Risk Factors for Sexually Transmitted Infections

Sexually transmitted infections (STIs) encompass a range of clinical syndromes which may be caused by bacteria, viruses, parasites, or fungi, transmitted through sexual activity, including vaginal, oral, and anal sex. Some STIs are often asymptomatic and can therefore spread easily as the index patient may not know that they are infected. Early detection and treatment can avoid complications and reduce the risk of transmission to other sexual partners.

Risk factors for STIs include:

• Younger age – more likely to have multiple partners and engage in sexual risk-taking.
• Condomless sex – condoms don’t eliminate the risk of STIs, however, other than abstinence, they are the most effective way to prevent STIs.
• Multiple sexual partners – due to increased risk of exposure to an STI.
• Anal penetrative sex – the anal and rectal lining is thin, fragile, and susceptible to damage, increasing the risk of entry of infection.
• Alcohol use – due to lowered inhibition and increased sexual risk-taking.
• Recreational drug use – those under the influence of drugs are more likely to engage in risky sexual behaviours. Intravenous drug use is also associated with the risk of blood-borne viruses such as hepatitis B, C and HIV.
• Commercial sex work – in some cases, this can increase difficulty in negotiating safe sex; however, risk varies, and many commercial sex workers are very diligent regarding STI prevention.

Aetiology of STIs

Bacterial STIs

Chlamydia

Presentation

Chlamydia is a very common STI, caused by Chlamydia trachomatis. Transmission can be via vaginal, anal, and oral sex, or through vertical transmission from an infected mother to the infant during childbirth. Chlamydia is commonly asymptomatic, resulting in the rapid spread of the infection between individuals. If symptoms are present, these can include vaginal or penile discharge, dysuria (due to urethritis), and testicular swelling. Chlamydia infection can be a cause of sexually acquired reactive arthritis (SARA), which in some cases may result in the classic triad of arthritis, urethritis, and conjunctivitis.

Diagnosis is now mostly by nucleic acid amplification tests (NAATs) on vulvovaginal or endocervical swabs in females or first catch urine (recommended choice in males) or urethral swabs in males.

Treatment

Treatment of chlamydia is with antibiotics; the current first line treatment is seven days of oral doxycycline 100mg twice daily. It has an excellent cure rate, and it is advised that all sexual contacts within the past 60 days should be informed of the risk of infection and seek investigation and treatment if required.

Untreated, there is an increased risk of spread of infection in women causing pelvic inflammatory disease, which can result in infertility or ectopic pregnancy, or Fitz-Hugh-Curtis syndrome, a form of infectious perihepatitis. In men, complications include epididymitis, which can rarely lead to sterility if untreated.

Gonorrhoea

Presentation

Gonorrhoea is another common STI, caused by Neisseria gonorrhoeae. Transmission can be via vaginal, anal or oral sex, or through vertical transmission from mother to child during childbirth. Infection can commonly involve the genitals, rectum, or pharynx but may be asymptomatic. Symptoms, if present, include vaginal discharge, dysuria, dyspareunia, and pelvic pain (in females) and dysuria, penile discharge, or testicular pain (in males). A sore throat may occur if the pharynx is the affected site; however, infection here is commonly asymptomatic. Infants born to women with gonorrhoea may develop gonococcal ophthalmia neonatorum, a form of neonatal conjunctivitis which can lead to blindness if left untreated.

Diagnosis is with NAATs on vulvovaginal, endocervical, rectal or pharyngeal swabs or first catch urine samples. In NAAT positive cases, culture should be performed to determine antibiotic sensitivities, as high rates of antimicrobial resistance against gonorrhoea infection are reported. Microscopy of Gram-stained genital samples at the time of examination in clinic may show direct visualisation of N. gonorrhoeae as Gram-negative diplococci within polymorphonuclear leucocytes. This facilitates immediate presumptive diagnosis and treatment in these patients.

Microscopy of gonococcal urethritis, as evidenced by Gram-negative diplococci inside polymorphonuclear neutrophils

Image Source: Wikimedia Commons (2014). Gonococcal urethritis PHIL 4085 lores, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Gonococcal_urethritis_PHIL_4085_lores.jpg (Accessed on: 11 January 2023).

Treatment

Treatment should be guided by local antibiotic guidelines. Uncomplicated infection is usually treated with a single intramuscular dose of ceftriaxone; however other treatment options exist depending on local susceptibility. Recent sexual partners within the past three months should also be tested and treated.

Untreated, gonorrhoea can lead to infertility or ectopic pregnancy due to pelvic inflammatory disease in females, and epididymitis in males. It can also cause disseminated infection, leading to skin pustules, septic arthritis, meningitis, endocarditis, or perihepatic abscess formation.

Chancroid

Chancroid is uncommon in the UK but is more prevalent in resource-poor countries. It is an STI caused by Haemophilus ducreyi and typically presents with a painful genital ulcer with associated painful inguinal lymphadenitis in some cases. The tender, enlarged inguinal lymph nodes can progress to draining abscesses, known as buboes.

Diagnosis is through Gram stain and culture of Haemophilus ducreyi from ulcer swabs or bubo aspirates, or with PCR testing. HIV should also be tested for, as chancroid is an important cofactor in HIV transmission. Sexual contacts within ten days of symptom onset should be treated, regardless of symptoms.

Treatment is with antibiotics; the first line choice is intramuscular ceftriaxone or oral azithromycin, however, the choice may vary depending on the HIV status of the patient. Lymph node aspiration or incision and drainage may be required in select cases.

Mycoplasma genitalium

Mycoplasma genitalium is the smallest known self-replicating bacterium and was not isolated until 1981. The majority of those infected are asymptomatic; however, symptoms in males include urethral discharge, dysuria, and recurrent urethritis, and in females, include dysuria, post-coital or intermenstrual bleeding.

Complications of infection include reactive arthritis, epididymitis (in males), and pelvic inflammatory disease (in females).

The recommended choice of test for diagnosis is a NAATs of first catch urine in men and vulvovaginal swab in women. M. genitalium is very slow-growing; therefore, culture is not useful for diagnosis. All M. genitalium-positive specimens should be tested for macrolide resistance mediating mutations.

Treatment is with doxycycline for seven days, followed by a short course of azithromycin, if the organism is known to be macrolide-sensitive, or moxifloxacin for ten days, if the organism is known to be macrolide-resistant.

Syphilis

Syphilis is caused by the spirochaete Treponema pallidum. It is transmitted through direct contact with an infectious lesion (usually during sexual activity), via infected blood products/needle-sharing, or by vertical transmission during pregnancy (transplacentally) or childbirth, leading to congenital syphilis. Risk factors include sexual intercourse with an infected person, men who have sex with men (particularly if HIV co-infection), commercial sex workers, and co-infection with other STIs.

Syphilis can present variably depending on the stage of infection: primary, secondary, latent, or tertiary.

Primary syphilis

Primary syphilis infection typically presents with a painless ulcer, called a chancre, in the anogenital region. In 40% of cases, multiple chancres may be present. There may be extragenital ulcers in some cases and associated regional lymphadenopathy. The primary lesion lasts several weeks before healing over, however, syphilis will progress to the secondary infection stage if left untreated.

Primary syphilitic chancre on the penis

Image Source: Wikimedia Commons (2005). Penis syphilis, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Penis_syphilis.png (Accessed on: 20 February 2023).

Secondary syphilis

Dissemination of the infection to cause multisystem symptoms usually occurs within two years of primary infection if untreated. Features of secondary syphilis include:

• Rash – this is a non-itchy, macular, papular or maculopapular rash affecting the trunk, extremities, palms, and soles. It is usually symmetrical.
• Condylomata lata – these are wart-like lesions which may be seen in moist areas such as the groin, vulva, or anus.
• Mucus membrane lesions may affect the mouth, vagina, and anus. These can coalesce.
• Lymphadenopathy – can be localised to the inguinal region or more generalised.
• Constitutional symptoms such as fever, malaise, weight loss, myalgia and arthralgia may be present.
• Less common symptoms include anterior uveitis, hepatitis, glomerulonephritis, meningitis, cranial nerve palsies, and alopecia.

Latent syphilis

The latent phase of syphilis can span many years and represents an asymptomatic phase of the disease; however, syphilis infection remains within the body unless treated, and therefore serology for Treponema Pallidum remains positive. Latent syphilis within two years of syphilis infection is called early latent disease; latent syphilis after two years of infection is called late latent syphilis.

Late (tertiary) syphilis

Approximately a third of patients with untreated syphilis may go on to develop late (tertiary) syphilis, sometimes decades following initial infection.

Presentation of tertiary syphilis is varied due to its ability to affect multiple organ systems, however, patients are not infectious during this phase. The main forms of tertiary syphilis include neurosyphilis, cardiovascular syphilis, and gummatous syphilis.

Neurosyphilis may result in damage to the dorsal columns of the spinal cord, leading to ‘tabes dorsalis’. Clinical features of this include ataxia, loss of vibration and proprioception, areflexia, and loss of control of the bladder and anal sphincter. Neurosyphilis can also present as generalised paresis. There may be more generalised brain or meningovascular involvement, which can lead to non-specific symptoms such as confusion, cognitive impairment, altered mood, altered personality, or seizures. Argyll-Robertson pupils (small, irregular pupils which do not constrict on light reflex, but accommodation reflex is preserved) are a frequent pupillary abnormality associated with tertiary syphilis.

Cardiovascular syphilis typically occurs 10-30 years after infection and causes an aortitis, which may result in aortic regurgitation, or aortic aneurysm formation.

Gummatous syphilis is a rare form of tertiary syphilis characterised by gumma lesions (granulomatous, rubbery lesions with a necrotic centre) affecting skin and viscera, which can lead to organomegaly. They are destructive granulomatous nodular lesions formed due to reactivation of residual treponemes and are not contagious.

Congenital syphilis

Congenital syphilis occurs when syphilis is transmitted transplacentally. Early congenital syphilis occurs in the first two years of life, whilst late congenital syphilis is detected after the age of two. It can result in a large range of symptoms and complications, including rash, hepatosplenomegaly, glomerulonephritis, neurosyphilis, and bone deformities such as ‘saber shins’ (malformation of the tibia), ‘Hutchinson’s teeth’ (smaller, widely spaced teeth), and ‘Mulberry molars’ (small molars with globular enamel growths). There is an associated risk of miscarriage, stillbirth, and neonatal death in early congenital syphilis.

Diagnosis

Diagnosis is most commonly by serology testing, however, dark-field microscopy and PCR can be used in some settings. Serology can take up to 3 months from infection exposure to become positive.

Serology tests involve an initial treponemal test (specific) and, if positive, a subsequent non-treponemal test (non-specific).

The treponemal tests detect antibiotics specific for syphilis and include:

• Treponemal enzyme immunoassay (EIA)
• Treponema pallidum particle agglutination assay (TPPA)
• Treponema pallidum haemagglutination assay (TPHA)
• Fluorescent antibody absorption (FTA-ABS)
• Immunocapture assay (ICA)

Treponemal antibodies appear earlier than non-treponemal antibodies and remain detectable for life, even following successful treatment.

A non-treponemal test is performed following a positive treponemal test to confirm the diagnosis and assess whether infection is active. Non-treponemal tests include:

• RPR (rapid plasma reagin) test
• VDRL (venereal disease research laboratory) test

Non-treponemal tests detect antibody response to the release of cardiolipin during syphilis infection and can provide a quantitative measure of disease activity. They become non-reactive with effective treatment. False positives of non-treponemal tests can occur with pregnancy, vaccination, autoimmune or connective tissue diseases, lymphoma, and other infections.

Dark field microscopy is a form of microscopy in which the object is lit by oblique beams of light, causing the sample to appear bright against a dark background. It is not commonly available at many centres. PCR has limited availability at some services but can be used to detect T. Pallidum on an ulcer swab.

Neurosyphilis can be diagnosed on CSF analysis and typically shows a raised CSF white cell count >10 cells/mm3, raised CSF protein >50 mg/dL and a positive CSF VDRL test.

Treponema pallidum spirochaetes on dark field microscopy

Image Source: Wikimedia Commons (2008). Treponema pallidum cropped, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Treponema_pallidum_cropped.png (Accessed on: 20 February 2023).

Treatment

Treatment of syphilis is typically with intramuscular benzathine benzylpenicillin or doxycycline. Duration of treatment is dependent on the stage of the disease. Jarisch-Herxheimer reaction is an acute reaction that can occur within 24 hours of treatment for syphilis. It occurs in response to the bacterial endotoxins and antigens released on destruction of spirochaetes following the initiation of antibiotic treatment. Most reactions are mild and self-limiting, consisting of acute fever, headache and myalgia; however, life-threatening reactions can occur if associated with significant hypotension, causing multi-organ failure.

Condoms provide an element of protection, however, skin lesions associated with primary and secondary syphilis, such as chancres or condylomata lata, can be highly infectious and may be exposed despite the use of a condom.

Bacterial vaginosis

Bacterial vaginosis (BV) is a result of an imbalance of normal vaginal flora (typically lactobacilli) with associated overgrowth of anaerobic bacteria. Normal vaginal flora creates a pH of 3.5-4.5, however, in BV, the anaerobic bacteria increase this to a pH >4.5. It is not usually directly sexually transmitted but it can be linked to increased sexual activity or new sexual partners. Another common risk factor for BV is the use of perfumed soaps around the vagina as this can alter the vaginal flora.

BV may be asymptomatic in approximately 50%, however, symptoms can include offensive, thin, grey, or white vaginal discharge, which may have a fishy odour, but usually without any itch or soreness unless co-existing with vulval candidiasis.

Since the make-up of vaginal flora is dynamic, BV can arise and resolve spontaneously in both sexually active and sexually inactive females. BV can be associated with complications in pregnancy, including late miscarriage, preterm rupture of membranes, or preterm birth, low birth weight, and postpartum or post-termination-of-pregnancy endometritis.

The Amsel criteria for diagnosis of BV state three of the following four criteria be fulfilled:

• Thin, white, homogenous discharge
• Clue cells on wet mount microscopy – these are vaginal epithelial cells coated in small Gram-variable bacilli.
• pH of vaginal fluid >4.5
• Positive amine test – release of fishy odour on adding alkali (10% potassium hydroxide); this is no longer widely used due to the caustic nature of potassium hydroxide.

The Hay-Ison criteria for diagnosis are based on the appearance of vaginal flora on Gram-stained smear:

• Grade 1 (normal flora): Lactobacillus morphotypes predominate
• Grade 2 (intermediate flora): Mixed flora with some lactobacilli present, but Gardnerella or Mobiluncus morphotypes also present.
• Grade 3 (BV flora): Predominantly Gardnerella and/or Mobiluncus morphotypes, with few or absent lactobacilli.

Management of BV includes education regarding avoidance of perfumed soap use around the vagina, including bubble baths, and avoidance of vaginal douching. Full STI screen should be offered as BV can co-exist with STIs. Treatment is typically with oral metronidazole, although intravaginal metronidazole or clindamycin creams exist as alternatives.

Viral STIs

Genital warts – HPV

Presentation

Genital warts (condylomata acuminata) are caused by a very common sexually transmitted infection called human papillomavirus (HPV); typically HPV types 6 and 11 cause genital warts. Genital warts are small, fleshy papules that arise anywhere in the genital or perianal region, including the mucosa. In some cases, the warts can coalesce to form plaques. They are commonly asymptomatic, however, they can be painful, itchy, or may bleed.

Diagnosis is based on clinical presentation, however, biopsy may be performed in some cases, particularly if ulceration is present or lesions refractory to treatment, to rule out dysplasia or carcinoma.

Genital warts follow a benign course and can resolve spontaneously within a few months in a third of those affected, however, treatments exist to remove visible lesions. There is not currently evidence to prove that treatment of genital warts decreases sexual transmission of HPV.

Treatment

The choice of treatment for genital warts is dependent on many factors, including location of lesions, immune status of the patient, pregnancy, and patient choice of application method.

Options include patient-applied topical therapy, such as podophyllotoxin 0.5% or imiquimod 5%, or provider-administered therapy, such as cryotherapy, trichloroacetic acid, or surgical removal. Immunocompromised patients tend to require a longer duration of treatment or a combination of treatments.

Prevention of HPV infection is through abstinence; condom use may reduce transmission but does not entirely prevent it. There are now 3 HPV vaccines available, consisting of bivalent (types 16 and 18 – these are most associated with the risk of development of cervical cancers), quadrivalent (types 6, 11, 16, 18) and 9-valent (types 6, 11, 16, 18, 31, 33, 45, 52, 58). The quadrivalent and 9-valent vaccines are approved for use against genital warts. HPV vaccination is now given to both female and male children from 11 years old as part of the school vaccination programme in the UK.

Herpes

Presentation

Infection with herpes simplex virus (HSV) is common; it classically presents with painful ulcers on the affected part of the body (e.g. orolabial, genital, ocular) however, infection can be asymptomatic, or there may be symptoms of tingling or burning without the presence of lesions. There are two main types of HSV: HSV-1 and HSV-2.

Orolabial herpes is usually caused by HSV-1 and refers to herpes infection affecting the lips and mouth, causing blisters and ulcers commonly known as ‘cold sores’. Initial infection may, in addition, present with fever, sore throat and lymphadenopathy; however, HSV-1 subsequently can remain dormant in the trigeminal nerve ganglion, periodically reactivating and causing episodes of ulcers on the lips or in the mouth. Lesions tend to crust over and heal within ten days.

Genital herpes can be caused by infection with either HSV-1 or HSV-2. Many infected people will be asymptomatic, however, symptoms can include a prodromal tingling sensation followed by the development of genital vesicles, which progress to painful ulcers. Primary infection may involve systemic symptoms such as fever, lymphadenopathy, and neuralgia. Transmission of the virus is via direct contact with lesions or bodily fluids of an infected person, and therefore genital herpes is considered a sexually transmitted infection. It should be noted that shedding of the virus can occur even in the absence of symptoms or lesions.

The median average recurrence rate for genital herpes after a symptomatic primary episode is approximately one recurrence per year for HSV-1 and four recurrences per year for HSV-2. Recurrence rates tend to decline over time, however, this is variable.

Diagnosis of both orolabial herpes and genital herpes can be made clinically, however, confirmation can be obtained by HSV PCR (high sensitivity) or HSV culture.

Treatment

Treatment can be divided into ‘episodic’ and ‘suppressive’ therapy. Episodic treatment with oral antiviral therapy such as aciclovir, valaciclovir or famciclovir is initiated within 2-3 days of symptoms, and can provide symptomatic relief, shorten the duration of symptoms, as well as reducing the severity and risk of neurological complications. Topical treatment of genital herpes is not recommended; oral therapy is also the preferred treatment of orolabial herpes, however topical antiviral therapy can have a small benefit (reducing duration of outbreak by a matter of hours) in those who do wish to take oral treatment. Daily suppressive therapy can be given to those with recurrent outbreaks (typically six or more recurrences per year) to reduce the rate of recurrence, and it can therefore reduce the risk of transmission of genital herpes to sexual partners.

Herpes simplex encephalitis (HSE) is a rare but life-threatening complication, thought to be caused by the spread of the infection from a peripheral site to the brain. In adults, it is more commonly caused by HSV-1 than HSV-2. Diagnosis is through HSV PCR on CSF analysis. Presentation and treatment of HSE is covered in more detail in the ‘Meningitis and Encephalitis’ section. As well as affecting the neurological system, disseminated HSV can also rarely cause a hepatitis or pneumonitis. Treatment is usually with high-dose intravenous aciclovir.

HIV

Human immunodeficiency virus (HIV) is a global pandemic disease which infects and destroys CD4⁺ T cells. Without treatment, this leads to progressive immune depletion and a wide array of opportunistic infections and malignancies, which form the diagnosis of Acquired Immune Deficiency Syndrome (AIDS). The advancement in treatment options for HIV with antiretroviral therapies over the past 30 years has transformed the trajectory of the disease, with significantly improved morbidity and mortality associated with HIV-positive patients on treatment. Many patients on antiretroviral therapy have an undetectable viral load, meaning they are unable to transmit the virus to others.

HIV is covered in significant detail in the HIV/AIDS section.

Hepatitis B

Presentation

Hepatitis B virus (HBV) is the most common liver infection worldwide and can be transmitted by exposure to infectious blood or bodily fluids, hence can be transmitted by sexual contact as well as by blood product transfusion, use of contaminated needles, or vertical transmission during childbirth.

70% of those infected with HBV are asymptomatic and can have a self-limiting course to the infection; however, some people develop chronic infection, which may present with complications such as liver failure, cirrhosis, or hepatocellular carcinoma, particularly if acquired in early life. Co-infection with HIV increases the risk of developing chronic infection. Acute infection may present with generalised symptoms such as fever, arthralgia, skin rash, or symptoms of right upper quadrant pain, jaundice, and nausea/vomiting.

Serology

Analysis of HBV serological markers to differentiate between acute and chronic HBV infection remains a common question topic in MRCP. The HBV serological profile includes:

• Hepatitis B surface antigen (HBsAg) – the first serological marker to appear following acute infection. A positive result indicates active infection (both acute and chronic).
• Antibody to hepatitis B surface antigen (anti-HBs) – a positive result indicates either recovery and immunity from previous HBV infection, or successful vaccination against HBV.
• Antibody to hepatitis B core antigen (anti-HBc) IgM and IgG – positive IgM anti-HBc indicates recent infection with HBV (<6 months) and acute infection. IgM anti-HBc is gradually replaced with IgG anti-HBc, which persists for life following HBV infection and can therefore represent previous resolved infection or chronic HBV infection.
• Hepatitis B envelope antigen (HBeAg) – this indicates active viral replication and is a marker of infectivity.
• Antibody to HBeAg (anti-HBe) – this marks the transition from active to inactive disease. It remains positive for life and therefore represents acquired immunity from previous infection (not from vaccination).
• HBV DNA – this can be tested in those with serology indicating active infection and quantifies the viral load. Those with high HBV DNA viral load are at increased risk of progression to complications such as cirrhosis or hepatocellular carcinoma.

HBsAg and anti-HBs can be used for screening of high-risk individuals to aid early diagnosis and treatment.

Treatment

Treatment of acute infection is usually through supportive care alone, as 95% of immunocompetent adults with acute HBV will clear the virus without treatment. A small proportion of patients, e.g. those developing acute liver failure, may benefit from antiviral treatment with entecavir, tenofovir disoproxil or tenofovir alafenamide for acute infection; there may also be a requirement for liver transplant in some of these cases.

The treatment of chronic HBV is dependent on several factors, including ALT and HBV DNA levels, the severity of hepatic dysfunction and the presence of cirrhosis. Complete eradication of HBV is rare, and the aim of treatment is to suppress HBV DNA to undetectable levels for a sustained period, thereby reducing the risk of complications such as liver failure, cirrhosis, and hepatocellular carcinoma. Currently, the agents used for the treatment of chronic HBV include the antivirals interferon alfa 2b, peginterferon alfa 2a, nucleoside analogues such as entecavir or lamivudine, and nucleotide analogues such as tenofovir disoproxil or tenofovir alafenamide. Local guidelines for the treatment of chronic HBV should always be consulted as therapy is frequently evolving and novel treatments are being developed.

Since 2017, Hepatitis B vaccination is given as part of the childhood immunisation programme in the UK at 8, 12 and 16 weeks of age. Immunisation is also recommended for those at high risk of exposure or those at risk of complications (e.g. individuals from countries with a high prevalence of hepatitis B, healthcare or custodial institution workers, incarcerated individuals, commercial sex workers, parenteral drug users, men who have sex with men, individuals known to be HIV or Hepatitis C positive, patients with severe liver disease or end-stage renal failure, and patients receiving regular blood transfusions.) Vaccination may be recommended before travelling to some countries with a high prevalence of hepatitis B and can also be used in post-exposure prophylaxis.

Hepatitis C

The most common routes of transmission of hepatitis C virus (HCV) are through shared drug injecting equipment and transfusion of infected blood products (prior to 1991 in the UK). Sexual transmission is less common however the risk is increased if the individual is co-infected with HIV.

Acute infection is asymptomatic in >60%, although acute icteric hepatitis is possible. <1% of acute cases develop fulminant hepatitis. Up to 85% of those infected become chronic carriers, with a third of those progressing to severe liver disease. Approximately 14% of all patients and 33% of those with cirrhosis will develop hepatocellular carcinoma.

Positive HCV RNA indicates current acute or chronic infection (positive six months after initial positive test); a positive HCV antibody test indicates previous infection, however, it can take three months to become positive and therefore may be negative during early initial infection.

Treatment is with direct-acting antiviral (DAA) medication taken over several months, which can clear the virus in the majority of people. There are many different DAA medications, and most are used in combination. Some examples include sofosbuvir, ledipasvir, paritaprevir, ritonavir. dasabuvir, and elbasvir.

Parasitic STIs

Trichomoniasis

Trichomoniasis is the most common non-viral STI worldwide, caused by the flagellated protozoan Trichomonas vaginalis. Symptoms in females can include abnormal or offensive vaginal discharge, itching of the vulva, and dysuria; however, up to half of infected women are asymptomatic. Men can become infected, usually as a result of sexual contact with an infected female; transmission between male partners is uncommon.

Trichomoniasis is associated with co-infection with other STIs, increased risk of HIV transmission, as well as fertility and perinatal complications such as preterm birth.

Current guidelines advise treatment with oral metronidazole or oral tinidazole. Any sexual partner within four weeks prior to presentation should also be treated and offered testing for other STIs.

Pubic lice

Pubic lice infestation (pediculosis pubis), commonly coined ‘crabs’, is caused by an ectoparasite called Pthirus pubis. As the name suggests, infestations typically occur within the pubic hair, however, they can also occur in other coarse hair such as axillary hair, chest/back hair, beards, eyebrows, and eyelashes. They do not typically infest head hair, unlike pediculosis capitis (head lice).

Symptoms of a pubic lice infestation include pruritis, often worse at night, and complications such as skin infection can occur due to excoriation. Lice and eggs may be seen on examination.

Transmission is commonly through sexual contact or close body contact, however, fomite transmission can also occur, e.g. via infested bedding or towels.

Treatment includes topical permethrin or malathion and decontamination of infested materials with hot water.

Scabies

Scabies is a contagious infestation transmitted by any prolonged skin-to-skin contact, but in young adults is commonly sexually transmitted. It is an infestation caused by the parasitic mite, Sarcoptes scabei. The female mites burrow into the skin (which may be seen as silvery lines in the skin) and lay 2-4 eggs per day in the stratum corneum layer. The eggs produce larvae which hatch and develop into adult mites over a period of two weeks. The symptoms of pruritus, erythema, papules, and nodules can take up to four weeks to present following initial infestation; this is due to the symptoms being a result of the host immune response to the mites. Commonly affected sites include between the fingers, wrists, elbows, and genitals. Norwegian scabies (also known as crusted scabies) is a highly contagious variant that typically affects people who are immunocompromised. It results in hyperkeratotic, crusting plaques affecting the torso, extremities, palms, and soles.

First-line treatment for non-crusted scabies is with permethrin 5% dermal cream (washed off after 12 hours), with repeat treatment after seven days. All close household contacts and sexual partners from the past two months must be treated at the same time, and recent bedding and clothing should be washed at 60 degrees Celsius or more.

Crusted scabies is usually treated with a combination of permethrin 5% and ivermectin.

Fungal STIs

Candidiasis

Vulvovaginal candidiasis (VVC) is not an STI but can be more common in those who are sexually active. It is very common, particularly between menarche and menopause, due to its association with vaginal exposure to oestrogen. VVC is caused by the yeast Candida albicans in the vast majority of those affected, but other non-albicans species, e.g. C. glabrata, C. tropicalis or C. krusei, can less commonly be implicated.

The most common symptoms include vulval itch and irritation, dysuria, curd-like discharge, and superficial dyspareunia. There may be evidence of erythema, excoriation, fissuring and discharge on examination. Diagnosis can be made via immediate microscopy, which can demonstrate pseudohyphae and spores. The highest sensitivity and specificity for diagnosis is through culture of Candida.

Affected individuals should be advised to avoid local irritants, such as perfumed soaps, and to wear cotton underwear. Treatment is with antifungals, such as clotrimazole (topical and/or vaginal pessary), or oral fluconazole. It should be explained that latex condoms and diaphragms may be damaged by the topical or vaginal preparations.

Genital ulcers

Genital ulceration can be caused by a number of STIs, including herpes, chancroid, syphilis, lymphogranuloma venereum, and donovanosis. However, it is also important to consider other non-sexually transmitted aetiologies of genital ulceration, such as malignancy, inflammatory bowel disease, herpes zoster virus, Behçet’s disease, and drug reactions.

Herpes, chancroid and syphilis have all been covered earlier and therefore will not be included in detail here. A summary of some of the differentiating features of genital ulcers can be seen in Table 1.

	Number of lesions	Pain	Lymphadenopathy
Herpes (Herpes simplex virus)	Multiple	Painful	Tender Bilateral
Chancroid (Haemophilus ducreyi)	Multiple	Painful	Tender Can suppurate to form buboes
Syphilis (Treponema pallidum)	Solitary (usually)	Painless	Non-tender Unilateral
Lymphogranuloma venereum (Chlamydia trachomatis L1,2,3)	Variable	Painless (though can be variable)	Tender Unilateral ‘Groove sign’
Granuloma inguinale/Donovanosis (Klebsiella granulomatis)	Variable	Painless (usually)	Uncommon Pseudobuboes may occur

Table 1: Comparison of genital ulcer aetiologies

Lymphogranuloma venereum

Lymphogranuloma venereum (LGV) is an STI caused by serovars L1, L2, and L3 of Chlamydia trachomatis, L2 being the most common strain involved. Transmission is via sexual contact, including orogenital and anal contact.

Clinical presentation is divided into three stages:

• Primary LGV
  • This usually presents with a small, painless, papule/pustule or shallow ulcer in the genital region. Extra-genital sites include lips, tonsils or perianal.
  • LGV proctocolitis and pharyngitis can occur, particularly in MSM.
• Secondary LGV
  • Dissemination within the inguinal region leads to tender inguinal or femoral lymphadenopathy, which is often unilateral. This can cause the ‘groove sign’ in some cases in which there are enlarged inguinal lymph nodes above the inguinal ligament and enlarged lymph nodes below, with the inguinal ligament forming a groove between the two lines of swellings (See image below).
  • This stage occurs 1-6 weeks after the primary lesion.
  • There may be systemic features such as fever, malaise, and arthritis.
• Tertiary LGV
  • Persisting infection in the anogenital tissues causes a chronic inflammation and oedema, which can result in enlargement and destructive ulceration of the genitals, leading to fistulae, scarring and fibrosis of the tissues.
  • This is the commonest presentation of LGV in women and can cause esthiomene (genital lymphoedema) secondary to lymph node destruction from LGV.

The ‘groove’ sign bilaterally in LGV

Image Source: Wikimedia Commons (2008). Lymphogranuloma venerum – lymph nodes, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Lymphogranuloma_venerum_-_lymph_nodes.jpg (Accessed on: 13 February 2023).

Diagnosis can be made with NAATs for LGV-specific DNA using swabs of the ulcer, rectum, pharynx or urethra. Culture is not readily available and has a much lower sensitivity than PCR. Lymph node aspiration or biopsy may occasionally be required to rule out other causes of lymphadenopathy. It is also important to complete a full STI screen to identify any co-infection.

Treatment is with antibiotics; in the UK, doxycycline for 21 days is the first-line choice, with erythromycin for 21 days being the second-line choice if tetracycline allergy, pregnancy, or breastfeeding. If buboes have formed, these should be aspirated. Sexual contacts within four weeks prior to the onset of LGV symptoms, or three months in asymptomatic LGV, should be tested and treated.

Donovanosis

Donovanosis, also known as granuloma inguinale, is a rare STI associated with genital ulceration, caused by Klebsiella granulomatis. It is endemic to tropical and sub-tropical countries such as Papua New Guinea, India, and Vietnam. It presents with a firm papule or nodule at the primary site of inoculation (usually the genitals but can be found orally), which later ulcerates, forming a characteristic painless ‘beefy-red’ ulcer. The lesions may heal spontaneously, however, without treatment, there is a risk of necrosis and local tissue destruction.

Lymphadenitis is uncommon, but pseudobuboes may occur (subcutaneous granulomatous nodules which may mimic buboes.)

Diagnosis is more reliably made through direct microscopy of material from a swab of the ulcer. This is stained with Giemsa and characteristically will show large mononuclear cells with intracytoplasmic cysts filled with deeply stained Gram-negative Donovan bodies.

Treatment is usually with azithromycin (first-line), doxycycline or erythromycin for three weeks minimum and until all lesions have healed.