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  •, picture of naples municipal coat of arms Treponema pallidum, picture from T. pallidum pallidum is a motile spirochaete that is generally acquired by close sexual contact, entering the host via breaches in squamous or columnar epithelium. The organism can also be transmitted to a fetus by transplacental passage during the later stages of pregnancy, giving rise to congenital syphilis. The helical structure of T. pallidum pallidum allows it to move in a corkscrew motion through viscous mediums such as mucus. It gains access to host's blood and lymph systems through tissue and mucus membranes.
  • Syphilis remains a public health problem in metropolitan areas with large populations of MSM. For the third consecutive year, San Francisco had the highest P&S rate of any U.S. city in 2004 (45.9). Other leading cities include Atlanta, Georgia (34.6); Baltimore, Maryland (33.2); New Orleans, Louisiana (16.4); St Louis, Missouri (14.1); Detroit, Michigan (13.5); Washington, D.C. (12.2); Dallas, Texas (11.6); Jersey City, New Jersey (10.8); and Chicago, Illinois (9.7).
  • March 17, 2006 MMWR report; titled: Primary and Secondary syphilis United States 2003-2004 After declining for 13 years the rate of syphilis has increased. Since 1991 this is the first time that the rate in women has not decreased This represents the first increase in the disparity between black and white rates since 1993. The increasing M:F rate ratio suggests that increases are still occurring among MSM. CDC has estimated that in 2004, approximately 64% of all P&S syphilis cases were among MSM.¶ After 13 years of decline, rates of P&S syphilis in 2004 increased in the South and did not decrease among women.
  • From 2004 to 2005 there is an increase of 24%
  • scanning electron microscope (SEM) image of a T-lymphocyte (right), a platelet (center), and a red blood cell (left). Image Innate response is nonspecific, exposure leads to immediate maximum response, cell are leukocytes,no immunological memory Adaptive response is specific per pathogen and antigen response, cells are called lymphocytes, have memory T cells - Cell mediated immunity is mediated by the T lymphocytes and is responsible for defense against intracellular microbes B cells-Humoral immunity protects against extracellular immunity
  • Apoptosis chronic activation of unifected cells responding to HIV itself or to common infections, leads to cell death, thus the numbers of CD4 cells that die are far greater than Gp41 inserts through host cell membrane and passes on RNA material Stages of HIV page 253, Kumar Picture: Immature HIV particle These are characterized by a disorganized central core but otherwise a complete virus able to infect the lymphocytes. This particle is tightly attached to the membrane of this cell. We believe that membrane transformation caused by direct attachment is significant to the progression of AIDS.
  • Outcomes projects for availability: Increase receipt of test results Increase identification of HIV-infected pregnant women so they can receive effective prophylaxis Increase feasibility of testing in acute-settings with same-day results Increase number of venues where testing can be offered to high-risk persons
  • The standard screening test for antibodies to HIV is the enzyme immunoassay (EIA) or ELISA OraQuick Advance, Uni Gold Recombin Reveal G2, Multispot Sure Check and Stat Pak (May 2006)
  • Transcript

    • 1. Depressed CD4: Is it always HIV? Aaron J. Loeb, BSN, RN Celine Hanson, MD Texas Children’s Hospital 12-14-2006
    • 2. Objectives
      • Case Presentation
      • Emerging Trends
        • Syphilis and HIV
      • Disease Management
        • CD4 function
        • Infectious Diseases and CD4
        • CD4 testing/guidelines
        • Counseling
    • 4. Case Presentation
      • Clinical History:
        • 30 year old HIV negative male with progressive rash
        • Excess fatigue and sleepiness
        • Topical/lotions use
        • Denied fever, headache, itching
    • 5. CD4 Testing 484-1159 699 600 710 273 471 510 CD4 # 32-54% 37 36 33 28 37 38 CD4 % NL Range 08/06 04/06 02/06 12/05 11/05 09/05 Date
    • 6. HIV Rapid Testing
      • Results
        • 05/05 Negative
        • 12/05 Negative
        • 01/06 Negative
        • 04/06 Negative
        • 09/06 Negative
    • 7. Case Presentation
      • Physical Examination
        • Fixed macular, reddish-brown rash
        • Central presentation with progression to extremities
        • Rash highlighted with temperature change
        • No alopecia, lymphadenopathy or pharyngitis
    • 8. Case Presentation
      • Diagnosis/Treatment
        • Clinical secondary syphilis confirmed by reactive RPR (1:128)
        • IM Pen G administration
        • Jarisch-Herxhemier’s reaction following penicillin delivery
    • 9. Case Presentation
      • Counseling
        • Contact by local Health Department
        • Possible co-infection with HIV
        • Contagious; avoid sexual encounters
        • Relevance lowered CD4 to syphilis
    • 10. Emerging Trends Syphilis and HIV
    • 11. History of Syphilis
      • Naples
        • First well recorded outbreak in 1494
        • CDC began tracking in 1941
      • Previous Names
        • Great Pox
        • The French Disease
        • The English Disease
    • 12. Syphilis Demographics Summary
    • 13. Cities with Highest Reported Rates of P&S Syphilis, 2004
    • 14. Primary and Secondary Syphilis: Rates
      • The South
        • Increased: 3.1 versus 3.6 cases per 100,000 population a 16% increase
      • Men
        • Increased from 2.6 to 4.7 during 2001-2004
        • Blacks: 5.1 times higher than whites in 2003 and 5.6 times higher in 2004
      • Women
        • Remained at 0.8 in 2004
        • Decreased from 1.7 to 0.8 from 2000 to 2003
    • 15. Syphilis Co-Infection with HIV: Harris County
    • 16. Disease Management
      • CD4 function and HIV
      • Other Infectious Diseases and CD4
      • CD4 testing/guidelines
      • Counseling
    • 17. Disease Management CD4 function and HIV
    • 18. The Immune System
      • The National Cancer Institute at Frederick
      • Protects against infectious pathogens
      • Mechanism of protection
        • Innate--natural or native immunity
        • Adaptive--acquired or specific immunity
    • 19. CD4 Function
      • Delayed T cell hypersensitivity responses
      • Influence other immune cell activity
        • Immunoglobulin synthesis
        • Cellular cytotoxicity
    • 20. HIV Replication
      • CD4 as a high affinity receptor
      • - gp120 attaches to CCR5 and CXCR4
      • - gp41 insertion through cell membrane
      • Stages
          • - Acute retroviral
          • - Middle, chronic phase
          • - Full-blown AIDS
      • Macrophages and monocytes vulnerable
    • 21. Impact of HIV on CD4
      • Precise mechanism for CD4 loss in HIV disease is not defined
      • Potential mechanisms for CD4 loss include:
        • HIV CD4+ cells home to the lymph system
          • Due to CD62 homing ligand receptor and Fas upregulation after HIV binding to CD4
          • Signaling to CD4+/HIV infected cells leads to programmed cell death (apoptosis) in lymph tissue
        • Naïve CD4+ T cells are depleted more rapidly in the thymus than memory cells
          • Results in impaired supply of CD4+ T cells to periphery
          • Increases division rate of naïve T cells and lowers emigration out of the thymus
    • 22. CD4 and HIV viral load Risk for AIDS (25 y/o) 1.2% 6.3% 25.1% 3 x 10 5 0.6% 3.2% 13.3% 3 x 10 4 0.3% 1.6% 6.8% 3 x 10 3 Viral load 500 200 50 CD4#
    • 23. Syphilis and CD4
      • Syphilis without HIV infection
        • Independent of gender CD4 decreases as CD8 increases
      • Syphilis with HIV infection
        • CD4 count decreases with increased viral load of primary and secondary syphilis
        • CD4 count increases with syphilis treatment with decreased HIV-RNA counts
    • 24. Disease Management Infectious Diseases and CD4
    • 25. Infections that lower CD4 or CD4/CD8 ratio
      • Tuberculosis (TB)
      • Cytolomegalovirus (CMV)
      • Herpes Simplex Virus (HSV)
      • Epstein Barr Virus (EBV)
    • 26. CD4 and TB
      • T cell apoptosis has been described in HIV negative individuals with disseminated TB
        • Affected cells include CD4 and CD8+ T cells
      • Individuals with extrapulmonary TB and/or more severe complications are more likely to have lower CD4+ T cells
    • 27. CD4 and Viral infections CMV, HSV and EBV
      • CD4 and CD8+ T cells and neutralizing antibody are pivotal in human responses to primary viral infections
      • CD8+ T cell expansion is typical in symptomatic CMV infection and causes an inverted CD4/CD8 ratio
        • Inverted CD4/CD8 ratio is not aytpical in HSV or EBV
      • Peripheral blood CD4 depletion rarely occurs in CMV infection
        • Diminished CMV specific CD4+ cells has been documented in pediatric CMV
    • 28. Screening for Syphilis
      • Syphilis Elimination Plan (SEE)
        • CDC formed campaign in 1999
        • Improve testing and laboratory services
        • Goal: make a rapid test available for use in the U.S. within the next few years
      • Current testing: RPR
        • Week waiting period
      • Target HIV testing sites
    • 29. Center’s For Disease Control HIV Guidelines
      • Revised September 2006
      • There is an urgent need to increase the proportion of persons who are aware of their HIV-infection status
      • Expanded, routine, voluntary, opt-out screening in health care settings is needed
      • Such screening is cost-effective
      • Bernard Branson MD Revised Recommendations for HIV Testing in Healthcare Settings in the U.S.
    • 30. Disease Management
      • Testing/Guidelines
        • Clinical lymphocyte subset testing provides most accurate results when consistent laboratory is used
        • Dual (CD3/CD4) and triple antibody staining (CD3/CD4/CD45) have eliminated inclusion of cells from other lineages
        • Single test assessment should be avoided
          • Repeat testing using specimens collected at separate dates
    • 31. Disease Management Counseling patients with CD4 depression
    • 32. Counseling Considerations
      • Counseling for depressed CD4 count
        • History of HIV risks
          • Recommend HIV testing
        • Consider other STDs and impact on CD4 test
          • History for STDs
          • Recommend syphilis, TB or viral testing
        • Consider other immune deficiencies
          • Idiopathic CD4+ T cell lymphocytopenia
    • 33. Screening For HIV
      • High rates of non-return for test results
      • In 2000, 31% did not return for results of HIV-positive conventional tests at publicly funded sites
      • HIV rapid testing availability is crucial
      • -Sure Check and Stat Pak approved in May 2006
      • Screen for high prevalence and high volume settings
      • Bernard Branson MD Revised Recommendations for HIV Testing in Healthcare Settings in the U.S.
    • 34. Testing for HIV
      • Recommendations for Adults and Adolescents
        • Routine, voluntary HIV screening for all persons 13-64 in health care settings, not based on risk
        • Repeat HIV screening of persons with known risk at least annually
        • Opt-out HIV screening with the opportunity to ask questions and the option to decline
        • Include HIV consent with general consent for care; separate signed informed consent not recommended
        • Prevention counseling in conjunctions with HIV screening in health care settings is not required
      • Bernard Branson MD Revised Recommendations for HIV Testing in Healthcare Settings in the U.S.
    • 35. Counseling Challenges
      • Identifying high risk behavior
      • Educate about mode of transmission
      • Possibility of reinfection
      • Co-infection with HIV
        • Correlating possible exposure to syphilis exposure
    • 36. Article References:
      • Antas, P.R., Ding, L., Hackman, J., Reeves-Hammock, L., Shintani, A.K., Schiffer, J., Holland, S.M., et al. (2004). Decreased CD4+ lymphocytes and innate immune responses in adults with previous extrapulmonary tuberculosis. Journal of Allergy Clinical Immunology 117(4).
      • Fan, Y.M., Zeng, W.J. & Li, S.F. (2004). Immunophenotypes, apoptosis, and expression of Fas and Bcl-2 from peripheral blood lymphocytes in patients with secondary early syphilis. Sexually Transmitted Diseases. 31(4).
      • Gamadia, L.E., Rentenaar, R.J., Van Lier, R.A., & Berge, I.J. (2004). Properties of CD4 (+) T cells in human cytomegalovirus infection. Human Immunology. 65 (5).
      • Grossman, Z., & Paul, W.E. (2000). The impact of HIV on naïve T-cell homeostasis. Nature Medicine (6)
      • Hatton, A.E., Montamat-Sicotte, D., Gudgeon, N., Rickinson, A.B., McMichael, A.J. & Calian, M.F. (2003). Characteristics of the CD4 + T cell response to Epstein-Barr virus during primary and secondary infection. Journal of Expert Medicine 198(6).
      • Kofoed, K., Gerstoft, J. Mathiesen, L.R., & Benfield, T. ( 2006). Syphilis and human immunodeficiency virus (HIV)-1 coinfection: influence on CD4 T-cell count, HIV-1 viral load, and treatment response. Sexually Transmitted Diseases. 33(3).
      • MMWR, (2006). Primary and Secondary Syphilis ---United States, 2003-2004. MMWR Weekly. 55(10), pp 269-273.
    • 37. Website References
      • AIDS Info
      • Centers for Disease Control, HIV
      • Centers for Disease Control, Syphilis
      • Texas Department of State Health Services, HIV
      • Wikipedia, treponema pallidum
    • 38. Would like to thank
      • Dr. Celine Hanson
      • Dr. William T. Shearer
      • Chivon McMullen-Jackson
      • Study Participant