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Regulations (Preambles to Final Rules) - Table of Contents
• Record Type: Occupational Exposure to Bloodborne Pathogens
• Section: 4
• Title: Section 4 - IV. Health Effects

IV. Health Effects

A. Introduction.

Certain pathogenic microorganisms can be found in the blood of infected individuals. For the purposes of this standard, OSHA is referring to these microorganisms as "bloodborne pathogens" and to the diseases that they cause as "bloodborne diseases." These bloodborne pathogens may be transmitted from the infected individual to other individuals by blood or certain other body fluids, for example, when blood-contaminated needles are shared by intravenous drug users. Because it is the exposure to blood or other body fluids that carries the risk of infection, individuals whose occupational duties place them at risk of exposure to blood or other potentially infectious materials are also at risk of becoming infected with these bloodborne pathogens, developing disease and, in some cases, dying. Infected individuals are also capable of transmitting the pathogens to others.

A discussion of two of the most significant bloodborne pathogens, hepatitis B virus, and human immunodeficiency virus, follows. This includes a discussion of each of the viruses, the disease each causes, modes of transmission, and documented risk of infection resulting from occupational exposure. In addition, a discussion of other bloodborne diseases, hepatitis C, delta hepatitis, syphilis, and malaria, is included.

B. Hepatitis Viruses

Hepatitis means "inflammation of the liver," and can be caused by a number of agents or conditions including drugs, toxins, autoimmune disease, and infectious agents including viruses. The most common causes of hepatitis are viruses. There are four types of viral hepatitis which are important in the U.S. (Exs. 6-449; 6-430; 6-199). Hepatitis A, formerly called "infectious" hepatitis, is spread by fecal contamination and is not generally considered to be a significant risk to healthcare workers, although episodes of transmission to healthcare workers in hospitals have been reported (Exs. 6-449; 6-456; 6-449; 6-456). Hepatitis B, formerly called "serum" hepatitis, is a major risk to healthcare workers and is extensively discussed in this document. Delta hepatitis may coinfect with hepatitis B or may infect persons already infected with HBV and can increase the severity of acute and chronic liver disease in these individuals (Ex. 6-470). Nosocomial infection with this virus has been reported (Ex. 234 Lettau, et. al., 1986). Non-A, non-B hepatitis is caused by viral agents other than hepatitis A and hepatitis B. Two that have been identified are hepatitis E, previously known as enterically transmitted (ET) non-A, non-B hepatitis and hepatitis C, previously known as parenterally transmitted (PT) non-A, non-B hepatitis. Hepatitis E transmitted by the fecal-oral route and has occurred both in epidemic and sporadic forms in parts of Asia, North and West Africa and Mexico. It is not known whether the virus is present in the United States or Western Europe. Parenterally transmitted non-A, non-B hepatitis is caused by at least one bloodborne virus, designated hepatitis C virus (HCV). This virus is efficiently transmitted by blood transfusion and by needle sharing among IV drug users (Exs. 6-430; 6-449; 6-286G) As there are reports of occasional transmission of HCV to healthcare workers, this virus is discussed further in this document (Exs. 6-39; 6-455; 286G).

(1) Hepatitis B

Hepatitis B virus (HBV) infection is the major infectious bloodborne occupational hazard to healthcare workers. The Hepatitis Branch of the Centers for Disease Control (CDC) estimates that there are approximately 8,700 infections in healthcare workers with occupational exposure to blood and other potentially infectious materials in the United States each year (Ex. 298). These infections cause over 2,100 cases of clinical acute hepatitis, 400-440 hospitalizations and approximately 200 deaths each year in healthcare workers. Death may result from both acute and chronic hepatitis. Infected healthcare workers can spread the infection to family members or rarely, to their patients. [For detailed discussion, see Section V, Quantitative Risk Assessment.] The use of hepatitis B vaccine, engineering and work practice controls, and personal protective equipment will prevent almost all of these occupational hepatitis B infections. Efforts to reduce blood exposure and minimize puncture injuries in the workplace setting will reduce the risk of transmission of all bloodborne hepatitis viruses.

HBV: Biology

Hepatitis B is caused by the hepatitis B virus (HBV) that attacks and replicates in liver cells (Exs. 6-430; 6-449). The virus has an inner core and an outer shell structure. The inner core contains DNA, enzymes, and various proteins, including the hepatitis B core antigen (HBcAg) and hepatitis B e antigen (HBeAg). The outer shell is composed of a lipoprotein called hepatitis B surface antigen (HbsAg), formerly called the Australia Antigen. The HbsAg is produced in great excess by liver cells replicating the virus, and is found in the form of small spheres and larger tubular particles in the blood of infected persons. The plasma derived hepatitis B vaccines are composed of a highly purified preparation of these excess HBsAg particles which are immunogenic but not infectious. There is a readily available laboratory test for HBsAg, and its presence in blood indicates than an individual is currently infected with the HBV, and is potentially infectious to others. Highly infectious HBV carriers and persons with acute Hepatitis B are also HBeAg-positive.

       TABLE IV-1. Hepatitis nomenclature (Ex. 286G p.6,7)

Abbreviation         Term                Definition/Comments

HBV                Hepatitis B       Etiologic agent of "serum"
                    virus            hepatitis also known as Dane

HBsAg              Hepatitis B       Surface antigen(s) of HBV
                    surface          detectable in a large quantity
                    antigen          in serum; several subtypes

HBeAg              Hepatitis Be      Soluble antigen of HBV; correlates
                    antigen          with HBV replication, high titer
                                     HBV in serum, and infectivity
                                     of serum.

HBcAg              Hepatitis B       No commercial test available.
                    Core antigen

Anti-HBs           Antibody to       Indicates past infection with
                    HBsAg            and immunity to HBV, passive
                                     antibody from HBIG, or immune
                                     response from HB vaccine.

Anti-HBe           Antibody to       Presence in serum of HBsAg
                     HBeAg           carrier indicates lower titer
                                     of HBV.

Anti-HBc           Antibody to       Indicates prior infection with
                     HBcAg           HBV at some undefined time.

IgM anti-HBc       IgM class         Indicates recent infection
                     antibody to     with HBV; detectable for 4-6
                     HBcAg           months after infection.

IG                  Immune           Contains antibodies to HBV
                    globulin         lower-titer antibodies to
                    (previously       HBV.
                    ISG, immune
                    serum globulin,
                    or gamma
HBIG                Hepatitis B      Contains high-titer anti-
                    immune           bodies to HBV.

HBV: Disease Outcomes

Infection with the hepatitis B virus in a susceptible person can produce two types of outcomes: self-limited acute hepatitis B and chronic HBV infection (Exs. 6-430; 6-449). Similarly, the human body can mount two types of response to HBV infection. The most frequent response seen in healthy adults is development of self-limited acute hepatitis and the production of an antibody against HBsAg, called anti-HBs. The production of this antibody coincides with the destruction of liver cells containing the virus, elimination of the virus from the body, and signifies lifetime immunity against reinfection. Persons having this response also develop an antibody against the core protein, called anti-HBc, and usually maintain both anti-HBc and anti-HBs in their blood for life.

Unfortunately, the destruction of liver cells in an attempt to rid the body of this infection often leads to clinically apparent acute hepatitis B. About one third of infected individuals have no symptoms when infected with the virus, one third have a relatively mild clinical course of a flu-like illness which is usually not diagnosed as hepatitis, and one third have a much more severe clinical course with jaundice (yellowing of the eyes and skin), dark urine, extreme fatigue, anorexia, nausea, abdominal pain, and sometimes joint pain, rash, and fever. These symptoms require hospitalization in about 20% of jaundiced cases, and often cause several weeks to months of work loss even in those cases that do not require hospitalization. Fulminant hepatitis, which is about 85% fatal with even the most advanced medical care, develops in about 1-2% of reported acute hepatitis B cases, and an estimated 1 per 1000 HBV infections (Ex. 6-217).

The second type of response - development of chronic HBV infection - has more severe long term consequences (Exs. 6-430; 6-449). About 6% to 10% of newly-infected adults cannot clear the virus from their liver cells and become chronic HBV carriers. These individuals continue to produce HBsAg for many years, usually for life. They do not develop anti-HBs, but do produce anti-HBc antibody. HBV carriers are at high risk of developing chronic persistent hepatitis, chronic active hepatitis, cirrhosis of the liver, and primary liver cancer. About 25% of carriers develop chronic persistent hepatitis, a relatively mild, non-progressive form of chronic liver disease, and 25% develop chronic active hepatitis. The latter is a progressive, debilitating disease that often leads to cirrhosis of the liver after 5-10 years (Exs. 5-5; 6-448). Patients with end-stage cirrhosis may develop ascites (fluid accumulation in the abdomen), esophageal bleeding from distended veins (causing patients to vomit large volumes of blood), coma, and death. Chronic HBV infection has been estimated to cause 10% of the 25,000-30,000 deaths that occur due to cirrhosis in the U.S. each year (Ex. 6-199).

The DNA of HBV in chronic carriers can integrate into the DNA of the host liver cell. This integration may lead to malignant transformation of the liver cell, and development of primary hepatocellular carcinoma (PHC) (Exs. 6-419; 6-443). PHC is almost uniformly fatal if diagnosed after symptoms appear. Patients with PHC usually die within four to six months after diagnosis. PHC usually develops in HBV carriers after a latency period of 20 to 60 years. In parts of the world where HBV infection is a common childhood infection, PHC is one of the leading causes of cancer death. In Taiwan, for example, Beasley and colleagues have found that 5 per 1000 adult male HBV carriers develop PHC each year, and estimate that approximately 25% of all HBV carriers, and 40% of male HBV carriers, will die from either PHC or cirrhosis (Ex. 6-419). The relative risk of developing PHC in an HBV carrier compared to a non-carrier in his studies is 100. Studies in the United States and in Great Britain, where HBV infection usually occurs in adulthood, have shown 13 to 40 fold increased risk of developing PHC among HBV carriers (Exs. 6-640; 6-444). This may be compared to the relative risk of lung cancer in smokers vs. non-smokers of 10-20. Studies in many other populations worldwide have confirmed this extremely high relative risk.

The causal link between HBV carriage and PHC is not only based on epidemiologic studies, but is confirmed by both animal and molecular biological studies (Exs. 6-449; 6-443). Other animal species can become infected with HBV-like viruses (which belong to the same virus family - Hepadna viruses), and woodchucks, Pekin ducks, ground squirrels, and other species that become infected may develop a carrier state. These carrier animals develop primary liver cancers at very high rates. Molecular biological studies have shown that PHC tumor cells contain integrated HBV DNA in virtually all humans and animals cases of PHC (Ex. 6-443).

There is likely a higher risk of developing PHC if infection occurs from perinatal (mother to child) transmission, or from infection during childhood than from infection in adulthood. Although persons who develop HBV carriage during adulthood are at increased risk of developing PHC, the exact risk of developing PHC following adult infection has not been established. The risk observed in blood donors in the United States is probably an underestimate, as PHC is most likely in persons with chronic liver disease or cirrhosis and who are excluded from such studies because they cannot be blood donors. In addition, many carriers will die of other causes before they develop PHC because of the long latency of this cancer. Nevertheless, it has been estimated that, in the U.S., about 25%-33% of all PHC cases, or 750-1000 PHC cases annually, result from HBV infection.

HBV: Modes of Transmission

Workplace: HBV is spread via several routes: parenteral (by direct inoculation through the skin), mucous membranes (blood contamination of the eye or mouth), sexual, and perinatal (from infected mother to newborn infant) (Exs. 6-430; 6-449). The most efficient mode of transmission is direct inoculation of infectious blood, such as might occur during blood transfusion, needle sharing by IV drug users, or needlestick or other sharp instrument injury in health care workers. One milliliter of HBsAg positive blood may contain 100 million infectious doses of virus; thus, exposure to extremely small inocula of HBV-positive blood may transmit infection. In different studies, 7% to 30% of susceptible healthcare workers sustaining needlestick puncture injuries from HBsAg positive patients became infected if they did not receive post-exposure prophylaxis (Exs. 4-27; 4-28). Since 1972, all units of blood collected for transfusion in the U.S. have been screened for HBsAg, greatly decreasing the incidence of transfusion related HBV infection.

Blood and blood-derived body fluids (serous exudates and fluids from internal body cavities) contain the highest quantities of virus and are the most likely vehicles for HBV transmission (Exs. 6-430; 6-449). Certain other body fluids such as saliva and semen contain infectious virus but at 1000-fold lower concentration (Ex. 6-445). Other body fluids such as urine or feces contain only small quantities of virus unless they are visibly contaminated with blood.

Direct inoculation of infectious blood may occur in less apparent ways. Preexisting lesions on hands from injuries incurred at the workplace or at home or from dermatitis may provide a route of entry for the virus (Ex. 6-427). In addition, transfer of contaminated blood via inanimate objects or environmental surfaces has been shown to cause infection in the healthcare workplace (Exs. 6-464; 6-433; 4-461.) In general, fewer than 20% of infected healthcare workers report discrete needlestick injuries from a known infected patient. The importance of this finding should not be underestimated. Although gloving will not stop direct puncture injuries, it can provide a barrier between blood and an open lesion.

Infectious sera placed in both the eye and mouth of experimental animals has induced HBV infection (Exs. 6-430; 6-449). Splashes of blood or serum into the individual's eye or mouth in clinical settings or in the laboratory must be regarded as potentially serious exposures. While there has been concern about the potential infectivity of aerosols generated by dental, medical, and laboratory equipment, and although HBsAg may be found in large particles of "spatter" that travel short distances, OSHA is not aware of any data that link HBV transmission with aerosols through inhalation.

Transmission in Other Settings: Sexual transmission of HBV infection is an efficient mode of viral spread as HBsAg has been found in both semen and vaginal secretions (Exs. 6-430; 6-445). Deposition of virus onto mucous membranes and trauma to tissue causing small lesions may both play roles in transmission. Approximately 30% of spouses or regular sexual partners of acutely infected HB patients become infected. Spouses of chronic carriers, who have a much longer duration of infectivity, escape infection less frequently. Preventing transmission of HBV infection to the spouse/sexual partners of infected healthcare workers is an additional benefit derived from and reason for controlling this disease (Ex. 6-425).

Non-sexual family contacts of HBV carriers are also at risk of infection. Although the relative importance of various transmission modes has not been determined in families, in various studies about 40-60% of household contacts of carriers identified by blood donation had markers of HBV infection (Exs. 6-420; 6-430). Daily exposure to the carrier for many years presents occasions for sharing razors or toothbrushes, exposure to blood and other events that could result in infection. Family contacts of adopted carrier children have been shown to have a higher prevalence of infection than families who do not live with a carrier.

Perinatal infection with the HBV is an efficient mode of transmission with particularly severe consequences. Mothers positive for both HBeAg and HBsAg will infect 70% to 90% of their newborns, most of whom will become chronic HBV carriers (Exs. 6-419; 6-199). These carriers have a 25% chance of dying from cirrhosis or PHC. They also remain infectious to others and can perpetuate the cycle of perinatal transmission. Fortunately, treatment of newborns at birth with hepatitis B immune globulin (HBIG) and hepatitis B vaccine is 85% to 95% effective in preventing these infants from becoming carriers (Exs. 6-419; 6-199). To be able to treat these infants at birth, their mothers must be recognized as carriers before delivery. The Immunization Practices Advisory Committee (ACIP) of the U.S. Public Health Service has recommended that all pregnant women in the U.S. be screened for HBsAg during an early prenatal visit (Ex. 6-424). Because pregnant healthcare workers may, if infected, transmit HBV to their newborn infants, prevention of HBV infection is critical in women of child bearing years who work in occupations where they are at risk for exposure.

HBV: Epidemiology

HBV infection does not occur uniformly in the U.S. population. There is a substantial difference in the reported numbers of hepatitis B cases by geographical region. The presence of certain populations with a high percentage of individuals who are carriers may result in higher prevalence rates for certain defined areas, such as parts of Alaska and the U.S. Trust Territories. HBV infection is more prevalent in certain ethnic and racial groups, and is especially prevalent in certain "high risk" groups defined by occupation and lifestyle (Exs. 6-430; 6-449; 6-199). The prevalence of HBV antibodies in the general population, reflecting the percentage of the population ever infected, is 3% to 4% for whites and 13% to 14% for blacks (Ex. 6-390). Foreign born Asians have a prevalence of antibody of greater than 50%. The HBsAg prevalence, reflecting the percentage of the population who are HBV carriers, is 0.2% for whites, 0.7% for blacks, and up to 13% for foreign born Asians. The high prevalence in the last group is a reflection of the fact that most HBV infections in Asia occur in childhood.

The ACIP has listed a number of groups who are at substantial risk for HBV infection and should receive the hepatitis B vaccine (Ex. 286G). Healthcare workers and public safety workers, who have contact with blood or certain body fluids, and staff of institutions for the developmentally disabled are included on this list.

Transmission to Healthcare Workers: Although outbreaks of clinical hepatitis have been reported for many years (Exs. 6-438; 6-459), it was not until the 1970's that the risk to healthcare workers from HBV infection was well defined. The first studies noted that dentists were more likely than attorneys to have had clinical hepatitis (Ex. 6-441). When HBsAg and antibody testing became available, it was possible to show that the type of hepatitis that occurred more commonly in healthcare workers was hepatitis B. Dentists and physicians were 4 to 10 times more likely to have serologic markers indicating previous HBV infection than first time blood donors, and the prevalence of markers increased significantly with years in practice (Exs. 6-440; 6-65; 4-13; 4-16; 4-12; 4-15; 6-68).

During the next decade, dozens of studies were published measuring the prevalence of HBV markers in various healthcare occupational groups, and in various healthcare settings (Exs. 6-427; 6-88; 6-72; 6-54; 6-53; 6-44; 640; 4-14). The prevalence of markers was studied in hospitals of all sizes and types, in various sized communities, serving all types of populations. Studies were also done on a wide variety of individual occupational groups at meetings and through special studies. Most of the studies relied upon the voluntary cooperation of the study population, so there is some chance for bias to be introduced into any estimate of HBV prevalence. Healthcare workers who know they are infected with HBV at the time of study or who know they are HBV carriers may decline to participate in a study which they may feel could jeopardize their careers. This would lead to an underestimate of the prevalence of HBV infection among health care workers. The most useful studies showed that risk of HBV infection in hospital personnel was increased several-fold over that in blood donors, that risk was closely related to frequency of contact with blood and not related to contact with patients per se, and that risk was directly related to duration in the occupation (Exs. 6-440; 6-65; 4-12; 4-13; 4-15; 4-16). Certain studies attempted to quantify the frequency of blood and needle exposure in various categories of healthcare workers, and relate this to risk of infection (Ex. 4-16). The following general observations can be made from these studies:

(1) These studies revealed that workers exposed to blood on the job had a prevalence of HBV markers several times that of non-exposed workers and the general population. The prevalence of markers increased with years on the job.

(2) The prevalence of HBV markers was related to the degree of blood exposure or frequency of needle exposure, and not to patient contact per se. Persons working in operating rooms, emergency rooms, labs, and dialysis units had a higher marker prevalence than persons working on medical or pediatric wards, who in turn had a higher prevalence than clerical workers, social workers, and administrators.

(3) Groups at high risk include (but are not limited to): medical technologists, operating room staff, phlebotomists and intravenous therapy nurses, surgeons and pathologists, oncology and dialysis unit staff, emergency room staff, nursing personnel, staff physicians, dental professionals, laboratory and blood bank technicians, emergency medical technicians, and morticians (Ex. 6-199).

Most infected healthcare workers are unaware that they have been exposed to or infected with HBV. Approximately 1% (or more) of hospitalized patients are HBV carriers; most HBV carrier patients seen in the healthcare setting are not symptomatic, are unaware that they are carriers, and their medical charts do not contain this information (Ex. 6-427). Health care workers may take extraordinary precautions when dealing with a known carrier, but are often unaware that they may treat five carriers for each one they recognize. This is a key point in understanding the rationale for the concept of "universal precautions", and for use of the hepatitis B vaccine in workers with exposure to blood. Although the risk of encountering HBV carriers may vary in the hospital setting, being highest in inner city referral hospitals dealing with high risk groups such as drug abusers and homosexual men, risk will be present in any work setting where human blood is encountered. The risk of HBV carriage in the general population is uniform (i.e. does not markedly vary within each region of this country), and high risk groups such as Southeast Asian refugees, the developmentally disabled individuals, and occult drug abusers may be found in rural as well as urban settings (Ex. 6-390).

Percutaneous exposure to blood through needlesticks and cuts with other sharp instruments are visible and efficient modes of transmission, but reported injuries do not account for the majority of infections in healthcare workers (Exs. 6-65; 6-427). This fact often goes unrecognized by worker's compensation boards, which sometimes deny coverage to infected workers unless they had reported a discrete needlestick or similar injury from a HBsAg positive patient. Some workers doing traumatic procedures get cuts, needlesticks or large blood exposures so frequently that they do not bother to report them; other workers become infected when the blood of an unsuspected HBV carrier gets into a small preexisting skin lesion or is rubbed into the eye. Prevention of these occupational infections is the goal of this standard.

Transmission from HCWs to Patients: Transmission of HBV from healthcare workers to patients is an uncommon but extremely serious consequence of healthcare worker infection. More than twenty clusters of patients infected in this way have been reported, although instances involving only one or a few patients may go unrecognized or unreported (Exs. 6-103; 6-446; 6-476; 4-471; 6-144). Most clusters of these cases have involved oral surgeons, dentists, gynecologists, or surgeons, occupations where significant blood exposure, trauma, and use of sharp instruments occur routinely. Some episodes have involved transmission to between 20 and 55 patients, with deaths and secondary transmission to family members of patients occurring (Exs. 6-103; 6-144).

Most healthcare workers who have transmitted to patients have several factors in common (Exs. 6-476; 6-471):

(1) The dentists and surgeons were chronic HBV carriers, had high titers of virus in their blood (HBeAg positive), and were unaware that they were infected.

(2) Transmission occurred most frequently during the most traumatic procedures.

(3) The dental personnel who transmitted did not routinely wear gloves. However, some infected HCWs continued to transmit HBV to patients in spite of the use of gloves and additional precautions.

(4) The dentists and surgeons often had a personal medical problem (such as exudative dermatitis on the hands), or used techniques that made transmission more likely. Several of the gynecologists used their index fingers to feel for the tip of the suture needle when they were performing deep abdominal surgery.

The most recent guidelines for HIV and HBV infected healthcare workers were published after the record for this rulemaking closed and are not contained in the record. These guidelines, "Recommendations for Preventing Transmission of Human Immunodeficiency Virus and Hepatitis B Virus to Patients During Exposure-Prone Invasive Procedures," were published in Morbidity and Mortality Weekly Report, Vol. 40, on July 12, 1991.

Transmission Via the Environment: Transmission of HBV infection from exposure to contaminated environmental surfaces has been documented to be a mode of HBV spread in certain settings, particularly hemodialysis units (Exs. 6-56; 6-446; 6-480; 6-461). The virus can survive for at least one week dried at room temperature on environmental surfaces, and medical procedures as well as disinfection and sterilization techniques must be adequate to prevent the spread of this virus (Exs. 6-422; 6-458). HBV contaminated blood from the surface of dialysis machines and carried on the hands of medical personnel to patients has been postulated as one mechanism of transmission in dialysis units. Unsterilized or improperly sterilized acupuncture needles have been implicated as the cause of two outbreaks of HBV infection in patients (Ex. 6-439). Potential problems of environmental contamination in the dental operatory have been discussed in the CDC guidelines for dentistry (Ex. 6-490).

HBV is thought to be far less resistant to sterilization and disinfection procedures than microbial endospores or mycobacteria used as reference criteria (Ex. 6-421). Any sterilization or disinfection procedure or sterilizing agent or high level disinfectant will kill the virus if used as directed. Diluted solutions (1:10-1:100) of sodium hypochlorite (household bleach) are particularly effective, if used properly, and inexpensive, although they may be corrosive or damaging to certain materials. Certain low-level "germicides" such as quaternary ammonium compounds are not considered to be effective against the virus (Ex. 6-422). Unfortunately, soaking medical and dental instruments in these solutions is a common and potentially dangerous procedure, since health workers may handle the sharp instruments soaked in these solutions with a false sense of security.

Hepatitis B Vaccine

In 1982 a safe, immunogenic and effective hepatitis B vaccine derived from human plasma was licensed in the U.S. and was recommended for use in healthcare workers with blood or needle exposure in the workplace (Ex. 6-199). A second vaccine, produced in yeast by recombinant technology was first licensed in 1987 (CDC, Ex. 6-200). Since the introduction of these vaccines, OSHA estimates a minimum of 2,568,974 persons in the United States have been vaccinated, 2,029,189 of whom are healthcare workers. HB vaccination is the most important part of any HBV control program, because gloving and other protective devices cannot completely prevent puncture injuries from needles and other sharp instruments.

Early efforts to immunize healthcare workers were hindered by fear that the plasma derived vaccine might be unsafe. The AIDS epidemic was just being recognized, and there was concern that the plasma derived hepatitis B vaccine might contain the infectious agent causing AIDS. Concerns about the safety of the plasma derived vaccine have been adequately studied and addressed (CDC, Ex. 6-199). The procedures used to manufacture the vaccine were shown to inactivate HIV virus and representatives of all known viral groups. The vaccine was shown not to contain HIV DNA, and those receiving vaccine do not develop anti-HIV antibodies. This vaccine is no longer available in the U.S. The yeast-derived vaccines contain no human plasma and there is no possibility that they could be infectious for HIV (6-200).

The currently licensed hepatitis B vaccines are given intramuscularly in the deltoid, in three doses over a six month period. These vaccines, when given according to manufacturers directions, induce protective antibody levels in 85% to 97% of healthy adults. Protection against both the illness and the development of the carrier state lasts at least nine years (the duration of follow-up studies) and perhaps considerably longer. Although antibody in many individuals will decay below detectable levels within seven years after immunization, if these individuals are exposed to HBV, they develop a rapid (anamnestic) antibody response and do not become ill or develop the HBV carrier state (Exs. 6-200; 6-435). For persons with normal immune status, the ACIP has not recommended that a booster dose of hepatitis B vaccine be given after the initial series but may do so in the future if it appears that immunity conferred by the vaccine wanes after some period of time. However, vaccine-induced protection is less complete for hemodialysis patients and may last only as long as antibody levels remain above 10 mIU/ml. For these individuals, the need for booster doses should be assessed by annual antibody testing. Booster doses should be given when antibody levels fall below 10 mIU/ml (Ex. 286G).

Persons planning hepatitis B vaccine programs may consider the need for pre-vaccination and post-vaccination testing for antibody (Exs. 6-200; 6-199). Prescreening may be cost-effective, depending on the likelihood of prior HBV infection. An algorithm to help assist with this determination has been published by the ACIP (Ex. 6-199). Discussions on the issues surrounding the option of post-vaccination testing have also been published. At this time post-vaccination testing is not considered necessary unless poor response to vaccine is anticipated (such as for those who have received vaccine in the buttock, persons > 50 years of age and persons known to have HIV infection), subsequent patient management depends on knowing the immune status (such as with dialysis patients and staff) or there may be a need to know whether the person ever responded to vaccine for management of post-exposure prophylaxis (Ex. 286G).

Post-exposure prophylaxis

Percutaneous and mucous membrane exposures to blood occur and will continue to occur in the healthcare setting (Exs. 6-431; 6-468). HBV infection is the major infectious risk that occurs from these exposures, and needlesticks from HBsAg positive individuals will infect 7% to 30% of susceptible healthcare workers (Exs. 6-27; 4-28). Pre-exposure vaccination is the most effective method for preventing such infection. However, it can be expected that some individuals, who initially decline vaccination, will experience an exposure incident. Fortunately, effective post-exposure prophylaxis exists for HBV exposures if appropriate protocols are followed. The February 9, 1990 recommendations of the Immunization Practices Advisory Committee specify that if the source individual is known to be HBsAg-positive then the exposed individual should be given hepatitis B immunoglobulin (HBIG) and the hepatitis B vaccine series be initiated (286G). Hepatitis B vaccine is recommended for any previously unvaccinated healthcare worker who has a needlestick or other percutaneous accident with a sharp instrument or permucosal (ocular or mucous membrane) exposure to blood (Ex. 286G, p. 19).

(2) Non-A, non-B hepatitis

Non-A, non-B hepatitis in the United States is caused by more than one viral agent. (Exs. 6-437; 6-429; 6-449). Studies have shown that parenterally transmitted (PT) non-A, non-B hepatitis accounts for 20-40% of acute viral hepatitis in the U.S. and has epidemiologic characteristics similar to those of hepatitis B (Ex. 6-39). Recently, a virus designated as Hepatitis C virus (HCV) was cloned and has been shown to account for a large proportion of parenterally transmitted non-A, non-B hepatitis in this country (CDC/NIOSH, Ex. 298). An immunoassay that detects antibody to HCV has been developed and was licensed in May 1990 for use in screening blood donors. Because the test is so new, there is not enough data to define how important this pathogen is in the occupational setting. Further research will help in clearly defining the importance of bloodborne transmission of this virus in the workplace.

The principal mode of transmission in the United States is bloodborne;

therefore, persons at greatest risk for infection include IV drug users, dialysis patients and transfusion recipients. Over 90% of all post-transfusion hepatitis is due to the non-A, non-B virus(es). These hepatitis viruses cause not only acute hepatitis, but may also lead to chronic hepatitis; an average of 50% of patients who have acute PT non-A, non-B hepatitis infection later develop chronic hepatitis with potential for progression to cirrhosis and for infectivity to others for the duration of life (Exs. 6-429; 6-449, 286G). The amount of virus present in the blood of acutely or chronically infected persons is modest, usually less than 1000 infectious doses per milliliter, although occasionally up to 1000 times higher (Ex. 6-423). Thus, relative infectivity of blood is 100 to 100,000 fold lower than with hepatitis B virus. Relative infectivity of other body fluids is not known.

Some evidence indicates that non-A, non-B hepatitis also presents an occupational risk to healthcare workers. At least one episode of transmission of non-A, non-B hepatitis from an acutely infected patient to a nurse by needlestick has been reported (Ex. 6-455). One case-control study has shown an increased risk of non-A, non-B hepatitis for patient care and lab workers (Ex. 6-39). Furthermore, non-A, non-B hepatitis transmission from infected patients to other patients and to staff has been reported in hemodialysis units; several outbreaks have been observed in this setting, and an incidence of 1.8% of non-A, non-B hepatitis among hemodialysis patients nationwide was observed in 1983 (Exs. 6-462; 6-386). While pathways of transmission in this setting have not been rigorously documented, nor has survival of HCV defined, bloodborne transmission by environmental contamination, similar to that of HBV, may occur.

In their May 1990 post-hearing comment, CDC/NIOSH supplied some additional information about non-A, non-B hepatitis and hepatitis C virus (HCV).

Non-A, non-B hepatitis is poorly reported at a national level and the best estimates of U. S. disease burden and risk groups come from the CDC Sentinel Counties Study of Viral Hepatitis. Extrapolating from this surveillance study, it is estimated that there were 170,000 non-A, non-B hepatitis infections in the U.S. 1988. Of these 3,400 (2%) were among health care workers. The estimates of non-A, non-B hepatitis attributable to occupational exposure come from the Sentinel Counties Study. In 1988, 2% of cases of non-A, non-B hepatitis were related to occupational exposure.

Recently, a virus has been cloned that appears to account for a large proportion of cases of non-A, non-B hepatitis in the U. S. and has been designated hepatitis C virus (HCV). In May 1990, an immunoassay that detects antibody to HCV (anti-HCV) was licensed for use in screening blood donors. Preliminary studies indicate that approximately 70% of patients with non-A, non-B hepatitis in the U. S. are anti-HCV positive when tested at the appropriate time in the course of their illness. At this time no data are available on the rate of HCV infection among health care workers or the risk of infection from various exposures. However, it is known that the risk of chronic liver disease following acute non-A, non-B hepatitis is approximately 50% (CDC/NIOSH Ex. 298).

Because the primary mode of transmission is blood to blood contact, and a large asymptomatic carrier reservoir exists, precautions to prevent non-A, non-B hepatitis transmission in the workplace are identical for those of other bloodborne viruses such as HBV (Exs. 6-461; 6-74; 6-426). Several studies have evaluated the efficacy of immunoglobulin (IG) prophylaxis following parenteral exposure, but results have been equivocal (Exs. 6-447; 6-436). Nevertheless, the CDC considers it reasonable to give IG as treatment to a healthcare worker after percutaneous exposure to blood from a known non-A, non-B infected patient (Ex. 6-199).

C. Human Immunodeficiency Virus

In June of 1981, the first cases were reported in the United States of what was to become known as Acquired Immunodeficiency Syndrome (AIDS) (Ex. 6-382). Investigators described an unusual illness characterized by Pneumocystis carinii pneumonia (PCP) and Kaposi's sarcoma (KS) that developed in young, homosexual men without a known underlying disease or cause for immunosuppression (Exs. 6-359; 6-380).

By early 1982, 159 AIDS cases had been identified in 15 states, the District of Columbia and 2 foreign countries. All but one of them were men and over 92% of them were homosexual or bisexual (Ex. 6-359). By the end of 1982, cases of AIDS were reported among children, intravenous (IV) drug users, blood transfusion recipients, hemophilia patients treated with clotting factor concentrates, and Haitians (Exs.6-380; 6-349). In 1983 the disease was also documented among female sexual partners of male IV drug users in the U.S. and among Africans (Ex. 6-349). By the end of 1985, all 50 states, the District of Columbia and three U.S. territories had reported AIDS cases (Ex. 6-359).

During 1983 and 1984, French and American scientists independently isolated a human virus associated with AIDS. Dr. Luc Montagnier and co-workers, of the Institute Pasteur in Paris, called it lymphadenopathy associated virus (LAV). Dr. Robert Gallo and co-workers at the National Cancer Institute identified this virus as human T-cell lymphotropic virus type III (HTLV-1) (Ex. 6-380). Eventually human immunodeficiency virus type 1 (HIV-1) became the universally accepted term for the virus (Ex. 6-383). (In this document, unless specifically noted, HIV refers to HIV-1.) The Centers for Disease Control estimates that in the United States, between 1 million and 1.5 million persons are infected with HIV-1 (Ex. 6-356). In addition, CDC reports in the August 1991 issue of HIV/AIDS Surveillance that as of July 1991, 186,895 cases of AIDS had been reported to the CDC, 3,199 of whom are children less than 13 years old. At least 116,734 (63.5%) of the adult/adolescent cases had died as well as 1,677 (52.4%) of the pediatric cases. Although the rate of spread of HIV-1 in the future is unknown, scientists with the U.S. Public Health Service have estimated that in the United States alone, a cumulative total of more than 365,000 cases of AIDS will have been reported by the end of 1992 with 80,000 new cases diagnosed during that year (Ex. 6-356). It is projected that there will be 66,000 deaths that year and 263,000 cumulative deaths. It is expected that a total of 172,000 AIDS patients will require medical care in 1992.

Of perhaps greater importance for healthcare workers is the 1.0 to 1.5 million persons who are infected with HIV, often unknowingly so, and who require medical treatment for related or unrelated conditions. For example, in 1987, Baker and colleagues examined 203 anonymous serum samples from a group of critically ill or severely injured patients with no history of HIV infection treated at the Johns Hopkins University Hospital Department of Emergency Medicine (Ex. 6-111). They found that six patients (3% of the sample) were seropositive for HIV antibody. In particular, all seropositives were trauma victims between the ages of 25 and 34 who were bleeding and their treatment involved multiple invasive procedures. In a more recent study in 1988 at an inner city emergency department, Kelen and co-workers tested blood samples from 2,302 consecutive adult patients for the presence of HIV antibodies. One hundred nineteen patients (5.2%) were seropositive for HIV. Of this group 92 (77%) had "unrecognized HIV infection" (Ex. 6-370).

There are reports of at least 30 healthcare workers who apparently were infected with HIV through occupational exposure to blood or other potentially infectious materials (Ex. 286U). Of the cases of HIV infection associated with occupational exposure discussed in this section, five occurred outside the United States. The number of known work related HIV seroconversions among healthcare workers is approximately 24 at present. However, many infections are likely to go unrecognized for several years until the HIV-infected individual develops AIDS. If effective preventive procedures are not instituted, the number of occupational HIV infections is likely to increase as the number of infected individuals requiring healthcare increases.

The increasing number of individuals with AIDS, the large number of unidentified HIV infections, and the reports of occupational infection all indicate that healthcare workers are at risk for occupationally acquired HIV infection.

HIV: Biology

HIV is a member of a group of viruses known as human retroviruses. Its genetic material is ribonucleic acid (RNA) rather than deoxyribonucleic acid (DNA), the genetic material found in most living organisms. The virus particle is comprised of a core containing the RNA and viral enzymes surrounded by an envelope consisting of lipids and proteins (Ex. 6-380, p.131-154).

Because they lack the cellular machinery necessary to reproduce, all viruses must reproduce intracellularly, that is, within the host cell. HIV replicates in human macrophages and T4 lymphocytes, two types of human cells that are vital components of the immune system. T4 lymphocytes and a few other cell types have protein molecules on their surfaces called CD4 antigens or receptors. HIV particles bind with the CD4 receptor sites of the hosts' cells and then release their viral RNA. The RNA is then transcribed by viral enzymes into double-stranded DNA that is incorporated into the DNA of the host cell. The viral DNA then serves as a template to produce more virus particles. The transcription of RNA to DNA is the reverse of what occurs in most organisms and thus HIV is called a retrovirus. The process occurs with the aid of the viral enzyme reverse transcriptase, which is considered to be a marker for retrovirus production (Exs. 6-384; 6-175; 6-380, pp. 186-249). HIV gradually depletes the number of cells which are essential for host immune function, rendering the infected individual increasingly susceptible to opportunistic infections (Exs. 6-360; 6-380, pp. 131-154).

Circulating macrophages are also considered a reservoir as well as another target for HIV infection. Since some macrophages can circulate freely throughout the body, they may actually transport HIV to the brain which may lead to neurologic complications (Ex. 6-384).

HIV: Serological Testing

Infection with HIV may be identified through testing the blood for the presence of HIV antibodies. Tests were first licensed for use in the United States in 1985 and have been used routinely to screen donated blood, blood components and blood products, and by physicians and clinics to diagnose HIV infection in patients (Ex. 6-380, pp. 1-17). The military also uses the antibody tests to screen recruit applicants and active duty personnel for HIV infection (Ex. 6-380, pp. 1-17). Although the antibodies do not appear to defend or protect the host against HIV, they serve as markers of viral infection. Most people infected with HIV have detectable antibodies within 6 months of infection, with the majority generating detectable antibodies between 6 and 12 weeks after exposure (Ex. 6-204).

The enzyme-linked immunosorbent assay (ELISA or EIA) technique used to detect HIV antibodies is sensitive, economical and easy to perform. However, as with all laboratory determinations, this test can produce a false positive result, that is, the test gives a positive result when HIV antibody is not present. Therefore, current recommendations include repeating the ELISA test if the first test is positive. If the second test is also positive, another test, usually employing the Western blot technique, is used to validate the ELISA results. A positive ELISA test and a positive Western blot result indicate the presence of HIV antibodies and HIV infection (Ex. 6-345).

Although many new tests are still in the experimental stages, one that is being developed uses the polymerase chain reaction (PCR) technique. This test detects integrated viral DNA rather than antibody and it may have the potential to detect HIV infection earlier than currently available antibody tests (Ex. 6-329).

HIV: Transmission

HIV has been isolated from human blood, semen, breast milk, vaginal secretions, saliva, tears, urine, cerebrospinal fluid, and amniotic fluid; however, epidemiologic evidence implicates only blood, semen, vaginal secretions and breast milk in the transmission of the virus (Ex. 6-317). Documented modes of HIV transmission include: engaging in sexual intercourse with an HIV-infected person; using needles contaminated with the virus; having parenteral, mucous membrane or non-intact skin contact with HIV-infected blood, blood components or blood products; receiving transplants of HIV-infected organs and tissues including bone, or transfusions of HIV-infected blood; through semen used for artificial insemination and perinatal transmission (from mother to child around the time of birth) (Exs. 6-349; 6-327; 6-310; 286U).

HIV is not transmitted by casual contact. Studies evaluating nearly 500 household contacts of individuals diagnosed with AIDS reveal no cases of HIV infection of household members who had no other risk factors for the virus (including no sexual contact with or exposure to blood from the infected person) (Ex. 6-349). Friedland and Klein examined household members who lived with a person with AIDS for at least 3 months and within an 18-month period prior to the onset of symptoms in the infected person (during which time infection was presumably present.) Other household members had been unaware of the infected individual's HIV status, and had not taken precautions during this time period (Ex. 6-349). This study produced no evidence that HIV was transmitted by shaking hands or talking, by sharing food, eating utensils, plates, drinking glasses or towels, by sharing the same house or household facilities or by "personal interactions expected of family members" including hugging and kissing on the cheek or lips. Other studies have shown that HIV is not transmitted by mosquitoes or other animals (Ex. 6-328).

The vast majority of people with AIDS in the United States can be placed in known transmission categories and the proportion of infected persons associated with each group has remained relatively stable since reporting began in this country in 1981. For adults and adolescents, the transmission categories are shown in Table IV-2. Table IV-3 displays the transmission categories for children less than 13 years old.

                             TABLE IV-2(1)

                                           Percent of cumulative
                                            total of AIDS cases
Transmission Group                        for Adults/Adolescents
Homosexual/bisexual men                            59%

Intravenous drug users                             22%
  (female and heterosexual male)

Homosexual/bisexual                                 7%
  contact and IV drug users

Hemophilia/coagulation                              1%

Heterosexual contact:                               5%
    Sex with IV drug user;
    Sex with person with
    Sex with bisexual male;
    Sex with transfusion recipient
      with HIV infection;
    Sex with HIV-infected person
      risk not specified;
    Born in Pattern II country.(2)
    Sex with person born in
      Pattern II country.

Receipt of blood transfusion,                       2%
  blood components or tissue(3)

Other/Undetermined(4)                               4%
  Footnote(1) HIV/AIDS Surveillance, August, 1991, p. 8.
  Footnote(2) Pattern II transmission is observed in areas of central,
eastern and southern Africa and in some Caribbean countries. In these
countries, most of the reported cases occur in heterosexuals and the
male-to-female ratio is approximately 1:1. Intravenous drug use and
homosexual transmission either do not occur or occur at a low level.
  Footnote(3) Includes 14 transfusion recipients who received blood
screened for HIV antibody and 1 tissue recipient.
  Footnote(4) "Other" refers to 3 healthcare workers who seroconverted to
HIV and developed AIDS after occupational exposure to HIV-infected blood.
"Undetermined" refers to patients whose mode of exposure to HIV is
unknown. This includes patients under investigation; patients who died,
were lost to follow-up, or refused interview; and patients whose mode of
exposure to HIV remained undetermined after investigation.
                             TABLE IV-3(1)
Pediatric (< 13 years old)              Percent of cumulative
   Exposure Category.                 total of pediatric AIDS cases.
Transmission Group Cases

Hemophilia/coagulation disorder                5%

Mother with/at risk for HIV infection:        84%
  IV drug use
  Sex with IV drug user
  Sex with bisexual male
  Sex with person with hemophilia
  Born in Pattern - II country
  Sex with person born in
    Pattern - II country
  Sex with transfusion recipient
    with HIV infection
  Sex with HIV-infected person,
    risk not specified
  Receipt of blood transfusion,
    blood components, or tissue
  Has HIV infection, risk not

Receipt of blood transfusion, blood            9%
  components, or tissue

Undetermined                                   2%
  Footnote(1) HIV/AIDS Surveillance, August, 1991, p. 9.

Some types of exposures are clearly more efficient at transmission than others. The risk of infection following receipt of transfused blood from an HIV-infected donor is approximately 90 percent (Ex. 6-371). The risk of perinatal transmission from an HIV infected mother is estimated to be 30-50 percent or higher (Exs. 6-384; 6-349). Besides the particular type of exposure, other variables contributing to the likelihood of transmission may include susceptibility of the host, the virulence of the particular strain, the stage of infection of the source, and the size of inoculum the individual is exposed to (Exs. 6-348; 6-349). This last factor, the actual amount of virus, may be very important in the likelihood of transmission since, it appears, there is a greater probability of infection from HIV contaminated blood transfusions (890 infections per 1,000 persons transfused with contaminated blood) than from accidental needlesticks with needles that have been contaminated with HIV (3-5 infections per 1,000 persons injured with contaminated needles) (Exs. 6-384; 6-349; 6-371).

HIV: Clinical Manifestations of Disease

HIV adversely affects the immune system, rendering the infected individual vulnerable to a wide range of clinical disorders. These conditions, some of which tend to recur, can be aggressive, rapidly progressive, difficult to treat, and less responsive to traditional modes of treatment. They usually lead to the death of the HIV infected patient (Ex. 6-361). The CDC has divided disease progression into several stages according to types of infections or symptoms reported.

Group I: Within a month after exposure, an individual may experience acute retroviral syndrome, the first clinical evidence of HIV infection. This is a mononucleosis-like syndrome with signs and symptoms that can include fever, lymphadenopathy, myalgia, arthralgia, diarrhea, fatigue, and rash. Acute retroviral syndrome is usually self-limiting and followed or accompanied by the development of antibodies (Ex. 6-270).

Group II: Although most persons infected with HIV develop antibodies to the virus within 6-12 weeks after exposure, most of these individuals are asymptomatic for months to years following infection. However, they can transmit the virus to others throughout this time (Ex. 6-270).

Group III: Although no other signs or symptoms are experienced, some HIV-infected patients will develop a persistent, generalized lymphadenopathy (PGL) that lasts more than 3 months (Ex. 6-270). Group IV:

Epidemiologic data indicates that most persons who are infected with HIV will eventually develop AIDS (Ex. 6-384). AIDS can result in severe opportunistic infections that an individual with a normal immune system would only rarely experience, as well as a wide range of neurologic and oncogenic or neoplastic processes (Ex. 6-270). The clinical manifestations of patients in this group may vary extensively. Some of these patients may experience "constitutional disease," also known as HIV "wasting syndrome," which may be characterized by severe, involuntary weight loss, chronic diarrhea, constant or intermittent weakness, and fever for 30 days or longer (Ex. 6-270). This syndrome in and of itself may result in death. Individuals with AIDS may also develop HIV encephalopathy, dementia, myelopathy or peripheral neuropathy. This may occur when HIV infects mononuclear cells present in the cerebrospinal fluid surrounding the brain and spinal cord or infects these cells within the brain or spinal cord. Persons with dementia experience varying degrees of cognitive disability or impairment of intellectual function and motor disability or dysfunction. Effects ranging from apathy and depression to memory loss and severe dementia may interfere with a person's occupation as well as activities of daily living and can ultimately be fatal (Exs. 6-270; 6-380, pp. 548-578). In addition, the virus is capable of affecting the peripheral nervous system causing severe pain and weakness or numbness in the limbs (peripheral neuropathy) (Ex. 6-270).

According to CDC's case definition, there are specific diseases that are considered indicators of AIDS if laboratory tests for HIV were not performed or gave inconclusive results and no other known causes of immunodeficiency are present (Ex. 6-157). Among these are parasitic diseases such as Pneumocystis carinii pneumonia, the most common opportunistic infection and cause of death in AIDS patients; fungal diseases such as candidiasis of the esophagus, trachea, bronchi or lungs; viral diseases such as cytomegalovirus disease of an organ other than the liver, spleen or lymph nodes; cancer/neoplastic diseases such as Kaposi's sarcoma affecting persons under 60 years of age; and bacterial infections such as Mycobacterium avium complex (Exs. 6-157; 6-361). In addition to the diseases listed above there are diseases caused by organisms such as disseminated or extra-pulmonary Mycobacterium tuberculosis (TB) which may be considered indicative of AIDS if substantiated by reactive HIV-antibody tests (Ex. 6-157). Unlike adults, children under 13 years of age can be classified as having AIDS if they experience lymphoid interstitial pneumonia or pulmonary lymphoid hyperplasia (LIP-PLH complex). Children who are seropositive for HIV can be classified as having AIDS if they experience recurring serious bacterial infections such as septicemia, pneumonia, meningitis, Hemophilus, Streptococcus or other pyogenic bacteria (Ex. 6-157).

AIDS is primarily managed by treating clinical disease symptoms, but conventional therapy cannot reverse the immunodeficiency (Ex. 6-361). Currently, researchers are testing experimental drugs and conducting a number of treatment protocols on patients at various stages of infection or disease. At this time, only one antiviral drug, Zidovudine or Retrovir TM, (formerly known as azidothymidine or AZT) has been approved by the FDA for some patients, specifically those who have experienced Pneumocystis carinii pneumonia (PCP), or are symptomatic for AIDS related illness and have less than 200 T4 cells/ml (Ex. 6-479). Although some patients have had to discontinue the drug due to severe side effects, clinical trials have shown the drug to prolong the life of AIDS patients (Ex. 6-383, pp. 153-165). There is no vaccine to prevent HIV infection (Ex. 6-384).

HIV: Workplace Transmission

Occupational transmission of HIV has been documented in healthcare workers. The information submitted to the public record indicates that as of May 1990, there are at least 65 case reports of healthcare workers whose HIV infections are associated with occupational exposure. Among these are 30 case reports that have been individually published in the scientific literature or are in press (CDC/NIOSH, Ex. 298). Eighteen of these cases seroconverted following a documented exposure incident. Thirteen of the seroconversions were caused by parenteral exposure to blood or blood-containing body fluids (11 by needlesticks and 2 by cuts with a sharp object). Five seroconversions involved blood contamination of mucous membranes or non-intact skin and one was due to parenteral exposure to concentrated HIV-I (Ex. 286U). The dates of seroconversion could not be documented for the remaining 12 individually published cases because no baseline serologic data had been obtained.

Documented cases of seroconversions in healthcare workers as of May 1990 are presented in Table IV-4. Additional cases of possible occupational transmission in healthcare workers as of May 1990 are presented in Table IV-5.

                           TABLE IV-4(1)
         Documented seroconversions in health workers
Author and             Country        Type of              ARS(2)
reference                             exposure
1.  Editorial           United          Needlestick           yes
2.  Stricof             USA             Needlestick           yes
3.  Oksenhandler        France          Needlestick           yes
4.  Neisson-Venant      Martinque       Needlestick           yes

5.  CDC(3)               USA             Non-intact skin      yes
6.  CDC                  USA             Mucous membrane      no
7.  CDC                  USA             Non-intact skin      yes
8.  Gioannini            Italy           Mucous membrane      yes
9.  Michelet             France          Needlestick          yes
10. Wallace              USA             Needlestick          yes
11. Barnes               USA             Sharp object         yes
12. Ramsey               USA             Needlestick          no
13. CDC                  USA             Needlestick          yes/AIDS
14. Marcus               USA             Needlestick          yes
15. Marcus               USA             Two needlesticks     yes
16. Gerberding           USA             Needlestick          yes
17. Weiss, CDC           USA             Sharp object         NR(4)
18. CDC                  USA             Cutaneous            NR(4)
  Footnote(1) From Marcus, R. et. al., Transmission of Human
Immunodeficiency Virus (HIV) in Health-care Setting Worldwide. Bulletin of
the World Health Organization, 67 (5); 577-582 (Ex. 6-286U).
  Footnote(2) ARS: acute retroviral syndrome.
  Footnote(3) CDC: Centers for Disease Control, USA.
  Footnote(4) NR: not reported.
                           TABLE IV-5
         Possible cases of occupational transmission of HIV(*)
Author and reference        Country              Type of
1.  Bygbjerg                 Denmark              Surgical practice
                                                  in Zaire
2.  Belani                   USA                  Palm prick from
                                                  hospital waste
3.  Anonymous                France               Worked in intensive
                                                  care unit
4.  Grint                    United Kingdom       Home-health provider,
                                                  non-intact skin
5.  Weiss, McCray            USA                  Colonic Biopsy
6.  Weiss, CDC               USA                  Two needlesticks
7.  Weiss, CDC               USA                  Two exposure/
                                                  unknown source
8.  Weiss, CDC               USA                  Concentrated virus
                                                  on skin
9.  Klein                    USA                  Multiple needlesticks
10. Ponce de Leon            Mexico               Needlestick
                                                  puncture wound
11. Schmidt                  Federal              Needlestick
                             Republic of
12. Lima                     Italy                Needlestick

  Footnote(*) From Marcus, R. et. al., Transmission of Human
Immunodeficiency Virus (HIV) in healthcare settings worldwide. Bulletin of
the World Health Organization, 67 (5); 577-582 (1989).

Twenty-five published cases of HIV infection associated with occupational exposure are summarized below. These cases represent a spectrum of healthcare personnel including, among others, nurses, laboratory workers and a dentist. For the 25 cases, HIV status was determined by HIV-antibody testing. Baseline blood samples analyzed for HIV-antibody revealed that at least 18 of these individuals were not infected with HIV at the time of the exposure incident. However, subsequent blood tests determined that eventually all of the 18 seroconverted to an HIV-positive-antibody status, indicating the presence of HIV infection. All 25 denied other known risk factors for HIV infection, but in cases where the baseline serologic data were unknown, other modes of transmission cannot be ruled out. Nevertheless, all cases were investigated for risk factors and none were identified.

Case Reports

CASE 1: A hospital healthcare worker sustained an accidental self-inflicted injection of "several milliliters of blood while obtaining blood in a vacuum collection tube from an AIDS patient" (Ex. 6-365). The healthcare worker subsequently seroconverted to an HIV-antibody-positive status and has since developed AIDS. Having determined there were no other HIV risk factors for this individual, investigators concluded the worker acquired the infection occupationally.

CASE 2: In November 1985, a previously healthy, 33 year old United States Navy hospital corpsman punctured his fingertip while disposing of a phlebotomy needle used to draw blood from a patient who was later diagnosed with Pneumocystis Carinii pneumonia and serologically tested HIV-positive (Ex. 6-337). Upon learning of this diagnosis two weeks after the incident, the corpsman submitted to HIV serology testing on a monthly basis and was HIV-negative for 3 months. Five months after the incident, he experienced a characteristic acute retroviral syndrome, which was self-limiting. Six months after the incident he tested HIV-positive. He reported a negative history of other risk factors for HIV, and his wife was seronegative.

CASE 3: Weiss and co-workers reported that a laboratory worker, who worked with concentrated HIV-1, tested seropositive for the virus (Ex. 6-187). Clinical evaluation revealed no signs or symptoms of HIV-related illness. As part of routine laboratory duties, this individual was involved in several possible exposure circumstances such as decontaminating equipment, cleaning up spills or touching potentially contaminated surfaces with gloved hands. Virus-positive culture fluid had occasionally leaked from equipment and contaminated centrifuge rotors. Although reportedly using Biosafety level 3 precautions, the subject was not fully knowledgeable with and did not strictly follow these practices all of the time.

The subject did not recall any direct skin exposure but did report having had a nonspecific dermatitis on the arm, although the "affected area was always covered by a cloth laboratory gown." The individual also reported incidents where he had pinholes or tears in his gloves and had to change them immediately.

Strains of HIV-1 isolated from different individuals generally differ significantly, but the HIV-1 isolated from this subject was indistinguishable from 1 of the 2 predominant HIV genotypes this individual worked with in the laboratory.

Although no specific exposure incident had been identified, the investigators concluded that the subject acquired the HIV infection in the laboratory, most likely through undetected skin contact with the concentrated virus.

CASE 4: A female phlebotomist reported that blood splattered on her face and in her mouth when the top of a 10-ml vacuum blood collection tube flew off while she was collecting a patient's blood (which subsequently tested HIV-positive) (Ex. 6-109). The HCW was wearing gloves and glasses and reported that no blood got in her eyes. She reported no open wounds but did have facial acne. She washed off the blood immediately after exposure. Her blood tested HIV-negative one day post-exposure and 8 weeks later. However, when donating blood 9 months after exposure, she was HIV-antibody positive. She denied having other known risk factors for HIV.

CASE 5: A female medical technologist was exposed to a blood spill that covered most of her hands and forearms while she was manipulating an apheresis machine; a machine that separates blood components, retains some, and returns the remainder to the donor (Ex. 6-109). Although she was not wearing gloves, she did not report any open wounds on her hands or any mucous membrane exposure. However, she did have dermatitis on her ear and may have touched that ear. Eight weeks after the incident she experienced symptoms of acute retroviral syndrome. She was HIV-negative 5 days post exposure; however, 3 months after exposure she was HIV-antibody positive. She denied having other known risk factors for AIDS. Her husband also denied any risk factors for AIDS and tested HIV seronegative.

CASE 6: Neisson-Vernant and co-workers reported that a "24-year-old female student nurse pricked the fleshy part of her index finger with a needle used to draw blood from an AIDS patient." She did not recall injecting blood. Two months later signs and symptoms of acute retroviral illness appeared, including fever and a macular eruption lasting 3 days. Although she tested HIV-negative 1 month after the incident, she tested positive 6 months after exposure. She denied all other risk factors for HIV and her husband tested HIV negative 6 and 9 months after her exposure (Ex. 6-93).

CASE 7: Michelet and co-workers reported a case of occupationally acquired HIV infection in a female nurse in France (Ex. 6-369). Having drawn a blood sample in a vacuum tube from an individual with AIDS, she stuck her finger with the large-bore needle of the adapter, but reportedly did not inject any blood. Immediately after the incident, she placed her finger in 0.5% sodium hypochlorite solution in accordance with the hospital's guidelines. Twenty-three days after exposure, she developed signs and symptoms of acute retroviral syndrome, including abdominal cramps, nausea, vomiting, and diarrhea. She later experienced anorexia, fatigue and facial palsy. Clinical evaluation found generalized lymphadenopathy. Although she tested HIV-antibody negative 13 days after the incident she was HIV-antibody positive 71 days post-exposure. Investigators failed to identify any risk factor for HIV for the nurse or her husband, who tested HIV-antibody negative 62 days after his wife's exposure incident.

CASE 8: An NIH clinical laboratory worker sustained a cut that penetrated through a glove and the skin when a vial of HIV-infected blood broke in the worker's hand (Ex. 6-348). Although initially testing negative, the individual subsequently tested positive and investigators have linked the infection with the accident.

CASE 9: Oksenhendler and co-workers reported that a female nurse in France stuck her finger superficially while recapping a needle contaminated by bloody pleural fluid from a patient positive for both HBsAg and HIV. Immediately post-exposure she received the hepatitis B vaccine and specific immunoglobulin. She experienced acute retroviral syndrome including fever, fatigue and vomiting 25 days after the incident. Fifty three days after exposure, she developed an acute "anicteric" hepatitis (possibly related to the primary HIV infection.) Although she tested HIV-negative after the exposure (days 1 and 13), she tested HIV-positive on day 68. She and her husband denied other known risk factors for HIV and her husband tested seronegative for HIV 110 days after the incident (Ex. 6-18).

CASE 10: A nurse from England received a needlestick injury to a finger while resheathing a hypodermic needle on a syringe containing an AIDS patient's blood from an arterial line (Ex. 4-41). A small amount of blood may have been injected as well. Signs and symptoms of acute retroviral syndrome presented 13 days after exposure with a rash developing 17 days after the incident. Although she tested HIV-negative 27 days post injury, she was determined to be HIV-positive on day 49. She denied other known risk factors for HIV.

CASES 11, 12 and 13: Marcus and co-workers reported 3 cases of healthcare workers who seroconverted to an HIV antibody-positive status (Ex. 6-372). One healthcare worker sustained a deep needlestick injury inflicted by a co-worker with a 21-gauge needle while attempting to resuscitate an AIDS patient. The healthcare worker was HIV-antibody and antigen negative the day after the exposure. Four weeks after the incident the worker experienced fever, "shaking chills," night sweats, lymphadenopathy, and malaise which lasted about 4 days. One hundred twenty-one days after the exposure the worker tested HIV-seropositive. The healthcare worker denied other known risk factors for HIV and a recent sex partner tested HIV-seronegative.

A second healthcare worker accidentally stuck herself on two occasions with needles that had been used on HIV-infected patients. The first exposure occurred while recapping a needle that had been used on a patient with AIDS. Ten days later the worker stuck herself with a needle that had been used to draw blood from a symptomatic HIV-infected individual. "After removing the tube of blood from the plastic needle holder, the healthcare worker placed the needle holder upright on its base, such that the needle was pointed vertically into the air. The healthcare worker then turned away and subsequently injured herself on the exposed needle." The worker tested positive for HIV-antibody and antigen 21 days after the first exposure (11 days after the second.) She developed an acute viral illness four weeks after the first incident, characterized by shaking chills, dehydration, nausea, malaise, bilateral lymphadenopathy and a weight loss of more than 10 pounds. During this illness she was HIV-antibody negative; however, lymphocyte cultures were positive for HIV-antigen and reverse transcriptase, an enzyme which serves as a marker for HIV. The healthcare worker tested HIV-antibody positive on day 121 after the first exposure (111 days after the second exposure.) Four months after the exposure incidents, the worker's spouse tested HIV-antibody negative.

A third case, a healthcare worker, received a deep intramuscular needlestick injury with a large bore needle and syringe unit visibly contaminated with blood from an AIDS patient (Exs. 4-39; 6-367). Fourteen days after the incident, acute retroviral syndrome developed. Although HIV-antibody negative 9 days post-exposure, the healthcare worker was determined HIV-antibody positive on day 184. The worker and the worker's spouse denied any other risk factors for AIDS and the spouse tested HIV-antibody negative 239 days after the incident.

CASE 14: Marcus and co-workers and McCray and co-workers reported a case where a female nurse received a puncture wound from a colonic biopsy needle (visibly contaminated with blood and feces) used in an AIDS patient (Exs. 6-372; 4-39). She tested HIV-positive approximately 10 months after exposure although there were no serologic baseline data before or immediately after the incident. She denied other risk factors for AIDS; however, her sexual partner also tested HIV-positive and heterosexual transmission therefore cannot be ruled out.

CASE 15: Gerberding and co-workers reported a case of a healthcare worker who acquired HIV infection after sustaining a deep needlestick injury with an HIV-contaminated needle (Ex. 6-375).

CASE 16: Ramsey and co-workers, conducted a prospective evaluation of 44 healthcare workers exposed to HIV and reported that one healthcare worker seroconverted to an HIV-antibody positive status after sustaining a needlestick from an HIV-contaminated needle (Ex. 6-373). The worker had been followed for at least 90 days after the exposure incident and had not reported any signs or symptoms of acute-retroviral illness.

CASE 17: Gioannini and co-workers reported that a 37-year-old intensive care nurse in Italy "had her hands, eyes and mouth heavily splashed" with blood from an HIV-infected hemophiliac. Beginning 11 days post-exposure, the nurse developed signs and symptoms of acute retroviral illness including fever, fatigue, chills, arthralgia, cervical and axillary lymphadenopathy and arthritis. She was hospitalized 18 days after the incident due to the severity of her symptoms plus progressive increases of aminotransferase levels. During her 55 day hospital stay the worker developed an acute, anicteric non-A non-B hepatitis, which may have been associated with HIV infection. HIV antigen was detected in her blood on day 21 and by day 43 she had seroconverted to an HIV-antibody-positive status (Ex. 6-334).

CASE 18: A 32-year-old mother tested HIV-positive subsequent to providing extensive healthcare to her male child with a "congenital intestinal abnormality" (Ex. 4-37). Having received multiple blood transfusions (one of which was from an HIV-positive source) the child was tested and determined HIV-positive at 24 months of age. Although the mother did not report any needlestick or other parenteral exposure to the child's blood, she recalled having had frequent hand contact with the child's blood and body fluids. She did not wear gloves and did not wash her hands immediately after exposure. She did not report having open wounds or exudative dermatitis on her hands. One month after the child tested HIV-positive, the mother was determined to be seronegative for HIV. However, 4 months later she was determined to be HIV-antibody-positive. She reported a negative history for other risk factors for HIV for herself and the child. The child's father was seronegative for HIV. Investigators concluded the mother most probably acquired the infection by providing her infected child healthcare that involved extensive exposure to blood and body fluids without using infection control practices.

CASE 19: A laboratory worker apparently became infected in a laboratory accident (Exs. 6-187; 6-368; 6-312). He handled large volumes of HIV in a high containment laboratory under contract with NIH, performed techniques to concentrate the virus as part of a commercial process and reportedly followed biosafety guidelines. He was tested and found to be HIV-seropositive. The lab worker was not informed of his HIV status until 16 weeks after he tested HIV-positive. At that time, he recalled having cut his finger with a blunt stainless steel needle while cleaning a piece of contaminated equipment. He had tested HIV-negative 4 to 6 months prior to the laboratory incident but tested HIV-positive 6 to 9 months post exposure. Biosafety officials were of the opinion that the accident probably caused the infection. The laboratory worker has not participated in any studies that could determine whether he is infected with a laboratory strain of HIV.

CASE 20: Klein and co-workers reported a male dentist who had tested HIV-seropositive (Ex. 6-366). He denied having other risk factors for the virus. Although he did not recall treating a patient with AIDS, he had treated patients at high risk for HIV infection. He reported having frequent open lesions or "obvious breaks in the skin" on his hands; however, he only intermittently used personal protective equipment. His wife, although refusing to be tested for HIV, denied other HIV-risk factors. There was no report of baseline or convalescent serology and exposure to HIV-positive blood cannot be documented.

CASE 21: A healthcare worker applied pressure to an HIV-infected patient's arterial catheter insertion site to stop bleeding (Ex. 6-109). During the procedure, she may have had a small amount of blood on her index finger for 20 minutes before washing her hand. She did not wear gloves during this procedure and although she reported no open wounds, her hands were chapped. Twenty days after exposure, she developed symptoms of acute retroviral syndrome lasting 3 weeks. Blood she had donated 8 months prior to the exposure was HIV-negative. However, blood donated 16 weeks after the incident was HIV-positive. She denied having other known risk factors for HIV. No baseline data or serologic testing results were obtained immediately following exposure for this case.

CASE 22: A female healthcare worker received accidental needlestick injuries when drawing blood from AIDS patients in two incidents separated in time by 4 months (Ex. 6-258). She had her first blood test for HIV 8 months after the second exposure and was found HIV-positive. Although previously healthy, she developed a persistent mild lymphadenopathy 3 months after the second incident and intermittent diarrhea which started 5 months after that incident. She denied other HIV risk factors. Her long-term sex partner also denied any HIV risk factors, and he repeatedly tested HIV-antibody-negative over an 8-month period following the healthcare worker's positive test result. HIV was obtained from the male partner's peripheral lymphocytes within 13 months after the second incident but could not be obtained several months later. Heterosexual transmission could not be ruled out for the healthcare worker but seems less likely than parenteral transmission in this case.

CASE 23: A male laboratory worker, was found to be HIV-positive when first tested (Ex. 6-258). The worker recalled having received 2 parenteral exposures to blood from persons of unknown HIV status. He sustained an accidental needlestick and a cut on the hand while processing blood 8 and 16 months respectively prior to being tested. Although asymptomatic when tested, he has experienced transient cervical lymphadenopathy. He denied all known risk factors for HIV, but non-occupational transmission could not be ruled out in this case as no serologic data were available immediately after the exposures.

CASE 24: Grint and co-workers reported that a 44-year-old woman from England, although not a healthcare worker, developed AIDS after providing healthcare services for a Ghanaian man with a postmortem diagnosis of AIDS (Ex. 6-333). She recalled having small cuts on her hands, an exacerbation of chronic eczema, and frequent skin contact with his body secretions and excretions. There was no report of baseline or convalescent serology.

CASE 25: Ponce de Leon and co-workers reported that a 39-year-old male laboratory technician in Mexico acquired AIDS occupationally and died as a consequence of this disease (Ex. 6-326). From 1971 to 1986 he worked as a laboratory technician in a company that processed blood and blood products and where infection control procedures were not "customary." He reported experiencing many accidental punctures and blood contact with his "teguments and mucosa". The worker also recalled a laboratory accident "in late 1985 in which a deep cut in his right hand was grossly contaminated with plasma." Early in 1986 he experienced an acute illness characterized by fever and lymphadenopathy lasting several days. In 1987 the worker experienced a seven-month illness characterized by persistent diarrhea, weight loss, persistent oral thrush, intermittent fever, generalized lymphadenopathy, anisocoria and signs of meningitis. He eventually was hospitalized on December 11, 1987 two weeks after dizziness, mental confusion and vomiting ensued. Tests revealed the presence of the opportunistic infection cryptococcoses. The worker tested HIV-antibody-positive and was diagnosed as having AIDS. The patient died on December 18,1987. He had denied other risk factors for HIV and his wife was seronegative for HIV-antibody.

HIV: Epidemiology

A number of prospective studies and surveys have been conducted to determine occupational risks for HIV infection. Marcus and co-workers reported that the Centers for Disease Control has been conducting a national prospective study which began in 1983, to assess initially the risk of Acquired Immunodeficiency Syndrome and later, with the advent of HIV-antibody testing, the risk of HIV among healthcare workers exposed to the blood or body fluids of persons with HIV infection (Ex. 6-372). In 1986, data were reported on the first 451 healthcare workers who had entered the study and had been tested for HIV antibody (Ex. 4-39). Initially, individuals were considered eligible for the study if they had been exposed to the blood or body fluids of a patient with AIDS or AIDS-Related illness by a needlestick, a cut with a sharp object or contamination of an open wound or mucous membrane. Thereafter, subjects were enrolled only if they had parenteral, mucous membrane or non-intact skin exposure to the blood of an HIV-infected individual.

As of July 31, 1988, a cohort of 1201 healthcare workers with exposure to HIV-contaminated blood has been followed. Of these, 751 (63%) were nurses, 164 (14%) were physicians or medical students, 134 (11%) were technicians or laboratory workers, 90 (7%) were phlebotomists, 36 (3%) were respiratory therapists and 26 (2%) were housekeeping or maintenance staff. Upon enrollment the subjects provided investigators with epidemiologic data including demographic information, medical history, details of the exposure circumstances, infection control precautions used and post-exposure treatment. Nine hundred sixty-two (80%) of the subjects had sustained needlestick injuries, 103 (8%) had been cut with a sharp object, 79 (7%) had contaminated an open wound and 57 (5%) have had a mucous membrane exposure. Seven hundred seventy-nine (65%) of the exposed healthcare workers were exposed in a patient room, on a ward or in an outpatient clinic; 161 (14%) in an intensive care unit; 87 (7%) in an operating room; 84 (7%) in a laboratory; 62 (5%) in an emergency room; and 28 (2%) in a morgue.

The 1,201 subjects had blood samples drawn and tested for the presence of HIV-antibodies. Acute blood specimens collected within 30 days after exposure were obtained and tested from 622 subjects. Exposed healthcare workers were retested at 6 weeks, 3 months, 6 months and 12 months after the exposure incident to determine if seroconversion had occurred. Seroconversions were defined as healthcare workers who were seronegative for HIV antibody within 30 days after occupational exposure and seropositive 90 days or more after the exposure incident.

Nine hundred sixty-three subjects had been followed for at least 6 months, 860 (89%) of whom had sustained either a needlestick injury or a cut with a sharp instrument. Of these, four were seropositive yielding a seroprevalence rate of 4/860 = 0.47%. One of the four was first tested for HIV-antibody 10 months after sustaining a needlestick exposure to blood of an HIV-infected patient (see CASE 14). As there was no available acute blood specimen collected within 30 days after exposure this case cannot by definition be considered a seroconversion. The remaining 3 HIV-seropositive subjects (see CASES 11, 12, and 13) had HIV-seronegative acute blood specimens and were thus considered seroconversions, yielding a seroconversion rate of 3/860 = 0.35%.

Weiss and co-workers, conducted a prospective study to assess the risk of HIV in laboratory workers (Ex. 6-187). Invitations to participate in the study were issued to workers with possible exposure risk in 15 laboratory facilities from 6 states. Of the 265 subjects studied, 225 had laboratory exposure (including 99 who worked with concentrated HIV and 126 who worked with blood containing HIV, non-infectious viral proteins, or cloned viral DNA), 30 worked with AIDS patients in support of the laboratory and 10 were clerical staff working in the laboratory environment. Of the 225 laboratory workers, 10 reported one or more episodes of parenteral exposure to HIV, including needlesticks or cuts, and 35 reported one or more episodes of skin contact with HIV. Participants completed a questionnaire focusing on workplace exposure to human retroviruses, biosafety precautions used at the facility and by the subject, accidents occurring in the laboratory or other areas and the non-occupational factors such as drug use, sexual activity and transfusion history. Eight (3%) of the 265 reported non-occupational risk factors for the virus. Of the 225 workers with laboratory exposure, ten reported parenteral virus exposure, and 35 reported 1 or more skin contacts. Thirteen workers reported that they did not wear gloves at all times when working with HIV-infective material. Blood samples from all subjects were analyzed for HIV antibodies by enzyme-linked immunosorbent assay and confirmed by tests such as immunoblots and radioimmune assays. One individual who worked with concentrated HIV-1 was seropositive for the virus upon entering the study (See CASE 3). The HIV isolated from the subject's blood was shown to be genetically identical to a strain of HIV used in the laboratory, thus strongly implicating occupational exposure as the source of infection. The authors concluded that the most plausible source of exposure was contact of the worker's gloved hand with culture supernatant fluid containing concentrated virus, followed by inapparent exposure to skin. No HIV seroconversions were identified in the other study participants during the period of prospective follow-up. The authors calculated that the rate of HIV infection was 0.48 per 100 person-years for laboratory personnel in this study.

Gerberding and co-workers are conducting a prospective cohort study to assess the risk of transmitting HIV to healthcare workers intensively and frequently exposed to the more than 1600 patients with AIDS and AIDS-related conditions at San Francisco General Hospital (Exs. 6-375; 6-353). After inviting the hospital healthcare workers to participate in the study, investigators recruited a cohort of 623 subjects between 1984 and 1988. At the time of enrollment blood samples from each subject were tested for HIV antibody. Upon entering the study, each subject was asked to complete a confidential, self-administered questionnaire designed to elicit information regarding demographic characteristics; employment history; medical history; type, frequency, duration and intensity of exposures to HIV-infected patients or laboratory specimens from such patients; a description of infection-control procedures; and non-occupational risk factors for HIV infection. Subjects who described non-occupational risk factors for AIDS on the questionnaire were excluded from this study, leaving 468 for prospective follow up. Forty-four percent were physicians (57 of whom were surgeons), 30% were nurses and 11% were laboratory technicians. Of these, 11% worked solely on AIDS units or research laboratories and 26% worked in the operating room, emergency room or intensive care unit. Two hundred twelve of the subjects reported having had accidental exposure (with some having had multiple exposures) to HIV-infected blood by needlestick or by splashes to mucous membranes or nonintact skin. Of the one hundred eighty subjects who received follow-up HIV-antibody testing at least 6 months after exposure, Gerberding and co-workers reported that only one, a healthcare worker who had sustained a deep needlestick injury with an HIV-contaminated needle seroconverted to HIV antibody positive (CASE 15), yielding a seroconversion rate of 1/212 = 0.47%.

Klein and co-workers, conducted a study to assess the occupational risk of HIV among individuals working in the dental profession (Ex. 6-366). Dental professionals in the boroughs of Manhattan and the Bronx in New York City received a mailing requesting their participation in the study. Others were also recruited during dental meetings in the New York City metropolitan area (between October 1985 and May 1987), and during the annual meeting of the American Dental Association in Miami Beach (October 1986). Written consent was given and questionnaires were completed by a cohort of 1,360 dental professionals. The questionnaires addressed the issues of demographics (including type, duration and location of practice), behavior or other risk factors related to AIDS, "precautions used when treating patients, type and estimated numbers of patients treated, estimated number of accidental parenteral inoculations," and HBV vaccination status. Blood samples were then obtained and analyzed for HIV antibodies by EIA and, if reactive, confirmed by Western blot assay. The blood samples of those subjects who had not received the hepatitis B vaccine were analyzed for HBV antibodies as well. Twenty-five participants who reported no or "uncertain" contact with patients and 13 subjects for whom blood samples were not obtained were excluded from the study. For 13 participants who reported non-occupational risk factors for HIV, including 10 homosexual or bisexual men, 2 heterosexual intravenous drug users and 1 homosexual or bisexual IV drug user, blood samples were analyzed separately. Among those who reported non-occupational risk factors, 4 were found to be HIV-antibody positive. The remaining cohort of 1,309 subjects consisted of 1,132 dentists, 131 dental hygienists and 46 dental assistants. Most of the dentists were male and 5% were oral surgeons. Nearly all of the dental hygienists and assistants were female. About half of the participants practiced in cities where large numbers of AIDS cases have been reported. Although the vast majority of subjects reportedly worked either with AIDS patients (15%) or with patients at high risk for AIDS (72%), only 31% of the dentists and 8% of dental assistants reported always wearing gloves when performing dental treatment; most of them did report using gloves intermittently. Seventy three percent of the hygienists reported always wearing gloves while working with patients. Most of the dentists and dental hygienists used masks, eye protection and disposable gowns intermittently, although the majority of dental assistants never used these infection control procedures. Nearly all subjects who used precautions reported they had increased their use of precautions since 1983 due to concern about AIDS. Approximately 94% of the subjects reported sustaining accidental "parenteral inoculations with sharp instruments," ranging from one to as many as 7,500 within a 5-year period. Serologic test results revealed that at least 21% of the subjects who had not receive the hepatitis B vaccine had been infected with HBV; however, only 1 subject, a male dentist, was seropositive for HIV (see CASE 20).

Klein and co-workers concluded that there is a risk of dental professionals acquiring HIV occupationally. Because the study represents a point prevalence survey, the HIV seroconversion rate among dental personnel cannot be estimated from it.

Henderson and co-workers are conducting a prospective study that began September, 1983, to assess the risk of nosocomial transmission of HIV to healthcare workers (Exs. 6-377; 6-352). Investigators invited healthcare workers with varying degrees of occupational exposure to more than 1000 HIV-infected patients seen at the Clinical Center at the National Institutes of Health (NIH) to participate in the study. As of October 1988, the cohort being followed consisted of healthcare workers, including clinical and research laboratory personnel as well as healthcare workers providing direct patient care. Blood was obtained from each subject at the time of enrollment and every 6 months thereafter. The samples were tested for the presence of HIV antibody by ELISA and if reactive, were then confirmed by Western blot. Upon enrollment and every six months thereafter, questionnaires were completed to obtain demographic information, job description, type and frequency of procedures performed on HIV-infected patients, type and frequency of patient blood or body fluid exposure, and type and frequency of exposure to patient specimens. Questions regarding non-occupational risk factors were not included. Two categories of exposure were defined: "physical contact with either a patient or specimen container in routine work"; and "adverse" exposure, either parenterally (by a needle, scalpel or other sharp object contaminated with blood or body fluids from HIV-infected patients) or by splash to the mouth, nasal or conjunctival membranes (by blood, urine, saliva, sputum or feces from an HIV-infected patient). Three hundred fifty-nine of the subjects in the cohort reported collectively 482 percutaneous or mucous membrane exposures to blood or body fluids from HIV-infected patients (Ex. 286U). These individuals were evaluated separately, given more comprehensive initial and follow-up questionnaires, and were requested to provide serologic baseline samples as close as possible to the time of exposure as well as yearly samples thereafter. All adverse exposures were followed for at least 6 months (ranging from 6 to 63 months.) One subject who had been cut with a sharp object subsequently experienced an acute retroviral syndrome and developed antibodies to HIV (Ex. 6-348). For 6 subjects, blood samples were positive for HIV antibody at the time of entry into the study. None of the 6 had reported an adverse exposure to blood or body fluids. However, upon reevaluation, all 6 described having at least one non-occupational risk factor for HIV infection.

Healthcare Workers with AIDS

Further evidence of occupational transmission is provided by reports of healthcare workers who have AIDS, but have no identifiable risk for infection (Ex. 6-378). As of September 30, 1990, there were at least 69 healthcare workers with AIDS for whom no risk factors have been identified after thorough investigation. This group was comprised of 13 physicians, 1 of whom was a surgeon; 2 dental workers; 8 nurses; 14 aides/ attendants; 12 housekeeping or maintenance workers; 7 technicians; 2 therapists; 3 embalmers; 1 paramedic and 7 others. Of these, 35 reported needlestick and/or mucous membrane exposures to the blood or body fluids of patients during the 10 years proceeding their diagnosis of AIDS. However, none of the source patients was known to be HIV-infected at the time of exposure, and none of the workers was evaluated at the time of exposure to determine HIV-infection status or to document seroconversion (Ex. L6-666). While data on these cases are less complete compared to the case reports mentioned earlier, it is reasonable to assume that at least some of them resulted from occupational exposure (CDC/NIOSH, Ex. 286).

Human Immunodeficiency Virus Type 2

A case of AIDS in a person from Africa, caused by another human retrovirus, human immunodeficiency virus type 2 (HIV-2), was diagnosed and reported for the first time in the United States in December, 1987 (Ex. 6-308). Since then the CDC has received reports of additional cases of HIV-2 occurring in the West Africans that were diagnosed in the United States. HIV-2 appears to be similar to HIV-1 in modes of transmission and natural history but has not yet been studied in as much detail. Although HIV-2 is unquestionably pathogenic, there is still much to be learned regarding its epidemiology, pathogenesis and efficiency of transmission. Although only a few cases of HIV-2 has been reported in the United States, the infection is endemic in West Africa, where it was first linked with AIDS in 1986. There have also been cases of HIV-2 infection reported among West Africans living in Europe. HIV-2 surveillance is being conducted in the United States to monitor the frequency of occurrence using specific tests not yet available commercially (Ex. 6-308). The National Institute for Occupational Safety and Health reports that it is likely that additional human retroviruses will be discovered in the future (Ex. 22-634) .

D. Other Bloodborne Pathogens

Several additional infectious diseases are characterized by a phase in which the causative agent may circulate in blood for a prolonged period of time. With the exception of syphilis and malaria, these diseases are rare in the United States.

Syphilis: Syphilis is caused by infection with Treponema pallidum, a spirochete. Syphilis, a sexually transmitted infectious disease, is increasingly prevalent in the United States; 35,147 cases were reported in civilians in 1987 (Ex. 6-465). Marked increases occurred in 1987. The 25% increase over the 1986 rate was the largest single-year increase since 1960. Moreover the incidence of 14.6 cases per 100,000 persons in 1987, equal to that of 1982, is the highest rate since 1950. The natural history of syphilis is characterized by an incubation period of 10 to 90 days during which the patient is seronegative and asymptomatic (Ex. 6-495). Subsequent to this incubation period, a primary stage occurs, usually characterized by the appearance of a single lesion, or chancre, and normally accompanied by reactivity in serologic tests. Untreated, the primary lesion heals in weeks. Within weeks to months, a variable systemic illness, the secondary stage, characterized by rash, fever and widespread hematogenous and lymphatic dissemination of spirochetes occurs. All infected persons have reactive serologic tests in this stage (Ex. 6-495). Furthermore, the highest levels of spirochetemia (spirochetes present in blood) are reached during this period. Over two-thirds of patients then go into a latent phase when they are asymptomatic. After a variable period of latency, the rest progress to a tertiary stage with high morbidity and mortality including involvement of skin, bones, central nervous and cardiovascular system (Ex. 6-495). During latency and tertiary syphilis, spirochetemia is markedly reduced, as is infectivity. However during the course of untreated syphilis, spirochetes may be intermittently found in the bloodstream, and syphilis can probably be transmitted through the course of the illness, though not as readily as during the primary and secondary stages (Ex. 6-495). Although syphilis is primarily transmitted sexually and in utero, a few cases of transmission by needlestick, by tattooing instruments, and by blood transfusion have been documented (Exs. 6-453; 6-496). A reported transmission has occurred by needlestick exposure to the blood of a patient with secondary syphilis, resulting in a chancre on the hand (Ex. 6-453). Preventive treatment of an exposed healthcare worker with an antibiotic during the incubation period would be expected to prevent serological test positivity and the potential for permanent reactivity on treponemal testing, as well as preventing the manifestations of infection.

Malaria: Malaria is a potentially fatal mosquito-borne parasitic infection of the blood cells characterized by paroxysms of fever, chills, and anemia; 944 cases were reported in the United States in 1987 (Ex. 6-465). Malaria is an important health risk to immigrants from numerous malaria-endemic areas of the world and to Americans who travel to such areas. Moreover, transmission by mosquito vector has been documented in some areas of the United States. Malaria is characterized by a prolonged erythrocytic phase during which the causative agent, one of several species of the Plasmodium genus, is present in the blood. In many nations, malaria is among the most common transfusion-related infectious diseases. In temperate countries, it is only occasionally reported (Ex. 498). Malaria has also been transmitted by needlestick injury; in one incident, malaria was transmitted to a child who received a unit of blood and to the recipient's physician, who stuck himself with a needle (Ex. 467).

Babesiosis: Babesiosis is a tick-borne, parasitic disease similar to malaria which is caused by the intraerythrocytic parasite Babesia microti. It is endemic in certain islands off the northeastern coast of the United States. Transmission by transfusion of fresh blood from asymptomatic donors has been reported (Ex. 454).

Brucellosis: Brucellosis is a febrile illness caused by members of the genus Brucella. It is typically associated with occupational exposure to livestock or with ingestion of unpasteurized dairy products; 129 cases were reported in 1987 (Ex. 6-465). It is characterized by fever and weakness, sweats and arthralgia. Transmission by blood transfusion has been reported; in one incident, brucellosis and syphilis were transmitted in the same unit of blood to one recipient (Ex. 6-496).

Leptospirosis: Leptospirosis, a prolonged illness characterized by fever, rash, and occasionally jaundice, is caused by strains of Leptospira interrogans, a spirochete. The septicemic phase, during which leptospira are present in the bloodstream of patients, usually resolves within 1-2 weeks. It is typically acquired by contact with urine of infected animals, including cattle, swine, dogs, and rats; 43 cases were reported in 1987 (Ex. 6-465). No cases of nosocomial transmission by blood have been reported.

Arboviral infections: Arboviral infections generally do not lead to high or sustained levels of viremia in humans, therefore, there is little potential for person-to-person transmission of these infections through blood products or needlestick exposure. The exception is Colorado tick fever (CTF) caused by a tick-borne virus which infects red blood cells. Within 3-14 days following tick exposures, the patient experiences fever, chills, headache, muscle and back aches. Several hundred cases are reported annually and transmission by blood transfusion has been documented (Ex. 6-416).

Relapsing fever: Relapsing fever is a rare disease, caused by pathogenic Borreliae, transmitted by lice or ticks and characterized by recurring febrile episodes separated by periods of relative well-being. In the United States, a few cases of tick-borne relapsing fever are reported in localized geographic areas (Western United States). Though very rare, occupational transmission as a result of patient care practices has been reported. Infections have been attributed to blood from the vein of a patient squirting into the nose of a technician and, in another incident, splashing into another HCW's eye from a placental specimen (Ex. 6-488).

Creutzfeldt-Jakob disease: Creutzfeldt-Jakob disease, a rare disease with worldwide distribution, is a degenerative disease of the brain caused by a virus. It is believed to be transmitted by ingestion of or inoculation with infectious material, primarily neural tissue. No cases of nosocomial transmission by blood have been reported, although rare instances of transmission have occurred secondary to homologous dura mater implants, receipt of human growth hormone, and insertion of unsterilized stereotactic electrodes which had been inserted into the brains of Creutzfeldt-Jakob disease patients and then used on others (Ex. 6-492). There is a report of a case of Creutzfeldt-Jakob Disease, confirmed by autopsy, in a neuropathology histopathology technician. She had been employed in the neuropathology facility for 22 years and her duties included rinsing formalin-fixed brains and processing, cutting and staining sections of brain. Log records indicated that during her tenure two individuals with CJD were autopsied, 16 and 11 years prior to the technicians illness. It is not known how this individual became infected (Ex. 6-546). The record contains a number of articles discussing suggested precautions for handling materials from patients with CJD (Exs. 6-541; 6-542; 6-543; 6-544; 6-545 6-548).

Human T-lymphotropic Virus Type I: Human T-lymphotropic virus type I (HTLV-I), the first human retrovirus to be identified, is endemic in southern Japan, the Caribbean, and in some parts of Africa, but it is also found in the United States, mainly in intravenous drug users (Ex. 6-493). The virus can be transmitted by transfusion of cellular components of blood (whole blood, red blood cells, platelets) (Ex. 6-499). HTLV-I has been associated with a hematologic malignancy known a adult T-cell leukemia/lymphoma and with a degenerative neurologic disease known as tropical spastic paraparesis or HTLV-I-associated myelopathy. There is some evidence that the neurologic disease may be associated in some cases with blood transfusion (Ex. 6-494). No cases of occupy-tonal acquisition of HTLV-I infection have been reported.

Viral hemorrhagic fever: The term viral hemorrhagic fever refers to a severe, often fatal illness caused by several viruses not indigenous to the United States, but very rarely introduced by travelers coming from abroad. These illnesses are characterized by fever, sore throat, cough, chest pain, vomiting, and in severe cases, hemorrhage, encephalopathy and death. Although a number of febrile viral infections may produce hemorrhage, only the agents of Laesa, Marburg, Ebola, and Crimean-Congo hemorrhagic fevers are known to have caused significant outbreaks of disease with person-to-person transmission, including nosocomial transmission (Ex. 6-417). Blood and other body fluids of patients with these illnesses are considered infectious. Any patient suspected of illness due to one of these agents should be reported immediately to the local and state health departments and to the Centers for Disease Control. The bacterial and parasitic diseases listed above are treatable with antibacterial or antimalarial drugs. No specific therapy is available for the viral diseases, with the exception of Laesa fever. Precautions designed to minimize transmission of the more important bloodborne viral diseases, namely HIV, hepatitis B, and non-A, non-B hepatitis, would be effective in minimizing occupational transmission of all the above agents in the clinical setting.

[56 FR 64004, Dec. 6, 1991; 57 FR 29206, July 1, 1992]

Regulations (Preambles to Final Rules) - Table of Contents

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