Occupational Exposures to Bloodborne Pathogens

1. Occupational Exposures to Bloodborne Pathogens Arjun Srinivasan Johns Hopkins Hospital

2. Outline What’s an exposure? 1st step in all exposures - Clean the site!! Specific pathogens Hepatitis C Hepatitis B HIV

3. Scope of the Problem Difficult to asses: up to 70% of exposures go unreported (Marcus, R. et. al. Ann Emerg Med 1995;25:776) 1990 estimate: 500,000 exposures/year (Henry, K. Minnesota Medicine 1995;78:41-44) Costs are also tough to asses but JHH spent $282,000 on post-exposure evaluation and treatment in 1998

4. Scope of the Problem Impossible to measure the psychological stress that an exposure places on a health care worker

5. At Risk Exposures 1. Percutaneous injury Hollow needle > Solid sharp Visible blood Deep injury Device in patient’s artery or vein 2. Splash on non-intact skin 3. Splash on mucous membrane

6. Risks From Body Fluids Known to be infectious: Blood Any fluid visibly contaminated with blood Semen Vaginal secretions Concentrated virus (used in labs)

7. Risks From Body Fluids Potentially infectious CSF Pleural fluid Pericardial fluid Peritoneal fluid Amniotic fluid Synovial fluid Tissue samples

8. Risks From Body Fluids Not Infectious (if not visibly bloody) Tears Saliva Urine Feces Sweat Emesis

9. The Solution to Pollution . . . Exposure site should be cleaned IMMEDIATELY! This may be the most important part of PEP Skin wounds should be washed with soap and water No evidence that antiseptics are useful and caustic agents (bleach) may do more harm than good

10. The Solution to Pollution (cont) Mucous membranes should be flushed thoroughly with water Eyes should be irrigated with a liter of saline

11. A word from our lawyers . . . ALL exposures should be reported to the proper people (Occupational health, Employee health etc.) Disability claims can be denied if follow up reporting was not done right

12. Hepatitis C

13. Hepatitis C: Risk of Exposure Risk of seroconversion following needlesticks involving Hep C positive patients is 0-7% (avg 1.8%) (Kiyosawa, K. et.al. Ann Int Med 1991;115:367) (Lanphear, B.P. et.al. Inf Ctrl Hosp Epi 1994;15:745) Transmission via mucous membrane exposure described in one case (Sartori, M. Jnl Inf Dis 1993;25:270)

14. Hepatitis C: Risk of Disease

15. Post Exposure Recommendations Clean the site immediately Hepatitis B immune globulin has NOT been effective Interferon is NOT recommended at this time (Infect Control Hosp Epi 1994;15:742-4) (MMWR 2001;50(RR-11):1-67)

16. Hepatitis C: Follow Up Enzyme linked immunoassay (EIA) is screening test of choice ALL exposed HCWs should have LFTs monitored Average interval between exposure and seroconversion with EIA is 8-10 weeks Follow up guidelines vary - CDC recommends follow up at 4-6 months

17. Hepatitis C: Follow up issues EIA is falsely positive in up to 50% of HCW and falsely negative in 5% - results must be confirmed by RIBA or VL PCR may catch infection earlier but detection is highly variable Immediate referral for treatment if HCW seroconverts

18. Hepatitis C: Counseling Risk of transmission to infants and partners is thought to be low Exposed HCW do not need to modify sexual practices, stop breast feeding or refrain from becoming pregnant Should not donate blood MMWR 2001;50(RR-11):23

19. Hepatitis B

20. Hepatitis B: Risk of Exposure Most infectious bloodborne pathogen Risk of clinical hepatitis up to 30% in percutaneous exposures to patients who are “e” antigen positive (Werner, B.J. et.al. Ann Int Med 1982;97:367) Risk from mucous membrane exposure less well defined but also felt to be high

21. Hepatits B: Outcome of Infection In patients who are infected with Hep B: 25% get jaundice 5% require hospitilization 6-10% become chronically infected .125% die of fulminant hepatitis

22. Hepatitis B: Good News Most HCWs have been vaccinated and vaccine offers virtually complete protection to responders

23. Hepatitis B: Bad News Some employees are NOT vaccinated 6-10% of vaccinees do NOT develop antibody Really bad news: CDC estimates that 50-75 HCW die from Hep B each year

24. Hepatitis B: Post Exposure Clean the site immediately Determine the vaccine status of the HCW Determine the surface antigen status of the source patient

25. Hep B: HCW Never Vaccinated HCW should receive vaccine ASAP 1. Source patient is sAg positive: HCW should also receive one dose of Hep B immune globulin (HBIG) .06ml/kg (1 vial=5 ml) ASAP and absolutely within 7 days of exposure 2. Source patient sAg neg or unknown Vaccine alone

26. Hep B: HCW Vaccinated(one or more doses) Source patient should be tested for sAg AND HCW should be tested for sAb If HCW has adequate Ab >10 IU/mL (now or at any time) then no additional treatment

27. Hep B: HCW Vaccinated IF HCW has inadequate Ab: 1. If pt is sAg negative: HCW should get booster dose of vaccine (or complete series) 2. If pt is sAg positive: HCW should receive HBIG AND a booster dose of vaccine at different sites (complete series if necessary)

28. Hep B: HCW Vaccinated (cont.) If HCW has inadequate Ab: 3. Unknown source: Give vaccine booster or complete series

29. Vaccine non-responders If HCW has inadequate Ab after 3 dose series they should get another series: 30-50% chance of responding to 2nd series If no response to 2nd series HCW should be considered susceptible PEP for known non-responders exposed to Hep B positive or high risk unknown sources: 2 doses of HBIG- 1 at exposure then 4 weeks later

30. Hep B: Follow Up Testing Hepatitis B sAg is the test of choice as it rises in about 6 weeks LFTs should be monitored at regular intervals

31. Post Exposure Counseling Risk of transmission to infants and partners is thought to be low Exposed HCW do not need to modify sexual practices, stop breast feeding or refrain from becoming pregnant Should not donate blood MMWR 2001;50(RR-11):23

32. HIV

33. HIV: Risk of Exposure Risk of transmission from percutaneous expsosures involving HIV positive pts estimated at 0.3% Risk from mucous membrane exposure estimated at 0.1% As of 2000 there were 56 confirmed and 138 possible cases of occupational transmission in the US

34. Rationale for PEP HIV infects dendritic cells and then regional lymph nodes before becoming systemic AZT blocks infectivity of HIV infected dendritic cells Goal of PEP is to halt viral replication before systemic infection is established

35. Does It Work? Several animal studies showing efficacy Peri-natal prophylaxis has been effective Retrospective study showed that risk of seroconversion after exposure was 81% lower in HCWs who took AZT PEP. (NEJM 1997;337:1485)

36. Time is Virus Animal studies show that PEP should be given within 2-8 hours of exposure for maximal effect (JID 1991;163:625 - Within 2 hrs optimal) (JID 1993;168:825 - Within 8 hrs optimal) PEP may have some benefit up to 36 hrs but seems to be ineffective if given later

37. What To Use? Before: AZT+3TC +/- IDV or NFV Now: Becoming more difficult to answer! Regimens may need to be tailored based on the treatment history of the source patient -Surveillance study from 1998-1999 found that 39% of virus from source patients had some NRTI resistance and 10% had some PI resistance.

38. Nucleoside Reverse Transcriptase Inhibitors (NRTI) Still form the backbone of most regimens AZT has been formally studied thus it should be included if possible Addition of 3TC is recommended because: 1. It appears non-toxic 2. It has some synergistic effect with AZT with respect to mutations

39. NRTI (cont) If source patient’s virus is felt to be resistant to AZT or 3TC alternatives include: d4T + 3TC d4T + ddI Role of abacavir? Role of tenofovir?

40. Protease Inhibitors (PI) Are very potent anti-virals and work very well in patients BUT they have significant side effects and can cause HCW to stop PEP altogether PI should be recommended primarily when the exposure is high risk Any PI can be used but indinavir and nelfinavir have been used the most

41. Non Nucleoside Reverse Transcriptase Inhibitors (NNRTI) Not much experience using these for PEP Use should be reserved for situations when source patient’s virus is thought to be resistant to all PIs Nevirapine should probably be avoided as PEP: from 1997-2000 there were 22 reports of serious toxicity in HCW taking it for PEP

42. Toxicity of PEP 50-90% of HCWs report some side effects from PEP 24-36% of HCWs stop PEP because of side effects PEP only works when taken - More may not be better!

43. Side Effects of PEP All side effects have been described in some degree in HCWs on PEP Serious side effects appear rare: isolated reports of hepatitis and pancytopenia Excluding problems with nevirapine, all side effects have reversed with stopping meds (MMWR May 15, 1998/ 47(RR-7);1

44. PEP Counseling Clean the site immediately Determine the HIV status of the source Determine the extent of the exposure

45. PEP management: Source Patient Testing Crucial 1st step as most exposures do NOT involve HIV positive patients Rapid test kit (SUDS) is available and yields an answer in about 30 minutes Rapid test is an EIA that is >99.9% sensitive Testing of blood on sharps is NOT recommended Patient consent is required in Maryland

46. HIV RNA Testing of Source No official recommendations and test is not approved for this indication Should be reserved for cases where there is a suspicion of acute retroviral conversion

47. Source Patient 1. Patient HIV negative - No PEP 2. Patient HIV positive Low viral load / high CD4 = class 1 High viral load / low CD4 = class 2 3. Patient HIV positive, unknown CD4, VL Use best judgement - err towards class 2 4. Unknown source

48. Exposure Types 1. Non-infectious fluids - No PEP 2. Mucous membrane, non-intact skin Small volume Large volume 3. Percutaneous injury Less severe More severe

49. HIV PEP Recommendations Percutaneous injuries Less severe Source pt HIV negative - No PEP Source pt class 1 - Recommend 2 drugs Source pt class 2 - Recommend 3 drugs Source of unknown status- Consider 2 drugs in setting where exposure to HIV positive pt likely or if pt has HIV risk factors

50. HIV PEP Percutaneous Injuries (cont.) More severe injury Source pt HIV negative - No PEP Source pt HIV class 1 or 2 - Recommend expanded 3-drug regimen Source of unknown status - Consider 2 drugs in setting where exposure to HIV positive pt likely or if pt has HIV risk factors

51. HIV PEP Mucous membrane exposures Small Volume Source pt HIV negative - No PEP Source pt class 1 - Consider 2 drugs Source pt class 2 - Recommend 2 drugs Source of unknown status- Consider 2 drugs in setting where exposure to HIV positive pt likely or if pt has HIV risk factors

52. HIV PEP Mucous membrane exposures Large volume Source pt HIV negative - No PEP Source pt class 1 - Recommend 2 drugs Source pt class 2 - Recommend 3 drugs Source of unknown status- Consider 2 drugs in setting where exposure to HIV positive pt likely or if pt has HIV risk factors

53. Duration of Treatment Current recommendation is 4 weeks but this is an arbitrary selection Animal studies suggest 10 days is too short but 28 days conferred protection

54. Resistance Becoming a significant problem now that so many patients are getting treated Treatment history can be helpful in the acute setting Recent history may be more important than remote

55. Resistance Issues Full medical history often not available when the exposure occurs - PEP should NOT be delayed Data from maternal transmission studies shows viral resistance does not preclude benefit

56. Resistance Issues Consultation with someone experienced in HIV treatment is recommended in cases where HIV resistance is possible PEP may need to be modified once more history is available Resistance testing is too slow to be of use right now

57. PEP and Pregnancy Women of child bearing age should be offered a pregnancy test before starting PEP BUT, recommendations on starting PEP should NOT change just because HCW is pregnant

58. HIV medications to avoid in Pregnant HCW d4T, ddI: have been associated with severe lactic acidosis in pregnant women Efavirenz: is teratogenic in primates Indinavir: causes hyperbilirubinemia in newborns if given near time of delivery

59. Post Exposure Testing Testing should be done at regular intervals (eg 6,12 weeks and 6 months) Testing should continue for 12 months if the HCW contracts HCV from the exposure Unclear if testing should be prolonged in exposures to pts with HIV and HCV or in HCW who have history of impaired Ab responses

60. Post Exposure Testing EIA is test of choice Viral loads and p24 assays should be reserved for suspected cases of acute seroconversion given high false pos rate

61. Counseling For 3 months following exposure HCW should avoid: -unprotected sex -donating blood -sharing razors, toothbrushes HCW should consider stopping breast feeding (risk of perinatal transmission and drugs may get into breast milk)

62. Time to Seroconversion Most HCW seroconvert in 6-12 weeks with median time of 46 days 95% seroconvert within 6 months 100% seroconvert in one year Co-infection with HCV may delay HIV seroconversion

63. Acute Retroviral Conversion Symptomatic seroconversion develops in 50-90% of cases Average time from exposure to symptoms is 2-6 weeks ANY HCW who develops a flu-like illness in the follow up period should be encouraged to get HIV RNA testing

64. Resources US Public Health Service Guidelines www.cdc.gov/ncidod/hip National PEP Hotline (run by UCSF) 1-888-448-4911 (24 hrs) www.ucsf.edu/hivcntr

65. Conclusion People react very differently to exposures - be prepared for anything! The psychological impact of an exposure can be enormous Your patience and understanding may be the best PEP of all