Emerging Issues in STDs and Resistance

Transcription

1 Emerging Issues in STDs and Resistance Toye H. Brewer, MD Asst. Professor of Clinical Medicine University of Miami School of Medicine Co-Director- Fogarty International Training Program

2 Outline Syphilis- re-emergence of an old disease Trichomoniasis- nuisance or threat? Gonorrhea- spread of drug resistance Will not discuss LGV- proctitis HSV-2 advances in HIV prevention

3 Primary and secondary syphilis cases by reporting source: United States, Cases (in thousands) non-std Clinic STD Clinic Note: Prior to 1996, the STD clinic source of report corresponded to public (clinic) source of report, and the non-std clinic category corresponded to private source of report. After 1996, as states began reporting morbidity data electronically, the specific source of report (i.e., STD clinic) began to be reported from an increasing number of states.

4 Primary and secondary syphilis Male-tofemale rate ratios: United States, Male-Female rate ratio 10: :1 6:1 4:1 2:

5 Recent Syphilis Outbreaks in USA Since 1997 syphilis rates have risen dramatically among MSM Seattle, San Francisco, Los Angeles and Miami have all reported increasing syphilis rates among MSM Up to 70% have been co-infected with HIV Treatment optimism secondary new HIV therapies is thought to be the cause of increased unsafe sex practices

6 Correlates of Infectious Syphilis among MSM Metamphetamine use Internet sexual networking Wong et al 2003, CDC MMWR 2003

7 Infectious (Primary & Secondary) Syphilis Miami-Dade County, % 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Source: STD MIS N: (31) (82) (125) (184) (231) (194) Women Heterosexual men MSM Current syphilis outbreaks in several counties appear to be driven largely by MSM. Trends in South Florida often precede similar trends in other areas of the state, and thus should be monitored closely. Among MSM with syphilis, the HIV co-infection rate was 24% (2001), 33% (2002), and 42% (2003).

8 Importance of HIV/Syphilis Co-infection Syphilis infection in an HIV positive person is evidence of on going high risk sexual behaviors Syphilis increases the transmission efficiency of HIV Syphilis may have atypical manifestations in HIV positive persons Syphilis requires more intense post treatment monitoring in HIV + persons to rule out treatment failure

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10 Darkfield Diagnosis of Primary Syphilis Treponema pallidum

11 Serologic Diagnosis of Syphilis Screening (non-treponemal) tests are quantifiable, easily and quickly performed, and very sensitive (except in early syphilis) RPR VDRL Confirmatory (specific treponemal) tests are qualitative, require more sophisticated lab work, and used to rule out false positive screening tests FTA MHA-TP Annual screening is recommended in HIV+ patients

12 Clinical Manifestations of Syphilis in HIV + Persons Syphilis may have atypical and aggressive forms of presentation in HIV+ persons Chancres are more likely to be persistent and multiple Syphilitic chancres can be misdiagnosed as genital herpes

13 Atypical Presentations of Primary Syphilis

14 Diagnostic Considerations: Secondary Syphilis in HIV + Persons Condyloma lata can be mistaken for genital warts. Rash of secondary syphilis can be confused with hypersensitivity or other reactions.

15 Secondary Syphilis Infection

16 Diagnostic Considerations: Syphilis in HIV + Persons Serologic responses may be unusual- higher than expected or, more rarely, false negative serologic tests. The majority of patients will have the same results that would be expected in the HIV- patient Accelerated courses of neurosyphilis and neurorelapses have not been found in prospective studies Neurosyphilis should be considered in the differential diagnosis of neurologic disease in the HIV infected patient.

17 Controversies in the Management of HIV+ Patients with Syphilis: To LP or not to LP? Marra et al found that RPR>= 1:32 and/ or CD4 < 350 are highly predictive of laboratory based definition of neurosyphilis. No association was found between laboratory diagnosis and clinical neurosyphilis in most patients LP for all HIV+ patients with any stage of syphilis and CD4<350 or RPR >1:32? OR Treat according to guidelines and LP if after 6 months the same criteria is met? Marra 2004.

18 Proposed algorithm for LP

19 Current CDC Lumbar Puncture Recommendations Neurologic or ophthalmic signs/symptoms Evidence of tertiary syphilis (i.e., aortitis) Treatment Failure HIV infection with latent syphilis or syphilis of unknown duration

20 Azithromycin: A New Treatment for Syphilis? RCT of Azithromycin for early syphilis in Tanzania showed comparable results for IM PCN and 2 grams Azithromycin Treatment failures with Azithromycin reported in the U. S. and Europe with isolation of T. Pallidum with a ribosomal mutation conferring functional macrolide resistance Azithromycin currently not recommended for use in treatment of syphilis in the US Lukehart CID HolmesNEJM 2005.

21 Benzathine Penicillin remains the drug of choice for all stages of syphilis, and the only drug recommended for use in pregnancy

22 Trichomonas vaginalis: Nuisance or Threat? The most common non-viral STD in the world 180 million incident cases per year 5 million cases in the US Not included in aggressive screening and control campaigns

23 Trichomonas vaginalis In women, associated with PID and adverse pregnancy outcomes Associated with increased risk of HIV seroconversion(aor1.5) in prospective and retrospective studies. McClellan et al. JID 2007

24 Trichomoniasis Clinical presentation Most men are asymptomatic and are not screened Symptomatic women may have profuse yellowish discharge, vaginal wall inflammation, and/or strawberry cervix -- Asymptomatic women have lower parasite loads, and are rarely screened outside of STD Clinic -- Men spontaneously clear infection rapidly, whereas infection in women persists for months

25 Trichomonas vaginalis and HIV Trichomonas leads to an inflammatory response and recruitment of CD4+ lymphocytes Punctate mucosal hemorrhages disrupt the mechanical barrier to HIV infection Increases vaginal ph promoting bacterial vaginosis Given high prevalence, even a modest increase in HIV transmission risk could account for a high attributable risk McClellan et al. JID 2007

26 Effect of Trichomonas infection on HIV RNA levels in seminal plasma HIV RNA (copies/ml seminal plasma) 1,000, ,000 10,000 1,000 N = 6 N =18 * P =.0218 T. vaginalis No pathogen (sole pathogen) identified STD patients Hobbs, MM et al., 1999 Sex Trans Dis 26:381; 1999

27 Diagnosis of Trichomoniasis Women Wet prep microscopy is easy but sensitivity is only 50-60% Culture is the gold standard, but results may take 5 days Two point of care rapid tests are FDA approved (antigen test, OSOM, and a nonamplified nucleic acid based test, Affirm) with sensitivities >80%. NAAT of vaginal swabs and urine very sensitive, available only in clinical research settings Men Wet mount is very insensitive Culture of urine, urethral swab or semen increases sensitivity, but is rarely undertaken NAAT have been reported to enhance sensitivities in men, but not FDA approved.

28 Trichomoniasis Treatment Metronidazole 500 mg po BID for 7 days Sex partner(s) must be treated Metronidazole 2 g po single dose, OR In Pregnancy Metronidazole 2 g po single dose Treatment Failures Retreat times 7 days If repeat failure, metronidazole 2 g dose daily for 3-5 days Tinidazole may be tried but cross resistance with metronidazole is common -- Non-nitroimidazole treatments are needed for refractory trichomonas

29 Quinolone Resistant Gonorrhea Gonorrhea has a long history of evolving resistance to commonly used antibiotics- sulfanilimide, penicillin, tetracycline Resistance to fluoroquinolones began in SE Asia and have rapidly spread in the US to Hawaii and California. MSM in the US have a higher prevalence than heterosexual men (18% vs. 2%).

30 Percentage of GISP isolates with intermediate resistance or resistance to ciprofloxacin, * Percent of isolates * Resistance *2003 data are preliminary. Intermediate resistance

31 Quinolone Resistance Among Gonococci Elsewhere in the World Australia 8.1% China 92.5% Japan 73.4% Philippines 57.5% Singapore 46.5% Vietnam 46.0% Israel 61% Source. Wong. CDC.

32 WHO s GASP Gonococcal Antimicrobial Surveillance Project ( ) 6 South American, 13 Caribbean laboratories Some monitored gonorrhea resistance continuously, others periodically and others were unable to start Penicillin resistance- up to 39% TCN - resistance up to 36% No quinolone resistance reported Some spectinomycin resistant isolates Dillon JA et al. Sex Trans Dis. 2007

33 CDC Recommendations for Treatment of Gonorrhea 2006 Heterosexuals without a history of recent travel: Ceftriaxone 125 mg IM Cefixime 400 mg PO Ciprofloxacin 400 mg PO Levofloxacin 250 mg PO MSM, heterosexuals with a history of travel Ceftriaxone 125 mg IM Cefixime 400 mg PO

34 Summary Syphilis incidence is increasing among MSM in many countries, especially among those that are HIV+ Neurosyphilis should always be considered in HIV+ patients with neuro/psychiatric symptoms Trichomoniasis is an extremely common and underdiagnosed STI which enhances HIV transmission Gonococcal resistance is ongoing and requires regional and local monitoring

35 Thank you Muchas Gracias