Hospital Infection Control

Antivirals (non-HIV drugs)

What is the impact of the specific agents (antibiotics or vaccines) in the prevention and control of health care-associated infections?

Influenza

Annual immunization of high-risk individuals and their contacts/caregivers, including health care workers, is the single most important measure for preventing hospital acquired influenza infection. Immunization is effective in decreasing virus transmission from infected individuals to contacts and reducing the number of institutional outbreaks in the long-term care and nursing home settings. Vaccination also substantially reduces influenza-related hospitalizations, complications and mortality in both elderly and high-risk patients.

Antiviral agents are the most effective means for containing and terminating influenza outbreaks within both acute care hospitals and long term/chronic care facilities. They are also effective in preventing influenza illness but not generally recommended for chemoprophylaxis due to increasing treatment resistance. However, antiviral chemoprophylaxis is an appropriate alternative to immunization in high-risk patients with vaccine contraindications and patients that may not develop an adequate protective antibody response.

RSV

Hand decontamination is the most important means of preventing health care-associated RSV infection. However, passive immunoprophylaxis with palivizumab is also effective in reducing the incidence of RSV infection in health care institutions. Prophylaxis of infants and children with prematurity, chronic lung disease or congenital heart disease is associated with a reduction (39-78%) in RSV-related hospitalization rates. Immunoprophylaxis has no effect on mortality rates of the development of subsequent reactive airway disease or asthma.

Limited information exists regarding the management of RSV outbreaks in health care institutions. In adult immunocompromised patients, treatment of infected individuals with aerosolized ribavirin effectively controls RSV outbreaks when used in conjunction with strict infection control practices. Treatment of infants with ribavirin has also been shown to reduce the duration and titers of viral shedding which could have important implications for control of nosocomial outbreaks. However, use of ribavirin is highly controversial and not generally recommended due to the cost, requirement for aerosolized administration, potential toxicity to exposed persons and questionable clinical significance and long-term importance of any apparent clinical benefits.

Limited data suggests that palivizumab may be useful in controlling nosocomial RSV outbreaks and preventing virus spread in neonatal intensive care and adult stem cell transplant units. Palivizumab may also reduce the duration of viral shedding. However, the utility of palivizumab in controlling institutional outbreaks is limited by its significant cost and its use for this indication is not currently recommended.

Hepatitis

Avoidance of exposures is the primary means of preventing health care-associated hepatitis A (HAV), B (HBV) and C (HCV) virus infections. By reducing the number of infected individuals and providing active immunity, however, vaccination is also highly effective in preventing transmission of HAV and HBV in health care facilities. Passive immunization with immune globulin similarly confers protection against hepatitis A although routine HAV vaccination or pre-exposure prophylaxis is not currently recommended for health care workers. Currently, there is no vaccine available for hepatitis C.

Hepatitis A and B vaccines confer a high rate of immunity in healthy children, adolescents and adults with over 90% of individuals developing protective antibody levels. Protective efficacy of the hepatitis A and B vaccines range from 94-100% and 80-100%, respectively. Administration of a combined hepatitis A and B vaccine offers safety and immunogenicity equivalent to that of separate vaccines.

As a consequence of recommended and/or required universal vaccination strategies in children (HAV and HBV) and health care workers (HBV), the numbers of individuals infected with HAV and HBV have decreased by approximately 75% over the last two decades. Routine vaccination of health care workers against hepatitis B has also significantly reduced the risk of patient to staff transmission of HBV.

Post-exposure prophylaxis with immune globulin and hepatitis B immune globulin (HBIG) are useful adjuncts in preventing HAV and HBV infections, respectively. When administered within 2 weeks of an exposure, immune globulin is 80-90% effective in preventing HAV and is recommended for persons who have close contact with infected individuals during documented hepatitis A outbreaks. Similarly, multiple doses of HBIG initiated within 1 week of exposure to hepatitis B surface antigen (HBsAg)-positive blood provides an estimated 75% protection from HBV infection in previously unvaccinated individuals. No protective antibody response has been observed with immune globulin following HCV exposure and antiviral agents are not recommended as post-exposure prophylaxis for HCV.

Hepatitis B vaccination is also effective as post-exposure prophylaxis against HBV. While limited data suggest that the hepatitis A vaccine might also be effective as post-exposure prophylaxis, it is not currently recommended for this indication. The usefulness of vaccination in controlling institutional outbreaks of HAV and HBV has also not been investigated.

Varicella

Vaccination is the most effective means of preventing and controlling health care associated varicella infections. The live attenuated varicella vaccine is highly immunogenic and provides approximately 70% protection against infection and 95% protection against severe disease. Institution of vaccination programs in the United States has dramatically reduced the incidence of varicella infections (57-90%), hospitalizations (75-88%) and deaths (> 74%). Vaccination has also been used successfully by state and local health departments and the military for prevention and control of varicella outbreaks and is recommended by the Advisory Committee on Immunization Practices (ACIP) for all individuals without evidence of immunity to limit disease transmission and susceptibility to subsequent exposures.

In patients with contraindications to the varicella vaccine, varicella zoster immune globulin (VZIG) is also effective as post-exposure prophylaxis although it is only available as an investigational drug product that requires informed consent prior to administration. Acyclovir has also demonstrated efficacy as post-exposure prophylaxis. Although use of acyclovir may be less costly and cumbersome than VZIG, additional data concerning its efficacy as post-exposure prophylaxis are required before such use can be recommended.

Which vaccine preparation or treatment stands out as contributing in a major way in the prevention and control for health care-associated infections?

Influenza

Influenza vaccination is the most effective means of protecting susceptible individuals and decreasing viral transmission within health care institutions. In the limited number of direct comparisons between the trivalent inactivated vaccine (TIV) and the live-attenuated influenza vaccine (LAIV) preparations, there is no apparent difference in protective efficacy in healthy young adults. In healthy infants and young children (6-59 months), however, current data suggest the LAIV is more effective than TIV.

RSV

Palivizumab is most the significant advancement to date in RSV pharmacotherapy. The primary benefit of palivizumab immunoprophylaxis is a decrease in the rate of RSV-associated hospitalization in patients at highest risk for severe RSV infection.

Hepatitis

The hepatitis B vaccine stands apart as the most significant contributor to the prevention and control of health care associated hepatitis infections over the last two decades. Before the widespread vaccination of health care workers, the prevalence of hepatitis B markers in this group was two- to three-fold higher than in the general population. Institution of a comprehensive immunization strategy to eliminate hepatitis B transmission, which included required vaccination (or declination) of health care workers, was highly successful in reducing HBV infection rates with a 95% decline in the incidence of hepatitis B infection among health care workers from 1983 to 1995.

Varicella

Immunization with the live attenuated varicella vaccine has had the greatest impact on preventing and controlling varicella infections in the health care setting. The varicella vaccination program in the United States has dramatically reduced the incidence of varicella and related complications, hospitalizations and deaths. Prevention of illness through comprehensive vaccination of personnel without evidence of immunity to varicella is also far more cost effective than case management and outbreak control.

Which are the vaccines or treatments used to prevent and control the infections, and what are key distinguishing features?

Influenza

A. Vaccines

There are two types of influenza vaccine: trivalent inactivated influenza vaccine (TIV) and live attenuated influenza vaccine (LAIV).Both TIV and LAIV are grown in chicken eggs and contain strains of influenza viruses that are antigenically equivalent to the annually recommended strains (one influenza A (H3N2), one influenza (H1N1) and one influenza B). TIV contains inactive viruses, cannot cause influenza, is administered intramuscularly and is licensed for use in healthy and high-risk patients > 6 months of age. In contrast, LAIV contains live attenuated viruses, is administered intranasally, is licensed for use in non-pregnant individuals ages 2 to 49 years and has the potential to cause mild signs and symptoms related to vaccine virus infection. It should therefore not be used in young children (< 2 years) or in high-risk individuals.

B. Antiviral agents

The neuraminidase inhibitors, oseltamivir (TamifluÒ) and zanamivir (RelenzaÒ) are the predominant antivirals used for chemoprophylaxis and control of influenza outbreaks. Both agents are work by preventing release of new virus particles through inhibition of viral neuraminidase and are active against influenza A and B. Oseltamivir is orally administered and is licensed for treatment and chemoprophylaxis in children > 1 year. Zanamivir has very poor oral bioavailability requiring administration via inhalation and is contraindicated in individuals with underlying respiratory disease. Given that it is administered via a disk inhaler, zanamivir cannot be used in young children who cannot actuate the inhalation.

Depending on the local resistance patterns of circulating influenza viruses within a given season, the adamantanes may also be used for influenza treatment and/or chemoprophylaxis. The adamantanes (amantadine and rimantadine) are M2 ion channel blockers and are thought to interfere with viral uncoating within the cell. They are active against influenza A but not influenza B. Both agents are equally effective in preventing and controlling influenza outbreaks but their use is limited by rapid resistance that develops during treatment. Both agents also cause central nervous system side effects but these effects are more pronounced with amantadine.

RSV

A. Monoclonal Anti-RSV antibodies

Palivizumab (SynagisÒ) is a humanized monoclonal antibody directed against the F glycoprotein of RSV. Antibody binding to the F protein prevents cellular infection by preventing the viral membrane from fusing with the respiratory epithelial cell membrane. It also prevents cell-to-cell spread of the virus, which, in turn, prevents formation of syncitia and release of inflammatory mediators in the lung. Palivizumab is effective in reducing hospitalization due to RSV infection in high-risk patients. Immediate administration of palivizumab may also have a therapeutic effect by reducing the duration of virus shedding although it is not currently approved or recommended for this indication.

B. Antiviral Agents

Ribavirin (VirazoleÒ), a nucleoside analog, is the only antiviral agent currently approved for treating RSV infection. However, its use remains controversial due to the marginal benefit, if any, for most patients. Cumbersome delivery requirements, potential health risks for caregivers and high costs are additional disincentives for its clinical use. Although ribavirin be considered for use in highly selected situations involving documented RSV with severe disease or in those who are at high risk for severe disease (immunocompromised and/or hemodynamically significant cardiopulmonary disease), its use is generally not recommended.

Hepatitis

A. Hepatitis A Vaccine

There are two hepatitis A vaccines currently available: HAVRIXÒ and VAQTAÒ. Both are inactivated vaccines and are highly effective in preventing clinical hepatitis A infection in adults (94-100%) and children (97-100%). They can also be used in children as young as 12 months of age, should be administered via intramuscular injection and are considered interchangeable. Both preparations are available in two formulations (one pediatric and one adult) and should be administered in a 2-dose schedule with the second dose administered 6-18 months after the first for VAQTAÒ and 6-12 months after the first for HAVRIXÒ. Hepatitis A vaccination is not routinely indicated for health care workers but is recommended for all children > 1 year of age.

B. Hepatitis B Vaccine

There are two single antigen hepatitis B vaccines currently available: Recombivax HBÒ and Engerix-BÒ. Both of these agents are produced via expression and purification of hepatitis B surface antigen (HBsAg) in yeast using recombinant DNA technology. Hepatitis B vaccine is also available in fixed combination with other vaccines: hepatitis A (TwinrixÒ), diphtheria and tetanus toxoids and acellular pertussis adsorbed (DtaP) and inactivated poliovirus (IPV) (PediarixÒ) and Haemophilus influenzae type B (Hib) polyribosylribitol phosphate conjugated to Neisseria meningitidis outer membrane protein complex (ComvaxÒ).Immunogenicity of the combined vaccines is equivalent to that of the individual antigens administered separately. In general, vaccine efficacy is typically 95% with a reported range of 80-100%.

C. Hepatitis B Immune Globulin (HBIG)

Hepatitis B Immune Globulin (HBIG) provides passively acquired antibodies to hepatitis B surface antigen (HBsAg) and temporary protection (3-6 months) when used in standard doses. The major determinant of HBIG effectiveness is the timing of administration following exposure and when initiated > 7 days after exposure the efficacy of HBIG is unknown. There are several different HIBIG currently available but all are prepared from the plasma of donors with high concentrations of anti-HBs and do not contain thimerosal. They may all be administered simultaneously with hepatitis B vaccine but must be given in a different injection site. Serious adverse effects with HBIG are rare and are reported no more frequently than with placebo.

D. Immune Globulin

Immune globulin is a sterile preparation of concentrated antibodies made from pooled human plasma that provides short-term protection (3-5 months) against hepatitis A via passive transfer of antibodies. When administered within 2 weeks of an exposure, immune globulin is 80-90% effective in preventing HAV and is recommended for persons who have close contact with infected individuals during documented hepatitis A outbreaks. Immune globulin should be administered as a single intramuscular dose (0.02 mL/kg) within 2 weeks of virus exposure. Serious adverse reactions to immune globulin are rare although anaphylaxis has been reported after repeated administration to persons with known IgA deficiency and it is contraindicated in this patient population.

Varicella

A. Varicella Zoster Vaccine

The varicella zoster vaccine is a live attenuated virus (Oka strain) vaccine licensed in 1995 for use in individuals > 12 months of age. It is available as a monovalent vaccine (VarivaxÒ) and in combination with the MMR vaccine (ProQuadÒ). Antibody concentrations achieved after administration of the combination product are comparable to those achieved with either vaccine alone. However, the combination vaccine is only licensed for use in children ages 12 months to 12 years and has had limited availability over the last few years due to manufacturing constraints. The Advisory Committee on Immunization Practices (ACIP) recommends a universal 2-dose administration schedule for children and for all health care workers without documented immunity to varicella. Vaccination is also recommended as post-exposure prophylaxis in susceptible individuals.

B. Varicella Zoster Immune Globulin (VZIG)

Varicella immune globulin (VGIZ) is a purified human immune globulin preparation made from human plasma containing high levels of anti-varicella antibodies. In 2004, the only US licensed manufacturer of varicella zoster immune globulin discontinued production of the product and an investigational (not licensed) VZIG product (VariZIGÒ) became available under an investigational new drug application (IND) in 2006. This product can be requested from the sole authorized US distributor for susceptible individuals who have been exposed to varicella and are either at increased risk for severe disease and complications or have contraindications to vaccination (pregnant and immunocompromised individuals). Administration of this investigational product requires informed consent from the patient prior to administration. Routine post-exposure use of VZIG in immunocompetent health care personnel is not recommended given that it can be costly, does not necessarily prevent varicella and may prolong the incubation period by > 1 week thus extending the time health care personnel may be infectious.

Available agents and their features, efficacy and safety.

Influenza

A. Vaccines (Table I)

Table I

B. Antiviral Agents (Table II)

Table II

RSV

Palivizumab is the only agent that is currently indicated for the prevention of RSV infection in high-risk infants (prematurity, chronic lung disease, hemodynamically significant congenital heart disease). It is administered via intramuscular injection on a monthly basis prior to and during the RSV season. Specific guidelines regarding the duration of palivizumab prophylaxis have been published by the American Academy of Pediatrics. Palivizumab is generally well tolerated and is effective and in reducing the incidence of RSV-related hospitalizations in high-risk infants. However, the cost of prophylaxis is extremely high (~ $6,000 per patient for a single RSV season).This agent is currently not recommended for treatment of RSV infection.

Ribavirin is the only antiviral agent approved for treatment of RSV bronchiolitis and pneumonia. This agent must be administered via the aerosolized route using a specialized small particle aerosol generator (SPAG) unit and can be highly toxic to health care workers administering the medication, particularly those who are pregnant (FDA pregnancy category X). Ribavirin has failed to show consistent beneficial effects on duration of hospitalization, need for ventilatory support, mortality or long term pulmonary function and its use is discouraged except in certain specialized situations (i.e., patients with documented RSV who are at high risk for severe disease).

Hepatitis

See answers to previous question

Varicella

A. Varicella Zoster Vaccine: The live attenuated varicella vaccine provides 70-90% protection against infection and 95% protection against severe disease for 7-10 years after administration. Effective vaccination requires 2 doses to achieve high seroconversion rates. Vaccination is also effective in preventing illness or modifying disease severity if administered within 3-5 days of exposure to rash. Studies have shown that vaccination administered within 3 days of exposure to rash is > 90% effective in preventing varicella while vaccination within 5 days of exposure to rash is approximately 70% effective in preventing varicella and 100% effective in modifying disease severity. Varicella vaccine is generally well tolerated with rash being the most frequently reported adverse event.

B. Varicella Zoster Immune Globulin (VZIG): Varicella zoster immune globulin (VZIG) is effective in preventing clinical varicella in susceptible patients and provides maximum benefit when administered as soon as possible after exposure. The attack rate among immunocompromised children administered VZIG is significantly lower following household exposure that in healthy household contacts not treated with VZIG (33-50% vs. 90%). It is unknown whether treatment more than 96 hours after exposure is of any benefit. VZIG is well tolerated with the most frequently reported adverse reaction following VZIG administration being local discomfort at the injection site.

Summary of available agents with important PK/PD data, dosing information for prevention versus treatment, drug-drug interactions and adverse reactions.

Influenza

A. Vaccines (Table III)

Table III

B. Antiviral agents (Table IV) RSV (Table V)

Table IV

Table V

Hepatitis (Table VI)

Table VI

Varicella (Table VII)

Table VII

Drugs in development.

Influenza

A. Vaccines

Cell-Based Vaccines: Mammalian cell cultures are a viable alternative system for vaccine production and a cell-culture based live attenuated vaccine is currently in late stage clinical development. Since the viruses are not inactivated and are only minimally purified, however, studies to assess residual cell-substrate DNA are needed before they can progress to clinical testing.

Adjuvants: Adjuvants, which amplify the immune response to antigen, are also being evaluated in clinical testing. Several hemagglutinin-based seasonal influenza vaccines with adjuvants (phospholipids, oil-in-water emulsions) have been approved and used in Europe although they have been viewed with some reservation in the US. Purified bacterial outer-membrane proteins, toll-like receptors and a variety of toll-like receptor agonists have also shown promise as next-generation adjuvants.

Novel Live Attenuated Vaccines: Early clinical data suggest that an intranasal live attenuated vaccines based on the influenza NS1 protein, which is involved in viral replication and inhibition of the host innate immune response, is well tolerated and generates neutralizing hemagglutinin antibodies.

Recombinant Vaccines: A recombinant, trivalent hemagglutinin protein-based influenza vaccine is currently in the late stages of clinical development. The safety, immunogenicity and efficacy profile of this vaccine has been reported and an application has been submitted to the FDA for its approval for use against seasonal influenza in healthy individuals > 18 years.

Use of non-infectious virus-like particles is another potential approach to vaccine production and multiple virus-like particle candidates have shown promise in animal studies. At least one of these candidates has progressed to phase 2 clinical trials. Viral vectors that are incapable of replicating or that replicate but are incapable of causing disease are also being evaluated as new ways of delivering influenza virus proteins to the immune system. Early clinical trials evaluating the safety and immunogenicity of intranasal and orally administered adenovirus-based hemagglutinin vaccines have been completed and/or are in progress with promising results. DNA-based vaccines may also be another potential strategy although clinical trials to date have not been encouraging.

B. Antiviral Agents

Parenteral neuraminidase inhibitors: An intravenous formulation of zanamivir has been evaluated in Phase 2a clinical testing and has demonstrated protective efficacy against experimental infection in healthy volunteers. The novel neuraminidase inhibitor, peramivir, is also currently in Phase 2 clinical trials for both intravenous and intramuscular routes of administration and data to date with this agent appear promising.

Long acting neuraminidase inhibitors: CS-8958, a long-acting, inhaled neuraminidase inhibitors has shown good activity in murine models of influenza treatment with once weekly dosing. A single inhaled dose was recently shown to be as effective as a standard 5-day course of oseltamivir in the treatment of uncomplicated influenza.

Polymerase Inhibitors: T-705 is an inhibitor of viral RNA polymerase and is active against all 3 influenza virus types. Preclinical data suggest that this agent is less toxic than ribavirin and is active in murine models of influenza A. Phase 2 PK, safety and efficacy studies in are ongoing.

Attachment Inhibitors: DAS181 (Fludase) is a sialidase catalytic domain/amphiregulin glycosaminoglycan binding sequence fusion protein. The sialidase catalytic domain selectively cleaves sialic acids from host cells thereby rendering them inaccessible to influenza virus particles. DAS181 has in vitro and preclinical activity against numerous seasonal influenza strains. In Phase 1 clinical studies, this agent was generally well tolerated with no severe adverse events noted. Phase 2 studies are currently ongoing.

RSV

Polyclonal antibodies: A new candidate hyperimmune IVIG product, RI-001, is currently being evaluated in phase II clinical trials in immunosuppressed, RSV-infected patients at risk for lower respiratory tract illness.

Monoclonal anti-RSV antibodies: Motavizumab (MEDI-524) is a new, enhanced potency humanized RSV monoclonal antibody derived from palivizumab that is currently pending FDA approval. This agent has a similar pharmacokinetic and safety profile to palivizumab but is 20-100 more active against RSV and is active in both the upper and lower airways. In a large, phase III non-inferiority study comparing motavizumab to palivizumab for RSV prevention in high-risk children, motavizumab demonstrated 26% fewer RSV hospitalizations and a 50% reduction in the incidence of RSV-specific outpatient lower respiratory tract infections. Motavizumab also significantly reduced viral load by 1 day after treatment in children hospitalized with RSV suggesting that it may be beneficial for both treatment and prevention.

Vaccines: MEDI-559, a recombinant vaccine, is the first and only vaccine candidate to be tested in the target infant population since the 1960s.The immunogenecity of MEDI-559 among infants is currently being evaluated in ongoing clinical trials.

Novel Antiviral Compounds: RSV-604 is a novel benzodiazepine that targets the RSV N protein and is thought to work by inhibiting viral RNA polymerase.RSV-604 displays submicromolar activity against many clinical isolates of A and B RSV antigenic subgroups and, unlike many fusion protein inhibitors, is active when administered after infection. It has also been shown to significantly reduce viral spread in vitro when given up to 24 hours after infection and is currently being evaluated in phase II clinical trials.

Small Interfering RNAs (siRNAs): ALN-RSV01 is an siRNA directed against the mRNA encoding the RSV nucleoprotein that has received a great deal of attention for its innovative mechanism of action and promising preliminary clinical data. In phase II studies, intranasal ALN-RSV01 demonstrated a 38% reduction in RSV infection when administered to healthy volunteers 2 days prior to and 3 days after viral inoculation. This agent was also found to be safe and well tolerated. Additional clinical studies with ALN-RSV01 are currently ongoing.

Hepatitis

Hepatitis B Vaccines: Several novel hepatitis B vaccines are currently under investigation. DNA vaccines, which can be administered intrasanally or intramuscularly, have been shown to induce vigorous immune responses in experimental animals and non-human primates. Small scale studies in selected groups have also taken place, although none of the candidate agents have progressed substantially through clinical development. Another promising approach is to express hepatitis B surface antigen (HBsAg) in plants and deliver them orally. In small-scale clinical studies, delivery of the antigen in the form of edible plant material from a variety of sources indicates both safety and immunogenicity of this approach although further investigation is needed.

Hepatitis C Vaccines: Development of hepatitis C vaccines has proven to be quite challenging although several approaches, including recombinant proteins, peptides, viruslike particles, naked DNA and recombinant viruses are currently being explored. All candidates are in currently the pre-clinical stages of investigation and, to date, none have progressed to human clinical trials.

Varicella

Several new technologies are being explored in the design of a potential new varicella vaccine including recombinant-derived proteins, live vectors and DNA vaccines. To date, however, none of these technologies have produced a product that has progressed to clinical trials in humans.

Current controversies about key agents.

Influenza

In an effort to improve compliance with immunization among health care workers it has been proposed that vaccination should be mandatory for all such individuals although this proposal remains controversial.

With respect to vaccines, the LAIV preparations offer improved ease of administration and potentially improved compliance since an injection is not required. However, use of this agent is limited to only certain patient populations. The TIV can be used in a wider range of patients although it does require IM administration.

The neuraminidase inhibitors have significant advantages over the adamantanes including an improved side effect profile and reduced propensity to cause resistance. However, amantidine is the only antiviral agent that does not rely on hepatic metabolism for elimination and it therefore may be a better choice in patients with hepatic insufficiency if the locally circulating viral strains are susceptible.

RSV

Ribavirin treatment for RSV infections is highly controversial because of the cost, need for aerosol administration, concern for potential toxicity of exposed persons, and questionable clinical significance and long-term importance of any apparent clinical benefits of therapy.

The biggest controversy associated with palivizumab immunoprophylaxis is the cost. A single dose of palivizumab costs about as much as the total cost of all vaccines received by one child from birth through 18 years of age. Economic analyses indicate that the increased cost associated with palivizumab prophylaxis far exceeds the cost savings from reduced hospitalizations. Furthermore, the increased costs are not offset by a reduction in mortality rates given that none of the trials to date have demonstrated a statistically significant reduction in mortality rates. Current guidelines are therefore targeted at providing immunoprophylaxis only to the infants who are most likely to experience severe RSV disease.

Hepatitis

All of these agents are effective in protecting against infection with and transmission of hepatitis viruses and there are no cons for any of these prophylactic agents.

Varicella

No significant controversies identified.

Are there specific guidelines for the use of some or all of these agents?

Influenza: The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) and the American Academy of Pediatrics publish annual guidelines regarding the prevention and control of influenza with vaccines. The CDC also publishes annual guidelines on the use of antiviral agents for chemoprophylaxis and treatment. Guidelines for the management of institutional outbreaks of influenza have been developed by the Infectious Disease Society of America (IDSA).

RSV: The American Academy of Pediatrics has published guidelines regarding the use of palivizumab for RSV prophylaxis and ribavirin for the treatment of RSV bronchiolitis. There are currently no guidelines available for the control of institutional RSV outbreaks.

Hepatitis: Guidelines for the prevention of hepatitis virus infection are available from the CDC Advisory Committee on Immunization Practices and the American Academy of Pediatrics.

Varicella: National guidelines for immunization of and post-exposure prophylaxis for health care personnel are provided by the U.S. Public Health Service’s Advisory Committee on Immunization Practices (ACIP).Guidelines for varicella outbreak investigation and control are also available from the National Immunization Program (NIP) of the CDC.

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Hepatitis

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"Centers for Disease Control and Prevention. Prevention of hepatitis A through active or passive immunization. Recommendations of the Advisory Committee on Immunization Practices". MMWR Morbid Mortal Wkly Rep. vol. 55. 2006. pp. 1-23.

Varicella

Bolyard, EA, Tablan, OC, Williams, WW, Pearson, ML, Shapiro, CN, Deitchmann, SD. "Guideline for infection control in healthcare personnel, 1998. Hospital Infection Control Practices Advisory Committee". Infect Control Hosp Epidemiol. vol. 19. 1998. pp. 407-63.

"CDC. A new product (VariZIG) for postexposure prophylaxis of varicella available under an investigational new drug application expanded access protocol". MMWR. vol. 55. 2006. pp. 209-10.

"CDC. Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP)". MMWR. vol. 45. 1996. pp. 1-25.

"CDC. Prevention of varicella: updated recommendations of the Advisory Committee on Immunization Practices (ACIP)". MMWR. vol. 48. 1999. pp. 1-5.

"National Center for Immunization and Respiratory Diseases. Centers for Disease Control and Prevention". Strategies for the control and investigation of varicella outbreaks. 2008.

"Centers for Disease Control. Immunization of Health Care Workers. Recommendations of the Advisory Committee on Immunization Practices (ACIP) and the Hospital Infection Control Practices Advisory Committee (HICPAC)". MMWR. vol. 46. 1997. pp. 1-35.

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