Normal flora and the natural defences of the genitourinary tract
Our understanding of the vaginal microbiome, its composition, structure and function has significantly broadened over the last decade due to the cultivation-independent methods based on the analysis of 16S ribosomal RNA (rRNA) and next-generation sequencing (NGS) technology.
Akin to the oral microbiome, the vaginal microbiome and the constituent microbiota form a mutually beneficial relationship with their host and have major impact on health and disease.
In asymptomatic, otherwise healthy adult women, a complex microbial community exists, but the predominant species belong to the genus Lactobacillus. They keep the vaginal pH low and appear to prevent the growth of potential pathogens. For instance, their suppression by antibiotics may lead to overgrowth of the yeast Candida albicans found in relatively low numbers in the healthy vagina.
Other common groups of vaginal organisms include diphtheroids, streptococci, coliforms and a diverse array of anaerobes. Approximately 20% of women of child-bearing age carry group B P-haemolytic streptococci in the vagina. These may be acquired by the neonate during its passage through the birth canal, resulting in serious infections such as meningitis and sepsis.
The urine in the bladder is normally sterile, but the voided urine often becomes contaminated by flora from the distal portions of the urethra, such as Staphylococcus epidermidis, coli- forms, diphtheroids and streptococci. Additionally, in females, the organisms present in the distal part of the urethra may include contaminants from the gut flora such as enterobacteria and lactobacilli. The flushing action of the urine is arguably the most important defence factor of the urethra in both males and females. Bactericidal mechanisms in the bladder mucosa, including local antibody response and lysozyme, play an important role in preventing ascending infection of the urinary tract.
Important pathogens
Important pathogens are listed in Fig. 27.1 and Table 27.1.
Sexually transmitted infections
More than one million sexually transmitted infections (STIs) are acquired every day worldwide. They are essentially transmitted by sexual intercourse and may affect both heterosexual and homosexual partners. Varying patterns of sexual behaviour can result in such infections manifesting in the oral cavity, oropharynx and the rectum; STIs frequently—but not invariably—produce genital lesions; several produce severe systemic disease that may even lead to death, such as human immunodeficiency virus (HIV) infection and hepatitis B.
Gonorrhoea
Gonorrhoea is caused by Neisseria gonorrhoeae (the gonococcus).
Clinical features
In women: acute urethritis, increased vaginal secretions with purulent discharge. In men: acute gonococcal urethritis with severe dysuria and purulent discharge. The disease may involve the rectum and oropharynx. Pharyngitis, sore throat, tonsillitis and gingivitis may occur because of gonococcal infection, especially from orogenital contact in homosexual men. Asymptomatic infection is common in both men and women. Complications include prostatitis, salpingitis and occasionally haematogenous spread, causing arthritis, septicaemia and meningitis.
Pathogenesis and epidemiology
Gonococcal infection has been reported only in humans. The infection is limited to the mucosa of the anterior urethra in men and the cervix of women. In the newborn, gonococcal conjunctivitis may occur due to cross infection from the mother's birth canal.
Fig. 27.1 Major infectious agents of the genitourinary tract.
Three virulence factors have been identified:
1. an endotoxin that inhibits the ciliary activity of the fallopian tubes and retards the expulsion of the gonococcus
2. an enzyme that destroys the protective immunoglobulins (secretory IgA) of the mucosa
3. β-lactamase is produced by some strains; for example, penicillinase-producing N. gonorrhoeae (PPNG).
Diagnosis
Gram smears show Gram-negative pairs of the typical kidney-shaped gonococci inside neutrophils (Fig. 27.2). Swabs from the urethra cultured on lysed blood or chocolate agar yield oxidase-positive, translucent colonies, and rapid carbohydrate utilization tests are also diagnostic (see Chapter 14).
Treatment
A choice of antibiotics is available: a large, single, curative oral dose of amoxicillin (with probenecid to delay renal excretion); ceftriaxone; spectinomycin (for P-lactamase-positive gonococci); or erythromycin (children or pregnant women).
Non-specific urethritis
One of the most common sexually transmitted diseases, nonspecific urethritis is seen more in men than in women. It is caused by more than one agent, but Chlamydia trachomatis is the most common cause. A mycoplasmal organism ('bacteria' without a cell wall), Ureaplasma urealyticum, may also cause significant morbidity.
Clinical features
Acute purulent urethral discharge resembles that of gonorrhoea; cervicitis occurs in women.
Diagnosis
Smears and swabs of urethral or cervical discharge are diagnostic. Culture is now rarely done. Smears are examined for intracytoplasmic inclusions by immunofluorescence. Serology for chlamydial antigens by indirect immunofluorescence with monoclonal antibody or by enzyme-linked immunosorbent assay (ELISA).
Treatment
Tetracycline is given for up to 10 days; relapses are common owing to the diverse aetiology of the disease.
Syphilis
The incidence of syphilis worldwide has increased in recent years, and in 2016, the figure was estimated to be 13 million worldwide and some 70 000 new cases were reported in the USA.
Syphilis is one of the classic diseases with protean manifestations (i.e., affecting virtually all organ systems of the body), and has re-emerged as an important disease associated with
Table 27.1 Sexually transmitted diseases
|
Disease |
Agent |
|
Bacterial infections |
|
|
Gonorrhoea |
Neisseria gonorrhoeae (the |
|
gonococcus) |
|
|
Syphilis |
Treponema pallidum |
|
Vaginitis |
Gardnerella vaginalis, anaerobes |
|
Chancroid |
Haemophilus ducreyi |
|
Viral infections |
|
|
Genital herpes |
Herpes simplex virus (type 2 mainly) |
|
Genital warts |
Papillomavirus |
|
Hepatitis Ba |
Hepatitis B virus |
|
AIDS |
Human immunodeficiency virus (HIV) |
|
Others |
|
|
Lymphogranuloma |
Chlamydia trachomatis types L1-L3 |
|
venereum |
|
|
Granuloma inguinale |
Calymmatobacterium granulomatis |
|
(donovanosis) |
(a Klebsiella-like microorganism) |
|
Pubic lice (crabs) |
Pthirus pubis |
|
Genital scabies |
Sarcoptes scabiei |
|
Non-specific urethritis |
Chlamydia trachomatis types D-K |
|
Trichomoniasis |
Trichomonas vaginalis |
|
Vaginal thrush |
Candida albicans |
|
aNot always sexually transmitted. |
|
HIV infection and sexual promiscuity. The disease, important due to its late and severe sequelae, is preventable, and treatable with effective and inexpensive antibiotics.
The disease is caused by Treponema pallidum, the syphilis spirochaete.
Clinical features
Syphilis has an incubation period of 10-90 days (average 3 weeks) and is characterized by four main clinical stages: primary, secondary, tertiary and late or quaternary (Fig. 27.3).
Primary syphilis
A painless red papule develops at the inoculation site of the spirochaete, some 3 weeks (range 9-90 days) after the contact;
Fig. 27.2 Smear of a urethral pus exudate in gonorrhoea showing polymorphs and intracellular Gram-negative gonococci.
Fig. 27.3 Natural history of untreated syphilis. *Approximate figures.
Fig. 27.4 Mucous patches (on the patient’s right) and a snail-track ulcer (left) of the oral mucosa in a patient with secondary syphilis.
Table 27.2 Serological tests for syphilis
|
Stage of disease |
VDRL |
TPHA |
FTA-Abs |
|
Primary |
+ or - |
- |
+ |
|
Late primary |
+ |
+ or - |
+ |
|
Secondary and tertiary |
+ |
+ |
+ |
|
Late (quaternary) |
+ |
+ |
+ |
|
Latent |
+ or - |
+ |
+ |
|
Treated syphilis |
- |
+ |
+ |
|
Congenital syphilis |
+ |
+ |
+ |
Note: The efficacy of treatment can be monitored by the VDRL test.
FTA-Abs, Fluorescent treponemal antibody-absorption test; TPHA, Treponema pallidum haemagglutination test; VDRL, Venereal Diseases Reference Laboratory.
this may be in the labia, vagina, cervix, penis or the oral mucosa. The papule then produces the chancre of primary syphilis: a flat, red, indurated, highly infectious ulcer with a serous exudate. Enlarged, painless regional lymphadenopathy is common. The chancre disappears spontaneously within 3-8 weeks.
Secondary syphilis
This stage is reached 6-8 weeks later and lasts for 1-3 months. A generalized mucocutaneous spread of the spirochaetes ensues at this stage and the lesions appear as papules on the skin and oral ulcers (see Chapter 35). The ulcers may coalesce to give the characteristic 'snail tracks' and mucous patches in about a third of those affected (Fig. 27.4). These lesions, like the primary chancre, are highly infectious. Other manifestations are generalized lymphadenopathy and condylomata (warts) of the anus and vulva; rarely, periostitis, arthritis and glomerulonephritis may be seen.
Tertiary syphilis
The most destructive phase of the disease occurs 3-10 years after primary syphilis. Lesions appear as characteristic gummata or granulomatous nodules of the skin, mucosa, bone and other internal organs. Gummata commonly break down to produce shallow, punched-out ulcers. In the oral cavity, gumma may rarely break down to produce palatal perforations, leading to oronasal fistulae. These lesions are not infective as the tissue damage is due to a delayed type of hypersensitivity reaction.
Late or quaternary syphilis
Occurs 10-20 years after primary syphilis. The two main clinical forms of late syphilis are cardiovascular syphilis and neurosyphilis, with resultant pathology of the aorta and the nervous system, respectively.
Latent syphilis
This may be seen in some after many years without any symptoms. The disease lies dormant without any clinical signs (except for positive serology) and may manifest as cardiovascular or neurosyphilis.
Congenital syphilis
Treponema pallidum is one of the few microorganisms that has the ability to cross the placental barrier; thus the foetus may be infected during the second or third trimester from a syphilitic mother (either in the primary or secondary stage of syphilis). The disease will manifest in the infant as:
■ latent infection: no symptoms but positive serology
■ early infection: lesions such as skin rashes, saddle nose, bone lesions and meningitis appear up to the end of the second year of age
■ late infection: after the second year of age: lesions include Hutchinson's incisors (notching of incisor teeth), mulberry molar teeth (due to infection of the enamel organ in the foetus), interstitial keratitis, bone sclerosis, arthritis, deafness.
Diagnosis
Direct microscopy
Spirochaetes in exudate from primary or secondary lesions are identified by dark-ground microscopy; now rarely done. Care should be taken to differentiate Treponema pallidum from commensal oral spirochaetes when oral lesions are examined. (Note: Treponema pallidum cannot be grown in laboratory media but can be propagated in the testes of rabbits.)
Serology
Antigens used for syphilis serology are of two types:
1. Cardiolipin or lipoidal antigen: although not derived from the spirochaete, it is sensitive for detecting antibody. The most popular test that uses this antibody is the Venereal Diseases Reference Laboratory (VDRL) test; it is simple and sensitive, but biological false-positive reactions are common. As the antibody disappears after treatment, it can be used to monitor the efficacy of antimicrobial therapy (Table 27.2).
2. Specific treponemal antigen: using Treponema pallidum as antigen gives fewer false-positive reactions and tests remain positive after treatment. The tests are Treponema pallidum haemagglutination test (TPHA), fluorescent treponemal antibody-absorption test (FTA-Abs), which detects both IgM and IgG antibody, and ELISA. The last is increasingly used as a screening test to detect IgG antibody, although some false positives may result.
The interpretation of syphilis serology is complex (because of the many medical conditions that yield false-positive reactions) and is not discussed here.
Recently, it has been shown that real-time polymerase chain reaction (PCR) is a fast, efficient and reliable test for the diagnosis of primary syphilis, but has no added value for the diagnosis of secondary syphilis.
Treatment
Penicillin (large doses, for up to 3 weeks) is the drug of choice. Erythromycin or tetracycline can be used if the patient is hypersensitive.
Notes on some common sexually transmitted diseases
HIV infection
This is a pandemic infection commonly transmitted by sexual intercourse and is also a disease of enormous importance for health care personnel (see Chapter 30).
Trichomoniasis
A common protozoal infection in women is caused by Trichomonas vaginalis. It is transmitted mainly by sexual intercourse: in men, the infection is often symptomless; in women, it manifests as a chronic vaginal infection ranging from a yellow, offensive discharge with vaginitis to symptomless or low-grade infection.
■ Diagnosis is by culture of swabs in special media or examination of direct smear for motile, flagellated protozoa
■ Treatment: metronidazole.
Candidiasis
Candidiasis is a yeast infection commonly transmitted by sexual intercourse; it is frequently seen in women but rare in men. Candida albicans is the most frequent causative yeast; the disease is characterized by white false membranes in the vulva and the vagina, which may be accompanied by a watery discharge; many cases are symptomless.
Diagnosis and treatment are as described in Chapter 22.
Herpes genitalis
Mainly due to herpes simplex type 2 virus, but as a result of sexual promiscuity, type 1 viruses (which are more or less confined to oral regions) are frequently implicated. The lesions are vesicular and painful, and seen in anogenital regions. The primary lesion, associated with fever and inguinal lymphadenopathy, is more protracted and painful than the secondary recurrences. Asymptomatic infection is common in both men and women; hence sexual spread of the disease is common.
Diagnosis and treatment are as described in Chapter 21.
Hepatitis B
See Chapter 29.
Control of sexually transmitted diseases
Although control is difficult, tracing of sexual partners of infected individuals is essential to prevent spread of disease in the community. Patients are requested to name consorts and the latter should submit themselves to examination and treatment. In the long term, prevention of sexually transmitted diseases, including HIV infection, is far more important in reducing health care costs of the community.
Urinary tract infections
Urinary tract infections are common, especially in women, despite the availability of a spectrum of antibiotics. They are defined as follows:
■ bacteriuria: multiplication of bacteria in urine within the renal tract (more than 105 organisms per millilitre of urine is considered to be significant bacteriuria, i.e., evidence of urinary tract infection)
■ pyuria: presence of pus cells (polymorphs) in urine
■ cystitis: infection of the bladder
■ pyelonephritis: infection of the pelvis and parenchyma of the kidney
■ urethritis: infection of the urethra.
Cystitis, pyelonephritis or urethritis may occur either singly or in combination.
Important pathogens
Causative agents are many and varied (see Fig. 27.1) but Escherichia coli is the most common, accounting for 60%-80% of infections. Some E. coli strains are more invasive than others, possibly as a result of the possession of capsular or K antigens, which inhibit phagocytosis, and their superior ability to adhere to the uroepithelium with the aid of the pili on cell surfaces. Other organisms that commonly cause infection include:
■ Staphylococcus saprophyticus: commonly seen in sexually active women under 25 years of age
■ Proteus mirabilis: causes about 10% of the infections
■ Klebsiella spp.: resistant to a number of antibiotics (multiple antibiotic resistant)
■ Staphylococcus aureus and Pseudomonas aeruginosa: seen after instrumentation or catheterization.
Note: acute urinary tract infection is mostly monomicrobial in origin, whereas polymicrobial infection with more than one organism is common in chronic infections.
Clinical features
Urinary tract infection is mainly a disease of women, with a male to female ratio of 1 : 10. Clinical features of cystitis include dysuria, urgency, suprapubic pain, increased frequency and haematuria. Fever, loin pain and tenderness are signs of pyelonephritis.
Laboratory diagnosis
■ Microscopy: wet films and Gram-stained films used for detection of red blood cells, polymorphs, bacteria and epithelial cells.
■ Culture: usually on nutrient agar and MacConkey's agar. As the number of organisms in the sample indicates the degree of infection, this can be assessed semiquantitatively by appropriate plating out.
Treatment
An array of oral antibiotics excreted in urine in high concentrations is available, including trimethoprim, co-trimoxazole, ciprofloxacin and nitrofurantoin. Therapy depends on the aetiological agent and its antibiotic-sensitivity pattern.
Dentistry and genitourinary infections
It is important that the dentist is aware of sexually transmitted diseases as many of them manifest in the oral cavity as a result of deviant sexual habits and the escalating sex industry in both developed and developing countries. Indeed, some would consider the oral cavity as a sexual organ. Furthermore, organisms that may cause sexually transmitted diseases (e.g., herpes, HIV infection) may have the propensity to be transmitted in the clinical setting, from the patient to the dentist, by direct contact or indirectly via contaminated instruments if appropriate infection control measures are not implemented.
Urinary tract infections are of no direct relevance to dentistry except insofar as patients are taking antibiotics, which may either affect the oral flora or, rarely, interact with drugs prescribed by the dentist. Indeed, the potential of metronidazole to kill anaerobic bacteria was first detected by an astute dentist who noted the resolution of acute ulcerative gingivitis in a patient under his care who was undergoing treatment for vaginal trichomonal infection with this drug (at that time prescribed solely as an antiprotozoal agent).
Key facts
• The predominant vaginal microbiota in adult women comprises lactobacilli; other microorganisms are diphtheroids, streptococci, anaerobes and coliforms.
• The urine in the bladder is normally sterile, but the voided urine often becomes contaminated with flora on the distal portions of the urethra.
• The flushing action of the urine is the most important defence factor of the urethra in both males and females.
• A large group of infections is transmitted by sexual intercourse (both heterosexual and homosexual), and varying patterns of sexual behaviour can result in infections manifesting in the oral cavity, oropharynx and the rectum.
• Gonorrhoea, caused by Neisseria gonorrhoeae (the gonococcus), causes acute urethritis with purulent discharge.
• Gonorrhoea may involve the rectum and oropharynx with resultant pharyngitis, sore throat, tonsillitis and gingivitis (especially from orogenital contact).
• Virulence factors of N. gonorrhoeae include an endotoxin, a protease that destroys secretory immunoglobulin A (IgA), and P-lactamase production in some (penicillinase-producing N. gonorrhoeae or PPNG).
• Syphilis caused by Treponema pallidum (syphilis spirochaete) is a classic disease with protean manifestations and is characterized by four main clinical stages.
In primary syphilis, chancre (a flat, red, indurated, highly infectious ulcer with a serous exudate) seen both on the oral and on the vaginal mucosae is the hallmark feature. Secondary syphilis is characterized by a generalized mucocutaneous spread of spirochaetes and lesions that appear as papules on the skin, and infectious oral ulcers (snail-track ulcers).
In tertiary syphilis, non-infective lesions appear as characteristic gummata or granulomatous nodules of the skin, mucosa, bone and other internal organs. I ntraorally, gummata may break down to produce palatal perforations, leading to oronasal fistulae.
The two main clinical forms of late or quaternary syphilis are cardiovascular syphilis and neurosyphilis.
Dental lesions in congenital syphilis include Hutchinson’s incisors (notching of incisor teeth) and mulberry molar teeth (due to infection of the enamel organ in the foetus).
Syphilis is mainly diagnosed by serology (Venereal Diseases Reference Laboratory (VDRL) test) with either the specific treponemal antigen or cardiolipin or lipoidal antigens. Causative agents of urinary tract infection are many, but Escherichia coli is the most common, accounting for 60%-80% of infections.
Review questions (answers on p. 366)
Please indicate which answers are true, and which are false.
27.1 Purulent urethral discharge in a sexually active male:
A. Is commonly of gonococcal origin
B. Should warrant investigations for other sexually transmitted diseases
C. Necessitates screening of the sexual partner/s
D. May not yield any organism in a Gram-stained smear
E. Is often associated with dysuria
27.2 In a healthy individual, which of the following anatomical loci are considered sterile?
A. Urinary bladder
B. Distal urethra
C. Vagina
D. Fallopian tubes
E. Ureters
27.3 The finding of Gram-negative intracellular diplococci in a direct smear from a throat swab:
A. Is indicative of gonococcal infection
B. Should be followed with culture and biochemical tests
C. May signify a sexually acquired infection
D. Needs empirical treatment with rifampicin
E. Indicates that the patient is at risk of developing meningitis
27.4 Genital ulcerations are seen in:
A. Gonorrhoea
B. Syphilis
C. Candidiasis
D. Genital herpes
E. Trichomoniasis
27.5 Oral manifestations of syphilis include:
A. Hutchinson's incisors in congenital syphilis
B. Snail-track ulcers in primary syphilis
C. Mulberry molars in tertiary syphilis
D. Chancre in secondary syphilis
E. Palatal perforation in tertiary syphilis
Further reading
Brooks, J. F., Carroll, K. C., Butel, J. S., et al. (Eds.). (2013). Neisseriae. In Jawetz, Melnick & Adelberg's medical microbiology (26th ed., pp. 285-293). New York: McGraw Hill. Chapter 20. [e-Book]
Brooks, J. F., Carroll, K. C., Butel, J. S., et al. (Eds.). (2013). Spirochetes and other spiral organisms. In Jawetz, Melnick & Adelberg's medical microbiology (26th ed., pp. 327-338). New York: McGraw Hill. Chapter 24. [e-Book]
Doherty, L., Fenton, K. A., Jones, J., et al. (2002). Syphilis: Old problem, new strategy. British Medical Journal, 325, 153-156.
Tramont, E. C. (2010). Treponema pallidum (syphilis). In G. L. Mandell, J. E. Bennett, R. Dolin, et al. (Eds.), Mandell, Douglas, and Bennett's principles and practice of infectious diseases (7th ed.). Amsterdam: Elsevier.