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Tag words: Neisseria, gonococcus, meningococcus, meningococcal meningitis, gonorrhea, nonatal ophthalmia, urethritis

Neisseria gonorrhoeae

Kingdom: Bacteria
Phylum: Proteobacteria
Class: Beta Proteobacteria
Order: Neisseriales
Family: Neisseriaceae
Genus: Neisseria
Species: N. gonohorrhoeae




Neisseria meningitidis

Kingdom: Bacteria
Phylum: Proteobacteria
Class: Beta Proteobacteria
Order: Neisseriales
Family: Neisseriaceae
Genus: Neisseria
Species: N. meningitidis


Common References: Neisseria, Neisseria meningitidis, Neisseria gonorrhoeae, N gonorrhoeae, N meningitidis, diplococcus, gonococcus, meningococcus, meningococcal meningitis, meningococcemia, meningitis, gonorrhea, nonatal ophthalmia, urethritis








Kenneth Todar currently teaches Microbiology 100 at the University of Wisconsin-Madison.  His main teaching interest include general microbiology, bacterial diversity, microbial ecology and pathogenic bacteriology.

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Pathogenic Neisseriae: Gonorrhea, Neonatal Ophthalmia and Meningococcal Meningitis (page 4)

(This chapter has 7 pages)

© Kenneth Todar, PhD

Host Defenses

Infection stimulates inflammation and a local immune (IgA) response. Inflammation focuses the host defenses but also becomes the pathology of the disease. It is not known whether the secretory immune response is protective. Serum antibodies also appear, and IgG and complement may be components of the inflammatory exudate. But whether the immune defenses provide much protection against reinfection has not been clearly shown. In any case, immunity is expected to be strain specific so that reinfection may occur.

Not everyone exposed to N. gonorrhoeae acquires the disease. This may be due to variations in the size or virulence of the inoculum, to natural resistance, or to specific immunity. A 50% infective dose (ID50) of about 1,000 bacteria has been determined based on experimental urethral inoculation of male volunteers. No data is available for females.

Nonspecific factors have been implicated in natural resistance to gonococcal infection. In women, changes in the genital pH and hormones may increase resistance to infection at certain times of the menstrual cycle. Urine contains bactericidal and bacteriostatic components against N. gonorrhoeae. Factors in urine that may be important are pH, osmolarity, and the concentration of urea. The variability in the susceptibility of gonococcal strains to the bactericidal and bacteriostatic properties of urine is thought to be one of the reasons some males apparently do not develop a gonorrhea infection when exposed.

Most uninfected individuals have serum antibodies that react with gonococcal antigens. These antibodies probably result from colonization or infection by various Gram-negative bacteria that possess cross-reactive antigens. Such "natural antibodies" may be important in individual natural resistance or susceptibility to infection. demonstrated.

Infection with N. gonorrhoeae stimulates both mucosal and systemic antibodies to a variety of gonococcal antigens. Mucosal antibodies are primarily IgA and IgG. In genital secretions, antibodies have been identified that react with Por, Opa, Rmp and LOS. Vaccine trials have suggested that specific anti-fimbrial antibodies inhibit the fimbrial-mediated attachment of the homologous gonococcal strain. In general, the IgA response is brief and declines rapidly after treatment; IgG levels decline more slowly.  Anti-Por antibodies apparently are bactericidal for the gonococcus. IgG that reacts with Rmp blocks the bactericidal activity of antibodies directed against Por and LOS. Genital infection with N. gonorrhoeae stimulates a serum antibody response against the LOS of the infecting strain. Disseminated gonococcal infection results in much higher levels of anti-LOS antibody than do genital infections.

Strains that cause uncomplicated genital infections usually are killed by normal human serum and are termed serum sensitive. This bactericidal activity is mediated by IgM and IgG antibodies that recognize sites on the LOS. Strains that cause disseminated infections are not killed by most normal human serum and are referred to as serum resistant. Resistance is mediated, in part, by IgA that blocks the IgG-mediated bactericidal activity of the serum. Serum from convalescent patients with disseminating infections contains bactericidal IgG to the LOS of the infecting strain.

Individuals with inherited complement deficiencies have a markedly increased risk of acquiring systemic neisserial infections and are subject to recurring episodes of systemic gonococcal and meningococcal infections, indicating that the complement system is important in host defense. Gonococci activate complement by both the classic and alternative pathways. Complement activation by gonococci leads to the formation of the C5b-9 complex (membrane attack complex) on the outer membrane. In normal human serum, similar numbers of C5b-9 complexes are deposited on serum-sensitive and serum-resistant organisms, but the membrane attack complex is not functional on serum-resistant organisms.

Treatment

The current CDC Guidelines recommend treatment of all gonococcal infections with antibiotic regimens effective against resistant strains. Currently recommended antimicrobial agents are ceftriaxone, cefixime, ciprofloxacin, or oflaxacin.

Cephalosporins remained the foundation of gonorrhea treatment in the 2010 CDC STD treatment guidelines. These updated guidelines increased the recommended dosage of ceftriaxone to 250 mg and included broadened recommendations for combination therapy: a cephalosporin, preferably ceftriaxone 250 mg as a single intramuscular dose, should be administered with a second antimicrobial. Combination therapy treats frequently co-occurring pathogens (e.g., Chlamydia trachomatis) and might hinder the spread of cephalosporin antimicrobial resistance. Sex partners should be referred and treated.

Control

There is no effective vaccine to prevent gonorrhea. Candidate vaccines consisting of PilE protein or Por are of little benefit. The development of an effective vaccine has been hampered by the lack of a suitable animal model and the fact that an effective immune response has never been demonstrated. Condoms are effective in preventing the transmission of gonorrhea.


The evolution of antimicrobial resistance in N. gonorrhoeae may ultimately affect the control of the disease. Soon after their introduction, gonococcal resistance to sulfonamides occurred rapidly and was common by the 1940s. Penicillin was then found to be effective for gonorrhea treatment and became the therapy of choice for several decades. During this time, however, the gonococcus acquired genetic mutations that conferred increasing penicillin resistance, necessitating increasingly higher doses of penicillin to ensure treatment success.
Penicillinase-producing strains of N. gonorrhoeae were first described in 1976. Strains that produce this enzyme are highly resistant to penicillin. Five related ß-lactamase plasmids of different sizes have been identified. The prevalence of penicillin-resistant strains has increased dramatically in the United States since 1984.

During the 1980s tetracycline-resistant strains of gonococci emerged and became widespread in the United States, complicating gonorrhea therapy.
Plasmid-mediated resistance of N. gonorrhoeae to tetracycline was first described in 1986 and has now been reported in most parts of the world. This resistance is due to the presence of the streptococcal tetM determinant on a gonococcal conjugative plasmid. Strains with multiple chromosomal resistance to penicillin, tetracycline, erythromycin, and cefoxitin have been identified in the United States and most other parts of the world.

Fluoroquinolone-resistant N. gonorrhoeae (QRNG) were observed sporadically in the United States during the 1990s and 2000s. During this period, fluoroquinolones were widely used for treatment of gonorrhea because they were safe, effective, inexpensive, and available in oral forms. Fluoroquinolone resistance is caused by the acquisition of parC and gyrA mutations that alter binding sites on enzymes DNA gyrase and topoisomerase IV. QRNG strains emerged in East Asia during the 1990s. In the early 2000s. QRNG emerged in the United States, initially in Hawaii and California. By 2007, the prevalence of QRNG was >5% among isolates collected throughout the United States, prompting CDC to no longer recommend the use of fluoroquinolones for gonorrhea treatment. Spectinomycin, an alternative treatment, had not been available in the United States since 2006, so cephalosporins (such as cefixime and ceftriaxone) were the only remaining antimicrobials recommended for treatment of gonococcal infections.

Cephalosporins remained the foundation of gonorrhea treatment in the 2010 CDC STD treatment guidelines. These updated guidelines increased the recommended dosage of ceftriaxone to 250 mg and included broadened recommendations for combination therapy: a cephalosporin, preferably ceftriaxone 250 mg as a single intramuscular dose, should be administered with a second antimicrobial. Combination therapy treats frequently co-occurring pathogens (e.g., Chlamydia trachomatis) and might hinder the spread of cephalosporin antimicrobial resistance.

Unsuccessful treatment of gonorrhea with oral cephalosporins, such as cefixime, was identified in East Asia, beginning in the early 2000s, and in Europe within the past few years. Ceftriaxone-resistant isolates have been identified in Japan, France and Spain. There is growing evidence that cephalosporin resistance might be emerging in the United States. Likewise, there is some evidence that cefixime susceptibility might be threatened. The acquisition of a penA gene encoding a penicillin binding protein (PBP2) and overproduction of an efflux pump in N. gonorrhoeae appears responsible, at least in part, for reduced susceptibility to cephalosporins.

The development and spread of cephalosporin resistance in N. gonorrhoeae, particularly ceftriaxone resistance, would greatly complicate treatment of gonorrhea. Previously recommended antimicrobials likely cannot again be routinely prescribed for empiric gonorrhea treatment. N. gonorrhoeae maintains previously acquired antimicrobial resistance phenotypes, even if the antimicrobial is no longer used for treatment. In 2011, 11.8% of isolates in the United States were penicillin-resistant, 22.7% were tetracycline-resistant, and 13.3% were fluoroquinolone-resistant.

Tailpiece

Gonorrhea is the second most commonly reported notifiable infection in the United States; >300,000 cases were reported in 2011. In the United States, health inequities persist; the incidence of reported gonorrhea among blacks is 17 times the rate among whites, likely because of structural socioeconomic factors.

The only natural host for N. gonorrhoeae is humans. Gonorrhea has all but disappeared in Scandinavia and several other European countries. However, the disease is very common in the United States. CDC estimates that more than 700,000 persons in the U.S. get new gonorrheal infections each year. Only about half of these infections are reported to CDC.

Gonorrhea is transmitted almost exclusively by sexual contact. Any sexually active person can be infected with gonorrhea. In the United States, the highest reported rates of infection are among sexually active teenagers, young adults, and African Americans. Persons who have multiple sex partners are at highest risk. Rates of gonorrhea are higher in males and in minority and inner-city populations.

Gonorrhea is usually contracted from a sex partner who is either asymptomatic or has only minimal symptoms. It is estimated that the efficiency of transmission after one exposure is about 35 percent from an infected woman to an uninfected man and 50 to 60 percent from an infected man to an uninfected woman. More than 90 percent of men with urethral gonorrhea will develop symptoms within 5 days; fewer than 50 percent of women with genital gonorrhea will do so. Women with asymptomatic infections are at higher risk of developing pelvic inflammatory disease and disseminated gonococcal infection.

Last year (2012) the World Health Organization reported that cases of drug-resistant gonorrhea had spread across the world.

In England, gonorrhea cases soared by 25% as drug-resistant strains began to take hold worldwide. The
UK Health Protection Agency (HPA) reported 21,000 new cases diagnosed in 2011, with more than a third of cases in men that have sex with men and more than a third in people who have had gonorrhea before. Effective treatment with antibiotics has been compromised by growing resistance to antibiotics, including cephalosporins that are normally recommended as treatment.

A strain of gonorrhea that was resistant to all recommended antibiotics was found in Japan in 2008. Public health officials have warned that it could transform a once easily treatable infection into a global health threat.




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