Sexually Transmitted Diseases

Urethritis/Mucopurulent Cervicitis

Urethritis (MEN) purulent penile discharge, dysuria.

Mucopurulent cervicitis (WOMEN) asymptomatic or new vaginal discharge, pain if ascends to upper tract causing pelvic inflammatory disease (PID). Diagnosis by mucopurulent cervical discharge (a white-tipped cotton swab inserted into the cervix turns yellow) many WBC on wet prep of cervical secretions

Niesseria gonorrheae

One of the oldest known illnesses. Gram (-) cocco-bacillus in pairs. Cultured on Thayer-Martin media, requires CO₂. Chromosomal resistance to PCN. Infects epithelium using pili and an outer membrane protein

Epidemiology: epidemic in urban minority groups, correlated with drug use

High rates of partner change are needed to maintain a substantial prevalence of disease because GC is treated or resolves spontaneously in a few wks. Chlamydia infections are milder and last longer, so lower rates of partner change can sustain the infection, therefore seen in broader socioeconomic spectrum. Herpes simplex and HPV last indefinitely so very low rates of partner change can sustain the infection, explaining the high prevalence in all segments of society.

Clinical: Incubation period 2-5 days (shorter than Chlamydia), in men, grossly purulent discharge with dysuria. In women, -vaginal discharge, dysuria, and intermenstrual bleeding

Complications: Disseminated Gonococcal Infection: bacteremic dissemination of GC to joints and skin. Complement def. predisposes to DGI (e.g. SLE). DGI- migratory polyarthritis, tenosynovitis, and frank arthritis. In women, ascending genital infection occurs 10-20% (PID) Þ endometritis, salpingitis, tuboovarian abscess, peritonitis.

Diagnosis: Gram stain of urethral discharge shows intracellular gram negative diplococci 95% of the time in symptomatic men. Culture on selective media > 95% yield

Treatment: 19% of strains in U.S. are PCN resistant; 20% are tetracycline resistant

Ceftriaxone 125mg IM x 1, Quinolones if PCN allergy. No quinolones in pregnant women
Chlamydia has been found in up to 30% of patients with GC, therefore must treat for both if GC found (add Doxycycline)

Chlamydia Trachomatis

The most common cause of nongonoccal urethritis (30-50% of NGU). The most common bacterial STD, 4 million US/ yr (1/2 million GC). Obligate intracellular bacteria with biphasic lifecycle (EB and RB)

Epidemiology: highest prevalence in sexually active adolescents, ~10%. Often asymptomatic. Risk factors include young age, large # of lifetime partners, current or previous GC

Transmission: maleÞ females > femaleÞ male, more difficult to transmit than GC

Clinical: incubation period 7-14 days. In men clear or grey urethral discharge; (lighter than GC), mild dysuria (25% of men infected with chlamydia are asymptomatic). In women, often asymptomatic, vaginal discharge, bleeding, and dysuria Complications: Epididymitis (chlamydia is most frequent cause in men < 35), sexually reactive arthritis (triggers Reiters syndrome; 80% of Reiters patients HLA-B27 positive). In women ascending disease to salpingitis, endometritis in 87% of infected women, major cause of infertility, perihepatitis also seen with chlamydia

Diagnosis: isolation in cell culture is gold std, Direct fluorescent antibody (DFA) uses labeled Ab specific for C. trachomatis protein to identify the chlamydia Ag in the clinical specimen. Also DNA probes and a Ligase chain reaction (LCR) test are being developed that will test urine.

Treatment: Doxycycline 100 mg po bid x 7 days($2) or Azithromycin 1 gm po x 1($16). Pregnant women Erythromycin.

Other less common pathogens in urethritis

Trichomonas vaginalis: 10% of nongonoccocal urethritis (NGU). Asymptomatic in men, causes sexually transmitted vaginitis in women (thin frothy discharge with high vaginal pH >5). Motile unicellar flagellate, can be seen 70% of time in wet prep of vaginal secretions in women. Treat with metronidazole 2 grams po x 1

Ureaplasma urealyticum: 20-40% of NGU, a mycoplasma which is small free-living prokaryote without a cell wall fastidious culture requirements, not routinely done in most labs. Treat with Doxycycline, but 10% are resistant therefore in NGU which failed Doxy, treat with Erythromycin covering tetracycline resistant ureaplasma

Herpes simplex virus: Men, causes 10% of NGU, usually with ulcer disease, Women: cervicitis in 10% of patients, usually with vaginal ulcer disease as well.

Genital Ulcer Disease

Important facilitator of transmission of HIV.

Prevalence varies geographically (3rd world, Chancroid. Industrialized HSV. Granuloma inguinale in New Guinea)

Non-infectious causes: Abrasions and Trauma, Fixed drug eruptions, Carcinoma, Reiter's syndrome, Bechet's syn.

(1) Infectious causes

Herpes Simplex Virus dsDNA virus can establish latent state in certain types of cells. The most common cause of genital ulcer disease in U.S.; 700,000 new cases/yr, with 20,000,000 recurrences/yr. Associated with (+) HSV-2 Ab: increasing age, lower levels of income or education, Ý # of sexual partners, AA or Hispanic men, and female gender

Most people who have it don’t know that they have it!

Transmission: male to female > female to male, can be spread without lesions, discordant couples have a 10% /yr transmission rate.

Clinical: Incubation period 2-7 days (Previous infection with HSV-1 decreases the severity of the initial HSV-2 infection). Initial episode often accompanied by systemic symptoms including fever, malaise, headache. Painful vesicular lesions. Lesions rapidly unroof to become superficial ulcers. Associated bilateral tender inguinal lymphadenopathy

Diagnosis: Gold std is culture in cell lines, with cytopathic effect noted in 24-72 hours. Rapid tests include Tzanck smear and direct fluorescent Ab which labels herpes simplex Ags in infected cells. Serology is helpful only in primary infection

(Current commercially available serological tests do not adequately distinguish between HSV-1 and HSV-2)

Treatment: For primary episode Acyclovir (Topical acyclovir is less effective than oral therapy). Recurrent episodes may be shortened by 1 day if acyclovir is started within 24 hrs of onset of symptoms (not worth the $ and effort unless severe)

Frequent recurrences (more than 6-12 per year) may be suppressed by chronic acyclovir (400 mg po bid)

Syphilis Spirochete, Treponema pallidum. Can not be cultured in vitro. Inoculated into rabbit testes to determine infectivity. Much more prevalent in 3^rd world than in U.S. (20/ 100,000 in U.S. in 1990 vs 360/ 100,000 in parts of Africa)

Remains 2^nd most common cause of genital ulcer disease in U.S. In the late 80s-early 90s disproportionately high in AAs, also significant Ý in midwest including Cleveland because of strong link with crack cocaine use (sex for drugs swapping)

Clinical: Traditionally divided into 3 stages

(1) Primary syphilis

painless chancre with raised edges with indurated clean base at site of inoculation
transmission occurs in 1/3rd of patients exposed to early syphilis
chancre occurs 10-90 days after infection (~21 days). heals spontaneously in 3-6 wks
firm non-tender inguinal lymphadenopathy may accompany primary syphilis

(2) Secondary syphilis

develops 4-10 wks after chancre, although 18-34% may still have chancre present
symptoms from dissemination of treponeme. Rash (75-100% of the time) non-pruritic involving palms and soles.
rash can also be pustular, eczematous or plaque-like
malaise, arthralgias
generalized lymphadenopathy (75-100% of cases)
patchy alopecia
condyloma lata (heaped up fleshy lesions in genital area occurring in 10-20% of patients with secondary syphilis)

(3) Tertiary syphilis

develops in 1/3rd of untreated patients an average of 10-20 years after infection

Gummas (chronic inflammatory lesions) most commonly found in skin and bone
aortitis (with resulting ascending aortic aneurysm) occurs in 10% of untreated patients

Neurosyphilis

CNS involved in all stages of disease. Tertiary neurosyphilis (tabes dorsalis: posterior column disease and generalized paresis: dementia, psychosis) occurs in 6-10% of infected patients
treponemes have been found in CSF of patients with primary disease
symptomatic neurosyphilis can be seen both in secondary and tertiarysyphilis
meningitis, otitis, uveitis, cranial nerve palsies (especially CN VII and VIII) with secondary syphilis
meningovascular syphilis (presents with stroke syn) usually 2-5 years after infection (do VDRL in young stroke patients)
Tabes and paresis 10-20 years

Diagnosis: primary disease: look at scraping under Darkfield microscopy for Spirochete; Diagnosis done by serology

Non treponemal tests (RPR, VDRL, STS)) are detecting Abs to lipids contained in treponemal cell membrane

good screening test, titer correlates with treatment, many causes of false positive tests must be confirmed by treponemal test

Treponemal tests (FTA, MHATP) detect Abs directed to treponeme therefore much more specific. Once positive, always remain positive despite treatment

Treatment: Penicillin remains drug of choice. Pregnant patients with PCN allergy, desensitization is recommended

primary and secondary disease, as well as early latent (infection < 1 year) benzathine PCN 2.4 million units is given IM.
for late latent syphilis (infection>1 yr or duration unknown) active secondary or tertiary disease should be ruled out by history and PE
Pts with neurological or ophthalmologic symptoms, other gummatous disease, HIV+, VDRL > 1:32, or nonPCN therapy planned should receive LP prior to treatment to r/o neurosyphilis. If neurosyphilis has been ruled out, treatment is benzathine PCN 2.4 million units IM q week x 3; PCN allergic patients get Doxycycline 100 po bid x 28 days
For neurosyphilis, IV penicillin is given at 18-24 million units/day x 10 days

Chancroid – Fastidious Gram (-) cocco-bacillary organism in a "school of fish" pattern. Requires chocolate agar, CO₂ supplementation and incubation at 33hr for growth. Difficult to culture, therefore diagnosis is often clinical after syphilis and HSV are ruled out. Common in 3rd world and a cofactor in HIV transmission. In U.S. outbreaks associated with prostitutes.

Clinical: Incubation period 4-7 days. Begins as pustule in genital area, which rapidly ulcerates. Ulcers are painful, deep, purulent with ragged undermined border. 1/2 of patients develop painful unilateral or bilateral lymphadenopathy

Treatment: several regimes to choose from:

Ceftriaxone 250 mg IM x 1
Azithromycin 1 gm po x 1
Erythomycin 500 mg qid x 7 days
Ciprofloxicin 500 mg po bid x 3 days

Lymphogranuloma venerum caused by serovars L1, L2, L3 of Chlamydia trachomatis. Endemic in Africa, India, Southeast Asia, South America and the Caribbean. Rare in US (~ 100cases/yr)

Clinical: initially a small papule or superficial ulcer at site of infection; lesion is not painful and usually not noticed. Days to wks after the primary lesion regional painful lymphadenitis develops with fever, headache, and myalgias. Lymph nodes involved are usually inguinal and femoral, and are unilaterally enlarged in 2/3 of patients

Diagnosis: serology with Chlamydial complement fixation titer greater than 1:32.

Treatment: Doxycycline (alternatively Erythromycin or Sulfisoxazole)

Granuloma Inguinale – caused by Calymmatobacterium granulomatosis, a pleomorphic Gram (-) bacillus. Bacteria show bipolar staining, the "Donovan bodies" (intracellular organisms) look like closed safety pins. Cannot be cultured

very rare in the US. Endemic in southeast India, New Guinea

Clinical: starts as small papule 8-80 days after exposure. Papule rapidly ulcerates to form velvety red, granulomatous painless ulcer with no associated lymphadenopathy.

Diagnosis: Bx or crush prep of tissue stained with Wright or Geimsa stain reveals intracellular Donovan bodies

Treatment: Doxycycline 100 bid until lesions healed (usually wks) alternatives (Erythromycin or Bactrim)

Disease	Pathogen	Ulcer	Lymphadenopathy	Diagnosis
Herpes	HSV-II (>70%) HSV-I (<30%)	Shallow, soft, painful, multiple	Firm, tender	Viral culture, Tzanck smear, DFA
Syphilis	Treponema pallidum	Indurated, painless, often single	Firm, non-tender	Dark field, RPR/FTA
Chancroid	Haemophilus ducreyi	Deep, painful, purulent	Fluctuant, tender	Often by exclusion (r/o HSV, syphilis)
Lymphogranuloma venerum	Chlamydia trachomatis serovars L1, L2, L3	Usually absent	Fluctuant, very tender	Chlamydia serology
Granuloma inguinale	Calymmatobacterium granulomatosis	Painless, velvety red, spreading	None	Biopsy with Donovan bodies

Genital Warts

Condylomata acuminata classic venereal warts, incidence Ý over past 15 yrs, Most common viral STD in US. DNA virus, Human papilloma virus (HPV). ~ 2/3 of sexual partners of patients with urogenital warts later develop warts themselves. Major cause of cervical cancer. Serotypes 16 and 18 most likely to progress to cervical cancer; also associated with penile and anal cancer

Clinical: flesh colored, raised papules that look like califlower, lesions turn white with application of 3-5% acetic acid

Treatment is cosmetic and to relieve local symptoms it does not eradicate the viral infection

Immune system plays important role in resolution of the infection (severe HPV disease noted in HIV infected patients)

Molluscum contagiosum Poxvirus infection, small papule, smooth with central umbilication. Resolves spontaneously in 6 months, not associated with malignancy. Seen in kids because of close skin contact.

Acute Retroviral Syndrome

Febrile illness associated with primary HIV infection. Incubation period 2-4 weeks

Clinical: fever, sore throat, generalized lymphadenopathy, truncal macular rash, also aseptic meningitis, oral and esophageal ulcers. Laboratory abnormalities including leukopenia followed by atypical lymphocytosis, transient CD4 cytopenia. Diagnosis is by viral culture or detection of p24 Ag. HIV Elisa will not yet be (+). HIV Elisa/Western Blot turn (+) with resolution of the illness