Neisseria gonorrhoeae Nealia House Gonorrhea n Topic Overview

Neisseria gonorrhoeae Nealia House

Gonorrhea n Topic Overview n Biology of Neisseria gonorrhoeae – Survival Within Host n Screening n Treatment n Control/Surveillance http: //www 2. chemie. unierlangen. de/education/medchem/harnsteine/urs_infektion. html

Gonorrhea n Sexually transmitted disease n Infection Rate – socioeconomic class – Age n Very common infectious disease – STI second only to chlamydia n Increasing antibacterial resistance n Increases efficiency of HIV transmission http: //www. cat. cc. md. us/courses/bio 141/labmanua/lab 1/dkngon. html

Affected Populations STI Rates World-Wide http: //www. agi-usa. org/pubs/ib_std. html

Gonorrhea n Humans host only natural – Reproductive tract n Infection can be asymptomatic – Infertility http: //evolution. berkeley. edu/evosite/relevance/images/Ku nkel_97210 C. jpg n Several tests available for detection of gonorrhea

Gonorrhea n Topic Overview n Biology of Neisseria gonorrhoeae – Survival Within Host n Screening n Treatment n Control/Surveillance http: //www. nature. com/genomics/images/neisseria_200. jpg

Transmission n 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/980215 ap/morrow. html

Transmission n 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 n Diplococcus n Gram-negative n Fimbriae extend several micrometers from cell surface http: //textbookofbacteriology. net/BSRP. html

http: //gsbs. utmb. edu/microbook/images/fig 97_2. JPG

Systemic Infection http: //www. infocompu. com/adolfo_arthur/ingles/gonorrea. htm http: //www. dermnet. com/thumbnail. Index. cfm? module. ID=16&module Group. ID=234&group. Index=0&numcols=0

Infection n N. gonorrhoeae attaches to mucosal cells via pili and other surface proteins http: //www. brown. edu/Courses/Bio_160/Projects 1999/av/gonorrhea. html n Induces production of inflammatory cytokines by epithelial cells

Infection http: //www. ncbi. nlm. nih. gov/books/bv. fcgi? rid=m med. figgrp. 898

n Evades Survival Within Host host immune system by changing surface proteins – Often asymptomatic infection http: //www. brown. edu/Courses/Bio_160/Projects 1999/av/gonorrhea. html n The Rdg. C protein is required for efficient pilin antigenic variation

Antigenic Variation n Pilus promotes attachment of gonococcal cell to host epithelial cell – Must retain some consistency n Conserved N-terminal and variable Cterminal regions – Constant regions – Semi-variable regions – Hypervariable regions n Phase variation from piliated to nonpiliated

Immune Memory n Infection history did not alter antibody levels in patients with current infection – Suggests immunological memory not induced by uncomplicated gonococcal infections n Local and systemic immune responses to gonococci extremely modest – Slight increase in serum immunoglobulin G (Ig. G) in infected males – Slight increase in serum Ig. A 1 antibodies in infected females

Survival Within Host n Pili, outer membrane proteins, lipopolysaccharides – – – Binding to epithelial surfaces Passage through epithelium Interaction with phagocytes Variations in outer membrane protein (P 1, Por) n Requires n – Carbon dioxide – Sulfur in form of cysteine – Iron http: //www. med. monash. edu. au/assets/images/mic robiology/gono. jpg

Antimicrobial Resistance n Gonococcal strains resistant to: – Penicillins – Tetracyclines – Spectinomycin – Fluoroquinolones n Presently, ciprofloxacin and ofloxacin recommended by CDC for treatment

Biotechnology n Oligonucleotide chips now used to screen for antimicrobial resistance – Point mutations in the gyr. A and par. C genes § Determine the prevalence of ciprofloxacin-resistant strains n Results identical to sequencing results n Rapid and reliable analysis

Gonorrhea n Topic Overview n Biology of Neisseria gonorrhoeae – Survival Within Host n Screening n Treatment n Control/Surveillance http: //thailabonline. com/bacteria 7. htm

Screening n “Gold Standard” – Nucleic acid amplification assays § Polymerase chain reaction n Cell culture to confirm diagnosis – Oxidase positive http: //education. med. nyu. edu/courses/microbiology/courseware/infect-disease/Gram_Neg_Bacilli 5. html

Types of Tests n 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/Infectious. Diseases/ID_Gonorrhea. asp

Types of Tests n 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 n 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%20 populations/STMaule 5. htm

Types of Tests n DNA Probe Hybridization – Specific chemiluminescent label on probe – Available commercially – 85% sensitivity – 99% specificity http: //www. ebiotrade. com

Types of Tests n Nucleic (NAAT) Acid-Based Amplification Assays – 95% accurate – False positives due to specimen crosscontamination, environmental contamination http: //www. biologicalprocedures. com/bpo/arts/1/6/m 6. htm

Current Screening n No test for samples from all major sites of gonococcal infection – Rapid – Inexpensive – Reliable n Such a test would improve case-finding – Efficient treatment – Disease management

Gonorrhea n Topic Overview n Biology of Neisseria gonorrhoeae – Survival Within Host n Screening n Treatment n Control/Surveillance http: //neisseria. org/ng/images/

Treatment http: //www. cdc. gov/STD/treatment/4 -2002 TG. htm#Gonococcal

Treatment n 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 n 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 n 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 n Hard to develop – No animal model n No immune memory to Neisseria gonorrhoeae – Antigenic variation strategy n Difficulty finding target common to all strains n Research continues to identify possible vaccine targets – DNA vaccines – Mucosal immunization

Gonorrhea n Topic Overview n Biology of Neisseria gonorrhoeae – Survival Within Host n Screening n Treatment n Control/Surveillance http: //www. mediscan. co. uk/cfm/img_coll. cfm? action=sear ch&image. ID=020864&collection. ID=21&name=Electron%2 0 Micrographs&log=nk#

Prevention n Abstinence n Safe/”smart” sex n Barrier contraceptives n Educational programs n Reduce misuse of antimicrobials http: //www. pueblo. gsa. gov/cic_text/health/contracept/co ndom. gif

Governmental Programs n Health Canada – Educational plans – STD Screening – Free STD clinics

Governmental Programs n CDC Gonococcal Isolate Surveillance Project (GISP)

Conclusions n More research – Reliable, fast screening – Preventative therapeutics n Non-biotechnological interventions n Prudent antimicrobial use http: //www. agma. med. uni-giessen. de/cfagma/andro/verz. dbm

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