Sexually Transmitted Infections

Sexually transmitted infections (STIs) constitute a major health burden in the U.S., and reported incidence among adolescents is increasing. These diseases are frequently asymptomatic and are most often caused by viruses or bacteria.

Diagnosis

Indications for Testing

Symptomatic individuals
- Urgency, frequency, dysuria in the absence of a documented urinary tract infection (UTI)
- Vaginal or penile discharge
- Pelvic pain
- Prostatitis symptoms
- Genital lesions – painful vesicles, nonpainful shallow ulcer
Asymptomatic individuals – see Screening for testing recommendations

Laboratory Testing

CDC – testing recommendations
Refer to the following ARUP Consult topics for sexually transmitted infection (STI) testing recommendations for
- Human papillomavirus (HPV)
- Treponema pallidum
- HIV
- Hepatitis B (HBV)
- Hepatitis C (HCV)
- Herpes simplex virus (HSV)
STI testing methods
- Wet mount
  - Bacterial vaginosis – presence of clue cells is diagnostic in appropriate clinical setting
- Nucleic acid amplification testing (NAAT)
  - Preferred for detecting Chlamydia trachomatis and Neisseria gonorrhoeae in a variety of specimens (U.S. Preventive Services Task Force [USPSTF], 2014; CDC, 2014)
  - Most sensitive test for Trichomonas vaginalis
  - Highly sensitive and specific
  - Specimen collection – for optimal specimen types and collection instructions, refer to ARUP's Sample Collection for the Diagnosis of STD Using Nucleic Acid Amplification Tests
- Culture
  - C. trachomatis
    - Not recommended for routine detection
    - May be considered for anatomic locations for which amplified testing has not been validated
    - May be used in medicolegal settings and to assess suspected treatment failure
    - High specificity; less sensitive than NAAT
  - N. gonorrhoeae
    - Not recommended for routine detection
    - Recommended in combination with antimicrobial susceptibility testing in cases of suspected or documented treatment failure
    - May be considered for anatomic locations for which amplified testing has not been validated
    - Sensitivity dependent on transport time – viability declines rapidly during transport
  - T. vaginalis – not recommended for routine detection
- DNA probes and direct fluorescent antibody (DFA)
  - Not recommended for routine detection
  - Lower sensitivity than NAAT

Differential Diagnosis

UTI
Vaginitis/cervicitis
Vulvovaginal candidiasis
Malignancy – ovarian cancer, cervical cancer
Nephrolithiasis
Ectopic pregnancy
Diverticulitis
Inflammatory bowel disease
Appendicitis
Pregnancy
Ovarian cyst

Screening

Specimen Collection

For optimal specimen types and collection instructions for sexually transmitted infection (STI) screening tests, refer to ARUP's Sample Collection for the Diagnosis of STD Using Nucleic Acid Amplification Tests

Women

STI screening recommendations for sexually active nonpregnant women

STI Screening Recommendations for Sexually Active Nonpregnant Women
STI	USPSTF/AAFP (Lee, 2016)^a	CDC, 2015
Chlamydia	Sexually active women <25 yrs and women ≥25 yrs at increased risk^b	Sexually active women <25 yrs and sexually active women ≥25 yrs at increased risk^d
Gonorrhea	Sexually active women <25 yrs and women ≥25 yrs at increased risk	Sexually active women <25 yrs and sexually active women ≥25 yrs at increased risk^d,e
Syphilis	Persons at increased risk	No specific recommendations
Trichomonas	No specific recommendations	Consider for women in areas of high prevalence (eg, STD clinics and correctional facilities) and in women at high risk^f
HIV	All persons 15-65 yrs regardless of risk and patients <15 yrs and >65 yrs at increased risk^b	All women 13-64 yrs and all who seek evaluation
HBV	Persons at increased risk	Women at increased risk^g
HCV	No specific recommendations	Women born 1945-1965 Other women with risk factors^h
HSV	Do not screen asymptomatic persons	Consider type-specific testing for women who seek evaluation
HPV	No specific recommendations	Women 21-29 yrs every 3 yrs with cytology Women 30-65 yrs every 3 yrs with cytology or every 5 yrs with cytology/HPV testing
Bacterial vaginosis	No specific recommendations	No specific recommendations
^aUSPSTF has determined that there is inadequate evidence to determine the optimal interval for repeat screening; clinicians should rescreen patients when their sexual history reveals new or persistent risk factors ^bUSPSTF defines persons at increased risk of STIs as those who have more than one sex partner, a new sex partner, or a sex partner with concurrent partners, and those who are not in mutually monogamous relationships and have inconsistent condom use; the risk is even higher in persons who have a sex partner with an STI, those who have a previous or current STI, and those who exchange sex for drugs or money ^cAAFP recommends routine screening for HIV infection starting at 18 years of age ^dCDC defines persons at increased risk as those who have a new sex partner, more than one sex partner, a sex partner with concurrent partners, or a sex partner who has a sexually transmitted infection ^eAdditional risk factors for gonorrhea include inconsistent condom use among persons who are not in mutually monogamous relationships, previous or coexisting sexually transmitted infections, and exchanging sex for money or drugs; clinicians should consider the communities they serve and may opt to consult local public health authorities for guidance on identifying groups that are at increased risk ^fEg, those with multiple sex partners, exchanging sex for payment, illicit drug use, and a history of STD ^gFor HBV, those at increased risk include persons born in regions of high endemicity (≥2% prevalence), injection-drug users, persons on immunosuppressive therapy, hemodialysis patients, HIV-positive individuals, and others ^hFor HCV, risk factors include past or current injection drug use, receipt of blood transfusion before 1992, long-term hemodialysis, born to mother with HCV, intranasal drug use, receipt of an unregulated tattoo, and other percutaneous exposures AAFP, American Academy of Family Physicians; CDC, Centers for Disease Control and Prevention; HBV, hepatitis B virus; HCV, hepatitis C virus; HPV, human papillomavirus; HSV, herpes simplex virus; STI, sexually transmitted infection; STD, sexually transmitted disease; USPSTF, U.S. Preventive Services Task Force

STI screening recommendations for pregnant women

STI Screening Recommendations for Pregnant Women
STI	USPSTF/AAFP (Lee, 2016)^a	CDC
Chlamydia	All pregnant women <25 yrs and women ≥25 yrs with risk factors^b	All pregnant women <25 yrs and those ≥25 yrs who are at increased risk^c; retest in third trimester for women <25 yrs or those at risk^c
Gonorrhea	All pregnant women <25 yrs and women ≥25 yrs with risk factors	All pregnant women <25 yrs and those ≥25 yrs who are at increased risk^c
Syphilis	All pregnant women	All pregnant women at first prenatal visit; retest in third trimester and at delivery for women at high risk
HIV	All pregnant women at first prenatal visit	All pregnant women at first prenatal visit; retest in third trimester for women at high risk^d
HBV	All pregnant women	Screen all at each first prenatal visit; retest at delivery if at high risk^e
HCV	No specific recommendations	Women born 1945-1965 Pregnant women with risk factors^f
HSV	Do not screen asymptomatic patients	Consider type-specific serologic testing
HPV	No specific recommendations	Women 21-29 yrs every 3 yrs with cytology Women 30-65 yrs every 3 yrs with cytology or every 5 yrs with cytology/HPV testing
Bacterial vaginosis	No specific recommendations	No specific recommendations
^aUSPSTF has determined that there is inadequate evidence to determine the optimal interval for repeat screening; clinicians should rescreen patients when their sexual history reveals new or persistent risk factors ^bPersons at increased risk of STIs include those who have more than one sex partner, a new sex partner, or a sex partner with concurrent partners, and those who are not in mutually monogamous relationships and have inconsistent condom use; the risk is even higher in persons who have a sex partner with an STI, those who have a previous or current STI, and those who exchange sex for drugs or money ^cCDC defines persons at increased risk as those who have a new sex partner, more than one sex partner, a sex partner with concurrent partners, or a sex partner who has a sexually transmitted infection ^dCDC defines persons at high risk as those with multiple sex partners, exchanging sex for payment, illicit drug use, and a history of STD ^eFor HBV, those at increased risk include persons born in regions of high endemicity (≥2% prevalence), injection-drug users, persons on immunosuppressive therapy, hemodialysis patients, HIV-positive individuals, and others ^fFor HCV, risk factors include past or current injection drug use, receipt of blood transfusion before 1992, long-term hemodialysis, born to mother with HCV, intranasal drug use, receipt of an unregulated tattoo, and other percutaneous exposures AAFP, American Academy of Family Physicians; CDC, Centers for Disease Control and Prevention; HBV, hepatitis B virus; HCV, hepatitis C virus; HPV, human papillomavirus; HSV, herpes simplex virus; STI, sexually transmitted infection; STD, sexually transmitted disease; USPSTF, U.S. Preventive Services Task Force

Men

U.S. Preventive Services Task Force (USPSTF) (2004; reaffirmed 2016)
- No screening if not engaging in high-risk behaviors
- If engaging in high-risk behaviors, screen for syphilis and HIV

Extragenital Sites

Women (CDC, 2014)
- No recommendations due to scarcity of published studies; however, available data suggests rectal and oropharyngeal infections are not uncommon in women
- Consider screening women with known risk factors
Men (CDC, 2014)
- Extragenital infections are common and mostly asymptomatic – most frequent for men who have sex with men (MSM) with multiple or anonymous sexual partners
- Screening recommended at least annually in MSM
  - Rectal specimen for men who have receptive anal intercourse
  - Pharyngeal specimen for men who have receptive oral intercourse

CDC STI screening recommendations for MSM

CDC STI Screening Recommendations for MSM
STI	CDC Recommendation
Chlamydia	Annually at sites of contact Every 3-6 mos if at increased risk^a
Gonorrhea	Annually at sites of contact Every 3-6 mos if at increased risk^a
Syphilis	Annually Every 3-6 mos if at increased risk^a
HIV	Annually if individual or partner have had new partner since previous test
HBV	All MSM
HCV	All MSM born 1945-1965, those at risk^b Annually for MSM with HIV
HSV	Consider type-specific testing
^aAll MSM including those with HIV infection if risk behaviors persist or if they or their sexual partners have multiple partners ^bHCV risk factors include past or current injection drug use, receipt of blood transfusion before 1992, long-term hemodialysis, born to mother with HCV, intranasal drug use, receipt of an unregulated tattoo, and other percutaneous exposure CDC, Centers for Disease Control and Prevention; HBV, hepatitis B virus; HCV, hepatitis C virus; HSV, herpes simplex virus; MSM, men who have sex with men; STI, sexually transmitted infection

HIV-Positive Individuals

CDC STI Screening Recommendations for HIV-Positive Individuals
STI	CDC Recommendation
Chlamydia	All sexually active individuals at first HIV evaluation, then at least annually More frequent screening may be appropriate depending on risk behaviors and local epidemiology
Gonorrhea	All sexually active individuals at first HIV evaluation, then at least annually More frequent screening may be appropriate depending on risk behaviors and local epidemiology
Syphilis	All sexually active individuals at first HIV evaluation, then at least annually More frequent screening may be appropriate depending on risk behaviors and local epidemiology
Trichomonas	Sexually active women at entry to care, then at least annually
HBV	Test for HBsAg and anti-HBc and/or anti-HBs27
HCV	All persons at initial evaluation of HIV Annually for MSM
HSV	Consider type-specific testing
HPV	All women within 1 yr of sexual activity or initial HIV diagnosis with conventional or liquid-based cytology; repeat 6 mos later
CDC, Centers for Disease Control and Prevention; HBV, hepatitis B virus; HCV, hepatitis C virus; HPV, human papillomavirus; HSV, herpes simplex virus; MSM, men who have sex with men; STI, sexually transmitted infection

Women Who Have Sex with Women (WSW)

Due to high rates of heterosexual activity in this population, STI screening should reflect individual partner type and reported activity (Wangu, 2017)

Transgender Individuals

STI screening should be based on current anatomy and sexual practices (Wangu, 2017)

Background

Most Common Viral STIs

Most Common Bacterial STIs

Chlamydia trachomatis

Epidemiology
- Incidence – 643/100,000 for females; 262/100,000 for males (CDC, 2014); most common reportable STI in U.S. and worldwide
- Age – highest incidence in 15-24 years
- Gram-negative obligate intracellular parasite

Risk factors
- >1 sex partner, a new sex partner, or a sex partner with multiple partners
- Sex partner with an STI
- Intermittent or lack of condom use
- Previous or current STI
- Exchange of sex for money or drugs

Clinical presentation
- Asymptomatic in >50% of infected patients
- Urethritis, salpingitis, epididymo-orchitis, prostatitis
- Oropharyngeal disease
- Pelvic inflammatory disease (PID)
- Infection during pregnancy increases risk of
  - Premature rupture of membranes
  - Preterm delivery
  - Low birth weight
  - Neonatal conjunctivitis
  - Neonatal pneumonia
- Complications
  - Ectopic pregnancy
  - Tubal factor infertility

Bacterial vaginosis (BV)

Epidemiology
- Prevalence – 10-30% of pregnant women (American Pregnancy Association, 2015); most common form of vaginitis (≥50% of women with BV are asymptomatic)
- Polymicrobial – caused by a combination of Gardnerella vaginalis with anaerobic bacteria overgrowth at the expense of commensal lactobacilli

Risk factors
- Douching
- Nonuse of barrier methods
- Multiple sex partners (>2)

Clinical presentation
- Malodorous vaginal discharge (fishy odor)
- Vulvovaginitis, cervicitis, salpingitis
- Infection during pregnancy increases risk of
  - Acquisition and transmission of HIV
  - Preterm labor
  - Premature rupture of membranes
  - Postpartum endometriosis

Neisseria gonorrhoeae (gonorrhea)

Epidemiology
- Incidence – 108/100,000 for females; 106/100,000 for males (CDC, 2014)
- Age – highest incidence in 15-24 years
- Nonmotile gram-negative diplococcus

Risk factors
- >1 sex partner, a new sex partner, or a sex partner with multiple partners
- Sex partner with an STI
- Intermittent or lack of condom use
- Previous or current STI
- Exchange of sex for money or drugs

Clinical presentation
- Cervicitis, urethritis, salpingitis
- Pelvic inflammatory disease (PID)
- Oropharyngeal disease
- Neonatal infection
- Proctitis (predominantly in men who have sex with men)

Treponema pallidum (syphilis)

Most Common Parasitic/Protozoan STI

Trichomonas vaginalis

Epidemiology
- Prevalence – ~3 million in U.S. (CDC, 2015)
- Age – highest incidence in 30-50 years
- Flagellated protozoan

Risk factors
- >1 sex partner, a new sex partner, or a sex partner with multiple partners
- Sex partner with an STI
- Intermittent or lack of condom use
- Previous or current STI
- Exchange of sex for money or drugs
- Coinfection with gonorrhea or HIV

Clinical presentation
- In females, symptoms include malodorous vaginal discharge, strawberry cervix, dysuria, vulvar irritation, vaginitis, and cervicitis
  - >50% of women with T. vaginalis infections have minimal or no symptoms
  - Trichomaniasis accounts for 15-20% of cases of vulvovaginitis
- In males, T. vaginalis causes urethritis, epididymitis, prostatitis
- Infection during pregnancy increases risk of
  - HIV transmission
  - Preterm labor
  - Premature rupture of membranes
  - Low birth weight

ARUP Lab Tests

Primary Tests

Detect Chlamydia trachomatis and Neisseria gonorrhoeae in a variety of specimens

Positive results are confirmed using an alternate nucleic acid target

Refer to Sample Collection for the Diagnosis of STD Using Nucleic Acid Amplification Tests for optimal specimen types and collection instructions

Culture may be required in certain clinical contexts for diagnosing C. trachomatis and N. gonorrhoeae infections

2011164

Chlamydia trachomatis and Neisseria gonorrhoeae (CTNG) by Transcription-Mediated Amplification (TMA) with Reflex to CT/NG Confirmation 2011164

Method

Qualitative Transcription-Mediated Amplification

Preferred test for detecting C. trachomatis, N. gonorrhoeae, and Trichomonas vaginalis in variety of specimens

Refer to Sample Collection for the Diagnosis of STD Using Nucleic Acid Amplification Tests for optimal specimen types and collection instructions

2006258

Sexually Transmitted Disease Panel 1 by Transcription-Mediated Amplification 2006258

Method

Qualitative Transcription-Mediated Amplification

Preferred test for detecting C. trachomatis and N. gonorrhoeae in variety of specimens

Requires APTIMA collection kit

Does not include confirmation of positive results by an alternate nucleic acid target; if confirmation of positive results by an alternate nucleic acid target is required, please refer to C. trachomatis and N. gonorrhoeae by transcription-mediated amplification (TMA) with confirmation

Refer to Sample Collection for the Diagnosis of STD Using Nucleic Acid Amplification Tests for optimal specimen types and collection instructions

Culture may be required in certain clinical contexts for diagnosing C. trachomatis and N. gonorrhoeae infections

0060241

Chlamydia trachomatis and Neisseria gonorrhoeae by Transcription-Mediated Amplification (TMA) 0060241

Method

Qualitative Transcription-Mediated Amplification

Detect C. trachomatis and N. gonorrhoeae in ThinPrep specimens

Refer to Sample Collection for the Diagnosis of STD Using Nucleic Acid Amplification Tests for optimal specimen types and collection instructions

Culture may be required in certain clinical contexts for diagnosing C. trachomatis and N. gonorrhoeae infections

0060734

Chlamydia trachomatis and Neisseria gonorrhoeae by Transcription-Mediated Amplification (TMA), ThinPrep 0060734

Method

Transcription-Mediated Amplification

Detect T. vaginalis in various specimens

Refer to Sample Collection for the Diagnosis of STD Using Nucleic Acid Amplification Tests for optimal specimen types and collection instructions

Performance of test on self-collected vaginal swab specimens and those from pregnant women has not been evaluated

2005506

Trichomonas vaginalis by Transcription-Mediated Amplification (TMA) 2005506

Method

Qualitative Transcription-Mediated Amplification

Preferred test for detecting C. trachomatis in a variety of specimens

Refer to Sample Collection for the Diagnosis of STD Using Nucleic Acid Amplification Tests for optimal specimen types and collection instructions

Culture may be required in certain clinical contexts for diagnosing C. trachomatis and N. gonorrhoeae infections

0060243

Chlamydia trachomatis by Transcription-Mediated Amplification (TMA) 0060243

Method

Qualitative Transcription-Mediated Amplification

Preferred test for detecting N. gonorrhoeae in a variety of specimens

Refer to Sample Collection for the Diagnosis of STD Using Nucleic Acid Amplification Tests for optimal specimen types and collection instructions

Culture may be required in certain clinical contexts for diagnosing C. trachomatis and N. gonorrhoeae infections

0060244

Neisseria gonorrhoeae by Transcription-Mediated Amplification (TMA) 0060244

Method

Qualitative Transcription-mediated Amplification

Detects but does not differentiate C. trachomatis L1-L3 serovars

2013768

Chlamydia trachomatis L serovars (LGV) by PCR 2013768

Method

Qualitative Polymerase Chain Reaction

Not recommended for routine detection of C. trachomatis

Use to detect C. trachomatis in medicolegal settings and to assess suspected treatment failure

May be considered for anatomic locations for which amplified testing has not been validated

Nucleic amplification testing is recommended for detection of C. trachomatis from endocervical or urethral specimens; refer to C. trachomatis by TMA

0060850

Chlamydia trachomatis Culture 0060850

Method

Cell Culture/Immunofluorescence

Can detect N. gonorrhoeae in specimens not approved for nucleic acid amplification testing

Preferred testing is combined C. trachomatis and N. gonorrhoeae by TMA

0060714

Unusual Organism Culture 0060714

Method

Culture

Related Tests

SurePath media is not preferred when testing for Chlamydia trachomatis and Neisseria gonorrhoeae by transcription-mediated amplification (TMA)

Preferred test is C. trachomatis and N. gonorrhoeae by TMA, or, if confirmation of positive results by an alternate nucleic acid target is required, refer to C. trachomatis and N. gonorrhoeae by TMA with confirmation

Refer to Sample Collection for the Diagnosis of STD Using Nucleic Acid Amplification Tests for optimal specimen types and collection instructions

Use of transport media other than APTIMA specimen collection kit may result in reduced sensitivity

Culture may be required in certain clinical contexts for diagnosing C. trachomatis and N. gonorrhoeae infections

2001551

Chlamydia trachomatis and Neisseria gonorrhoeae by Transcription-Mediated Amplification (TMA), SurePath 2001551

Method

Transcription-Mediated Amplification

Viral transport media (eg, M4/UTM) are not preferred for C. trachomatis and N. gonorrhoeae by TMA

Use of transport media other than APTIMA specimen collection kit may result in reduced sensitivity

The preferred test is C. trachomatis and N. gonorrhoeae by TMA, or, if confirmation of positive results by an alternate nucleic acid target is required, refer to C. trachomatis and N. gonorrhoeae by TMA with confirmation

Refer to Sample Collection for the Diagnosis of STD Using Nucleic Acid Amplification Tests for optimal specimen types and collection instructions

0060774

Chlamydia trachomatis and Neisseria gonorrhoeae by Transcription-Mediated Amplification (TMA), M4/UTM 0060774

Method

Transcription-Mediated Amplification

Detect and speciate Ureaplasma parvum, Ureaplasma urealyticum, Mycoplasma hominis, and Mycoplasma genitalium; consider ordering for cases of nongonococcal urethritis

2011172

Urogenital Ureaplasma and Mycoplasma Species by PCR 2011172

Method

Qualitative Polymerase Chain Reaction

Detect and differentiate Candida albicans, C. glabrata, C. parapsilosis complex (C. parapsilosis, C. orthopsilosis, C. metapsilosis), C. tropicalis, C. krusei, and C. dubliniensis in patients with suspected vulvovaginal candidiasis

2013701

Vulvovaginal Candida Species by PCR 2013701

Method

Qualitative Polymerase Chain Reaction

Detect common vaginal pathogens associated with vaginitis/vaginosis

Not recommended as stand-alone test for sexually transmitted infection testing or screening

0065153

Vaginal Pathogen Panel by DNA Probe 0065153

Method

Qualitative Nucleic Acid Probe

Panel includes Candida spp, Gardnerella vaginalis, and Trichomonas vaginalis

Use to detect Mycoplasma hominis and Ureaplasma spp

0065031

Ureaplasma Species and Mycoplasma hominis Culture 0065031

Method

Culture

Not recommended for routine detection of gonorrheal disease

3001291

Neisseria gonorrhoeae Antibody by CF, Serum 3001291

Method

Semi-Quantitative Complement Fixation

Limited value in the diagnosis of most oculogenital (eg, eyes, genitalia) chlamydial infections

0065100

Chlamydia Antibody Panel, IgG & IgM by IFA 0065100

Method

Semi-Quantitative Indirect Fluorescent Antibody

Limited value in the diagnosis of most oculogenital (eg, eyes, genitalia) chlamydial infections

0065105

Chlamydia Antibody Panel, IgM by IFA 0065105

Method

Semi-Quantitative Indirect Fluorescent Antibody

Limited value in the diagnosis of most oculogenital (eg, eyes, genitalia) chlamydial infections

0065139

Chlamydia Antibody Panel, IgG by IFA 0065139

Method

Semi-Quantitative Indirect Fluorescent Antibody

Medical Experts

Contributor

Fisher

Mark A. Fisher, PhD, D(ABMM)

Associate Professor of Clinical Pathology, University of Utah

Medical Director, Bacteriology, and Special Microbiology, Antimicrobial Susceptibility Testing, at ARUP Laboratories

Contributor

Schlaberg

Robert Schlaberg, MD, MPH

Assistant Professor of Clinical Pathology, University of Utah

Medical Director, Microbial Amplified Detection, Virology, and Fecal Chemistry, and Assistant Medical Director, Virology and Molecular Infectious Disease at ARUP Laboratories

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