Chapter 185 Neisseria gonorrhoeae (Gonococcus) Toni Darville Neisseria gonorrhoeae produces several forms of gonorrhea, an infection of the genitourinary tract mucous membranes and rarely of the mucosa of the rectum, oropharynx, and conjunctiva. Gonorrhea transmitted by sexual contact or perinatally is 2nd only to chlamydial infections in the number of cases reported to the Centers for Disease Control and Prevention (CDC) in the USA. This high prevalence and the development of antibiotic-resistant strains have produced significant morbidity in adolescents. Etiology N. gonorrhoeae is a nonmotile, aerobic, non–spore-forming, gram-negative intracellular diplococcus with flattened adjacent surfaces. Optimal growth occurs at 35-37°C and at pH 7.2-7.6 in an atmosphere of 3-5% carbon dioxide. The specimen should be inoculated immediately onto fresh, moist, modified Thayer-Martin or specialized transport media because gonococci do not tolerate drying. Thayer-Martin medium contains antimicrobial agents that inhibit hardier normal flora present in clinical specimens that may otherwise overgrow gonococci. Presumptive identification may be based on colony appearance, Gram stain appearance, and production of cytochrome oxidase. Gonococci are differentiated from other Neisseria species by the fermentation of glucose but not maltose, sucrose, or lactose. Gram-negative diplococci are seen in infected material, often within polymorphonuclear leukocytes. Like all gram-negative bacteria, N. gonorrhoeae possesses a cell envelope composed of an inner cytoplasmic membrane, a middle layer of peptidoglycan, and an outer membrane. The outer membrane contains lipo-oligosaccharides (endotoxin), phospholipid, and a variety of proteins that contribute to cell adherence, tissue invasion, and resistance to host defenses. The 2 systems primarily used to characterize gonococcal strains are auxotyping and serotyping. Auxotyping is based on genetically stable requirements of strains for specific nutrients or cofactors as defined by an isolate’s ability to grow on chemically defined media. The most widely used serotyping system is based on a porin called PorI, a trimeric outer membrane protein that makes up a substantial part of the gonococcal envelope structure. Antibodies generated to PorI have been used to serotype gonococci (e.g., PorIA-4 and PorIB-12), and changes in PorI proteins present in a community are believed to occur, at least in part, as a result of selective immune pressure. Epidemiology N. gonorrhoeae infection occurs only in humans. The organism is shed in the exudate and secretions of infected mucosal surfaces and is transmitted through intimate contact, such as sexual contact or parturition, and rarely by contact with fomites. Gonococcal infections in the newborn period are generally acquired during delivery. Gonorrhea is the most common sexually transmitted infection found in sexually abused children. Rarely, N. gonorrhoeae may be spread by sexual play among children, but the index patient is likely to be a victim of sexual abuse. Gonococcal infections in children are acquired rarely through household exposure to infected caretakers. In such cases, the possibility of sexual abuse should be seriously considered. The number of reported cases of gonorrhea increased steadily in the USA from 1964 to 1977, fluctuated through the early 1980s, and increased until 1987, when reported rates were 323/100,000. Rates decreased annually from 1987 to 1996, when reported rates were 123/100,000 population. Since 1996, rates declined or were stable, although in 2005 the national rate (116/100,000 population) increased for the first time since 1999. The decline in gonorrhea prevalence may be attributed to recommendations by the CDC that only highly effective antimicrobial agents be used to treat gonorrhea. The incidence of gonorrhea is highest in high-density urban areas among persons < 24 yr of age who have multiple sex partners and engage in unprotected sexual intercourse. Increases in gonorrhea prevalence have been noted among men who have sex with men (MSM). Risk factors include nonwhite race, homosexuality, increased number of sexual partners, prostitution, presence of other sexually transmitted infections, unmarried status, poverty, and failure to use condoms. Auxotyping and serotyping techniques and, more recently, molecular typing methods have been used to analyze the spread of individual strains of N. gonorrhoeae within a community. Maintenance and subsequent spread of gonococcal infections in a community require a hyperendemic, high-risk core group such as prostitutes or adolescents with multiple sexual partners. This observation reflects the fact that most persons who have gonorrhea cease sexual activity and seek care, unless economic need or other factors (e.g., drug addiction) drive persistent sexual activity. Thus, many core transmitters belong to a subset of infected persons who lack or ignore symptoms and continue to be sexually active, underscoring the importance of seeking out and treating the sexual contacts of infected persons who present for treatment. Gonococcal infection of neonates usually results from peripartum exposure to infected exudate from the cervix of the mother. An acute infection begins 2-5 days after birth. The incidence of neonatal infection depends on the prevalence of gonococcal infection among pregnant women, prenatal screening for gonorrhea, and neonatal ophthalmic prophylaxis. Pathogenesis and Pathology N. gonorrhoeae infects primarily columnar epithelium, because stratified squamous epithelium is relatively resistant to invasion. Mucosal invasion by gonococci results in a local inflammatory response that produces a purulent exudate consisting of polymorphonuclear leukocytes, serum, and desquamated epithelium. The gonococcal lipo-oligosaccharide (endotoxin) exhibits direct cytotoxicity, causing ciliostasis and sloughing of ciliated epithelial cells. Once the gonococcus traverses the mucosal barrier, the lipo-oligosaccharide binds bactericidal immunoglobulin M (IgM) antibody and serum complement, causing an acute inflammatory response in the subepithelial space. Tumor necrosis factor and other cytokines are thought to mediate the cytotoxicity of gonococcal infections. Gonococci may ascend the urogenital tract, causing urethritis or epididymitis in postpubertal males and acute endometritis, salpingitis, and peritonitis (collectively termed acute pelvic inflammatory disease or PID) in postpubertal females. Dissemination from the fallopian tubes through the peritoneum to the liver capsule results in perihepatitis (Fitz-Hugh–Curtis syndrome). Gonococci that invade the lymphatics and blood vessels may cause inguinal lymphadenopathy; perineal, perianal, ischiorectal, and periprostatic abscesses; and disseminated gonococcal infection (DGI). A number of gonococcal virulence and host immune factors are involved in the penetration of the mucosal barrier and subsequent manifestations of local and systemic infection. Selective pressure from different mucosal environments probably leads to changes in the outer membrane of the organism, including expression of variants of pili, opacity or Opa proteins (formerly protein II), and lipo-oligosaccharides. These changes may enhance gonococcal attachment, invasion, replication, and evasion of the host’s immune response. For infection to occur, the gonococcus must first attach to host cells. A gonococcal IgA protease inactivates IgA1 by cleaving the molecule in the hinge region and may be an important factor in colonization or invasion of host mucosal surfaces. Gonococci adhere to the microvilli of nonciliated epithelial cells by hairlike protein structures (pili) that extend from the cell wall. Pili are thought to protect the gonococcus from phagocytosis and complement-mediated killing. Pili undergo high-frequency antigenic variation that may aid in the organism’s escape from the host immune response and may provide specific ligands for different cell receptors. Opacity proteins, most of which confer an opaque appearance to colonies, are also thought to function as ligands to facilitate binding to human cells. Gonococci that express certain Opa proteins adhere to and are phagocytosed by human neutrophils in the absence of serum. Other phenotypic changes that occur in response to environmental stresses allow gonococci to establish infection. Examples include iron-repressible proteins for binding transferrin or lactoferrin, anaerobically expressed proteins, and proteins that are synthesized in response to contact with epithelial cells. Gonococci may grow in vivo under anaerobic conditions or in an environment with a relative lack of iron. Approximately 24 hr after attachment, the epithelial cell surface invaginates and surrounds the gonococcus in a phagocytic vacuole. This phenomenon is thought to be mediated by the insertion of gonococcal outer membrane protein I into the host cell, causing alterations in membrane permeability. Subsequently, phagocytic vacuoles begin releasing gonococci into the subepithelial space by means of exocytosis. Viable organisms may then cause local disease (i.e., salpingitis) or disseminate through the bloodstream or lymphatics. Serum IgG and IgM directed against gonococcal proteins and lipo-oligosaccharides lead to complement-mediated bacterial lysis. Stable serum resistance to this bactericidal antibody probably results from a particular type of porin protein expressed in gonococci (most contain PorIA), predisposing to disseminated disease. N. gonorrhoeae differentially subverts the effectiveness of complement and alters the inflammatory responses elicited in human infection. Isolates from cases of DGI typically resist killing by normal serum (i.e., are serum resistant), inactivate more C3b, generate less C5a, and result in less inflammation at local sites. PID isolates are serum sensitive, inactivate less C3b, generate more C5a, and result in more inflammation at local sites. IgG antibody directed against gonococcal reduction-modifiable protein (Rmp) blocks complement-mediated killing of N. gonorrhoeae. Anti-Rmp blocking antibodies may harbor specificity for outer membrane protein sequences shared with other neisserial species or Enterobacteriaceae, may be directed against unique Rmp upstream cysteine loop–specific sequences, or both. Preexisting antibodies directed against Rmp facilitate transmission of gonococcal infection to exposed women; Rmp is highly conserved in N. gonorrhoeae, and the blocking of mucosal defenses may be one of its functions. Gonococcal adaptation also appears to be important in the evasion of killing by neutrophils. Examples include sialylation of lipo-oligosaccharides, increases in catalase production, and changes in the expression of surface proteins. Host factors may influence the incidence and manifestations of gonococcal infection. Prepubertal girls are susceptible to vulvovaginitis and, rarely, experience salpingitis. N. gonorrhoeae infects noncornified epithelium, and the thin noncornified vaginal epithelium and alkaline pH of the vaginal mucin predispose this age group to infection of the lower genital tract. Estrogen-induced cornification of the vaginal epithelium in neonates and mature females resists infection. Postpubertal females are more susceptible to salpingitis, especially during menses, when diminished bactericidal activity of the cervical mucus and reflux of blood from the uterine cavity into the fallopian tubes facilitate passage of gonococci into the upper reproductive tract. Populations at risk for DGI include asymptomatic carriers; neonates; menstruating, pregnant, and postpartum women; homosexuals; and immunocompromised hosts. The asymptomatic carrier state implies failure of the host immune system to recognize the gonococcus as a pathogen, the capacity of the gonococcus to avoid being killed, or both. Pharyngeal colonization has been proposed as a risk factor for DGI. The high rate of asymptomatic infection in pharyngeal gonorrhea may account for this phenomenon. Women are at greater risk for development of DGI during menstruation, pregnancy, and the postpartum period, presumably because of the maximal endocervical shedding and decreased peroxidase bactericidal activity of the cervical mucus during these periods. A lack of neonatal bactericidal IgM antibody is thought to account for the increased susceptibility of neonates to DGI. Persons with terminal complement component deficiencies (C5-C9) are at considerable risk for development of recurrent episodes of DGI. Clinical Manifestations Only gold members can continue reading. Log In or Register to continue Share this:Click to share on Twitter (Opens in new window)Click to share on Facebook (Opens in new window) Related Related posts: Rumination, Pica, and Elimination (Enuresis, Encopresis) Disorders Adolescent Pregnancy Yersinia Fever without a Focus Stay updated, free articles. 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Chapter 185 Neisseria gonorrhoeae (Gonococcus) Toni Darville Neisseria gonorrhoeae produces several forms of gonorrhea, an infection of the genitourinary tract mucous membranes and rarely of the mucosa of the rectum, oropharynx, and conjunctiva. Gonorrhea transmitted by sexual contact or perinatally is 2nd only to chlamydial infections in the number of cases reported to the Centers for Disease Control and Prevention (CDC) in the USA. This high prevalence and the development of antibiotic-resistant strains have produced significant morbidity in adolescents. Etiology N. gonorrhoeae is a nonmotile, aerobic, non–spore-forming, gram-negative intracellular diplococcus with flattened adjacent surfaces. Optimal growth occurs at 35-37°C and at pH 7.2-7.6 in an atmosphere of 3-5% carbon dioxide. The specimen should be inoculated immediately onto fresh, moist, modified Thayer-Martin or specialized transport media because gonococci do not tolerate drying. Thayer-Martin medium contains antimicrobial agents that inhibit hardier normal flora present in clinical specimens that may otherwise overgrow gonococci. Presumptive identification may be based on colony appearance, Gram stain appearance, and production of cytochrome oxidase. Gonococci are differentiated from other Neisseria species by the fermentation of glucose but not maltose, sucrose, or lactose. Gram-negative diplococci are seen in infected material, often within polymorphonuclear leukocytes. Like all gram-negative bacteria, N. gonorrhoeae possesses a cell envelope composed of an inner cytoplasmic membrane, a middle layer of peptidoglycan, and an outer membrane. The outer membrane contains lipo-oligosaccharides (endotoxin), phospholipid, and a variety of proteins that contribute to cell adherence, tissue invasion, and resistance to host defenses. The 2 systems primarily used to characterize gonococcal strains are auxotyping and serotyping. Auxotyping is based on genetically stable requirements of strains for specific nutrients or cofactors as defined by an isolate’s ability to grow on chemically defined media. The most widely used serotyping system is based on a porin called PorI, a trimeric outer membrane protein that makes up a substantial part of the gonococcal envelope structure. Antibodies generated to PorI have been used to serotype gonococci (e.g., PorIA-4 and PorIB-12), and changes in PorI proteins present in a community are believed to occur, at least in part, as a result of selective immune pressure. Epidemiology N. gonorrhoeae infection occurs only in humans. The organism is shed in the exudate and secretions of infected mucosal surfaces and is transmitted through intimate contact, such as sexual contact or parturition, and rarely by contact with fomites. Gonococcal infections in the newborn period are generally acquired during delivery. Gonorrhea is the most common sexually transmitted infection found in sexually abused children. Rarely, N. gonorrhoeae may be spread by sexual play among children, but the index patient is likely to be a victim of sexual abuse. Gonococcal infections in children are acquired rarely through household exposure to infected caretakers. In such cases, the possibility of sexual abuse should be seriously considered. The number of reported cases of gonorrhea increased steadily in the USA from 1964 to 1977, fluctuated through the early 1980s, and increased until 1987, when reported rates were 323/100,000. Rates decreased annually from 1987 to 1996, when reported rates were 123/100,000 population. Since 1996, rates declined or were stable, although in 2005 the national rate (116/100,000 population) increased for the first time since 1999. The decline in gonorrhea prevalence may be attributed to recommendations by the CDC that only highly effective antimicrobial agents be used to treat gonorrhea. The incidence of gonorrhea is highest in high-density urban areas among persons < 24 yr of age who have multiple sex partners and engage in unprotected sexual intercourse. Increases in gonorrhea prevalence have been noted among men who have sex with men (MSM). Risk factors include nonwhite race, homosexuality, increased number of sexual partners, prostitution, presence of other sexually transmitted infections, unmarried status, poverty, and failure to use condoms. Auxotyping and serotyping techniques and, more recently, molecular typing methods have been used to analyze the spread of individual strains of N. gonorrhoeae within a community. Maintenance and subsequent spread of gonococcal infections in a community require a hyperendemic, high-risk core group such as prostitutes or adolescents with multiple sexual partners. This observation reflects the fact that most persons who have gonorrhea cease sexual activity and seek care, unless economic need or other factors (e.g., drug addiction) drive persistent sexual activity. Thus, many core transmitters belong to a subset of infected persons who lack or ignore symptoms and continue to be sexually active, underscoring the importance of seeking out and treating the sexual contacts of infected persons who present for treatment. Gonococcal infection of neonates usually results from peripartum exposure to infected exudate from the cervix of the mother. An acute infection begins 2-5 days after birth. The incidence of neonatal infection depends on the prevalence of gonococcal infection among pregnant women, prenatal screening for gonorrhea, and neonatal ophthalmic prophylaxis. Pathogenesis and Pathology N. gonorrhoeae infects primarily columnar epithelium, because stratified squamous epithelium is relatively resistant to invasion. Mucosal invasion by gonococci results in a local inflammatory response that produces a purulent exudate consisting of polymorphonuclear leukocytes, serum, and desquamated epithelium. The gonococcal lipo-oligosaccharide (endotoxin) exhibits direct cytotoxicity, causing ciliostasis and sloughing of ciliated epithelial cells. Once the gonococcus traverses the mucosal barrier, the lipo-oligosaccharide binds bactericidal immunoglobulin M (IgM) antibody and serum complement, causing an acute inflammatory response in the subepithelial space. Tumor necrosis factor and other cytokines are thought to mediate the cytotoxicity of gonococcal infections. Gonococci may ascend the urogenital tract, causing urethritis or epididymitis in postpubertal males and acute endometritis, salpingitis, and peritonitis (collectively termed acute pelvic inflammatory disease or PID) in postpubertal females. Dissemination from the fallopian tubes through the peritoneum to the liver capsule results in perihepatitis (Fitz-Hugh–Curtis syndrome). Gonococci that invade the lymphatics and blood vessels may cause inguinal lymphadenopathy; perineal, perianal, ischiorectal, and periprostatic abscesses; and disseminated gonococcal infection (DGI). A number of gonococcal virulence and host immune factors are involved in the penetration of the mucosal barrier and subsequent manifestations of local and systemic infection. Selective pressure from different mucosal environments probably leads to changes in the outer membrane of the organism, including expression of variants of pili, opacity or Opa proteins (formerly protein II), and lipo-oligosaccharides. These changes may enhance gonococcal attachment, invasion, replication, and evasion of the host’s immune response. For infection to occur, the gonococcus must first attach to host cells. A gonococcal IgA protease inactivates IgA1 by cleaving the molecule in the hinge region and may be an important factor in colonization or invasion of host mucosal surfaces. Gonococci adhere to the microvilli of nonciliated epithelial cells by hairlike protein structures (pili) that extend from the cell wall. Pili are thought to protect the gonococcus from phagocytosis and complement-mediated killing. Pili undergo high-frequency antigenic variation that may aid in the organism’s escape from the host immune response and may provide specific ligands for different cell receptors. Opacity proteins, most of which confer an opaque appearance to colonies, are also thought to function as ligands to facilitate binding to human cells. Gonococci that express certain Opa proteins adhere to and are phagocytosed by human neutrophils in the absence of serum. Other phenotypic changes that occur in response to environmental stresses allow gonococci to establish infection. Examples include iron-repressible proteins for binding transferrin or lactoferrin, anaerobically expressed proteins, and proteins that are synthesized in response to contact with epithelial cells. Gonococci may grow in vivo under anaerobic conditions or in an environment with a relative lack of iron. Approximately 24 hr after attachment, the epithelial cell surface invaginates and surrounds the gonococcus in a phagocytic vacuole. This phenomenon is thought to be mediated by the insertion of gonococcal outer membrane protein I into the host cell, causing alterations in membrane permeability. Subsequently, phagocytic vacuoles begin releasing gonococci into the subepithelial space by means of exocytosis. Viable organisms may then cause local disease (i.e., salpingitis) or disseminate through the bloodstream or lymphatics. Serum IgG and IgM directed against gonococcal proteins and lipo-oligosaccharides lead to complement-mediated bacterial lysis. Stable serum resistance to this bactericidal antibody probably results from a particular type of porin protein expressed in gonococci (most contain PorIA), predisposing to disseminated disease. N. gonorrhoeae differentially subverts the effectiveness of complement and alters the inflammatory responses elicited in human infection. Isolates from cases of DGI typically resist killing by normal serum (i.e., are serum resistant), inactivate more C3b, generate less C5a, and result in less inflammation at local sites. PID isolates are serum sensitive, inactivate less C3b, generate more C5a, and result in more inflammation at local sites. IgG antibody directed against gonococcal reduction-modifiable protein (Rmp) blocks complement-mediated killing of N. gonorrhoeae. Anti-Rmp blocking antibodies may harbor specificity for outer membrane protein sequences shared with other neisserial species or Enterobacteriaceae, may be directed against unique Rmp upstream cysteine loop–specific sequences, or both. Preexisting antibodies directed against Rmp facilitate transmission of gonococcal infection to exposed women; Rmp is highly conserved in N. gonorrhoeae, and the blocking of mucosal defenses may be one of its functions. Gonococcal adaptation also appears to be important in the evasion of killing by neutrophils. Examples include sialylation of lipo-oligosaccharides, increases in catalase production, and changes in the expression of surface proteins. Host factors may influence the incidence and manifestations of gonococcal infection. Prepubertal girls are susceptible to vulvovaginitis and, rarely, experience salpingitis. N. gonorrhoeae infects noncornified epithelium, and the thin noncornified vaginal epithelium and alkaline pH of the vaginal mucin predispose this age group to infection of the lower genital tract. Estrogen-induced cornification of the vaginal epithelium in neonates and mature females resists infection. Postpubertal females are more susceptible to salpingitis, especially during menses, when diminished bactericidal activity of the cervical mucus and reflux of blood from the uterine cavity into the fallopian tubes facilitate passage of gonococci into the upper reproductive tract. Populations at risk for DGI include asymptomatic carriers; neonates; menstruating, pregnant, and postpartum women; homosexuals; and immunocompromised hosts. The asymptomatic carrier state implies failure of the host immune system to recognize the gonococcus as a pathogen, the capacity of the gonococcus to avoid being killed, or both. Pharyngeal colonization has been proposed as a risk factor for DGI. The high rate of asymptomatic infection in pharyngeal gonorrhea may account for this phenomenon. Women are at greater risk for development of DGI during menstruation, pregnancy, and the postpartum period, presumably because of the maximal endocervical shedding and decreased peroxidase bactericidal activity of the cervical mucus during these periods. A lack of neonatal bactericidal IgM antibody is thought to account for the increased susceptibility of neonates to DGI. Persons with terminal complement component deficiencies (C5-C9) are at considerable risk for development of recurrent episodes of DGI. Clinical Manifestations Only gold members can continue reading. Log In or Register to continue Share this:Click to share on Twitter (Opens in new window)Click to share on Facebook (Opens in new window) Related Related posts: Rumination, Pica, and Elimination (Enuresis, Encopresis) Disorders Adolescent Pregnancy Yersinia Fever without a Focus Stay updated, free articles. 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