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Neisseria gonorrhoeae

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Title: Neisseria gonorrhoeae


1
Neisseria gonorrhoeae
  • Nealia House

2
Gonorrhea
  • Topic Overview
  • Biology of Neisseria gonorrhoeae
  • Survival Within Host
  • Screening
  • Treatment
  • Control/Surveillance

http//www2.chemie.uni-erlangen.de/education/medch
em/harnsteine/urs_infektion.html
3
Gonorrhea
  • Sexually transmitted disease
  • Infection Rate
  • socioeconomic class
  • Age
  • Very common infectious disease
  • STI second only to chlamydia
  • Increasing antibacterial resistance
  • Increases efficiency of HIV transmission

http//www.cat.cc.md.us/courses/bio141/labmanua/la
b1/dkngon.html
4
Affected Populations
STI Rates World-Wide
http//www.agi-usa.org/pubs/ib_std.html
5
Gonorrhea
  • Humans only natural host
  • Reproductive tract
  • Infection can be asymptomatic
  • Infertility
  • Several tests available for detection of gonorrhea

http//evolution.berkeley.edu/evosite/relevance/im
ages/Kunkel_97210C.jpg
6
Gonorrhea
  • Topic Overview
  • Biology of Neisseria gonorrhoeae
  • Survival Within Host
  • Screening
  • Treatment
  • Control/Surveillance

http//www.nature.com/genomics/images/neisseria_20
0.jpg
7
Transmission
  • Does not survive in the environment, must be
    transmitted through contact
  • Unprotected sex
  • Contact with eyes, mouth
  • Mother to child during birth

Neonatal hyperacute purulent conjunctivitis
http//www.aafp.org/afp/980215ap/morrow.html
8
Transmission
  • Transmissibility dependent on
  • Strain
  • Male to female transmission more effective
  • Higher number of organisms present in male
    urethral discharge than female vaginal secretions

http//www.biology.arizona.edu/human_bio/problem_s
ets/stds/graphics/Gonorrhea.gif
9
Structure
  • Diplococcus
  • Gram-negative
  • Fimbriae extend several micrometers from cell
    surface

http//textbookofbacteriology.net/BSRP.html
10
http//gsbs.utmb.edu/microbook/images/fig97_2.JPG
11
Systemic Infection
http//www.infocompu.com/adolfo_arthur/ingles/gono
rrea.htm
http//www.dermnet.com/thumbnailIndex.cfm?moduleID
16moduleGroupID234groupIndex0numcols0
12
Infection
  • N. gonorrhoeae attaches to mucosal cells via pili
    and other surface proteins
  • Induces production of inflammatory cytokines by
    epithelial cells

http//www.brown.edu/Courses/Bio_160/Projects1999/
av/gonorrhea.html
13
Infection
http//www.ncbi.nlm.nih.gov/books/bv.fcgi?ridmmed
.figgrp.898
14
Survival Within Host
  • Evades host immune system by changing surface
    proteins
  • Often asymptomatic infection
  • The RdgC protein is required for efficient pilin
    antigenic variation

http//www.brown.edu/Courses/Bio_160/Projects1999/
av/gonorrhea.html
15
Antigenic Variation
  • Pilus promotes attachment of gonococcal cell to
    host epithelial cell
  • Must retain some consistency
  • Conserved N-terminal and variable C-terminal
    regions
  • Constant regions
  • Semi-variable regions
  • Hypervariable regions
  • Phase variation from piliated to non-piliated

16
Immune Memory
  • Infection history did not alter antibody levels
    in patients with current infection
  • Suggests immunological memory not induced by
    uncomplicated gonococcal infections
  • Local and systemic immune responses to gonococci
    extremely modest
  • Slight increase in serum immunoglobulin G (IgG)
    in infected males
  • Slight increase in serum IgA1 antibodies in
    infected females

17
Survival Within Host
  • Pili, outer membrane proteins, lipopolysaccharides
  • Binding to epithelial surfaces
  • Passage through epithelium
  • Interaction with phagocytes
  • Variations in outer membrane protein (P1, Por)
  • Requires
  • Carbon dioxide
  • Sulfur in form of cysteine
  • Iron

http//www.med.monash.edu.au/assets/images/microbi
ology/gono.jpg
18
Antimicrobial Resistance
  • Gonococcal strains resistant to
  • Penicillins
  • Tetracyclines
  • Spectinomycin
  • Fluoroquinolones
  • Presently, ciprofloxacin and ofloxacin
    recommended by CDC for treatment

19
Biotechnology
  • Oligonucleotide chips now used to screen for
    antimicrobial resistance
  • Point mutations in the gyrA and parC genes
  • Determine the prevalence of ciprofloxacin-resistan
    t strains
  • Results identical to sequencing results
  • Rapid and reliable analysis

20
Gonorrhea
  • Topic Overview
  • Biology of Neisseria gonorrhoeae
  • Survival Within Host
  • Screening
  • Treatment
  • Control/Surveillance

http//thailabonline.com/bacteria7.htm
21
Screening
  • Gold Standard
  • Nucleic acid amplification assays
  • Polymerase chain reaction
  • Cell culture to confirm diagnosis
  • Oxidase positive

http//education.med.nyu.edu/courses/microbiology/
courseware/infect-disease/Gram_Neg_Bacilli5.html
22
Types of Tests
  • Gram-Stained Smear
  • Sensitivity reduced in asymptomatic infections
  • Less that 50 sensitive as cell culture
  • Not useful in rectal infections

http//www.lahey.org/Medical/InfectiousDiseases/ID
_Gonorrhea.asp
23
Types of Tests
  • Culture Based Systems
  • High degree of specificity
  • Expensive
  • Trained personnel
  • Media requirements
  • Presumptive identification
  • Growth on selective GC agar, gram stain, oxidase
    and superoxol positivity

http//www.asu.edu/it/spotlight/archive/genesis/
24
Types of Tests
  • Antigen Detection and Enzyme Immunoassays
  • Extensively investigated
  • Low/high prevalence
  • Symptomatic/asymptomatic
  • Few to no situations for which this assay
    recommended
  • Because of antigenic variation

http//wfrc.usgs.gov/research/fish20populations/S
TMaule5.htm
25
Types of Tests
  • DNA Probe Hybridization
  • Specific chemiluminescent label on probe
  • Available commercially
  • 85 sensitivity
  • 99 specificity

http//www.ebiotrade.com
26
Types of Tests
  • Nucleic Acid-Based Amplification Assays (NAAT)
  • 95 accurate
  • False positives due to specimen
    cross-contamination, environmental contamination

http//www.biologicalprocedures.com/bpo/arts/1/6/m
6.htm
27
Current Screening
  • No test for samples from all major sites of
    gonococcal infection
  • Rapid
  • Inexpensive
  • Reliable
  • Such a test would improve case-finding
  • Efficient treatment
  • Disease management

28
Gonorrhea
  • Topic Overview
  • Biology of Neisseria gonorrhoeae
  • Survival Within Host
  • Screening
  • Treatment
  • Control/Surveillance

http//neisseria.org/ng/images/
29
Treatment
http//www.cdc.gov/STD/treatment/4-2002TG.htmGono
coccal
30
Treatment
  • Fluoroquinolones

Levofloxacin
Ciprofloxacin
http//www.ncbi.nlm.nih.gov/books/bv.fcgi?ridmmed
.figgrp.686
http//www.alchemchina.com/products/apis_l.files/L
evofloxacin.gif
Ofloxacin
http//www.m-ww.de/pharmakologie/arzneimittel/anti
infektiva/antibiotika/ofloxacin.html
31
Treatment
  • Ceftriaxone (Rocephin)
  • Single dose intramuscularly
  • Introduced as treatment in 1985
  • Retained resistance
  • Beta-lactam antibiotic
  • Action against penicillinase

http//www.m-ww.de/pharmakologie/arzneimittel/anti
infektiva/antibiotika/ceftriaxon.html
32
Treatment
  • Possible co-infection with Chlamydia trachomatis

Azithromycin
Doxycycline
http//www.cbwinfo.com/Pharmaceuticals/Structures/
Doxycycline.gif
http//www.bmb.leeds.ac.uk/mbiology/ug/ugteach/icu
8/images/antibiotics/azithromycin.gif
33
Vaccine
  • Hard to develop
  • No animal model
  • No immune memory to Neisseria gonorrhoeae
  • Antigenic variation strategy
  • Difficulty finding target common to all strains
  • Research continues to identify possible vaccine
    targets
  • DNA vaccines
  • Mucosal immunization

34
Gonorrhea
  • Topic Overview
  • Biology of Neisseria gonorrhoeae
  • Survival Within Host
  • Screening
  • Treatment
  • Control/Surveillance

http//www.mediscan.co.uk/cfm/img_coll.cfm?action
searchimageID020864collectionID21nameElectro
n20Micrographslognk
35
Prevention
  • Abstinence
  • Safe/smart sex
  • Barrier contraceptives
  • Educational programs
  • Reduce misuse of antimicrobials

http//www.pueblo.gsa.gov/cic_text/health/contrace
pt/condom.gif
36
Governmental Programs
  • Health Canada
  • Educational plans
  • STD Screening
  • Free STD clinics

37
Governmental Programs
  • CDC Gonococcal Isolate Surveillance Project
    (GISP)

38
Conclusions
  • More research
  • Reliable, fast screening
  • Preventative therapeutics
  • Non-biotechnological interventions
  • Prudent antimicrobial use

http//www.agma.med.uni-giessen.de/cfagma/andro/ve
rz.dbm
39
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