Sexually Transmitted Infections

Sexually Transmitted Infections

Plummer XD, Liang A

Clinical Case Applicability: pelvic inflammatory disease, infertility, chronic pelvic pain

Learning Objectives:

1. Understand the pathophysiology of common STIs

2. Describe the long-term sequelae of STIs

3. Understand the mechanism of action for treatment of common STIs

What is the pathophysiology of infectivity & treatment of these organisms? (HPV: see CIN script)

HSV (herpes) (figure 1):

– Primary infection: entry through mucous membrane -> viral entry into sensory nerves -> retrograde axonal transport to dorsal root ganglion -> lifelong latency

– Reactivation: viral particles/proteins transported anterograde into skin/mucous membranes -> viral shedding and cell lysis -> vesicles/ulceration

– Treatment: Not curable; Nucleoside analogs (acyclovir) can ↓ frequency and severity of flares

–Acyclovir -> converted to acyclovir triphosphate -> acyclovir triphosphate competitively inhibits and inactivates HSV DNA polymerases -> prevents further viral DNA synthesis

C trachomatis (chlamydia) (figure 2): Obligate intracellular organism that exists in 2 forms: extracellular infectious elementary bodies (EBs) and intracellular non-infectious reticulate bodies (RBs)

– EBs attach and invade vaginal epithelial cells through cell surface receptors -> EBs reorganize into a large RB inside a phagosome that migrates towards the cell nucleus -> RBs replicate via binary fission and forms an inclusion -> inclusion condenses into EBs -> cell lysis releases EBs that infect other cells

– Treatment: Curable with a single dose of azithromycin -> binds to 50S subunit of bacterial ribosome -> inhibits mRNA translation -> arrests RNA-dependent bacterial protein synthesis -> inhibits bacterial growth

N gonorrhoeae (gonorrhea): Gram-negative diplococci that are obligate intracellular bacterium

– Pili allows N gonorrhoeae to adhere to mucosal membrane -> bacteria penetrate mucosal membrane & invade cells

– Treatment: Curable with a single dose of ceftriaxone binds to bacterial transpeptidases  disruption of bacterial cell wall cross-linking damage to cell wall cell lysis

T. pallidum (syphilis): Gram negative spirochetes

– Outer membrane promotes attachment to mucous membranes -> travels via lymphatic system to regional lymph nodes -> production of hyaluronidase which facilitate perivascular invasion -> disseminated disease

– Treatment: Curable in early stages with single dose of intramuscular penicillin binds bacterial transpeptidasesdisruption of bacterial cell wall cross-linkingdamage to cell wall cell lysis

T. vaginalis (trichimonas): Anaerobic flagellated protozoan

– Pathogenesis not well understood: postulated to involve contact-dependent and contact-independent mechanisms

– Treatment: Curable with a single dose of metronidazole  nitro group of metronidazole reduced by ferredoxin in anaerobic bacterianitro radical causes oxidative damage to bacterial DNAcell death

What are the long-term consequences of untreated STIs?

– Pelvic inflammatory disease (PID): ascending infection to the uterus & tubescan cause infertility

– ↑ susceptibility to HIV: inflammation caused by trichomoniasis can ↑ risk of acquiring and spreading HIV

– Tertiary disease: untreated, disseminated syphilis can infect many organs including the CNS

What is the pathophysiology underlying PID?

– Proliferative phase of the menstrual cycle cervical mucosal barrier is thinner  allows bacteria to enter the uterus and subsequently the fallopian tubes

– Bacteria cause destruction of the epithelial cells, cilia and microvilli  localized inflammatory reactionchronic inflammation with tissue remodeling and scarring Plummer XD, Liang A

Figure 1

Figure 2

References

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