Gonorrhea pathophysiology: Difference between revisions

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====HIVinfection====
====HIVinfection====
Gonorrhea is associated with increased susceptibility to the transmission and acquisition of [[HIV|HIV infection]] by following mechanisms:<ref name="pmid9217758">{{cite journal| author=Cohen MS, Hoffman IF, Royce RA, Kazembe P, Dyer JR, Daly CC et al.| title=Reduction of concentration of HIV-1 in semen after treatment of urethritis: implications for prevention of sexual transmission of HIV-1. AIDSCAP Malawi Research Group. | journal=Lancet | year= 1997 | volume= 349 | issue= 9069 | pages= 1868-73 | pmid=9217758 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9217758  }} </ref><ref name="pmid23733950">{{cite journal| author=Malott RJ, Keller BO, Gaudet RG, McCaw SE, Lai CC, Dobson-Belaire WN et al.| title=Neisseria gonorrhoeae-derived heptose elicits an innate immune response and drives HIV-1 expression. | journal=Proc Natl Acad Sci U S A | year= 2013 | volume= 110 | issue= 25 | pages= 10234-9 | pmid=23733950 | doi=10.1073/pnas.1303738110 | pmc=3690901 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23733950  }} </ref><ref name="pmid23733950">{{cite journal| author=Malott RJ, Keller BO, Gaudet RG, McCaw SE, Lai CC, Dobson-Belaire WN et al.| title=Neisseria gonorrhoeae-derived heptose elicits an innate immune response and drives HIV-1 expression. | journal=Proc Natl Acad Sci U S A | year= 2013 | volume= 110 | issue= 25 | pages= 10234-9 | pmid=23733950 | doi=10.1073/pnas.1303738110 | pmc=3690901 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23733950  }} </ref>
Gonorrhea is associated with increased susceptibility to the transmission and acquisition of [[HIV|HIV infection]] by following mechanisms:<ref name="pmid9217758">{{cite journal| author=Cohen MS, Hoffman IF, Royce RA, Kazembe P, Dyer JR, Daly CC et al.| title=Reduction of concentration of HIV-1 in semen after treatment of urethritis: implications for prevention of sexual transmission of HIV-1. AIDSCAP Malawi Research Group. | journal=Lancet | year= 1997 | volume= 349 | issue= 9069 | pages= 1868-73 | pmid=9217758 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9217758  }} </ref><ref name="pmid23733950">{{cite journal| author=Malott RJ, Keller BO, Gaudet RG, McCaw SE, Lai CC, Dobson-Belaire WN et al.| title=Neisseria gonorrhoeae-derived heptose elicits an innate immune response and drives HIV-1 expression. | journal=Proc Natl Acad Sci U S A | year= 2013 | volume= 110 | issue= 25 | pages= 10234-9 | pmid=23733950 | doi=10.1073/pnas.1303738110 | pmc=3690901 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23733950  }} </ref><ref name="pmid23733950">{{cite journal| author=Malott RJ, Keller BO, Gaudet RG, McCaw SE, Lai CC, Dobson-Belaire WN et al.| title=Neisseria gonorrhoeae-derived heptose elicits an innate immune response and drives HIV-1 expression. | journal=Proc Natl Acad Sci U S A | year= 2013 | volume= 110 | issue= 25 | pages= 10234-9 | pmid=23733950 | doi=10.1073/pnas.1303738110 | pmc=3690901 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23733950  }} </ref>
*Increased HIV expression and viral production by activation of HIV infected CD4
*Increased HIV expression and viral production by activation of HIV infected [[CD4 cell|CD4]] (transmission)
*Altered HIV specific CD8 cell response
*Altered HIV specific [[CD8 cell]] response (acquisition)
It seems HIV RNA concentrations in [[semen]] is eightfold higher among those with gonococcal urethritis.<ref name="pmid8442924">{{cite journal| author=Laga M, Manoka A, Kivuvu M, Malele B, Tuliza M, Nzila N et al.| title=Non-ulcerative sexually transmitted diseases as risk factors for HIV-1 transmission in women: results from a cohort study. | journal=AIDS | year= 1993 | volume= 7 | issue= 1 | pages= 95-102 | pmid=8442924 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8442924  }} </ref>
It seems HIV RNA concentrations in [[semen]] is eightfold higher among those with gonococcal urethritis.<ref name="pmid8442924">{{cite journal| author=Laga M, Manoka A, Kivuvu M, Malele B, Tuliza M, Nzila N et al.| title=Non-ulcerative sexually transmitted diseases as risk factors for HIV-1 transmission in women: results from a cohort study. | journal=AIDS | year= 1993 | volume= 7 | issue= 1 | pages= 95-102 | pmid=8442924 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8442924  }} </ref>



Revision as of 18:53, 19 September 2016

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sara Mehrsefat, M.D. [2]

Overview

Pathophysiology

Gonorrhea is a sexually transmitted disease (STD) that is caused by Neisseria gonorrhea. Neisseria gonorrhea is gram-negative intracellular diplococcus, oxidase-positive, utilizes glucose, but not sucrose, maltose, or lactose. It can infectmucus-secreting epithelial cells both in men and women.

Transmission

The recognized routes of transmission of the Neisseria gonorrhoeae include:

  • Male to female via semen. The transmission rate is estimated to be 50%-70% per episode of vaginal intercourse
  • Female vagina to male urethra. The transmission rate is estimated to be 20% per episode of vaginal intercourse and increases to 60%-80% after 4 or more exposures.
  • Rectal intercourse
  • Fellatio and less commonly cunnilingus can result in pharyngeal gonorrhea
  • Perinatal transmission

Virulence factors

The recognized virulence factors of the Neisseria gonorrhoeae include:

  • The main pathogenicity of the Neisseria gonorrhea obtains from the surface pili by following mechanisms:[1][2][3]
  • Opa proteins (opacity-associated protein) is a surface proteins that helps gonococcus binds to receptors on immune cells[4][5][6]
    • Down-regulate activated CD4 cells (prevent an Immune response)
    • Inhibit B-cell antibody production (unable immunological memory against gonorrhea)
  • Porin, two main serotypes have been identified:[7][8][9]
    • PorB.1A strains
      • Have ability to bind to complement inhibitory molecules and resulting in a diminished inflammatory response (disseminated gonococcal infection)
    • PorB.1B strains
      • Cause local genital infections only
  • Lipooligosaccharides (LOS)[10][11]
    • LOS binds to human asialoglycoprotein receptor (ASGP-R) expressed on sperm cells and urethral epithelial cells
  • Gonococcal ribosomal protein L12[12][13]
    • allows attachment to and invasion of an endometrial cell line via interaction with the lutropin receptor (LHr) which lead to pelvic inflammatory disease (PID) or disseminated gonococcal infection (DGI) in women
  • Release of IgA1 proteases[14][15]
    • The exact pathogenesis is not fully understood. It is though that IgA protease may play a role gonococcal infection in women

In pregnancy, gonococcus can be transmitted to the fetus at the time of delivery. This results in infection of the conjuctiva. This appears 1 to 4 days after birth as severe discharge with marked swelling and redness of the eyelids and conjunctiva.

Associated Conditions

HIVinfection

Gonorrhea is associated with increased susceptibility to the transmission and acquisition of HIV infection by following mechanisms:[16][17][17]

  • Increased HIV expression and viral production by activation of HIV infected CD4 (transmission)
  • Altered HIV specific CD8 cell response (acquisition)

It seems HIV RNA concentrations in semen is eightfold higher among those with gonococcal urethritis.[18]

References

  1. Sparling PF (1966). "Genetic transformation of Neisseria gonorrhoeae to streptomycin resistance". J Bacteriol. 92 (5): 1364–71. PMC 276432. PMID 4958881.
  2. Swanson J (1973). "Studies on gonococcus infection. IV. Pili: their role in attachment of gonococci to tissue culture cells". J Exp Med. 137 (3): 571–89. PMC 2139381. PMID 4631989.
  3. Wolfgang M, Lauer P, Park HS, Brossay L, Hébert J, Koomey M (1998). "PilT mutations lead to simultaneous defects in competence for natural transformation and twitching motility in piliated Neisseria gonorrhoeae". Mol Microbiol. 29 (1): 321–30. PMID 9701824.
  4. Jerse AE, Cohen MS, Drown PM, Whicker LG, Isbey SF, Seifert HS; et al. (1994). "Multiple gonococcal opacity proteins are expressed during experimental urethral infection in the male". J Exp Med. 179 (3): 911–20. PMC 2191399. PMID 8113683.
  5. Boulton IC, Gray-Owen SD (2002). "Neisserial binding to CEACAM1 arrests the activation and proliferation of CD4+ T lymphocytes". Nat Immunol. 3 (3): 229–36. doi:10.1038/ni769. PMID 11850628.
  6. Pantelic M, Kim YJ, Bolland S, Chen I, Shively J, Chen T (2005). "Neisseria gonorrhoeae kills carcinoembryonic antigen-related cellular adhesion molecule 1 (CD66a)-expressing human B cells and inhibits antibody production". Infect Immun. 73 (7): 4171–9. doi:10.1128/IAI.73.7.4171-4179.2005. PMC 1168567. PMID 15972507.
  7. Young JD, Blake M, Mauro A, Cohn ZA (1983). "Properties of the major outer membrane protein from Neisseria gonorrhoeae incorporated into model lipid membranes". Proc Natl Acad Sci U S A. 80 (12): 3831–5. PMC 394146. PMID 6407021.
  8. Ram S, Cullinane M, Blom AM, Gulati S, McQuillen DP, Monks BG; et al. (2001). "Binding of C4b-binding protein to porin: a molecular mechanism of serum resistance of Neisseria gonorrhoeae". J Exp Med. 193 (3): 281–95. PMC 2195916. PMID 11157049.
  9. Ram S, McQuillen DP, Gulati S, Elkins C, Pangburn MK, Rice PA (1998). "Binding of complement factor H to loop 5 of porin protein 1A: a molecular mechanism of serum resistance of nonsialylated Neisseria gonorrhoeae". J Exp Med. 188 (4): 671–80. PMC 2213355. PMID 9705949.
  10. Harvey HA, Jennings MP, Campbell CA, Williams R, Apicella MA (2001). "Receptor-mediated endocytosis of Neisseria gonorrhoeae into primary human urethral epithelial cells: the role of the asialoglycoprotein receptor". Mol Microbiol. 42 (3): 659–72. PMID 11722733.
  11. Harvey HA, Porat N, Campbell CA, Jennings M, Gibson BW, Phillips NJ; et al. (2000). "Gonococcal lipooligosaccharide is a ligand for the asialoglycoprotein receptor on human sperm". Mol Microbiol. 36 (5): 1059–70. PMID 10844691.
  12. Spence JM, Clark VL (2000). "Role of ribosomal protein L12 in gonococcal invasion of Hec1B cells". Infect Immun. 68 (9): 5002–10. PMC 101722. PMID 10948117.
  13. Tsampalas M, Gridelet V, Berndt S, Foidart JM, Geenen V, Perrier d'Hauterive S (2010). "Human chorionic gonadotropin: a hormone with immunological and angiogenic properties". J Reprod Immunol. 85 (1): 93–8. doi:10.1016/j.jri.2009.11.008. PMID 20227765.
  14. Lin L, Ayala P, Larson J, Mulks M, Fukuda M, Carlsson SR; et al. (1997). "The Neisseria type 2 IgA1 protease cleaves LAMP1 and promotes survival of bacteria within epithelial cells". Mol Microbiol. 24 (5): 1083–94. PMID 9220014.
  15. Hobbs MM, Sparling PF, Cohen MS, Shafer WM, Deal CD, Jerse AE (2011). "Experimental Gonococcal Infection in Male Volunteers: Cumulative Experience with Neisseria gonorrhoeae Strains FA1090 and MS11mkC". Front Microbiol. 2: 123. doi:10.3389/fmicb.2011.00123. PMC 3119411. PMID 21734909.
  16. Cohen MS, Hoffman IF, Royce RA, Kazembe P, Dyer JR, Daly CC; et al. (1997). "Reduction of concentration of HIV-1 in semen after treatment of urethritis: implications for prevention of sexual transmission of HIV-1. AIDSCAP Malawi Research Group". Lancet. 349 (9069): 1868–73. PMID 9217758.
  17. 17.0 17.1 Malott RJ, Keller BO, Gaudet RG, McCaw SE, Lai CC, Dobson-Belaire WN; et al. (2013). "Neisseria gonorrhoeae-derived heptose elicits an innate immune response and drives HIV-1 expression". Proc Natl Acad Sci U S A. 110 (25): 10234–9. doi:10.1073/pnas.1303738110. PMC 3690901. PMID 23733950.
  18. Laga M, Manoka A, Kivuvu M, Malele B, Tuliza M, Nzila N; et al. (1993). "Non-ulcerative sexually transmitted diseases as risk factors for HIV-1 transmission in women: results from a cohort study". AIDS. 7 (1): 95–102. PMID 8442924.

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