Viral Infections

Jennifer Janelle

CASE SUMMARY

A 32-year-old anesthesiologist sustained an injury from a 16-gauge, hollow-bore needle left on a tray after placement of a central catheter. The needle was visibly contaminated with blood. Upon removal of his gloves, the anesthesiologist found a bleeding wound on his left thenar eminence. He washed the wound with soap and water, called in a colleague to take over the case, and went to his occupational health department for further evaluation and treatment.

The source patient was a homeless man with a history of intravenous drug abuse. He was infected with hepatitis C, hepatitis B (HB), and advanced acquired immunodeficiency syndrome (AIDS), and had been admitted for infective endocarditis. He had been on multiple antiretroviral agents, but had significant medication noncompliance and had not had medical follow-up for his human immunodeficiency virus (HIV) infection in >6 months. Prior resistance testing showed that his HIV virus was resistant to many antiretroviral drugs.

The anesthesiologist’s records were reviewed. He had completed the HB vaccine series and had adequate antibody on subsequent testing. He was tested for antibodies against hepatitis C and HIV and was found to be negative for these infections at baseline. Liver function testing at baseline was normal. He was offered and accepted prophylactic therapy against HIV with a combination of three medications selected by an infectious disease specialist based on the source patient’s prior resistance testing. Despite mild nausea, he completed 4 weeks of antiretroviral therapy and subsequently tested negative for both hepatitis C and HIV at 12 weeks, 6 months, and 1 year.

What Baseline Knowledge Is Relevant?

▪ DEFINITIONS

See Table 51.1

▪ HISTORIC CONSIDERATIONS

It has long been known that infections can be transmitted in the health care setting. As early as the 1880s, investigators recognized that jaundice was occurring in persons receiving smallpox vaccinations prepared from “human lymph”, and an infectious etiology was suspected. Subsequently, outbreaks of jaundice in those vaccinated with human serum were recognized in the 1930s and 1940s. In 1949, Liebowitz et al. recognized occupationally acquired jaundice in a blood bank nurse who sustained needle pricks to her hands in the performance of her work.¹ Subsequently, multiple similar reports of jaundice in health care workers (HCWs) were published. It was later recognized that viral hepatitis spread through blood and body fluids was the cause of these infections. In the 1980s, another infectious agent spread by blood and other bodily fluids was identified, which caused severe abnormalities of the immune system with subsequent development of unusual infections. This infection became known as the human immunodeficiency virus.

Avoiding exposure to bloodborne pathogens is the primary way to prevent transmission of these infections in health care settings. Over the years, multiple modifications have been made in the way health care is provided, such as the establishment of universal precautions and modifications in needles and other sharps in an attempt to prevent sharps injuries. In addition to these efforts, vaccination against HB and guidelines for management in the event of exposure to bloodborne pathogens are now important parts of workplace safety.

Although most infections from bloodborne pathogens have been transmitted from patient to HCW, sometimes the care provider can serve as the source of infection. Information related to HCWs infected with bloodborne pathogens will also be covered in this chapter.

What Are Universal Precautions?

The Centers for Disease Control (CDC) and Prevention have published extensive recommendations for preventing
transmission of HIV and other bloodborne pathogens such as HB and C.²,³ These precautions are applicable to clinical and laboratory staffs, to workers in health care settings, and in other occupational settings in which exposure to blood or body fluids may occur. The recommendations share the objective of minimizing exposure of personnel to blood and body secretions from infected patients, whether through needle stick injury or through contamination of mucous membranes or open cuts.

TABLE 51.1 Definitions

Viral Hepatitis: An infectious disease transmitted by blood, feces, or other body fluids that affects the liver and leads to abnormalities in liver function; the three main viruses of concern follow:
	HEPATITIS A: A viral infection spread by fecal-oral contact that is typically transient; it is not typically acquired in the hospital setting, and because it is not a bloodborne pathogen, is not a focus of this chapter
	HEPATITIS B AND HEPATITIS C: Infectious agents that can be transmitted in the health care setting through contact with blood and other body fluids; these viruses can cause acute or chronic liver disease and cirrhosis, and can potentially lead to hepatic failure or hepatocellular carcinoma
Human Immunodeficiency Virus (HIV): A viral infection that causes severe immunodeficiency, with subsequent infections and malignancies, that is spread through contact with infected blood or body fluids
Advanced AIDS: A subset of patients with HIV infection will have AIDS; the criteria for AIDS diagnosis is a CD4 count <200 or the presence of certain opportunistic infections or malignancies such as Kaposi sarcoma, toxoplasmosis, cytomegalovirus retinopathy, or colitis
Source: A term used in the event of an exposure to a bloodborne pathogen to indicate the person who was the source of the blood or body fluid
Exposed: A term used in the event of an exposure to a bloodborne pathogen to indicate the person in contact with blood or other potentially infectious material
Antiretroviral Agent: A drug used to treat HIV infection; there are several different classes of drugs used for HIV treatment, and patients are treated with a combination of at least two different classes
Resistance Testing: Testing (genotype or phenotype) done on HIV virus to detect the presence of changes in the virus that would predict drug failure
AIDS, acquired immunodeficiency syndrome.

The CDC recommends enforcement of these precautions, as well as other standard infection control precautions, regardless of whether HCWs or patients are infected with HIV or other bloodborne viruses. The CDC also has taken the position that blood and body fluid precautions should be used consistently for all patients because medical history and physical examination cannot reliably identify all infected patients, and because emergencies may not allow time for serologic testing. If these universal precautions are implemented, no additional precautions should be necessary for patients known to be infected with HIV. Universal precautions include the following standards:

All HCWs should routinely use appropriate barrier precautions to prevent skin or mucous membrane exposure when contact with blood or body fluids is expected. Gloves should be worn for contact with blood, body fluids, or mucous membranes or nonintact skin of all patients. Gloves should be changed and hands washed or cleaned with alcohol-based hand antiseptics between each patient. Masks and protective eyewear should be used during any procedure likely to generate aerosolized droplets of blood or other body fluids. Gowns or aprons should be worn during procedures likely to generate splashes of blood or body fluids.
Hands and other skin surfaces should be washed with soap immediately should contamination with blood or body fluids occur.
All HCWs should take precautions to prevent injuries caused by sharp instruments during and after procedures. To prevent needle stick injuries, needles should not be recapped, bent or broken by hand, removed from disposable syringes, or otherwise manipulated by hand. After they are used, disposable needles or other sharp instruments should be placed in puncture-resistant containers for disposal. The puncture-resistant containers should be located as close as practical to the area of use, and should be disposed of when two thirds full. Large bore, reusable needles should be placed in a puncture-resistant container for transport to the reprocessing area.
Although saliva has not been implicated in HIV transmission, equipment such as mouthpieces, resuscitation bags, or other ventilation devices should be available to use in areas where the need for resuscitation is predictable to minimize the need for emergency mouthto-mouth resuscitation.
HCWs with exudative skin lesions or weeping dermatitis should refrain from direct patient care and should not handle patient care equipment until this condition resolves.

What Are the Relevant Considerations Involving Hepatitis B?

The hepatitis B virus (HBV) is a member of the Hepadnaviridae family of DNA viruses and is most prevalent in the Far East, Middle East, Africa, and parts of South America. In the United States, high-risk groups include intravenous drug abusers, homosexual men, individuals with multiple sexual partners, household contacts and sexual partners of HBV carriers, HCWs, patients on long-term hemodialysis, and organ transplant recipients.⁴

Infection with HBV can have a variable clinical course. It can result in mild infection that resolves
completely, fulminant hepatitis with rapid decompensation and death, or a chronic infection that leads to progressive cirrhosis and eventual liver failure. Chronic HBV infection is also associated with increased lifetime risk for hepatocellular carcinoma. Approximately 55% of adults infected with HBV have no symptoms despite serologic evidence of infection and serve as the main reservoir for continued HBV transmission.

Diagnosis

The serologic markers associated with HBV infection for which there are commercially available assays include HBV DNA by polymerase chain reaction (PCR), HB surface antigen (HBsAg) and antibody to HB surface antigen (anti-HBs), antibody to HB core antigen (anti-HBcAg), HB e antigen (HBeAg), and antibody to HBeAg (anti-HBe).

HBsAg is indicative of infection with HBV, and all persons with confirmed positive HBsAg should be considered infectious. This marker of infection appears an average of 30 days from the time of exposure (range: 6 to 60 days).⁵,⁶ It is possible to detect the presence of HB DNA (HBV DNA) in the serum of an infected person 10 to 20 days before detection of HBsAg.⁷ HBsAg will persist in those patients who become chronically infected with HBV. In those who recover from HBV infection, HBsAg is eliminated from the blood and anti-HBsAg develops. The presence of anti-HBsAg typically indicates immunity from HBV infection and can develop after natural infection or after successful vaccination against HBV. In addition, anti-HBs can be detected for several months after HB immune globulin (HBIG) administration, but will eventually wane, and therefore there will not be indicative of long-standing protection.

HB core antibody develops at the onset of symptoms or biochemical abnormalities in acute HBV infection, and persists for life. The presence of HB core antibody is not necessarily indicative of immunity because it can be present in those with chronic infection.⁸ In most people who recover from natural infection, both anti-HBc and anti-HBsAg will be present, whereas those responding to the HBV vaccine will have only anti-HBsAg. In those who are chronically infected with HBV, HBsAg and anti-HBc will persist.

HBeAg can be detected in the serum of persons with acute or chronic HBV infection and is indicative of high levels of viral replication and increased risk of infectivity.⁹ Anti-HBeAg is associated with lower levels of virus, but it is possible to revert to HBeAg positivity.¹⁰

▪ RISK OF ACQUIRING HEPATITIS B IN THE EVENT OF AN EXPOSURE

The risk of transmission from a single needle stick exposure varies depending on the HBeAg status of the source case. If the source is HBeAg-negative, the risk is approximately 3%. If the source blood is HBeAg-positive, the risk increases 20% to 40%.¹¹,¹² Precise risk estimates for mucocutaneous and other exposures are not available but are presumably lower.

▪ PREVENTION

Passive Immunization

Prophylaxis against HB infection takes two forms. Passive immunization in the form of HBIG provides temporary protection from HBV. It is typically used as an adjunct to HBV vaccination in those with percutaneous or mucous membrane exposure to HB. It is used alone in the event of percutaneous or mucous membrane exposure to HBV in nonresponders to HBV vaccination. Passive prophylaxis with HBIG should begin as soon as possible after exposure—preferably within 24 hours.

Active Immunization

Active immunoprophylaxis against HB infection is achieved by vaccination with HB vaccine. This vaccine uses HBsAg, and immunity from vaccination results in development of anti-HBsAg in the serum at levels >10 mIU per mL. Although there are two types of HB vaccines licensed in the United States—plasma-derived vaccine (Heptavax-B) and recombinant vaccine (Recombivax HB and Engerix-B)—only the recombinant vaccine is commercially available in the United States. In addition, there are combination vaccines against both HBV and hepatitis A virus. Currently available HB vaccines are thimerosal-free because of concerns regarding mercury present in thimerosal-containing vaccines.¹³,¹⁴ For primary vaccination, three intramuscular injections (into the deltoid muscle in adults and children, and into the anterolateral thigh muscle in infants and neonates) are given, with the second and third doses 1 and 6 months after the initial dose.¹⁵

HB vaccine provides virtually complete protection against the acquisition of HBV in persons who develop adequate antibody. Routine testing for immunity after vaccination is not needed in most cases for the general public, but it should be done for HCWS who have direct patient contact or those with risk of needle stick or sharps injury. Postvaccination testing should be done 1 to 2 months after the last dose of vaccine. If the HCW is anti-HBs negative 1 to 2 months after the last dose of vaccine, the complete 3-dose vaccination series should be repeated. Testing for anti-HBs 1 to 2 months after the last dose of vaccine should be repeated. Failure to respond to the second vaccination series indicates that the HCW is a nonresponder to the HB vaccine. In the absence of HBsAg, this worker should be considered susceptible to HBV and should receive HBIG prophylaxis for any known or likely exposure to HBsAg-positive blood. In those that are known to respond to HBV vaccination, there is no need for booster vaccination at a later date. Even if the HBsAg becomes undetectable over time, protection against HBV exists.

In the event of needle stick exposure, knowledge of the vaccination status of the exposed person is important. If the source of the blood is known to be HBsAg-positive, and the person exposed is unvaccinated against HB, treatment with HBIG (one dose) is given and the HB vaccine series is begun. If the source blood is HBsAg-negative, the exposed person should still get the HB vaccine series because he or she may be exposed again in the future, but there is no need for HBIG. If the status of the source is unknown or was not tested, the person exposed should receive the HB vaccine series. If the exposed person was known to have adequate antibody after vaccination against HB, no treatment is needed to prevent HB transmission in the event of sharps injury.

As mentioned earlier, some people do not develop adequate antibody response following vaccination. If percutaneous or mucous membrane exposure to HBV occurs, and the exposed person is a known nonresponder to HB vaccine and has not been revaccinated, that person should receive one dose of HBIG and begin a revaccination series. If the exposed person has already gone through two series of vaccinations but still has not developed adequate antibody response, then two doses of HBIG should be given. Table 51.2 lists recommendations for postexposure prophylaxis after percutaneous or mucosal exposure to HBV in an occupational setting.

TABLE 51.2 Recommendations for Postexposure Prophylaxis after Percutaneous or Mucosal Exposure to Hepatitis B Virus in an Occupational Setting

Vaccination and Antibody Response Status of Exposed Persons^a	Treatment
			Source is Unknown or Not Tested
	Source is HBsAg Positive	Source is HBsAg Negative	High Risk	Low Risk
Unvaccinated	HBIG^b (1 dose) and begin a hepatitis B vaccine series	Begin a hepatitis B vaccine series	Begin a hepatitis B vaccine series	Begin a hepatitis B vaccine series
Known responder^c	No treatment	No treatment	No treatment	No treatment
Nonresponder^c	—	—	—	—
Not revaccinated^d	HBIG (1 dose) and begin a revaccination series	Begin a revaccination series	HBIG (1 dose) and begin a revaccination series	Begin a revaccination series
After revaccination^d	HBIG (2 doses)^e	No treatment	HBIG (2 doses)^e	No treatment
Antibody response unknown	Test for anti-HBs^f	No treatment	Test for anti-HBs^f
	If adequate,^c no treatment		If adequate,^c no treatment
	If inadequate, HBIG × 1 and vaccine booster		If inadequate, give vaccine booster and check anti-HBs in 1 -2 mo
^aPersons known to have had HBV infection in the past or who are chronically infected do not require HBIG or vaccine. ^bHepatitis B immune globulin (0.06 mL/kg) administered IM. ^cAdequate response is anti-HBs of at least 10 mIU/mL after vaccination. ^dRevaccination, additional 3-dose series of hepatitis B vaccine administered after the primary series. ^eFirst dose as soon as possible after exposure and the second dose 1 mo later. ^fTesting should be done as soon as possible after exposure.
HBsAg, HB surface antigen; HBIG, hepatitis B immune globulin.