Occupational Exposures to Bloodborne Pathogens 
By:Arjun Srinivasan
Johns Hopkins Hospital
Outline 
    * What’s an exposure?
    * 1st step in all exposures - Clean the site!!
    * Specific pathogens
          o Hepatitis C
          o Hepatitis B
          o HIV
Scope of the Problem 
    Impossible to measure the psychological stress that an exposure places on a health care worker
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 
Risks From Body Fluids 
    * Known to be infectious:
          o Blood
          o Any fluid visibly contaminated with         blood
          o Semen
          o Vaginal secretions
          o Concentrated virus (used in labs)
    * Potentially infectious
          o CSF
          o Pleural fluid
          o Pericardial fluid
          o Peritoneal fluid
          o Amniotic fluid
          o Synovial fluid
          o Tissue samples
    * Not Infectious (if not visibly bloody)
          o Tears
          o Saliva
          o Urine
          o Feces
          o Sweat
          o Emesis
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
    * Mucous membranes should be flushed thoroughly with water
    * Eyes should be irrigated with a liter of saline
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
Hepatitis C
Hepatitis C: Risk of Exposure 
Hepatitis C: Risk of Disease
Post Exposure Recommendations 
    * Clean the site immediately
    * Hepatitis B immune globulin has NOT been effective
    * Interferon is NOT recommended at this time
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
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
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
Hepatitis B
Hepatitis B: Risk of Exposure 
Hepatits B: Outcome of Infection 
    * In patients who are infected with Hep B:
          o 25% get jaundice
          o 5% require hospitilization
          o 6-10% become chronically infected
          o .125% die of fulminant hepatitis
Hepatitis B: Good News 
    * Most HCWs have been vaccinated and vaccine offers virtually complete protection to responders
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 
Hepatitis B: Post Exposure 
    * Clean the site immediately
    * Determine the vaccine status of the HCW
    * Determine the surface antigen status of the source patient
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  
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
    * 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)
If HCW has inadequate Ab:
3. Unknown source:
    Give vaccine booster or complete series 
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
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
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  
HIV
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
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
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.
Time is Virus 
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.
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 
    * 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?
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
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
Toxicity of PEP 
Side Effects of PEP 
PEP Counseling 
    * Clean the site immediately
    * Determine the HIV status of the source
    * Determine the extent of the exposure 
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
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
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
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 
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
HIV PEP 
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
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
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
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
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
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
    * 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
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
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
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
    * EIA is test of choice
    * Viral loads and p24 assays should be reserved for suspected cases of acute seroconversion given high false pos rate
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)
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
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
Resources 
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
Occupational Exposures to Bloodborne Pathogens.ppt
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