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SUNY Downstate

SUNY Downstate. Kings County Hospital Center. Brooklyn VA. The Division Infectious Diseases. 16 full time faculty 3 part time faculty Fellowship program: 2 years 8 total fellows Areas of interest: HIV STI antimicrobial resistance chlamydia research

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SUNY Downstate

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  1. SUNY Downstate

  2. Kings County Hospital Center

  3. Brooklyn VA

  4. The Division Infectious Diseases • 16 full time faculty • 3 part time faculty • Fellowship program: 2 years 8 total fellows • Areas of interest: HIV STI antimicrobial resistance chlamydia research Hepatitis C virus global health

  5. Pediatric Infectious DiseasesChlamydia Research LaboratorySUNY Downstate Medical Center Stephan A. Kohlhoff, MD Margaret R. Hammerschlag, MD

  6. Seroepidemiology of C. trachomatis in children • Screening and treatment programs have been successful in some populations, but overall infection rates in the U.S. are still high • Prevention of C. trachomatis infections would be an ideal application for a vaccine program and promising vaccine candidates could soon enter clinical trials • Ideally the vaccine should be administered before infections occur, similar to vaccination against HPV • Seroprevalence in published studies (1980’s) has been around 20% raising questions about mechanism of acquisition of the organism (perinatal?), biological plausibility as well as specificity of the tests being used • There are no current population-based pediatric epidemiologic studies of age-specific prevalence of anti-C. trachomatis IgG

  7. Impact of Universal Chlamydia trachomatis Screening during Pregnancy on Pediatric Seroprevalence: 1991-2011.1 • Pilot study indicates decreased seroprevalence in young children in Group 2 (post CDC recommendation on screening/treatment in pregnancy) • Prospective multi-site serosurvey will further define seroprevalence in 1-year age strata to inform future vaccine trials and policies 1 Chotikanatis K., Hammerschlag MR, Kohlhoff S. Presented at IDWeek 2012; San Diego, CA

  8. Cellular immune responses to C. pneumoniae (Cpn) in patients with asthma • The obligate intracellular pathogen Cpn can cause persistent infection, which may contribute to ongoing asthma symptoms • Pathogen-specific effector memory T lymphocytes (TEM) are commonly found in patients with persistent viral infections • However, there are no data on presence of Cpn-specific TEM in persistent Cpn infection • Identification of Cpn-specific TEM in asthmatics may help identify patients with persistent Cpn infection and allow specific treatment • We are studying the presence of Cpn-specific lymphocyte memory responses in asthmatics and non-atopic healthy controls

  9. Cellular immune responses to C. pneumoniae in patients with asthma • In a pilot study 59% of pediatric asthmatics (n=22) had evidence of effector T lymphocyte responses compared to 0% of healthy controls (n=11) (p=0.012; figure 1) 1 • Only asthmatics had in vitro Cpn-induced IL-4 and IgE production, which was suppressed by doxycycline 2 1 Chotikanatis K et al. J Allergy Clin Immunol 2013 Feb; 131 (2): ab190 2 Dzhindzhikhashvili M et al. J Antimicrob Chemother 2013 (in press)

  10. Antimicrobial Resistance-Dr. Landman and Dr. Quale • Characterization of resistance mechanisms • Beta lactamases • Porin defects • Efflux pumps • Alterations in penicillin binding proteins • Activity of novel antimicrobial agents and combination • Epidemiology of antimicrobial resistance

  11. Highlights of select studies • A. baumanii • Temporal declines in susceptibility to CPM, FQ, amikacin , tigecycline • CPM res associated with cephalosporin use • 2 dominant strains • Porin defects +increased class C beta lactamases • Res to tigecycline,cefepime, gentamicin associated with efflux pump AdeB • OXA23 and OXA27 • Despite improved IC no decrease in res rates seen • Combo Rx with polymyxin most effective

  12. Klebsiella pneumonia • ESBLs associated with cephalosporin use • Rapid spread of KPC strains before 2005 • 2 dominant strain • MICs inversely proportional to OmpK36 not efflux system • Carbapenemase related res in Kp and enterobacter best identified using Meropenem, in E coli best using ertapenem • Some success with IC measures • No NDM, OXA48

  13. Temporal trends demonstrate decline in KPC rates although this is site specific • Combo Rx with polymyxin demonstrates some efficacy

  14. Pseudomonas aeruginosa • Progressive decline in susceptibility • Small number of strains • CPM res related to decreased OprD and increased class C cephalosporinase expression • Efflux pumps MexA and MexX associated with meropenem res • CPM res associated with FQ use • Temporal trends demonstrate no decline • Combo Rx with polymyxin demonstrates some efficacy

  15. Ongoing and planned studies 2013 • Citywide surveillance- antimicrobial susceptibility standard and novel agents, PCR detection of carbapenemase and ESBL genes, genetic fingerprinting of isolates • Animal model of pneumonia and sepsis due to MDR Acinetobacter baumanii, Klebsiella pneumonia and Enterobacter cloacae: testing novel antimicrobial combinations • Evaluation of novel anti-sense compounds versus MDR pathogens

  16. STI Research • Kings County Hospital STD Clinic • 5000 patient visits per year • Long history STI research: syphilis, HSV, chlamydia, GC, trich • Collaborations with CDC, NYC-DOHMH, industry • Current activities: • new diagnostics for Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis • new therapeutics for vulvovaginal candidiasis • STI vaccines

  17. HIV • Two large HIV Clinics: • Kings County Hospital Center for Hope • UHB STAR • Total ~3000 patients • Large Caribbean population • Substance abuse • HCV coinfection

  18. Hepatitis C • The Swan Project-NIH funded: Dr. Brian Edlin PI • Since 2005 • 700 young IDUs screened • 300 enrolled in longitudinal follow up • 65 acute HCV infections • Access to care • Repository • Data bank CHOICES-integrated care model

  19. New York State International Training and Research Program

  20. History of NYS-ITRP • Two components • AIDS International Training and Research Program (AITRP) • PI: Dr. Jack DeHovitz; Co-director Dr. Dale Morse • Global Infectious Diseases Research Training Program (GID) • PI: Morse; codirector DeHovitz • AITRP funded since 1993; renewed in 2005; again in 2010 • Czech Republic, Poland, Hungary • Next phase: Baltics, Georgia, Armenia, Russia • Newest add-ons: Ukraine, Kazakhstan • Emerging Infections grant funded 1996 – 2005 • Expanded with TB training grant • GID Funded in 2005 • Focus on hepatitis in Georgia

  21. Current US Partners (All in NYS) • State University of New York at Albany SPH • New York State Department of Health - Division of Epidemiology - Albany, NY • Wadsworth Center • SUNY Downstate Medical Center (Brooklyn, NY) • Center for Drug Use and HIV (NIDA P30) - New York University School of Nursing (Deren) - Beth Israel Medical Center (Des Jarlais)

  22. Training Opportunities (AITRP) • MS Degree in Epidemiology or Biostatistics (1-2 years) • Pre and Postdoctoral Laboratory Training (1-2 years) • Tb, HIV, parasitology, mycology • Certificate Program (6-9+ months) • School of Public Health • Substance Use Behavioral Research Training (3+ months) • Center for Drug Use and HIV Research (CDUHR), New York University School of Nursing

  23. Training Accomplishments • Total number of Fogarty Trainees = 171 (86 long-term, 85 short-term) • More then 60 short-term training courses held • In-Country training/workshops: > 6100 health care professionals in the region • More then 706 books and journal articles published. • First authors on over 200. • Over 200 Abstracts.

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