Microbiology and Impact of STIs Part 1 Flashcards
1. Describe the major sexually transmitted disease syndromes. (MKS-1b) 2. Describe the microbiological characteristics of the major sexually transmitted pathogens. (MKS-1b) 3. Describe the disease manifestations caused by the sexually transmitted pathogens as well as tests and therapies used to diagnose and treat them. (MKS-1d, MKS-1e)
1
Q
What are some ofthe common results of sexually transmitted infections?
A
- Urethritis (males): Chlamydia trachomatis, Neisseria gonorrhoeae, herpes simplex viruses (HSV)
- Epididymitis: C. trachomatis, N. gonorrhoeae, urinary tract pathogens
- Cervicitis/cystitis/urethritis/vaginitis (females): C. trachomatis, N. gonorrhoeae, HSV, Trichomonas vaginalis, bacterial vaginosis-associated organisms (Gardnerella, etc.)
- Pelvic inflammatory disease: N. gonorrhoeae, C. trachomatis, vaginal flora (including anaerobes)
- Lesions of the genitalia: HSV, Treponema pallidum, Haemophilus ducreyi, C. trachomatis (LGV strains), Human papillomavirus
- Proctitis: N. gonorrhoeae, C. trachomatis, T. pallidum, HSV
- AIDs: Human Immunodeficiency Virus (HIV)
2
Q
What are the risk factor, symptoms, diagnosis, and treatment of pelvic inflammatory disease (PID)?
A
- Ascending infection of the uterus, fallopian tubes, and peritoneal cavity
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Risk factors include:
- IUD use
- Vaginal douching
- History of PID
- Frequent cause of infertility and ectopic pregnancy
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Symptoms:
- mucopurulent vaginal discharge
- then midline abdominal pain and abnormal vaginal bleeding
- then bilateral lower abdominal and pelvic pain with nausea and vomiting
- often occur during or soon after menses
- Sometimes leads to a perihepatitis (Fitz-Hugh-Curtis syndrome), which is inflammation of the liver capsule
- Exam shows evidence of mucopurulent cervicitis, cervical motion tenderness, and uterine and adnexal tenderness
- other signs include fever and adnexal swelling
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Treatment:
- most recommended PID antibiotic regimens are active against N. gonorrhoeae, C. trachomatis, and anaerobes. For example, doxycycline + cefoxitin
3
Q
What are the determinants of pathogenicity for Neisseria gonorrhoeae?
A
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General
- gram-negative diplococci, also called “gonococci”, aerobic
- closely related to N. meningitidis (cause of meningitis and sepsis)
- infects only humans, causes gonorrhea.
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Determinants of Pathogenicity
- pili: undergo antigenic variation, thought to function in initial adherence.
- opa (opacity associated) proteins: multiple different gene copies occur even in the same bacterium.
- opa’sare thought to anchor the bacterium onto the host cell surface following initial pilus-mediated adherence
- this intimate contact allows bacterial internalization
- IgA1 protease which is of unclear significance in disease
- endotoxin
4
Q
What is the clinical disease of Neisseria gonorrheae?
A
- In males, gonorrhea (“clap”) develops following an incubation period of 2-7 days.
- Patients report burning on urination (dysuria) and purulent urethral discharge.
- Females often have asymptomatic infections, but may present with dysuria, frequent urination, and increased vaginal discharge.
- Women are often mistakenly diagnosed as having urinary tract infections (UTI). Sterile pyuria (white blood cells in urine in the absence of a bacteria) should suggest to the physician that STI may be the correct diagnosis, not UTI.
- Complications in women include pelvic inflammatory disease (PID–fever, abdominal tenderness, malaise), which may lead to sterility.
- In men, epididymitis occurs in 5-10% of untreated individuals, and prostatitis may also occur.
- Both sexes may get disseminated gonococcal disease (fever, joint pain, septic arthritis, tenosynovitis (inflammation of the sheath that surrounds a tendon, and rash), which follows spread of the organism to the bloodstream.
- Newborns may acquire gonococcal ophthalmia (infection of the conjunctiva) during passage through an infected birth canal.
- Application of erythromycin or tetracycline eye drops at birth prevents infection.
5
Q
What are the diagnostic laboratory tests for Neisseria gonorrheae?
A
- If smears of urethral exudates show gram-negative diplococci in neutrophils, a diagnosis of gonorrhea can be made in males (not females, because of other diplococci that are part of normal vaginal flora).
- Bacteria from exudate samples grow on Mueller-Hinton or Thayer-Martin media.
- Nucleic acid amplification assays can be used on first-void urine samples to make the diagnosis.
6
Q
What is the treatment and prevention of Neisseria Gonorrheae?
A
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Treatment
- Historically, penicillin was the treatment of choice. Resistance, however, is now common, dictating that alternatives be used.
- Ceftriaxone is appropriate. Quinolone resistance has become common and has resulted in the recommendation that these agents no longer be used. Don’t forget to treat sex partners at the same time!
- Anti-chlamydial treatment should be given to all individuals diagnosed with gonorrhea because of the high frequency of co-infection with these two bacteria (25-50%).
- All individuals diagnosed with gonorrhea should also be tested for syphilis and HIV.
- The public health department should be notified for contact-tracing.
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Prevention
- Condom use and appropriate public health measures.
- Screening pregnant women at high risk.
- Antimicrobial eye drops for newborns.
7
Q
What are the determinants of pathogenicity for Chlamydia trachomatis?
A
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General
- Bacteria have gram-negative structure (but are not gram-stained); obligate intracellular pathogen
- Other related species are C. pneumoniae (respiratory infections) and C. psittaci (pneumonia). Note that both of these organisms have an infectious cycle very similar to C. trachomatis. (These organisms will be discussed further in the “Bacterial Respiratory Pathogens” lecture.)
- Most common bacterial cause of STI in U.S. (3-4 million cases/year).
- All chlamydia share a genus-specific antigen that allows them to be typed into “serovars.” Serovars A, B, and C are associated with endemic trachoma, D-K with classic chlamydial STI, and L1, L2, and L3 with lymphogranuloma venereum (LGV).
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Determinants of Pathogenicity
- Inert, spherical elementary body (EB) is extracellular form; metabolically active reticuate body (RB) is the intracellular form. RBs multiply and form intracellular inclusions. In contrast, C. pneumoniae have EB’s that are pear-shaped.
- A type III secretion system is thought to play an important role in infection.
8
Q
What is the clinical disease of Chlamydia trachomatis?
A
- C. trachomatis causes urethritis (sometimes referred to as “nongonococcal urethritis”) and cervicitis similar to that caused by N. gonorrhoeae except usually less severe. Both males and females may be asymptomatic. Complications include epididymitis, prostatitis, and PID.
- Inclusion conjunctivitis is a chlamydial infection of the eye acquired by a newborn during passage through the birth canal of a mother infected with chlamydia.
- Certain serovars (see above) may cause an STI called LGV. In LGV, an initial ulcerative genital lesion is followed by fever and the development of swollen, tender inguinal lymph nodes. This disease is now rare in the U.S.
- C. trachomatis also causes trachoma, which is a chlamydial infection of the eye that is a common cause of preventable blindness in developing countries. Transmission is usually eye-to-eye via hands, towels, flies, and other fomites.
9
Q
What are the diagnostic laboratory tests used for Chlamydia trachomatis?
A
- C. trachomatis in exudates can be grown in McCoy cells in the laboratory (rarely done).
- More commonly, tests such as DFA (direct fluorescent antibody) or EIA (enzyme-linked immunoassay) are used. These tests utilize labeled antibodies that specifically bind to C. trachomatis in collected samples of cells or secretions.
- DNA and RNA amplification tests (nucleic acid amplification tests—NAATs) are available that are more sensitive and as specific as culture. These tests allow screening for C. trachomatis by testing urine samples or vaginal swabs, which are easier to obtain than urethral or cervical swabs.
10
Q
What is the treatment and prevention of Chlamydia trachomatis?
A
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Treatment
- Azithromycin or doxycycline is recommended, but erythromycin, ofloxacin, and levofloxacin are also active.
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Prevention
- Condom use and appropriate public health measures.
- Screening of all pregnant women.
11
Q
What are the determinants of pathogenicity for Treponema pallidum?
A
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General
- Spirochete, 6-14 spirals, 6-15 µm in length and 0.15 µm in width (too slender to see by conventional light microscopy).
- Slow dividing time (approximately once every 30 hours)
- May have been carried by Columbus’ crew from the New World back to Europe.
- T. pallidum subspecies pallidum causes syphilis. T. pallidum subspecies pertenue causes yaws, T. pallidum subspecies endemicum causes bejel, and T. carateum causes pinta. These diseases are usually seen in tropical climates, are not sexually transmitted, and manifest as infectious skin lesions.
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Determinants of Pathogenicity
- T. pallidum is motile and has flagella, but they are located in the periplasm instead of the exterior of the bacterium.
- Only a small number of proteins are exposed on the outer surface of T. pallidum, providing few targets for the host immune system.
- During sexual activity, the organism gains access to subcutaneous tissue through microscopic abrasions. A chancre (open sore) develops at this site as the organism slowly multiplies. At this time, a humoral immune response develops, which is useful diagnostically (see below). The immune response results in successful resolution of the chancre, yet the organism is still able to disseminate throughout the body, leading to secondary syphilis (see below). Again, a partially effective immune response may result in resolution of the symptoms of secondary syphilis even in the absence of therapy, and the patient may become asymptomatic. However, the organism often persists for years and may subsequently cause late manifestations of disease, known as tertiary syphilis (see below).
12
Q
What is the clinical disease of Chlamydia trachomatis?
A
- T. pallidum causes syphilis, a chronic STI that has three clinical stages.
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Primary syphilis manifests itself as an ulcerative genital lesion (chancre) that occurs 2-10 weeks after infection and that spontaneously heals in about a month.
- Unlike similar lesions caused by Haemophilis ducreyi, the ulcer of syphilis is nontender.
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Secondary syphilis typically consists of a generalized rash, especially on the soles and palms, and generalized nontender enlarged lymph nodes.
- These lesions also spontaneously resolve but may recur.
- The disease next enters a prolonged latent phase that in 1/3 of untreated patients is followed by manifestations of tertiary syphilis.
- These include general paresis (personality and cognitive changes), tabes dorsalis (changes in gait, bladder control, and sensation), cardiovascular syphilis (enlargement of the ascending and transverse aorta), and gummas (granulomatous lesions that may occur in any organ).
- Congenital syphilis occurs when a fetus is infected in utero. This can lead to stillbirth, prematurity, hydrops fetalis (accumulation of fluid/edema), cutaneous lesions, hepatosplenomegaly, bone abnormalities (e.g. sabre shins—sharp anterior bowing of the tibia), and snuffles (rhinitis).
13
Q
What are the diagnostic laboratory tests used to detect Treponema pallidum?
A
- The organism can be detected in clinical specimens by dark-field microscopic examination.
- Presumptive diagnosis can be made using nontreponemal serologic assays: Venereal Disease Research Laboratory (VDRL) and rapid plasma reagin (RPR). These tests are quantitative and can also be used to measure treatment response.
- Treponemal serologic tests are used to confirm the diagnosis, as they are more specific. Fluorescent treponemal antibody absorption (FTA-ABS) and T. pallidum passive particle agglutination (TP-PA) assays are examples of such tests. Once positive, they tend to remain positive for the remainder of the patient’s life.
- The organism cannot be cultured.
14
Q
What is the treatment and prevention of Treponema pallidum?
A
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Treatment
- Penicillin G remains the drug of choice for syphilis. A Jarisch-Herxheimer reaction (fever, headache, muscle aches) is sometimes noted within the first 24 hours of treatment and is due to release of bacterial components into the bloodstream following death of the organisms.
- Doxycycline or tetracycline are alternative treatments for some penicillin-allergic individuals.
- Sex partners must be tested and/or treated; HIV testing is recommended for all individuals with syphilis.
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Prevention
- Condom use and appropriate public health measures.
- Screening of pregnant women
15
Q
What are the determinants of pathogenicity for Trichomonas vaginalis?
A
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General
- Pear-shaped protozoa
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Determinants of Pathogenicity
- The organism is flagellated and motile.
