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Unformatted text preview: Lecture 18
Neisseria Classification Classification Family Genera Species 10 Neisseriaceae Neisseria/Eikenella/Kingella N. gonorrhoeae N. meningitidis Very Common Common General Characteristics General Characteristics N. gonorrhoeae and N. meningitidis Aerobic Nonspore forming Gramnegative cocci (diplococcal) Nonmotile Oxidase and Catalase positive Strict human pathogens Fastidious 35oC37oC and capnophile (prefer higher CO2) Contain Lipooligosaccharides, LOS (like LPS without Oantigen) Characteristics Characteristics N. meningitidis (“Meningococcus”) ~10% of population can be asymptomatic carrier Acid produced from glucose AND maltose oxidation (not fermentation=anaerobic) Polysaccharide capsule; 12 serogroups Serogroups associated with disease: A,B,C,Y , W135 and unknown serogroup Very sensitive to temperature above or below 37oC Morphology Morphology N. Meningitidis In vitro growth In vivo usually diplococcic!! Low prevalence, high mortality Colonizes posterior nasopharynx before manifestation of symptoms Asymptomatic carrier can be up to 20% in contact group and up to 80% during epidemic Household members are at 500800fold increased risk to be infected!! Transmitted via aerosol Epidemiology N. meningitidis Epidemiology Epidemiology 10002000 cases per year, most are meningitis common cause of communityacquired meningitis in adults Meningitis Meningitis Abrupt onset no fever in neonates (<2months) Fever, severe headache, nausea , vomiting , altered mental status (disoriented), coma Petechiae (hemorrhagic spots) may occur Mortality up to 100% in untreated cases Prompt treatment reduces it to 10% Clinical manifestation N. meningitidis Meningococcemia: Meningococcemia: Develops in 515% of menigococcal disease Abrupt onset High fever, chills, nausea, vomiting, headache Restlessness and delirium occur within hours Widespread purpuric skin lesions in trunk and lower extremities May coalesce to form large hemorrhagic lesions Pulmonary insufficiency develop Many patient die within 24h after being admitted to hospital Clinical manifestation N. meningitidis Clinical manifestation Clinical manifestation N. meningitidis
Characteristic skin rash (purpura) induced by septicemia of N. meningitidis Petechial lesion Hemorrhagic lesion/bullae Bacteria present in large numbers in CSF, blood and sputum Culture (oxidase , catalase positive), but sensitive to cold and dry environments Gramneg. diplococci PCR amplification Diagnosis N. meningitidis Diagnosis Diagnosis N. meningitidis Gramstain of CSF Prophylaxis: Prophylaxis: Breast feeding, passive immunization with antibodies from mother Subunit vaccine with polysaccharide capsular antigens for children older than 2years Problem: antigenic variation of capsule!! Chemoprophylaxis of household members of patient (Rifampin and Ciprofloxacin) Treatment and prevention N. meningitidis Possible proteins used for Possible proteins used for conjugation Antigenic Variation A) Polysaccharidebased subunit vaccines: bacterial resistance develops by changing capsule composition Microbial Challenges to vaccine Microbial Challenges to vaccine development Antigenic variation Antigenic variation of streptococcus capsule Treatment: Treatment: Susceptible to penicillin (difference to N. gonorrhea) Alternatively use broadspectrum cephalosporin Treatment and prevention N. meningitidis History History N. gonorrhoeae (“Gonococcus”) Gonorrhea initially thought to be first sign of syphilis (two diseases often found in the same individuals) First isolated and described in pus from patient by Neisser in 1879 1885 first pure culture and later fulfillments of Koch’s postulates on healthy volunteers Characteristics N. gonorrhoeae Oxidizes glucose only No capsule Fastidious 35oC36oC Morphology Morphology In vitro In pustular exudate; inside of neutrophils Morphology Morphology Fimbriae/pili extend several micrometer from bacteria Neisseria gonorrhoeae infects mucosal surfaces of urogenital track and induces a local inflammation response Ng Epithelial cells Major surface proteins of N. gonorrhoeae Pili Opa LOS PMN Virulence Factor
Pilin Por protein (protein I) Opa protein (protein II) Transferrinbinding proteins Lactoferrinbinding proteins Hemoglobinbinding proteins LOS IgA1 protease β-Lactamase Pathogenesis Pathogenesis
Protein that mediates initial attachment to nonciliated human cells; interferes with neutrophil killing Porin protein: promotes intracellular survival by preventing phagolysosome fusion in neutrophils Opacity protein: mediates firm attachment to eukaryotic cells Mediate acquisition of iron for bacterial metabolism Mediate acquisition of iron for bacterial metabolism Mediate acquisition of iron for bacterial metabolism Lipooligosaccharide: has endotoxin activity Destroys immunoglobulin A1 (role in virulence is unknown) Hydrolyzes the β-lactam ring in penicillin found mainly in extracellular pathogens IgA proteases IgA proteases IgA structure and bacterial targets IgA structure and bacterial targets 1) 3) 2) LOS Schematic of LPS
Glc Glc Glc Hep Hep
KDO KDO Schematic of LOS Gal Hep Core Domain
GlcN KDO Hep Hep
KDO Glc Glc Glc Gal
GlcN Gal GalN O O P O O O O O O O O CH2 O O O CH2 o
HO O CH2 o
O NH O P O OH O O P O o
HO O CH2 NH O O o
O NH O P O O O O O O HO O O O NH O O O O O O Major biological functions/effects of LOS
-attachment to epithelial tissue - stimulation of the production of bactericidal antibodies -regulation of complement activation on the surface of organisms -Induces inflammatory response (similar to LPS) mediation of toxic damage in the fallopian tube (sterility!) Concept: Phase variation Concept: Phase variation Alteration in the expression of surface antigens by bacteria (no mutation!) How? 1)multiple genes for surface antigen differentially expressed (environmental signal?) 2) use different reading frames Colony blot Western blot +1 +2 In frame lgtD reading frame Conclusions Conclusions LOS structures undergo high frequency antigenic variation The relative proportion of each LOS can vary due to different reading frames used for translation of proteins involved in LOS biosynthesis Phase variation helps to evade antibody mediated immune response Cause of 2nd most common STD ~300,000 reported cases per year but probably closer to 700,000 Most common in sexually active 1524YO Risk factor: multiple sex partners Efficiency of transmission: 35% infected women to men; 5060% infected man to women More than 50% of women remain asymptomatic but only less than 10% of men Epidemiology N. gonorrhoeae Epidemiology Epidemiology Epidemiology Overall rates falling, but incidence in certain groups remains high Chlamydia trachomatis co-infection with gonorrhea cases remains at about 40% Cofactor for HIV infection Gonorrhea Rates: U.S.
1970–2002 and the Healthy People 2010 objective 1970–2002
Rate (per 100,000 population) 500 400 300 200 100 0 1970 73 76 79 82 85 88 91 94 97 2000 Gonorrhea 2010 Objective Note: The Healthy People 2010 objective for gonorrhea is 19.0 cases per 100,000 population.
Gonorrhea Gonorrhea Age- and sex-specific rates: U.S., 2002
750 600 450 300 Rate (per 100,000 population)
150 7.4 287.9 538.1 320.4 199.2 131.4 92.1 48.1 17.3 4.4 124.5 0 Women
300 450 600 750 Age
10-14 15-19 20-24 25-29 30-34 35-39 40-44 45-54 55-64 65+ Total 0 150 46.6 675.6 650.3 251.4 113.1 57.4 31.3 10.6 2.1 0.8 125.5 Clinical Manifestations Gonorrhea in Men Usually symptomatic restricted to urethra; purulent discharge (white and thick) and dysuria (painful urination) develop after 25 days in 95% of infected individuals Complications are rare but include: prostatitis, orchitis/Epididymitis (infection of testis) Clinical Manifestations Gonorrhea in women Women: main infection site is cervix; in 50% of cases symptoms develop; vaginal discharge/ bleeding , dysuria and abdominal pain 50% of infections are ASYMPTOMATIC About 15% of infected women develop pelvic inflammatory disease; may lead to sterility Fallopian tube Fallopian tube Fallopian tubes transport the egg from the ovary to the uterus (the womb). The Fallopian tubes have small hairlike projections called cilia on the cells of the lining. These tubal cilia are essential to the movement of the egg through the tube into the uterus. If the tubal cilia are damaged by infection, the egg may not get 'pushed along' normally but may stay in the tube. Clinical Manifestations Bacteremia/Gonococcemia Disseminating infection with septicemia and infection of skin and joints occur in 13% of women (less frequent in men) Increase incidences in women is due to asymptomatic (untreated) cases Fever, suppurative arthritis, pustular rash on extremities but not head and trunk N. gonorrhoeae leading cause of purulent arthritis Clinical Manifestations Clinical Manifestations N. gonorrhoeae disseminating infection pustular rash necrotic grayish central lesion Clinical Manifestations Ophthalmia Neonatorum Infection of eyes of newborn during passage through birth canal (see also Chlamydia lecture) Serious consequences of corneal scarring Gram staining of purulent discharge or cervical swap (gramneg. diplococci) PCR Diagnosis N. gonorrhoeae Diagnosis Diagnosis N. gonorrhoeae Gonococcus in urethral exudate Prevention N. gonorrhoeae Use condoms No vaccine Preventive treatments of newborn with antibiotic eye drops! (contain various antibiotics: Erythromycin (mostly used), providoneiodine (not in USA), silver nitrate (less common now, first used in 1881)) Treatment N. gonorrhoeae Penicillin resistance! For uncomplicated infections use cephalosporin or fluoroquinolone; plus Tetracycline (Doxycycline) or Macrolide (Erythromycin) to treat for Chlamydia (co infections!!) Treat sex partner also (even if asymptomatic!) High chance they are also infected or it will spread Case Study Case Study
A 1weekold neonate has a yellowish exudate in the corners of both eyes. The child is otherwise well, afebrile and feeding normally. Gram stain of the exudate reveals no gramneg diplococci. A Giemsastained (stains nucleic acid) smear of the exudate reveals a large cytoplasmic inclusion. N. gonorrheae from diplococci gives it away ...
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This note was uploaded on 01/24/2011 for the course BSCI 424 taught by Professor Staff during the Fall '08 term at Maryland.
- Fall '08