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Transcript
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
Hep C serconversion
15% Clear Spontaneously
85% Chronically Infected
80% Chronic Stable
20% Chronic Progressive
(Cirrhosis)
Risk of cirrhosis from needlestick= (.0-.07)(.85)(.2)= .0-1%
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: 3050% 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