新細明體: Neisseria Dr.Gogoi, University of Fiji Arial: Neisseria German physician A. L. S. Neisser, who originally described the organism response for gonorrhea Calibri: Neisseria gonorrhoeae Neisseria meningitidis Important Human Pathogens Other species normally colonize mucosal surfaces of oropharynx and nasopharynx and occasionally anogenital mucosal membranes. These species have limited virulence and generally produce disease only in compromised patients. Comic Sans MS: Neisseria N. gonorrhoeae (gonococcus): gonorrhea N. meningitidis : meningitis Gram-negative cocci (kidney-shaped), usually in pairs. Human pathogens (i.e. N. gonorrhoeae and N. meningitidis ) are typically found associated with or inside PMN cells . They are able to multiply inside the phagocytes, epithelial and endothelial cells. Morphology and Identification www.buddycom.com Verdana: Morphology and Identification Both meningococci and gonococci are encapsulated: menigococci have a polysaccharide capsule ; gonococci have a loose capsule-like structure. Grow best under aerobic conditions Produce cytochrome oxidase (oxidase-positive). Meningococci and gonococci grow best in medium containing complex organic substances (e.g. blood, hemin, and animal proteins), and in a humid atmosphere containing 5% CO 2 . Meningococci and gonococci are rapidly killed by drying, sunlight, moist heat and many disinfectants. Poor survival at cooler temperature. 預設簡報設計: N. gonorrhoeae (Gonococcus) 1. Pili: enhancing attachment to host cells and resistance to phagocytosis; antigenically different among strains, and a single strain can make many antigenically distinct forms of pilin. 2. Por proteins: form porins and mediate resistance to neutrophil and serum killing. 3. Opa: associated with opaque colonies ; an outer membrane protein functioning in attachment to host cells. 4. Rmp: stimulates antibodies that block serum bactericidal activity. 5. Lipooligosaccharide (LOS): lacking long-antigenic side chains; endotoxic. 6. Other proteins. Antigenic structure N. gonorrhoeae is capable of changing its surface antigens (particularly pilin) rapidly to avoid host defenses. Photo Editor 影像: Pathogenesis Attachment to mucosal cells (requires pili) Invade into the cells and multiply (Opa mediates tighter association with and invasion of host cells; Por inhibits phagolysosome fusion) Pass through the cells into the subepithelial space Establish infection (LOS stimulates inflammatory response; Rmp blocks bactericidal activity) Neisseria : Back Lipopolysaccharide (LPS) is also called endotoxin . LPS is composed of lipid A, core polysaccharide, and O-specific polysaccharide. Lipid A anchors LPS in the lipid bilayer. It causes symptoms associated with endotoxin. O-specific polysaccharide can be used to identify certain species and strains. Neisseria: Pathogenesis and Pathology Gonococci attack mucous membrane of the genitourinary tract, eye, rectum, and throat, producing acute suppuration that lead to tissue invasion; this is followed by chronic inflammation and fibrosis . PowerPoint Presentation: Gonorrhea occurs only in humans. Gonorrhea is transmitted by sexual contact, often by women and men with asymptomatic infections. Women have a 50% risk of acquiring the infection with a single exposure to an infected man while men have a 20% risk in the same situation. 95% infected men and 50% infected women have acute symptoms. So, asymptomatic carriage is more common in women than in men. Rectal and pharyngeal infections are more commonly asymptomatic than genital infections. Epidemiology PowerPoint Presentation: Symptoms 1. Male: urethritis with yellow, creamy pus and painful urination . The process may extend to the epididymis As suppuration subsides in untreated infection, fibrosis occurs, sometimes leading to urethral strictures ( sterility ). PowerPoint Presentation: 2. Female: infection starts from the endocervix , and results in vagina discharge, dysuria , and abdominal pain. Uterine tubes may be involved, causing salpingitis , fibrosis, and obliteration of the tubes (20% may become infertile ). When gonococcal cervicitis is either asymptomatic or unrecognized, the patient may progress to pelvic inflammatory disease (PID). PowerPoint Presentation: Neisseria gonorrhoeae Often asymptomatic Can infect the cervix and other parts of the uterus, including the Fallopian tubes Can result in pelvic inflammatory disease (PID) Can result in ectopic pregnancy or sterility Gonococcal infection of children can occur during childbirth producing inflammation of the cornea or blindness PowerPoint Presentation: 3. Gonococcal ophthalmia neonatorum : bilateral conjunctivitis often follows vaginal delivery from an infected mother. The symptoms are eye pain, redness, and a purulent discharge. The organism can cause permanent injury to the eye in a very short time; prompt recognition and treatment are essential to avoid blindness. prevention: tetracycline, erythromycin or silver nitrate. PowerPoint Presentation: 4. Gonococcal bacteremia (1-3% of infected women and much lower percent of infected men) can lead to fever, pustular rash over the extremities, tenosynovitis and suppurative arthritis. PowerPoint Presentation: 16 Genital Infection in Men Urethritis – Inflammation of urethra Epididymitis – Inflammation of the epididymis Clinical Manifestations PowerPoint Presentation: 17 Male Urethritis Symptoms Typically purulent or mucopurulent urethral discharge Often accompanied by dysuria Discharge may be clear or cloudy Asymptomatic in 10% of cases Incubation period: usually 1-14 days for symptomatic disease, but may be longer Clinical Manifestations PowerPoint Presentation: 18 Epididymitis Symptoms: unilateral testicular pain and swelling Infrequent, but most common local complication in males Usually associated with overt or subclinical urethritis Clinical Manifestations PowerPoint Presentation: 19 Genital Infection in Women Most infections are asymptomatic Cervicitis – inflammation of the cervix Urethritis – inflammation of the urethra Clinical Manifestations Neisseria gonorrhoeae: 20 Cervicitis Non-specific symptoms: abnormal vaginal discharge, intermenstrual bleeding, dysuria, lower abdominal pain, or dyspareunia Clinical findings: mucopurulent or purulent cervical discharge, easily induced cervical bleeding 50% of women with clinical cervicitis have no symptoms Incubation period unclear, but symptoms may occur within 10 days of infection Clinical Manifestations PowerPoint Presentation: 21 Urethritis Symptoms: dysuria, however, most women are asymptomatic 40%-60% of women with cervical gonococcal infection may have urethral infection Clinical Manifestations PowerPoint Presentation: 22 Complications in Women Accessory gland infection Bartholin’s glands Skene’s glands Pelvic Inflammatory Disease (PID) Fitz-Hugh-Curtis Syndrome Perihepatitis Clinical Manifestations Genital Infection in Men: 23 Syndromes in Men and Women Anorectal infection Pharyngeal infection Conjunctivitis Disseminated gonococcal infection (DGI) Clinical Manifestations Male Urethritis: 24 Gonococcal Ophthalmia Clinical Manifestations Source : CDC/NCHSTP/Division of STD Prevention, STD Clinical Slides Epididymitis: 25 Disseminated Gonorrhea— Skin Lesion Clinical Manifestations Source : CDC/NCHSTP/Division of STD Prevention, STD Clinical Slides Genital Infection in Women : 26 Gonorrhea Infection in Children Perinatal: infections of the conjunctiva, pharynx, respiratory tract Older children (>1 year): considered possible evidence of sexual abuse Clinical Manifestations Cervicitis: Age In the United States, the highest rates of gonorrhea are found in young (15-24 y) unmarried persons and in groups of low educational and socioeconomic status. Infection in children is a marker for child sexual abuse. Urethritis: Repeated gonococcal infections are common, because protective immunity to reinfection does not develop due to the antigenic variation of gonococci. This makes development of effective vaccines difficult. Resistance to penicillin G (PPNG: penicillinase-producing N. gonorrhoeae ) and tetracycline is common. Resistance to fluoroquinolones has also become prevalent. Ceftriaxone can be used for uncomplicated gonorrhea. In gonococcal infections other than urethritis in men, cure should be established by follow-up, including cultures from the involved sites. Immunity Treatments Complications in Women: Laboratory Diagnosis Gram stain (gram-negative diplococci in PMNs): Sensitive (>90%) and specific (98%) for men with purulent urethritis. Less sensitive for asymptomatic men (<60%). Relatively insensitive for both symptomatic and asymptomatic women. * Negative results must be confirmed by culture. Culture: Avoid drying of specimen (genital or rectal) and low temperature. Direct inoculation of specimens onto prewarmed media is preferred. Inoculate both the selective media (e.g., modified Thayer-Martin) and non-selective media (e.g., chocolate blood agar; for strains that are sensitive to vancomycin). Syndromes in Men and Women : Prevention and Control Chemoprophylaxis is ineffective except for eye infections. Areas with high incidence of PPNG: Asia, parts of Africa and some places in USA. Infection rate can be reduced by: 1. avoiding multiple sexual partners; 2. early diagnosis and treatment; 3. finding cases and contacts through education and screening of population at high risk. 4. combined with doxycycline or azithromycin for dual infections with Chlamydia Gonococcal Ophthalmia: Neisseria meningitidis (meningococcus) Disseminated Gonorrhea— Skin Lesion: 1. Capsular polysaccharide: more than 13 serogroups have been identified (serogroups A, B, C, X, Y, and W135 are most commonly isolated). 2. Pili (allow bacterial colonization of nasopharynx). 3. Outer membrane proteins: these are analogues to the Por and Opa proteins of gonococci. 4. Lipooligosaccharide (LOS): responsible for diffuse vascular damage in meningococcal infections. Antigenic structure Gonorrhea Infection in Children : Pathogenesis, Pathology, and Clinical Finding Meningococci are pathogenic only for humans under natural conditions. Like gonococci, meningococci are able to invade the epithelial cells. The capsule of meningococci protects the bacteria from phagocytic destruction. Nasopharynx is the portal of entry attach to epithelial cells with the aid of pili (may colonize without producing symptoms) reach the blood stream, producing bacteremia. Upper respiratory tract infection. Fulminant meningococcemia . Age: Fulminant meningococcemia High fever and hemmorrhagic rash. There may be disseminated intravascular coagulation (with shock, and circulatory collapse (Waterhouse-Friderichsen syndrome: bilateral destruction of adrenal gland.) Meningitis is the most common complication of meningococcemia. A milder septicemia with low-grade fever, arthritis, and petechial skin lesions that persist for days or weeks may be observed. Other syndromes: pneumonia, arthritis, and urethritis. Meningococcemia can be prevented by specific bactericidal antibodies in serum. PowerPoint Presentation: Meningitis Symptoms: begins suddenly, with intense headache, vomiting, and stiff neck, and progress to coma within a few hours. Mortality: nearly 100% if untreated; <10% in patients treated promptly with appropriate antibiotics. Neurologic sequelae: uncommon; hearing deficit. Skin lesions in a patient with meningococcemia PowerPoint Presentation: Immunity Protective immunity is the group- or type-specific, complement-dependent, bactericidal antibodies. Serogroup B, whose capsule contains sialic acid, is relatively non-immunogenic. Treatment Penicillin G is the drug of choice. Laboratory Diagnosis Specimen: blood and cerebrospinal fluid (CSF). >10 7 bacteria/ml of CSF are normally found in untreated patients. Gram stain: gram-negative diplococci in PMNs. Culture: alternative blood culture methods are required because additives in the blood culture broths can be toxic for this organism. Identification: acid formation with glucose and maltose, but not others. PowerPoint Presentation: Epidemiology, Prevention, and Control Meningococcal meningitis occurs in epidemic (in developing countries) and sporadic cases (in developed countries). Transmitted by respiratory droplets among people in close contact (family members; soldiers in military barracks; direct contact with the respiratory secretions of an infected person.) Reduction of personal contacts in a population with a high carrier rate is important for prevention. Rifampin, ceftriaxone, or ciprofloxacin can often eradicate the carrier state and serve as chemoprophylaxis. Persons with deficiencies in the complement system are at high risk for meningococcal disease. Vaccination of specific capsular polysaccharides of groups A, C, Y, and W-135 is used for protecting susceptible persons against infection. Outer membrane vesicle vaccines for group B are being developed recently.