XIII: OCCUPATIONAL EXPOSURE
Rani Lewis, MD

I. INTRODUCTION

The risk of HIV transmission to medical personnel has been recognized since 1984, with the first reported case of HIV transmitted to a health care worker (HCW) following needlestick injury (Anonymous, 1984). Since that time, information regarding occupational exposure and outcomes has been collected. As of October 1998, there were 187 reported cases in the medical literature of HIV transmission in the United States (CDC, 1998a) and 264 cases worldwide (Ippolito, 1999), presumably related to occupational exposure. A HCW is defined as any person whose activities involve contact with patients or with blood and/or body fluid from patients in a health care setting or laboratory setting. An exposure is defined as a percutaneous injury (needlestick or other cut with a sharp object), mucous membrane or nonintact skin (e.g., chapped or abraded skin, dermatitis), or prolonged contact and/or contact involving an extensive area with blood, tissue, or certain other body fluids. Table 13-1 lists types of exposure that yield a significant health care risk for HIV transmission. Table 13-2 lists body fluids with their relative relationship to risk to exposure. Table 13-3 lists the occupations of people who have been suspected of infection from occupational exposure. When possible, biomolecular assays, including nucleic acid sequencing, have been used to determine the similarity in viral strain between the infected HCW and the possible source (Diaz, 1999).

     In 1995, the Centers for Disease Control and Prevention (CDC) published a report of known cases of occupational exposure in France, the United Kingdom, and the United States (CDC, 1995). This retrospective case-control study gave improved information regarding risk factors for transmission. An important finding in this document was that postexposure prophylaxis (PEP) with zidovudine (ZDV) was associated with an overall 79% reduction in transmission with the use of ZDV (odds ratio=.21; 95% confidence interval, .06–.57) to decrease the risk of seroconversion. This prompted the formation of a U.S. Public Health Service interagency working group, composed of members from the CDC, the Food and Drug Administration, the Health Resources and Services Administration, the National Institutes of Health, and other expert consultants, who developed guidelines for the use of PEP for HCWs after occupational HIV exposure; these recommendations were updated in 1997 (CDC, 1996; CDC, 1998b) (Table 13-4).

     This chapter will review risk factors for transmission and the magnitude of risk for HIV transmission from an occupational exposure, prevention of exposures, and postexposure management, including PEP with antiretro-viral medications.

II. MAGNITUDE OF RISK

Correct estimation of the likelihood of transmission following occupational exposure is limited by the relative infrequency with which HIV transmission to HCWs is reported. In addition, the retrospective nature of this reporting leads to an increased potential for invalid analysis of the risks. There have been prospective and retrospective reviews of all published cases that implicate occupational exposure. The most complete prospective study performed on data from the United States estimates that the risk of HIV transmission following occupational exposure via single needlestick injury is .3% (Bell, 1997). This is compared to a risk of approximately 30% for hepatitis B transmission after percutaneous exposure to HBeAg-positive blood (Alter, 1976; Grady, 1978) and 1.8–10% infection with hepatitis C virus (HCV) after accidental percutaneous exposure to an HCV-positive source (Alter, 1994; Mitsui, 1992; Puro, 1995). Ippolito and coworkers reviewed the world literature on occupational exposure from an HIV-seropositive source and determined risk to be approximately .09% following a mucocutaneous exposure (Ippolito, 1993). As noted in Table 13-2, the risk from skin exposure or exposure to body fluids/tissues other than blood has not been clearly defined. Risk of HIV transmission increases with multiple exposures and with presence of risk factors listed below.

III. RISK FACTORS FOR OCCUPATIONAL HIV TRANSMISSION

The likelihood of HIV infection following exposure is affected by the presence of certain risk factors. Cardo and coworkers (1997) performed a case-control study of internationally gathered cases of percutaneous exposure of HCW in an attempt to determine factors that increased or decreased the risk of transmission (see Tables 13-5 and 13-6). Their data indicate that HCWs who took ZDV after potential exposure had an 81% lower risk of becoming infected (95% confidence interval, 48–94%) than those who did not take this medication.

In general, risk factors include:

• Type of contact or exposure. Exposure has been classified into several risk categories (Table 13-1), including percutaneous, mucocutaneous, and intact skin contact, with different risks of transmission.
  
• Quantity of blood. Exposure to larger quantities of blood from an HIV source, as indicated by a deep needlestick, exposure to needle placed directly into a vessel, or visible blood on the injuring device is associated with an increased risk of transmission. While the rates of transmission have been best studied regarding the use of large-bore needles (< 18 gauge), suture needles appear to have a comparable rate of transmission (p=.08) (Alter, 1976).

• Disease status of source patient. Exposure to blood from patients with terminal illness increases risk. This likely reflects risk associated with exposure to higher levels of virus in blood (higher viral loads). HIV-RNA level has been shown to be a significant factor in the risk of perinatal transmission. Individuals with acute HIV infection also have very high HIV-RNA levels and probably represent an increased risk of transmission if occupational exposure occurs. HCW seroconversion has been reported after exposure to an HIV-infected patient with undetectable viral load (CDC, 1998b). Other factors often present in late-stage disease, such as more virulent syncytia-inducing HIV strains, may also increased risk.
  
• Host defenses. There is some limited evidence that the immune response of the HCW may affect the risk of transmission (Pinto, 1997). Pinto et al. demonstrated an HIV-specific cytotoxic T-lymphocyte response among HIV-exposed but uninfected HCWs when the peripheral blood mononuclear cells were stimulated in vitro by HIV mitogens. Along with similar responses seen in other groups with repeated exposure without infection, this suggests the possibility that the host immune response may prevent HIV infection after exposure.
  
• Postexposure prophylaxis. The data of Cardo et al. (1997) confirm the efficacy of PEP in limiting the risk of HIV transmission to HCWs. Several case reports of transmission in the setting of prompt initiation of PEP, however, indicate that this therapy is not 100% effective. There are greater than 14 known cases of ZDV PEP failure following HCW exposure around the world (Jochimsen, 1997). HIV resistance to ZDV or delay in initiation of medication has been hypothesized to play a role in these (and other, non-HCW) prophylaxis failures.
  

IV. PREVENTING OCCUPATIONAL EXPOSURE

Limiting HCWsí exposure to potentially infectious materials is the key to reducing the risks of occupational exposure. Universal precautions, as recommended by the Occupational Safety and Health Administration (OSHA), reflect the concept that all blood and body fluids are potentially infectious and must be handled accordingly. Personal protective equipment (Table 13-7) should be used to prevent blood and other potentially infectious material from reaching a HCWís clothing, skin, eyes, mouth, or mucous membranes (CDC, 1987). Handwashing should be done after touching blood, body fluids or secretions, or contaminated items, whether or not gloves are worn. Hands should also be washed after removing gloves and and between patient contacts. Gloves should be worn when in contact with blood or body fluids (including blood drawing), mucous membranes or nonintact skin, or items contaminated with possibly infectious material; it is strongly recommended that gloves be worn when performing any invasive procedure. Clinicians performing surgery, deliveries, or other invasive procedures likely to generate splashes of blood or other body fluids should wear a mask and eye protection or face shield. The use of double-gloving in surgical procedures has been shown to reduce the risk of direct blood contact for operating room personnel (Greco, 1995; Konig, 1992). Needles and other sharp instruments should be handled with great care and disposed of in approved sharps containers. As a rule, do not recap, bend, or break used needles. During surgery hand-to-hand passage of sharp instruments (e.g., needles, scalpels) should be minimizedóconsider passing these instruments first onto a surgical tray or pan.

     Risk of occupational exposure and need for universal precautions applies not only to physicians, nurses, and laboratory workers, but also to medical, nursing, or dental students, and to dentists. Since reports of patient-to-dentist and dentist-to-patient HIV transmission seen in the late 1980s (CDC, 1991a), both the CDC and the American Dental Association have included recommendations regarding the use of barrier precautions in dental settings and sterile technique in the preparation of dental equipment (American Dental Association, 1988).

     Another group at increased but less well defined risk are emergency medical technicians, paramedics, and law enforcement agents. These individuals are frequently in contact with patients of unknown or noncommunicated HIV status, in emergency situations. Whereas 6 of the 133 well-documented U.S. cases (.045%) of possible transmission were among dental workers, twice that many transmissions have been reported among emergency workers (12/133, .09%), placing this group behind only laboratory technicians and nurses/phlebotomists in risk for occupational transmission. OSHA regulations requiring the availability of face masks, mouth shields, and ventilation masks are designed to reduce the risk to emergency technicians and other public safety workers. Given the highly unpredictable nature of their risk for exposure, general infection control measures are recommended, even when the risk appears low (International Association of Fire Fighters, 1988). Given the prevalence of HIV infection within prison populations, correctional officers are also at increased risk for occupational exposure and should use universal precautions (Hammett, 1991). Intentional human bites and exposure to saliva are more common in correctional facilities and may present a risk of infection transmission and should be evaluated appropriately. Although hepatitis B has been transmitted via saliva in cases involving human bites (Cancio-Bello, 1982; Mac-Quarrie, 1974); in the absence of visible blood in the saliva, exposure to saliva is not considered a risk for HIV transmission (CDC, 1998b).

There is limited information regarding the symptomatology seen in HCWs experiencing seroconversion from occupational exposure. Approximately four fifths of cases were associated with symptoms consistent with primary HIV infection a median of 25 days after exposure (CDC, 1998b). The average time to seroconversion is 65 days, and 95% of infected HCWs have seroconverted within 6 mo after exposure (Busch, 1997). There are rare reported cases of HCWs who remain negative for HIV antibody at 6 mo, but seroconvert by 12 mo after exposure (Ciesielski, 1997; Konig, 1992). Delayed seroconversion has been associated with simultaneous exposure to hepatitis C in two cases, one of which resulted in fulminant and fatal HCV (Ridzon, 1997). Further information regarding the effect of coinfection with other viral illnesses remains to be determined.

     HCWs presenting for HIV exposure PEP need to be counseled regarding risks of other viral illnesses to which they may have been exposed. Occupational exposure to both hepatitis B and hepatitis C virus has been reported. Although all three of these viruses have similar routes and modes of exposure, the risk of transmission differs because of the differing prevalence of infection. The probability of a source patient from the general population being HBsAg-positive ranges from 5 to 15%; 6–30% of nonimmunized HCWs will become infected following a needlestick injury (CDC, 1989). HCWs at risk for occupational exposure to hepatitis B should therefore assure appropriate vaccination against this virus. PEP for hepatitus B virus is available.

     Hepatitis C virus is the most common chronic blood-borne infection in the United States. The Third National Health and Nutrition Examination Survey (NHANES III) data estimate 3.9 million Americans have been infected with HCV, with 36,000 new infections reported per year (CDC, 1998c). The average incidence of HCV seroconversion following a single needlestick exposure from an HCV-seropositive source is 1.8%. Exposure via mucous membranes, although extremely rare, has been reported (Sartori, 1993). Of note, there is no vaccine or immunoglobulin available for HCV PEP.

VI. POSTEXPOSURE MANAGEMENT

Health care organizations are required to have exposure-control plans, including postexposure management and follow-up for employees at risk. OSHA mandates reporting of exposure incidents.

A. EXPOSURE SITE MANAGEMENT

Wounds and puncture sites should be washed with soap and water; mucous membranes exposed should be flushed with water. The application of bleach to skin or mucosal surfaces is not recommended.

B. EXPOSURE EVALUATION

The type of body fluid involved, type of exposure (percutaneous, mucosal, intact skin, etc.), and the severity of the exposure (quantity of blood, duration of contact, etc.) should be evaluated and will affect decisions about PEP (see Table 13-1).

C. SOURCE PATIENT EVALUATION

The source individual of the exposure should be evaluated for possible HIV infection and, if status is unknown, should be tested, after appropriate consent. Medical information such as previous HIV test results; clinical signs, symptoms, or diagnoses; and history of risk exposures (e.g., injection drug use) may be relevant in making initial decisions regarding PEP. Rapid HIV testing, if available, may be particularly useful in the setting of occupational exposure. Initiation of PEP, if indicated, should not be delayed while awaiting test results. If the source is known to be HIV infected, information about clinical stage of infection, recent CD4 counts, viral load testing, and antiretro-viral treatment history are important in choosing an appropriate PEP regimen; however, initiation of PEP should not be delayed if this information is not immediately available.

     The source patient should also be tested for anti-HCV and HBsAg to assess the HCW’s risk for hepatitis B and C.

D. BASELINE AND FOLLOW-UP TESTING

Baseline testing for HIV antibody should be performed to establish serostatus at the time of exposure and should be repeated at 6 wk, 12 wk, and 6 mo post-exposure, regardless of the use of PEP. An extended duration of follow-up may be considered with simultaneous exposure to HCV or use of highly active antiretroviral therapy regimens for PEP because of theoretical concerns about delay in HIV seroconversion in these situations. Pregnancy testing should be offered to HCWs of reproductive age if pregnancy status is unknown.

     In addition to HIV, hepatitis B and C are significant concerns. For the HCW exposed to an HCV-positive source, baseline and follow-up testing (at 4–6 mo) for anti-HCV and serum alanine aminotransferase is recommended. Confirmation by a supplemental assay (such as recombinant immunoblot assay) is recommended for all positive anti-HCV results by enzyme immunoas-say (CDC, 1998b).

     If the HCW has previously received the hepatitus B virus (HBV) vaccine and anti-HBsAg level, which reflects vaccine-induced protection, is unknown, this should be tested; if inadequate, hepatitus B immune globulin is recommended, as well as a booster dose of vaccine.

• Decisions regarding appropriate postexposure management should be individualized; the HCW should be counseled about their personal risk based on considerations outlined above, and recommendations made about initiating PEP.
  
• The HCW should be informed that knowledge about the effectiveness and the toxicity of the antiretroviral drugs used for PEP is limited; only ZDV has been shown to reduce the risk of HIV transmission in occupational settings to date and failures of ZDV prophylaxis have been reported (Jochim-sen, 1997). The addition of other antiretroviral drugs to a PEP regimen is based on the superiority of combination antiretroviral regimens over monotherapy in the treatment of HIV-infected individuals and the theoretical considerations regarding possible resistance concerns and the utility of using drugs having activity at different stages in the viral replication cycle.
  
• The medical history of the HCW, including medications, presence or possibility of pregnancy, or other medical conditions, should be obtained and may influence decisions or recommendations about PEP, including choice of regimen.
  
• A specific PEP regimen should be recommended, when indicated, and the rationale for its selection should be discussed (see Table 13-4). Information should be given about how to take the medications, potential side effects and measures to minimize these, possible drug-drug interactions with recommended regimen and any medications that should not be taken while taking PEP, clinical monitoring for toxicity, and symptoms that should prompt immediate evaluation (such as back or abdominal pain or blood in the urine, possibly suggesting renal stones in those taking indinavir). Emphasize the importance of adherence.
  
• PEP may be declined by the HCW.
  
• The HCW should be urged to seek medical evaluation with the development of any acute illness during the follow-up period. The differential diagnosis in this situation must include acute HIV infection, drug reaction, toxicity from the PEP regimen, or other medical illness.
  
• Measures to reduce the risk of possible secondary transmission during follow-up (especially in the 6–12 wk after exposure) should be discussed and recommended. These include use of condoms or abstinence to prevent sexual transmission and pregnancy; not donating blood, plasma, tissue, or organs; and, in lactating mothers, perhaps discontinuing breastfeeding.
  
• There is no need to modify clinical responsibilities based on HIV exposure.
  
• Each HCW should be given a contact name and/or number to call for concerns or questions.
  
• HBV prophylaxis: If the patient source of exposure is HBsAg-positive and the HCW has not been vaccinated, hepatitis B vaccination should be initiated and a single dose of hepatitis B immune globulin should be administered as soon as possible after exposure and within 24 hr if possible. If the source patient is HBsAg-negative and the HCW has not been vaccinated against HBV, vaccination should be initiated (CDC, 1991b).
  

The decision regarding which and how many antiretroviral agents to use is largely empiric. Current recommendations are to use a two- or three-drug regimen based on level of HIV transmission risk and possibility of drug resistance (see Table 13-4). PEP should be initiated as soon as possible following exposure and continued for 4 wk. The HIV PEP Registry demonstrated no specific adverse events associated with HIV PEP in HCWs; the registry was closed in December, 1998. Information regarding this program can be obtained through the CDC’s Hospital Infections Program: (404) 639-6425, or on the Internet at: http://www.cdc.gov/ncidod/hip/Blood/PEPRegistry.

     Of the HCWs receiving PEP (ZDV or a combination of agents), 50–90% report subjective side effects and these have led to discontinuation of therapy in 24–36% of cases (CDC, 1998b). Common side effects in those on ZDV include nausea, vomiting, fatigue, headache, and insomnia. Serious side effects, including renal stones and pancytopenia, have been reported with combination PEP regimens. For more details about side effects with different antiretroviral agents, see Chapter XIV on Pharmacology. Laboratory monitoring should include a complete blood count and renal and hepatic function tests at baseline and 2 wk after initiation of PEP; more in-depth testing may be indicated based on underlying medical conditions or specific toxicity associated with drugs in the PEP regimen (e.g., glucose testing if on a protease inhibitor).

VII. SPECIAL CONSIDERATIONS

A. ANTIRETROVIRAL RESISTANCE

It is unclear whether or how antiretroviral resistance influences risk of HIV transmission. Transmission of drug-resistant strains has been reported (Imrie, 1997) and therefore is a possible concern in PEP situations. If resistance of the source patient’s virus to one or more of the drugs in the PEP regimen is known or suspected, drugs should be selected to include agents to which the virus is likely to be sensitive. Clinical consultation with an expert in HIV treatment should be obtained for guidance in this situation. However, it is important not to delay starting PEP because of resistance concerns; if resistance is known or suspected, a third or fourth drug may be included in the regimen until consultation is obtained.

B. THE PREGNANT HCW

In addition to the counseling issues noted above, the pregnant HCW should be informed about what is known and not known about potential risks, benefits, and side effects for the fetus and herself related to the antiretroviral agents used in PEP. (Issues relating to the use of antiretroviral drugs in pregnancy are discussed in Chapter VII: HIV and Reproduction and in Chapter XIV: Pharmacology.) PEP should not be denied on the basis of pregnancy and pregnancy should not prevent the use of an optimal PEP regimen. For breastfeeding HCWs, temporary discontinuation of breastfeeding should be considered while on PEP to avoid infant exposure to these drugs.

VIII. THE HIV-SEROPOSITIVE HCW

There has been great controversy about HCWs who are infected with HIV and continue to work. The infection of several patients by an HIV-seroposi-tive dentist is well known although poorly understood. However, in four separate studies involving a total of 896 surgical and dental patients exposed to HIV-infected providers, only one patient was found to be HIV seropositive and this individual had other risk factors for HIV (CDC, 1991c). Health care workers with HIV may also themselves be at risk for contracting a communicable disease; appropriate precautions should be taken and appropriate immunizations given.

     All clinicians with exudative or transudative skin lesions should refrain from direct patient care until these lesions have healed. It is believed that HIV-positive HCWs who follow universal precautions and do not perform invasive procedures pose no risk to their patients. Furthermore, there are no current data suggesting that HIV-positive HCWs performing nonexposure-prone invasive procedures should have their practice restricted, assuming they use universal precautions, appropriate technique, and adequate sterilization and disinfection of instruments.

     “Exposure-prone” procedures require more consideration. Exposure-prone characteristics include digital palpation of a needle point in a body cavity or the simultaneous presence of the HCW’s fingers and a needle or sharp instrument in a poorly visualized or highly confined anatomic space. These procedures are associated with increased risk for percutaneous injury to the HCW and potential increased risk to the patient. It is recommended that all HCWs who perform these procedures know their HIV status. HIV-positive HCWs performing exposure-prone procedures should seek counsel from an expert review panel on a case-by-case basis. Mandatory testing of HCWs is not recommended. The ethics of patient notification of exposure to an HIV-infected HCW continues to be argued (Blatchford, 2000; Donnelly, 1999).

     It is imperative that institutions have a standard policy on the management of HIV-infected HCWs, as well as policies on the management of a HCW potentially infected by a patient (CDC, 1991c).

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