Transcript House-Final-Gonorrhea

Neisseria gonorrhoeae
Nealia House
Gonorrhea
Topic Overview
 Biology of Neisseria gonorrhoeae

– Survival Within Host
Screening
 Treatment
 Control/Surveillance

http://www2.chemie.unierlangen.de/education/medchem/harnsteine/urs_infektion.html
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/lab1/dkngon.html
Affected Populations
STI Rates World-Wide
http://www.agi-usa.org/pubs/ib_std.html
Gonorrhea

Humans only natural
host
– Reproductive tract

Infection can be
asymptomatic
– Infertility

http://evolution.berkeley.edu/evosite/relevance/images/Ku
nkel_97210C.jpg
Several tests available
for detection of
gonorrhea
Gonorrhea
Topic Overview
 Biology of Neisseria gonorrhoeae

– Survival Within Host
Screening
 Treatment
 Control/Surveillance

http://www.nature.com/genomics/images/neisseria_200.jpg
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
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_sets/stds/graphics/Gonorrhea.gif
Structure
Diplococcus
 Gram-negative
 Fimbriae extend several micrometers from
cell surface

http://textbookofbacteriology.net/BSRP.html
http://gsbs.utmb.edu/microbook/images/fig97_2.JPG
Systemic Infection
http://www.infocompu.com/adolfo_arthur/ingles/gonorrea.htm
http://www.dermnet.com/thumbnailIndex.cfm?moduleID=16&module
GroupID=234&groupIndex=0&numcols=0
Infection

N. gonorrhoeae attaches to mucosal cells via pili
and other surface proteins
http://www.brown.edu/Courses/Bio_160/Projects1999/av/gonorrhea.html

Induces production of inflammatory cytokines by
epithelial cells
Infection
http://www.ncbi.nlm.nih.
gov/books/bv.fcgi?rid=m
med.figgrp.898
Survival Within Host

Evades host immune system by changing
surface proteins
– Often asymptomatic infection
http://www.brown.edu/Courses/Bio_160/Projects1999/av/gonorrhea.html

The RdgC protein is required for efficient
pilin antigenic variation
Antigenic Variation

Pilus promotes attachment of gonococcal
cell to host epithelial cell
– Must retain some consistency

Conserved N-terminal and variable Cterminal regions
– Constant regions
– Semi-variable regions
– Hypervariable regions

Phase variation from piliated to nonpiliated
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
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/mic
robiology/gono.jpg
Antimicrobial Resistance

Gonococcal strains resistant to:
– Penicillins
– Tetracyclines
– Spectinomycin
– Fluoroquinolones

Presently, ciprofloxacin and ofloxacin
recommended by CDC for treatment
Biotechnology

Oligonucleotide chips now used to screen
for antimicrobial resistance
– Point mutations in the gyrA and parC genes
 Determine the prevalence of ciprofloxacin-resistant
strains
Results identical to sequencing results
 Rapid and reliable analysis

Gonorrhea
Topic Overview
 Biology of Neisseria gonorrhoeae

– Survival Within Host
Screening
 Treatment
 Control/Surveillance

http://thailabonline.com/bacteria7.htm
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
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
Types of Tests

Culture Based Systems
– High degree of specificity
– Expensive
– Trained personnel
– Media requirements
– Presumptive identification
http://www.asu.edu/it/spotlight/archive/genesis/
 Growth on selective GC agar, gram stain, oxidase
and superoxol positivity
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/fish%20populations/STMaule5.htm
Types of Tests

DNA Probe Hybridization
– Specific chemiluminescent label on probe
– Available commercially
– 85% sensitivity
– 99% specificity
http://www.ebiotrade.com
Types of Tests

Nucleic Acid-Based Amplification Assays
(NAAT)
– 95% accurate
– False positives due to specimen crosscontamination, environmental contamination
http://www.biologicalprocedures.com/bpo/arts/1/6/m6.htm
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
Gonorrhea
Topic Overview
 Biology of Neisseria gonorrhoeae

– Survival Within Host
Screening
 Treatment
 Control/Surveillance

http://neisseria.org/ng/images/
Treatment
http://www.cdc.gov/STD/treatment/4-2002TG.htm#Gonococcal
Treatment

Fluoroquinolones
Levofloxacin
Ciprofloxacin
http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mmed.figgrp.686
http://www.alchemchina.com/products/apis_l.files/Levofloxacin.gif
Ofloxacin
http://www.m-ww.de/pharmakologie/arzneimittel/antiinfektiva/antibiotika/ofloxacin.html
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/antiinfektiva/antibiotika/ceftriaxon.html
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
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
Gonorrhea
Topic Overview
 Biology of Neisseria gonorrhoeae

– Survival Within Host
Screening
 Treatment
 Control/Surveillance

http://www.mediscan.co.uk/cfm/img_coll.cfm?action=sear
ch&imageID=020864&collectionID=21&name=Electron%2
0Micrographs&log=nk#
Prevention
Abstinence
 Safe/”smart” sex
 Barrier contraceptives
 Educational programs
 Reduce misuse of
antimicrobials

http://www.pueblo.gsa.gov/cic_text/health/contracept/co
ndom.gif
Governmental Programs

Health Canada
– Educational plans
– STD Screening
– Free STD clinics
Governmental Programs

CDC Gonococcal Isolate Surveillance
Project (GISP)
Conclusions

More research
– Reliable, fast screening
– Preventative
therapeutics
Non-biotechnological
interventions
 Prudent antimicrobial
use

http://www.agma.med.uni-giessen.de/cfagma/andro/verz.dbm
References
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Title Slide picture:
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