Screening

There are guidelines for routine screening in pregnancy in the UK, and the current programme screens all pregnant women at booking for syphilis, hepatitis B and HIV after a pretest discussion. In addition, screening for hepatitis C should be undertaken in intravenous drug users. There is also a national screening programme for Chlamydia trachomatis.

In the UK, the National Institute for Health and Clinical Excellence (NICE) issued guidelines entitled ‘Prevention of sexually transmitted infections and under 18 conceptions’ in 2007. These guidelines were not specifically aimed at gynaecologists but more at primary care agencies. In summary, these guidelines set recommendations as follows.

History

Whilst in the UK, STIs are principally managed by specialist clinics (GUM), STIs also commonly present to the gynaecologist. The threshold at which the gynaecologist should take a sexual history is correspondingly low. The essentials are establishment of a rapport, privacy and confidence in the manner of questioning. Embarrassment on the part of the patient is quite understandable and should be dealt with empathetically. Phrases can be couched in terms such as ‘I am sorry to have to ask you this, please don’t be offended, it is important’. Essential elements of the sexual history, taken in combination with a general gynaecological and medical history, are shown in Box 63.1.

One of the markers for women at risk of STIs is the age range (15–34 years). This takes the age range down to childhood, and these patients frequently present with a parent. It is highly unlikely that a girl will reveal all matters regarding her sexual activity in front of her mother. Such questions relating to this may be more profitably asked in the examination room with the mother back in the waiting room. In such cases, confidentiality should be emphasized and reassurance given that the information will not get back to her parents.

Examination

It is essential that a chaperone is present (irrespective of the gender of the examining doctor) and that consent has been obtained for intimate examination. Ideally, examination should be performed in lithotomy; in any case, there should be adequate exposure to allow thorough examination in good light of the external genitalia, mons pubis, perineum and perianal area. One should observe for Pediculosis pubis (crabs), scabies, molluscum contagiosum, warts, ulceration, excoriation, scars and any discharge from the introitus; and palpate for inguinal lymphadenopathy and tenderness. A bivalve speculum should be passed, gently, as the patient may find this uncomfortable. The cervix should be examined, looking for ectropion, warts, cervicitis and mucopurulent discharge. The vaginal walls should be observed for inflammation or warts. At this time, ‘triple swabs’ should be taken.

The first swab is taken from the posterior fornix and is placed into Stuart’s transport medium (agar and charcoal). This swab essentially screens for Trichomonas vaginalis, bacterial vaginosis and Candida spp. The second swab is taken from the endocervix and is a screen for Neisseria gonorrhoeae; this is also placed into Stuart’s transport medium. The third swab is also taken from the endocervix and is a screen for C. trachomatis. This last swab needs to be taken in a particular way as C. trachomatis is an obligate intracellular organism. Thus, to be sampled, the swab needs to pick up some cells from the sampled area. The swab should be rotated in the endocervix for at least a count of 10 and placed into chlamydia transport medium.

The speculum should then be removed and a digital examination performed. The patient should be examined for cervical excitation, uterine and adnexal tenderness, and adnexal masses.

Specialist clinic tests

In a GUM clinic, further refinements to this examination include a test of vaginal pH using narrow-range pH paper. The normal vaginal pH is 3.8–4.5. Bacterial vaginosis, trichomoniasis and atrophic vaginitis often cause a vaginal pH higher than 4.5. For a ‘whiff test’, several drops of a potassium hydroxide solution are added to a sample of the vaginal discharge. A strong fishy odour (ammonia) from the mix means that bacterial vaginosis is present. For a wet mount, a sample of the vaginal discharge is placed on a glass slide and mixed with a salt solution. The slide is looked at under a microscope (under dark ground illumination) for yeast cells, trichomoniasis and treponemes. A Gram stain is made of any discharge and examined for N. gonorrhoeae (Gram-negative diplococci) and the clue cells of bacterial vaginosis. Further swabs are frequently taken from the urethra, anus and throat, and sent in Stuart’s transport medium for culture (looking for N. gonorrhoeae). Any woman reporting anal intercourse will also undergo proctoscopy looking for warts.

If one STI is present, there may be others. In practice, a patient with an STI will be referred to a GUM clinic, counselled and offered a full screen including serological tests for syphilis, hepatitis B, HIV and hepatitis C, if indicated. The GUM clinic will also arrange for contact tracing to break the chain of infection. They may also arrange for a follow-up test of cure.

If drug treatment is given, it is better to use simple, if possible, single-dose regimes and advise the woman to abstain from intercourse during treatment to prevent reinfection until her partner is also treated. In practice, regimens are given that will cover N. gonorrhoea, C. trachomatis, T. vaginalis and bacterial vaginosis.

In the spirit of the NICE guidelines, time should be allocated to discuss modification of any high-risk activity to prevent reinfection (National Institute for Health and Clinical Excellence 2007). This should be non-judgmental and should be accompanied by written information on the subject to reinforce the message.

Aetiology

Herpes simplex virus 1 and 2 (HSV-1 and HSV-2) are species of Herpesviridae, which cause genital herpes. Herpes viruses are composed of relatively large double-stranded, linear DNA genomes encoding 100–200 genes encased within an icosahedral proteinaceous capsid which is wrapped in a lipid bilayer envelope. They are nuclear, replicating the viral DNA being transcribed to RNA within the infected cell’s nucleus. HSV enters a latent phase within the neurones (local sensory ganglia) between active symptomatic episodes. Reactivation leads to production of virions, which may then be passed to a new host by sexual contact (in the case of genital herpes). Genital HSV-2 recurs and sheds more often than genital HSV-1; the converse is true for oral herpes.

Clinical features

Only about half those infected will get symptoms at the time of infection. Some may become symptomatic at a later date and some not at all. The seropositivity rates are 7% in the UK, 22% in the USA and 40% in 19-year-old females in Tanzania. In those cases that become symptomatic, the incubation period is 7–14 days.

The first episode presents with multiple painful genital ulcers (see Figure 63.2). It is less severe in those with a history of oral herpes. Typical lesions begin as vesicles, at any or all sites from the introitus to the cervix, which become superficial tender ulcers with an erythematous halo and a yellow or grey base (Figure 63.3). Immunocompromised patients may have an atypical appearance which is an elongated ‘knife cut’ ulcer. There may be bilateral inguinal lymphadenopathy. Viral shedding continues until the lesions crust over. One-third of patients have systemic symptoms of fever and general malaise. Ten percent will experience viral meningitis with photophobia and headache. A few patients experience retention of urine, either because of pain due to passing urine over the lesions (in which case, micturating in a bath may help) or because of a viral autonomic neuritis. Involvement of other nerves may lead to hyperaesthetic buttocks, thighs or perineum for a time. Severe encephalitis is rare but may be seen more frequently in immunocompromised patients. Without treatment, the first episode lasts for 3–4 weeks.

Figure 63.2 Primary genital herpes: multiple painful ulcers are present.

From Bolognia J et al, Dermatology 2e, with permission of Elsevier.

Figure 63.3 Primary genital herpes: ulcers on cervix.

Complications of the first episode are common. There may be secondary bacterial infection of lesions. Autoinoculation may occur, often to fingers and eyes.

Recurrent episodes occur in approximately half of patients, tend to be less severe and are relatively less common after the first year. HSV-2 is more likely to become recurrent than HSV-1. There does not necessarily have to be a precipitating event, although stress, menstruation, trauma (sexual intercourse) and ultraviolet light are implicated. Immunosuppression increases the frequency and duration of episodes; herpetic ulceration persisting for over 1 month in a patient with HIV is AIDS defining.

Diagnosis

In the UK, guidelines for diagnostic criteria for herpes were drawn up by the British Association for Sexual Health and HIV (BASHH) in 2006. These are summarized below.

Screening of asymptomatic GUM clinic attendees by either HSV antibody testing or HSV detection in genital specimens is not recommended at present, although this area is under active review.

Treatment

Aetiology

Treponema pallidum venereum or Treponema pallidum pallidum is a motile spirochaete, entering the host via breaches in epithelium. The organism can also be transmitted vertically to a fetus in the later stages of pregnancy, giving rise to congenital syphilis.

The subspecies of T. pallidum causing yaws (pertenue), pinta (carateum) and bejel or endemic syphilis (endemicum) are morphologically and serologically indistinguishable from T. pallidum pallidum (syphilis); however, their transmission is not venereal in nature and the course of each disease is significantly different. They are worthy of mention as they can cause diagnostic confusion. Yaws occurs in sub-Saharan Africa, the Caribbean and most of the humid tropics. Bejel occurs in desert regions, and pinta occurs in parts of Central and South America. If venereal syphilis cannot be excluded in someone originating from one of these areas, it is safest to treat.

Clinical features

Primary syphilis

The incubation period after inoculation is 9–90 days (mean 21 days). The lesions may be extragenital and may be multiple. Chancres are usually painless, raised, well-circumscribed ulcers (Figure 63.4). There is a non-tender regional lymphadenopathy. The lesion may well go unnoticed, especially if it is intravaginal or rectal. It will heal spontaneously in 3–10 weeks.

Figure 63.4 The chancre of primary syphilis.

From Morse S et al., Atlas of Sexually Transmitted Diseases and AIDS, 3e, with permission of Elsevier.

Secondary syphilis

The lesions of secondary syphilis usually manifest some 4–8 weeks after the appearance of the chancre, but sometimes up to 6 months later. In one-third of cases, the chancre is still there. There is a systemic eruption of a non-itchy maculopapular rash, symmetrical and involving the palms and soles (Figure 63.5). Papular lesions may coalesce into large fleshy wart-like lesions, condylomata lata, in areas such as the anus and the labia. Mucous patches and linear (snail-track) ulcers are seen on the mucosae. There may be a generalized lymphadenopathy. The secondary stage involves a bacteraemia with fever, headache, bone pain, alopecia, arthritis and meningitis. There may be hepatitis, optic neuritis and papilloedema. A sensorineural deafness can occur due to destruction of hair cells in the inner ear.

Figure 63.5 Secondary syphilis: the maculopapular rash.

Without treatment, the lesions of secondary syphilis resolve. Approximately one-quarter of cases will have a recurrence of secondary syphilis; although unusual after 1 year, it can recur up to 2 years later, during which time the infection can be transmitted to a sexual partner.

Syphilis is transmissible to other adults through sexual contact in primary and secondary syphilis and, occasionally, in early latent syphilis.

Diagnosis

Dark ground microscopy of a wet preparation scraped from the base of a chancre or a lesion of secondary syphilis will display the treponeme as a bluish-white thread-like organism with a coiled body, some 6–20 µm long (Figure 63.6). It is motile and displays three distinct movements: watch-spring, corkscrew and jack-knife. Due to sensitivity and specificity issues with serological testing, this is by far the best chance of establishing a firm diagnosis.

Figure 63.6 Dark ground microscopy showing bluish-white thread-like treponeme.

From Cohen J et al., Infectious Diseases, 3e, with permission of Elsevier.

Dark ground/dark field microscopy (DGM) of lesion exudate or lymph nodes should be performed by experienced clinicians because of interference from commensal spirochaetes that are found in the normal flora of the genital and rectal mucosae. DGM is considered to be less reliable in examining rectal and non-penile genital lesions, and is not suitable for examining oral lesions.

If the initial examination is negative, DGM should be repeated daily for at least 3 days. Antibiotics should be withheld during this period, and local saline lavage may be used to reduce local sepsis.

Testing of material submitted on dry swabs by PCR is recommended for oral or other lesions where contamination with commensal treponemes is likely.

PCR is also useful in the diagnosis of primary syphilis and is available via local laboratories sending samples to the Sexually Transmitted Bacteria Reference Laboratory at the Health Protection Agency.

Serological tests can be divided into non-specific tests [Venereal Disease Reference Laboratory (VDRL) and rapid plasmin reagin (RPR)] and specific tests [T. pallidum enzyme immunoassay (EIA), fluorescent treponemal antibody (FTA), T. pallidum haemagglutination assay (TPHA) and T. pallidum particle assay]. Non-specific tests usually become negative after successful treatment, whereas specific tests remain positive. All tests, specific or otherwise, are positive for bejel, yaws and pinta.

Non-specific tests become positive 3–5 weeks post inoculation, and as they are quantitative, they may be used to monitor treatment. However, they may also decay naturally, even yielding false-negative results. They may also give false-positive results in the presence of active herpes, measles, mumps, chronic autoimmune disease and rheumatoid arthritis, and also after immunization for typhoid or yellow fever.

EIA tests become positive soon after infection (3–4 weeks, similar to the FTA) and have the advantage of being easy to automate.

A guide to interpretation of tests is given in Table 63.2.

Table 63.2 Diagnosis and serological interpretation

EIA, enzyme immunoassay; FTA, fluorescent treponemal antibody; VDLR, Venereal Disease Reference Laboratory; TPHA, Treponema pallidum haemagglutination assay; RPR, rapid plasmin reagin.

The UK Department of Health has reviewed the current practice of offering syphilis testing routinely for pregnant women, and has recommended that screening for syphilis should continue. EIA is gradually replacing VDRL/RPR and TPHA as a screening tool by recommendation of the UK Public Health Laboratory Service.

Management

Box 63.2 shows the guidelines of therapeutic regimens approved by BASHH in 2008 for the treatment of syphilis.

With parenteral therapy with penicillin, the Jarisch–Herxheimer reaction is common in both primary and secondary syphilis. Patients should be warned about the possibility of flu-like illness after the first injection. The chancre may become larger initially or the rash may become more widespread. Reassurance and therapy with paracetamol and non-steroidal anti-inflammatory drugs are usually all that is necessary.

Congenital syphilis is preventable. Antenatal testing has always been cost-effective, and this is even more so with the increase in the prevalence of syphilis in the UK. T. pallidum can infect the fetus transplacentally at any time. This is less likely in late or latent syphilis (5%), but is very common in the first two stages (50%). In sub-Saharan Africa, it is associated with 25% of all stillbirths.

Aetiology

Lymphogranuloma venereum (LGV) is a systemic disease caused by one of three invasive serovars (L1, L2 or L3) of C. trachomatis, but other strains may occasionally be involved

LGV has been a rare occurrence in industrialized countries since the mid-1960s. Since 2003, however, a series of LGV outbreaks have been reported in several European cities, starting in the Netherlands. In the UK, more than 290 cases had been confirmed by December 2005. The majority of cases have been diagnosed in GUM clinics in London. At that time, all new cases were among male homosexuals, the majority of whom were HIV positive.

LGV is endemic in several tropical areas, including East, West and Southern Africa; Madagascar; India; South-east Asia; Papua New Guinea; and some Caribbean islands. A large epidemic has been reported recently among crack cocaine users in the Bahamas.

Clinical features

The clinical course of LGV is classically divided into three stages.

Diagnosis

Positive diagnosis of LGV is difficult, requiring a combination of good clinical acumen and supportive investigations. LGV can be suspected on positive chlamydial serology, isolation of C. trachomatis from the infected site or histological identification of chlamydia in infected tissue. Traditional methods for LGV diagnosis have been reviewed based on nucleic acid amplification tests (NAATs).

Chlamydiae are intracellular organisms, so samples must contain cellular material which can be obtained from the ulcer base exudate or from rectal tissue, or by aspiration from fluctuant lymph nodes or buboes. A urethral swab or first-catch urine (FCU) sample can be used when lymphadenopathy is present and LGV is suspected as the cause.

Treatment

Aetiology

An infection caused by Haemophilus ducreyi, the global distribution is similar to that of LGV. Co-infections of H. ducreyi with T. pallidum or HSV are frequent and occur in over 10% of patients in many African studies. Chancroid is characterized by painful anogenital ulceration (multiple) and lymphadenitis with progression to bubo formation. The incubation period ranges between 3 and 10 days, and the initial lesion may progress rapidly to form an open sore. There are no prodromal symptoms.

In males, most ulcers are found on the prepuce near the frenulum or in the coronal sulcus. In females, most lesions are found at the entrance of the vagina, particularly the fourchette. Several lesions may merge to form gigantic ulcers.

Diagnosis

The main methods revolve around the identification of H. ducreyi by: culture of material obtained from the ulcer base on specialized agar; detection of nucleic acid (DNA) by amplification techniques such as PCR; using nested techniques; microscopy of a Gram-stained smear (or other stains) of material from the ulcer base or of pus aspirate from the bubo; or demonstration of characteristic Gram-negative coccobacilli, with occasional characteristic chaining. The test has low sensitivity and is not recommended as a diagnostic test.

Treatment

Aetiology

Donovanosis is seen chiefly in small endemic foci in tropical countries. In recent years, active foci of disease have been described in India, Papua New Guinea, the Caribbean, Brazil, the Guyanas, South Africa, Zambia, Vietnam and in Australian aboriginals. The causative organism, formerly Calymmatobacterium granulomatis, has recently been officially redesignated Klebsiella granulomatis.

Clinical features

At the site of primary inoculation, one or more papules/nodules develop into friable ulcers or hypertrophic lesions which gradually increase in size. Lesions do not tend to be painful. Regional lymphadenopathy is followed by either abscess formation (pseudobubo) or ulceration of the overlying skin. Untreated infections may either resolve spontaneously or persist and slowly spread. Primary lesions of mouth and cervix occur, and the latter have often been mistaken for malignant lesions. Complications include haemorrhage, genital lymphoedema, genital mutilation and cicatrization, development of squamous carcinoma and, on rare occasions, haematogenous dissemination to bone and viscera (particularly during pregnancy). Rare cases of vertical transmission have been reported. Lesions of the ears of infants are characteristic in such cases.

Diagnosis

The main method of diagnosis is the demonstration of Donovan bodies (Figure 63.7) in cellular material taken by scraping/impression smear/swab/crushing of pinched off tissue fragments on to a glass slide, or a tissue sample collected by biopsy. Either can be stained by Giemsa.

Figure 63.7 Granuloma inguinale: the histiocytes contain characteristic Donovan bodies (Warthin–Starry stain).

Image courtesy of W. Grayson MD, University of Witwatersrand, Johannesburg, South Africa.

Management

Treatment should continue until the lesions have healed. Healing times vary considerably between patients. The CDC recommends a minimum of 3 weeks.

Clinical features

Figure 63.8 Gonococcal cervicitis: the purulent endocervical discharge.

From Cohen J et al., Infectious Diseases, 3e, with permission of Elsevier.

Transluminal spread of N. gonorrhoeae may occur from the urethra or endocervix to involve the epididymis and prostate in men (≤1%), and the endometrium and pelvic organs in women (probably <10%). Haematogenous dissemination may also occur from infected mucous membranes, resulting in skin lesions, arthralgia, arthritis and tenosynovitis. Disseminated gonococcal infection is uncommon (<1%).

Diagnosis

The diagnosis is established by the identification of N. gonorrhoeae at an infected site. Culture offers a readily available, specific, sensitive and cheap diagnostic test that readily allows confirmatory identification and antimicrobial susceptibility testing. Alternative tests include NAATs and nucleic acid hybridization tests. NAATs are more sensitive than culture and can also be used as diagnostic/screening tests on non-invasively collected specimens (urine and self-taken vaginal swabs). The sensitivity of culture may be less than 75% for endocervical swabs.

Rapid diagnostic tests can be performed to facilitate immediate diagnosis and treatment. Microscopy (×1000) of Gram-stained genital specimens allows direct visualization of N. gonorrhoeae as Gram-negative diplococci within polymorphonuclear leukocytes (Figure 63.9).

Figure 63.9 Gram-negative diplococci within polymorphonuclear leukocyte.

Management

Referral to a GUM department for management is strongly encouraged. Patients should be given a detailed explanation of their condition with particular emphasis on the long-term implications for the health of themselves and their partner(s). This should be reinforced with clear and accurate written information. Patients should be advised to avoid unprotected sexual intercourse until they and their partner(s) have completed treatment.

Screening for coincident STIs should be performed routinely in patients with or at risk of gonorrhoea.

Treatment

Surveillance data for 2004 show significant levels of N. gonorrhoeae resistance to penicillin (11.2%), tetracyclines (44.5%) and ciprofloxacin (14.1%) in the UK. Most resistant infections are acquired in the UK. The following alternative regimens may be used when an infection is known to be sensitive to these antimicrobials or where the regional prevalence of resistance to them is less than 5%.

Clinicians using alternative regimens are recommended to review local antimicrobial sensitivity testing regularly with microbiology colleagues.

Aetiology

C. trachomatis is an obligate intracellular human pathogen. It is Gram-indeterminate (i.e. cannot be stained with the Gram stain), but structurally the organism is Gram-negative.

Chlamydia is the most common curable STI in the UK. It is frequently asymptomatic in both men and women, and ongoing transmission in the community is sustained by this unrecognized infection.

If untreated, infection may persist or resolve spontaneously. Two-thirds of sexual partners of chlamydia-positive individuals are also chlamydia-positive.

Clinical features

Chlamydia is asymptomatic in approximately 70% of infected women, but may cause any of the following: postcoital or intermenstrual bleeding, lower abdominal pain, purulent vaginal discharge, mucopurulent cervicitis (see Figure 63.10) and/or contact bleeding or dysuria. Rectal infections are usually asymptomatic, but may cause anal discharge and anorectal discomfort (proctitis).

Figure 63.10 Chlamydia cervicitis: a purulent discharge and inflamed follicles are seen.

Complications

In the absence of treatment, 10–40% of infected women will develop PID, with a significant proportion of these cases being asymptomatic or having mild, atypical symptoms. PID can result in tubal factor infertility, ectopic pregnancy and chronic pelvic pain. Other complications include Fitz–Hugh–Curtis syndrome (perihepatitis), transmission to neonate (neonatal conjunctivitis, pneumonia), epididymo-orchitis, adult conjunctivitis and sexually acquired reactive arthritis/Reiter’s syndrome (more common in men).

Figure 63.11 Chlamydia perihepatitis violin-string adhesions are visible.

Diagnosis

Management

Uncomplicated genital tract infection with C. trachomatis is not an indication for removal of an intrauterine contraceptive device.

Aetiology

Mucopurulent cervicitis is the female equivalent of non-gonococcal urethritis (NGU), 40% of cases being due to infection with C. trachomatis. Mycoplasma genitalium is an unproven cause of PID.

There are a number of uncertainties with NGU in men. Urethral inflammation can occur without a known pathogen being isolated in the majority of patients, even using more sensitive detection methods. The most common organisms implicated are C. trachomatis and M. genitalium, with the latter perhaps causing more symptoms. In 30–80% of cases with NGU, neither C. trachomatis nor M. genitalium is detected. The exact role of ureaplasmas in NGU has been controversial due to the conflicting observations in clinical studies. Ureaplasmas are ubiquitous micro-organisms which have recently been divided into two biovars; U. urealyticum biovar 2 may account for 5–10% of cases of acute NGU. There is no clear indication for its treatment in women.

Management

The importance of evaluation and treatment of sexual partners is stressed in cases of NGU as C. trachomatis may be detected in the woman.

Treatment

Treatment as for C. trachomatis will eradicate Mycoplasma spp. including ureaplasma. However, it seems that resistant strains are emerging.

Aetiology

The causative organism is the HPV (a DNA virus of the papovavirus group), especially types 6 and 11 (also 16, 18, 31, 33 and 35). Subclinical infection is extremely common, and trigger factors for an eruption of warts are not known. Occasionally in pregnancy, they may become very large and confluent. In men, similar giant and destructive warts may appear on the penis (Buschke–Löwenstein tumour) associated with types 6 and 11.

Cervical dysplasia and subsequent carcinoma is strongly associated with types 16 and 18; these types are associated with 70% of cervical cancers. Types 31, 33 and 35 represent the majority of other cases. Whilst cervical warts are seen in 10% of women with obvious warts elsewhere in the anogenital area, one-third will have evidence of wart infection on cytology or at colposcopic examination. In terms of risk for cervical cancer, the greatest threat seems to be from latent or subclinical infections with types 16 and 18.

Diagnosis

Between 1998 and 2007, the diagnosis of genital warts rose by 28%. The diagnosis is solely on clinical appearance. Warts in women are most commonly found on the vulva, but may appear anywhere in the anogenital area. They are usually painless. The presence of another STI is common (25%), and a full screen should be undertaken (see Figures 63.12 and 63.13).

Figure 63.12 Vulval warts.

Courtesy of Dr I H Ahmed.

Figure 63.13 Cervical warts.

Prevention

A decision by the UK Department of Health to introduce vaccination against HPV types 16 and 18 (Cervarix) was taken in October 2007. This decision follows the advice of the Joint Committee on Vaccination and Immunisation which, based on a detailed review of evidence surrounding HPV vaccination, recommended the routine vaccination of girls aged 12–13 years, recommended a catch-up programme of girls under the age of 18 years, and acknowledged that the evidence that a catch-up programme for all women aged 18–25 years was unlikely to be cost-effective but could benefit some individual women. The Department of Health will consider this further.

Two vaccines, Cervarix and Gardasil, were competing for the contract. Both vaccines demonstrate highly effective protection against HPV 16 and 18, which are responsible for the majority of cases of cervical cancer. However, only one of the vaccines, Gardasil, protects against HPV types 6 and 11, as well as 16 and 18.

Treatment

Aetiology and clinical features

Molluscum contagiosum is a benign viral skin infection most commonly seen in children. However, sexual contact in adults may lead to the appearance of lesions in the genital area. The condition is harmless.

Molluscum contagiosum is caused by a pox virus passed on by direct skin-to-skin contact, and may affect any part of the body. There is anecdotal evidence associating facial lesions with HIV-related immunodeficiency.

After an incubation period of 3–12 weeks, discrete, pearly, papular, smooth or umbilicated lesions appear (Figure 63.10). In immunocompetent individuals, the size of the lesions seldom exceeds 5 mm, and if untreated, there is usually spontaneous regression after several months. Secondary bacterial infection may result if lesions are scratched. In the immunocompromised, lesions may become large and exuberant, and secondary infection may be problematic. As other STIs may coexist, a full screen for these should be undertaken. HIV testing is recommended in patients presenting with facial lesions.

Treatment

Cryotherapy: liquid nitrogen should be applied until a halo of ice surrounds the lesion. Repeat applications may be necessary. The pearly core should be expressed either manually or using forceps, and the lesion can be pierced with an orange stick with or without the application of tincture of iodine or phenol. Curettage or diathermy may be carried out under local anaesthesia.

In patients with HIV infection, the introduction of highly active antiretroviral therapy may lead to resolution of lesions. Contact tracing of partners is unnecessary.

Hepatitis A

Hepatitis A is caused by a picorna (RNA) virus, and is particularly common in areas of the world where sanitation is poor. It largely affects children, although 784 cases were reported in England and Wales in 2004.

Transmission can be oral (via food, water, close personal contact), by anal or digital-rectal contact, and via contaminated batches of factor VIII. The incubation period lasts 15–45 days. Most children and up to half of adults are asymptomatic or have mild non-specific symptoms with little or no jaundice. In clinical cases, there are two phases of symptoms: flu-like symptoms (malaise, myalgia, fatigue), often with right upper abdominal pain, which last for 3–10 days; followed by anorexia, nausea and fatigue, which usually lasts for 1–3 weeks. It can persist for 12 or more weeks in a minority of patients who have cholestatic symptoms (itching and deep jaundice). Fever is not found in this phase. There may be jaundice with pale stools and dark urine. Liver enlargement/tenderness and signs of dehydration are also common.

Fifteen percent of patients may require hospital care, of whom one-quarter will have severe hepatitis (prothrombin time >3 s prolonged, or bilirubin >170 mmol/l). The infection does not have any teratogenic effects but there is an increased rate of miscarriage and premature labour, proportional to the severity of the illness. There have been case reports of possible vertical transmission.

Hepatitis B

Hepatitis B is caused by an hepadna (DNA) virus. It is endemic worldwide with very high carriage rates (up to 20%), particularly in South and East Asia, but also in Southern Europe, Central and South America, Africa and Eastern Europe. In the UK, carriage varies from 0.01–0.04% in blood donors to more than 1% in intravenous drug users and homosexual men. In 2003, 1151 cases were notified in England and Wales. There are eight distinct genotypes (A–H) which vary in geographical distribution, pathogenicity and treatment susceptibility.

Transmission occurs in immune men who have sex with men and correlates with multiple partners, unprotected anal sex and oroanal sex. Transmission also occurs after heterosexual contact (e.g. 18% infection rates for regular partners of patients with acute hepatitis B). Sex workers are also at higher risk, as are intravenous drug users. Vertical transmission of infection occurs in 90% of pregnancies where the mother is hepatitis B e antigen positive, and in approximately 10% of surface-antigen-positive, e-antigen-negative mothers. Most (>90%) infected infants become chronic carriers. Infants born to infectious mothers are vaccinated from birth, usually in combination with hepatitis-B-specific immunoglobulin 200 iu intramuscularly; this reduces vertical transmission by 90%.

Asymptomatic infection is also found in 10–50% of adults in the acute phase and is especially likely in those with HIV coinfection. Chronic carriers are usually asymptomatic but may have fatigue or loss of appetite. The prodromal and icteric phases are very similar to hepatitis A, but may be more severe and prolonged.

Fulminant hepatitis occurs in less than 1% of symptomatic cases but carries a worse prognosis than that caused by hepatitis A. Concurrent hepatitis C infection can lead to fulminant hepatitis, more aggressive chronic hepatitis and increased risk of liver cancer.

If chronic infection occurs (as it does in 5–10% of symptomatic cases, higher in the immunocompromised), there are often no physical signs. After many years of infection, depending on the severity and duration, there may be signs of chronic liver disease including spider naevi, finger clubbing, jaundice and hepatosplenomegaly, and in severe cases, thin skin, bruising, ascites, liver flap and encephalopathy.

Mortality is less than 1% for acute cases. Between 10% and 50% of chronic carriers will develop cirrhosis, leading to premature death in approximately half. Ten percent or more of cirrhotic patients will progress to liver cancer.

Concurrent HIV infection increases the risk of progression to cirrhosis and death.

The serology profiles are shown in Table 63.4.

Patients should be advised to avoid unprotected sexual intercourse until they have become non-infectious or their partners have been successfully vaccinated. They should have a full STI screen. Further management is undertaken by hepatologists or physicians with experience in the management of hepatitis.

Hepatitis B testing in asymptomatic patients should be considered in men who have sex with men, sex workers (of either sex), injecting drug users, HIV-positive patients, sexual assault victims, people from countries where hepatitis B is common, and women attending antenatal clinics. If patients are non-immune, vaccination should be considered. If patients are found to be chronic carriers, referral for therapy should be considered. The simplest initial screening test in someone who is unvaccinated or is of unknown infection status is anti-hepatitis B core antigen, with the addition of other tests as necessary. Some also screen for hepatitis B surface antigen initially.

Hepatitis D

This is caused by a defective RNA virus which cannot thrive in the absence of chronic hepatitis B. In such patients, the clinical course is severe. Simultaneous coinoculation with hepatitis B usually resolves. Hepatitis D may be acquired sexually but the population at greatest risk is intravenous drug users. Diagnosis is by antibody assay. The management belongs properly in the hands of hepatologists.

Hepatitis C

Hepatitis C is another RNA virus causing chronic hepatitis. It may be transmitted sexually but this has proved inefficient with less than 5% of long-term partners becoming infected. Injecting drug users are the highest risk group. Vertical transmission is rare but the risk increases if there is coexisting HIV infection. Exposure to the virus from contaminated blood and blood products used in health care has been eliminated. There is no vaccine. Diagnosis is on serology; however, an antibody response may be delayed by up to 4 weeks so the test may need repeating. The management is undertaken by hepatologists and the virus may be cleared by combination therapy with interferon and ribavirin.

Hepatitis E

Hepatitis E is an RNA virus which usually causes an acute and self-limiting infection. It is spread by orofaecal transmission. It has a high mortality rate in pregnant women (17–30%). It causes sporadic cases and waterborne epidemics in the Indian subcontinent, South-east and Central Asia, Africa and North America. Cases in the UK are usually only seen in travellers returning from these areas. It is detected on serology.

Bacterial vaginosis

An elevation in pH may allow other commensals of the vagina to replicate in greater quantity and this may result in bacterial vaginosis. This is a common cause of attendance at GUM clincs, as it is mistaken by the woman as a possible STI, which it is not. The prevalence in the UK is of the order of 15% but it may be under-reported.

Bacterial vaginosis is characterized by an overgrowth of predominantly anaerobic organisms (Gardnerella vaginalis, Prevotella spp., Mycoplasma hominis, Mobiluncus spp.) in the vagina, leading to replacement of lactobacilli and an increase in pH from less than 4.5 to as high as 7.0.

Clinical features and complications

There is an offensive fishy smelling, thin, white vaginal discharge not associated with soreness, itching or irritation. However, in many women (approximately 50%), bacterial vaginosis is asymptomatic (see Figure 63.14).

Figure 63.14 Bacterial vaginosis.

The prevalence of bacterial vaginosis is high in women with PID, and it is common in some populations of women undergoing elective TOP, and associated with post-TOP endometritis and PID. In pregnancy, bacterial vaginosis is associated with late miscarriage, preterm birth, preterm premature rupture of the membranes and postpartum endometritis.

Diagnosis

Two approaches are available.

Amsel criteria

At least three of the following four criteria need to be present for the diagnosis to be confirmed.

• Thin, white, homogeneous discharge.

• Clue cells (Figure 63.15) on microscopy of wet mount.

• pH of vaginal fluid >4.5.

• Release of a fishy odour on adding alkali (10% potassium hydroxide).

Figure 63.15 Clue cells: vaginal squamous cells covered in bacteria.

Image courtesy of Dr I.H. Ahmed, Nottingham University Hospitals, UK.

Gram-stained vaginal smear

This is evaluated with the Hay (note: not the author)/Ison criteria or the Nugent criteria. The Hay/Ison criteria are defined as follows.

• Grade 1 (normal): lactobacillus morphotypes predominate.

• Grade 2 (intermediate): mixed flora with some lactobacilli present, but gardnerella or mobiluncus morphotypes also present.

• Grade 3 (bacterial vaginosis): predominantly gardnerella and/or mobiluncus morphotypes. Few or absent lactobacilli.

Candidiasis

This is a common non-STI cause of infective vaginal discharge that will affect approximately 75% of women at some stage during their reproductive life.

Aetiology and clinical features

The causative agent is C. albicans in 80–92% of cases. Non-albicans species (e.g. C. glabrata, C. tropicalis, C. krusei, C. parapsilosis and Saccharomyces cerevisiae) account for the remainder of cases.

Vulval itch and/or soreness, vaginal discharge (typically curdy but may be thin, non-offensive), superficial dyspareunia and external dysuria are common complaints. There may be erythema, fissuring, oedema, satellite lesions and excoriation. None of these symptoms or signs are pathognomonic for vulvovaginal candidiasis. Many women may have other conditions, such as dermatitis, allergic reactions and lichen sclerosus. In addition, symptoms/signs are no guide to species (see Figure 63.16).

Figure 63.16 Candida vaginitis: note the thick adherent discharge.

Ten to twenty percent of women of reproductive age may be colonized with Candida spp. but have no clinical signs or symptoms. These women do not require treatment.

Trichomoniasis

Aetiology and clinical features

T. vaginalis is a flagellate protozoan (Figure 63.17). In women, the organism is found in the vagina, urethra and paraurethral glands. While the urinary tract is the sole site of infection in less than 5% of cases, urethral infection is present in 90% of episodes. In adults, transmission is almost exclusively sexual. Due to site specificity, infection can only follow intravaginal or intraurethral inoculation of the organism.

Figure 63.17 Trichomonas vaginalis.

Ten to fifty percent of infected women are asymptomatic. In those with symptoms, these include vaginal discharge, vulval itching, dysuria or offensive odour. Occasionally, the presenting complaint is low abdominal discomfort.

Vaginal discharge occurs in up to 70% of cases, varying in consistency from thin and scanty to profuse and thick; the classical frothy yellow discharge occurs in 10–30% of women. Approximately 2% of patients will have strawberry cervix appearance to the naked eye. Higher rates are seen on colposcopic examination. No abnormalities will be seen in 5–15% of women on examination.

There is increasing evidence that T. vaginalis infection can have a detrimental outcome on pregnancy, and is associated with preterm delivery and low birth weight. However, further research is needed to confirm causality. Moreover, recent trials have found that treatment does not improve pregnancy outcome, and may be harmful. Screening of asymptomatic individuals for T. vaginalis infection is therefore not currently recommended (see Figure 63.18A,B).

Figure 63.18 Trichomonas: (A) grey watery discharge, (B) strawberry cervix with petechial haemorrhage.

Pediculosis pubis (Phthirus pubis)

Aetiology and clinical features

The crab louse Phthirius pubis (Figure 63.19) is transmitted by close body contact. The incubation period is usually between 5 days and several weeks, although occasional individuals appear to have more prolonged, asymptomatic infestation.

Figure 63.19 The crab louse: Phthirius pubis or Pediculosis pubis.

Source: World Health Organization.

Adult lice infest coarse hairs of the pubic area, body hair and, rarely, eyebrows and eyelashes. Eggs (nits) are laid which adhere to the hairs. There may be no symptoms or there may be itching due to hypersensitivity to feeding lice. Blue macules (maculae caeruleae) may be visible at feeding sites.

Scabies