Non-HIV sexually transmitted infections

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CHAPTER 63 Non-HIV sexually transmitted infections

Daniel P. Hay, Eimear P. Kieran

Introduction

Sexually transmitted infections (STIs) are infections whose primary route of transmission is through sexual contact. They are common, often occult in nature, have serious sequelae and are synergistic with human immunodeficiency virus (HIV). In developing countries, they are the second most common cause of death amongst women aged 15–44 years, after maternal mortality. The serious nature of many of these conditions and the fact that the presence of one STI suggests the possibility of others is a caution to the gynaecologist to manage such patients with appropriate input from others, notably genitourinary physicians and microbiologists.

More than 20 pathogens are transmissible through sexual intercourse. Many are curable but, in spite of the availability of effective treatment, they remain a major public health concern in both industrialized and developing countries.

Globally, the exact prevalence of STIs is largely unknown. Surveillance systems exist in some countries but the data rendered are not always reliable or complete. The quality and completeness of the available data and estimates depend on the quality of STI services, the extent to which patients seek health care, the intensity of case finding and diagnosis, and the quality of reporting.

The completeness is further affected by the natural history of STIs, since a large number of infections are asymptomatic. Moreover, only part of the symptomatic population seeks health care and an even smaller number of cases are reported. The social stigma that is usually associated with STIs may result in people seeking care from alternative providers or not seeking care at all. As a result, report-based STI surveillance systems tend to underestimate the total number of new cases substantially.

World Health Organization (WHO) estimates suggest that more than 12 million new cases of syphilis, 62 million new cases of gonorrhoea, 92 million new cases of chlamydial infection and 174 million new cases of trichomoniasis occurred throughout the world in 1999 (World Health Organization 2001). Congenital syphilis, prevention of which is relatively easy and cost-effective, may still be responsible for as many as 14% of neonatal deaths. Up to 10% of women who are untreated, or inadequately treated, for chlamydial and gonococcal infections may become infertile as a consequence. On a global scale, up to 4000 newborn babies each year may become blind because of gonococcal and chlamydial ophthalmia neonatorum (note: ophthalmia neonatorum is a notifiable disease).

Both symptomatic and asymptomatic infections can lead to the development of serious complications with severe consequences. The most serious complications and long-term consequences of untreated STIs tend to be in women and newborn babies. Sequelae in women include recurring herpes episodes, pelvic inflammatory disease (PID), ectopic pregnancy, spontaneous miscarriage, premature rupture of the membranes, puerperal sepsis, tubal factor infertility and cervical cancer consequent to human papilloma virus (HPV) infection. Neonates may be born premature or even stillborn. They may be born with infection or the consequences of congenital syphilis.

STIs also enhance the sexual transmission of HIV infection. The presence of an untreated STI can increase the risk of both acquisition and transmission of HIV by a factor of up to 10. Ulcerative STIs disrupt the integrity of the protective tegument and increase the presence of HIV-susceptible cells (e.g. CD4 lymphocytes). Non-ulcerative STIs similarly increase HIV-susceptible cells in the area. Moreover, improvement in the management of STIs can reduce the incidence of HIV-1 infection in the general population by approximately 40%. STI prevention and treatment are, therefore, important components in HIV prevention.

Guidelines covering the majority of STIs exist within the UK. They discuss aspects relating to screening, diagnostic criteria, management and prevention. Crucially, they also set standards for audit, providing a tool for improvement in all these aspects in all units across the UK. They will be quoted from heavily in this chapter in condensed form. The guidelines are not primarily directed per se at gynaecologists, but it is of vital importance that specialists in this area are aware of them.

Epidemiology

WHO estimated that 340 million new cases of STIs occurred worldwide in 1999. The largest number of new infections occurred in South and South-east Asia, followed by sub-Saharan Africa, Latin America and the Caribbean. However, the highest rate of new cases per 1000 population occurred in sub-Saharan Africa (World Health Organization 2001).

In developing countries, STIs and their complications are among the top five disease categories for which adults seek health care. In women of childbearing age, STIs (excluding HIV) are second only to pregnancy as causes of morbidity and mortality.

Globally, the highest rates of STIs are generally found in urban men and women aged 15–35 years. On average, women become infected at a younger age than men.

In the UK, peaks in STI diagnoses occurred in the mid-to-late 1940s (post World War II) and from the mid 1960s through to the early 1980s [from the age of sexual liberation to the advent of acquired immunodeficiency syndrome (AIDS)]. From 1998 to 2007, there was a substantial increase in diagnoses of most STIs (overall 6%). Cases of uncomplicated gonorrhoea increased by 42%, while chlamydia increased by 150%. Chlamydia has been the most commonly reported STI since 2001, overtaking genital warts (see Figure 63.1).

Figure 63.1 All new episodes of sexually transmitted infections seen in genitourinary medicine clinics 1998–2007.

Source: Health Protection Agency 2008 All new episodes seen at GUM clinics: 1998–2007. United Kingdom and country specific tables.

The rapid increase in reports of STIs is probably, in part, due to a general deterioration in sexual health amongst young people and men who have sex with men. However, the greater acceptability of using genitourinary medicine (GUM) services and new campaigns to encourage testing have also made a contribution. In 2000, the UK survey of sexual attitudes and lifestyle over 10 years reported that 30% of 15-year-old girls were sexually active and half of all UK teenagers were sexually active before 17 years of age. Consistent condom usage decreased by 3% over the period of study. Male homosexual activity increased, as did the prevalence of unsafe sex in this group, especially in London. The number of heterosexual partners also increased, and more people were engaging in concurrent relationships.

Certain ethnic minority groups are disproportionately affected by some STIs. In 2005, the GRASP (Gonococcal Resistance to Antimicrobials Surveillance Programme) survey found that Black Caribbeans accounted for 18% of gonorrhoea diagnoses at the clinics studied.

The UK population is mobile and certain groups are at particular risk, including tourists, professional travellers, immigrants and members of the armed forces. In addition, poverty, urbanization, social migration and war often increase levels of prostitution.

The important features in maintaining an STI in a community have been factored into the following formula:

where Ro is the average number of new infections that result from one infection, β is transmissibility, c is the average rate of acquiring partners, and d is the duration of infection.

If Ro >1, the rate of spread in a community will rise; if Ro <1, the rate of spread will fall. This gives the principles behind effective STI control. β can be reduced by promoting condom use and vaccination, c can be reduced by encouraging behavioural change, and d can be reduced by encouraging diagnosis, treatment and contact tracing. These principles then translate into effective health education. d can also be reduced by screening.

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.

Recommendations 1 and 2: for key groups at risk of STIs

• Identify individuals at high risk of STIs using their sexual history. Opportunities for risk assessment may arise during consultations on contraception, pregnancy or abortion, and when carrying out a cervical smear test, offering an STI test or providing travel immunization. Risk assessment can also be carried out during routine care or when a new patient registers.

• Have one-to-one structured discussions with individuals at high risk of STIs (if trained in sexual health), or arrange for these discussions to take place with a trained practitioner. The discussions should be structured on the basis of behaviour change theories. They should address factors that can help to reduce risk-taking and improve self-efficacy and motivation. Ideally, each session should last for at least 15–20 min. The number of sessions will depend on individual need.

Recommendation 3: patients with an STI

• Help patients with an STI to get their partners tested and treated (partner notification), when necessary. This support should be tailored to meet the patient’s individual needs. If necessary, refer patients to a specialist with responsibility for partner notification. Partner notification may be undertaken by the health professional or by the patient.

• Provide the patient and their partners with infection-specific information, including advice about possible reinfection. For chlamydia infection, also consider providing a home sampling kit.

Information given to patients for any condition should be supported by written evidence-based information, in a clear, jargon-free format, to reinforce the message.

Principles of Management of Sexually Transmitted Infections

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.

Clinical Presentations

Patients present with clinical syndromes rather than microbiological presentations. In fact, the most common presentation is none whatsoever! The patient is picked up on opportunistic screening, by partner notification or by chance when presenting with another condition. This emphasizes the importance of the NICE guidelines, especially in the light of increasing prevalences of STIs in the UK.

Vaginal infection and/or cervicitis may present with a discharge, and cervicitis may also present as postcoital bleeding. Endometritis may cause erratic bleeding and pelvic pain. Adnexitis is synonymous with acute PID and may produce dyspareunia and pelvic pain. Fitz–Hugh–Curtis syndrome consists of right upper quadrant pain resulting from ascending pelvic infection and inflammation of the liver capsule or diaphragm.

Genital Herpes

Genital ulcers have a broad differential diagnosis, but the most common cause of de-novo and recurring multiple painful ulceration is herpes simplex virus (HSV). The infection is lifelong and has the potential for recurrence. It can be managed but not eradicated. It is a disease that has long been in the public domain with varying levels of informed and misinformed knowledge. A patient with this diagnosis needs careful counselling, explanation and support. Between 1998 and 2007, diagnoses of genital herpes rose by 51% in the UK.

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.

Virus detection and characterization

The confirmation and characterization of the infection and its type, by direct detection of HSV in genital lesions, are essential for diagnosis, prognosis, counselling and management. Methods should be used that directly demonstrate HSV in swabs taken from the base of the genital lesion. Virus typing to differentiate between HSV-1 and HSV-2 should be performed in all patients with newly diagnosed genital herpes. HSV isolation in cell culture is the current routine diagnostic method in the UK. Virus culture is slow, labour-intensive and expensive. Specificity is virtually 100%, but levels of virus shedding, quality of specimens, and sample storage and transport conditions influence sensitivity. Delayed sample processing and lack of specimen refrigeration after collection and during transport significantly reduce the yield of virus culture at all stages of infection.

HSV DNA detection by polymerase chain reaction (PCR) increases HSV detection rates by 11–71% compared with virus culture. PCR-based methods allow less stringent conditions for sample storage and transport than virus culture, and new real-time PCR assays are rapid and highly specific. Real-time PCR is recommended as the preferred diagnostic method for genital herpes.

Serology

Testing for HSV type-specific antibodies can be used to diagnose HSV infection by the detection of HSV-1 IgG or HSV-2 IgG or both. It is difficult to say whether the infection is recent, as immunoglobulin M (IgM) detection is unreliable. Collection of serum samples a few weeks apart can be used to show seroconversion. HSV-2 antibodies are indicative of genital herpes, whereas HSV-1 antibodies do not differentiate between genital and oropharyngeal infection.

Western blot is the diagnostic gold-standard, but it is not commercially available. Several commercial assays, as well as validated in-house methods, are available which show 91–99% sensitivity and 92–98% specificity relative to Western blot in sexually active adults.

Caution is needed in interpreting serology results because even highly sensitive and specific assays have poor predictive values in low-prevalence populations. Local epidemiological data and patient demographic characteristics should guide testing and interpretation of results. In patients with a low likelihood of genital herpes, a positive HSV-2 antibody result should be confirmed in a repeat sample or by a different assay.

The differential diagnosis of vulval ulcers is shown in Table 63.1.

Table 63.1 The differential diagnosis of genital ulcers

Infective	Non-infective
Herpes simplex virus	Aphthous ulcers
Primary syphilis	Trauma
Lymphogranuloma venereum	Skin disease (e.g. lichen sclerosis et atrophicus) Chancroid
Donovanosis	Behçet’s syndrome
Human immunodeficiency virus	Other multisystem disorder (e.g. sarcoidosis)
	Dermatitis artefacta