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Update on Emerging Infections from the Centers for Disease Control and Prevention
CDC U P D A T E
U p d a t e on Emerging Infections From the Centers for Disease Control and Prevention Influenza: ED Considerations for the 1997-98 Season
Guy L Merchant William R Mower, MS, MD David A Talan, MD Section Editors
David A Talan, MD GregoryJ Moran, MD Olive View-UCIA Medical Center 5ylmar, CA
Editors'note: Thisarticle is part of a regular series on emerging infections from the Centers for Disease Control and Prevention (CDC)and the EMERGEncyID NET, an ED-based, CDCcollaborative surveillance network. Important public health information on infectious disease with relevance to emergencyphysicians is reported. The goal of this series is to advance knowledge about communicable diseases in emergency medicine and foster cooperation between the front line of clinical medicine and public health agencies.
Robert W Pinner, MD Centers for Disease Control and Prevention Atlanta, CA
Influenza: ED Considerations for the 1997-98 Season [Merchant GL, Mower WR, Talan DA: Influenza: ED considerations for the 1997-98 season. Ann Emerg Med November 1997;30:692-694.] Influenza is a seasonal malady, commonly perceived as relatively benign and self limited, for which the threat to public health is frequently underestimated. Annual outbreaks and occasional pandemics of influenza present a major source of morbidity and mortality, with approximately 20,000 deaths and $1 to 12 billion in health care costs in the US annuallyF.2 The purpose of this article is to review the current epidemiology, vaccine composition, and prevention and treatment strategies relevant for emergency practice. Influenza is caused by one of two distinct virus types, A and B. Influenza A, subtyped on the basis of the surface antigens hemagglutinin (H) and neuraminidase (N), is less antigenically stable, with a propensity for surface-antigen variations that can result in the production of
692
new strains. Influenza B has been responsible for approximately 20% of outbreaks,3 and the illness is often less severe. Nevertheless, influenza B was the main circulating strain in the United States in 1990-91 and 1992-93, found in about three quarters of isolates tested. In 1996-97, influenza A was the predominant strain, with 81% of isolates. However, influenza B activity began increasing late in the season and was the predominant strain from February 9-April 5, 1997.4 The distinction between influenza types A and B is important in that both chemoprophylaxis and treatment are ineffective against influenza B.5 Influenza control has focused on vaccination programs involving inactivated virus and encouraging use of chemoprophylaxis with antiviral agents when appropriate. Vaccination of persons at high risk of complications before the influenza season each year can dramatically reduce influenza-related morbidity and mortality. 5 Vaccination can achieve 50% to 60% reductions in hospitalization among older nursinghome residents and an 80% reduction in risk of death from influenza and its complications. 5 The vaccine is 70% to 90% effective in preventing infection in healthy adults when a close match exists between the vaccine and the predominant circulating strain. ~ Influenza vaccine is prepared each year with inactivated virus to target the three virus strains expected to circulate during the upcoming season. The trivalent vaccine prepared for the 1997-98 season will be directed against A/Bayern/0795-1ike (H1N1), A/Wuhan/359/95like (H3N2), and B/Beijing/184-93-1ike antigens.s Live attenuated trivalent cold-adapted influenza vaccine (CAIV-T) is under development. In a recent study, CAIV-T, given as intranasal drops or spray, effected antibody re-
ANNALS OF EMER6ENCY MEDICINE
30:5 NOVEMBER 1997
CDC UPDATE
sponse in a group of children, who serocenverted to two of the trivalent antigens.6 Livevirus vaccines may ultimately prove more immunogenic than killed-virus vaccines, 3 and a route of administration that does not require the use of a needle may be more widely accepted among children. Because influenza is most prevalent in school-age children, who are typically the first group affected in an outbreak, 7 development of effective vaccines with live, attenuated virus may have far-reaching implications in disease control. According to the Advisory Committee for Immunization Practices (ACIP) of the Centers for Disease Control and Prevention, the target population for vaccination includes older people (_>65years), nursing-home residents, and people with chronic pulmonary or cardiovascular disorders. People with chronic metabolic diseases such as diabetes mellitus, kidney dysfunction, hemoglobinopathies, and immunosuppression should also receive the influenza vaccine, as should pediatric patients receiving long-term aspirin therapy. Pregnant women who will be in the second or third trimester during the influenza season and those with underlying medical conditions placing them at high risk should be vaccinated. The optimal timing for immunization is between October and mid-November; outbreaks occur almost exclusively during the winter months. 5 Children with moderate to severe asthma should be vaccinated. Currently only 10% are vaccinated, in part because of unwarranted concerns on the part of physicians about the
safety of vaccination during asthma exacerbation, concurrent febrile illness, or prednisone therapy. Influenza vaccination may be given to these children and should be considered in the ED.a,9 Health care workers may expose high-risk patients to influenza and should therefore be immunized, as should family members of these high-risk patients. Any person who requests vaccination may be immunized, provided no contraindications exist (specifically, hypersensitivity to egg products), s Two antivira[ drugs, amantadine and rimantadine, block the replication of influenza A, but neither drug is effective against influenza B. Chemoprophylaxis with either of these US Food and Drug Administration-approved drugs, when administered to healthy adults or children 1 year or younger, can be 50% to 90% effective in preventing influenza A-related illness.5 Because neither of these antiviral agents interferes with antibody response to the vaccin-e, chemoprophylaxis may also protect vaccinated patients until antibody protection is present, which may take as long as 2 weeks. Given that outbreaks in nursing homes place all residents at considerable risk, emergency physicians may wish to treat influenza in nursing-home patients as a sentinel event and encourage prompt chemoprophylaxis for all other nursing-home residents, regardless of immunization status, to minimize spread and reduce the overall impact of the outbreak. Children who receive the influenza vaccine for the first time requ'ire two separate immunizations. They may
also require 6 weeks of chemoprophylaxis, culminating 2 weeks after the second dose of vaccine is received) When influenza does occur, it typically produces sudden onset of high fever, myalgias, and cough, a relatively distinct syndrome compared with common upper respiratory tract infections. Other symptoms include sore throat, shivering, headache, and weakness. 3,10 When these symptoms are encountered during the winter months, in the presence of a known outbreak in the community, a presumptive diagnosis may be made. Diagnostic testing to confirm the presence of influenza is unusual, given the time it takes for results to become available. 11 Nevertheless, physician diagnoses of influenza are reportedly 80% accurate. 12,13Diagnosing influenza is important because treatment with amantadine or with rimantadine within 48 hours of symptom onset may be effective in reducing systemic symptoms and fever by I or 2 days and may shorten the period during which virus is shed.3,14Antibiotic therapy is both ineffective and inappropriate. Specific prophylaxis and treatment recommendations are summarized in the Table. A recent report indicates zanamivir (GG167), a new antiviral drug, may reduce symptom duration in adults with both influenza A and B. This could provide clinicians with an additional further option in treating patients with influenza, particularly since currently available antiviral drugs are effective only against Influenza A. 15
Table.
Recommended dosagesfor amantadine and rimantadine. Agent
1-9 Years
10-13 Years
14-64 Years
>_65Years
5 mg/kg/day,* up to 150 mg in two divided doses 5 mg/kg/day,*up to 150 mg in two divided doses
100 mg, twice daily*
100 mg, twice daily
<100 mg/day
100 mg, twice daily*
100 mg, twice daily
_<100mg/day
NA 5 mg/kg/day, up to 150 mg in two divided doses
NA 100 mg, twice daily*
100 mg, twice daily 100 mg, twice daily
t00 or 200 mg/day r{ 100 or 200 mg/dayU
Amantadine* Treatment Prophylaxis
Rimantadine~ Treatment Prophylaxis
Modified from reference5. *The drug package insert should be consulted for dosage recommendationsfor the administration of amantadine to personswith creatinine clearanceof !ess than 50 mL/minute. tl teaspoon per 22 pounds. ¢Children ailed 10 years and youngerwho weigh less than 40 kg should be given a dose of 5 mg/kg/day. ~A reduction in dose to 100 rag/day is recommendedfor personswith severe liver dysfunction and those with creatinine clearance_<10mL/minute. Other personswith lees severe liver or kidney dysfunction who are taking more than 100 rag/day rimantadine should be observedclosely and the dosage reducedor the drug discontinued if necessary. "Older nursing-home residentsshould be given only 100 rag/day. A reduction in dose to 100 rag/day should be considered in all personsaged 65 years and cider who experienceside effects at 200 mg/day.
NOVEMBER 1997
30:5
ANNALS OF EMERGENCY MED(CINE
6 93
CDC UPDATE Vaccination has been underused in primary care settings. Vaccination rates in high-risk groups are around 40%, far below the 60% goal outlined in Healthy People 2000.16The uninsured and underinsured, who lack access to preventive services and primary care, are undoubtedly part of this shortfall. However, undervaccination is a problem despite access to primary care. In one study, 28% of HIV-infected patients were immunized for influenza, and only 45% of the health maintenance organization patients in this cohort were vaccinated. 17 ED use has been found to be a marker for undervaccination, regardless of primary-care access. Patients from high-risk groups often present to the ED during the period in which immunization is most effective. Studies have shown that 54% of these patients were willing to undergo immunization in the ED if it was offered and that ED-based vaccination programs are feasible. 1,18 Emergency physicians may be reluctant to offer their patients influenza vaccination, in part because it is seen as the province of primary care practitioners. However, the Centers for Disease Control and Prevention encourages emergency physicians to offer high-risk patients influenza vaccine, or provide appropriate referral, including written information on where, why, and how to obtain the vaccine. 5
13. Hall CB, Dolin R, Gala C, et al: Children with influenza A infection: Treatment with rimantadine. Pediatrics 1987; 80:275-282. 14. Hayden FG, Monto AS: Oral rimantadine hydrochloride therapy of influenza A virus H3N2 subtype infection in adults. Antimicrob Agents Chemother 1986;29:339-341. 15. Hayden FG, Osterhaus A, TreanordJ, et al: Efficacy and safety of the neuraminidase inhibitor zanamivir in the treatment of influenza virus infections. N Engl J Med 1997; 337:874-880. 16. Berry BB, Murthy VS: Exceeding the Healthy People 2000 goalfor influenza vaccination through a collaborative effort at eight primary care clinics. Wisc Med J 1996;95: 705-710. 17. 8orvillo FJ, Nahlen BL: Influenza immunization for HIV-infected persons in Los Angeles. Vaccine I995;13:377380. 18. Wrenn K Zeldin R, Miller O: Influenza and pneumococcal vaccination in the emergency department: Is ti feasible? J Gedatr Intern Med 1994;9:425-429.
1. Rodriguez RM, Baruff LJ: Emergency department immunization of the elderly with pneumococcal and i~fluenza vaccines. Ann Emerg Med 1993;22:I 729-I 732. 2. Schoenbaum 8C: Economic impact of influenza: The individual's perspective. Am J Med 1987; 82 (suppl 6A): 26-30. 3. Douglas RG: Prophylaxis and treatment of influenza. N Engl J Med 1990;322:443-450. 4. Centersfor Disease Control and Prevention: Influenza surveillance: United States, 1992-93 and 1993-94. MMWR Morbid Mortal Wkly Rep I997;46(SS-I):1-12. 5. Centersfor Disease Control and Prevention: Prevention and control of influenza: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morbid Mortal Wkly Rep 1997;46(RR-9). 6. KingJ, Belshe R, Bryant M: Safety and immunogenicity of intranasal live attenuated trivalent cold-adapted influenza vaccine (CAW-T) fftven as drops or spray in children. Pediatr Res 1997;41 (suppl):I23A. 7. Care TR: Clinical manifestations and consequences of influenza. AmJ Med 1987;82(suppl 6A):I5-19. 8. Park CL, Frank AL, Sullivan M, et ah Influenza vaccination of children during acute asthma exacerbation and concurrent prednisone therapy. Pediatrics 1996;98:196-200. 9. ACIP issues recommendationfor the prevention and control of influenza in the I996-1997 season [specialmedical report]. American Family Physician 1996;54:767-774. 10. Nicholson KG: Clinicalfeatures of influenza. Semin Resp Infect 1992;7:26-37. 11. Rosenthal M: ZymeTX developingflu test. Infect Dis News 1997;10:27. 12. Van Voris LP, Betts RF, Hayden FG, et aI: Successful treatment of naturally occurring influenza A/USSW77 H1N1. lAMA 1981;245:1128-113I.
69 4
ANNALS OF EMERGENCY MEDICINE
30:5 NOVEMBER 1997
U p d a t e on Emerging Infections From the Centers for Disease Control and Prevention Influenza: ED Considerations for the 1997-98 Season
Guy L Merchant William R Mower, MS, MD David A Talan, MD Section Editors
David A Talan, MD GregoryJ Moran, MD Olive View-UCIA Medical Center 5ylmar, CA
Editors'note: Thisarticle is part of a regular series on emerging infections from the Centers for Disease Control and Prevention (CDC)and the EMERGEncyID NET, an ED-based, CDCcollaborative surveillance network. Important public health information on infectious disease with relevance to emergencyphysicians is reported. The goal of this series is to advance knowledge about communicable diseases in emergency medicine and foster cooperation between the front line of clinical medicine and public health agencies.
Robert W Pinner, MD Centers for Disease Control and Prevention Atlanta, CA
Influenza: ED Considerations for the 1997-98 Season [Merchant GL, Mower WR, Talan DA: Influenza: ED considerations for the 1997-98 season. Ann Emerg Med November 1997;30:692-694.] Influenza is a seasonal malady, commonly perceived as relatively benign and self limited, for which the threat to public health is frequently underestimated. Annual outbreaks and occasional pandemics of influenza present a major source of morbidity and mortality, with approximately 20,000 deaths and $1 to 12 billion in health care costs in the US annuallyF.2 The purpose of this article is to review the current epidemiology, vaccine composition, and prevention and treatment strategies relevant for emergency practice. Influenza is caused by one of two distinct virus types, A and B. Influenza A, subtyped on the basis of the surface antigens hemagglutinin (H) and neuraminidase (N), is less antigenically stable, with a propensity for surface-antigen variations that can result in the production of
692
new strains. Influenza B has been responsible for approximately 20% of outbreaks,3 and the illness is often less severe. Nevertheless, influenza B was the main circulating strain in the United States in 1990-91 and 1992-93, found in about three quarters of isolates tested. In 1996-97, influenza A was the predominant strain, with 81% of isolates. However, influenza B activity began increasing late in the season and was the predominant strain from February 9-April 5, 1997.4 The distinction between influenza types A and B is important in that both chemoprophylaxis and treatment are ineffective against influenza B.5 Influenza control has focused on vaccination programs involving inactivated virus and encouraging use of chemoprophylaxis with antiviral agents when appropriate. Vaccination of persons at high risk of complications before the influenza season each year can dramatically reduce influenza-related morbidity and mortality. 5 Vaccination can achieve 50% to 60% reductions in hospitalization among older nursinghome residents and an 80% reduction in risk of death from influenza and its complications. 5 The vaccine is 70% to 90% effective in preventing infection in healthy adults when a close match exists between the vaccine and the predominant circulating strain. ~ Influenza vaccine is prepared each year with inactivated virus to target the three virus strains expected to circulate during the upcoming season. The trivalent vaccine prepared for the 1997-98 season will be directed against A/Bayern/0795-1ike (H1N1), A/Wuhan/359/95like (H3N2), and B/Beijing/184-93-1ike antigens.s Live attenuated trivalent cold-adapted influenza vaccine (CAIV-T) is under development. In a recent study, CAIV-T, given as intranasal drops or spray, effected antibody re-
ANNALS OF EMER6ENCY MEDICINE
30:5 NOVEMBER 1997
CDC UPDATE
sponse in a group of children, who serocenverted to two of the trivalent antigens.6 Livevirus vaccines may ultimately prove more immunogenic than killed-virus vaccines, 3 and a route of administration that does not require the use of a needle may be more widely accepted among children. Because influenza is most prevalent in school-age children, who are typically the first group affected in an outbreak, 7 development of effective vaccines with live, attenuated virus may have far-reaching implications in disease control. According to the Advisory Committee for Immunization Practices (ACIP) of the Centers for Disease Control and Prevention, the target population for vaccination includes older people (_>65years), nursing-home residents, and people with chronic pulmonary or cardiovascular disorders. People with chronic metabolic diseases such as diabetes mellitus, kidney dysfunction, hemoglobinopathies, and immunosuppression should also receive the influenza vaccine, as should pediatric patients receiving long-term aspirin therapy. Pregnant women who will be in the second or third trimester during the influenza season and those with underlying medical conditions placing them at high risk should be vaccinated. The optimal timing for immunization is between October and mid-November; outbreaks occur almost exclusively during the winter months. 5 Children with moderate to severe asthma should be vaccinated. Currently only 10% are vaccinated, in part because of unwarranted concerns on the part of physicians about the
safety of vaccination during asthma exacerbation, concurrent febrile illness, or prednisone therapy. Influenza vaccination may be given to these children and should be considered in the ED.a,9 Health care workers may expose high-risk patients to influenza and should therefore be immunized, as should family members of these high-risk patients. Any person who requests vaccination may be immunized, provided no contraindications exist (specifically, hypersensitivity to egg products), s Two antivira[ drugs, amantadine and rimantadine, block the replication of influenza A, but neither drug is effective against influenza B. Chemoprophylaxis with either of these US Food and Drug Administration-approved drugs, when administered to healthy adults or children 1 year or younger, can be 50% to 90% effective in preventing influenza A-related illness.5 Because neither of these antiviral agents interferes with antibody response to the vaccin-e, chemoprophylaxis may also protect vaccinated patients until antibody protection is present, which may take as long as 2 weeks. Given that outbreaks in nursing homes place all residents at considerable risk, emergency physicians may wish to treat influenza in nursing-home patients as a sentinel event and encourage prompt chemoprophylaxis for all other nursing-home residents, regardless of immunization status, to minimize spread and reduce the overall impact of the outbreak. Children who receive the influenza vaccine for the first time requ'ire two separate immunizations. They may
also require 6 weeks of chemoprophylaxis, culminating 2 weeks after the second dose of vaccine is received) When influenza does occur, it typically produces sudden onset of high fever, myalgias, and cough, a relatively distinct syndrome compared with common upper respiratory tract infections. Other symptoms include sore throat, shivering, headache, and weakness. 3,10 When these symptoms are encountered during the winter months, in the presence of a known outbreak in the community, a presumptive diagnosis may be made. Diagnostic testing to confirm the presence of influenza is unusual, given the time it takes for results to become available. 11 Nevertheless, physician diagnoses of influenza are reportedly 80% accurate. 12,13Diagnosing influenza is important because treatment with amantadine or with rimantadine within 48 hours of symptom onset may be effective in reducing systemic symptoms and fever by I or 2 days and may shorten the period during which virus is shed.3,14Antibiotic therapy is both ineffective and inappropriate. Specific prophylaxis and treatment recommendations are summarized in the Table. A recent report indicates zanamivir (GG167), a new antiviral drug, may reduce symptom duration in adults with both influenza A and B. This could provide clinicians with an additional further option in treating patients with influenza, particularly since currently available antiviral drugs are effective only against Influenza A. 15
Table.
Recommended dosagesfor amantadine and rimantadine. Agent
1-9 Years
10-13 Years
14-64 Years
>_65Years
5 mg/kg/day,* up to 150 mg in two divided doses 5 mg/kg/day,*up to 150 mg in two divided doses
100 mg, twice daily*
100 mg, twice daily
<100 mg/day
100 mg, twice daily*
100 mg, twice daily
_<100mg/day
NA 5 mg/kg/day, up to 150 mg in two divided doses
NA 100 mg, twice daily*
100 mg, twice daily 100 mg, twice daily
t00 or 200 mg/day r{ 100 or 200 mg/dayU
Amantadine* Treatment Prophylaxis
Rimantadine~ Treatment Prophylaxis
Modified from reference5. *The drug package insert should be consulted for dosage recommendationsfor the administration of amantadine to personswith creatinine clearanceof !ess than 50 mL/minute. tl teaspoon per 22 pounds. ¢Children ailed 10 years and youngerwho weigh less than 40 kg should be given a dose of 5 mg/kg/day. ~A reduction in dose to 100 rag/day is recommendedfor personswith severe liver dysfunction and those with creatinine clearance_<10mL/minute. Other personswith lees severe liver or kidney dysfunction who are taking more than 100 rag/day rimantadine should be observedclosely and the dosage reducedor the drug discontinued if necessary. "Older nursing-home residentsshould be given only 100 rag/day. A reduction in dose to 100 rag/day should be considered in all personsaged 65 years and cider who experienceside effects at 200 mg/day.
NOVEMBER 1997
30:5
ANNALS OF EMERGENCY MED(CINE
6 93
CDC UPDATE Vaccination has been underused in primary care settings. Vaccination rates in high-risk groups are around 40%, far below the 60% goal outlined in Healthy People 2000.16The uninsured and underinsured, who lack access to preventive services and primary care, are undoubtedly part of this shortfall. However, undervaccination is a problem despite access to primary care. In one study, 28% of HIV-infected patients were immunized for influenza, and only 45% of the health maintenance organization patients in this cohort were vaccinated. 17 ED use has been found to be a marker for undervaccination, regardless of primary-care access. Patients from high-risk groups often present to the ED during the period in which immunization is most effective. Studies have shown that 54% of these patients were willing to undergo immunization in the ED if it was offered and that ED-based vaccination programs are feasible. 1,18 Emergency physicians may be reluctant to offer their patients influenza vaccination, in part because it is seen as the province of primary care practitioners. However, the Centers for Disease Control and Prevention encourages emergency physicians to offer high-risk patients influenza vaccine, or provide appropriate referral, including written information on where, why, and how to obtain the vaccine. 5
13. Hall CB, Dolin R, Gala C, et al: Children with influenza A infection: Treatment with rimantadine. Pediatrics 1987; 80:275-282. 14. Hayden FG, Monto AS: Oral rimantadine hydrochloride therapy of influenza A virus H3N2 subtype infection in adults. Antimicrob Agents Chemother 1986;29:339-341. 15. Hayden FG, Osterhaus A, TreanordJ, et al: Efficacy and safety of the neuraminidase inhibitor zanamivir in the treatment of influenza virus infections. N Engl J Med 1997; 337:874-880. 16. Berry BB, Murthy VS: Exceeding the Healthy People 2000 goalfor influenza vaccination through a collaborative effort at eight primary care clinics. Wisc Med J 1996;95: 705-710. 17. 8orvillo FJ, Nahlen BL: Influenza immunization for HIV-infected persons in Los Angeles. Vaccine I995;13:377380. 18. Wrenn K Zeldin R, Miller O: Influenza and pneumococcal vaccination in the emergency department: Is ti feasible? J Gedatr Intern Med 1994;9:425-429.
1. Rodriguez RM, Baruff LJ: Emergency department immunization of the elderly with pneumococcal and i~fluenza vaccines. Ann Emerg Med 1993;22:I 729-I 732. 2. Schoenbaum 8C: Economic impact of influenza: The individual's perspective. Am J Med 1987; 82 (suppl 6A): 26-30. 3. Douglas RG: Prophylaxis and treatment of influenza. N Engl J Med 1990;322:443-450. 4. Centersfor Disease Control and Prevention: Influenza surveillance: United States, 1992-93 and 1993-94. MMWR Morbid Mortal Wkly Rep I997;46(SS-I):1-12. 5. Centersfor Disease Control and Prevention: Prevention and control of influenza: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morbid Mortal Wkly Rep 1997;46(RR-9). 6. KingJ, Belshe R, Bryant M: Safety and immunogenicity of intranasal live attenuated trivalent cold-adapted influenza vaccine (CAW-T) fftven as drops or spray in children. Pediatr Res 1997;41 (suppl):I23A. 7. Care TR: Clinical manifestations and consequences of influenza. AmJ Med 1987;82(suppl 6A):I5-19. 8. Park CL, Frank AL, Sullivan M, et ah Influenza vaccination of children during acute asthma exacerbation and concurrent prednisone therapy. Pediatrics 1996;98:196-200. 9. ACIP issues recommendationfor the prevention and control of influenza in the I996-1997 season [specialmedical report]. American Family Physician 1996;54:767-774. 10. Nicholson KG: Clinicalfeatures of influenza. Semin Resp Infect 1992;7:26-37. 11. Rosenthal M: ZymeTX developingflu test. Infect Dis News 1997;10:27. 12. Van Voris LP, Betts RF, Hayden FG, et aI: Successful treatment of naturally occurring influenza A/USSW77 H1N1. lAMA 1981;245:1128-113I.
69 4
ANNALS OF EMERGENCY MEDICINE
30:5 NOVEMBER 1997