Lecture 3 Sexually Transmitted Diseases Nisseria gonorrheae

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1 Al Balqa App[lied University College of Medicine Lecture 3 Sexually Transmitted Diseases Nisseria gonorrheae Dr. Hala Al Daghistani Sexually Transmitted Diseases could be Exudative (Gonorrhea, Chlamydia) Ulcerative (Syphilis, Chancroid, Genital herpes) Other (HIV, Human Papillomavirus (HPV) Routes of infection Intimate person-to-person sexual contact Mother to child during pregnancy and childbirth Through blood products and tissue transfer Urethritis Urethritis is the most common STD syndrome recognized in men and is often seen in women with cervicitis. Acute infection with dysuria and urethral discharge within 2 to 7 days Urethritis can be caused by Mechanical injury (catheterization) Chemical irritation (antiseptics) Infectious disease. Infectious urethritis is more commonly associated with organisms that cause sexually transmitted disease, such as Neisseria gonorrhoeaeandchlamydia trachomatis. In male, cases can be divided into two types based on its causation A. Gonococcal urethritis (GU) B. Nongonococcal urethritis (NGU).

2 Common risk factors for development of disease Beginning sexual activity at an early age Engaging in high-risk sexual behaviors Having a history of sexually transmitted diseases Having multiple sex partners. Neisseria gonorrhoeae The family Neisseriaceae includes the genera Neisseriaand other genus. The neisseriae are gram-negative cocci that usually occur in pairs (diplococci), are pathogenic for humans and typically are found associated with or inside PMN cells. The Neisseriae are: 1) Human pathogens - Neisseria gonorrhea (gonococcus) cause genital infection. - Neisseria meningitidis (meningococcus) cause acute meningitisor subacute septicemia with petechial rash. 2)Non pathogenic: - Neisseria sicca - Neisseria subflava - Neisseria lactamica - Neisseria mucosa These are normal inhabitants of human respiratory tract. Epidemiology Gonorrhea is second only to chlamydia as the most commonly reported STD in the U.S.

3 Transmission may occur from infected urethral, cervical, rectal and pharyngeal surfaces. The incubation period is 1 to 14 days, but usually 2 to 5 days. Transmission from male to female after one exposure is 50-70%, whereas transmission from female to male is 20%. Recurrent infection is common. Pelvic inflammatory disease due to gonorrhea is an enormous public health problem leading to infertility and ectopic pregnancy. Asymptomatic carriage is more common in women than in men. Morphology and identification A. Typical Organisms A non-motile diplococcus, kidney shaped; when the organisms occur in pairs, the flat or concave sides are adjacent. B. Culture - cultured on enriched media (MTM, Martin-Lewis, and NYC) - Gonococci are transparent or opaque, non-pigmented, and non-hemolytic. C. Growth Characteristics - The neisseriae grow best under aerobic conditions, but some grow in an anaerobic environment. They have complex growth requirements. - Most neisseriae oxidize carbohydrates, producing acid but not gas.gonococci oxidize only glucose - The neisseriae produce oxidase and give positive oxidase reactions - Gonococci grow best on media containing heated blood, hemin, and animal proteins, and 5% CO 2. - The organisms are rapidly killed by drying, sunlight, moist heat, and many disinfectants. - They produce autolytic enzymes that result in rapid lysis in vitro at 25 C and at an alkaline ph. Virulence factors Pili:Gonococci have many pili on their surface that extend through the peptidoglycan and outermembrane. Pili are composed of repeating protein subunits (pilins), whose expression iscontrolled by the pil gene complex. Pili are responsible for tight binding of the bacteria to nonciliated mucosal cells. The tight binding prevents the gonococci from being washed away byvaginal discharge or urine. The presence of pili has also been shown to inhibit phagocytosis byneutrophils. The pilins of almost all strains of N gonorrhoeae are antigenically different, and a single strain can make many antigenically distinct forms of pilin.

4 - Opa Proteins. These proteins function in adhesion of gonococci within colonies and in attachment of gonococci to host cell receptors. A strain of gonococcus can express different types of Opa. - Por protein extends through the gonococcal cell membrane. It occurs in trimers to form pores in the surface. Gonococcus expresses two types of Por (A, and B), and the Por of different strains is antigenically different. 18 serovars of PorA and 28 serovars of PorB. - RMP(protein III) - reduction modifiable protein)is associates with Por in the formation of pores in the cell surface. - Lipooligosaccharide: gonococcal (LPS) does not have long O-antigen side chains and is called a lipooligosaccharide. Gonococci can express more than one antigenically different LOS chain ( 8). LOS causes ciliary loss and mucosal cell death (in fallopian tube models). - TheFbp (ferric-binding protein), expressed when the available iron supply is limited - Gonococci elaborate an IgA1 protease that splits and inactivates IgA1, a major mucosal immunoglobulin of humans. Genetics and Antigenic Heterogeneity Frequent changes in antigens are one of the most prominent features of N. gonorrhoeae. A single clone of N. gonorrhoeae can give rise to variants expressing different antigenic forms of both pili and Opa proteins, due to multiple copies of the pilin and Opa genes in the Neisseria chromosome. This antigenic variation helps the organism survive the host immune response. Antibodies specific for one form of pilin or Opa protein are not effective against another form. Each isolate of the gonococcus may have a unique antigen profile allowing the organism to reinfect a host repeatedly.gonococci have evolved mechanisms for frequently switching from one antigenic form (pilin, Opa, or LOS) to another antigenic form of the same molecule. Because pilin, Opa, and LOS are surface-exposed antigens on gonococci, they are important in the immune response to infection. Gonococci attack mucous membranes of the genitourinarytract, eye, rectum, and throat, producing acute suppuration that may lead to tissue invasion; this is followedby chronic inflammation and fibrosis.

5 Men usually haveurethritis, with yellow, creamy pus and painful urination.the process may extend to the epididymis. As suppuration subsides in untreated infection, fibrosis occurs. In Women, the primary infection is in the endocervix and extends to the urethra and vagina, giving rise to mucopurulent discharge. It may then progress to the uterine tubes, causing salpingitis, fibrosis, and obliteration of the tubes. Infertility occurs in 20% of women with gonococcal salpingitis. Chronic gonococcal cervicitis and proctitis are often asymptomatic. Gonococcal bacteremia leads to skin lesions (especiallyhemorrhagic papules and pustules) on the hands, forearms,feet, and legs and to tenosynovitis(inflammation of a tendon and its enveloping sheath) and suppurative arthritis. Gonococcal endocarditis is anuncommon but severe infection. Gonococci sometimes cause meningitis and eye infections in adults; these have manifestations similar to those caused by meningococci. Gonococcal Ophthalmia Neonatorum, an infection ofthe eye in newborns, is acquired during passage through aninfected birth canal. The initial conjunctivitis rapidly progresses and, if untreated, results in blindness. Rectal infection/proctitis can occur in both men and women. In men rectal gonorrhea is common among men who have sex with men. In women, rectal infection can occur from contamination of the rectum by infected vaginal secretions or by rectal intercourse. Symptoms include anal irritation, painful defecation, bleeding, cramping, constipation and mucopurulent rectal discharge. Many patients with rectal infection are asymptomatic. Pharyngeal infection results from orogenital contact and is usually asymptomatic, but can causeexudative pharyngitis and cervical adenitis, and can be a source of further transmission.

6 Disseminated gonococcal infection DGI results from gonococcal bacteremia and occurs in 1-3% of infected patients. Symptoms include fever, skin lesions (pustules,hemorrhagic, or necroticon an erythematous base), located mostly on the extremities), oligoarthritis (inflammation of a few joints, most commonly knee, also elbows, ankles, wrists, small joints of hands and feet), and polyarthralgias (joint pain). This presentation is called the Arthritis-Dermatitis Syndrome. A. Specimens Pus and secretions are taken from the urethra, cervix, rectum, conjunctiva, throat, or synovial fluid for culture and smear. Blood culture is necessary in systemic illness, but a special cultural system is helpful because gonococci (and meningococci) may be susceptible to the polyanethol sulfonate present in standard blood culture media. B. Smears Gram-stained smears of urethral or endocervical exudates reveal many diplococci within pus cells. Stained smears of the urethral exudates from men have a high sensitivity Stained smears of conjunctival exudates can also be diagnostic Specimens from the throat or rectum are generally not helpful. C. Culture D. Nucleic Acid Amplification Tests E. Serology

7 In infected individuals, antibodies to gonococcal pili and outer membrane proteins can be detected by immunoblotting, radioimmunoassay, and ELISA (enzyme- linked immunosorbent assay) tests. Immunity Repeated gonococcal infections are common. Protective immunity to reinfection does not appear to develop because of the antigenic variety of gonococci. Epidemiology, Prevention, and Control Gonorrhea is exclusively transmitted by sexual contact, often by women and men with asymptomatic infections.

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