Post-Exposure Prophylaxis for Needlesticks and Other Occupational Exposures

By Theodore C. Chan, MD, FACEP

Special Feature

Despite awareness of universal precautions, occupational exposures to blood and body fluids remain a constant threat to health care personnel (HCP). A growing number of HCP have reported at least one percutaneous exposure.1 One group found that more than half of EPs surveyed reported an occupational blood exposure in the recent past.2 In addition, the ED often serves as the after-hours access point-of-care for occupational exposures. Staff may not be familiar with what constitutes a high-risk exposure, or the benefits and risks of post-exposure prophylaxis (PEP).3 In recognition of these complexities, the Centers for Disease Control and Prevention (CDC) published exposure guidelines in 1998, and an update of these guidelines in 2001 (available at www.cdc.gov/mmwr/PDF/RR/RR5011.pdf).4,5 These guidelines focus on three main risks—namely, the transmission of human immunodeficiency (HIV), hepatitis B (HBV), and hepatitis C (HCV) viruses.

Overall Risk and General Approach

The first step in caring for an exposed person is to wash the involved wounds and skin with soap and water. Water also should be used to flush any sites of mucous membrane (MM) exposure. There is no proven benefit to antiseptics, disinfectants, or caustic agents. In addition, debridement or attempts to express fluid by squeezing or suctioning has no utility.6 Overall risk of transmission depends on multiple factors, including HCP status, body fluid(s) involved, type of exposure, and source status (if known).

HCP Exposed. At-risk personnel include any employee, student, clinician, public safety worker (e.g., emergency medical service [EMS] personnel), volunteer, or other individual who has contact with patients or their blood or body fluids in the health care, laboratory, or public safety setting. Information should be obtained on whether the individual received a full HBV vaccination series and his or her response status. In addition, baseline HBV, HCV, and HIV immunity status should be assessed.

Fluid/Tissue Exposure. Blood and body fluids containing visible blood have the highest risk of transmission. Semen and vaginal secretions are considered potentially infectious. Cerebrospinal, synovial, pleural, peritoneal, pericardial, and amniotic fluid carry an unknown risk, but also are considered potentially infectious. On the other hand, feces, nasal secretions, saliva, sputum, sweat, tears, urine, and vomitus are not considered infectious unless they contain blood.

Types of Exposure. Percutaneous exposures, such as needlesticks or cuts with sharp objects, carry a higher risk of transmission than other exposures. Contact with blood or other potentially infectious fluids on MM or non-intact skin (e.g., open wound, skin abrasion, chapped skin, or dermatitis) also represents a potentially infectious exposure. Bites must be considered a risk for both the individual bitten and the person who inflicted the bite. Finally, laboratory personnel in direct contact without barrier protection to materials with concentrated virus also must be considered at increased risk.5

Source Status. If the source is known, information should be assessed regarding history of HIV, HBV, and HCV infection. If unknown, the source person should be informed of the incident and serologic testing performed. If the source cannot be tested, an assessment of the specific circumstances and epidemiology of the exposure should be conducted to determine overall risk. Testing of needles and other sharp instruments involved in the exposure is not recommended.

HIV Risk and PEP

The overall risk of HIV transmission by percutaneous and MM exposure from an HIV-infected source remains quite low (estimates of 0.3% and 0.09% transmission rates, respectively).7,8 As of June 2000, the CDC had documented 56 cases of HIV seroconversion after occupational exposures, and reported another possible 138 cases.9 Risk of transmission increases with the quantity of blood involved (e.g., when the needle or device is visibly contaminated with blood), and with the depth of injury.10 In addition, the status of the source also may affect transmission, as those with terminal disease carry higher viral loads and possibly more infectious strains.

The goal of PEP is to interrupt viral replication early after exposure, during the so-called "window period" prior to systemic infection. Within the first 24-48 hours after exposure, the virus infects dendritic-like cells and migrates to regional lymph nodes, leading to extensive viral replication. Early therapy may interrupt this initial infection, viral replication, and proliferation.5 Although definitive studies are limited, benefit of PEP has been demonstrated in animal studies; human studies of maternal-infant transmission where PEP reduced transmission; and smaller, retrospective, case-control studies in which PEP reduced the transmission after occupational exposure by 81%.10,11

Occupational HIV PEP has been in use since 1988.12 The development of new antiretroviral medications has altered the PEP regimen over time. There are three main classifications of PEP medications. (See Table 1.) Each has significant toxicities, including nausea and diarrhea (nucleoside reverse transcriptase inhibitors [NRTIs]), hyperglycemia, dyslipidemia (protease inhibitors [PIs]), severe skin reactions (non-nucleoside reverse transcriptase inhibitors [NNRTIs]), nephrolithiasis (indiavir [IDV]), pancreatitis (didanosine [ddI]), hepatotoxicity (nevirapine [NVP]), and a potentially fatal hypersensitivity reaction that presents like a viral syndrome (abacavir [ABC]).

Table 1: PEP Agents for Occupational HIV Exposure
Nucleoside reverse transcriptase inhibitors (NRTIs)
Zidovudine (AZT, ZDV) Didanosine (ddI)
Lamivudine (3TC) Abacavir (ABC)
Stavudine (d4T)

Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
Nevirapine (NVP) Delavirdine (DLV)
Efavirenz (EFV)

Protease inhibitors (PIs)
Indinavir (IDV) Saquinavir (SQV)
Nelfinavir (NFV) Amprenavir (AMP)
Lopinavir/ritonavir (Kaletra) Ritonavir (RTV)

The CDC has defined two levels of PEP: a basic two-drug regimen (often a combination of NRTIs such as azidothymidine [AZT] and 3TC, known by the trade name Combivir), and an expanded three-drug regimen in which an additional NNRTI or PI is included. The composition of the basic and expanded regimens should be determined in consultation with local community HIV experts when developing a PEP program. The decision on which therapy to recommend—basic, expanded, or no regimen at all—depends on both the exposure type and source status. (See Table 2.) PEP generally is given for four weeks; monitoring of adverse effects, including serologic monitoring (e.g., complete blood count, liver profile, renal function) is recommended. A website has been developed to assist clinicians in the management of exposures (www.needlestick.mednet.ucla.edu/help/conting.htm).13

Table 2: HIV PEP for Occupational Exposures
EXPOSURE SOURCE STATUS
HIV Positive, Class 1 HIV Positive, Class 2 HIV Status Unknown Unknown Source HIV
Negative

Percutaneous: less severe Recommend
basic 2-drug
Recommend expanded 3-drug No PEP warranted; but consider basic 2-drug if source with HIV risk  factors No PEP warranted; but consider basic 2-drug if setting such that exposure to HIV-infected persons is likely No PEP warranted
Percutaneous: more severe Recommend
expanded 3-drug
Recommend expanded 3-drug As above As above As above
MM or non-intact skin: small volume Consider
basic 2-drug
Recommend basic 2-drug As above As above As above
MM or non-intact skin: large volume Recommend
basic 2-drug
Recommend expanded 3-drug As above As above As above

KEY
HIV Positive Class 1:
Asymptomatic or known low viral load (< 1500 RNA copies/mL); HIV Positive Class 2: Symptomatic HIV, AIDS, acute seroconversion, high viral load; Percutaneous—less severe: Solid needle, superficial injury; Percutaneous—more severe: large-bore hollow needle, deep puncture, visible blood on device, or needle used in artery or vein; MM: Mucous membrane; MM/Skin—small volume: few drops, etc.; MM/Skin—large volume: major blood splash, etc.

While pregnancy is not a contraindication to PEP, exposed women must be counseled on the potential risks of both HIV transmission and PEP toxicity to the fetus (e.g., efavirenz is contraindicated in pregnancy). All exposed individuals should be referred for follow-up, generally within 72 hours, for additional education and counseling. At that time, PEP can be adjusted or halted based on additional information obtained, such as source testing results. HIV antibody screening should be performed at baseline, six weeks, 12 weeks, and six months.

There has been a growing concern regarding the potential impact of resistant strains on PEP failure.3 The decision to alter PEP to address potential viral resistance can be done at follow-up; it should be made in conjunction with expert consultation, and should not delay the initiation of PEP. The National Clinicians’ Postexposure Prophylaxis Hotline (PEPline) is available 24 hours a day for consultation on any complex PEP cases (1-888-448-4911; www.ucsf.edu/hivcntr).

HBV Risk and PEP

Despite the HBV vaccine, HCP have a much higher rate of infection than the general population and HBV remains a well-recognized occupational risk.14 After percutaneous injury, the risk of developing clinical hepatitis is 22-31% (and serologic evidence of infection 37-62%) when the source is both HBsAg-positive and HBeAg-positive. Those risks drop to 1-6% and 23-37%, respectively, for HBsAg-positive-only sources.15 Blood exposure remains the chief means of transmission. Other body fluids, such as cerebrospinal fluid, saliva, urine, and breast milk are not efficient vehicles of transmission. However, HBV has been demonstrated to survive in dried blood on environmental surfaces for up to one week, and occupational transmission has been documented from such contact.16

PEP with multiple doses of hepatitis B immunoglobulin (HBIG) has been shown to reduce the risk of transmission by 75% if administered within one week of exposure.17 Recommended regimens with HBIG, vaccination, or both depends on the exposed HCP immunity status, as well as the source HBsAg status. (See Table 3 for detailed recommendations on HBV PEP). Both HBIG and the hepatitis vaccine are considered safe in pregnancy, with few associated adverse effects. As with HIV exposures, HCP should be referred for follow-up testing and counseling.

Table 3: HBV and Recommended PEP

Vaccination and Anti body Status of Exposed HBsAg- positive HBsAg- negative Unknown/NA

Unvaccinated HBIG x 1 and initiate HB vaccine series Initiate HB vaccine series Initiate HB vaccine series
Previously vaccinated: Known responder (those with prior HBV infection are immune and require no Rx) No treatment No treatment No treatment
Previously vaccinated: Known non-responder HBIG x 1, initiate revaccination OR HBIG x 2 (preferred for those who failed to respond to 2nd vaccine series) No treatment If high risk source, treat as HBsAg- positive

KEY: HBsAG=Hepatitis B surface antigen; HBIG= Hepatitis B immunoglobulin

HCV Risk and PEP

The risk of transmission of HCV through occupational exposure is lower than HBV. The incidence of seroconversion after percutaneous exposure from an HCV-positive source is 1.8%. Transmission is rare with MM exposures and no documentation of transmission from skin contact has been reported.5 There has been no proven benefit to prophylaxis with either immunoglobulin or antiviral medications (e.g., interferon or ribavarin) to reduce the risk of transmission. As such, the CDC currently does not recommend the administration of PEP for HCV exposures. Management should include source testing for anti-HCV, baseline testing of the exposed individual for anti-HCV as well as liver profile, and referral for close follow-up, monitoring, counseling, and education given the risk of HCV seroconversion and potential for developing liver disease over time. 

Dr. Chan, Associate Clinical Professor of Medicine, Emergency Medicine, University of California, San Diego, is on the Editorial Board of Emergency Medicine Alert.

References

1. Moran J. Emergency department management of blood and body fluid exposures. Ann Emerg Med 2000;35:47-62.

2. Goldberg R, et al. Antibody titers to hepatitis B surface antigen among vaccinated emergency physicians: Three years’ experience with a wellness booth. Ann Emerg Med 1999;33:156-159.

3. Henderson DK. HIV postexposure prophylaxis in the 21st century. Emerg Infect Dis 2001;7:1-8.

4. Centers for Disease Control. Public Health Service guidelines for the management of health-care worker exposures to HIV and recommendations for postexposure prophylaxis. MMWR Morb Mortal Wkly Rep 1998; 47:1-33.

5. US Public Health Service. Updated US public health service guidelines for the management of occupational exposures to HBV, HCV, and HIV and recommendations for postexposure prophylaxis. MMWR Morb Mortal Wkly Rep 2001;50:1-57.

6. Mikulich VJ, et al. Abridged version of the updated US public health service guidelines for the management of occupational exposures to hepatitis B virus, hepatitis C virus, and human immunodeficiency virus and recommendations of postexposure prophylaxis. Ann Emerg Med 2002;39:321.

7. Bell DM. Occupational risk of human immunodeficiency virus infection in healthcare workers: An overview. Am J Med 1997;102 (suppl 5B):9-15.

8. Ippolito G, et al, and the Italian Study Group on Occupational Risk of HIV Infection. The risk of occupational human immunodeficiency virus in health care workers. Arch Intern Med 1993;153:1451.

9. Centers for Disease Control and Prevention. HIV/AIDS Surveillance Report. Atlanta, GA: Department of Health and Human Services. MMWR CDC Surveill Summ 2000:24.

10. Cardo DM, et al. A case-control study of HIV seroconversion in health care workers after injury. N Engl J Med 1997;337:1485-1490.

11. Connor EM, et al. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zido-vudine treatment. N Engl J Med 1994;331:1173-1180.

12. Henderson DK, et al. Prophylactic zidovudine after occupational exposure to the human immunodeficiency virus: An interim analysis. J Infect Dis 1989;160:321-327.

13. Schriger DL, et al. Implementation of clinical guidelines using a computer charting system. Effect on the initial care of health care workers exposed to body fluids. JAMA 1997;278:1585.

14. West DJ. The risk of hepatitis B infection among health professionals in the United States: A review. Am J Med Sci 1984;287:26-33.

15. Werner BG, et al. Accidental hepatitis-B-surface-antigen-positive inoculations: Use of e antigen to estimate infectivity. Ann Intern Med 1982;97:367-369.

16. Snydman DR, et al. Hemodialysis-associated hepatitis: A report of an epidemic with further evidence on mechanisms of transmission. Am J Epidemiol 1976;104:563-570.

17. Grady GF, et al. Hepatitis B immune globulin for accidental exposures among medical personnel: Final report of a multicenter controlled trial. J Infect Dis 1978;138:625-638.