Occupational Exposures to Bloodborne Pathogens

Arjun Srinivasan

Johns Hopkins Hospital

Outline

• What’s an exposure?

• 1st step in all exposures - Clean the site!!

• Specific pathogens– Hepatitis C– Hepatitis B– HIV

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

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:

– Blood

– Any fluid visibly contaminated with blood

– Semen

– Vaginal secretions

– Concentrated virus (used in labs)

Risks From Body Fluids

• Potentially infectious– CSF– Pleural fluid– Pericardial fluid– Peritoneal fluid– Amniotic fluid– Synovial fluid– Tissue samples

Risks From Body Fluids

• Not Infectious (if not visibly bloody)

– Tears

– Saliva

– Urine

– Feces

– Sweat

– 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

The Solution to Pollution (cont)

• 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

• 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)

Hepatitis C: Risk of Disease

R isk o f c irrh os is from n eed les tick= (.0 -.0 7 )(.8 5 )(.2 )= .0 -1 %

1 5 % C lear S p on tan eou s ly

8 0 % C h ron ic S tab le 2 0 % C h ron ic P rog ress ive(C irrh os is )

8 5 % C h ron ica lly In fec ted

H ep C sercon vers ion

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)

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

MMWR 2001;50(RR-11):23

Hepatitis B

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

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

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

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)

Hep B: HCW Vaccinated (cont.)

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

MMWR 2001;50(RR-11):23

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.

(NEJM 1997;337:1485)

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

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

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?

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

• 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!

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

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

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

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

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

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

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

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

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

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

• 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

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