Transcript Document

STD UPDATE
Bryan Larsen, PhD
Marian University College of Osteopathic Medicine
Here Lies
Penicillin
1980
“TET”
A
great
run
1985
Age
Groups
STD
Clinical
Infection
High Risk
Groups
Culture
Antibody
Tests
Molecular
Technol.
Bacteria
STI
Subclinical
Infection
Education/
Counseling
Prevention
Strategy
Immunoprophylax
Ed/SES
Population
Diversity
Diagnostic
Options
Geography
Genetics
History
Risk
Profile
Organism
Diversity
Treatment
Virus
Protozoon
Metazoon
Epidemiolog
Synergy
Behaviors
Efficacy
Fungi
Behaviors
Resistance
Alphabet Soup
PID
GC
HAV
CDC STDTG Areas of Emphasis
Prevention
(everyone
participates)
Populations
(special risks)
Particulars
(11 new key
recommendations)
In the hands of the physician
and the patient
Prevention Strategies
Identify asymptomatic
infected and symptomatic
unlikely to seek treatment
Education and
Counseling of
At risk persons
Effective diagnosis and treatment of those infected
Education, treatment,
counseling for partners of
infected individuals
Pre-exposure vaccination of
individuals at risk for
vaccinepreventable disease
CDC STD TG 2010
Interactive Counseling Basics
Partners: past 2 months, 12 months, m/f/both?
Prevention of Pregnancy: How are you
preventing pregnancy?
Protection from STDs: What do
you use to protect from STD
and HIV?
Practices: What kind of sex; safe?
Past History of STDs: You? Any of your partners?
CDC STD TG 2010
Physical and Chemical Barriers
• Proper use yields benefit! (structural failure 2%)
• Female condoms are available but relatively
more expensive than male condoms (PE or
Nitrile), relatively few studies, recommended.
• Chemical barriers have long been used as
spermicides (OTC N9)
• Spermicides gave birth to a decade of research
on chemical barriers to STDs
www.cdc.gov/condomeffectiveness/latex.htm
Prevention via microbicide
•
•
•
•
•
•
N9 (surfactant) irritant, not recommended
Buffer gel (pH control), not effective so far
Carraguard ( HIV entry inhibitor), not effective
Cellulose sulfate (entry inhibitor), not effective
SAVVY (surfactant), not effective
Pro2000 (polyanion), not effective
• Hopeless?
www.microbicide.org
Microbicide Promise
• Study in South Africa (CAPRISA)
• Tenofovir Gel (Reverse Transcriptase Inhibitor)
• Double Blind, Placebo Controlled, Randomized
Prevention Trial
• 18-30 y.o. / 30 month study (660-680 womenyears)
• 39% overall reduction in HIV (54% in high
adherence participants)
Karim et al. Science 329: 1168 (September 2010)
Research Continues…
•
•
•
•
HIV is the major goal (other STDs also targeted)
HIV focuses on NRTI, NNRTI, fusion inhibitors
HSV is also on the radar
Multivalent prevention is of interest but broad
spectrum compounds did not succeed
• Delivery is important not just vaginal gel
• Vaginal rings, 30 day efficacy, coital
independence
• Vaccine?
Vaccine Preventable Disease
• Molecular biology is bringing new potential vaccines
into the pipeline
• Molecules that bind pathogen to host cell, factors
that are essential to pathogenesis, common
antigens for all strains of a pathogen can be
identified and cloned
• Cloned antigens can be used to produce
monoclonal antibodies, antibody fragments, or
immunizing carriers for STDs
• But, molecular biology can move faster than
product development and testing
• Conserved antigens and mutation rate a key
Knowing People
Knowing Place
Who needs special attention?
•
•
•
•
•
•
Pregnant women
Adolescents
Children
Persons in correctional facilities
MSM
WSW
Pregnancy Issues
• Screening
– For what (HIV, TP, HBV, CT, GC, HCV)
– When to screen first, when to repeat
• Concerns
– Perinatal infections, preterm birth
– Transplacental drugs
– Vaccinations for mother and newborn
• Referral
– Circumstances requiring referral
Pregnancy Recommendations 2010 (Screening)
Do not screen BV or Trich (unless symptomatic) or HSV-2 unless previously diagnosed
Organism
HIV
First Screening
Test all
Repeat Screening
High risk re-tested in
3rd
D
Details
Late testing is before 36 weeks
Laboring patient, unknown HIV status – use
rapid saliva kit
T. pallidum
HB (HBsAg)
Test all
Test all
High risk re-tested in 3rd D
Test at first prenatal visit
Re-test at about 28 weeks
Mother of stillborn
(Stillbirth Certificate is to state if STS done and
if not why not)
Test late those not previously screened
High risk patients
Test at first or early prenatal visit (even if
vaccinated)
Risk: multiple partners in past 6 months,
current IVDU, HBsAg+ partner, clinical hepatitis
Helps interpret transient positive after
vaccination
Test before vaccination
Chlamydia
Test all
Selective re-test in 3rd D
Test at first prenatal visit
Re-testing for < 25y/o; >1 sex partner
N. gonorrhea
All at risk women
All at risk
Risk: < 25y/o; multiple partners, prior GC
Hepatitis C
Test high risk
Risk: IVDU history, blood transfusion or organ
transplant before 1992
The final common pathway to parturition
• Pathogen engages TLR
• Signal transduction leads to cytokine and
chemokine production
• Cytokines recruit inflammatory cells which
provide matrix metalloproteinases
(membranes, cervical remodeling)
• Cytokines induce COX, PG, NOS (cervical
ripening and uterine contractions)
Preterm Birth. IOM. National Academies Press 2007
Adolescent Issues
•
•
•
•
•
Early initiation of sex -> risk
Parental consent not required for STD services
Biological susceptibility may be greater
Unfamiliar with obtaining medical care
Protecting confidentiality (EOB mailed to
parents)
• Screening (for CT, GC, HIV, Cx Ca)
• Prevention (HPV, Education and Counseling)
STD and Children
• GC, CT, TP acquired in the neonatal period is a
virtual guarantee of sexual contact
• HPV and vaginitis are not definitely indicative
of sexual contact
• Investigation involves clinicians, laboratorians,
child protection officials
• Time is of the essence
Issues of Incarcerated Individuals
• High rates of STD (especially Juvi)
• Concentrated correlates of risk
–
–
–
–
–
Low SES
Urban centered
Racial minority
Commercial or coerced sex
History of poor or no medical care
• Protocols for care are not uniform
• Funding for facilities and STD services uncertain
MSM Issues
•
•
•
•
•
•
Shifting landscape in recent past
HIV infected persons living longer and healthier
Substance abuse patterns changing
Demographic shifts in MSM populations
Partner networking via social media
Actual practices (ie oral sex) influence which
organisms are spread (not HIV, but other STIs)
• Specific risks must be assessed on an individual basis
• Diagnostic testing (HIV, CT, GC, TP, HSV2, HBsAg, anal
cytology)
• Vaccination (HAV, HBV)
WSW Issues
• Do not assume WSW are not at risk
• Risks are linked to specific behaviors
• Research data is limited by sexual transmission
of HSV2, TV, BV have been reported
• Some WSW also have had sex with men, or are
having sex with men
CDC STD TG 2010
GC and CT (2009 Summary)
USA 99.1 (20.5 th)
GC
107.2 /
100 K
(19th)
7.2 /
100 K
159.7 /
100 K
340.8 /
100 K
(34th)
246.2 /
100 K
802.7 /
100 K
CT
USA 409 (20.5 th)
CDC STD Surveillance 2009
GC and Antibiotics
•
•
•
•
•
Recommendation CTX + AZITH or DOX
Dual coverage (CT/GC) advocated for either
CTX dosage recommended doubled since 2007
GISP noted creeping MICs for urethral GC
MIC creep is a harbinger of resistance
– % R in past 10 years: 0.2% -> 1.4% for Cefixime
– % R in past 10 years: 0.1% -> 0.3% for Ceftriaxone
– Cephalosporin resistance from Asia and minimally HI
(travel history may influence therapy)
GC and Azithromycin
• AZITH not primary drug for GC, but exposure to drug
may select for resistance
• Mutation of mtrR releases GC from repression of drug
efflux pump (stuck in on position)
• Genetic transfer of mtrR mutation to wild type
bacterium increases AZITH resistance 10 fold (lab)
• Now known that mtrR regulates 70 genes
• 23s rRNA mutation blocks macrolide binding site on
50s bacterial ribosome [C2599T or A2143G]
• In 2010, 22% of 149 GC isolates in one month were
ERY/AZITH resistant
Zarantonelli 1999 AAC 43:2468 / Galarza 2010 AAC 54: 1652
The power of 2
• CT and GC are simultaneously treated because of
similar epidemiology and sequelae
• Two antibiotics have an advantage for preventing
resistance development
• Hypothetical: Development of resistance to
antibiotic A occurs 1 in 1 million bacteria;
resistance to antibiotic B occurs 1 in one million
bacteria. The chance of simultaneous resistance
is 1 x 10-12
• Transferrable resistance is a different matter
Azithromycin for Chlamydia
•
•
•
•
•
•
AZTH named before DOX in recommendations
Single 1g dose AZTH vs 7days DOX (100 mg BID)
Meta analysis of 12 RCT
AZTH 97% and DOX 98% microbiologic cure rate
Clinically equivalent for genital tract infection
AZTH supports DOT therapy when multi-dosing is
uncertain
• Regardless of AZTH or DOX, abstinence for 7 days is
recommended
Lau et al. Sex. Transm. Dis. 2002; 29: 479
Mycoplasma genitalium
Urethritis and Cervicitis
• GC and CT most common, but NGU may involve MG
15-25% of the time, but no standardized MG test
• Other mycoplasmas and Ureaplasma are
inconsistent as etiologies
• Cervix, like urethra, shows pus or muco pus
• GC and CT may be found, but most often no
organism cultured
• MG has been implicated in cervicitis (also
HSV,Trich,BV).
• Treatment is single dose AZTH
CDC STDTG 2010
Expanded diagnostic guidelines for
Trichomonas vaginalis cervicitis
• Cervicitis may imply upper tract inflammation;
look for PID signs
• Along with GC/CT(NAAT) evaluate for BV and TV
• Microscopy is <50% sensitive for TV
• If microscopy is negative use TV culture or FDA
cleared method (OSOM, Affirm)
• Alternate to metronidazole is tinidazole
• CDC recommends treatment of BV or TV
CDC STDTG 2010
Syphilis and HIV (2009 Summary)
USA 4.6 (13.5 th)
Syphilis
0/
100 K
2.3 /
100 K
2.5 /
100 K
(26th)
16.8 /
100 K
8.3 /
100 K
33 / 100 K
HIV (estimates)
USA 17.4
CDC STD Surveillance 2009
Azithromycin and syphilis
• Guidelines emphasize that syphilis remains
susceptible to penicillin which is the
recommended treatment
• Desensitization is recommended for allergy
• AZTH has been used as an alternative
• A SNP in the rRNA gene of the 23S ribosome
inactivates the macrolide binding site in TP
• Concern probably mostly theoretical now
Katz and Klausner. Curr Opin I D. 2008; 21: 83
Neuro-Syphilis (NS) and CSF
• HIV with Syphilis has significant implications for NS
(HIV causes CSF pleiocytosis and risk for NS)
• Syphilis: common comorbidity w/HIV (MSM especially)
• NS may occur early in the infection (not just tertiary)
• Older recommendations conservative regarding LP
• Experts are moving toward universal LP for HIV with
syphilis (CSF VDRL: specific but insensitive)
• NS treatment is more aggressive than early syphilis
alone
CDC STDTG 2010
New NS Biomarkers
• With HIV, a >20 WBC/uL increases specificity for
NS diagnosis
• CSF FTA-Abs is less specific than VDRL but more
sensitive (with Neg FTA, NS unlikely)
• Marra discovered that CXCL 13 elevated in CSF
and serum of NS but not in HIV (OR 2.23 / log
titer) and declines after NS treatment
• CXCL 13 test is independent of CSF WBC, plasma
HIV RNA, peripheral CD4+ and RV meds
Marra et al. STD 2010; 37:283
Bacterial Vaginosis
• Not really an infection but dysbiosis (often
asymptomatic)
• Diagnosis by Gram Stain smear or Amsel Criteria
• Concern relates to risk associations
– HIV, GC, CT, HSV2
– Premature birth, postop infections
– PID
• Treatment is oral Metronidazole or topical
metronidazole or clindamycin
• Alternative is Tinidazole
CDC STD TG 2010
Genital Warts
• Approach may be patient administered or
provider administered
• In addition to Podofilox or Imoquomid, patient
may use Sinecatechins
• Provider may administer cryotherapy,
podophyllin resin, TCA or BCA, surgical
excision
Concluding Thoughts…
• STD is not the sole domain of public health officials
• Medical history taking and health counseling
provides opportunity to impact STD
• Updated opinions on best practices are routinely
update by the CDC
• “Putting our mouth where our money is” will
emphasize viral rather than bacterial STD
• While 11 new topics did not emphasize virus
attention to HIV and HPV still need to remain
elements of concern