Cardiac & Resuscitation, Operations, Patient Care, Training

Infection Protection: A review of post-exposure prophylaxis

Issue 9 and Volume 33.

A paramedic is referred to the emergency department (ED) physician for evaluation. He and his partner transported a female patient in labor, who reported having had no prenatal care. En route to the hospital, the mother delivered a healthy term infant, but the paramedic was splashed in the face and eyes with amniotic fluid and maternal blood.

Two paramedics from Medic 11 are referred to the ED physician following an encounter with a combative patient. In attempting to secure the patient, both paramedics were bitten, one on the arm, the other on the hand. Upon arrival at the ED, the patient_s medical record reveals an HIV-positive status.

The primary strategy for preventing infections that result from occupational exposure to contaminated blood and body fluids (BBF) is to prevent exposure. Standard precautions, as defined by the Centers for Disease Control and Prevention (CDC), is a set of guidelines designed to prevent transmission of human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C (HCV) and other bloodborne pathogens when providing first aid or health care.1„

Despite adherence to these standards, occupational exposures continue to occur. This review will present the guidelines for post-exposure prophylaxis (PEP) that have been developed to safeguard health-care providers, with emphasis on prophylaxis of HIV, HBV and HCV.

The principles of standard precautions apply to blood, other body fluids containing visible blood, semen and vaginal secretions during sexual contact, and other potentially infections materials (OPIM). OPIM includes body tissues, cerebrospinal fluid, synovial fluid, pleural fluid, peritoneal fluid, pericardial fluid and amniotic fluid. Standard precautions do not apply to feces, nasal secretions, sputum, sweat, tears, urine or vomitus, unless these fluids contain visible contamination by blood. Nor do standard precautions apply to saliva unless it_s visibly contaminated with blood or is encountered in oral/dental injury.1

Protective barriers, such as aprons, gloves, gowns, masks and shields, may reduce the risk of exposure to skin and mucous membranes. However, no barrier device completely eliminates the risk of exposure to infected BBF, especially for professionals who use needles, scalpels and other sharp instruments. Employing standard precautions is still recommended.

HIV, HBV and HCV infections present the greatest threat to health-care workers.2 This article will focus on the pathophysiology of infection and recommendations for post-exposure management.

HIV Infection & AIDS
HIV_s manifestation of infection is the acquired immune deficiency syndrome (AIDS). The time from initial infection with HIV to clinical disease manifestations of AIDS is highly variable, with a median time of approximately 10 years.3 During that period, an HIV-infected individual may harbor and spread the infection although they demonstrate no signs of infection.„

Primary HIV infection, or acute seroconversion syndrome, occurs two to six weeks following initial exposure to HIV and is described as a non-specific systemic infection characterized by fever, weight loss, pharyngitis, lymphadenopathy, diarrhea, neuropathy and generalized rash. These systemic complaints last for one to three weeks and are most often misdiagnosed as a viral syndrome.4„

Hepatitis Infection
Hepatitis, or inflammation of the liver, occurs from viral infection. Myriad viruses cause hepatic inflammation as part of systemic infection, including but not limited to herpes simplex virus, varicella-zoster virus, yellow fever virus, coxsackievirus and adenovirus. The clinical presentation of hepatitis, however, is virtually indistinguishable; the symptoms associated with hepatitis are similar, whether the infection is caused by one type of virus or another. The symptoms of hepatitis are generally self-limited and resolve spontaneously without residual liver damage, although certain forms of hepatitis can result in chronic infection and irreparable liver injury.

Hepatitis B: HBV is a double-stranded DNA virus transmitted by percutaneous or mucosal exposure to blood or OPIM, usually through IV drug use, sexual contact or vertical transmission from mother to infant during delivery.5 It_s believed that 400 million people worldwide are infected with HBV.6„

Although most individuals infected with HBV develop immunity following infection, a number of individuals ultimately develop chronic hepatitis. The rate of progression to chronic hepatitis B is determined by the age at which the individual is infected with HBV: Some 90% of patients who acquire HBV perinatally develop chronic hepatitis, compared with 20Ï50% of patients who contract it between one and five years of age, and 5% of patients who acquire HBV as adults.7 Of patients with chronic hepatitis, 12Ï20% will develop cirrhosis, 20Ï30% will develop liver failure and 6Ï15% will develop hepatocellular carcinoma.7

Hepatitis C: HCV is believed to infect 4 million people worldwide, 3 million of whom have developed chronic HCV infection. It_s estimated that 150,000 new cases of HCV occur annually in the U.S. HCV may be acquired parenterally, perinatally or sexually, and is associated with transfusion of contaminated blood and blood products, transplantation from HCV-infected donors, and needle-sharing among IV drug abusers.8 Body art (piercing and tattooing) is also associated with the risk of acquiring HCV, HBV and HIV.9

HCV is responsible for approximately 20% of acute hepatitis cases in the„U.S., partly because in many individuals the acute infection goes unnoticed.10 HCV is the most common cause of chronic viral hepatitis and the most common indication for liver transplantation in the„U.S. Some 60Ï80% of individuals who are infected with HCV progress to chronic hepatitis; 20Ï30% of those individuals develop fulminant cirrhosis over two to three decades; and HCV accounts for approximately one-third of the cases of hepatocellular carcinoma diagnosed in the U.S.11

Epidemiology of BBF Exposure
The proportion of source patients infected with bloodborne pathogens varies by geographic setting, type of facility and treatment setting. Although urban areas demonstrate higher HIV seropositivity rates, HIV infection has been documented in all„U.S. states and territories.4 In general, ED patients have higher seroprevalence for HIV, HBV and HCV when compared with patients in other clinical settings. Inner-city EDs demonstrate higher HIV seroprevalence when compared with rates in most other ED settings.12 Seroprevalence of HIV has been cited among ED patients at rates ranging from 3.5Ï11.8%, and research has demonstrated a persistent rise in HIV seroprevalence among ED patients despite attempts to implement universal testing among ED patients.13,14

In a 2000 study, 24% of ED patients were found to be infected with HIV, HBV or HCV.12 The incidence of HBV has declined 90% since the mid-1980s and correlates with the implementation of a national strategy to vaccinate against HBV. The 2006 rate of 1.6 cases per 100,000 individuals was the lowest recorded since HBV surveillance began in 1966. A disproportionate incidence of HBV, however, exists among males aged 25Ï44, particularly among injection drug users, men who have sex with men, and males with multiple sex partners. The decline in HBV among health-care workers is attributable to improved infection control and ongoing vaccination programs.5

The incidence of HCV peaked in the 80s and declined through the 1990s, although it has been at a plateau since 2003, with intravenous drug use remaining the most commonly identified risk factor for HCV infection. Although the number of new cases of acute HCV has declined, the disease burden of chronic hepatitis infection persists.5

Seroconversion Risk
The risk of HIV transmission after percutaneous exposure is approximately 0.3%, and after mucous-membrane exposure, the risk is approximately 0.09%. The risk of HIV transmission after exposure to non-intact skin hasn_t been precisely quantifiedƒonly one case has been documented since 1985ƒbut is estimated to be lower than the risk for mucous-membrane exposure. The risk of HIV transmission following exposure to fluids or tissues other than blood hasn_t been quantified, but it_s considered lower than for blood exposures.15 HIV transmission from health-care workers to patients is an extremely rare phenomenon, so much so that routine screening of health-care workers isn_t considered to be cost-effective and isn_t indicated.16

The risk of HBV transmission is related to the degree of contact with blood and the HBV envelope antigen (HBeAg) status of the source patient. HBeAg and HBV surface antigen (HBsAg) are serum markers for HBV infection, and the risk of developing clinical hepatitis and serologic evidence of HBV infection are 22Ï31% and 37Ï62%, respectively, following exposure to blood positive for both HBeAg and HBsAg. The risk of developing clinical hepatitis and serologic evidence of HBV infection following exposure to HBeAg-negative blood are 1Ï6% and 23Ï37%, respectively.1„

The risk of HCV transmission following accidental percutaneous exposure to HCV is 1.5%, with one study demonstrating transmission only after injury with a hollow-bore needle compared with other sharps.1

The CDC Public Health Guidelines define an exposure that might place the health-care provider at risk for HIV, HBV and HCV„„ as ˙a percutaneous injury (e.g., a needlestick or cut with a sharp object) or contact of mucous membrane or non-intact skin (e.g., exposed skin that_s chapped, abraded or afflicted with dermatitis) with blood, tissue or other body fluids that are potentially infectious.Ó The definitions of health-care personnel and occupational exposures are unchanged from those used in 2001.15„

The Occupational Safety and Health Administration (OSHA) estimates that 600,000Ï800,000 needlestick injuries occur annually in hospitals.16,17 Nurses reported the most frequent number of exposures to HBV, HCV and HIV among health-care workers in-hospital.18„

Although the unique environment and unpredictable nature of conditions place prehospital providers at an increased risk for exposure, seroconversion risk is similar to that of other health-care workers. A 2002 study demonstrated an 8.6% prevalence rate of HBV infection among firefighters, sheriffs_ officers, correctional officers and police officers, although when adjusted for age and race, that was comparable to the overall U.S. prevalence and didn_t vary by occupation.19„

There_s limited data, however, among firefighters and EMS providers with respect to HBV surveillance.20 Because the implementation of standard precautions and HBV vaccination for health-care workers, HBV infections among them is rare, and the incidence of HBV infection among them has been lower than among the general population.21 Further, the prevalence of HCV among EMS providers and public safety personnel doesn_t vary from that of the general population.20,22 There have been no published prevalence rates of HIV/AIDS among firefighters or EMS personnel.4

Vaccination is the most effective measure to prevent HBV infection.21 The HBV vaccine is recommended for adult populations at high risk for HBV infection, especially health-care workers. Other populations for which vaccination is recommended include those who work in environments where they_re exposed to BBF, such as institutions for inmates or mentally challenged people, and individuals who work among high-risk patients, including those on hemodialysis or with hematologic disorders or bleeding abnormalities who are chronic recipients of blood products.23„

For an adult, three injections are required. The seroconversion rate in healthy adults is 90%. Although documentation of immune status isn_t universally recommended, health-care and public safety workers should be tested for post-vaccination anti-HB antibodies within one to two months as mandated by OSHA. Those who don_t respond to the first vaccine series should repeat the three-dose series and should be counseled regarding precautions to prevent infection.24„

Unfortunately, there_s no pre-exposure prophylaxis against HCV or HIV except for avoiding exposure through implementation of standard precautions and avoiding high-risk behavior.„

After exposure, you should immediately wash affected skin with soap and water and flush exposed mucous membrane with copious amounts of water. Eyes should be flushed with water or saline. There_s no evidence to suggest squeezing fluid out of a wound reduces risk of infection.18„

OSHA requires employers to provide a confidential medical evaluation to any exposed worker. The evaluation determines the potential of the exposure to transmit HIV, HBV and HCV. This process involves:

> Collecting information regarding the route of exposure and the circumstances surrounding the incident reported to the designated infection control officer. (See sidebar, opposite.)

> Identifying the source, unless impossible or prohibited by state or local law.

> Testing the source individual_s blood as soon as possible for HBV, HCV and HIV after informed consent is obtained (if consent is required by law). The testing need not be repeated if the source is already known to be infected.

> Communicating test results to the exposed employee.

> Obtaining the exposed employee_s blood as soon as possible for baseline testing and employee_s consent to HIV testing.„

> Administering PEP when medically indicated according to CDC guidelines.

> Providing the employee with a copy of the evaluating health-care professional_s written opinion within 15 days of exposure.26

The evaluation following exposure to BBF at risk for HIV infection includes a risk stratification based on the nature of the injury and probability of HIV transmission. This is done to weigh the risks and benefits of initiating PEP.„

Injuries are considered low risk when they occur through percutaneous injury from a solid-bore needle, when they appear superficial in depth, and when they occur from a low-risk source patient, namely an individual with asymptomatic HIV infection or known low viral load.

Injuries are considered to be high risk when injury occurs from a hollow-bore needle with blood visible on the device or from an exposure to a needle that was in an artery or vein of a source patient.18„„ Mucocutaneous exposures are considered low risk, except in cases of exposure to large volumes of blood from a source patient who has a high viral burden.18„

HIV-positive patients may be classified as class 1 or class 2 depending on their degree of illness. Class 1 patients are asymptomatic or have viral loads < 1,500 copies/mL, and class 2 have symptomatic HIV infection or AIDS, have viral high viral loads, or are in a state of acute seroconversion.„

Following exposure, the health-care worker should be questioned regarding HBV vaccination status; post-immunization titers if known; previous testing for HIV, HBV and HCV; tetanus immunization status; current medications; allergies; baseline bloodwork; and current medical conditions that may influence drug selection for PEP.17

HIV Post-exposure Prophylaxis
Once the risk assessment has been completed, antiviral therapy should be selected; combination therapy is the preferred standard for HIV management. Two-drug therapy is recommended for low-risk exposures.18 The choice of two nucleoside-reverse transcriptase inhibitors (NRTI) or one NRTI and one nucleotide reverse transcriptase inhibitor (NtRTI) is acceptable.15 For high-risk exposures, three-drug therapy with two NRTIs and a protease inhibitor (PI) is recommended.18

Initiating therapy with a three-drug regimen of zidovudine, lamivudine and efavirenz is the optimal choice, because in studies it demonstrated a longer time to first regimen failure and a shorter time to viral suppression.27, 28 The public health guidelines note that the addition of a third or fourth agent, although based on demonstrated effectiveness in reducing viral burden in HIV infected persons, had no definitive data to support its use.15„

The current recommendation for PEP initiation is within one to two hours following exposure, and the recommended duration of therapy is four weeks.18 Three-day starter packs are routinely prescribed while relevant data are pending, and rapid HIV testing of source patients may eliminate the need for PEP if they are HIV negative and testing doesn_t delay initiation of PEP by more than two hours.18 Exposed health-care workers often don_t complete the recommended four-week course due to side effects.15 The most common symptoms are nausea, malaise, fatigue, diarrhea, vomiting and headache.„

HBV Post-exposure Prophylaxis
PEP is determined not only by the infection risk from the exposure, but also by the immunization status of the exposed person.23„

Unvaccinated: Administer one dose of hepatitis B immune globulin (HBIG) and initiate the vaccine series if the source is positive for HBsAg. HBIG is administered in a dose of 0.06 mL/kg via intramuscular injection and should be given within 24 hours following the exposure.17 If the source patient tests negative, initiate the vaccine series but don_t give HBIG. For unknown sources, initiate the vaccine series. Those in the process of receiving but who haven_t completed the vaccine series should also receive HBIG when indicated.

Vaccinated, known responders: No treatment is needed regardless of the infection status of the source patient.

Vaccinated, known non-responders: If the source patient is HBsAg positive and the exposed person hasn_t completed a second vaccine series, give one dose of HBIG and reinitiate the vaccine series. If the person has previously failed to respond to two vaccine series, give two doses of HBIG, one dose at the time of exposure and the second dose one month later. No treatment is indicated for non-responders exposed to an HBsAg-negative source. For an unknown high-risk source, treat as though HBsAg positive.

Unknown antibody response: If the source patient is HBsAg positive, test the exposed person for anti-HBV antibodies. If the response is adequate, no treatment is needed. If response is inadequate, give HBIG and vaccine booster. No treatment is needed if the source is HBsAg negative. If the source is unknown, no treatment is needed if the antibody response is adequate. If the antibody response is inadequate, administer a booster vaccine and recheck the titer in one to two months.

HCV Post-Exposure Management
There_s no means of preventing HCV infection except for avoidance of high-risk behavior and exposure through standard precautions. Immunoglobulin therapy hasn_t demonstrated prevention of HCV transmission and isn_t approved for PEP. Antiviral therapy with interferon with or without ribavirin hasn_t been studied as PEP and isn_t approved for this indication.25„

People exposed to an HCV-positive source should demonstrate baseline HCV RNA, anti-HCV, and alanine aminotransferase levels at one and six months. Such monitoring allows for early recognition of acute infection. Some studies have shown that early treatment during acute infection with peginterferon with or without ribavirin for 24 weeks results in resolution of disease and loss of the HCV RNA in 90% of patients. This treatment may be delayed two to three months after onset of infection.

Prehospital health-care providers perform their duties in unique and unpredictable environments. The nature of their work routinely exposes them to blood and body fluids.„

Standard precautions and pre-exposure prophylaxis, namely the HBV vaccination, have greatly reduced the transmission of bloodborne pathogens. Exposures to HIV- and HCV-infected individuals create special cases for health-care workers because there_s no approved regimen of pre-exposure prophylaxis.„

Once an exposure occurs, expeditious evaluation and management are the keys to reducing the likelihood of transmission. PEP of HBV and HIV infection exists, and it_s recommended that health-care workers be evaluated and have treatment initiated as soon as possible following exposure. JEMS

Timothy Rupp, MD, FACEP, FAAEM, is the former associate director of the emergency medicine residency training program at the University of Texas Southwestern Medical Center at„Dallas. He_s a staff emergency physician at Methodist Health System in„Dallas, Children_s„Medical„Center in„Dallas and„Centennial„Medical„Center in„Frisco,„Texas. Contact him at[email protected]

Katherine Christensen, MD, attended medical school at„Thomas„Jefferson„University in„Philadelphia,„Pa., and recently completed residency training in emergency medicine at the University of Texas Southwestern Medical Center at„Dallas.

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11. Chopra S: ˙Hepatitis G virus

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15. Panlilio AL, Cardo DM, Grohskopf LA, et al: ˙Updated„U.S. public health service guidelines for the management of occupational exposures to HIV and recommendations for post-exposure prophylaxis.Ó MMWR. 54(RR 11):1Ï17, 2005.

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23. Yu AS, Cheung RC, Keeffe EB: ˙Hepatitis B vaccines.Ó Infectious Disease Clinics of„North America. 20(1):27Ï45, 2006.

24. Teo EK, Lok ASF: ˙Epidemiology, transmission, and prevention of hepatitis B virus infection.Ó

25. Centers for Disease Control and Prevention: ˙Updated„U.S. Public Health Service Guidelines for the Management of Occupational Exposures to HBV, HCV, and HIV and Recommendations for Post-exposure Prophylaxis.Ó MMWR. 50(RR 11):1Ï42, 2001.

26. National Institute for Occupational Safety and Health. What Every Worker Should Know: How to Protect Yourself From Needlestick Injuries. NIOSH Publication No.

27. Shafer RW, Smeaton LM, Robbins GK: ˙Comparison of four-drug regimens and pairs of sequential three-drug regimens as initial therapy for HIV-1 infection.Ó„New England Journal of Medicine. 349(24):2304Ï2315, 2003.

28. Robbins GK, De Gruttola V, Shafer RW: ˙Comparison of sequential three-drug regimens as initial therapy for HIV-1 infection.Ó New England Journal of Medicine. 349(24):2293Ï2303, 2003.