A. Overview

1. Includes a large number of infectious diseases of all types
2. Most common in USA is probably HPV
   1. Often asymptomatic in men
   2. Causes genital warts in both sexes
   3. Causes cervical cancer, particularly in HIV+ persons
3. Urethritis is second most common STD
   1. More than 50% is sexually transmitted
   2. Caused by Chlamydia trachomatis in ~40% of cases
   3. N. gonorrhea causes ~30% and Ureaplasma urealyticum ~10%
   4. May progress to pelvic inflammatory disease (PID) in women
   5. In men, often asymptomatic by may manifest with pain, dysuria, pyuria
4. Other STDs are discussed in separate sections
   1. Human Immunodeficiency Virus (HIV)
   2. Human Papilloma Virus (HPV)
   3. Syphilis
   4. Hepatitis B, C, and D Viruses
   5. Herpes Simplex Viruses
   6. Pubic Lice
   7. Bacterial Vaginitis
5. Internet Web Site www.cdc.gov/std/treatment [1]

B. Gonorrhoea

1. Caused by gram negative diplococcus Neisseria gonorrhoea (gonococcus)
2. Usually symptomatic in women and men
3. Spectrum of Disease
   1. Urethritis
   2. Causes about ~50% of cases of PID
   3. Pharyngitis (from genital-oral contact)
   4. Complications of Primary Infection
4. Complications of Gonococcal Infection
   1. Infertility and Ectopic Pregnancy
   2. Tubo-ovarian Abscess
   3. Peri-oophoritis
   4. Fitz-Hugh-Curtis Syndrome (rare perihepatitis from gonococcal infection)
   5. Disseminated Gonococcemia (see below)
   6. Gonococcal arthritis - including septic arthritis and arthritis-dermatitis syndrome [19]
5. Symptoms of Gonococcal Urethritis
   1. Incubation 1-5d with abrupt onset
   2. Dysuria and discharge found in majority (>70%) of patients
   3. Discharge is nearly always (>90%) purulent
6. Gonococcal Arthritis Syndromes [19]
   1. Disseminated Infection - organisms may be cultured from joint (localized septic arthritis)
   2. Disseminated gonococcal infection may cause arthritis-dermatitis syndrome (ADS)
   3. ADS resembles systemic vasculitis with macules, petechiae, purulent vessicles and arthritis, and usually includes positive blood cultures
7. Detection
   1. Gram stain of vaginal or penile swab
   2. Culture on Thayer-Martin Plates
   3. Transcription mediated amplification on urine samples detects ~90% of gonorrhea [10]
   4. Polymerase chain reaction (PCR) on urine samples detects 55% of gonorrhea in women [10]
8. Urethritis Treatment Overview
   1. In general, patients should be treated for both gonococci and chlamydia
   2. This is because these organisms frequently track together
   3. Chlamydia treatment covered below
   4. Sexual partners of affected persons should be treated as well
   5. Some low grade PID may be treated as outpatient
   6. Nonoxynol-9 gel does not reduce urogenital gonococcal or chlamydial infection [5]
9. Treatment of Gonococcal Infection [1,2,9]
   1. Ceftriaxone (Rocephin®) 125mg im x 1
   2. Cefixime (Suprax®) 400mg po qd x 1
   3. Azithromycin is effective and resistance is low [9]
   4. Increasing fluoroquinolone resistance (~4%)
   5. Therefore, ofloxacin 400mg po x 1 or ciprofloxacin 500mg po x 1 are second line [9]
   6. Spectinomycin 2gm im x 1
   7. Patients should abstain from sexual intercourse for 7 days [1]
   8. Patients with gonorrhea should be treated empirically for chlamydia [16]
10. Treatment in Pregnant Women
    1. Erthromycin (non-estolate) 500mg po qid x 7 days
    2. Amoxicillin 500mg po tid x 7 days is as effective as erythromycin in pregnancy
    3. Azithromycin may be safe in pregnancy, but data are not currently sufficient
11. Disseminated Gonococcemia
    1. Rash and Arthralgias - true arthritis may occur in arthritis-dermatitis syndrome [19]
    2. Pelvic Pain ± Discharge
    3. High Fever
    4. Waterhouse-Friedrickson Syndrome: Adrenal Destruction
12. Treatment of Disseminated Gonococcemia
    1. All IV regimens for 1-2 days AFTER improvement, then 1 week of oral therapy
    2. Recommend 1gm ceftriaxone IV or IM qd
    3. Alternative: cefotaxime or ceftizoxime 1gm IV q8 hours
    4. Alternative: levofloxacin 250mg IV qd
    5. Alternative: ciprofloxacin or ofloxacin 400mg IV q12 hours
    6. Alternative: sepctinomycin 2gm IM q12 hours
    7. Ceftriaxone 1-2gm IV q12 hours recommended for endocarditis or meningitis
    8. Oral therapy: cefixime 400mg bid or levofloxacin 500mg qd
    9. Alternative oral: ciprofloxcain 500mg bid or ofloxacin 400mg bid
13. Treatment of pelvic inflammatory disease (PID)
14. Strongly Consider Hospitalization for (Suspected) PID if:
    1. Diagnosis is uncertain and surgical emergencies cannot be ruled out
    2. Pelvic abscess suspected
    3. Failure to take adequate fluids (severe nausea and vomiting)
    4. Pregnancy
    5. HIV infection
    6. Failed response to outpatient therapy (progression on oral antibiotics)
    7. Unable to followup after 48-72 hours of outpatient therapy

C. Chlamydia Trachomatis

1. Obligate intracellular gram negative bacterium [20]
   1. Serotypes A, B, Ba and C generally associated with trachoma, a major cause of blindness
   2. Serotypes D-K mainly affect aepithelial surfaces of genital tract causing STDs
2. Asymptomatic chlamydial infection occurs ~10% of women ages 14-20
3. Screening [11,12]
   1. Screening sexually active women age <24 years is generally recommended
   2. General screening in high risk female populations at any age reduce PID incidence
   3. Screening pregnant women <24 years recommended; for age >25 at increased risk
   4. Annual screening is probably adequate
   5. Positive screening should prompt eradication with azithromycin or doxycycline
   6. Sexual partners currently and in previous 60 days should be tested or empirically treated
   7. Screening in men is not generally recommended
4. Spectrum of Disease
   1. Asymptomatic in most persons
   2. ~6% of asymptomatic sexually active girls 14-18 screened positive for chlamydia [15]
   3. Causes ~40% of urethritis
   4. Causes ~25% of PID
   5. Also causes Lymphogranuloma Venerium (see below)
   6. Can also cause conjuctivitis and blindness (see below) g Increases risk for tubal occlusion and infertility [7]
   7. Serotype G may increase the risk for development of cervical squamous carcinoma [8]
   8. May be associated with reactive arthritis and/or Reiter's Syndrome [3,19]
5. Symptoms of Chlamydial Urethritis
   1. Incubation 5-21 days with gradual onset
   2. Symptoms milder compared to gonococcal urethritis
   3. Dysuria alone occurs in ~15% of cases
   4. Discharge alone occurs in ~47% of cases
   5. Both dysuria and discharge occur in ~38% of cases
   6. Discharge is usually mucoid (58%); purulent in the remainder
   7. Purulent discharge may be associated with gonococcal infection or early PID
6. Detection
   1. Culture is gold standard with specificity ~100%; sensitivity is now questionable
   2. Culture is expensive, requires animal cells, and is not routinely available
   3. Enzyme immunoassays and direct fluorescent antibody tests are now available
   4. Specificity is 95-99% (sensitivity ~80%) so that positive tests require culture
   5. Ligase Chain Reaction (LCR) is more sensitive than culture with good specificity
   6. LCR use on urine and genital swab will lead to increased incidence
   7. New polymerase chain reaction and LCR have sensitivity close to 100% [11]
   8. Patient obtained samples are as reliable as clinician obtained samples
   9. Urine testing with DNA or RNA amplification detects ~90% of chlamydia [10]
7. Treatment [1]
   1. As noted above, patients should be treated for both gonococcus and chlamydia
   2. Azithromycin 1gm po x 1 (safety in pregnancy is unknown)
   3. Doxycycline - 100mg po bid (contraindicated in pregnancy) x 7 days
   4. Azithromycin is more cost effective (fewer complications) than doxycycline
   5. Ofloxacin 300mg bid x 7 days (also kills gonorrhea)
   6. Levofloxacin 500mg qd x 7 days
   7. Erythromycin base 500mg qid x 7 days
   8. Partner(s) should be identified and treated for both chlamydia and gonorrhea
   9. Patients with gonorrhea should be treated empirically for chlamydia [16]
8. Lymphogranuloma Venerium (LGV)
   1. Caused by serotypes L1, L2, L3 of Chlamydia trachomatis
   2. Fewer than 1000 cases / year in USA
   3. Initial lesion after 7 day incubation, on genitalia
   4. May have papule, eroded or ulcerated nodule, herpetiform lesions, urethritis
   5. Also causes proctitis in patients with (frequent) anal intercourse, particularly with AIDS [18]
   6. Bubos may develop and become fluctuant; may rupture
   7. 20% of patients present with enlarged lymph nodes; usually resolves in 2-3 months
   8. Diagnosis. by culture of C. trachomatis
   9. Treatment: Doxycycline 100mg bid x 21d, Azithromycin 2gm x 1
9. Chronic Onset Conjunctivitis [6,20]
   1. Trachoma is chronic keratoconjunctivitis caused by repeated reinfections
   2. Chlamydia trachomatis ocular serovars A, B, Ba, and C cause trachoma
   3. Occurs over several weeks
   4. Stringy mucous discharge, preauricular lymphadenopathy
   5. Trachoma is endemic in 48 countries, mainly Middle East, Africa
   6. Active trachoma affects ~150 million worldwide
   7. Neonatal transmission during delivery leads to neonatal conjunctivitis
   8. In USA, C. trachomatis eye disease is usually an inclusion conjunctivitis
   9. Doxycycline (100mg bid) with adjuvant topicals for 2-3 weeks recommended
   10. Single dose azithromycin (Zithromax®) 20mg/kg up to 1gm is as effective as doxycycline
   11. Treatment of sexual partners is critical

D. Vaginitis

1. Common, especially in sexually active young women
   1. Usually related to alterations of vaginal pH in sexually active women
   2. Usually not strictly an STD
   3. However, presence of vaginitis increases concern for transmission of other STDs
2. Main Symptoms
   1. Can vary depending on type of vaginitis, but unreliable for definitive diagnosis
   2. Pain
   3. Itching
   4. Unpleasant vaginal odor
   5. Dyspareunia (painful intercourse)
3. Common Types
   1. Fungal - usually Candida albicans, ~25%
   2. Bacterial - usually Gardnerella, other species such as Bacteroides ~45%
   3. Protozoan - trichomonas, ~15%
   4. Atrophic vaginitis

E. Trichomonas

1. Flagellated Protozoan
2. May be sexually transmitted
   1. Primarily symptomatic in women
   2. Most men are asymptomatic; some have nongonococcal urethritis
3. Symptoms
   1. Itchy
   2. Thick, yellow-green discharge (seen usually in severe cases only)
   3. Foul odor
   4. Vulvar irritation
4. Diagnosis [13]
   1. Organsisms are often seen micoscopically on wet preparation or Pap smear
   2. Positive Pap smear in areas where prevalance of trichomoniasis <10% requires confirmation
   3. Large, motile, "tennis racquet" shaped organisms seen in 60% of cases
   4. Very large numbers of neutrophils
   5. Vaginal pH 5-6.0
   6. Culture if microscopy is negative
5. Treatment [14]
   1. Metronidazole (Flagyl®) single dose 2gm po is recommended
   2. Alternatively metronidazole 500mg bid bid x 7 days
   3. Metronidazole gel (Metrogel®) has been approved but is only ~ 50% efficacious
   4. Tinidazole (Tindamax®) 2gm x 1 also approved [17]
   5. Partner must be treated as well
   6. Avoid during pregnancy, but single dose may be used in first trimester
   7. Recurrence or poor response treated with 2gm metronidazole qd x 3-5 days
   8. Presence of HIV infection does not alter therapy

F. Mycoplasma and Ureaplasma

1. Mycoplasma genitalium and Ureaplasma urealyticum
2. Usually asymptomatic in women
3. Cause mild to severe urethritis in men and sometimes in women
4. Usual part of standard screening for gynecologic examinations
5. Appear to be a risk factor for preterm delivery in pregnant women
6. Treatment
   1. Recommend azithromycin 1gm po x 1 dose
   2. Doxycycline100mg po bid x 7 days
   3. Some strains are resistant to doxycycline, especially Mycoplasma

G. Chancroid [2,3]

1. Caused by Haemophilus ducreyi
2. Gram negative coccobacillus, difficult to culture
3. Uncommon in USA
4. Symptoms
   1. Initially, small papule or pustule, red lesions on genitalia
   2. Progresses to very painful ulceration
   3. Painful adenopathy, inguinal region, ~50% of cases
5. Treatment
   1. Azithromycin 1gm x 1 OR Ceftriaxone 250mg IM x 1 OR
   2. Alternatives: Ciprofloxacin 500mg bid x 3d OR Erythromycin 500mg qid x 7d,
   3. All sexual contacts should be treated
6. No adverse effects of chancroid on pregnancy

H. Granuloma Inguinale (Donovanosis) [2]

1. Caused by Gram negative rod Calymmatobacterium granulomatis
2. Endemic to tropics including India, Paua, New Guinea, Central Australia, Southern Africa
3. Very rare in USA
4. Symptoms
   1. Incubation period usually ~30 (8-80) days
   2. Painless progressive ulcerative lesions
   3. Nodule progresses to ulcerating papule then to friable granulation tissue
   4. Lesions are highly vascular, bleed easily on contact
   5. Pseudo-bubos may form, are actually deep granulomas
   6. True ymphadenopathy does not occur
5. Secondary anaerobic infection common; other STDs may be present as well
6. Diagnosis
   1. Difficult to culture
   2. Visualization of dark-staining Donovanbodies on tissue crush or biopsy
   3. Rule out syphilis, amoebiasis
7. Treatment
   1. At least 3 weeks or until all lesions heal
   2. Doxycycline 100mg bid OR
   3. Trimethoprim/Sulfamethoxazole (Bactrim®, Septra®): double strength bid
   4. Alternative: Ciprofloxacin 750mg po bid OR
   5. Azithromycin 1gm qd
   6. May add geentamicin 1mg/kg IV q8 hours if no improvement in first few days

References

1. Sexually Transmitted Disease Treatment Guidelines. 2002. MMWR. 51(RR6):1
2. Workowski KA, Levine WC, Wasserheit JN. 2002. Ann Intern Med. 137(4):255
3. Rosen T. 2003. JAMA. 290(8):1001
4. Donovan B. 2004. Lancet. 363(9408):545
5. Roddy RE, Zekeng L, Ryan KA, et al. 2002. JAMA. 287(9):1117
6. Mabey DCW, Solomon AW, Foster A. 2003. Lancet. 362(9379):223
7. Hubacher D, Lara-Ricalde R, Taylor DJ, et al. 2001. NEJM. 345(8):561
8. Anttila T, Saikku P, Koskela P, et al. 2001. JAMA. 285(1):47
9. Wang SA, Harvey AB, Conner SM, et al. 2007. Ann Intern Med. 147(2):81
10. Cook RL, Hutchison SL, Ostergaard L, et al. 2005. Ann Intern Med. 142(11):914
11. Peipert JF. 2003. NEJM. 349(25):2424
12. US Preventive Services Task Force. 2007. Ann Intern Med. 147(2):128
13. Wiese W, Patel SR, Patel SC, et al. 2000. Am J Med. 108(4):301
14. Metronidazole. 1994. Med Let. 36(913):5
15. Shafer MB, Tebb KP, Pantell RH, et al. 2002. JAMA. 288(22):2946
16. Lyss SB, Kamb ML, Peterman TA, et al. 2003. Ann Intern Med. 139(3):178
17. Tinidazole. 2004. Med Let. 46(1190):70
18. Davis BT, Thiim M, Zukerberg LR. 2006. NEJM. 354(3):284 (Case Record)
19. Davis BT and Pasternack MS. 2007. NEJM. 256(25):2631 (Case Record)
20. Wright HR, Turner A, Taylor HR. 2008. Lancet. 371(9628):1945