JH IM Board Review - Infectious Disease III Flashcards
Urogenital ulcer disease - 5 main ulcerative diseases:
- Genital herpes (HSV-2>HSV-1).
- Syphilitic chancre (T.pallidum)
- Chancroid (H.ducreyi).
- Donovanosis or granuloma inguinale (Klebsiella granulomatis).
- Lymphogranuloma venereum (C.trachomatis serovar L1, L2, L3).
Genital herpes - Clinical presentation:
- Cluster of vesicles on erythematous base.
- PAINFUL and pruritic.
- Dysuria.
- LAN.
Genital herpes - Dx:
- Tzanck prep, multinucleated giant cells (low se).
- Viral culture (70% se).
- PCR.
- Glycoprotein G-based serologies.
Genital herpes - Tx:
- Acyclovir.
- Famciclovir.
- Valacyclovir.
Syphilitic chancre - Clinical presentation:
- Single, PAINLESS ulcer at the site of inoculation.
- Clean base and raised, firm border.
- PAINLESS LAN.
Syphilitic chancre - Dx:
- Darkfield examination.
- Serology ==> Nontreponemal (RPR, VDRL).
- Treponemal (FTA-ABS, MHA-TP, TP-PA, EIAs).
Syphilitic chancre - Tx:
PCN.
Chancroid - CP:
- PAINFUL ulcer.
- TENDER inguinal LAN.
- Occurs in outbreaks.
Chancroid - Dx:
- CLINICAL.
2. Culture available but NOT widely used.
Chancroid - Tx:
Azithro OR ceftriaxone OR cipro.
Donovanosis or granuloma inguinale - CP:
- Painless papule or nodule erodes into beefy-red granulomatous ulcer with rolled edges.
- ENDEMIC in Far East Asia and Southern Africa.
Donovanosis or granuloma inguinale - Dx:
Donovan bodies on biopsy.
Donovanosis or granuloma inguinale - Tx:
Doxycycline or TMP-SMX ==> Tx AT LEAST 3 WEEKS.
Lymphogranuloma venereum - CP:
- PAINLESS genital ulcer.
- PAINFUL inguinal LAN (with GROOVE SIGN).
- Proctitis.
Lymphogranuloma venereum - Dx:
- CLINICAL syndrome.
- Serology.
- Complement fixation titers of at least 1:64.
- Nucleic acid amplification tests.
Lymphogranuloma venereum - Tx:
Doxycycline for 3 WEEKS.
Genital herpes - Predominant cause among young people?
NOW the HSV-1.
Seroprevalence of HSV-2 and HSV-1 in adults in the United States is …?
17% and 60% respectively.
Up to …% of cases of genital herpes are asymptomatic and unrecognized.
70%.
Genital herpes - Incubation period:
2-7 days.
Genital herpes - Viral shedding occurs EVEN …?
IN THE ABSENCE OF LESIONS.
==> The amount of shedding declines over time.
Prior infection with HSV-1 does not …?
PROTECT against incident HSV-2 infection.
==> Although incident HSV-1 in persons infected with HSV-2 is RARE.
Genital herpes - PRIMARY GENITAL HERPES LESIONS:
Primary genital herpes lesions are classically ==> PAINFUL.
==> Multiple, grouped on erythematous base.
==> Beginning as macules and papules, evolving to vesicles and ulcers.
Genital herpes - Local symptoms:
- Pain.
- Itching.
- Dysuria.
- Tender inguinal adenopathy.
Genital herpes - Primary lesions may accompanied by:
- Fever.
- Headache.
- Malaise.
- Myalgias.
Recurrent disease is less or more severe than primary?
LESS severe.
==> May be severe in immunocompromised.
Genital herpes - Extragenital complications:
- CNS involvement (Meningitis, encephalitis).
2. Urinary retention.
Genital herpes - Dx - Preferred method when NO active lesions are present?
SEROLOGY.
Genital herpes - Serology may be neg in …?
PRIMARY INFECTION.
Genital herpes - Serologic false pos may occur:
If the pretest probability of having HSV is LOW.
IgM serology for genital herpes?
Neither sensitive nor specific for primary infections.
==> There are no universal recommendations.
Presence of IgG antibodies to HSV-2?
Diagnostic of genital infection. (Anti-HSV-1 may reflect either orolabial or genital infection).
Genital herpes - Tx:
Systemic antiviral drugs (eg acyclovir, famciclovir, or valacyclovir) can be used as episodic or suppressive therapy.
==> They are ALL equally efficacious.
Genital herpes - Episodic Tx does NOT …?
Eradicate the virus OR reduce frequency of recurrences.
Genital herpes - DAILY suppressive Tx:
For patients with 6 or more recurrences per year can reduce the frequency by up to 80%.
==> Also prevents recurrences in 25-30% of pts; freq of episodes may diminish over time.
Genital herpes - Suppressive Tx does NOT …?
ELIMINATE SUBCLINICAL VIRAL SHEDDING.
Once-daily valacyclovir in the infected partner, in addition to consistent condom use, may help decrease transmission to an uninfected partner by approx. …%.
55%.
Primary syph - Chancre:
- Quickly erodes and becomes indurated with a CLEAN base + raised, firm borders.
- Atypical lesions occur in 60% of cases.
- Primary lesions may be accompanied by regional painless bilateral adenopathy.
Secondary or disseminated syph:
- Begins 2-8 weeks after appearance of chancre.
- May be associated with flu-like symptoms, generalized LAN, and temporary alopecia.
- Characteristic rash may be macular, maculopapular, papular, or pustular ==> May involve the whole body OR palms/soles.
Secondary or disseminated syph - Condylomata lata:
- Appear as raised, painless, gray-white lesions.
- Highly infectious.
- Develop in intertriginous areas and on mucous membranes.
Latent syph:
- Definition = Lack of clinical manifestations with positive serology.
- Latent syph acquired within the preceding year is EARLY LATENT SYPH.
- LATE latent syph implies acquisition more than 1 yr before Dx.
Tertiary syph:
- Implies late manifestations of syph.
- Gummatous syph results in skeletal, mucosal, ocular, and visceral lesions.
- Average time of onset is 4-12yrs after infection.
- Cardiovascular syph causes endarteritis of the aortic vasa vasorum ==> Average time of onset is 15yr (Aortic aneurysm, or Aortic valve insufficiency).
Neurosyph:
Can occur AT ANY SYPHILIS STAGE (ie may be an early manifestation or a tertiary one).
Neurosyph - Early:
MENINGOVASCULAR syph.
==> During the 1st yr after infection as meningitis (often, a basilar meningitis involving cranial nerves) particularly among HIV-infected persons.
Neurosyph - Late:
Occurring many years after primary infection:
- May be meningovascular (presenting as stroke).
- Parenchymatous (manifesting as tabes dorsalis, electrical pains shooting down the legs).
- General paresis (personality changes, hallucinations).
Auditory manifestations in syph:
May also occur during any stage of syph.
Ophthalmic syph:
May occur at ANY STAGE + includes:
- Iritis.
- Uveitis.
- Neuroretinitis.
- Optic neuritis.
Syph - Dx:
Darkfield exam of genital lesions + direct fluorescent antibody tests of lesion exudates or tissue ==> DEFINITIVE EVIDENCE.
Syph - Dx - 2 types of serologic tests are used for presumptive Dx:
- Non treponemal tests (RPR + VDRL).
2. Treponemal tests (FTA-ABS, TP-PA, EIA and CIA).
Nontreponemal tests:
- Often used as screening tests.
- Because of LOW SP, must be confirmed by a treponemal test.
- May revert to NEGATIVE, EVEN IN THE ABSENCE OF THERAPY.
Syph - Dx - Treponemal tests:
- CIA or EIA now being used as screening tests instead of non treponemal tests.
- A positive test should reflex to a nontreponemal test; if the nontreponemal test is negative, a 2nd different treponemal test (usually the TP-PA) should be done to confirm the first positive treponemal test.
Syph - Dx - Serologic tests may be NEGATIVE in approx. …?
- 30% of primary syph cases.
- 100% sens in secondary syph.
==> A negative RPR essentially rules out the diagnosis of SECONDARY SYPH in the absence of a prozone reaction.
A confirmed positive treponemal test and a NEGATIVE non treponemal test may be seen with:
- Old treated syph.
- Old UNtreated syph.
- Prozone reaction.
- Early syph ==> Where the treponemal tests became reaction before the non treponemal ones.
Neurosyph - Dx:
- Combination of serologic tests.
- CSF abnormalities (greater than 5 WBC/mm^3 +/- abnormal protein).
- Reactive CSF VDRL.
CSF VDRL:
Highly specific but insensitive (50%).
==> Negative study does NOT exclude the diagnosis.
CSF FTA-ABS:
Less specific but VERY SENSITIVE.
==> Negative study probably excludes neurosyph if the pretest probability is moderate to low.
CSF exam is indicated in cases of …?
- NEUROLOGIC or OPHTHALMOLOGIC abnormalities.
- Evidence of active tertiary syph.
- Evidence of serologic treatment failure.
Asymptomatic neurosyph?
HIV infection with a CD4 count less than or equal to 350 cells/mm3, or an RPR greater than or equal to 1/32, is associated with incr. risk of ASYMPTOMATIC neurosyph.
==> CSF exam may be considered.
Syph - Tx:
Parenteral PCN G is the drug of choice.
==> Only accepted therapy with documented efficacy for neurosyph + syph during pregnancy is DESENSITIZATION followed by PCN therapy.
The Jarisch-Herxheimer reaction:
Acute febrile reaction associated with headache and myalgias.
==> Thought to be activation of inflammatory cascade associated with lysis of spirochetes.
==> Can occur within the first 24h after Tx (particularly in early syph).
==> Tx = supportive.
Syph - Tx - Response to Tx is monitored by …?
Change in titer of a non treponemal test (eg RPR) 12 (for primary, secondary, and early latent stages of syph) to 24 (for late syph) MONTHS after therapy.
Syph - Tx - Response to Tx:
A 4-fold (or 2-dilution) decrease in RPR or VDRL tite (eg from 1:64 to 1:16) indicates CURE.
==> No change or increase in titer indicates failure of therapy.
==> Documentation of a titer response followed by a 4-fold increase indicates reinfection.
Treponemal test (eg FTA-ABS) titers correlate with disease activity?
DO NOT correlate with disease activity or therapy and usually remain positive for life.
In neurosyph - Quantitative non treponemal serologic tests should be repeated at …?
6-12-24 months.
==> CSF exam should be repeated 6 months after Tx.
Recommended Tx regimens for syph - Primary, secondary, and early latent syph:
Benzathine PCN G - 2.4 million units IM in a single dose.
==> if PCN allergic - Doxy 100mg PO bid for 2 weeks, except pregnant patients, who should be desensitized and treated with PCN.
Recommended Tx regimens for syph - Late latent syph, syph of unknown duration, or tertiary syph (gummatous and CVS syph):
Benzathine PCN G: 7.2 million units, administered as 3 doses of 2.4 million units IM each at 1-week intervals.
Recommended Tx regimens for syph - Neurosyph:
Aqueous crystalline PCN G: 18-24 million units per day for 10-14 days.
Urethritis and cervicitis - Basic info:
Discharge of mucopurulent or purulent material.
==> Principal etiologic agents are:
- N.gonorrhoeae.
- C.trachomatis.
- M.genitalium.
- T.vaginalis.
Gonorrhea - Can involve:
- Genital tract.
- Rectum.
- Oropharynx.
or be DISSEMINATED.
Gonorrhea - Incubation period is …?
3-7 DAYS.
Gonorrhea - Symptoms manifest within:
10-14 days after exposure.
Disseminated gonococcal infection (DGI) occurs in …?
1-3% of cases.
Gonorrhea in men:
- Symptomatic in approx. 50%, with purulent urethral discharge or dysuria.
- Causes 30% of epididymitis cases in young men.
Gonorrhea in women:
Women with cervicitis may have vaginal discharge or bleeding.
==> 50% may be asymptomatic.
==> Other syndromes in women: Urethritis, Bartholin gland abscesses, PID.
DGI may present as triad of:
- Dermatitis with petechial or pustular acral skin lesions.
- Tenosynovitis.
- Asymmetrical migratory polyarthralgias, or as purulent arthritis without skin lesions.
==> Perihepatitis, endocarditis, meningitis, and osteomyelitis occur less commonly.
Gonorrhea - Dx:
NAA tests are the tests of choice for genital and extragenital sites.
==> Extragenital testing is NOT FDA cleared but is routinely performed.
Gonorrhea - Dx - Gram stain?
May show gram(-) intracellular diplococci.
==> Low sens in asymptomatic persosn and women.
Dx of gonorrhea - Culture:
Thayer-Martin modified medium, Se approx. 85-90%.
Gonorrhea - Retest?
Retest all patients 3 MONTHS after completing Tx because REINFECTION rates are HIGH.
Gonorrhea - Tx:
Ceftiaxone 250mg IM x 1 PLUS 1g or oral azithromycin is first-line therapy.
==> ORAL cephalosporins are approved alternate agents but they may have lower activity against pharyngeal gonorrhea.
Patients with pharyngeal gonorrhea require a …?
Test-of-cure 2 WEEKS after Tx to verify response if treated with oral cephalosporins.
Gonorrhea Tx - Monotherapy?
NOT recommended due to incr. resistance.
Azithro for gonorrhea?
Azithro monotherapy (2g) effective for BOTH gonorrheal infections + Chlamydial infections, but use is limited by GI distress and emerging resistance.
DGI - Tx:
Should be hospitalized and treated parenterally with ceftiaxone and a single 2g oral dose of azithro.
==> May be discharged 24hours after clinical response to complete a 7-day course of ORAL cephalosporin.
C.trachomatis - Basic info:
- D-K serotypes are the MC bacterial STD in the USA (C.trachomatis L1-L3 serotypes cause lymphogranuloma venereum (LGV)).
- Single biggest risk factor for D through K serotypes is YOUNG AGE.
C.trachomatis - CP in women:
May present as cervicitis or urethritis.
==> May also have vaginal discharge + Lower abdominal pain + Dysuria.
==> Most cases are asymptomatic.
C.trachomatis - CP in men:
May develop urethritis with dysuria and mucopurulent discharge ==> Most are asymptomatic.
C.trachomatis - Epididymitis:
Manifests as unilateral testicular pain and tenderness, edema, and/or hydrocele.
C.trachomatis - Dx:
Because asymptomatic infection is MC, annual screening of all sexually active women aged 25yrs or younger + older at-risk women is recommended to prevent sequelae.
Untreated chlamydial infection in women is a major cause of …?
- PID.
- Ectopic pregnancy.
- Infertility.
C.trachomatis - In men, untreated infection may result in …?
Prostatitis.
C.trachomatis - Dx method of choice is:
NAA test.
C.trachomatis - Tx:
Azithromycin or doxycycline are 1st-line agents.
==> Doxycycline is preferred for rectal infections.
C.trachomatis - Tx - Alternatives:
FQ and erythromycin.
C.trachomatis - Tx - In pregnancy:
Doxy and FQ ==> CONTRA.
C.trachomatis - Tx - Test for cure:
Recommended after Tx with amoxicillin or erythromycin because these regimens may NOT be as efficacious, and side effects may discourage compliance.
C.trachomatis - Reinfection:
COMMON - Increases PID risk - Repeat testing is warranted 3 months after therapy.
C.trachomatis - Sexual partners in the preceding …?
60 DAYS (or the last sexual partner) should be referred for evaluation and Tx.
Mycoplasma genitalium:
Causes acute and chronic urethritis.
==> Moderate to strong association with cervicitis and PID.
Mycoplasma genitalium is the MCC of …?
Persistent urethritis in men.
M.genitalium - Dx:
NAA tests are sensitive but NONE ARE FDA cleared.
M.genitalium - Tx:
1g azithro orally is effective ==> BUT associated with emergence of resistance.
==> Longer azithro courses are probably better.
M.genitalium - If resistant to azithro?
Moxiflox 500mg orally for 7-14 days.