Micro Chapter 69 - Sexy times
Magnitude of the Problem
 United States in highest rates of STDs of any developed country in the world
 Adolescent girls (age 15-19) had most Chlamydia and gonorrhea cases of any age group
 50% of all preventable infertility among women is result of Chlamydia and gonorrhea
 Neisseria gonorrhoeae growing resistance to antibiotics for past 2 decades
 Chancroid (STD that causes genital ulcer disease) declined since 1987, but remains problem in southern U.S. and
inner cities (along w/syphilis)
o Syphilis increasing in African Americans and MSM
 Seroprevalence of genital herpes (HSV-2) decreased over past 20 years
Population Dynamics
 Rate of spread of STD depends on (all affected by biological, behavioral, and social risk factors)
o Transmissibility of infectious agent
o Rate of new partner acquisition and partner’s sexual history
o Duration of infectiousness
 Infectivity rate – risk of acquiring infection during single contact w/infected partner
 HIV possesses specific surface molecules for attachment to host cell receptors found primarily on rectal
epithelial cells as well as lymphocytes; anal intercourse spreads faster
 Core – small number of people who have large number of sexual partners over lifetime
 Duration of infectivity – length of time that individual capable of transmitting infection
o Chlamydiae causes asymptomatic disease; carriers then transmit disease
o If agent drug resistant, treatment will fail and infective period will be increased
Groups at Risk
 Features of cervical anatomy of adolescents (primarily cervical ectopy) increase likelihood of chlamydial or
gonococcal infection and thus increase risk of PID
 Most STD-causing agents enter body at local sites, through mucosal or squamous epithelial layers of cervix,
urethra, rectum, oral pharynx, or (to lesser extent) vagina
o HIV transmitted primarily by sexual contact but contaminated blood products and needles also work
o Nearly all agents of STDs relatively sensitive to chemical and physical factors and are almost never found
free in the environment; animal reservoirs unknown for most agents
 Acute manifestations of most frequent STDs are
o Mucopurulent cervicitis and urethritis (gonorrhea and chlamydia)
o Genital ulcer disease (syphilis, chancroid, and genital herpes)
 STD-causing agents tend to cause primary lesions at or near site of entry; often not very noticeable
 Most serious consequences of STDs relate to progression to chronic infections
o Pelvic inflammatory disease (PID) – ascending infection of uterus and fallopian tubes most commonly
caused by gonococci and chlamydia
o Anogenital cancer – includes cervical cancer caused by some HPV types
o Secondary and tertiary syphilis
o Recurrent herpes infection
o Fallopian tube scarring and adhesions of surrounding tissues, resulting in ectopic pregnancy, infertility,
and chronic pelvic pain
o Congenital diseases (syphilis, herpes, papillomatosis, and chlamydia)
o Increased risk of acquiring HIV due to genital ulcers (syphilis, chancroid, and herpes) or altered genital
mucosa (gonorrhea and chlamydia)
o Adverse outcomes of pregnancy – premature termination, fetal wastage, low birth weight, and
premature rupture of membranes
Pelvic Inflammatory Disease
 Frequently results in severe, irreversible sequelae of infertility, ectopic pregnancy, and chronic pelvic pain
 60% of cases subclinical and women only present when they have ectopic pregnancy or infertility
 Most cases caused by N. gonorrhoeae or C. trachomatis and follow cervicitis and urethritis
o Can also be caused by endogenous bacteria

Primary episode followed by subsequent episodes caused by endogenous organisms
o Pathogenesis of gonococcal and chlamydial PID includes nonspecific inflammatory responses to bacterial
invasion that result in tissue damage, as well as specific immune responses to gonococci or chlamydiae
 Gonococcal or chlamydial cervical infection may damage endocervical canal, break down mucus plug in
endocervix and allow pathogens, as well as endogenous vaginal organisms to ascend into upper genital tract
o Adolescent females have larger zone of ectopy (extension of columnar epithelium from endocervical
canal to ectocervix) than older women; no cervical mucus here; increased susceptibility because
columnar cells preferential sites of microbial attachment and invasion
 Host defenses that prevent centripetal spread of organisms
o Tubal ciliary movement (unidirectional toward uterus)
o Flow of mucus in tubal lumen (toward uterus)
o Myometrial contractions during menses (sloughing of endometrium)
 Contraceptive risks of PID
o Oral contraceptives may decrease risk of chlamydial PID
o IUDs increase risk of PID within first few months of placement
o Vaginal douching increases risk
 Most cases of gonococcal PID occur during or near end of menses; hormonal changes during menstrual cycle
may lead to changes in cervical mucus plug, permitting passage of organisms, particularly when estrogen levels
high and progesterone levels low
o Reflux of infected blood during menstrual uterine contractions provides route of entry to fallopian tubes
 Gonococcal PID – strain typing of N. gonorrhoeae based on defining specific amino acid and nucleoside
nutritional requirements of isolate (auxotype) and serotyping based upon another membrane protein (porin)
divided into PorA and PorB, each of which composed of many serovars
o Strain variation of gonorrhea based on porin classification associated w/likelihood of progression to PID
o In fallopian tube, motility of ciliated epithelial cells slows and ultimately ceases due to toxic action of LPS
or murein fragments
 Gonococci attach to nonciliated epithelial cells via pili after which they are internalized, move to
basal portion of cells, and exit into subepithelium to cause inflammation
o PMN WBC response contributing to local inflammation, microabscess formation, and purulent exudate
o Tissue damage from lipooligosaccharide (LOS) and peptidoglycan; toxic portion is lipid A of LOS
 Chlamydial PID – infection starts by attachment of organisms to cells via specific receptor-ligand interactions
(chlamydial major outer membrane protein involved)
o Organisms actively induce uptake by stimulating endocytosis; no phagolysosomal fusion because of
surface components of elementary bodies (infectious form of organism)
o Chlamydia-containing inclusions visible in histologic preparations
o In phagosomes, elementary bodies differentiate into reticulate bodies (metabolic form of organism)
o Reticulate bodies reorganize into new elementary bodies and in time are released from host cell to
infect adjacent cells
o Incites greater mononuclear immune response than gonococci, but neutrophils also seen, mainly in
early phases of inflammatory response
 High prevalence of gonoccal and chlamydial coinfection caused recommendations that patients w/either
infection be treated for both
o Simultaneous gonococcal infection facilitates chlamydial replication in cervical epithelia 100x;
stimulation of endocytosis in nonciliated epithelial cells by first parasite leads to alterations in surface
structure of cells, allowing ready uptake of second parasite
 Bacterial vaginosis (BV) – most common vaginal infection worldwide; disruption of normal vaginal flora
characterized by malodorous vaginal discharge
o Normally dominant colonizing lactobacilli (especially species that produce H2O2) markedly reduced, and
Gardnerella vaginalis, Atopobium vaginalae, anaerobic streptococci, Prevotella species, and genital
mycoplasmas increase in numbers
HIV and STDs
 Other STDs increase transmission of HIV; HIV affects treatment options of other STDs




Risk of HIV transmission increased in presence of both genital ulcer diseases and nonulcerative diseases,
including vaginal diseases (BV, candida vaginitis, and trichomonal vaginitis)
o HPV infection and anogenital warts don’t facilitate HIV transmission because they don’t usually cause
breaks in skin or mucous membranes
Compromised immune system of patients w/AIDS may result in more severe manifestations of other STDs
o Molluscum contagiosum (cutaneous poxvirus infection) seen more often in HIV-infected people and can
cause extensive disfiguring lesions
o Kaposi sarcoma (malignancy partially attributable to sexually transmitted herpes virus (type 8)) AIDSdefining condition
o Genital warts due to HPV more likely to cause cervical dysplasia; chancroid less responsive to treatment
Intercourse during menses increases risk of HIV transmission (mucosal irritation, friability, and bleeding shorten
route to target cells and impair function of natural defenses)
o All STDs w/enhanced superficial inflammation provide inflammatory cells as targets for viral invasion
and dissemination
o Local inflammation results in proinflammatory cytokine production (can enhance local HIV replication)
HIV gene products are potent intracellular transactivating factors, enhancing growth of HSV and HPV