Transcript Treating Opportunistic Infections Among HIV

Guidelines for Prevention and Treatment of
Opportunistic Infections in HIV-Infected Adults
and Adolescents
Syphilis Slide Set
Prepared by the AETC National Resource Center
based on recommendations from the CDC,
National Institutes of Health, and HIV Medicine
Association/Infectious Diseases Society of America
About This Presentation
These slides were developed using recommendations
published in May 2013. The intended audience is
clinicians involved in the care of patients with HIV.
Users are cautioned that, because of the rapidly
changing field of HIV care, this information could
become out of date quickly. Finally, it is intended that
these slides be used as prepared, without changes in
either content or attribution. Users are asked to honor
this intent.
– AETC National Resource Center
http://www.aidsetc.org
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Syphilis: Epidemiology
 Caused by Treponema pallidum
 Associated with increased risk of HIV sexual
acquisition and transmission
 Increased incidence in men who have sex with
men
 HIV infection may somewhat alter diagnosis,
natural history, and management of syphilis, but
principles of management are the same with or
without HIV infection
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Syphilis: Clinical Manifestations
 HIV may make clinical lesions more
apparent and accelerate progression of
syphilis
 Primary syphilis
 Painless nodule at site of contact, rapidly
ulcerates (chancre)
 In HIV-infected patients, may see multiple or
atypical chancres, or no primary lesion
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Syphilis: Clinical Manifestations (2)
Chancres of primary syphilis
Credit: Centers for Disease Control and Prevention
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Syphilis: Clinical Manifestations (3)
 Secondary syphilis (2-8 weeks after primary
inoculation)
 Protean symptoms, may involve almost any organ
system and include:
 Rash (macular, maculopapular, papulosquamous, or pustular);
or condyloma lata
 Generalized lymphadenopathy
 Constitutional symptoms (fever, malaise, anorexia, arthralgias,
headache)
 CNS symptoms
 Symptoms last days-weeks
 In advanced HIV infection, may be more severe or
progress more rapidly
 Distinguish from primary HIV infection
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Syphilis: Clinical Manifestations (4)
Rash of secondary syphilis
Credit: Centers for Disease Control and Prevention
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Syphilis: Clinical Manifestations (5)
 Latent syphilis: no overt signs/symptoms
(but serologic evidence of syphilis), though
relapse of manifestations of secondary
syphilis may occur
 Late syphilis: cardiovascular syphilis,
gummatous syphilis; or slowly progressive
disease in any organ system
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Syphilis: Clinical Manifestations (6)
Neurosyphilis: May occur at any stage of syphilis,
with various symptoms
 Cranial nerve dysfunction, stroke, meningitis,
acute or chronic mental status change, loss of
vibration sense, auditory or ophthalmic
abnormalities, similar in HIV-uninfected patients
 Concomitant uveitis and meningitis more
common in HIV-positive patients
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Syphilis: Diagnosis
 Direct detection of T pallidum
 Darkfield microscopy of mucocutaneous lesion, DFATP, biopsy with silver stain
 Presumptive serologic diagnosis tests
 Nontreponemal serologic tests (VDRL, RPR)
 Treponemal tests (eg, FTA-ABS, TP-PA, EIAs,
chemiluminescence immunoassays)
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Syphilis: Diagnosis (2)
 Testing algorithms:
 Traditional: screening for nontreponemal antibodies +
confirmation of reactive tests by treponemal assay
 Newer: screening with treponemal test (EIA or CIA),
with reflex nontreponemal test if positive
 May identify previously treated syphilis infection more often
than untreated infection
 If positive treponemal screening test and negative reflex
nontreponemal test: second treponemal test should be done
(using different antigens) to confirm
 If second treponemal test is positive: assess risk factors and
prior syphilis treatment
 If suspected primary syphilis: treat empirically, retest with
nontreponemal test in several weeks to confirm diagnosis
 If no evidence of primary syphilis: treat for late-latent
syphilis (unless past treatment can be confirmed)
 If second treponemal test is negative: no treatment indicated
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Syphilis: Diagnosis (3)
 Early-stage disease:
 Nontreponemal serologic tests (VDRL, RPR)
may show atypical responses (higher, lower,
or delayed) in HIV-infected patients
 False-negative tests possible (as in HIVuninfected patients); pursue other diagnostic
tests if high suspicion of syphilis (eg, repeat
serology, biopsy, DFA of lesion material;
exclude prozone phenomenon)
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Syphilis: Diagnosis (4)
 Latent syphilis:
 Serologic tests positive but no clinical
manifestations
 Early latent: evidence of infection <1 year
 Late latent: evidence of infection >1 year or
duration is not known
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Syphilis: Diagnosis (5)
 Late-stage disease:
 Cardiovascular and gummatous: same
as for HIV-uninfected patients
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Syphilis: Diagnosis (6)
 Neurosyphilis:
 All with syphilis (regardless of stage) should be
evaluated for clinical evidence of CNS or ocular
involvement
 CSF exam should be done for any patient with:
 Neurologic, auditory, or ophthalmic symptoms or signs
 Tertiary syphilis
 Treatment failure (on basis of serologic tests)
 CSF abnormalities (elevated protein, mononuclear
pleocytosis) common in early syphilis and in HIV,
without neurologic symptoms: no evidence that clinical
and prognostic significance is different in HIV-infected
and HIV-uninfected with early syphilis
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Syphilis: Diagnosis (7)
 Neurosyphilis:
 No single test used to diagnose; instead, various
combinations of reactive serologic tests, CSF
cell count and protein, and reactive CSF-VDRL
with or without clinical manifestations support
the diagnosis
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Syphilis: Diagnosis (8)
 Neurosyphilis:
 CSF examination
 Mild mononuclear pleocytosis (6-200 cells/µL),
normal or mildly elevated protein
 CSF VDRL
 Specific; not sensitive (reactive test establishes
neurosyphilis; nonreactive test does not exclude it)
 CSF FTA-ABS
 Highly sensitive; less specific (reactive test does not
establish the diagnosis; nonreactive test excludes
neurosyphilis)
 PCR-based methods not recommended
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Syphilis: Diagnosis (9)
 Neurosyphilis testing, considerations:
 Reactive CSF VDRL plus CSF WBC ≥10 cells/µL
supports diagnosis of neurosyphilis
 Mild mononuclear CSF pleocytosis (6-15 cells/µL)
may be associated with HIV infection itself and may
complicate diagnosis of neurosyphilis; using cutoff of
>20 cells/µL may improve specificity of neurosyphilis
diagnosis in HIV-infected patients
 Elevated CSF protein concentration should not be
used as sole diagnostic criterion
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Syphilis: Preventing Exposure
 Risk screening should be routine
 Client-centered risk-reduction messages; give
specific actions to reduce risk of acquiring STIs
and for transmitting HIV
 Routine serologic testing for syphilis at least
annually; Q 3-6 months if multiple partners,
unprotected intercourse, injection drug or
methamphetamine use, or partners with risks
 Consider referral for behavioral intervention
 Evaluate for other STIs
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Syphilis: Preventing Disease
 For persons exposed sexually to someone with
syphilis: evaluate clinically and serologically and
treat presumptively
 Persons exposed within the 90 days preceding
diagnosis of primary, secondary, or early-latent
syphilis in a sex partner may be infected even if tests
are seronegative: treat presumptively
 Persons exposed >90 days before diagnosis of
primary, secondary, or early-latent syphilis in a sex
partner: treat presumptively if serologic test results
are not available immediately and follow-up is
uncertain
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Syphilis: Treatment
 Management similar to that for HIV-uninfected
persons, but rates of serologic treatment failure
and neurologic complications may be higher in
HIV infection; closer follow-up is recommended
 Penicillin is treatment of choice
 Patients with penicillin allergy whose compliance or
follow-up cannot be ensured: desensitize and treat with
penicillin
 Use alternatives to penicillin only with close clinical and
serologic monitoring
 Azithromycin resistance and treatment failure;
especially in men who have sex with men (MSM)
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Syphilis: Treatment (2)
Early stage (primary, secondary, early-latent)
 Preferred:
 Benzathine penicillin G 2.4 million units IM, single dose
 Alternative (for penicillin-allergic patients; monitor
closely):
 Doxycycline 100 mg PO BID for 14 days
 Ceftriaxone 1 g IM or IV QD for 10-14 days
 Azithromycin 2 g PO for 1 dose (note: reports of
treatment failure and resistance; should not be used in
MSM or pregnant women)
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Syphilis: Treatment (3)
Late-latent (no signs of neurosyphilis)
 Preferred:
 Benzathine penicillin G 2.4 million units IM weekly
for 3 weeks
 Alternative (for penicillin-allergic patients):
 Doxycycline 100 mg PO BID for 28 days (not
thoroughly evaluated in HIV-infected patients;
monitor closely)
Late-stage (cardiovascular or gummatous)
 CSF examination; consult ID specialist
 Preferred: Benzathine penicillin G 2.4 million units
IM weekly for 3 weeks
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Syphilis: Treatment (4)
Neurosyphilis, otic syphilis, ocular syphilis
 Preferred:
 Aqueous crystalline penicillin G, 18-24 million units
daily, as 3-4 million units IV Q4H or continuous
infusion for 10-14 days
 Consider addition of benzathine penicillin 2.4 million units IM weekly
for 3 weeks after completion of IV therapy
 Alternative:
 Procaine penicillin G 2.4 million units IM QD +
probenecid 500 mg PO QID for 10-14 days
 Consider addition of benzathine penicillin 2.4 million units IM weekly
for 3 weeks after completion of above
 Patients with sulfa allergy should not receive probenecid, so this
regimen is not recommended for them
 Penicillin allergy:
 Desensitization to penicillin is preferred; if not feasible,
ceftriaxone 2 g IM or IV QD for 10-14 days
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Syphilis: Starting ART
 No special considerations, no evidence that ART
should be delayed until after treatment for syphilis
 IRIS is uncommon
 Use of ART associated with:
 Decreased risk of serologic failure of syphilis treatment
 Lower risk of neurosyphilis
 Normalization of CSF parameters after treatment
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Syphilis: Monitoring and Adverse Events
 Monitor clinical and serologic response to treatment;
assure at least 4-fold decline from titer done at time of
treatment:
 Early stage: at 3, 6, 9, 12, 24 months
 Late-latent: at 6, 12, 18, 24 months
 Consider treatment failure: persistence or recurrence in
clinical signs and symptoms or sustained 4-fold increase
in nontreponemal test titer
 Neurosyphilis: if CSF pleocytosis present initially, repeat
CSF exam at 6 months; also repeat if symptoms recur or
nontreponemal titer increases by 4-fold
 Consider retreatment if no decrease in CSF WBC by 6 months
or if WBC not normal by 2 years
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Syphilis: Monitoring and Adverse Events (2)
 After successful treatment, nontreponemal tests
may remain “serofast,” ie, reactive at stable titer,
usually low (≤1:8)
 Sustained ≥4-fold increase in titer indicates
reinfection
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Syphilis: Monitoring and Adverse Events (3)
 Jarisch-Herxheimer reaction may occur in the first
24 hours after start of syphilis treatment
 Fever, headache, myalgia
 Manage symptoms with antipyretics
 Most frequent in those with early syphilis, high
nontreponemal titers, and prior penicillin treatment
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Syphilis: Treatment Failure
Early stage
 Consider CSF evaluation and retreatment if:
 ≤4-fold decrease in serum nontreponemal test titer 6-12
months after therapy, or
 Sustained 4-fold increase in titer after initial 4-fold
reduction after treatment, or
 Persistent or recurring signs or symptoms of syphilis
 Reinfection is difficult to document and treatment
failure is difficult to rule out
 If no appropriate titer response after CSF evaluation
and retreatment, management is unclear
 >15% of early syphilis patients (HIV infected and
uninfected) do not have 4-fold decline in titer after
treatment
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Syphilis: Treatment Failure (2)
Early stage
 Retreatment: benzathine penicillin G, 2.4 million
units weekly for 3 weeks (if neurosyphilis present,
treat for that)
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Syphilis: Treatment Failure (3)
Late-latent stage
 Repeat CSF exam and retreat if:
 Clinical signs or symptoms of syphilis, or
 Sustained 4-fold increase in titer after initial
reduction after treatment, or
 ≤4-fold decrease in serum nontreponemal test titer
within 12-24 months after therapy
 Treatment: benzathine penicillin G, 2.4 million
units weekly for 3 weeks (if neurosyphilis
present, treat for that)
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Syphilis: Treatment Failure (4)
Neurosyphilis
 Consider retreatment if:
 CSF WBC count has not decreased 6 months after
completion of treatment, or
 CSF WBC count is not normal 2 years after
treatment
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Syphilis: Preventing Recurrence
 Secondary prevention and
maintenance therapy not indicated
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Syphilis: Considerations in Pregnancy
 Screening:
 At 1st prenatal visit in all women; in high-prevalence
areas or high-risk women, repeat early in 3rd trimester
and at delivery
 Transmission to the fetus and adverse pregnancy
outcomes highest with early-stage syphilis
 Pregnancy does not alter the clinical course or
diagnostic test results of syphilis in adults
 Syphilis associated with increased risk of
perinatal HIV transmission to infants
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Syphilis: Considerations in Pregnancy (2)
 Use penicillin, if possible, as in nonpregnant HIV-infected
adults
 Penicillin is effective for preventing syphilis transmission
to the fetus and for treatment of fetal infection
 Optimal penicillin regimen is not clear
 In early syphilis, consider second injection of benzathine
penicillin G 1 week after first dose
 No alternatives to penicillin proven effective and safe for
treatment of syphilis during pregnancy or prevention of
fetal infection
 Pregnant women with syphilis and history of penicillin
allergy should undergo desensitization and treatment
with penicillin
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Syphilis: Considerations in Pregnancy (3)
 Jarisch-Herxheimer reaction in 2nd half of pregnancy
may precipitate preterm labor or fetal distress
 In 2nd half of pregnancy, sonographic evaluation for
fetal or placental syphilis
 Consult with OB specialists
 After treatment, repeat serologic titers in 3rd
trimester and at delivery
 Insufficient data on serologic responses after therapy
 Treatment likely inadequate if delivery ≤30 days of
treatment, if woman has sign of infection at delivery, or
if maternal titer is 4-fold higher than pretreatment titer
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Websites to Access the Guidelines
 http://www.aidsetc.org
 http://aidsinfo.nih.gov
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About This Slide Set
 This presentation was prepared by Susa Coffey,
MD, for the AETC National Resource Center in
June 2013
 See the AETC NRC website for the most current
version of this presentation:
http://www.aidsetc.org
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