SEXUALLY TRANSMITTED INFECTIONS (STI) III

F.S. Southwick, Infectious Diseases in 30 Days, 1^st edition, McGraw Hill. p. 289-318.

References: 

1. Burstein GR, Zenilman JM. Nongonococcal urethritis--a new paradigm. Clin Infect Dis 1999 Jan;28 Suppl 1:S66-73

2. Hoeprich, PD., MC. Jordan, and AR. Ronald. Infectious Diseases: A Treatise of Infectious Processes. 5th edition. 1994. J.B. Lippincott Company, Philadelphia, PA.

3. CDC. The national plan to eliminate syphilis from the United States. Atlanta, Georgia: US Department of Health and Human Services, CDC, National Center for HIV, STD, and TB Prevention, 1999:1--84.

4. Primary and Secondary Syphilis --- United States, 1999. MMWR. 50(01);113-117.

5. Sexually Transmitted Disease Guidelines 2002. Recommendations and Reports
   May 10, 2002/Vol. 51/No.RR-6 (http://www.cdc.gov/std/treatment/TOC2002TG.htm)

6. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2002 Supplement, Chlamydia Prevalence Monitoring Project. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, October 2003.

II. Pelvic inflammatory disease (PID) is a disease of women defined as the clinical syndrome resulting from the ascending spread of microorganisms from the vagina and endocervix to the endometrium, the fallopian tubes and/or to contiguous structures.

PID is caused by more than one organism. May include endometritis, salpingitis, tuba-ovarian abscess, and pelvic peritonitis.

A. Etiology

1. N. gonorrhoeae most common
2. C. trachomatis most common- there are 4-8 million chlamydial infections per year in the U.S. (number includes men and women; week 45 of 2000 there have been 561,649 reported cases. not all cases result in PID.)
3. Anaerobic bacteria (ex. Bacteroides)
4. Facultative Gram negative rods (ex. E. coli)
5. Mycoplasma hominis
6. Actinomyces israelii (often seen in women with long-standing intrauterine devices (IUD).

Prior infections of the fallopian tubes (usually of N. gonorrhoeae or C. trachomatis) take place resulting in damage to the ciliary cells lining the fallopian tubes.

C. Epidemiology

1. The morbidity produced by PID is greater than that of any other serious infection. In the U.S. about 850,000 women, requiring more than 212,000 hospital admissions and 115,000 surgical procedures are reported each year.

2. Risk factors include:

• Multiple sex partners
• History of previous PID
• Menstruation.
• IUD use (oral contraceptives however decrease the risk)
• Marital status (single women are at higher risk)
• Asymptomatic gonococcal infection in either sexual partner.

1. Moderate fever (generally above 99°F)
2. Bilateral lower abdominal pain that is maximal in the region of the fallopian tubes and generally lasts no longer than 14 days.
3. Increased vaginal discharge
4. Irregular bleeding
5. Tenderness on cervical motion
6. Tender adnexal mass(es)
7. Purulent endocervical discharge
8. Nausea and vomiting

E. Sequelae

1. The most common cause of involuntary infertility in women.
2. Dissemination to liver resulting in a perihepatitis.
3. Fitz-Hugh-Curtis syndrome; "Violin Strings" form between the abdominal wall and liver capsule (may occur in both gonococcal and nongonococcal types of PID).
4. Unilateral or bilateral ovarian abscesses (image 2).
5. Tubal occlusion, scarring, and adhesions (the adhesions can result in chronic abdominal pain).
6. Death due to rupture of the ovarian abscesses.

1. Definitive Dx consists of direct visualization of inflamed fallopian tube(s) on laparoscopy, laparotomy, or biopsy evidence of salpingitis (laparoscopic image of salpingitis)(sonograph of salpingitis). Only a confirmed culture of a biopsy of the fallopian tube positively identifies the etiology of salpingitis.
2. A presumptive Dx can be made on clinical grounds alone.

1. Positive culture for N. gonorrhoeae or C. trachomatis from the cul-de-sac or endocervix.   PCR tests are available.
2. Positive Gram stain for intracellular gonococci from the cul-de-sac or endocervix.
3. Elevated white blood cell count.
4. Elevated erythrocyte sedimentation rate.
5. A "recent recommendation" is to check sexually active adolescent females twice a year for C. trachomatis. This is due to the high prevalence (29%) of infection with this organism.

1. Can be treated on an outpatient basis only if their temperature is <38^oC, WBC <11,000/mm³, there is minimal evidence of peritonitis, active bowel sounds, and they are able to tolerate oral nourishment and treatment.
2. Hospitalize the patient if:
• the patient fails the first set of tests in item number 1
• the Dx is uncertain
• surgical emergencies such as appendicitis and ectopic pregnancy must be excluded
• a pelvic abscess is suspected
• severe illness precludes outpatient management e. the patient is pregnant
• the patient is unable to follow or tolerate outpatient regimen
• the clinical follow-up after 48-72 hours of starting antibiotics cannot be arranged
3. Unfortunately, no single antibiotic will be active against all possible pathogens.
4. Hospitalized patients
• Start out with parenteral therapy. Clinical experience should guide decisions regarding transition to oral therapy, which usually can be initiated within 24 hours of clinical improvement.
• Cefotetan 2 g IV every 12 hours
       OR
  Cefoxitin 2 g IV every 6 hours
       PLUS
  Doxycycline 100 mg orally or IV every 12 hours.
• Switching to oral therapy can include: Ofloxacin 400 mg orally twice a day for 14 days
  OR Levofloxacin 500 mg orally once daily for 14 days WITH or WITHOUT Metronidazole 500 mg orally twice a day for 14 days.
5. Ambulatory therapy:
   • Ofloxacin 400 mg orally twice a day for 14 days
     OR Levofloxacin 500 mg orally once daily for 14 days WITH or WITHOUT Metronidazole 500 mg orally twice a day for 14 days.

1. Close medical follow-up is essential in PID patients due to the higher failure rates of therapeutic regimens.
2. Patients should demonstrate substantial clinical improvement (e.g., defervescence; reduction in direct or rebound abdominal tenderness; and reduction in uterine, adnexal, and cervical motion tenderness) within 3 days after initiation of therapy. Patients who do not improve within this period usually require hospitalization, additional diagnostic tests, and surgical intervention.
3. If the patient is being treated as an outpatient, oral or parenteral therapy, a follow-up examination should be performed within 72 hours using the criteria for clinical improvement described above. If the patient has not improved, hospitalization for parenteral therapy and further evaluation are recommended.
4. Some specialists recommend confirmation of clinical resolution by repeating exam and endocervical culture 4-6 weeks after completing therapy.
5. Sex partners should be check for STD's.
6. Removal of IUD (this can take place during therapy).

II. Genital warts (condyloma acuminata)

A. Etiology

• Human Papilloma virus (HPV). There are more than 100 different types of the virus. Different types of the virus are associated with distinct clinical manifestations.

• Other types cause warts of the skin such as plantar warts.

• 20 million people are infected with genital warts with 6.2 million new cases of this disease every year.
• More than 50% of sexually active adults will acquire HPV in their lifetime.
• Most infections are transient; persistent infection is a major risk factor for cancer.
• In the United States, there are 2.8 million abnormal Pap tests according to annual estimates, as well as 10,520 cases of cervical cancer, 3,900 deaths and 500,000 to 1 million cases of genital warts from HPV.
• Worldwide, cervical cancer is the second leading cause of cancer-related deaths in women, mostly in developing countries (80%) where there are no Pap screening programs. There are 400,000 to 500,000 cases and 230,000 deaths from cervical cancer each year.
• Subclinical Genital HPV Infection- HPV DNA (types 16, 18 (70%)) has been found in over 93% of the cervical carcinomas and is believed to be the major cause of invasive cervical carcinoma.
• Infection is almost always sexually transmitted, but the incubation period is variable and it is often difficult to determine the source of infection. Within ongoing relationships, sex partners usually are infected by the time of the patient's diagnosis, although they may have no symptoms or signs of infection.
• The natural history of genital warts is generally benign; the types of HPV that usually cause external genital warts are not associated with cancer. Recurrence of genital warts within the first several months after treatment is common and usually indicates recurrence rather than reinfection.
• Cervical cancer is the third most common gynecologic malignancy and the eighth most common malignancy among women in the USA. The mean age for developing cervical cancer is about 50 yr; however, it can affect women as young as 20.
• Cervical cancer is essentially a sexually transmitted disease. Risk is inversely related to age at first intercourse and directly related to the lifetime number of sexual partners. Risk is also increased for sexual partners of men whose previous partners had cervical cancer.
• However, other factors appear to contribute to malignant transformation. For example, cigarette smoking is associated with an increased risk of CIN and cervical cancer.

• Soft, fleshy, cauliflower-like lesions (exophytic) lesions on the skin, genitalia, perineum, and perianal regions. The HPV infected cells of the cervix do not have any recognizable lesion. Only after the addition of dilute acetic acid can one see an "acetowhite" epithelium.

• For the cauliflower-like lesions, clinical presentation is enough. These must be differentiated from condyloma lata and molluscum contagiosum.
• Placing dilute acetic acid on the cervix can reveal the acetowhite epithelium. A "PAP" smear should be performed and the pathologist will look for koilocytosis.
• Precursor cells (cervical dysplasia, CIN) develop into invasive cervical cancer over a number of years. CIN grades I, II, and III correspond to mild, moderate, and severe cervical dysplasia. CIN III, which includes severe dysplasia and carcinoma in situ, is unlikely to regress spontaneously and, if untreated, may eventually penetrate the basement membrane, becoming invasive carcinoma.
• In situ DNA hybridization or PCR of the biopsy material. Not very commonly performed.

• Cryotherapy, surgical excision, laser vaporization, cautery, podophyllin, podophyllotoxin, 5-fluorouracil, trichloroacetic acid or interferon for exophytic lesions.
• Annual pap smears to stage subclinical infections with various treatments depending of the stage of the disease progression (squamous intraepithelial lesions (SIL)) or to cervical carcinoma.
• Invasive squamous cell carcinoma usually remains localized or regional for a considerable time; distant metastases occur late. The 5-yr survival rates are 80 to 90% for CIN stage I, 50 to 65% for stage II, 25 to 35% for stage III, and 0 to 15% for stage IV.

• Avoid contact with lesions. 
• The likelihood of transmission to future partners and the duration of infectivity after treatment are unknown. The use of latex condoms has been associated with a lower rate of cervical cancer, an HPV-associated disease.

III. Epididymitis

Etiology

Among sexually active men aged <35 years, epididymitis is most often caused by C. trachomatis or N. gonorrhoeae. Epididymitis caused by sexually transmitted enteric organisms (e.g., Escherichia coli) also occurs among men who are the insertive partner during anal intercourse.

Nonsexually transmitted epididymitis that is associated with urinary-tract infections caused by Gram-negative enteric organisms occurs more frequently among men aged >35 years, men who have recently undergone urinary-tract instrumentation or surgery, and men who have anatomical abnormalities of the urinary tract.

Signs and Symptoms

Sexually transmitted epididymitis usually is accompanied by urethritis, which often is asymptomatic. Men who have epididymitis typically have unilateral testicular pain and tenderness; hydrocele and palpable swelling of the epididymis usually are present. 

Testicular torsion which is not an infection but has similar symptoms is a surgical emergency and should be considered in all cases. It occurs more frequently among adolescents and in men without evidence of inflammation or infection.

Diagnosis

The evaluation of men for epididymitis should include the following procedures.

• A Gram-stained smear of urethral exudate or intraurethral swab specimen for diagnosis of urethritis (i.e., >5 polymorphonuclear leukocytes per oil immersion field) and for presumptive diagnosis of gonococcal infection.
• A culture of intraurethral exudate or a nucleic acid amplification test (either on intraurethral swab or first-void urine) for N. gonorrhoeae and C. trachomatis.
• Examination of first-void uncentrifuged urine for leukocytes if the urethral Gram stain is negative. A culture and Gram-stained smear of this urine specimen should be obtained.
• Syphilis serology and HIV counseling and testing.

Therapy

Empiric therapy is indicated before culture results are available. Treatment of epididymitis caused by C. trachomatis or N. gonorrhoeae will result in a) microbiologic cure of infection, b) improvement of signs and symptoms, c) prevention of transmission to others, and d) a decrease in potential complications (e.g., infertility or chronic pain). As an adjunct to therapy, bed rest, scrotal elevation, and analgesics are recommended until fever and local inflammation have subsided.

For epididymitis most likely caused by gonococcal or chlamydial infection:

Ceftriaxone 250 mg IM in a single dose
     PLUS
Doxycycline 100 mg orally twice a day for 10 days.

For epididymitis most likely caused by enteric organisms, for patients allergic to cephalosporins and/or tetracyclines, or for epididymitis in patients aged >35 years:

Ofloxacin 300 mg orally twice a day for 10 days
     OR
Levofloxacin 500 mg orally once daily for 10 days

Although most patients can be treated on an outpatient basis, hospitalization should be considered when severe pain suggests other diagnoses (e.g., torsion, testicular infarction, or abscess) or when patients are febrile or noncompliant in taking an antimicrobial regimen. 

IV. Proctitis, Proctocolitis, and Enteritis

Proctitis and proctocolitis are usually transmitted following anal intercourse. Enteritis is acquired among persons whose sexual practices include oral-fecal contact. 

Etiology

Proctitis- is an inflammatory condition involving the anus and rectum (the distal 10--12 cm). There are many causes of proctitis. They can be broken down into four basic groups:

• sexually-transmitted disease
• non-sexually transmitted infection
• autoimmune disease
• noxious agents

The agents that can cause sexually-transmitted proctitis include N. gonorrhoeae , HSV, T. pallidum, Chlamydia trachomatis and the lymphogranuloma venereum serotypes of Chlamydia trachomatis. Entamoeba histolytica is another agent which can cause proctitis and can be transmitted by ano-oral sex.

Non-sexually transmitted infections causing proctitis are seen less frequently than STD proctitis. The classical example of non-sexually transmitted infection occurs in children and the proctitis is caused by Streptococcus pyogenes, the same organism which causes strep throat. 

Autoimmune proctitis is associated with diseases such as ulcerative colitis or Crohn's disease.

Proctitis may also be caused by physical agents including chemicals inserted into the rectum, medications and radiation. Radiation proctitis is seen in association with radiotherapy as part of cancer treatment.

Risk factors include high-risk sexual practices, homosexuality, and autoimmune disorders.

Proctocolitis- Pathogenic organisms include Campylobacter sp., Shigella sp., Entamoeba histolytica, and, rarely, LGV serovars of C. trachomatis. CMV or other opportunistic agents may be involved in immunosuppressed HIV-infected patients. 

Enteritis- In otherwise healthy persons, Giardia lamblia is most frequently implicated.

Manifestations

Proctitis is inflammation limited to the rectum (the distal 10--12 cm) that may be associated with anorectal pain, tenesmus, or rectal discharge.

Proctocolitis is associated with symptoms of proctitis plus diarrhea or abdominal cramps and inflammation of the colonic mucosa extending to 12 cm above the anus.

Enteritis usually results in diarrhea and abdominal cramping without signs of proctitis or proctocolitis; it occurs among persons whose sexual practices include oral-fecal contact.

Diagnosis

Evaluation for these syndromes should include appropriate diagnostic procedures (e.g., anoscopy or sigmoidoscopy, stool examination, and culture).

Proctocolitis- Fecal leukocytes may be detected on stool examination depending on the pathogen.  

Enteritis- Multiple stool examinations may be necessary to detect Giardia. 

Treatment

When laboratory diagnostic capabilities are available, treatment decisions should be based on the specific diagnosis.