(s) Should Abstain from Sexual Activity Until the Course of Therapy is Completed
Without Culture Data (and Without Certain Patient Follow-Up with the Provider), the Patient Should Be Treated for Both Neisseria Gonorrhoeae and Chlamydia Trachomatis Infections: as per both of the regimens below
Infectious Diseases Society of America (IDSA) Guideline Recommended Regimens (see [MEDLINE])
xxxx
Azithromycin PO (1000 mg x 1) + Ceftriaxone IM (250 mg IM x 1) (see Azithromycin and Ceftriaxone)
Azithromycin is Now a Less Preferred Regimen (vs Doxycycline) for Chlamydia Trachomatis Infection
Doxycycline PO (100 mg BID x 7 days) + Ceftriaxone IM (250 mg IM x 1) (see Doxycycline and Ceftriaxone)
Expedited Partner Therapy (EPT)
Legal Statute: allowed in 27 states (including California)
Procedure
Health Care Provider is Allowed to Give Treatment Medications to the Patient to Pass Along to their Sexual Partner(s), as Well as Information Recommending that the Partner Seek Medical Care
While the Provider Can Assist with Notification of the Patient’s Sexual Partners (at the Patient’s Request), They are Not Legally Obligated to Do So
Provider or Laboratory Where Testing was Done are Required to Notify the Public Health Department of the Infection, as Described Below
Per CDC Guidelines
EPT is Beneficial in Heterosexual Males/Females for the Treatment of Neisseria Gonorrhoeae and Chlamydia Trachomatis Urethritis
EPT has a Limited Role in Partner Management for Trichomoniasis
No Data Support to Support EPT Use in the Routine Management of Syphilis
Sexually Transmitted Infections Required to Be Reported to California Public Health Department
Report Required Immediately
Outbreak of Any Sexually Transmitted Disease
Report Required Within One Day (Fax/Telephone/Email)
Chlamydia trachomatis among patients infected with and treated for Neisseria gonorrhoeae in sexually transmitted disease clinics in the United States. Project RESPECT Study Group. Ann Intern Med. 2003;139(3):178 [MEDLINE]
Sexually transmitted diseases treatment guidelines, 2015. Centers for Disease Control and Prevention. MMWR Recomm Rep. 2015;64(RR-03):1 [MEDLINE]
