Bacterial Sexually Transmitted Infections

1. Bacterial Sexually Transmitted Infections

2. Gonorrhoea

3. Clinical and epidemiological aspects • 2nd commonest bacterial STI • 2004: 22,335 cases reported to HPA • Most common age groups: males 20-24 females 16-19 • Males: usually symptomatic • Females: often asymptomatic • Complications: untreated females – PID, infertility, ectopic pregnancy

8. Symptoms • Males: urethral discharge, severe burning on urination • Rectal infection gives rise to pain and discharge • Females: vaginal discharge, yellow or blood-stained, pain on urination

9. Both sexes: disseminated infection on rare occasions – septic arthritis, pustular rash, even infective endocarditis • Infection during pregnancy ophthalmia neonatorum of baby (conjunctivitis) • Dual genital infection with Chlamydia trachomatis – usual to treat for both at time of gonorrhoea diagnosis

10. Microbiological aspects • The causative organism is Neisseria gonorrhoeae, a Gram-negative diplococcus. The genus Neisseria contains one other pathogenic species, N. meningitidis, which is the principle cause of bacterial meningitis. Approximately 1% of cases of clinical gonorrhoea are caused by N. meningitidis, which may in such circumstances behave as a sexually transmitted infection.

11. N. gonorrhoeae is phagocytosed by polymorphonuclear neutrophils (pus cells) but resists intracellular destruction, remaining intact within the pus cell. • It is readily cultivable, although it is sensitive to desiccation and requires aerobic incubation with 5 to 10% carbon dioxide for growth. It prefers a slightly lower temperature than most pathogenic bacteria, growing best at around 36ºC (range 33 to 38ºC). It grows as a small colony, often requiring 48 hours’ incubation for a primary culture. The colonies are grey, shiny, often with an irregular edge and showing colonial variation suggestive of a mixed culture. The organism is catalase positive and rapidly oxidase positive. • No protective antibody response to gonorrhoea: recurrent infections are common in people who are at risk.

12. DiagnosticTests for Gonorrhoea • For urethral, cervical and rectal infections, microscopy is a very useful investigation • Gram-negative diplococci, with a coffee bean shape, are looked for within poymorphonuclear neutrophils (PMN) • For pharyngeal infections, microscopy is of no value because of the presence of commensal Gram-negative diplococci in the throat

13. Intracellular, Gram-negative diplococci - N. gonorrhoeae

14. Culture is mandatory - for identification and antibiotic sensitivity tests • Selective medium containing antibiotics and growth supplements • Thayer Martin or New York City • PCR tests have been developed for the detection of N. gonorrhoeae infection and a single swab may be used in a double test to detect N. gonorrhoeae and Chlamydia trachomatis.

15. Identification Tests • Oxidase test • Gram stain • Phadebact GC – uses monoclonal antibody • API NH – utilizes carbohydrates plus enzymes as a dual identification scheme

16. Treatment The recommended treatment of gonorrhoea is either ceftriaxone (injectable) or cefixime (oral). As yet, no resistance has been reported to these third generation cephalosporins. In either case, a single dose is all that is necessary for the treatment of non-disseminated gonorrhoea

17. ChlamydiaClinical and epidemiological aspects • The most common bacterial sexually transmitted infection, with 104,155 cases reported to the Health Protection Agency in 2004 • The causative organism is Chlamydia trachomatis • The number of cases has risen steadily since the mid 1990s

20. The infection has a longer incubation period than gonorrhoea, of 1 to 3 weeks • Asymptomatic infection is common in both sexes – at least 50% in males and 70% in females • The highest rates of infection occur in young people under the age of 24

21. Signs and symptoms Females: • unusual vaginal discharge • bleeding (intramenstrual) • pain on urination • lower abdominal pain Males: • urethral discharge • burning and itching in genital area • pain on urination • epididymitis • Reiter’s Syndrome

22. In some cases the symptoms subside after a few days • In either sex, complications may ensue in the case of untreated infection • In males, untreated infection may lead to epididymitis and Reiter’s Syndrome (arthritis) • In females, the consequences of untreated infection are pelvic inflammatory disease (PID) in 10 to 40% of cases

23. In up to 20% of patients with PID, infertility develops and the risk of ectopic pregnancy increases • The risk of infertility also increases if there has been more than one episode of PID • Infection in pregnancy can lead to infection of the baby - trachoma inclusion conjunctivitis or pneumonia

24. Two other species of Chlamydia are known to be pathogenic for humans – C. pneumoniae is a cause of pneumonia and one of the agents of “atypical pneumonia” C. psittaci is a respiratory pathogen in psittacine birds, such as parrots. The infection (a zoonosis) is transmissible to man, and may cause a severe pneumonia

25. Life cycle 1 • obligate intracellular bacterial pathogen • all chlamydiae undergo a similar life cycle within the cell they are infecting Elementary Bodies • the infective form of Chlamydia is the Elementary Body (EB), a dense, circular body, about 0.3μm in diameter. EBs are fairly inert and can survive outside the cell

26. Life cycle 2 Attachment • EBs carry glycosaminoglycan molecules on their surfaces that bind to receptors on the surface of certain cells • after attachment, the EB is taken into the cell by endocytosis and remains inside the endocytotic vacuole for the next phase of the life cycle

27. Life cycle 3 Reticulate Body Formation • the EB develops into a Reticulate Body (RB) which is larger (0.5 to 1.0μm) and metabolically active, although it uses host cell ATP-generating systems • inside the vacuole, the RB grows and replicates its DNA • during this phase, the contents of the vacuole are termed an “Inclusion Body”

28. Staining of the Inclusion Body with iodine todemonstrateinfection of cellcultures Life cycle 4

29. EB Formation and Release after 18 to 24 hours,the RB reorganisesinto many Ebswhich are releasedon cell rupture(24 to 48 hoursafter infection) Life cycle 5

30. Chlamydia trachomatis • Many different serotypes and these can be grouped according to the type of disease that they cause • Serotypes A, B and C cause a serious eye infection that begins with conjunctivitis and may progress (particularly with repeated infection) to conjunctival scarring and blindness – trachoma • Serotypes D to K cause a less severe form of conjunctivitis that does not usually result in trachoma

31. Trachoma • very common in tropical countries and when sufferers don’t get treated for the initial infection • transmitted via handsetc. and via flies

32. C.trachomatis STIs The more common type of infection associated with D to K is sexually transmitted: • NGU (non-gonococcal urethritis) in males (also called NSU: non-specific urethritis) • urethritis, cervicitis, salpingitis in females • can lead to PID (pelvic inflammatory disease) and resulting infertility due to scarring of Fallopian tubes • also increased risk of ectopic pregnancy

33. Lymphogranuloma venereum • Serotypes L1, L2 and L3 cause LGV (lymhogranuloma venereum) • begins with a genital ulcer,next inguinal lymph nodesenlarge and break down,discharging pus • if untreated, can lead toenlargement &granulomatoushypertrophy of glands

34. Diagnosis of Chlamydial Infection • Direct immunofluorescence using monoclonal antibodies • Culture in cycloheximide-treated McCoy cells – detection of inclusion bodies by iodine staining or IF • ELISA for chlamydial antigen detection • Nucleic acid amplification tests (NAAT): polymerase chain reaction (PCR) ligase chain reaction (LCR) strand displacement amplification (SDA) transcription mediated amplification (TMA) For descriptions, please see: www.chlamydiae.com/diagnostics_index.asp

35. Syphilis

36. Clinical aspects • Caused by the spirochaete bacterium, Treponema pallidum ssp pallidum • Highly infectious • Starts with the development of one or more ulcers at the point of entry of the organism – CHANCRE • A chancre is the lesion of primary syphilis • Typically painless

37. Appears up to 3 weeks post exposure • Heals in 2 to 6 weeks • If untreated, 40% of patients go on to develop secondary syphilis • 2º syphilis develops 2-6 weeks after appearance of a chancre • Rash including palms/soles, lymphadenopathy, flu-like symptoms • If still untreated, 2º syphilis may be followed by tertiary syphilis

38. Tertiary syphilis develops 4 or more years after untreated primary syphilis • Tertiary syphilis(late syphilis) may affect many parts of the body • Characterized by slow growing granulomatous lesions which affect the nervous system, leading to general paralysis of the insane and demyelination of the spinal cord resulting in pains, loss of feeling and difficulty walking. Changes in the joint - so-called Charcot's joints may develop owing to loss of nerve supply. Dementia may occur. Very rarely changes in the aorta may result in an aneurysm.

39. The other 60% of untreated cases will develop latent syphilis • Latent syphilis may reactivate at any time to give rise to symptoms of later stages of syphilis • If infection is acquired in pregnancy, usually miscarriage or still-birth ensues. However, if the foetus survives, it may show signs of congenital syphilis: the Hutchinson’s Triad – Hutchinson’s teeth (pointed), deafness & keratitis

40. There is a statutory requirement to test all pregnant women for anti-treponemal antibodies, so as to reduce the likelihood of congenital syphilis. • Syphilis is a potentially devastating disease that is easy to treat, but it is essential that it is caught in the early stages. Treatment of later stages of the disease will halt its progress but not reverse any damage that has already occurred.

42. There are other treponemal diseases, known as non-venereal treponematoses, which have to be born in mind when interpreting diagnostic tests for antibody. These are yaws, bejel and pinta. They are not endemic in the UK, but yaws is a common infection of childhood in parts of Africa and the West Indies.

43. Treatment of syphilis • Benzathine penicillin, given by intramuscular injection, is the first line treatment for syphilis. A single dose is sufficient to cure primary syphilis, although longer treatments are required for later stages, including the treatment of late latent syphilis. • Alternative drugs for penicillin-hypersensitive patients are ceftriaxone (injection) or doxycycline (oral).

44. Epidemiology of syphilis • In 2004 there were 2,254 cases of syphilis diagnosed in sexual health clinics in the UK • Most common in males aged 20-24 years, females aged 25-34 years • Syphilis was most prevalent during the late 1940s, but a resurgence occurred around the beginning of this century

49. MicrobiologicalAspects • Treponema pallidum ssp pallidum is a very long, slender bacterium, which is about 0.1μm in diameter and 22μm in length • Since the maximum resolution of a bright-field microscope is 0.2μm, the organism cannot be seen in a Gram-stained slide • Cannot be grown in artificial culture

50. Treponema pallidum ssp pallidum(electron micrograph)