Gynecologic Infections

Vulcovaginal Infections – sexually transmitted, recurrent

(A) Ulcerating – natural history: microabrasion Þ systemic dissemination Þ local proliferation Þ immune response Þ persistence in latent state Þ recurrence

(1) Syphilis (Treponema pallidum - spirochete) – hallmark is local lymphoplasmacytic response: lesions of palms and soles, periarteritis Þ obliterative endarteritis, Granulation tissue Þ fibrous scarring

Risks: transmission to fetus (enteritis, pancreatitis), late complications (aortic aneurysms, neurosyphilis)

(2) Genital Herpes (Herpes Simplex Virus I/II – dsDNA virus)

epithelial necrosis Þ bullae Þ perivasculitis: productive infection – VP16 transactivator protein (squamous epithelium) induces immediate-early genes

spread through sensory nerves to dorsal root ganglia

tissue-specific latency in ganglia (ganglia lack VP16 activator function)

Reinfection via retrograde spread: activation induced by stress, tissue damage, or adjacent infections

Histology: viral inclusion body (crystal at center of nucleus), multinuclated aggragate

Risks: transmission to fetus during delivery (affects liver and adrenal), dissemination (encephalitis), indolent inguinal lesions

(3) Lymphogranuloma Venerum (Chlamydia trachomatis, LGV subtypes)

(4) Chancroid (Hemophilus ducrey - gram negative coccobacilli)

(5) Granuloma Inguinale (Calymmatobacter granulomatis - gram negative bacillus, similar to Klebsiella)

(B) Proliferative – squamous epithelial hyperplasia

(1) Human Papilloma Virus – small nonenveloped dsDNA virus

Infects: stratum basalis; Replicates: in Stratum Spinosum and Granulosum; Capsid assembly: in Keratinocytes
low cancer risk (types 6 and 11)–cause condyloma acuminatum (anogenital warts); circular nonintegrated DNA
high cancer risk (types 16 and 18)–intraepithelial neoplasia; integrated DNA, overproduce E6 and E7 oncoproteins

Oncogenic mechanism:

dysregulation of viral E6 and E7 oncoproteins by integration or mutation of viral E2 regulatory factor binding sites
altered host cell cycle and DNA repair via binding of tumor suppressor genes (E6-p53, E7-Rb binding)
E6 affects other cellular responses as well

Pathology: acanthosis, hyerkeratosis, papilomatosis (monoclonal)

(2) Molluscum Contagiosum (small dsDNA poxvirus): umbilicated vulvar papules (pearly white), not inflammatory, venereal spread, self-limited - no risk of malignancy

(C) Vaginal

(1) Vaginitis – infections with leukocytic inflammatory responses:

Candida albicans: branching pseudohyphae, Trichomonas vaginalis; strawberry cervitis, flagellum

(2) Bacterial "vaginosis"–imbalance in normal flora/"clue cells"/itching and malodorous discharge; not truly infection

ß Lactobacilli (ß pH, ß redox potential)Þ overgrowth of facultative and strict anaerobic bacteria (Gardnerella, Bacteroides, Peptostreptococci)

Risks: Ý in premature labor with pregnancy postoperative gynecologic infections

Cervical Infection – sexually transmitted venereal diseases

Organisms: Neisseria gonorrhea – mucosal pathogen with multiple virulence factors

virulence factors: can shuffle DNA sequence (varying pili and outer membrane proteins), elicits blocking antibody, IgA₁ protease, Antibiotic resistance
Gram stain: neutrophiles with intracellular gram-negative diplococci

Chlamydia trachomatis – obligate intracellular bacteria with distinct 48 hour growth cycle

Life cycle: 48hrs, attachment and phagocytosis of elementary body (outside cell), RNA and protein synthesis, intracellular assembly of reticulate bodies, replication in inclusions, maturation to elementary bodies and lysis

Histology: reticular bodies within the cell

Risks: spread to upper genital tract – can infect fallopian tubes, preterm labor

Pathology:

(1) Acute fulminant (mucopurulent) cervicitis: N.gonorrhea and C.trachomatis

(2) Chronic persistent (follicular) cervicitis: C.trachomatis

Upper Genital Tract Infections – pelvic inflammatory disease/Endometritis-Salpingitis-Peritonitis

(A) Acute pelvic inflammatory disease (Acute PID) – exudative infection (neutrophils) spreading along and around Mullerian-type epithelium; Risks: venereal transmission, chronic PID

N.gonorrhea, C.trachomatis – intracanalicular spread
Nongonococcal/Nonchlamydial – intracanalicular, extracanalicular (virulent aerobic and canalicular; spread facultative anaerobic from adjacent organs bacteria - e.g. E.Coli, Group A streptococci)

(B) Chronic pelvic inflammatory disease (Chronic PID) – long-term complication of acute PID with scarring, obstruction, and localized abscess formation Þ requires prior tubal damage

Progression: Pyosalpinx Þ hydrosalpinx (blockage Þ balloning of tube) followed by Tubo-Ovarian Abscess (TOA) complex and/or Salpingitis Isthmica Nodosum (SIN; blockage Þ passageway in muscular walls Þ ectopic pregnancy)

Risks: chronic pelvic pain, septic shock, infertility, ectopic pregnancy

(1) Post-acute pelvic inflammatory disease (ß tissue redox potential, emergence of facultative and strict anaerobic bacteria)

(2) IUD-associated: (Actinomyces israeli) – typical site of infection: foreign body communicating with vaginal flora