Sexually transmitted infections

21 Sexually transmitted infections

The incidence of most STIs is increasing

This is typified by the situation in the UK where, in 2009, 482 700 new STD cases were reported by genitourinary medicine clinics, an increase of over 12 000 from the previous year. A similar situation exists in other countries, including the USA. The reasons for this increase include:

The last two factors may change. There is evidence of changes in male homosexual behaviour, leading to decreased transmission of some STIs in this group, and vaccines for infections such as human papillomavirus have been developed.

HIV infection and AIDS have overshadowed other STIs with immense impact as a highly lethal infectious disease. Measuring plasma HIV-1 RNA load, CD4 counts and percentage, together with antiretroviral resistance and tropism testing by sequence analysis have become mainstays in the management of HIV infection with regard to monitoring disease progress and response to antiretroviral therapy in resource-rich countries.

The most common STIs are listed in Table 21.1. Table 21.2 gives examples of the strategies used by the microorganisms to overcome host defences.

Table 21.2 Strategies adopted by sexually transmitted microorganisms to combat host defences

Host defences Microbial strategies Examples
Integrity of mucosal surface Specific attachment mechanism Gonococcus or chlamydia to urethral epithelium
Urine flow (for urethral infection) Specific attachment; induce own uptake and transport across urethral epithelial surface in phagocytic vacuole Gonococcus
Infection of urethral epithelial or subepithelial cells Herpes simplex virus (HSV), chlamydia
Phagocytes (especially polymorphs) Induce negligible inflammation Treponema pallidum, mechanism unclear, perhaps poorly activates alternative complement pathway due to sialic acid coating
Resist phagocytosis Gonococcus (capsule) T. pallidum (absorbed fibronectin)
Complement C3d receptor on microbe binds C3b/d and reduces C3b/d-mediated polymorph phagocytosis Candida albicans
Inflammation Induce strong inflammatory response, yet evade consequences Gonococcus, C. albicans, HSV, chlamydia
Antibodies (especially IgA) Produce IgA protease Gonococcus
Cell-mediated immune response (T cells, lymphokines, natural killer cells, etc.) Antigenic variation; allows re-infection of a given individual with an antigenic variant Gonococcus, chlamydia
Poorly understood factors cause ineffective cell-mediated immune response T. pallidum, HIV

STIs and sexual behaviour

The general principles of entry, exit and transmission of the microorganisms that cause STIs are set out in Chapter 13.

The spread of STIs is inextricably linked with sexual behaviour

There are therefore many more opportunities for controlling STIs than, for instance, respiratory infections. Infected but asymptomatic individuals play an important role, and important determinants are promiscuity and sexual practices involving contact between different orifices and mucosal surfaces (see Ch. 13). For example, transmission between heterosexuals or male homosexuals can take place following oral or anal intercourse. The gonococcus, for instance, causes pharyngitis and proctitis, although it infects stratified squamous epithelium less readily than columnar epithelium. As described more fully in Chapter 31, calculations regarding the number of infected secondary cases resulting from each primary STD case depends on a variety of behavioural factors since the number of sexual partners acquired by a given individual, i.e. the level of promiscuity, varies considerably. Those who have many sexual partners are both more likely to acquire and to transmit infection and play a key role in the persistence of such infections in the community of sexually active individuals. People with many sexual partners are therefore an obvious target for treatment and education about safer sex practices (e.g. condom use, etc.)


Syphilis is caused by the spirochete Treponema pallidum

Treponema pallidum is closely related to the treponemes that cause the non-venereal infections of pinta and yaws (Table 21.3; Fig. 21.1). T. pallidum has a worldwide distribution, and syphilis remains a serious problem not only in resource-rich countries but especially in resource-poor areas, due to the serious sequelae and the risk of congenital infection. Although syphilis rates in the USA fell to an all-time low in 2000, the incidence has since increased with a 70% greater risk in men during the past 5    years. A similar trend has also been seen in the UK.

T. pallidum enters the body through minute abrasions on the skin or mucous membranes. Transmission of T. pallidum requires close personal contact because the organism does not survive well outside the body and is very sensitive to drying, heat and disinfectants. Horizontal spread (see Ch. 13) occurs through sexual contact, and vertical spread via transplacental infection of the fetus (see Ch. 23).

Local multiplication leads to plasma cell, polymorph and macrophage infiltration, with later endarteritis. The bacteria multiply very slowly, and the average incubation period is 3    weeks.

Classically, T. pallidum infection is divided into three stages

The three classical stages of syphilis are primary, secondary and tertiary syphilis (Table 21.4). However, not all patients go through all three stages; a substantial proportion remains permanently free of disease after suffering the primary or secondary stages of infection. The lesion of primary syphilis is illustrated in Figure 21.1. The secondary stage may be followed by a latent period of some 3–30    years, after which the disease may recur – the tertiary stage. Unlike most bacterial pathogens, T. pallidum can survive in the body for many years despite a vigorous immune response. It has been suggested that the healthy treponeme evades recognition and elimination by the host by maintaining a cell surface rich in lipid. This layer is antigenically unreactive and the antigens are only uncovered in dead and dying organisms when the host is then able to respond. Tissue damage is mostly due to the host response.

Table 21.4 The pathogenesis of syphilis

Stage of disease Signs and symptoms Pathogenesis
Initial contact
  Multiplication of treponemas at site of infection; associated host response
2–10    weeks (depends on inoculum size)
Primary chancrea at site of infection  
Primary syphilis
Enlarged inguinal nodes, spontaneous healing Proliferation of treponemas in regional lymph nodes
1–3    months
Secondary syphilis
2–6    weeks
Flu-like illness; myalgia, headache, fever; mucocutaneous rasha; spontaneous resolution Multiplication and production of lesion in lymph nodes, liver, joints, muscles, skin and mucous membranes
Latent syphilis
  Treponemas dormant in liver or spleen
3–30    years   Re-awakening and multiplication of treponemas
Tertiary syphilis Neurosyphilis; general paralysis of the insane, tabes dorsalis Further dissemination and invasion and host response (cell-mediated hypersensitivity)
  Cardiovascular syphilis; aortic lesions, heart failure  
  Progressive destructive disease Gummas in skin, bones, testis

A feature of Treponema pallidum infection is its chronic nature, which seems to involve a delicately balanced relationship between pathogen and host.

a Chancre: Initially a papule; forms a painless ulcer; heals without treatment within 2    months. Live treponemas can be seen in dark-ground microscopy of fluid from lesions; patient highly infectious.

Despite many years of effort, T. pallidum still cannot be cultivated in the laboratory in artificial media. It has therefore been difficult to study possible virulence factors at a molecular level, although a variety of genes have been cloned, the entire chromosome has been sequenced, and major proteins have been characterized.

Laboratory diagnosis of syphilis

As T. pallidum cannot be grown in vitro, laboratory diagnosis hinges on microscopy and serology.

Non-specific tests (non-treponemal tests) for syphilis are the VDRL and RPR tests

The term non-specific is used because the antigens are not treponemal in origin, but are from extracts of normal mammalian tissues. Cardiolipin, from beef heart, allows the detection of anti-lipid IgG and IgM formed in the patient in response to lipoidal material released from cells damaged by the infection, as well as to lipids in the surface of T. pallidum. The two tests in common use today are:

Both are available in kit form.

Non-specific tests show up as positive within 4–6    weeks of infection (or 1–2    weeks after the primary chancre appears) and decline in positivity in tertiary syphilis or after effective antibiotic treatment of primary or secondary disease. Therefore, these tests are useful for screening. However, they are non-specific and may give positive results in conditions other than syphilis (biologic false positives, Table 21.5). All positive results should therefore be confirmed by a specific test. However, treatment (e.g. especially during the primary and secondary stages) tends to result in seroreversion to these tests. Thus, with confirmed disease (see below), these tests can provide at least an indication of therapeutic efficacy.

Table 21.5 Serologic tests for syphilis and conditions associated with false-positive results

Test Conditions associated with false-positive results
Non-specific (non-treponemal)
Viral infection, collagen vascular disease, acute febrile disease, post-immunization, pregnancy. leprosy, malaria, drug misuse
Specific (non-treponemal)
Diseases associated with increased or abnormal globulins, lupus erythematosus, Lyme disease, autoimmune disease, diabetes mellitus, alcoholic cirrhosis, viral infections, drug misuse, and pregnancy

FTA-ABS, fluorescent treponemal antibody absorption test; MHA-TP, microhaemagglutination assay for T. pallidum; RPR, rapid plasma reagin test; TPHA, T. pallidum haemagglutination test; TP-PA, T. pallidum particle agglutination test; VDRL, Venereal Disease Research Laboratory test.


The gonococcus has special mechanisms to attach itself to mucosal cells

The usual site of entry of gonococci into the body is via the vagina or the urethral mucosa of the penis, but other sexual practices may result in the deposition of organisms in the throat or on the rectal mucosa. Special adhesive mechanisms (Fig. 21.3) prevent the bacteria from being washed away by urine or vaginal discharges. Following attachment, the gonococci rapidly multiply and spread through the cervix in women, and up the urethra in men. Spread is facilitated by various virulence factors (Fig. 21.3), although the organisms do not possess flagella and are non-motile. Production of an IgA protease helps to protect them from the host’s secretory antibodies.

Gonorrhoea is initially asymptomatic in many women, but can later cause infertility

Symptoms develop within 2–7    days of infection and are characterized:

At least 50% of all infected women have only mild symptoms or are completely asymptomatic. They do not therefore seek treatment and will continue to infect others. Asymptomatic infection, however, is not the usual course of events in men. Women may not be alerted to their infection unless or until complications arise, such as:

Ophthalmia neonatorum is characterized by a sticky discharge (see Fig. 23.5).

Gonococcal infection of the throat may result in a sore throat (see Ch. 18), and infection of the rectum also results in a purulent discharge.

In men, local complications of urethral infection are rare (Fig. 21.5). Invasive gonococcal disease is much more common in infected women than in men, but prompt treatment is important in containing local infection. The common occurrence of asymptomatic infection in women is an important factor in the occurrence of complications (i.e. the infection is unrecognized and untreated). In 10–20% of untreated women, infection spreads up the genital tract to cause pelvic inflammatory disease (PID) and damage to the fallopian tubes.

Disseminated infection occurs in 1–3% of women, but is less common in men (see above and Fig. 21.6). It is a function not only of the strain of gonococcus (see above), but also host factors (e.g. about 5% of people with disseminated infection have deficiencies in the late-acting components of complement (C5–C8)).

A diagnosis of gonorrhoea is made from microscopy and culture of appropriate specimens

Urethral and vaginal discharges and other specimens where indicated are used for microscopy and culture. Although a purulent discharge is characteristic of local gonococcal infection, it is not possible to distinguish reliably between gonococcal discharge and that caused by other pathogens such as Chlamydia trachomatis on clinical examination.

With experience, the finding of Gram-negative intracellular diplococci in a smear of urethral discharge from a symptomatic male patient is a highly sensitive and specific test for the diagnosis of gonorrhoea.

Culture is essential in the investigation of infection in women and asymptomatic men, and for specimens taken from sites other than the urethra. Specimens from symptomatic men should also be cultured:

Because of the organism’s sensitivity to drying, cultures should be made on warmed selective (i.e. modified Thayer Martin) and non-selective (chocolate blood agar) medium to insure recovery. Inoculation into appropriate transport medium is required if transfer to the laboratory will be delayed (no more than 48    h). Blood cultures should be collected if disseminated disease is suspected, and joint aspirates may yield positive cultures.

Serologic tests are unsatisfactory. Commercial nucleic acid-based approaches (specific probes, amplification, etc.) are now available, providing reliable results within a few hours.

Antibacterials used to treat gonorrhoea are cefixime or ceftriaxone

The antibacterial agents of choice are shown in Table 21.1. Penicillinase-producing N. gonorrhoeae were first observed in 1976 with increasing resistance that has severely compromised the effective treatment of gonorrhoea in many parts of the world, especially SE Asia. Resistance to fluoroquinolones has also occurred. Since patients with gonorrhoea may also be infected with chlamydia (see below), treatment regimens often include a combination of agents targeting both organisms (e.g. ceftriaxone and doxycycline, respectively). Early treatment of a significant proportion of sexually promiscuous patients achieves a striking reduction in the duration of infectiousness and transmission rates. Prophylactic use of antibacterials has no effect in preventing sexually-acquired gonorrhoea, but the application of antibacterial eye drops to babies born to mothers with gonorrhoea or suspected gonorrhoea is effective. Infection can be prevented by the use of condoms.

Follow-up of patients and contact tracing are vital to control the spread of gonorrhoea. At present, effective vaccines are not available, but the possibility of using some of the pilus proteins or other outer membrane components of the gonococcal cell as antigens has been under investigation. However, immunization may prevent symptomatic disease without preventing infection, and the dangers of asymptomatic infection have been discussed above.

Repeated infections can occur with strains of bacteria with different pilin proteins (e.g. antigenic variation; see Ch. 16).

Chlamydial infection

C. trachomatis serotypes D–K cause sexually transmitted genital infections

The chlamydiae are very small bacteria that are obligate intracellular parasites. They have a more complicated life cycle than free-living bacteria because they can exist in different forms:

Traditionally, three species of Chlamydia were recognized: C. trachomatis, C. psittaci and C. pneumoniae. However, the latter two have been moved to the genus, Chlamydophila (Table 21.6). Chlamydophila psittaci and Chlamydophila pneumoniae infect the respiratory tract and have been discussed in Chapter 19. The species Chlamydia trachomatis can be subdivided into different serotypes (also known as serovars) and these have been shown to be linked characteristically with different infections:

C. trachomatis serotypes D–K have a worldwide distribution, whereas the distribution of LGV serotypes is more restricted.

Table 21.7 Clinical syndromes and complications caused by C. trachomatis, serotypes D–K

Infection in Clinical syndromes Complications
Men Urethritis, epididymitis, proctitis, conjunctivitis Systemic spread, Reiter’s syndromea
Women Urethritis, cervicitis, bartholinitis, salpingitis, conjunctivitis Ectopic pregnancy, infertility, systemic spread: perihepatitis arthritis dermatitis
Neonates Conjunctivitis Interstitial pneumonitis

a Urethritis, conjunctivitis, polyarthritis, mucocutaneous lesions.

The majority of infections are genital and are acquired during sexual intercourse. Asymptomatic infection is common, especially in women. Ocular infections in adults are probably acquired by autoinoculation from infected genitalia or by ocular–genital contact. Ocular infections in neonates are acquired during passage through an infected maternal birth canal, and the infant is also at risk of developing C. trachomatis pneumonia (see Ch. 19).

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Jul 9, 2017 | Posted by in MICROBIOLOGY | Comments Off on Sexually transmitted infections

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