Continuing Education Activity

Sexually transmitted infections (STIs), previously known as sexually transmitted diseases, involve the transmission of an organism between sexual partners through different routes of sexual contact, either oral, anal, or vaginal. STIs affect all people and can be prevented with proper education and barrier control. The most common STIs include both curable (gonorrhea, chlamydia, syphilis, trichomonas) and treatable (herpes viruses, human papillomavirus, human immunodeficiency virus) conditions. The correlating symptoms generally fall into 2 categories: discharge/dysuria or ulcerative lesions. The likelihood of contracting these conditions depends on the prevalence of the disease, patient behavior, and underlying comorbidities. Early screening and recognition of STIs are key to preventing disease spread, morbidity, and mortality. These infections are more frequently underrecognized and have a higher incidence in medically underserved populations.

This course explores the complexities of STIs, encompassing both curable and treatable conditions transmitted through various routes of sexual contact. Emphasizing prevention through education and barrier control underscores the significance of early screening and recognition to prevent disease spread and associated morbidity and mortality. STIs disproportionately affect medically underserved populations, highlighting the need for heightened awareness and proactive intervention strategies. Participants in this course gain comprehensive knowledge of STI evaluation and management, including diagnostic approaches, treatment modalities, and preventive measures. Collaborating with an interprofessional team comprising healthcare professionals such as physicians, nurses, counselors, and public health specialists enhances patient outcomes by facilitating holistic care delivery. Through interdisciplinary collaboration, clinicians optimize screening efforts, ensure prompt treatment initiation, and provide ongoing support and education to patients.

Objectives:

• Assess the most likely sexually transmitted infections based on patients' history and symptomatology, community prevalence, and diagnostic testing.

• Identify the long-term complications of a sexually transmitted infection and appropriate post-treatment follow-up.

• Determine the management of patients with sexually transmitted infections through therapeutic interventions and behavioral modification.

• Optimize screening efforts through interdisciplinary communication and collaboration to ensure prompt treatment initiation, and provide ongoing support and education to patients.

Introduction

Sexually transmitted infections (STIs), previously known as sexually transmitted diseases, involve the transmission of an organism between sexual partners through different routes of sexual contact, either oral, anal, or vaginal.[1] STIs become a concern and burden on healthcare systems, as many infections go untreated and lead to potentially serious complications. The natural history and patterns of spread of the most common sexually transmitted infections are discussed as well as disease prevention, evaluation, diagnosis, and treatment.[2]

Etiology

STIs are a worldwide health problem and should be recognized by all public health agencies. STIs are more frequently underrecognized and have a higher incidence in medically underserved populations. The presenting condition or disease depends on the specific organism, route, signs, and symptoms. Risk factors that increase the transmission of STIs include having unprotected sexual contact with multiple partners, having a history of STIs, sexual assault, prostitution, having a sexual partner who has additional concurrent sexual contacts or a prior history of an STI, and using alcohol or recreational drugs. Specific causative organisms are outlined below.

Male circumcision appears to significantly reduce the likelihood of acquiring several STIs, including human papillomavirus, genital herpes, and especially human immunodeficiency virus (HIV), where the infective risk decreases by 50% to 60%.[3][4] The 7 most common STIs include 5 curable infections (chlamydia, gonorrhea, syphilis, and trichomonas) and three incurable but treatable conditions (herpes simplex virus, HIV, and human papillomavirus (HPV). Of note, hepatitis B and hepatitis C can also be transmitted sexually but are more commonly spread through other forms of exposure. See each companion StatPearls reference for more detail.

The most common and relevant STIs include the following:

Chancroid 

• Haemophilus ducreyi is the causative organism of chancroid.
• This fastidious Gram-negative coccobacillus (very short rod) requires special media and environmental conditions to grow in the culture.
• Microscopically, the organism will tend to form long strands, forming a pattern described as "railroad tracks" or "a school of fish."
• The organism significantly increases the risk and transmissibility of HIV.
• This infection is exceedingly rare in the United States (US) and developed countries globally.[5]

Chlamydia 

• Gram-negative obligate, nonmotile intracellular bacteria known as Chlamydia trachomatis (C trachomatis)[6]
• Typically, serotypes D-K
• The most common curable sexually transmitted infection in the United States, according to the Centers for Disease Control (CDC) and the World Health Organization (WHO)
• Two infectious forms exist: the elementary (EB) and reticulate body (RB) 
• The EB form invades the cell, and the RB form will produce other infectious EB that will infect other non-infectious forms [7]

Genital Herpes 

• Genital herpes is caused by the herpes simplex virus 1 (HSV-1) or herpes simplex virus 2 (HSV-2).[8]
• HSV is a double-stranded DNA virus coated by a lipoglycoprotein with an affinity to infect target cells.[9]
• HSV-1 is usually associated with orolabial infections, but according to the CDC, HSV-1 is now leading in the cause of genital herpes in young and homosexual patients.[8]
• There is an estimation that 50 million people in the US are infected with HSV.[9][10]

 Gonorrhea

• This condition is caused by Gram-negative diplococci bacteria Neisseria gonorrhoeae. (N gonorrhoeae).
• This is the second most common sexually transmitted infection in the US (the first is C trachomatis.)[8]
• Gonorrhea uses glucose to invade mucus epithelial cells. 
• Gonorrhea modifies cellular proteins that allow further penetration of other organisms.
• The proliferation of gonorrhea leads to a localized inflammatory reaction, leading to signs and symptoms of an STI.[11][12]

Granuloma inguinale 

• This is caused by Gram-negative intracellular Klebsiella granulomatis, formerly known as Calymmatobacterium granulomatis. (This is also referred to as Donovanosis.)
• Rarely found in the US, granuloma inguinale is seen mostly in developing countries, especially in the tropics.
• This condition is most commonly found in the Caribbean, southern Africa, South America, New Guinea, and India.[13]

Human Immunodeficiency Virus and Acquired Immunodeficiency Syndrome 

• These are enveloped retroviruses encapsulated with 2 single-stranded ribonucleic acids. 
• Primary HIV signs and symptoms are described as flu-like and often diagnosed as an acute viral syndrome.[14]
• The duration of onset of symptoms ranges from 4 to 10 weeks.
• Most HIV infections in the US are HIV1.
• Acquired immunodeficiency syndrome (AIDS) is described as the late stage of HIV disease.[15]
• The median time to progression from HIV to AIDS is about 11 years but is highly variable.
• The risk of syphilis in patients infected with HIV is 77 times greater than in the general population.[16]

Human Papillomavirus 

• HPV is a double-stranded deoxyribonucleic acid virus that replicates in the basal cell layer of the stratified squamous epithelial cells. This replication cycle induces hyperplasia and possible conversion carcinoma.
• HPV types 16 and 18 are oncogenic strains that induce malignant transformation.[17]
• Types 6 and 11 are common strains that induce anogenital warts, known as condyloma acuminata.[1]
• By far, HPV is the most common sexually transmitted infectious organism in the US and worldwide.

Lymphogranuloma venereum

• This condition is caused by Chlamydia trachomatis, a Gram-negative obligate, nonmotile intracellular bacteria but a different serotype from the more common chlamydial infections.
• The bacteria are serotypes or serovars L1, L2, and L3.
• This infection is rare in the US but common in tropical and subtropical regions.
• Lymphogranuloma venereum is most frequently found in men who have sex with other men.
• Closely associated with HIV infections.[18]

Mycoplasma genitalium

• Mycoplasma genitalium is the second most common cause of nongonococcal urethritis after chlamydia and a common cause of female cervicitis and resistant or recurrent urethritis.
• Mycoplasma is very slow growing in a culture, which can take up to 6 months.
• Since it lacks a cell wall, it cannot be Gram-stained.
• Risk factors include young age (<25 years), smoking, frequent sexual contact, and a large number of sexual partners.
• This condition is closely associated with HIV infections.[19]

Syphilis 

• This illness is caused by a spirochete bacterium, Treponema pallidum (T pallidum).
• T pallidum is very slow-growing and cannot be cultured nor seen on standard light microscopy.
• The initial immune response is muted because T pallidum has few exposed proteins and no lipopolysaccharides in its outer membrane.
• According to the CDC, infections of this type are increasing compared to previous reports.[8]
• Syphilis is far more common in the developing world, particularly among the poorest populations with the most limited access to healthcare.[20]
• This condition presents with a painless chancre, a well-demarcated lesion at the inoculation site.[21]
• Syphilis presents in various forms and, depending on the duration, is classified as primary, secondary, or tertiary.[8]
• Globally, this condition affects about 12% of men who have sex with men.

Trichomoniasis 

• This condition is caused by single-celled flagellated anaerobic protozoa known as Trichomonas vaginalis. 
• Trichomoniasis causes direct damage to the epithelium. The injuries lead to microulcerations primarily in the vagina, cervix, urethra, and paraurethral glands.[22][23]

Epidemiology

The most common STI in the US is the human papillomavirus or HPV. At any given time, about 80% of sexually active people are estimated to be infected, including 42% of adults 18 to 59 years. Of those infected, 7% will have oral HPV, and roughly 14 million new cases of this condition are estimated to be reported yearly. HPV is very common; the CDC estimates that virtually all sexually active persons who are not vaccinated will become infected at some point in their lives. Worldwide, at least 291 million women have been infected with HPV. 

The CDC has determined that roughly 2.4 million non-HPV-related STIs were reported in the US in 2020. Chlamydia was the most common of these at 1.6 million cases. Next, 677,769 cases of gonorrhea were reported in 2020, up 45% from 2016, and 133,945 cases of primary and secondary syphilis, up 52% over the same period. In 2020, congenital syphilis was identified in 2148 infants, up 235% from 2016.

Over 80% of the reported cases of primary and secondary syphilis are found in men. Men who have sex with men account for almost half (47%) of the reported cases of men. The CDC also estimates that 44% of men who have sex with men and bisexual men who test positive for syphilis will also have HIV.

In general, the overall rate of STIs is increasing in the US.

According to the WHO, global epidemiological data for STIs indicates the following:

• Worldwide, over 1 million new potentially curable STIs are acquired daily, most of which are asymptomatic. 
• There is an estimation that 376 million new infections occur annually, with one of the four curable STIs (chlamydia, gonorrhea, syphilis, and trichomoniasis).
• Of these, trichomonas is the most common globally, with 156 million new cases yearly, followed by chlamydia at 127 million, gonorrhea at 87 million, and syphilis at 6.3 million.
• The US incidence of STIs is rising; there was close to a 30% increase in reportable STIs between 2015 and 2019.
• About 12% of the US population between 14 and 49 years is estimated to be infected with herpes currently.
• Herpes simplex virus type 2 has a global prevalence estimated at over 500 million people.[24]
• About one million pregnant women were estimated to have an STI in 2016, causing over 350,000 birthing or neonatal complications.
• HPV infections have been linked to over 310,000 cervical cancer deaths annually.[25]
• Syphilis is the second leading cause of stillbirths worldwide.
• HIV/AIDS affected about 37 million people worldwide in 2016.[14]
• About 15% of HIV-infected individuals in the US are unaware they have the infection and are responsible for 40% of all new HIV infections.[26]
• According to the CDC, there are approximately 35,000 new cases of HIV in the US annually.
• Mycoplasma genitalium causes 15% to 20% of all non-gonococcal urethritis (NGU), 20% to 25 % of all non-chlamydial NGU cases, and 40% of all recurrent or persistent urethritis infections.

Ideally, physicians, public health officials, political leaders, international and regional healthcare organizations, and other healthcare professionals should have a centralized data collection system to analyze and fully assess the incidence, distribution, progression, and treatment of all STIs. As health professionals, the best available sources include various published studies and official government agencies and healthcare organizations assessing the statistical importance of STIs, such as geographic areas of increasing incidence or particular demographics of affected populations.[27] STI rates are high in most countries, especially between the ages of 15 and 50.[28] Undiagnosed STIs are responsible for an estimated 20,000 cases of infertility in women annually in the US. 

Pathophysiology

This review is intended to serve as a general presentation of STIs, including the most common infections such as HIV, gonorrhea, chlamydia, genital herpes, HPV, trichomoniasis, and syphilis. Sexually transmitted infections can be bacterial, viral, or parasitic. STIs invade the human body through microscopic abrasions within the mucosal membranes of the penis, vagina, anus, or any other mucosal surfaces. Transmission of STIs can include intravenous drug use and exposure during childbirth or breastfeeding.[15] Organisms invade normal cells and overburden the immune system, creating typical signs and symptoms of the disease. 

Basic symptomatology, including genital, extragenital, or disseminated, with a history and physical exam to assist with differential diagnosis and recommended treatments, will be reviewed. Updated treatment guidelines by the CDC and WHO, as well as a general overview of all common sexually transmitted infections, will be presented. Physicians and other healthcare professionals must understand curable versus incurable sexually transmitted infections. Untreated STIs can lead to severe, lifelong health disorders, including infertility, scarring, chronic pain, sexual dysfunction, and cancers.

History and Physical

Medical professionals are trained to communicate with patients, partners, and families to understand their chief complaints and formulate an effective and useful differential diagnosis. At the same time, taking a detailed history is mandatory, whether it occurs in a primary clinic or the emergency department. The clinician's role is to effectively communicate with the patient who presents with signs and symptoms suggestive of a previously undiagnosed sexually transmitted infection. Clinicians should be aware that all adolescents under 18 have the right to an STI screening and treatment without parental consent in the US.[6]

Clinicians should recognize that STIs closely correlate with patient behavior; this should be addressed kindly, diplomatically, and nonjudgmentally during the clinical evaluation.[29] Healthcare professionals' roles are to help, treat, and educate patients about their illnesses and promote and suggest healthy behaviors that minimize re-infections.

Further details should be investigated with individual state health care systems or reference the "Sexually Transmitted Disease Treatment Guidelines 2021" published by the CDC.[29]

While performing the sexual history collection, an easy mnemonic that can help guide clinical questions can be remembered as the "other 5 Ps":

1. Partners
2. Practices 
3. Prevention against pregnancy
4. Prior history of STIs
5. Protection against STIs [30]

The physical exam should be guided by the presenting chief complaint and symptoms collected in the review of systems.[7] The exam should be conducted privately with a chaperone at the bedside whose name can then be documented in the patient's medical record.[8] At the end of the exam, present the patient with an open-ended question to ensure there is an open dialogue and to determine if the patient has any other details about their sexual practice not previously discussed.

This is a brief overview of the most common signs and symptoms and physical exam findings of sexually transmitted infections that can be evaluated in an acute setting. Each STI has a separate StatPearls reference that should be used for a more in-depth approach.

The physical exam will be broken down by the most common signs and symptoms, physical exam findings, and diagnosis.

Chancroid 

• Women and men:
• Signs and symptoms: This condition often occurs in the 20 to 30-year-old age group, frequently among sex workers and their clients. The areas most often affected include the distal portion of the penis in men, while in women, the vagina, labia, and perianal regions are involved. The most significant symptom is the extremely high pain level noted when the lesion reaches the ulcerative stage.[5]
• Physical exam: The lesion starts as a reddish papule, rapidly progressing to a pustule, followed by an extremely painful ulcer. The ulcer, sometimes called a "soft chancre," will have soft and irregular margins with a friable base and a grayish-yellowish exudate; the ulcer tends to bleed easily. The ulcers are typically 1 to 2 cm in diameter and usually resolve spontaneously within 3 months, even if left untreated. Close to half of the affected individuals will develop regional lymphadenopathy, which may be tender. A minority (about 25%) of these patients will progress to infected bulla or abscesses that can rupture and become superinfected, leading to significant tissue destruction and damage to the genitalia. There is an estimation that 10% of affected individuals will also have syphilis or genital herpes.

Chlamydia 

• Women:
• Signs and symptoms: Most infections can be asymptomatic but may present with vaginal discharge, abnormal vaginal bleeding, lower pelvic pain, urinary frequency, or dysuria.[31] If systemic infection is present, the patient may be febrile, with abdominal pain, nausea, vomiting, fatigue, and malaise.[7]
• Physical exam: Inflammation of the cervix with mucopurulent discharge can be seen, and ectropion, vaginal discharge, increased sensitivity of the cervix, and tenderness of the adnexal regions and abdomen are present.[31] If systemic infection or Fitz-Hugh-Curtis syndrome is considered in the differential, right upper quadrant tenderness may be secondary to perihepatitis.[7]
• Men: 
• Signs and symptoms: The most common presenting symptoms are dysuria, testicular pain, and pain with defecation secondary to inflammation of the rectal area and prostate.[7] This common cause of male urethral discharge is typically beige or yellowish.
• Physical exam: Tenderness to the testicles (specifically over the epididymis) or discomfort with palpation to the prostate or rectum.[7]

 Genital Herpes 

• Women and men: 
• Signs and symptoms: Primary infections tend to induce systemic symptoms, including painful vesicular lesions over affected areas, pruritus, dysuria, fever, headaches, malaise, and lymphadenopathy. Initial infections typically resolve spontaneously, starting at about 2 weeks. Reactivation usually presents with a prodromal phase, including tingling, itching, and rash consistent with vesicular lesions.[9][10] Recurrent infections tend to be less intense and have a shorter duration.[32]
• Physical exam: The affected area may be localized or systemic. A primary herpes infection tends to be worse with diffuse symptomatically involving various systems, possibly resulting in pneumonitis, hepatitis, meningitis, and encephalitis. Women may have diffuse vesicular lesions in the internal and external vaginal areas.[32] Men may have diffuse vesicular lesions to the glans of the penis, penile shaft, scrotum, perineal/perianal area, and rectum, both internally and externally. Recurrent herpes infections may cause isolated vesicular lesions over a neuronal tract where the virus is dormant.[33]

Gonorrhea 

• Women:
• Genitourinary exam: This may include inflammation of the external vagina, causing excoriations from pruritus, mucopurulent discharge, and friable inflamed mucosal tissue of the cervix.[11][34]
• Signs and symptoms: Patients may present with dysuria, urgency, urinary frequency, lower pelvic pain, and abnormal vaginal bleeding.[7]
• Physical exam: A thorough physical exam should be performed if you suspect systemic infection.[12]
• Men: 
• Signs and symptoms: Patients may present with testicular pain, dysuria, purulent discharge from the meatus, and pain with defecation secondary to inflammation of the rectum or prostate.[30] The clinician should also observe carefully for systemic signs and symptoms consistent with disseminated gonococcal infection, ie, sore throat, redness of the eyes, joint pain, and cutaneous lesions.[12]
• Physical exam: There may be palpable tenderness over the epididymis, purulent discharge from the meatus, or palpable tenderness to the prostate or rectum.[30] A thorough general physical examination is required due to concerns about disseminated gonococcal infections, particularly in the joints.[12]

Granuloma Inguinale 

• Women and men:
• Signs and symptoms: Patients will present with highly vascularized lesions over the genitals and perineum that tend to be painless but can cause severe scarring.[35][36][37] 
• Physical Exam: Typical findings include beefy, red ulcer-like lesions consistent with high vascularization that bleeds easily with manipulation. Subcutaneous granulomas may be present, but lymphadenopathy is uncommon. The lesions are relatively large and irregular and often associated with secondary infections.
• Four main lesions can be seen on examination: 

1. Ulcerovegetative: Large painless ulcer on the patient's physical exam
2. Nodular: Soft and erythematous that tend to ulcerate throughout the infectious process
3. Cicatricial: Dry ulcerations that tend to transition into plaques. 
4. Hypertrophic: Lesions are thick and painless

HIV 

• Women and men: 
• Signs and symptoms: Patients may be asymptomatic or present with an acute viral syndrome, including systemic symptoms: malaise, fatigue, anorexia, fever, chills, arthralgias, myalgias, or cutaneous presentations.[15] Signs of a more advanced infection include fever, diarrhea, shortness of breath, cough, and oral candidiasis. Acute retroviral syndrome may occur with non-specific symptoms, including fatigue, muscle pain, skin rash, headache, sore throat, swollen lymph nodes, arthralgia, night sweats, and diarrhea. Acute retroviral syndrome will occur early in 50% to 90% of new HIV-infected individuals, usually before their antibody tests turn positive.[14]
• Physical exam: The chief complaint will guide the physical exam. The patient should have a thorough history and physical exam to rule out a broad differential diagnosis.[14] Secondary and opportunistic infections are common, especially with AIDS.

HPV and Genital Warts 

• Women and men:
• Signs and symptoms: Most complaints are cosmetic or incidental findings due to the asymptomatic nature of common HPV types 6 and 11. These are usually asymptomatic but are responsible for most (90%) venereal and anogenital warts. Patients may also present with ulcerative lesions secondary to oncogenic HPV types 16 and 18, which can progress to malignancies when triggered or stimulated by folate deficiency, ultraviolet light exposure, pregnancy, immunosuppression, or smoking.[17]
• Physical exam: On exam, an exophytic lesion may be described as a cauliflower-like growth known as condylomata acuminata.[17] Lesions can be observed over the external genital region, perineum, or perianal area. An examination for women includes a speculum exam with screening to rule out cervical cancer.[38]

Lymphogranuloma Venereum 

• Women and men: 
• Signs and symptoms: Patients will present with painful lymphadenopathy localized to the inguinal area. Patients may note the initial presentation of a pustule that gradually progresses to extensive painful ulceration.[39] Men present with early or acute stages, while women present much later.[18]
• Physical exam: Lymphogranuloma venereum presents with 2 stages. The primary phase is a small, painless papule/pustule that will ulcerate and can be visualized throughout the affected genital area. During the secondary phase, patients present with unilateral lymphadenopathy that is fluctuant with palpation or may be suppurative in a presentation known as buboes.[37] Buboes tend to rupture in the acute phase and progress to a thickened mass.[40]

Mycoplasma genitalium

• Women
• Signs and symptoms: Patients may present with pelvic pain, dysuria, and similar type symptoms to gonorrhea or chlamydia infection, including vaginal irritation, discharge, foul odor, or even pelvic inflammatory disease.[19][41]
• Physical exam: Common findings would be irritation of the external and internal vagina, vaginal discharge, cervical tenderness, cervicitis, adnexal tenderness, or abnormal vaginal spotting.[42]
• Men: 
• Signs and symptoms: Patients may present with suprapubic pain, dysuria, urinary frequency, urgency, or testicular pain. This is a common cause (40%) of persistent or recurrent urethritis.[19]
• Physical exam: The examination may be painless and benign, or there may be tenderness to the epididymis with palpation or discomfort from the prostate on the rectal exam.[43]

Pelvic Inflammatory Disease in Women

• Pelvic inflammatory disease (PID) is a sexually transmitted infection that involves the upper female genital tract and can affect long-term fertility, and the infections can be serious.[35]
• Risk factors include multiple sexual partners, prior episodes of pelvic inflammatory disease, intrauterine device implants, history of tubal ligation, and younger age.
• The most common causative organisms are chlamydia and gonorrhea, but Mycoplasma genitalium can also cause PID. There is no specific test for pelvic inflammatory disease, as the diagnosis is primarily clinical.
• The typical physical finding is tenderness on cervical motion or pain on palpation of the pelvic area.
• Other findings include cervical friability or discharge and increased white blood cells on wet prep.
• Typical symptoms include the following:
• Abdominal tenderness
• Adnexal tenderness
• Cervical motion tenderness
• Fever (>38 °C or >100.4 °F)
• Increased vaginal discharge
• Irregular menstrual bleeding
• Lower abdominal pain
• Mild pelvic pain
• Pain with intercourse
• Painful and frequent urination
• Uterine tenderness

Syphilis 

• Women and men:
• Primary: The patient presents with a painless, well-demarcated lesion/ulcer known as a chancre at the inoculation site.[21] This is typically within 3 months of the inoculating event. If untreated, the lesions will heal on their own in 3 to 8 weeks, but 30% will progress to tertiary syphilis.[21]
• Secondary: Presents 2 to 4 weeks after initial chancre with systemic symptoms involving a cutaneous lesion and characteristic maculopapular rash. Cutaneous wart-like lesions known as condylomata lata may present and resolve during this phase. The rash does not itch and specifically includes mucus membranes as well as the palmar regions of the hands and soles of the feet, which are generally spared in other disorders.[21]
• Latent: No clinical signs or symptoms are present, but serological tests are positive.[21]
• Tertiary: About 33% of untreated patients will show tertiary symptoms presenting months, years, or decades after the original inoculation. Systemic symptoms can range from cardiovascular and neurologic to cutaneous gummatous lesions. Neurosyphilis can present with stroke-like symptoms, cranial nerve deficits, a change in mental status, general paresis, or tabes dorsalis.[44] (See the companion StatPearls reference reviews on "Neurosyphilis" and "Tabes dorsalis.")[45][46]
• Signs and symptoms: Presenting symptoms of a syphilis infection depends on the phase of the infection at the time of evaluation. Symptoms can be categorized into primary, secondary, latent, and tertiary phases, which are best detailed and discussed in the companion StatPearls reference review on "Syphilis."[21]
• Physical Exam: The physical exam depends on the presenting phase of the syphilis infection. 

Trichomoniasis 

• Women:
• Signs and symptoms: Women can remain asymptomatic or may present with a complaint of foul-smelling discharge, pruritus, dyspareunia, dysuria, and vaginal spotting.[22]
• Physical exam: The exam will show irritation of the external and internal vagina, including classic physical findings of "strawberry cervix," known as colpitis macularis. A foul frothy vaginal discharge may be present on exam.[47]
• Men: 
• Signs and symptoms: Men can remain asymptomatic with a trichomonas vaginalis infection but can also present with testicular pain, dysuria, or rectal pain. 
• Physical exam: Tenderness will be present, with palpation of the epididymis and prostate on rectal exam. No overlying skin lesions or inflammatory processes will be seen.[47] 

Evaluation

Screening and evaluation recommendations are included in a detailed presentation in the CDC's "Sexually Transmitted Disease Treatment Guidelines 2021."[29]

The information provided is extrapolated from the guidelines and should be used at the physician's discretion in conjunction with the patient.[30] In general, all patients presenting with STI symptoms should also be screened for HIV and all other community-prevalent STIs.

Chancroid 

• Women/Men: Diagnosis is by clinical history and examination, together with the exclusion of alternative ulcerative infections such as herpes and syphilis. One or more deep, relatively large, painful ulcers on the genitalia associated with inguinal adenopathy that are tender and suppurative are highly suggestive of chancroid. (Herpetic ulcers are usually smaller, and chancres from syphilis are typically painless.)[5]
• Gram stain may show a typical "school of fish" pattern, but this is only 80% sensitive. The definitive diagnosis requires growing Haemophilus ducreyi in culture; this is difficult and requires using specially enriched media grown under conditions of high humidity and high CO2, which is not generally available to most clinical laboratories. No Food and Drug Administration (FDA)-approved polymerase chain reaction (PCR) serological test is available for H ducreyi.[31] 
• The CDC recommends using the following clinical criteria:

• One or more painful genital ulcers
• Clinical findings, such as the appearance of genital ulcers and regional lymphadenopathy consistent with chancroid
• No evidence of Treponema pallidum infection by darkfield microscopy of the exudate or by serologic testing within 1 week after the onset of ulcers
• A negative Herpes simplex virus culture or PCR test was performed on the exudate

Chlamydia:

• Women: Diagnosis is made by using a nucleic acid amplification test (NAAT) on a vaginal swab, first-catch urine sample, or self-endocervical swab. 
• Men: Diagnosis is made using NAAT of a first-catch urine or urethral sample.[7][29]

Genital Herpes 

• Women/Men: Diagnosis is by clinical examination, NAAT from genital ulceration, or viral culture. 
• Fluorescein-labeled monoclonal antibodies are available using a direct immunofluorescence assay for herpes simplex virus antibodies, but this is not currently recommended due to the test's insensitivity.
• Cellular changes on cytologic examination associated with HSV infections are also not recommended for diagnosis. They are considered too nonspecific and insensitive.
• HIV testing is recommended in all patients who test positive for genital herpes.[9][10][32]

Gonorrhea 

• Women: Diagnosis is made using a NAAT vulvovaginal or endocervical swab. 
• Men: Diagnosis is made using NAAT of a first-catch urine or urethral sample.[11][12]

Granuloma inguinale 

• Women/Men: The diagnosis is primarily clinical, based on the gross appearance of the lesions and microscopic findings of intracellular Donovan bodies on a scraping, tissue, or biopsy specimen. 
• Donovan bodies are rod or oval-shaped intracellular inclusions in the cytoplasm of histiocytes or mononuclear phagocytes of infected patients, which stain dark purple with Wright stain.
• The infecting organism is difficult to culture, and no FDA-approved molecular diagnostic laboratory test is currently available.[33]

HIV 

• Women/Men: Diagnosis involves using a blood sample or saliva for antibodies as a preliminary test, followed by more specific tests, including PCR or specific immunoassays.[14][15]
• The CDC recommends at least one HIV test for all adults from 15 to 65.
• High-risk individuals (eg, multiple sexual partners, sex workers, men who have sex with multiple men) should be tested at least annually.
• PCR testing is essentially diagnostic of an HIV infection.
• The CDC recommends HIV1/HIV2 antigen-antibody immunoassay. 
• Patients who are unlikely to return for follow-up should be offered a rapid point-of-care HIV test. Results are available in less than 20 minutes but may be negative in early infections.
• A reverse transcriptase (RT)-PCR-based viral load test is also recommended.
• HIV ribonucleic acid testing is best for acute HIV infections.
• An HIV1/HIV2 antibody differentiation assay is confirmatory.
• HIV-infected individuals should be screened for chlamydia, gonorrhea, and syphilis when diagnosed and at least annually afterward.
• Individual assays to isolate specific antibodies or viral antigens can be used for confirmation. (See the companion StatPearls reference review on "HIV Testing.")[26] 

HPV and Genital Warts 

• Women/Men: Diagnosis is primarily clinical, based on the gross appearance of any cutaneous or other lesions discovered on the physical examination.
• A biopsy can be performed for confirmation, but this is usually reserved for the following situations:
• Patients who are immunocompromised patients (cancer risk is highest)
• Diagnosis is uncertain
• Atypical lesions
• Lesions that do not respond to standard therapy
• Women: Reflex HPV testing can be done on cervical cells from a Pap smear to identify HPV subtypes.
• Suspicious Pap smear results can be further evaluated by colposcopy using acetic acid to highlight specific white-colored areas that can be biopsied.

Lymphogranuloma venereum

• Women/Men: Initial diagnosis is primarily by clinical suspicion in regions where this infection is common and by eliminating other causes of genital ulcerations with inguinal lymphadenopathy.
• Ulcerative infections of the genitalia to exclude, which also cause inguinal lymphadenopathy, would be chancroid, herpes, granuloma inguinale, and syphilis.
• Lymphoma, penile cancer, and HIV are additional causes of lymphadenopathy.
• Serological testing with complement fixation, micro-immunofluorescence, or NAAT can confirm the diagnosis, but PCR-based genotyping is the most definitive.
• Due to availability, NAAT testing is usually preferred and recommended for all patients with proctocolitis.
• Finding Chlamydia trachomatis in a genital, lymph node, or rectal specimens through culture, direct immunofluorescence, or NAAT is diagnostic and confirmatory.
• Men who have sex with men and have proctocolitis should be tested for all strains of C trachomatis.
• HIV testing is especially recommended in this patient population.[18][34][35]

Pelvic Inflammatory Disease 

• Women: Diagnosis is primarily clinical based on the presence of lower abdominal pain, pelvic discomfort, purulent vaginal discharge, abnormal vaginal bleeding, or dyspareunia.
• Findings suggestive of pelvic inflammatory disease include:
• Fever higher than 101 °F (38.3 °C)
• Cervical friability
• Mucopurulent cervical discharge
• Saline microscopy of vaginal fluid shows abundant WBCs
• Elevated erythrocyte sedimentation rate (ESR) or C-reactive protein
• Laboratory confirmation of N gonorrhea or C trachomatis by NAAT or culture
• A diagnosis of pelvic inflammatory disease is unlikely if the cervical discharge is normal and no white blood cells are seen on a wet prep of the vaginal fluid.
• NAAT testing for N gonorrhea, C trachomatis, and M genitalium is recommended. 
• Serological testing for HIV and T pallidum should also be performed.
• Pregnancy testing should be done, and pelvic ultrasonography should be considered if there is any suspicion of a tubo-ovarian abscess.[33]

Mycoplasma genitalium 

• Women/Men: Initial diagnosis is primarily clinical based on symptoms and the exclusion of chlamydia and gonorrhea.
• NAAT assays for M genitalium are now available and FDA-approved, with a 96% or higher sensitivity.
• M genitalium should be suspected in all patients with recurrent or persistent gonorrhea or chlamydia infections and intractable urethritis.
• Presumptive treatment can be initiated in suspected cases even without diagnostic confirmation.[19]

Syphilis

• Women/Men: The diagnosis is confirmed by a positive finding on serological tests, which include at least one nontreponemal and one treponemal assay.
• No NAAT tests for syphilis are currently available. PCR tests for T pallidum have been developed, but none are FDA-approved.
• Nontreponemal testing, including the Venereal Disease Research Laboratory (VDRL) and rapid plasma reagin (RPR) assays, are non-specific serum antibody tests for syphilis.
• A negative test would be non-reactive, while a positive test would demonstrate a titer of at least 1:8.
• If the titer is lower than 1:8, the test should be repeated, and a treponemal assay should also be performed.  
• Nontreponemal tests are simple, inexpensive, and are usually the initial screening tests for syphilis.
• They will identify roughly 80% of patients with primary syphilis and close to 100% with secondary syphilis.
• They typically turn positive only after the appearance of the primary chancre.
• When quantified, they can be used for disease tracking as a four-fold change in activity is generally considered significant.
• However, they are not specific for syphilis and can often give false-positive results, so they are inadequate for a definitive diagnosis alone without confirmation from a treponemal test.
• Treponemal testing, including the fluorescent treponemal antibody absorption and the Treponema Pallidum particle agglutination assays, are needed to confirm the diagnosis.
• While specific treponemal antibodies appear early, their level does not correlate well with disease activity or stage.
• They typically remain positive for life even after successful treatment, making them ineffective for disease tracking.
• A positive result on at least 1 nontreponemal and 1 treponemal test is required to confirm a syphilis diagnosis definitively.
• Only quantifiable nontreponemal tests can be used for disease tracking.
• Darkfield microscopy can identify the infecting spirochete in 80% of cases even before serological testing becomes positive but is rarely performed due to technical difficulties.
• Patients who present with possible neurosyphilis will need a cerebral spinal fluid sample to assist with the diagnostic workup.
• VDRL testing of the cerebrospinal fluid is highly specific for neurosyphilis but not very sensitive (opposite of blood testing).
• Treponemal testing of the cerebrospinal fluid is highly sensitive but less specific than the VDRL test for neurosyphilis (the treponemal antibodies often diffuse from the blood into the cerebral spinal fluid, which can also be contaminated by blood cells).
• HIV testing should especially be performed on all patients testing positive for syphilis.
• For further details on the complexities of diagnostic testing, see StatPearls' companion reference on "Syphilis." [21]

Trichomoniasis 

• Women: Diagnosis using NAAT of the vagina, endocervical swab, urine analysis, or urethral sample.
• Alternatively, a wet mount will show motile flagellated protozoa.
• Patients diagnosed with trichomoniasis should also be tested for chlamydia, gonorrhea, HIV, and syphilis.[22][36]

Pregnancy—STI Screening Recommendations from the CDC 2021 Guidelines: 

Sexually transmitted infections can potentially cause serious health consequences for the mother and fetus.[29] Therefore, the CDC currently recommends the following routine STI screenings in pregnancy:

• First Prenatal Visit:
• All pregnant women should be tested for HIV, hepatitis B, hepatitis C, and syphilis. 
• All pregnant women who are at increased risk for infection should also be tested for chlamydia and gonorrhea.
• Pregnant women who test positive for chlamydia should be retested 3 to 4 weeks after treatment and again within 3 months.
• Third Trimester Visit (preferably at or before 36 weeks):
• Rescreen women younger than 25 years of age or at continued high risk and all those not previously tested for chlamydia, gonorrhea, and syphilis.
• Pregnant women with high-risk factors or who were not previously tested should be screened for HIV and hepatitis B.
• Those patients who tested positive for syphilis at the prenatal visit should be retested.

High-Risk Factors Include:

• New or multiple sex partners
• Inconsistent use of condoms
• A sexual partner with concurrent or multiple partners
• A sexual partner who has a sexually transmitted infection 
• History of illegal drug use or prostitution
• Living in an area with a high rate of STIs
• Incarcerated individuals

The CDC does not recommend routine testing in pregnancy for bacterial vaginosis, herpes, HPV, or trichomoniasis.

Treatment of STIs in Pregnancy

Curable STIs (chlamydia, gonorrhea, syphilis, and trichomonas) can be successfully treated with appropriate antibiotics deemed safe for administration during pregnancy. While viral STIs cannot be cured, they can generally be controlled with various antivirals and other preventive measures to minimize perinatal transmission. 

For detailed information on specific STI treatments in pregnancy, readers are referred to the 2021 WHO and CDC STI Guidelines.[29]

Treatment / Management

The Centers for Disease Control and Prevention published an update to their Sexually Transmitted Diseases Treatment Guidelines in 2021. There are sections in this treatment guideline that direct specific care for select populations such as pregnant women, adolescents, persons in correctional facilities, men who have sex with men, women who have sex with women, and transgender men/women.[6][30] These topics should be explored and reviewed on a case-by-case basis.

Primary preferred treatments will be discussed, and further reference articles will be cited for different management options.[8] If the primary treatment is not tolerated or the patient is allergic, clinicians should consult their pharmacy department or an infectious disease specialist for further recommendations. 

Each topic has a separate StatPearls review, which should be consulted for further information. The following recommendations are from the 2021 Centers for Disease Control CDC STI 2021 Treatment Guidelines.[30]

Acute Epididymitis: 

• In men younger than 35, this is most likely caused by sexual transmission of chlamydia or gonorrhea: 
• Ceftriaxone 500 mg is administered intramuscularly (IM) or intravenously (IV) in one dose, PLUS doxycycline 100 mg two times daily for 10 days.
• In men older than 35 most likely caused by enteric organisms only:
• Levofloxacin 500 mg orally once daily for 10 days.
• In men where the underlying etiology is uncertain or who practice sex with other men:
• Ceftriaxone 500 mg IM or IV one dose PLUS levofloxacin 500 mg daily by mouth for 10 days [30][34]

Chancroid: Subjective and objective improvement are typically noted within 1 to 2 weeks.[5] Failure to respond suggests an incorrect initial diagnosis, a coinfection such as HIV, treatment non-compliance, or drug resistance.

• Azithromycin 1 g, orally as a single dose 
• Ceftriaxone 250 mg, IM as a single dose 
  • Azithromycin and ceftriaxone have the benefit of single-dose therapy.
• Erythromycin 500 mg, orally 3 times per day for 7 days
• Ciprofloxacin 500 mg, orally twice a day for 3 days

Patients should be evaluated for treatment response 3 to 7 days after therapy. Some resistance to erythromycin and ciprofloxacin has been reported, but data on antimicrobial resistance is limited.

Chlamydia: Coinfections with the most common STIs should be considered and treated simultaneously.

• Doxycycline 100 mg twice daily by mouth for 7 days is preferred.
• Alternative therapy would be one dose of azithromycin 1 g or levofloxacin 500 mg daily for 7 days.
• In pregnancy, azithromycin 1 g orally or amoxicillin 500 mg 3 times daily for 7 days is recommended.
• Other formulations can be taken but should be evaluated case-by-case, considering the patient's concerns.
• For persistent or recurrent nonspecific urethritis, specific Mycoplasma genitalium testing is recommended. If unavailable, the course of doxycycline 100 mg 2 times daily for 7 days should be repeated, followed by oral moxifloxacin 400 mg daily for 7 days. 
• After initial treatment, follow-up testing should be scheduled with the patient.[7][30]

Genital Herpes: Treatment and management of a primary infection should include systemic infection with antivirals and treatment for symptomatic pain or itching.[9][10] The clinician and patient should discuss medication options, including any financial strain that may hinder appropriate treatment.

• Acyclovir, famciclovir, and valacyclovir are three primary antiviral treatments that can be started on patients for initial therapy.
• Acyclovir 400 mg 3 times daily for 7 to 10 days or
• Famciclovir 250 mg 3 times daily for 7 to 10 days or
• Valacyclovir 1 g 2 times daily for 7 to 10 days
• There are various formulations and treatment courses that should be started after the best management plan is discussed with the patient.[8] 
• Suppressive therapy for recurrent outbreaks is effective at the following dosages:
• Acyclovir 400 mg 2 times daily 
• Famciclovir 250 mg 2 times daily
• Valacyclovir 500 mg to 1 g daily
• A higher dose schedule of these same agents can be used for episodic outbreaks, and IV therapy is utilized for particularly severe cases.
• Topical antiviral therapy is not recommended due to its minimal proven clinical effectiveness.
• Patients who are asymptomatic who test positive on serological testing only do not need antiviral therapy.
• The efficacy of antiviral therapy in preventing viral transmission in asymptomatic individuals has not been adequately studied.
• Neonatal herpes is generally treated with systemic acyclovir at 20 mg/kg intravenously every 8 hours.[9] 

Gonorrhea: The history, physical exam, and clinical presentation should support primary treatment and management. Consideration of coinfections with the most common sexually transmitted infections should be considered and treated simultaneously.[11][12]

• One dose of a 3rd generation of cephalosporin, specifically ceftriaxone 500 mg, should be given IM or IV.
• Complicated or disseminated infections will need ceftriaxone 1 g once or every 24 hours, depending on the clinical presentation.
• If the patient is allergic to ceftriaxone or cephalosporins, the recommended alternative regimen is a single dose of gentamicin 240 mg IM plus a single oral dose of 2 g of azithromycin.
• If ceftriaxone is unavailable, the recommended alternative is a single oral dose of cefixime 800 mg.
• Doxycycline 100 mg 2 times daily for 1 week is recommended for chlamydial coinfections.
• After initial treatment, follow-up tests should be discussed with the patient.[11] 

Granuloma inguinale: Treatment and management should be guided by the history, physical exam, and clinical presentation, as granuloma inguinale is uncommon in the US.[13][33][35]

• Azithromycin 1 g weekly or 500 mg daily should be taken orally for at least 3 weeks or until the lesions resolve completely.
• Other formulations and dosages can be given depending on clinical presentation and the guidance of an infectious disease specialist, including the following:
• Doxycycline 100 mg orally 2 times daily for a minimum of 3 weeks or until all lesions resolve completely (whichever is longer) 
• Erythromycin base 500 mg orally 4 times daily for at least 3 weeks or until all lesions resolve completely or
• Trimethoprim-sulfamethoxazole: 1 double-strength (160 mg/800 mg) tablet orally 2 times daily for at least 3 weeks or until all lesions resolve completely.[8][13]

HIV: Primary treatment and management consist of establishing viral load and CD4 count and starting a patient on highly active antiretroviral therapy (HAART).[36] Advice from an infectious disease specialist experienced in HIV treatments is suggested to help determine whether antiretroviral therapy is necessary and the optimal regimen. If a patient is seen for an acute concern, such as sexual assault or exposure to an STI through high-risk sexual activity with a concern for HIV, a single combination medication should be started with close follow-up.[14] Antiviral therapy should be started as soon as possible. A viral load of fewer than 200 copies/mL is essentially non-transmissible. For further details on treatment, see our companion reference StatPearls article on "HIV Antiretroviral Therapy."[37]

• Pre-exposure prophylaxis is recommended for all high-risk, sexually active patients who test negative for HIV-1.
• HAART includes the following classes:
• Nucleoside/nucleotide reverse transcriptase inhibitors 
• NRTI fixed-dose combinations
• Non-nucleoside reverse transcriptase inhibitors 
• Integrase inhibitors 
• Protease Inhibitors 
• Fusion inhibitors 
• Chemokine receptor 5 antagonist 
• Postattachment inhibitors

 HPV and Genital Warts: 

• The CDC recommends HPV vaccinations for all children starting at age 12 and up to age 21 in men and 26 in women.[17]
• Treatment of genital warts depends on location, size, physician experience, and patient preference.
• The application of acetic acid will tend to make HPV-affected skin turn white.
• High-grade cervical dysplasia in older women or any persistent cervical dysplasia is treatable with cryotherapy, loop electrosurgical excision, or cold knife cone resection. 
• If the lesion progresses to a malignancy, additional resection, surgery, chemotherapy, or radiation may be required.
• Accepted treatment methods for anogenital warts include surgical removal, cryotherapy (freezing the infected tissue), laser vaporization, and topical medications.
• Available topical therapies for venereal and anogenital warts include the following: 
• Imiquimod is a topical immunomodulating therapy that stimulates local interferon and cytokine production, inducing an inflammatory reaction.
• Podofilox causes wart necrosis by interfering with cell mitosis.
• Sinecatechins work in an unknown fashion but appear effective as a topical therapy. They are not recommended for patients who are pregnant or immunocompromised.
• Irritant (podophyllin) based topical therapy is no longer recommended by the CDC as safer topical alternatives are available.
• HPV testing can also be done on tissue samples of various squamous cancers (head and neck, penis) to help determine susceptibility to various treatment options such as radiation therapy.
• For further details on treatment, see the companion StatPearls reference reviews on "Human Papillomavirus," "Colposcopy," "Cervical Cancer," and "Genital Warts."[17][38][39][40]

Lymphogranuloma venereum: Treatment and management should be guided by the history, physical exam, and clinical presentation, as lymphogranuloma venereum (LGV) is uncommon in the United States.[18]

• The preferred treatment is doxycycline 100 milligrams, taken by mouth twice daily for at least 21 days or until there is a complete resolution of the presenting symptoms.[8]
• Alternative regimens would be azithromycin 1 gram orally per week for three weeks or erythromycin base 500 mg 4 times daily for 21 days.
• Needle aspiration or incision and drainage may be needed from some buboes.[18]

Mycoplasma genitalium: Concern for an M genitalium infection should be considered if a patient is suspected of resistant chlamydia or gonorrhea infection, especially if recurrent or persistent.[41] Specific testing for resistance is recommended, although Mycoplasma is notoriously slow-growing in culture. Since M genitalium lacks a cell wall, antibiotics that attack the cell wall (penicillins and cephalosporins) are ineffective.[30]

• Doxycycline is 100 mg twice daily for 7 days, followed by azithromycin 1 g orally on the first day, and azithromycin 500 mg once daily for 3 days.
• If macrolide resistance testing is unavailable or not performed, add oral moxifloxacin 400 mg daily for 7 days after completing the above. 
• Increasing macrolide resistance is being reported. A NAAT for M genitalium and macrolide resistance is available only outside the US.
• Fluoroquinolones are still over 90% effective. Moxifloxacin and Sitafloxacin (unavailable in the US) have been the most utilized agents.
• A test-of-cure should be performed 21 days after the completion of therapy.
• If treating for pelvic inflammatory disease:
• Start with doxycycline 100 mg 2 times daily for 14 days.
• If the NAAT test is positive for M genitalium, add 400 mg of moxifloxacin daily for 14 days.[30]

Pelvic Inflammatory Disease: 

• Ceftriaxone 1 g IV every 24 hours plus doxycycline 100 mg orally/IV every 12 hours plus metronidazole 500 mg orally/IV every 12 hours
• Alternative therapies would be:
• Cefotetan 2 g IV every 12 hours plus doxycycline 100 mg orally/IV every 12 hours 
• Cefoxitin 2 g IV every 6 hours plus doxycycline 100 mg orally/IV every 12 hours 
• Clindamycin 900 mg IV every 8 hours plus gentamicin 3 to 5 mg/k IV once daily
• If there is any suspicion of trichomonas, metronidazole 500 mg orally or by IV every 12 hours for 14 days should be added.
• Consider NAAT testing and initiating treatment for Mycoplasma genitalium if the above measures fail.
• For further details on treatment, see the companion StatPearls reference review on "Pelvic Inflammatory Disease."[33]

Syphilis: Treatment and management of secondary, latent, and tertiary syphilis should be independent of treatment of the primary syphilitic infection.

• Primary, secondary, and early syphilis infection can be treated with benzathine penicillin G 2.4 million units to be given by a single intramuscular injection.[21]
• Treatment for infants and children is also benzathine penicillin G 50,000 units/kg body weight IM as a single dose up to a maximum of 2.4 million units.
• Tertiary syphilis should be treated with benzathine penicillin G 2.4 million units IM once a week for a total of 3 weeks.
• Neurosyphilis should be treated as an inpatient with intravenous aqueous penicillin G 18 to 24 million units daily administered as 3 to 4 million units every 4 hours or by continuous infusion for a total of 14 days.[8]
• Procaine penicillin G 2.4 million units IM once daily (if available) PLUS probenecid 500 mg orally 4 times/day for 10 to 14 days can be an acceptable alternative in highly reliable patients.
• After neurosyphilis treatment, normal rapid plasma reagin (RPR) titers correlate well with negative cerebral spinal fluid findings so that further lumbar punctures can be safely avoided in immunocompetent patients.
• Patients with a penicillin allergy should consider penicillin skin testing unless they have a history of anaphylaxis, hemolytic anemia, Stevens-Johnson syndrome, interstitial nephritis, or toxic epidermal necrolysis. If the skin testing is negative, this is usually followed by an oral penicillin challenge. Desensitization to penicillin can be considered in selected cases as penicillin remains the preferred antibiotic for syphilis, particularly during pregnancy and neurosyphilis, where no alternatives are recommended.
• Alternative therapies would include ceftriaxone or doxycycline. Azithromycin is no longer recommended due to increasing resistance in the US and elsewhere.
• Of these, doxycycline is usually preferred as it is inexpensive and easily administered. However, it cannot be used in pediatrics or during pregnancy.
• If azithromycin is used, the neonate would need treatment immediately after birth as azithromycin does not cross the placenta.
• Follow-up clinical examinations and serological testing are recommended at 6, 12, and 24 months after treatment or every 3 months for the first year and at 24 months in high-risk populations.
• A nontreponemal titer (VDRL or RPR) increased 4-fold or more from previous levels suggests a reinfection or treatment failure.
• A high initial titer that does not fall fourfold by 24 months after therapy suggests a treatment failure, reinfection, or central nervous system involvement.
• For further details on treatment, see the companion StatPearls references on "Syphilis," "Neurosyphilis," and "Maternal and Congenital Syphilis."[21][42][43]

The Jarisch-Herxheimer reaction is an acute but self-limiting febrile syndrome characterized by headache, fever, chills, nausea, vomiting, muscle aches, tachycardia, flushing, hyperventilation, hypotension, exacerbation of skin lesions, and rigors that occur within the first 24 hours after initiation of antimicrobial therapy for syphilis. This condition may also occur with other infections caused by spirochetes, such as Lyme disease, leptospirosis, tick-borne relapsing fever, and certain other infections. The most common symptoms are fever and skin changes. The severity of the reaction is directly related to the patient's individual bacterial load. The reaction typically starts about 2 hours after the initial administration of an antimicrobial, lasts an average of about 9 hours, and generally resolves without treatment by 24 hours; this is most frequently seen when starting treatment of seropositive primary and secondary syphilis, most likely from the high bacterial loads.[44]

Patients should be informed of this possible reaction before initiating treatment, that it is a common, expected response to therapy and not a penicillin allergy. Early labor can be induced, and fetal distress has been reported when syphilis treatment is begun during pregnancy and a Jarisch-Herxheimer reaction is precipitated. The incidence of the reaction in pregnancy has been estimated at 40%. Nevertheless, it is recommended that syphilis therapy not be delayed, although fetal monitoring is recommended in late pregnancy.[44] (See the companion StatPearls reference review on the "Jarisch Herxheimer Reaction.")[44]

Trichomoniasis: Treatment and management should be established with patients after diagnosis.

• For men, a single dose of metronidazole 2 g is taken orally.
• For women, metronidazole 500 mg by mouth twice daily with food for 7 days.
• Alternate therapy for both men and women is a single dose of tinidazole 2 g to be taken by mouth.
• Desensitization therapy is recommended for patients allergic to nitroimidazoles (which include both metronidazole and tinidazole).
• Retesting all women (but not men) 3 months after therapy is recommended.[22][45]

Evaluation and Treatment of Patients After a Sexual Assault

Victims of sexual assault may be exposed to unknown potential infections. They may also have poor follow-up, so prophylactic antibiotics for chlamydia, gonorrhea, and trichomoniasis are recommended. Emergency contraception, along with testing for hepatitis B, HIV, and HPV, is recommended by the CDC.[46] They should also be counseled regarding the need for follow-up testing and the possible signs of an STI. (See the companion StatPearls reference review on "Sexual Assault Infectious Disease Prophylaxis.")[46] 

Summary

For patients with urethral or vaginal discharge and women with lower abdominal or pelvic pain suspicious of pelvic inflammatory disease, the following should be done:

• NAAT for N gonorrhoeae and C trachomatis should be performed.
• Same-day treatment, based on test results when possible, should be initiated.
• If test results are unavailable, the WHO recommends treating patients symptomatic for N gonorrhoeae and C trachomatis. Treatment of their sexual partners depends on test results.
• If a urethral discharge is present, but test results for N gonorrhoeae and C trachomatis are negative, Mycoplasma genitalium or Trichomonas vaginalis can be treated.
• Patients with persistent or recurrent discharge after 3 weeks should have repeat NAAT testing for N gonorrhoeae, C trachomatis, M genitalium, and T vaginalis.
• If N gonorrhoeae is positive, antibiotic resistance should be checked.
• HIV and syphilis testing is recommended for all STI patients regardless of other findings.

For patients with ulcerative genital lesions, the following should be performed:

• NAAT for HSV and T pallidum, as well as serological tests for syphilis.
• Same-day treatment for syphilis or herpes if test results are available.
• If test results are unavailable, treatment should be started immediately based on the clinical impression and revised later when the information is forthcoming.
• Similar molecular assays on lesions for lymphogranuloma venereum, where this is endemic, should be performed.
• Lymphogranuloma venereum should be treated only with positive test results.
• Chancroid should be treated only in those regions where the disease has been identified.
• HIV and syphilis testing is generally recommended for all those with STIs, regardless of other findings.

Differential Diagnosis

A broad differential should be approached when evaluating a patient, whether in an emergency department or a primary care setting. STIs can be localized to the oropharynx, integumentary system, external and internal genitals. Clinicians should initially establish a primary or preliminary diagnostic impression and differential diagnosis, then formulate a confirmatory plan. The history, physical exam, and clinical presentation should all support the definitive diagnosis and also rule out your differential diagnosis.

When approaching a differential diagnosis specifically for sexually transmitted infections, each system should be evaluated separately, ie, cardiovascular, respiratory, gastrointestinal, genitourinary, central nervous system, musculoskeletal, and integumentary systems. Breaking the signs and symptoms down into systems specifically for each STI will help differentiate a primary associated infectious process from a secondary, unrelated disorder or coinfection.[34]

Differential STIs should be assessed by system and symptomatology: 

• Cardiovascular: HIV, syphilis, HSV-1/HSV-2
• Central nervous system: HIV, syphilis, HSV-1/HSV-2, gonorrhea, HPV
• Gastrointestinal: HIV, HSV-1/HSV-2, chlamydia, gonorrhea, HPV
• Genitourinary: HIV, HSV-1/HSV-2, chlamydia, gonorrhea, HPV
• Integumentary system:HIV, HSV-1/HSV-2, chlamydia, gonorrhea, HPV
• Musculoskeletal: HIV, HSV-1/HSV-2, chlamydia, gonorrhea, HPV
• Respiratory: HIV, chlamydia

The use of different resources, diagnostic methods, and laboratory tests should be optimized to quickly arrive at the proper diagnosis and better serve the patient population.[35]

Prognosis

The prognosis depends on the diagnosis of the specific disease, its extent and severity at the time of initial presentation, the general health and comorbidities of the patient, and their willingness to comply with necessary treatment, follow-up, and preventive measures. If the disease process is found in the acute phase and can be treated effectively with antimicrobials, the outcome depends on the treatment course and patient compliance. Medication adherence plays a primary role in treating and managing STIs.[2]

Worldwide, health services for diagnosing and treating STIs are frequently underfunded, often neglected, and generally inadequate. Problems include the cultural stigmatization of patients with STIs, inadequate education of healthcare workers in some areas, limited resources, and the frequent need for patients to bear a significant financial burden for their own treatment, which many cannot afford. Populations at the highest risk (workers in the sex trade, prostitutes, illegal drug users, prisoners, and young people in countries with high rates of STIs and HIV) often lack access to proper, affordable healthcare and STI treatment services. In many parts of the world, STI services are not seen as significant or important, so they are underfunded and neglected. This only leads to higher numbers of infected but untreated patients, poorer training of healthcare workers, reduced laboratory testing ability, and inadequate supplies of appropriate medications.

Complications

Sexually transmitted infections that remain untreated result in systemic infections leading to prolonged medical recovery, as well as psychological, financial, and general health deterioration. An increase in complications can be seen if adequate public health resources are not allocated to the public sector to provide needed services, as well as reliable public education about safe sex practices.[36] Women tend to be at higher risk for complications from STIs, including systemic infection from untreated pelvic inflammatory disease, sterility, and infertility from complicated gonorrhea/chlamydial infections.

STIs in those who are pregnant can cause increased preterm labor, premature rupture of membranes, newborns with low birth weight, chorioamnionitis, miscarriages, stillbirths, and early infant mortality. Newborns may become infected as the baby is exposed to various infections during passage through the birth canal. Newborns so exposed are at particular risk for lung and eye infections. Infants born to mothers with untreated syphilis may develop problems in many organ systems, including bones, brain, ears, eyes, heart, skin, and teeth.  HPV strain types predispose to cancers, especially in women.[37] HIV infections, if not properly managed, can progress to AIDS, a fatal late complication secondary to a severely immunocompromised state.[38]

Consultations

For further information and details on specific infections, consult the companion StatPearls reference reviews on the following:

• "Acquired Immune Deficiency Syndrome"[38]
• "Chancroid"[5]
• "Chlamydia"[7]
• "Congenital Syphilis"[39]
• "Epididymitis"[40]
• "Herpes Simplex Type 1"[9]
• "Herpes Simplex Type 2"[10]
• "Gonorrhea"[11]
• "Granuloma inguinale"[13]
• "HPV"[17]
• "Lymphogranuloma venereum"[18]
• "Mycoplasma infections"[19]
• "Pelvic Inflammatory Disease"[33]
• "Syphilis"[21]
• "Trichomoniasis"[22]

Deterrence and Patient Education

Healthcare professionals should understand the most common sexually transmitted diseases in their area and should be comfortable with counseling patients on modifiable human behavior while providing a gold standard of care in line with the presenting disease. Patients should be provided information on prevention, counseling, and proper treatment for sexually transmitted infections.[36]

HPV Vaccine: This widely-tested vaccine is over 99% effective, requiring 2 dosages given 6 to 12 months apart. According to the CDC, these can be given starting at age 9, are optimal at ages 11 to 12, and are recommended for everyone not previously vaccinated up to age 26. 

Vaccination is not automatically recommended between 27 and 45 years old, but it may be reasonable for those at high risk for HPV infections, as the benefits of prophylactic vaccination decrease as people age. 

Beyond age 45, vaccinations are not recommended as most adults of this age have already been exposed and will see minimal, if any, benefit. Please see StatPearls' companion reference, "Human Papilloma Virus Vaccine," for further information.

HIV Pre-Exposure Prophylaxis: While not a vaccine, pre-exposure prophylaxis (PrEP) is 99% effective in preventing HIV infections in those taking the medication. Ideal candidates would be those at high risk, such as individuals with multiple sexual partners or open relationships. Patients must test negative for HIV-1 before starting this therapy and at least every 3 months while on prophylaxis (or every 2 months if receiving injections). Please see StatPearls' companion reference, "Preexposure Prophylaxis for HIV Prevention," for further information.

Of the 1.2 million individuals in the US who are considered at high risk for HIV, where PrEP is recommended, only about 25% are taking the therapy. Strict compliance is essential to maintain the protective effects. The treatment is not considered adequate as the sole therapy for active HIV infections and will not prevent other STIs. Current recommended PrEP treatments include:

• Oral emtricitabine with tenofovir disoproxil fumarate is FDA-approved for PrEP. 
• Oral emtricitabine with tenofovir alafenamide is FDA-approved for PrEP except for people born as women who engage in vaginal intercourse, as this group has not been adequately studied.
• Injectable cabotegravir is given every 2 months after the first 2 monthly administrations.

Doxycycline Post-Exposure Prophylaxis: Taking 200 mg of doxycycline, preferably within 24 hours (but no more than 72 hours) of condomless sexual contact, has been found to reduce the subsequent incidence of chlamydia, gonorrhea, and syphilis by about two-thirds in a large open-label randomized study of over 500 patients.[41] Such prophylactic treatment has been cautiously recommended for high-risk populations, such as non-monogamous men who have sex with men, as has been recently implemented in San Francisco, which has since seen a significant drop in STIs of about 50%.

However, there are serious concerns regarding potential side effects, the lack of long-term safety data, and the effect of broad implementation of such prophylactic measures on increasing bacterial antibiotic resistance patterns.[42] There is also a lack of consensus in the healthcare community regarding which groups should be offered this treatment modality. The CDC is reviewing the issue and are expected to publish guidelines on this therapeutic measure. Given the rapid increase around the world in STIs (and especially syphilis), more effective measures are clearly necessary.

Pearls and Other Issues

The key to managing sexually transmitted infections is to have an open dialogue with the patient regarding their sexual history, current practices, risk factors, and follow-up. Establishing a good relationship creates a neutral environment and optimizes the treatment course. Shaming or judging a person's sexual history or practices can lead to patients' reservations about discussing their general and sexual health openly.

Whether a patient is seen in the emergency department or a primary care office, the patient's disposition should be determined solely by the clinical presentation. If the patient has a complicated systemic infection, admission is most likely warranted, but if they have a self-limiting complaint that can be easily treated with proper follow-up, the patient can be discharged home. Pitfalls a clinician may encounter would most likely be limited education or familiarity with the newest guidelines on prevention and treatment, as well as limited local resources for their patient population.

Enhancing Healthcare Team Outcomes

Sexually transmitted infections are a worldwide concern and issue. Untreated patients often suffer disastrous effects, including health issues, financial burdens, psychological disorders, and physical damage. Vaccines and prophylactic therapy should be recommended for all appropriate patients. Data collection for STIs is limited by country and geographical area. Access to a national and international data collection service can help identify the prevalence and incidence of certain STIs to better allocate limited community resources directed towards prevention and treatment.

Treatment will be headed by a primary clinician, but depending on the disease and its progression, specialists in infectious disease or other affected organ systems may be involved. Nurses will assist in patient examinations, provide counseling, and serve as liaisons for all interprofessional team members. Pharmacists can verify the appropriateness of antimicrobial therapy, check dosing, monitor for adverse events, counsel patients on medication compliance, and answer patient questions; advanced cases may require an infectious disease specialty pharmacist. Mental health professionals may also need to be involved in these cases.

Open communication channels are essential so that any team member can reach out to other practitioners on the case to voice concerns or report any issues. Meticulous record-keeping goes hand-in-hand with open communication so that every care team member can access the same updated patient information on which to base their decisions and interventions. The interprofessional model will lead to optimal patient care.

The WHO and public health departments can help an interprofessional team and care coordinators to provide these services, as well as collect valuable data on disease prevalence.[41] Patient-centered care should remain the priority whether patients are seen in the emergency department, their primary care office, or specialized regional STI clinics.