Preventing Transmission of Bloodborne Pathogens in the Healthcare Setting

David K. Henderson

INTRODUCTION

Bloodborne pathogens present clearly identifiable occupational hazards to healthcare workers. Transmission of what was then called “serum hepatitis” to healthcare providers was detected as early as the 1940s (1). The past seven decades have provided a clear explication of the various risks associated with handling and processing blood in the healthcare setting. The purpose of this chapter is to identify the bloodborne pathogens that have been clearly characterized as associated with occupational risks for infection, to describe the factors associated with occupational risk for infection, to discuss other aspects of the epidemiology of occupational infections with bloodborne pathogens, and to address both primary and secondary prevention/control strategies that have been developed to mitigate the risks for occupational infections with these pathogens. The chapter will specifically address the risks associated with managing patients who are infected with hepatitis B, hepatitis C, hepatitis D, and HIV. The chapter will not discuss issues related to several other potentially bloodborne agents, including cytomegalovirus, West Nile virus, bovine spongiform encephalopathy/prion disease, the hepatitis A virus, and the agent called hepatitis French (origin) virus; the bloodborne “GB” agents that seem to infrequently cause disease in humans; and the hepatitis G virus. This chapter focuses on the etiology of the major occupationally acquired blood-borne pathogen infections in healthcare providers, the epidemiology of these viruses in the healthcare setting, and the specific prevention and control strategies that may be relevant to these occupational risks.

ETIOLOGY/PATHOGENS

The agents and selected epidemiologic characteristics considered in this chapter as major occupational risks are listed in Table 43.1. Whereas the risks vary substantially by pathogen, all of these agents present a risk to healthcare providers in association with occupational exposures to blood and blood-containing body fluids. Occupational infection with each of these agents is influenced by a host of factors including the relative infectivity of each of the individual pathogen, the occupations and work responsibilities of the individual healthcare worker under consideration, the prevalences of infection of each of these pathogens in the populations of patients being served, and the individual worker’s attention to detail of, and adherence to, accepted work practice standards, as well as accepted infection prevention strategies, among numerous others.

An issue that remains perplexing with respect to occupational infections with bloodborne pathogens is the fact that many practitioners are not aware of precisely what constitutes an occupational exposure. For purposes of this chapter, I will consider transcutaneous injuries that offer the potential for parenteral exposure to blood- (or other blood-containing body fluid-) contaminated devices; mucous membrane contamination with blood (or other blood-containing body fluid); and blood (or other blood-containing body fluid) contamination of “nonintact skin” (e.g., chapped, abraded, or whose integrity is compromised by dermatitis) as constituting occupational exposures (2).

HEPATITIS B VIRUS

As the primary agent responsible for “serum hepatitis” of the 1930s, 1940s, and 1950s, hepatitis B has long presented the most significant risk for occupational infection to healthcare providers. Before the development and use of the hepatitis B virus vaccine, hepatitis B virus was characterized as the single largest occupational risk for healthcare workers whose jobs entailed exposure to blood (3).

Several studies have demonstrated definitively that exposure to blood is the single most important risk factor for occupational infection with hepatitis B virus (4,5). In an elegant seroepidemiologic survey assessing occupational risk for hepatitis B virus infection among healthcare providers, Denes and colleagues (6) found that occupational risk for infections increased with practice in an urban location, with the numbers of years in practice, and with careers in either surgery or pathology. In one of the most definitive studies of its type ever published, Dienstag and Ryan (7) correlated the presence of hepatitis B virus serologic markers in healthcare providers with: (a) the frequency of direct contact with blood in the individual’s healthcare occupation, (b) years in a healthcare occupation (also identified as a risk for infection among providers who have frequent exposures to blood by Snydman and colleagues) (8), and (c) practitioner age. Interestingly, several factors that intuitively might have been suggested as likely to be associated with occupational risks for bloodborne pathogen infection were found not to be associated with serologic markers for hepatitis B virus infection, including the extent of the healthcare worker’s contact with patients, years of medical education,

documented history of needlestick exposures, past history of receipt of a transfusion, and a prior history of having received a gamma-globulin injection. Among the healthcare occupations studied, the highest seroprevalences of hepatitis B virus markers were found among workers in several occupations that are known to have high risks for occupational exposures to blood, including surgeons and surgical house officers, laboratory medicine (clinical pathology) staff, emergency room nurses, and transfusion medicine staff.

TABLE 43.1 Bloodborne Viruses Considered to Present Substantial Occupational Risks to Healthcare Providers

	Hepatitis B (HBV)	Hepatitis C (HCV)	Hepatitis D (HDV)	Human Immunodeficiency Virus (HIV)
Occupational risk	Historically extremely common	Becoming increasingly more common	Uncommon	Common
Recommended isolation precautions	Standard precautions	Standard precautions	Standard precautions	Standard precautions
Occupational risk for infection associated with parenteral exposure	6%-37% per exposure	1%-3% per exposure	Unknown	0.3% per exposure
Major primary prevention strategies	Preventing exposure to blood and blood-containing body fluids Hepatitis B vaccine	Preventing exposure to blood and blood-containing body fluids	Preventing exposure to blood and blood-containing body fluids Hepatitis B vaccine	Preventing exposure to blood and blood-containing body fluids
Efficacy of prophylaxis	Postexposure administration of hepatitis B vaccine and hepatitis B immune globulin (HBIG) (see text and Table 43.2); the role of newer antivirals remains to be delineated	Postexposure prophylaxis strategies appear to be ineffective; newer protease inhibitors as yet untested in this setting Current USPHS recommendations are for no interventions; I suggest consideration be given to either “preemptive therapy” or “watchful waiting” strategies (see text) and aggressive early treatment of infection with interferon with or without additional agents	Hepatitis B vaccine and HBIG for persons who are not already infected with hepatitis B; No current options available for HCWs who are already chronic carriers of hepatitis B	Postexposure antiretroviral chemoprophylaxis (appears to be efficacious, based on indirect evidence) (see text and Table 43.6)
Controversy/alternative approaches Unresolved issues	Need for, and potential efficacy of, booster dose(s) of HBV vaccine for HCWs who fail to maintain protective antibody levels; the role of newer anti-HBV antiviral agents in postexposure management remains to be delineated	Despite lack of formal recommendations, careful monitoring and early therapeutic intervention appears sensible (see text); the role of new anti-HCV antiviral agents in postexposure management remains to be delineated	Need for therapeutic management strategies	Many issues poorly understood, or poorly delineated (see text)
IG, immune globulin; HBIG, hepatitis B immune globulin; HCWs, healthcare workers.

Subsequently, Hadler and his coworkers conducted a similarly designed study that also controlled for nonoccupational risk factors (9), again underscoring the findings of Dienstag and Ryan’s study, and demonstrating that occupational blood exposure, and not patient contact, was associated with risk for serologic markers of hepatitis B virus infection among healthcare providers. In a retrospective review, West found the risk for hepatitis B virus infection among healthcare providers to be four times the risk for the general adult population (10). He found that surgeons, dialysis personnel, personnel providing care for developmentally disabled individuals, as well as clinical laboratorians were at 10-fold higher risk for infection and also found that physicians and dentists were between 5- and 10-fold more likely to have serologic markers of prior hepatitis B virus infection than the general population (10).

In addition to occupational exposure to blood, several additional factors influence the risk for hepatitis B virus infection in healthcare providers, among them: (a) the prevalence of hepatitis B virus infection in the population being served, (b) practice in an urban setting (because the prevalence of infection is higher than in rural settings), (c) practice involving dialysis patients, and (d) healthcare workers who provide care for other populations of patients known to be at increased risk for hepatitis B virus infection (e.g., injecting drug users, men who have sex with men, prison inmates, the developmentally disabled, and/or immigrants from highly endemic areas) (11).

The source patient’s viral burden (i.e., presumably due to an inoculum effect) also influences the risk for transmission. Historically, practitioners have used hepatitis B virus “e” antigen (HBeAg) status (because individuals who are “e” antigen-positive generally have substantially higher circulating viral burdens than those who are “e” antigen-negative) to assess the risk for transmission associated with either occupational or iatrogenic exposures. Hepatitis B virus infectivity also correlates directly with the levels of hepatitis B virus DNA in the circulation (12).

The characteristics of the exposure itself influence the risk for acquiring occupational infection. For example, parenteral exposures are associated with increased risks for occupational infection. Conversely, because of the extraordinary levels of viremia in HBeAg-positive patients, even what might be considered trivial inocula of HBeAg-positive blood may produce infection. Patients who are HBeAg-positive chronic carriers of hepatitis B virus, as well as certain chronic carriers of so-called “precore” mutants of hepatitis B virus (Incident Team) may harbor as many as 10¹³ virus particles of hepatitis B virus per milliliter of blood (3). Because of these remarkable levels of viremia, miniscule amounts of blood contaminating inanimate objects or environmental surfaces may actually present significant occupational risks for infection. Whereas parenteral exposures account for the large majority of occupational infections with hepatitis B virus, several episodes document that contaminating mucous membranes may produce occupational hepatitis B virus infection as well (13).

One of the most significant developments in the past 50 years in terms of mitigating risks for occupational infection with bloodborne pathogens was the development of the hepatitis B virus vaccine. Studies conducted since the introduction of the hepatitis B virus vaccine demonstrate its substantial efficacy in preventing occupational infections. For example, a seroprevalence study conducted by Thomas and his associates at Johns Hopkins Hospital in inner city Baltimore, Maryland identified “absence of hepatitis B vaccination” as the only factor independently associated with risk for hepatitis B infection in a large cohort of healthcare workers (14). Similarly, Panlilio and her colleagues at the Centers for Disease Control and Prevention (CDC) evaluated a cohort of surgeons for prior hepatitis B virus infection and found only two factors associated with risk for infection: (a) not having been immunized with the hepatitis B virus vaccine and (b) having practiced surgery for at least the previous 10 years (15).

HEPATITIS C VIRUS

Hepatitis C virus continues to present occupational risks for infection to healthcare providers for a variety of reasons. The population of patients chronically infected with hepatitis C virus, particularly among injecting drug users, continues to expand aggressively. Whereas the epidemiology and pathogenesis of hepatitis B virus infection are understood with a great deal of clarity, our current understanding of the pathogenesis and immunopathogenesis of hepatitis C virus infection remains far less clear, especially with respect to the early events in the course of the infection. In addition, despite the fact that the pathogen responsible for this disease was identified with certainty in 1989 (16), we still have no vaccine for this disease and have no proof that any intervention is efficacious in preventing infection following occupational exposure to the virus. One study that attempted to assess interferon postexposure prophylaxis efficacy was unable to demonstrate a benefit (17). The development and introduction into the therapeutic armamentarium of highly effective hepatitis C virus protease inhibitors and the promise of the availability of additional classes of drugs specifically targeting the hepatitis C virus in the foreseeable future may at least offer the possibility of altering that landscape significantly within the next few years.

Since hepatitis C virus is known to be a major cause of post-transfusion hepatitis, the thought that healthcare providers would be at occupational risk for transmission of hepatitis C virus makes implicit sense. Numerous anecdotal case reports of occupational infection have been reported in the literature (18). Whereas parenteral inoculation (e.g., needlestick exposure) presents the highest level of risk for occupational hepatitis C virus infection, inapparent parenteral transmission (including mucous membrane exposures) likely accounts for many of the remaining cases. To date, to my knowledge, all instances of occupational hepatitis C virus infection have been associated with exposures to blood, despite the fact that hepatitis C virus has been isolated (albeit generally in much lower concentrations) from a variety of other body fluids. With respect to circumstances of occupational exposure, the most frequent type of exposure resulting in hepatitis C virus infection in the healthcare setting to date has been a needlestick with a hollow-bore needle.

Several prevalence studies evaluating healthcare providers either for the presence of antibody directed against hepatitis C virus or for the presence of circulating hepatitis C virus RNA
have been published. Whereas these studies do have substantial limitations, they do demonstrate that healthcare workers’ risk for acquiring occupational hepatitis C virus infection is only minimally higher than that of volunteer blood donors, and approximately 10-fold lower than the comparable occupational risks associated with exposure to hepatitis B virus in the healthcare setting. Most of these studies were designed as seroprevalence surveys and were not designed to investigate the risk factors for hepatitis C virus infection in their respective cohorts. The few studies that were designed to detect the risk factors for hepatitis C virus infection found increasing age (19,20), years of employment in healthcare occupations (19,21,22), a history of blood transfusions (19,23), and a history of prior needle-stick injuries (23,24) to be associated with risk for hepatitis C virus infection (as detected by assays for circulating antibody directed against hepatitis C virus).

Study and technologic limitations cloud the issue of the risk for transmission of hepatitis C virus associated with single parenteral exposures. The primary technologic limitation is the fact that a variety of different tests have been used in these studies to detect prior infection. Some of the published studies used only the first-generation antibody test (that was neither highly sensitive nor specific). Others have used subsequent iterations of the antibody tests that have substantially improved sensitivities and specificities. Some have used direct detection of the hepatitis C virus genomic material by polymerase chain reaction to detect infection. These various kinds of studies provide highly disparate estimates of the risk for hepatitis C virus infection following discrete occupational exposures (18).

Studies conducted during the past decade have suggested that the detection strategies for hepatitis C virus infection in these seroprevalence and longitudinal cohort studies may have been relatively insensitive, with some studies suggesting that both antibody tests as well as tests for circulating hepatitis C virus nucleic acid underestimate the risk. In these studies, the investigators suggest that the most sensitive test for detecting prior infection/exposure to hepatitis C virus is the measurement of specific cellular immunity directed against this flavivirus (25).

HEPATITIS D VIRUS

Hepatitis D virus by itself presents no occupational risk to healthcare workers. The hepatitis D virus is an “incomplete” virus that requires coinfection with the hepatitis B virus to produce infection. In addition, although ˜5% of all hepatitis B virus carriers are coinfected with hepatitis D virus, substantial demographic, risk-group, and geographic variations exist. For example, hepatitis D virus infection is particularly endemic in the Middle East, in parts of the Amazon river basin, in a few of the Pacific Islands, and in southern Italy. Injecting drug users and hemodialysis patients are more likely to be coinfected with hepatitis D virus than are other groups known to be at risk for hepatitis B virus infection (e.g., men who have sex with men).

Exposure to hepatitis D virus represents a risk to those healthcare workers who are already chronically infected with hepatitis B virus, or to uninfected healthcare workers who experience an exposure to blood from someone who is chronically infected with both viruses. Occupational infection with hepatitis D virus has been infrequently detected to date, in part, because of the requirement for simultaneous infection with hepatitis B virus, and, in part, because tests to detect hepatitis D virus infection are rarely conducted (26,27).

HUMAN IMMUNODEFICIENCY VIRUS

The introduction of a novel bloodborne pathogen—HIV—into the healthcare workplace in the 1980s was associated with significant fear and anxiety on the part of healthcare professionals. Despite the fact that the risk for occupational infection with other bloodborne pathogens (e.g., hepatitis B virus) had been common knowledge since the late 1940s, the epidemic of HIV infection in the United States and its association with almost monumental societal fear and anxiety fueled healthcare workers’ concerns. In the years since the widespread introduction of HIV infection into society, we have learned that exposure to blood from an HIV-infected patient is associated with measurable occupational risks for infection, that such occupational infections occur infrequently, and that sensible procedural interventions can reduce the risk for exposure (and therefore infection) with this bloodborne retrovirus. We also have learned that postexposure interventions offer the potential to reduce the risk for occupational infections further.

In the past 30 years, I am aware of only 57 documented HIV infections in U.S. healthcare workers, and the majority of those infections occurred in the first 15 years of the epidemic (28) in the “pre-antiretroviral” era. These definitive cases are instances in which a healthcare worker sustained an occupational exposure to blood from someone known to be HIV-infected, the healthcare worker had a baseline sample drawn to demonstrate that he/she was not infected at the time of the exposure, was followed by serologic evaluation over time, and, in temporal association with the exposure, the healthcare worker developed serologic, virologic, and/or, in some instances, clinical evidence of HIV infection. In addition to these definitive infections, the U.S. Public Health Service has identified nearly 150 other cases that might be categorized as possible or probable occupational HIV infections among U.S. healthcare providers. These latter individuals did not have a “baseline” serologic sample drawn at the time of an occupational exposure to demonstrate absence of infection at the time of the exposure. Despite the fact that these individuals all denied having nonoccupational risks for HIV infection, when one compares the demographics of this population with those of the “definitive” cases described above, substantial differences in these two populations become apparent, strongly suggesting that confounding community-based risks are present in the possible/probable population (29).

PATHOGENESIS

Transmission of each of the major bloodborne pathogens identified above has been most closely associated with transcutaneous injuries with sharp objects in the healthcare setting. The preponderance of these exposures has been needlestick injuries with hollow-bore needles; however, a variety of other blood-contaminated sharp objects have been implicated in the transmission of one or more of these infectious diseases. Mucosal exposures to blood also transmit infection. For example, six or seven of the definitive occupational HIV infections described above were associated with mucosal exposures to blood from patients known to harbor HIV infection. Whereas other body fluids may present some risk for occupational infection, the primary risk for all of the pathogens discussed above is associated with exposures to blood from infected individuals.

MAGNITUDE OF RISK FOR OCCUPATIONAL INFECTION ASSOCIATED WITH OCCUPATIONAL EXPOSURE

For all of these significant bloodborne pathogens, the risk for infection associated with a single discrete exposure to blood from a patient known to be infected with one of these viruses depends on a number of variables, including (but not limited to) circulating viral burden in the source-patient, inoculum size, significance/magnitude of the exposure, and the route of exposure, among others. For example, the risk for transmission of hepatitis B virus following parenteral (e.g., needlestick) occupational exposure ranges from 6% to 37% per exposure, depending on a variety of factors, including the type of exposure, the inoculum size and type, as well as the source-patient’s circulating viral burden and/or hepatitis “e” antigen status (30).

For hepatitis C virus infection, taking all the codicils into consideration about the different methods that have been used to detect infection (discussed above), when taken together, these studies suggest that the risk for transmission of hepatitis C virus following a parenteral exposure to blood from a patient known to be infected with hepatitis C virus is between 1% and 3% per exposure (18). Thus, for hepatitis C virus, the 1% to 3% risk for transmission per exposure places the occupational risk for transmission of hepatitis C virus between the infection risk for occupational HIV exposures discussed below and the risk for hepatitis B virus exposures discussed above.

For HIV exposures, more than 20 longitudinal studies were conducted in the pre-antiretroviral era attempting to measure the risk for transmission following an individual occupational exposure. The results from these studies have been summarized previously (31,32). When one combines data from all these studies, the risk for transmission of HIV associated with a single percutaneous exposure to blood from a patient known to be HIV-infected is 0.32%, or roughly one infection for every 325 percutaneous occupational exposure to blood from an HIV-infected patient (31). Many of these same studies also attempted to assess the risk for infection associated with mucous membrane exposures to blood from patients known to be HIV-infected. Pooling data from these studies, the risk for occupational infection associated with a single mucosal exposure to blood from an HIV-infected patient is estimated to be 0.03% (31); however, this approximation may be an overestimate, since the single infection in this series was actually reported as an anecdotal case report in the literature (33) before prospective data were purportedly begun to be collected for the longitudinal study. Thus, this case would have clearly occurred before the prospective study of risk began (32).

For hepatitis D virus, no prospective studies have been able to measure the risk associated with either a single exposure to blood from a patient harboring hepatitis D virus or for a single exposure to blood from a patient coinfected with hepatitis B and hepatitis D viruses.

Several other factors likely influence the risk for transmission of these viruses associated with individual exposures. Clearly, inoculum is a major determinant, and the viral inoculum is related both to the volume of material involved in the exposure as well as the source-patient’s circulating viral burden. As might be anticipated, studies of needlestick exposures demonstrate that the volume of the exposure increases with the size of the needle causing the injury and the depth of penetration of the needle. In several studies, hollow needles have been shown to be associated with higher inocula of blood than are comparably sized solid suture needles (34,35).

The amount of virus present in the source-material may vary by several logs, depending on the stage of the source-patient’s illness and the effect of antivirals or immunomodulators. For most, if not all of these infections, viral burden is likely to be one of the single best predictor of infection risk.

In 1997, CDC published the results from a retrospective case-control study of percutaneous exposures to HIV among healthcare personnel to attempt to define the factors associated with transmission risks (36). The investigators identified four factors that were associated with an increased risk for occupational infection with HIV following percutaneous exposures: deep, rather than superficial injuries; injuries with sharp devices that were visibly bloody when compared with devices on which no blood was visible; injuries with sharp devices that had been used in arteries or veins, as compared with those that had not been placed in vascular channels; and injuries associated with source-patients who had preterminal acquired immunodeficiency syndrome (AIDS) (defined as source-patients who expired within 2 months of the time of the exposure) rather than to sources who had earlier stages of infection. Each of these factors is likely a surrogate marker for viral inoculum.

The specific characteristics of the pathogens to which a healthcare worker is exposed may also influence the risk for infection. For example, some strains of HIV may be more aggressive than others (e.g., some strains may produce infection by inducing syncytia more efficiently than others, and some clearly are able to attach to macrophages more efficiently than others). Patients with late-stage HIV or hepatitis C virus infection will harbor numerous quasispecies of these viruses, also possibly increasing the transmission risk.

A final factor that likely influences the risk for occupational infection relates to host factors in the exposed healthcare worker. Variation in an individual healthcare worker’s immunologic responses also likely affects the probability of HIV transmission. Three possible outcomes have been postulated to result from occupational exposures to HIV: infection (usually with detectable antibody responses directed against the invading pathogen); no infection with absent immunologic responses; or so-called “transient infection” that is characterized by measurable and persistent T cell responses (i.e., directed against HIV peptides and envelope antigens or hepatitis C virus envelope proteins), absence of protracted or systemic infection, and absence of an antibody response directed against the infecting virus. With respect to HIV exposures, several populations of exposed, but uninfected individuals have been studied to gain these insights, including the steady sexual partners of infected individuals (37,38,39), children born to mothers who are infected with HIV (40), prostitutes (41,42) and healthy, occupationally-exposed healthcare workers (43,44,45,46). Neither the efficacy nor the precise role for this cellular immune response in the overall defense against initial HIV infection is understood with precision.

PRIMARY PREVENTION—PREVENTING OCCUPATIONAL EXPOSURES

If one examines the possible strategies for preventing occupational infections with bloodborne pathogens, by far the most efficient approach is to implement the strategies designed
to prevent occupational exposures to blood. Despite the fact that preventing occupational exposures to blood is, perhaps, counterculture in medicine, this strategy affords the healthcare provider with the most cost-effective, most efficient strategy for reducing the risks for occupational infection with all blood-borne pathogens. In 1987, the CDC published its “Universal Precautions” guidelines (47). The recommendations were designed to reduce the risk for exposure to blood and, therefore, to reduce the risk for bloodborne pathogen transmission. Others broadened these guidelines to incorporate the concept of body substance isolation, initially promulgated by Lynch and coworkers (48). These broadened guidelines are now referred to as Standard Precautions. Effective use of these precautions will unquestionably reduce cutaneous, mucocutaneous, and percutaneous exposures to blood. Thus, effective implementation of Universal/Standard Precautions will decrease the risks for occupational infection with all bloodborne pathogens.

When one assesses the specific detailed recommendations in these guidelines—the specific components among them, the effective use of hand hygiene strategies, the use of appropriate personal protective equipment (e.g., gloves), and the need for attention to the appropriate use and disposal of needles and other sharp objects—the reasons for the efficacy of these precautions become readily apparent. A number of additional approaches have been demonstrated as effective in reducing occupational exposures and injuries, including the comprehensive education of staff about the attendant occupational risk associated with providing care for patients who have bloodborne pathogen infection, educating staff about the occupational risks that are present and highly prevalent in the healthcare workplace, the need to modify procedures and work practices that are intrinsically associated with risks for occupational exposure, as well as the need to monitor staff for adherence to Standard/Universal Precautions and other relevant infection control guidelines (47,48,49). The institutions also should develop strategies to be able to monitor the healthcare marketplace for technologic advancements that can be implemented to replace existing approaches while simultaneously reducing occupational risks. I also believe that all healthcare institutions should collect information prospectively about occupational exposures that occur in their institutions and that these institutions should use these data to drive performance-improvement activities to reduce the attendant risks.

Lastly, the appropriate use of vaccines (e.g., hepatitis B virus vaccine) already plays a crucial role with respect to hepatitis B virus in primary prevention of occupational infection with bloodborne pathogens. When additional vaccines become available (e.g., hepatitis C virus, HIV), such vaccines would clearly play an increasingly important role in primary prevention.

IMMEDIATE POSTEXPOSURE MANAGEMENT

One of the most important considerations for immediate postexposure management is first to determine that an occupational exposure presenting a risk for transmission of one of these bloodborne pathogens has actually occurred. To make such a determination, the practitioner must thoroughly evaluate the exposure event, the potential for susceptibility of the exposed healthcare provider (e.g., immunity to hepatitis B virus, preexisting infection with hepatitis B virus, hepatitis C virus, or HIV), as well as the information available about the patient who was the source for the exposure. If the source-patient’s bloodborne pathogen infection status is not known, the source-patient should be tested for all of these bloodborne infections, making certain that the testing is appropriately conducted within the constraints of relevant state and local laws. Currently marketed rapid tests for HIV are highly reliable when negative. Positives must be followed-up with standard immunoassay and confirmatory tests. In addition, the fourth-generation, combination p24 antigen-HIV antibody (Ag/Ab) tests for HIV diagnosis are both rapid and accurate and allow identification of most patients in the so-called “window period” (50). In instances in which the source-patient is determined to be infected with one or more of these pathogens, obtaining as much additional information about each of the source-patient’s infection(s) makes implicit sense. Determining the duration of the source-patient’s infection, the current therapy for the infection(s), key immunologic and/or virologic parameters for each pathogen, such as viral burden(s), as well as a variety of other risk factors that relate to each of the pathogens may help the practitioner understand the significance of the exposure. If information about the source-patient’s viral isolate is available (i.e., phenotypic or genotypic information, information about prior resistance, and so on), this information should be considered as well. In instances in which such practices are practical, saving a sample of the source-patient’s pathogen is both sensible and advisable. The practitioner responsible for management also should obtain as much information as possible about additional factors likely to increase the risk for transmission of bloodborne infections (e.g., if a volume of blood was injected; if the exposure was to a hollow-bore, rather than solid, needle; if the needle was of a large-, rather than small-gauge; if blood was visible on the device causing the injury; or if the device had been placed in one of the source-patient’s arteries or veins) (36).

In instances in which source-patient testing is not either possible or readily available, I advocate offering prophylaxis and beginning immediately, if the healthcare worker elects to take the prophylaxis, then sorting out the exposure data as quickly as possible. If the source-patient’s infection status for these pathogens cannot be discerned, the practitioner should make his/her best epidemiologic assessment about the likelihood of exposure and manage the healthcare worker in accord with that assessment. Factors that may be considered in making such an epidemiologic assessment include (but are certainly not limited to) the severity of the exposure, the precise circumstances of the exposure, the location where the exposure occurred and the likelihood that pathogens were present, the demographics of the source-patient, and the presence of other epidemiologic factors known to be associated with risk for one or more of these infections. Such “source-unknown” exposures must, logically and of necessity, be managed on a case-by-case basis.

Although determining whether or not an exposure has actually occurred seems straightforward, in actuality this determination is, in my view, the “Achilles’ heel” of postexposure management. Summary data from the National Clinicians’ Post-Exposure Prophylaxis Hotline (PEPLINE) at the University of California at San Francisco have consistently suggested that postexposure prophylaxis often is prescribed and administered for instances in which the PEPLINE professionals felt that an exposure had not occurred (51). Although these data appear to be improving a bit over time, the number of
instances in which postexposure prophylaxis is prescribed for circumstances felt not to represent exposures remains far too high. One reason for the problem of overtreatment may be that the practitioners who ultimately end up managing these exposures (very often emergency room practitioners) are often unfamiliar with the exposure definitions as well as with the drugs recommended for administration as postexposure prophylaxis. Further, because the practitioners are often colleagues of the exposed individuals, they may be more easily influenced by their putatively exposed colleague’s anxiety. I advocate that institutions develop systematic procedures and a multidisciplinary team approach to occupational exposures to assure that these exposures are managed both consistently and with the highest possible quality. Occupational Medicine, Hospital Epidemiology, Hospital Safety, and the infectious diseases/HIV team should be the key members of this team. Qualified, knowledgeable staff should be available 24 hours a day, 7 days a week, to assist with the management of these exposures. As part of this multidisciplinary approach, I recommend that the team also collect information about occupational exposures to blood in their institution to be able to assess their data for common circumstances of exposure or for intrinsic problems with patient-care processes that might be improved in order to mitigate the risk.

Effective exposure management is a healthcare institution’s responsibility. Staff need to know precisely what to do when an exposure occurs and precisely when to do it. Access to information about appropriate exposure management procedures must be readily available to all potentially exposed staff and also must be user-friendly.

Healthcare institutions are required by law to provide systems for reporting exposures and assuring rapid access to appropriate postexposure care (52). Despite the development of elegant strategies to facilitate reporting and management of such exposures, many occupational exposures are never reported. Since the early 1980s, underreporting of these injuries has been identified as a significant problem and it persists as a major problem well into the 21st century.

At my own institution, we recommend that wounds, punctures, or other skin areas that have had direct contact with blood or body fluids should be initially washed thoroughly with soap and water (2,53). Some authorities have recommended that antiseptics be used to decontaminate the wound; however, no data, to my knowledge, actually provide scientific support for this recommendation. Flushing and washing the wound should not be delayed until antiseptics can be obtained.

For mucous membrane exposures, we recommend flushing the exposure site aggressively with tap water; eyes should ideally be flushed with sterile water or a commercial eye irrigant; if neither is readily available, clean tap water will suffice.

An important aspect of early postexposure management is counseling. The emotional impact of an occupational exposure to a bloodborne pathogen should never be underemphasized. In addition to ensuring that the staff who are providing care to exposed healthcare workers are knowledgeable about the epidemiology, risks for transmission, treatment options, and known complications of treatment, institutions should also ensure that staff who sustain these exposures have access to skilled counseling. The clinician providing care for the exposed healthcare worker must be able to provide the exposed staff member with understandable, objective information about the risks for infection associated with the type of exposure that the employee has sustained as well as what is known about the risks and benefits of the various possible treatment options. Clinical staff should guard against minimizing or trivializing the risks and should work hard to express empathy and reassurance. These events are incredibly troubling to the exposed worker and he or she may not be able to assimilate all of the information that the clinicians provide. Staff providing care for individuals sustaining these kinds of exposures should be ready and willing to answer the same questions repeatedly—both for the exposed worker as well as his/her spouse or significant other. Irrespective of the treatment course elected, the exposed worker should be scheduled for a follow-up appointment at 48 to 72 hours following the initial appointment to assess how he/she is doing and to answer outstanding questions for the exposed worker.

Healthcare workers who are too upset or confused to make a decision about chemoprophylaxis can sometimes be helped by suggesting that treatment be started immediately, with the option to stop it later (i.e., “Because some evidence suggests that the timing of the first dose influences the success of treatment, I suggest that you start treatment now, and then tomorrow, or even later, if need be, we can decide if continuing is your best option.”). This approach modulates the acute pressure the healthcare worker may feel to make an immediate decision and also empowers workers to be able to decide about their own treatments.

Counseling the HIV-exposed worker should include a clear discussion of several important issues related to occupational exposures and their management: (a) More than 99% of individuals who sustain occupational exposures will not become infected, even if they elect not to take postexposure antiretroviral chemoprophylaxis; (b) although a great deal of indirect evidence suggesting efficacy for postexposure antiretroviral prophylaxis (discussed below) has been assembled over the years, no agent or combination of agents has been approved as safe and effective by the FDA for use in this setting; (c) data about the efficacy and safety of the use of these potentially toxic agents in this setting are far from complete; and (d) exposed workers should be counseled to take precautions to prevent secondary transmission, especially during the first 3 months following exposure, including precautions to prevent sexual transmission (e.g., abstinence or condom use), as well as the avoidance of blood and organ donation and discontinuation of breast-feeding.

Exposed staff should be counseled about the magnitude of risk associated with occupational exposures, about the institutional measures that have been put in place to protect the confidentiality of exposed healthcare workers’ medical records, and about the typical concerns of sexual partners, coworkers, family, and friends of the exposed worker. Finally, counseling staff should be prepared to answer questions for spouses, significant others, and family who have major concerns about the associated risks.

PATHOGEN-SPECIFIC POSTEXPOSURE MANAGEMENT AND FOLLOW-UP

HEPATITIS B VIRUS

A large body of evidence demonstrates that postexposure immunoprophylaxis (both active and passive) is effective in preventing infection with hepatitis B virus following occupational
exposures to hepatitis B virus. Postexposure prophylaxis should be provided to all susceptible healthcare workers who sustain occupational exposures to hepatitis B virus. As is the case for each of the commonly encountered bloodborne pathogens, healthcare institutions should establish protocols for providing appropriate management of hepatitis B virus exposures. As described above, the management of hepatitis B virus exposures includes assessing the type, source, and circumstances of the exposure; evaluating the source-patient for clinical, epidemiologic, and laboratory evidence of hepatitis; and evaluating the hepatitis B virus vaccination history and hepatitis B virus infection/immunity status of the exposed healthcare worker. Additionally, I would underscore that institutions should strive to provide prophylactic treatment as soon as possible following occupational exposures to hepatitis B virus. The current recommendations include the administration of both hepatitis B virus immune globulin as well as the hepatitis B virus vaccine series. The U.S. Public Health Service has published recommendations for the use of both hepatitis B virus immune globulin and postexposure use of the hepatitis B virus vaccine (11). These guidelines are summarized in Table 43.2. Practitioners must be aware that certain of these bloodborne pathogens travel together. Simply because a patient is admitted for treatment of complications of hepatitis B virus infection does not mean that one should ignore the other pathogens. For this reason, even when the patient is known to harbor hepatitis B virus, I still recommend that the source-patient also be tested for hepatitis C virus and HIV, in addition to testing for his/her current hepatitis B virus infection status.

TABLE 43.2 Strategies for Managing Occupational Exposures to Hepatitis B Virus

Exposed Worker’s Hepatitis B Vaccination History and Extent to which Immunologic Status is Understood^b	Recommended Treatment Strategies^a
	*Source HBsAg*^e-Positive	*Source HBsAg*^e-Negative	*Source Unknown*
Never vaccinated	Assess the worker’s HBV status (draw anti-HBs, anti-HBc^e)^b; if susceptible, HBIG^c 1-2 doses^d; begin hepatitis B vaccine series	Assess the worker’s HBV status (draw anti-HBs^e, anti-HBc^e)^b; if susceptible, begin hepatitis B vaccine series	Assess the worker’s HBV status (draw anti-HBs^e, anti-HBc^e)^b; conduct epidemiologic risk assessment (see text); if risk present, and if -susceptible, consider HBIG^c; begin hepatitis B vaccine series
Vaccinated
Known responder^f with known positive titer	No treatment needed	No treatment needed	No treatment needed
Known responder^f with unknown titer	Draw anti-HBs; if titer negative, consider booster; if positive, no treatment needed	Draw anti-HBs	Draw anti-HBs; conduct epidemiologic risk assessment; consider booster
Known responder^f with known negative titer	Draw anti-HBs; administer booster	Draw anti-HBs	Draw anti-HBs; conduct epidemiologic risk assessment; consider booster
Known nonresponderf with known negative titer	Draw anti-HBs; consider new vaccination series; administer HBIG, 1-2 doses^d	Draw anti-HBs	Draw anti-HBs; conduct epidemiologic risk assessment; consider booster
Vaccinated but antibody status unknown	Draw anti-HBs; if positive, no treatment; if negative, HBIG 1 dose; administer booster	Draw anti-HBs; consider booster	Draw anti-HBs; conduct epidemiologic risk assessment; if risk present, treat as an exposure: HBIG, 1 dose; administer booster
^aAlthough this table refers to the management of exposures to hepatitis B, in every instance in which exposure to blood occurs, the clinician managing the exposure should consider the potential for exposure to multiple bloodborne pathogens; thus, at a minimum, someone sustaining an exposure to hepatitis B should also have an assessment for potential exposures to hepatitis C and HIV. ^bResolved natural infection (associated with anti-HBs and anti-HBc antibody production) produces lifelong immunity ^cHBIG, hepatitis B immune globulin; dose is 0.06 mL/kg, second dose at 4 weeks. ^dValue of the second dose of HBIG is only suggested from one study. ^eHBsAg, hepatitis B surface antigen; anti-HBs, antibody against HBsAg; anti-HBc, antibody directed against hepatitis B core antigen (signifies prior natural infection, present in those who have resolved infection and chronic carriers). ^fResponder, vaccinated, with measurable anti-HBs >10 mIU/mL; nonresponder, vaccinated, but anti-HBs never exceeds 10 mIU/mL. Modified from Centers for Disease Control and Prevention. Updated U.S. Public Health Service Guidelines for the management of occupational exposures to HBV, HCV, and HIV and recommendations for postexposure prophylaxis. MMWR Recomm Rep. 2001;50(RR-11):1-52.

The issue of booster doses of hepatitis B virus vaccine for staff who have occupational exposures who are shown to have undetectable levels of antibody remains controversial. The U.S. Public Health Service does not currently recommend booster doses for workers who initially responded to the vaccine but whose antibody levels have declined to the undetectable level. Several studies have addressed the issue of the durability of vaccine-induced immunity. One study suggested that between 30% and 60% of vaccines had suboptimal levels of antibody 8 years following immunization (54); however, several other studies have suggested that the vaccine response may be quite durable even 10 years after immunization (55,56,57). In point of fact, productive hepatitis B virus infection has been relatively rare in vaccine recipients, irrespective of antibody levels. Recent studies have suggested a high level of immunologic memory among patients who were vaccinated as infants when challenged 10 or 15 years later (58). Nonetheless, some institutions, including my own, do offer booster doses of vaccine to healthcare workers who have previously responded to hepatitis B virus vaccination, whose antibody levels have become undetectable, and who remain in jobs associated with risk for blood exposure and hepatitis B virus infection. Other aspects of the management and follow-up of staff sustaining occupational exposure to hepatitis B virus are summarized in Table 43.2.

HEPATITIS C VIRUS

For occupational exposures to hepatitis C virus, the immediate postexposure management is identical to that described above for all bloodborne pathogens. As is the case for known exposures to hepatitis B virus, practitioners must be aware that these bloodborne pathogens often travel together. For this reason, even when the source-patient is known to harbor hepatitis C virus, I still recommend that the source-patient also be tested for hepatitis B virus and HIV, in addition to testing for his/her current hepatitis C virus infection status. Practitioners ordering these tests must be cognizant of the local and state laws that are relevant to informed consent for these tests. Further, practitioners should be mindful of the fact that the majority of the screening tests are designed to detect antibody directed against some of these pathogens, and these tests clearly do not detect all patients who have been previously infected. Specifically with respect to hepatitis C virus, detecting antibody against hepatitis C virus in a source-patient’s serum is not an ironclad indicator of an individual source-patient’s infectivity.

The most recent CDC guidelines for managing occupational exposures to hepatitis C virus recommend the following: (a) testing the source-patient for antibody against hepatitis C virus at the time of exposure; (b) baseline testing of the healthcare worker sustaining the exposure for both antibody against hepatitis C virus and alanine aminotransferase levels; (c) repeat testing of the healthcare worker (for hepatitis C virus antibody and alanine aminotransferase levels) at 6 months following the exposure or at any time when symptoms suggest possible infection; (d) use of confirmatory tests, including direct antigen detection, direct genome detection, and supplementary or confirmatory antibody tests (e.g., recombinant immunoblot assays [RIBA]) to investigate positive results of hepatitis C virus antibody testing in more detail; (e) that clinicians do not provide immunoglobulin, antiviral agents, or immunomodulators as postexposure prophylaxis; and (f) providing comprehensive information to the exposed worker about the magnitude of occupational risks associated with the exposure, the risks for secondary transmission, and strategies known to be effective in preventing exposure to blood and/or transmission of hepatitis C virus in occupational settings (59).

Some individuals have advocated more aggressive monitoring and interventional strategies (18,60). One suggested approach is to monitor healthcare workers periodically using polymerase chain reaction detection of hepatitis C virus RNA at some defined interval (e.g., monthly, every 6 weeks, at 3 months following exposure, and so on) in addition to the antibody testing described above. If an exposed healthcare worker is repeatedly detected as positive for hepatitis C virus RNA by the polymerase chain reaction assay (because of frequent false-positives in low-prevalence settings, one should never rely on a single positive sample), the worker can be referred to a specialist in the management of hepatitis C virus for definitive therapy (discussed in more detail below).

Historically, some investigators advocated the use of immune serum globulin to attempt to decrease the risk for transmission of what has been subsequently identified to be hepatitis C virus (61,62,63). As additional details of the pathogenesis and immunology of hepatitis C virus infection have been delineated, most experts now agree that postexposure immunoglobulin prophylaxis is of no value. Similarly, no information, to my knowledge, has provided scientific support for a role for interferon or other immunomodulators administered as true “postexposure prophylaxis” (i.e., in the immediate postexposure period) for occupational exposures to hepatitis C virus (17

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