Term
| Taxonomy of the family Neisseriaceae |
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Definition
•Based on 16s rRNA sequences and hybridization studies.
•Genus Neisseria 16 species. N. gonorrhoeae, N. meningitidis, N. lactamica, N. sicca, N. subflava, N. mucosa, N. flavescens, N. cinerea, N. polysaccharea, N. elongata, N. weaveri, N. canis, N. macacae, N. denitrificans, N. iguanae, N. dentium
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Term
| Neisseria gonorrhoeae History |
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Definition
•Historical: recognized in the Second century A.D. Named after the Greek word “Seed” and “Flow”.
•It was well described as sexually transmitted by the 13th Century.
1897 Neisser, first observed the species in purulent exudates from the genital tract.
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Term
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Definition
•Gram negative, coccal shaped bacteria
•Oxidase +, Catalase +, nonmotile
•Produce acids from carbohydrates, in a reduced environment. CTA sugars, cystine trypticase agar.
•All species inhabit the mucous membranes of warm blooded hosts
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Term
| Virulence factors Neisseria |
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Definition
•Pili present in both N. gonorrhoeae, N. meningitidis.
•Gonococcal pili, 2 types of variation:
–1. Phase, pilated (P+ and P++) or “nonpilated”(P-) state In vitro. Switching between the “+” or “-” state is called phase variation.
–2. Antigenic, genes(pil) that encode for the pili undergo a recombinational event, “new pili”. The structural gene for pilus proteins are encoded on pilE, the genes associated with the recombinational event are pilS. The changes in gene sequences that lead to changes in amino acid composition of the pilin. This change interferes with the immune response, since the immunoglobulins no longer bind.
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Term
Historical Outbreaks of
N. meningitidis |
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Definition
•1887, the organism was isolated by Weichselbaum.
•1929-1943, outbreaks of this strain occurred in Chile and cities in the US. During the late 1930’s, sulfonamide agents were found to eradicate the meningococcal carrier state.
•In the early 1960’s, resistance to sulfonamides was observed. This stimulated the development of effective polysaccharide vaccines.
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Term
| Function of Pili in N. gonorrhoeae |
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Definition
•The pili mediate gonococcal attachment to several cell types, including buccal and vaginal epithelial cells, erythrocytes, neutrophils and sperm cells. Pili also impede gonococcal phagocytosis by PMN’s.
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Term
| Virulence Factor of N. gonorrhoeae |
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Definition
•Lipooligasaccharides: these bacteria possess an inner cytoplasmic membrane, a thin peptidoglycan layer, an outer membrane containing LPS. But unlike other Gram negative bacteria, the LPS, it has a shorter nonrepeating “O” antigen, hence the term lipooligosaccharides (LOS). These molecules stimulate inflammatory response, activate complement, induce lysis of PMN’s, cause some of the tissue damage seen with PID.
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Term
Outer Membrane Proteins
N. gonorrhoeae |
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Definition
•Confer resistance to the destructive properties of normal serum. Examples Por or protein I, and protein III or Rmp. Antibodies produced to Rmp block the binding of antibodies to LOS and Por, thus helping the bacteria to survive.
•Function in attachment in mucosal adhesion opacity (Opa) proteins usually 3 different types are expressed.
•Function in iron acquisition, important in infection. N. gonorrhoeae, can acquire 2 ways: through the use of siderophores produced by other bacteria in the vacinity, and it has a surface receptor for the binding of human transferrin.
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Term
Capsular polysaccharides of
N. meningitidis |
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Definition
•Makes 13 different polysaccharide capsules. Groups A, B,C,D,H,I,K,L,W125, X,Y,Z, and 29E. With the exception of Group A, the polysaccharide is composed of repeating groups of N-acetyl-neuraminic acid.
•Function is to make the bacterium resistant to phagocytosis, and to enhance survival during bloodstream and CNS invasion. The capsule does not seem to mediate adherence to epithelial cells.
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Term
| Virulence factors made by both strains: N.meningitidis, and N.gonorrhoeae |
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Definition
•IgA1 protease that splits the molecule IgA1 into the Fab and Fc fragment, at the hinge region. This enzyme acts as a virulence factor by inactivating IgA1 at the mucosal surfaces, thus enabling initial attachment and subsequent invasion. Other research indicates that the exoenzyme can trigger release of proinflammatory cytokines from human monocytes. It also modifies an intracellular protein involved with phagosome/lysosome fusion.
•LOS, lipooligosaccharides.
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Term
Clinical Information
N. gonorrhoeae |
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Definition
•Method of transfer- sexual, humans the only natural reservoir.
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Term
| Clinical symptoms in the male |
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Definition
•Burning urination (acute urethritis), with purulent urethral discharge.
•Incubation period, acquistion to onset of symptoms 1 to 14 days, (Avg 2 – 7 days)
•95-99% all males have discharge, discharge is purulent in 75% of cases, cloudy in 20% and mucoid in 5%.
–Complications, impacts penile veins, tender prostate- “Skenitis”, inflamed bladder, inflamed testis.
–20% males infected after single exposure
–10% males asymptomatic
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Term
| Clinical symptoms in the female |
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Definition
•Primary site of infection is the endocervix and urethral infection, vaginal discharge, pelvic pain bleeding.
•Most females present symptoms, 8 to 10 days post acquisition, cervicovaginal discharge, intermenstrual bleeding, abdominal/pelvic pain.
•Complications:
–15% PID, pelvic inflammatory disease or salpingitis. An ascending gonococcal infection.
–Bartholinitis, “Greater Vestibular Gland”, involved with making vagina moist.
–50% females infected after single exposure
–50% females may be asymptomatic
–In 1% of infected females, the disease becomes systematic. A common phase of this disease is arthritis, which if left untreated destroys the joint.
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Term
| In both males and females |
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Definition
•In 0.5-3% of infected individuals the gonococci may invade the blood stream, resulting in a disseminated gonococcal infection (DGI). Women are at greater risk for this than men.
•In 30-40% of cases the organisms localize in one or more of the joints to become destructive gonococcal arthritis.
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Term
Body sites to culture for
N. gonorrhoeae |
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Definition
•Female- endocervix--rectum, urethra, pharynx
•Male, heterosexual- urethra--pharynx
•Male, homosexual / bisexual- urethra, rectum, pharynx
•Over 90% of oropharyngeal gonococcal infections are asymptomatic and are diagnosed by throat culture.
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Term
| Treatment of N. gonorrhoeae |
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Definition
•Antibiotic resistant N. gonorrhoeae spreading across the US. Resistance to Cipro is observed. Data from 26 cities demonstrates that resistance has risen from 1% to 13% in < 5 yrs. Therefore use cephalosporins instead, which is given via a shot.
•Development of a vaccine is not in the picture due to the hypervariability of bacterial surface proteins.
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Term
History of antibiotic resistant
N. gonorrhoeae |
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Definition
•Gonorrhea, one of the most prevalent diseases in the US. Approximately, 1 million cases/yr, many unreported. In 1976, from SE Asia, a new variant emerged, penicillinase (β-lactamase), producing strains. These genes were expressed on a plasmid, the genes were acquired from a transposon found in enteric species or H. influenzae. Africa was also a source for these genes. Another chromosomal gene that encodes a mutant penicillin binding protein that no longer binds penicillin has also been discovered for penicillin resistant strains.
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Term
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Definition
•Occurs in newborns via birth canal, prevent with 1% AgNO3 drops.
•Ophthalmia neonatorum.
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Term
Isolation and Identification
N. gonorrhoeae |
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Definition
•Isolation:
–Gram stain
–Transport medium
–Culture on Modified Thayer Martin or Martin Lewis media.
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Term
| Modified Thayer Martin Medium |
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Definition
•Vancomycin
•Colistin
•Nystatin
•Trimethoprim
•Medium contains:
–Bacto GC Medium base
–Bacto hemoglobin
–Bacto supplement B or VX
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Term
Identification of
N. gonorrhoeae |
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Definition
•Colony types T 1 through T 5
•T1 and T2 are pilated, small and raised, T3-T5 non pilated large and flat.
•Oxidase test
•Superoxol test (30% hydrogen peroxide solution)
•CTA sugars, glucose +, ( negative, maltose, fructose, lactose and sucrose)
•Immunological tests
•DNA probe
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Term
General Information
N.meningitidis |
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Definition
•Gram negative coccobacillus, oxidase +, catalase +.
•CTA sugars utilization test : glucose +, maltose +, (negative: fructose, sucrose and lactose).
•13, meningococcal capsular polysaccharides, (A,B, C, D, H, I, K, L, X, Y, Z, W135 and 29E).
•Most infections due to serogroups A, B, C, Y and W135.
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Term
| Pathogenesis of N. meningitidis |
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Definition
•Primary disease: Initiated in the nasophrynx by droplet nuclei from case or carrier. Adherence to the nasopharynx mucosal surface is mediated by pili and facilitated by cleavage of sIgA by IgA1 protease. Phagocytosis by PMN’s is inhibited by the capsule.
•Disseminated disease: Septicemia, the bacteria invade the blood stream from the nasopharynx, and release LOS, which gives the clinical signs. Meningitis, the bacteria cross the blood brain barrier and reach the meninges where they induce an acute inflammatory response.
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Term
| Infections caused by N. meningitidis |
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Definition
•The organism may be carried asymptomatically in the oropharynx and nasopharynx of a percentage of individuals.
•Carriage rates tend to be 8-20% with older children and 20-40% of young children.
•The rate of carriage does not appear to be seasonal, however most meningococcal disease occurs during late winter early spring.
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Term
Clinical information
N. meningitidis |
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Definition
•Inflammation of the membrane surrounding the brain and spinal cord, “ meninges”.
•Causes a spectrum of disease from mild to overwhelming, death.
•Clinical signs, confusion, headache, high fever, rigidity of the neck. Nausea, vomiting, sensitivity to light, confusion sleepiness, seizures, purple rash may appear.
•Mortality 100% in untreated children, 10-12% of young adults, sometimes within hours. Each year < 3,000 people, college students and children <1yr. Survivors 20% have brain damage, hearing loss, kidney damage.
•Disease is spread via droplet nuclei, sharing glasses, cigarettes.
•Once the infection has spread, see small hemorrhagic skin lesions, worsens to necrosis, death from disseminated intravascular coagulation, organs shut down.
•Outbreaks occur on college campuses usually at rate of 5.4/100,000 undergraduates. Sometimes “Bars” frequented by undergraduates are hotbeds of colonized people. Outbreaks occur in the winter when heat dries out mucous membranes.
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Term
| Risk factors Diagnosis and treatment N. meningitidis |
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Definition
•Risk factors: Freshman in dorms, crowded, new people, lack of sleep, sharing items orally.
•Diagnosis: spinal tap and culture cerebrospinal fluid.
•Treatment: high dose IV penicillin, chloramphenicol or cephalosporin. Antibiotic administration is ineffective in eradicating the carrier state.
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Term
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Definition
•“Menactra”, cost $120. FDA approved for children 11yrs and older. Made from 4-5 strains, 83% effective, required in 23 states. Side effects1.25 times/1 million shots.
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Term
Isolation and Identification of
N. meningitidis |
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Definition
•Usually from cerebrospinal fluid or blood.
•Gram stain
•Culture in Modified Thayer-Martin and Martin-Lewis media, aerobic incubation 48hr at 35-37C in the presence of 3-10% CO2.
•CTA sugars test
•Immunological probes, and slide agglutination test
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Term
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Definition
•N. lactamica
•N. flavescens
•N. sulflava
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Term
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Definition
•Resembles N. meningitidis in colony morphology, a resident in the throat in children and adults. Carriage of this organism stimulates the production of antibodies to N. meningitidis groups A,B and C.
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Term
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Definition
•Large type colonies that resemble N.gonorrhoeae, normal flora upper respiratory tract. It is also recovered from genital sites and is associated with syndromes caused by gonococci, such as ophthalmia neonatorum.
•Differentiate from N.gon, via the colistin disk test, this strain is susceptible, will have a zone.
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Term
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Definition
•Is found in the respiratory tract, rarely associated with the infectious process.
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Term
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Definition
•This family was originally part of the Neisseriaceae, now separate on the basis of 16s rDNA. The genus Moraxella which has 3 groups. M. catarrhalis, aerobic, Gram negative diplococcus, oxidase +, catalase +, reduces both NO3 and NO2, negative acid from all CTA sugars. Normal flora human respiratory tract, considered low pathogenicity. But is currently important infection with individuals with chronic bronchitis.
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