Sexually Transmitted Infections

What host factors influence the risk of contracting STIs?

Complement deficiency (C5-C8)

HIV status

Syphilis

Spirochete *Treponema pallidum*

Transmission requires close contact (horizontal spread through sexual contact; vertical spread – transplacental infection)

Organism sensitive to drying

*Treponema pallidum*

Limited ability to grow organism in labs

Replicates __**VERY**__ slowly → Incubation\~ 3 weeks

DO NOT HAVE A TCA CYCLE (rely on host cells for purines, pyrimidines, & a.a.)

Microaerophilic/anaerobic (extremely sensitive to O2)

How is *T. pallidum* transmitted?

MSM are at greatest risk (anyone who has sex w/ barrier protection)

Exclusive to humans (can **NOT** spread through inanimate objects)

Transferred during early stages of disease

Contact with cutaneous/mucosal lesions

How is someone infected with *T. pallidum?*

Enters the body through small abrasions on skin/mucous membranes → Local multiplication → Infiltration of plasma cells, PMNs, & macrophages → Immune response reduces bacterial burden → Resolution of lesion

DOES NOT RELIABLY ELIMINATE INFECTION

Endarteritis

inflammation of the inner lining of an artery

Primary Syphilis

2-10 weeks after initial contact: bacteria multiply at site of infection

Primary chancre appears at site of infection – usually painless

Enlarged inguinal nodes (proliferation of bacteria in regional lymph nodes)

Spontaneous healing may/can occur

Patient still highly infectious

Secondary Syphilis

1-3 months after primary syphilis symptoms

Flu-like illness (myalgia, fever, headache, mucocutaneous rash)

Symptoms can spontaneously resolve

Multiplication of bacteria and production of lesions in: lymph nodes, liver, joints, muscles, skin, mucous membranes

Latent Syphilis

\~2-6 weeks after 2º syphilis resolves

Treponemas are dormant in liver and spleen (bacterial hepatitis)

Reactivation of treponemas → multiplication

Can last anywhere between 3-30 years

Tertiary Syphilis

Progressive destructive disease (dissemination & invasion; cell mediated HS)

Neurosyphilis (“General paralysis of the insane”; Tabes dorsalis)

Cardiovascular syphilis (Aortic lesions; heart failure)

Gummas in skin, bones, testes

Tabes dorsalis

loss of coordination of movement, especially as a result of syphilitic infection of the spinal cord

Congenital Syphilis

Infected mother transmits *T. pallidum* to baby in utero

Acquired after first 3 months of pregnancy (serious infection results in intrauterine death; congenital abnormalities)

Silent infection (not apparent until \~2 years of age; facial & tooth deformities)

How can we diagnose syphilis?

*T. pallidum* can __**NOT**__ be grown (easily) in (most) laboratory

Exudate from 1º chancre can be examined w/ dark-field microscopy

UV microscopy after staining w/ fluorescein antibodies

Silver staining

Cardiolipin

non-specific syphilis test that allows for detection of anti-lipid IgG and IgM; Lipoidal material released from damaged cells → lipids in the surface of *T. pallidum*

ELISA use in syphilis can be used to detect what?

IgM or IGG

FTA-ABS (Fluorescent treponemal antibody absorption) test

specific syphilis test where a patient’s serum is absorbed w/ nonpathogenic treponemes → removes cross reacting Ab → detection of reaction w/ *T. pallidum* antigens

How can we treat syphilis?

Penicillin (drug of choice; reliably tx fetus when given to mother)

•Doxycycline if allergy to penicillin

Prevention of 2º & 3º disease depends on early dx & appropriate tx

How is congenital syphilis treated?

treatable w/ early screening of mother'; Treatment w/ penicillin

Gonorrhea

*Neisseria gonorrhoeae (*Gram - coccus; Gonococcus – diplococci)

Gonococcus does __**not**__ survive well outside humans

Asymptomatically infected people are major reservoir (women > men)

2nd most reported STI in USA

What are the gonococcal virulence factors?

**Pili –** mediate attachment; responsible for antigenic variation

**PorB** – must be functionally active for gonococcus to survive

**LOS –** increases TNFα activity

What is the site of entry of *N. gonorrhoeae*?

Vagina or urethral mucosa of penis are sites of entry

Can enter through throat or rectal mucosa

Infection is **USUALLY** localized – can disseminate

How does *N. gonorrhoeae* evade host antibodies?

Produce IgA protease

What is the pathogenesis of gonorrhoeae?

Gonococci invade non-ciliated epithelial cells → Multiplication in intracellular vacuoles (protected from phagocytes & antibodies) →

Vacuoles move down & fuse w/ basement membrane of the cell → Release bacterial contents into subepithelial connective tissues → Damage is result of host inflammatory response (untreated can cause chronic inflammation & fibrosis)

How is gonorrhea transmitted?

Direct transmission, person to person (sexual contact)

Vertical transmission from mother to baby (childbirth)

Women have a 50% chance of becoming infected after contact, men have 20% chance

What are the symptoms of gonorrhea in women?

Initially asymptomatic

Vaginal discharge

Untreated can lead to: PID, chronic pelvic pain, infertility

More likely to develop invasive disease

Sore throat

Rectal purulent discharge

What are the symptoms of gonorrhea in men?

Urethral discharge, dysuria

Sore throat

Rectal purulent discharge

How can we diagnose gonorrhea?

Microscopy & culture (urethral & vaginal discharges(

Cultures are needed for women/asymptomatic men

Cultures also aid in antibiotic susceptibility tests

Cultured on selective (Thayer Martin) & non-selective medium (chocolate)

Blood cultures for suspected disseminated disease

Joint aspirates

How do we treat gonorrhea?

Cefixime or ceftriaxone (+ azithromycin)

Antibiotic eyedrops for affected babies

How can we prevent Gonorrhea?

Follow-up & contact tracing are vital to control spread

Condoms for prevention

What can compromise the treatment of gonorrhea?

penicillinase producing strains (resistance to fluroquinolones also observed)

Chlamydia

*Chlamydia trachomatis* (very small, intracellular bacteria)

Exists in different forms: Elementary body (EB) & Reticulate body (RB) – adapted for intracellular multiplication

What form of chlamydia is adapted for extracellular survival and initiation of infection?

\
A. Elementary body (EB)

B. Reticulate body (RB)

A. Elementary body (EB)

What form of chlamydia is adapted for intracellular multiplication?

\
A. Elementary body (EB)

B. Reticulate body (RB)

B. Reticulate body (RB)

What serotypes of Chlamydia cause trachoma?

\
A. A, B, C

B. D-K

C. L1, L2, L3

A. A, B, C

What serotypes of Chlamydia cause cervicitis, urethritis, proctitis, conjunctivitis, pneumonia (in neonates)?

\
A. A, B, C

B. D-K

C. L1, L2, L3

B. D-K

What serotypes of Chlamydia cause lymphogranuloma venereum?

\
A. A, B, C

B. D-K

C. L1, L2, L3

C. L1, L2, L3

Trachoma

serious eye infection

Cervicitis

infection/inflammation of cervix

Urethritis

infection/inflammation of urethra

Proctitis

infection/inflammation of prostate

Conjunctivitis

infection/inflammation of conjunctiva; eye infection

Pneumonia

infection in the lungs

Lymphogranuloma venereum

chronic infection of the lymphatic system

What is the most common bacterial STI?

*Chlamydia trachomatis*

What type of cells are infected with *Chlamydia trachomatis?*

Nonciliated columnar, cuboidal, and transitional epithelial cells

What form of *Chlamydia trachomatis* is a metabolically inactive infectious form?

Elementary body (EB)

What form of *Chlamydia trachomatis* accumulates in the phagosome and are called inclusions?

Reticulate body (RB)

How is *C. trachomatis* transmitted?

Most infections are genital, acquired through sexual contact

Neonates develop ocular infections from passage through birth canal

Adult ocular infections can also occur

What is the pathogenesis of chlamydia?

Chlamydiae enter host through small abrasions in mucosal surfaces → Bind to specific receptors on host cell → “parasite induced” endocytosis → Inside the cell lysosomal fusion is inhibited → EB begins its developmental cycle → EB differentiate into metabolically active RBs → RBs divide and produce fresh EB progeny → Released into extracellular environment

What serotypes of Chlamydia are restricted to columnar and transitional epithelial cells?

\
A. A, B, C

B. D-K

C. L1, L2, L3

B. D-K

What serotypes of Chlamydia can cause systemic disease?

\
A. A, B, C

B. D-K

C. L1, L2, L3

C. L1, L2, L3

What are the symptoms of *C. trachomatis?*

Most genital tract infections are asymptomatic (can result in PID in women)

Clinical manifestations can include cervicitis & endometritis

Bartholinitis, perihepatitis, salpingitis, urethritis

Mucopurulent discharge is seen in symptomatic infections

How can we diagnose chlamydia?

Microscopy using direct fluorescent antibody test (EBs stain bright yellow-green)

Nucleic-acid-based tests are capable of directly testing (Nucleic acid probe and amplification tests; Specimen from cervix, urethra, urine, etc. can be used; Commercially available – rapid results)

How can we treat chlamydia?

__**NOT**__ susceptible to β-lactam antibiotics

Azithromycin along w/ β-lactam antibiotics for concurrent infections (Prescribed to partners too)

Erythromycin used in babies

Prevention = condoms

Lymphogranuloma venereum

*C. trachomatis* serotypes L1, L2, L3

Systemic infection involving lymphoid tissue

Common in Africa, Asia, and South America

Affects males > females (especially men who have sex w/ men)

What are the clinical features of Lymphogranuloma venereum?

Primary lesion is an ulcerating papule at site of inoculation (occurs after 1-4 weeks)

Accompanied w/ fever, headache, myalgia

Systemic complication can include fever, hepatitis, pneumonitis, meningoencephalitis

What is a complication associated with Lymphogranuloma venereum?

Chronic granulomatous reactions in lymphatics & neighboring tissues

Can cause fistula in ano or genital elephantiasis

How do we diagnose Lymphogranuloma venereum?

Cell culture, immunofluorescence, nucleic-acid based tests for diagnosis

How can we treat Lymphogranuloma venereum?

Doxycycline or erythromycin

Pregnant women and children < 9 years old should be treated w/ erythromycin

Chancroid

*Haemophilus ducreyi* infection 

Characterized by a **painful** non-indurated genital ulcers

Local lymphadenitis

Endemic in some areas of USA (occurs in outbreaks)

What is the most common cause of genital ulcers in Africa and Asia?

chancroid

*Haemophilus ducreyi*

Gram-negative

Requires specialized media – chocolate agar (Hemin (X factor) & Nicotinamide adenine dinucleotide (V factor))

Causes tender papule 5–7 days after exposure → 2 days later–lesion ulcerates → Inguinal lymphadenopathy

How do we diagnose chancroid?

Gram stain of aspirates from ulcer (also can use enlarged lymph node aspirates)

*H. ducreyi* is hard to grow in laboratory (use rich media & lower temps (33C))

Slow growth – 2 to 9 days

How do we treat chancroid?

erythromycin, azithromycin, or ceftriaxone

Donovanosis

*Klebsiella granulomatis* infection (granuloma inguinale or granuloma venereum)

Common in tropical and subtropical regions (Caribbean, New Guinea, India & central Australia)

Nodules → erode to granulomatous ulcers → ulcers bleed on contact

Bacteria invade and multiply within mononuclear cells → Cause lysis

*Klebsiella granulomatis*

Gram negative

Prolonged incubation (weeks-months)

Transmitted via sexual contact or nonsexual trauma to the genitalia

Causes painless granulomatous lesions (can resemble syphilis)

How do we diagnose donovanosis?

Wright’s or Giemsa stain on smear from lesion

Appearance of Donovan bodies (clusters of blue/black stained organisms in cytoplasm of mononuclear cells)

How do we treat donovanosis?

doxycycline, azithromycin, or co-trimoxazole

What are potential causes of genital tract infections?

*Mycoplasma hominis*

*Mycoplasma genitalium*

*Ureaplasma urealyticum*

What pathogen may cause non-gonococcal urethritis?

\
A. *Mycoplasma genitalium*

B. *Mycoplasma hominis*

C. *Ureaplasma urealyticum*

A. *Mycoplasma genitalium*

What pathogen may cause PID, postabortal and postpartum fevers, pyelonephritis?

\
A. *Mycoplasma genitalium*

B. *Mycoplasma hominis*

C. *Ureaplasma urealyticum*

B. *Mycoplasma hominis*

What pathogen may cause non-gonococcal urethritis and prostatitis?

\
A. *Mycoplasma genitalium*

B. *Mycoplasma hominis*

C. *Ureaplasma urealyticum*

C. *Ureaplasma urealyticum*

What are treatment options for genital tract infections?

doxycycline or azithromycin

Candidiasis

*Candida albicans (n*ormal flora of vagina)

Can be transmitted sexually (presence does not imply sexual transmission)

Increase in candida causes an intensely irritant vaginitis

Can be accompanied by urethritis and dysuria

May present as UTI

Balanitis is seen in \~10% of male partners of infected women

Balanitis

Inflammation of glans penis

*Candida albicans*

Exist as an oval yeastlike form that produce buds or blastoconidia

Forms germ tubes

Primary site of colonization is the GI tract (whole tube)

Opportunistic pathogen (can infect many sites)

What are predisposing factors for Candidiasis?

Oral contraceptives

Pregnancy

Diabetes mellitus

Systemic corticosteroids

HIV

Antibiotic use

How can we diagnose candidiasis?

microscopy or culture of discharge

How can we treat candidiasis?

Treated w/ topical antifungal – clotrimazole (oral antifungal – fluconazole)

*Trichomonas vaginalis*

Protozoan parasite

Inhabits vagina (women) and urethra/prostate (men)

Causes vaginitis w/ copious amounts of discharge

One of the most prevalent non-viral STIs in USA (higher incidence in HIV+ population)

Associated w/ PID in HIV+ women

How is *Trichomonas vaginalis* transmitted?

transmitted as fomite

*T. vaginalis* infection is associated with what?

associated with preterm delivery

Heavy infection with what pathogen leads to copious foul-smelling vaginal discharge?

*T. vaginalis* infection

How do we diagnose *T. vaginalis?*

Detected by wet preparation microscopy of secretions or swab

Rapid immunochromatographic tests & nucleic acid detection test

How do we treat *T. vaginalis?*

nitroimidazoles, metronidazole, or tinidazole

Sexual partners should __**BOTH**__ be treated

Bacterial Vaginosis

Associated w/ *Gardnerella vaginalis*

Causes a fishy smelling discharge

Can be associated w/ an anaerobic infection

Can be sexually transmitted

Disruption of the normal acidity of vagina & of equilibrium between constituents of normal flora

Bacterial vaginosis is characterized by what?

Excessive malodorous vaginal discharge

Vaginal pH > 4.5

Presence of clue cells (vaginal epithelial cells coated with bacteria)

A fishy/amine-like odor

*G. vaginalis* is consistently found in what?

found in vaginosis

How can we diagnose bacterial vaginosis?

Can be cultured on human blood agar plates from swab (Urethra & Vaginal)

How can we treat bacterial vaginosis?

metronidazole

Genital Herpes

Most commonly caused by Herpes simplex virus 2 (HSV2) (HSV1 can also be cause)

HSV2 is transmitted sexually (most common STI, \~500 million infected worldwide)

Herpes Simplex Virus - 2

Large, enveloped virus (dsDNA)

Encodes crucial enzymes (DNA-dependent DNA polymerase, deoxyribonuclease, thymidine kinase, ribonucleotide reductase, protease)

Very little cross immunity w/ HSV1 (infect mucoepithelial cells)

Can cause lytic or latent infection

Infection can result in 2-fold increased risk of developing HIV (breach in mucosal barrier due to ulcers)

Ribonucleotide reductase

converts ribonucleotides to deoxyribonucleotides

Thymidine kinase

phosphorylates the deoxyribonucleosides to provide substrates for replication of the viral genome

How does HSV infect cells?

Binds to cell surface receptor → Penetration through fusion of envelope & cell surface membrane → Interaction w/ nectin-1 → Virion releases capsid into cytoplasm → enters nucleus → transcription → replication → assembly → capsid buds into trans-golgi network → released by exocytosis or cell lysis

Infection of what can establish HSV2 latency?

infection of neurons

What enzyme is necessary for HSV2 latency?

thymidine kinase

What are the only regions to be transcribed on HSV2 virus?

Latency-associated transcripts (LATs)

Reoccurrence of HSV2 can be activated by which type of stimuli?

Stress, trauma, fever, sunlight

What is the process of latency in HSV2?

Lesion → Virus travels up sensory nerve endings → Establishes latent infection in dorsal root ganglion neurons → Reactivation (sunburn, stress, trauma) → Travels down nerves to same area → Recurrent lesions