Influenza cost-effectiveness of therapy

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For more information about zoonotic (variant) influenza virus that may infect humans, see Avian influenza or Swine influenza

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alejandro Lemor, M.D. [2]

Overview

Influenza produces direct costs due to lost productivity and associated medical treatment, as well as indirect costs of preventative measures. In the United States, influenza is responsible for a total cost of over $10 billion per year, while it has been estimated that a future pandemic could cause hundreds of billions of dollars in direct and indirect costs. However, the economic impact of past pandemics have not been intensively studied, and some authors have suggested that the Spanish influenza actually had a positive long-term effect on per-capita income growth, despite a large reduction in the working population and severe short-term depressive effects.[1] Other studies have attempted to predict the costs of a pandemic as serious as the 1918 Spanish flu on the U.S. economy, where 30% of all workers became ill, and 2.5% were killed. A 30% sickness rate and a three-week length of illness would decrease gross domestic product by 5%. Additional costs would come from medical treatment of 18 million to 45 million people, and total economic costs would be approximately $700 billion.[2]

Cost-Effectiveness of Therapy Adapted from CDC [3][4]

Antiviral Drugs

  • Randomized, controlled trials conducted primarily among persons with mild illness in outpatient settings have demonstrated that zanamivir or oseltamivir can reduce the duration of uncomplicated influenza A and B illness by approximately 1 day when administered within 48 hours of illness onset compared with placebo[5][6][7][8]
  • One randomized, controlled trial of oseltamivir treatment among 408 children aged 1--3 years reported that when oseltamivir was started within 24 hours of illness onset, the median time to illness resolution was shortened by 3.5 days compared with placebo.
  • Minimal or no benefit was reported in healthy children and adults when antiviral treatment was initiated more than 2 days after onset of uncomplicated influenza.
  • The amount of influenza viral shedding was reduced among those treated, but studies on whether the duration of viral shedding is reduced have been inconsistent [9][10][11][12][13] and the temporal and causal relationships between changes in influenza viral shedding and clinical outcomes have not been well-established.
  • One evidence review concluded that neuraminidase inhibitors were not effective in reducing the severity or duration of ILI (defined as acute respiratory infection with fever and cough).
  • However, a variety of pathogens can cause ILI besides influenza viruses, and this review did not conclude that neuraminidase inhibitors were ineffective in reducing laboratory-confirmed influenza among adults.[14]
  • Data are limited about the effectiveness of zanamivir and oseltamivir treatment in preventing serious influenza-related complications (e.g., bacterial or viral pneumonia or exacerbation of chronic diseases).
  • In a study that combined data from 10 clinical trials, the risk for pneumonia among those participants with laboratory-confirmed influenza receiving oseltamivir treatment was approximately 50% lower than among those persons receiving a placebo and 34% lower among patients at risk for complications (p is less than 0.05 for both comparisons).[15]
  • Although a similar significant reduction also was determined for hospital admissions among the overall group, the 50% reduction in hospitalizations reported in the small subset of high-risk participants was not statistically significant.[15]

One randomized, controlled trial found a decreased incidence of otitis media among children treated with oseltamivir. [8]

  • A randomized, controlled trial among children aged 1--3 years found an 85% reduction in acute otitis media when oseltamivir treatment was started within 12 hours of illness onset, but no reduction when treatment was started more than 24 hours from symptom onset.[16]
  • Another randomized, controlled study conducted among influenza virus-infected children with asthma reported greater improvement in lung function and fewer asthma exacerbations among oseltamivir-treated children compared with those who received placebo but did not determine a difference in symptom duration.[16]
  • Insufficient data exist regarding the effectiveness of any of the influenza antiviral drugs for use among children aged younger than 1 year.

Vaccination

  • A RCT conducted among 1,602 healthy children initially aged 15–71 months assessed the efficacy of trivalent LAIV against culture-confirmed influenza during two seasons.[17]
  • In season one, when vaccine and circulating virus strains were well-matched, efficacy in preventing laboratory-confirmed illness from influenza was 93% for participants who received two doses of LAIV.
  • In season two, when the A (H3N2) component was not well-matched between vaccine and circulating virus strains, efficacy was 86% overall.
  • A randomized, double-blind, placebo-controlled trial among 4,561 healthy working adults aged 18–64 years assessed multiple endpoints (i.e., targeted outcome measures), including reductions in self-reported respiratory tract illness without laboratory confirmation, absenteeism, health care visits, use of antibiotics, and use of over-the-counter medications for illness symptoms during peak and total influenza outbreak periods[18]). The study was conducted during the 1997-1998 influenza season, when the influenza vaccine and circulating A (H3N2) viruses were poorly matched. Vaccination was associated with reductions in severe febrile illnesses of 19%, and febrile upper respiratory tract illnesses of 24%.
  • Vaccination was also associated with fewer days of illness, fewer days of work lost, fewer days with health care provider visits, and reduced use of prescription antibiotics and over-the-counter medications. Among a subset of 3,637 healthy adults aged 18–49 years, LAIV recipients (n = 2,411) had 26% fewer febrile upper-respiratory illness episodes; 27% fewer lost work days as a result of febrile upper respiratory illness; and 18%–37% fewer days of health care provider visits caused by febrile illness, compared with placebo recipients (n = 1,226). Days of antibiotic use were reduced by 41%–45% in this age subset.
  • One study included 2,187 children aged 6–71 months who had recurrent respiratory tract infections[19] and found overall influenza rates of 2.3% among live vaccine recipients and 4.8% for TIV, for a 52.7% decrease in children receiving live vaccine compared to those receiving inactivated vaccine.
  • In a randomized study of 2,229 children aged 6–17 years with asthma, 4.1% of live vaccine recipients and 6.2% of TIV recipients developed influenza, for a relative reduction of 34.7%.[20]
  • Finally, in 2004-2005 a multinational RCT was conducted among 8,352 children aged 6–59 months. For the primary endpoint in this trial, culture-confirmed influenza-like illness, there were 45% fewer cases of influenza for well-matched influenza strains and 58% fewer for mismatched strains among live versus inactivated vaccine recipients.[21]

Chemoprophylaxis

  • In randomized, placebo-controlled trials, both oseltamivir and zanamivir were efficacious in the prevention of influenza illness among persons administered chemoprophylaxis after a household member or other close contact had laboratory-confirmed influenza (zanamivir: 72%--82%; oseltamivir: 68%--89%)[22][23][24][25][26][27]
  • Postexposure chemoprophylaxis with neuraminidase inhibitors generally should be reserved for those who have had recent close contact with a person with influenza.
  • Persons who can be considered for antiviral chemoprophylaxis include family or other close contacts of a person with a suspected or confirmed case who are at higher risk for influenza complications but have not been vaccinated against the influenza virus strains circulating at the time of exposure [28]
  • Unvaccinated health-care workers who have occupational exposures and who did not use adequate personal protective equipment at the time of exposure are also potential candidates for chemoprophylaxis [28].
  • Because of widespread resistance among currently circulating influenza A virus strains and inherent non-susceptibility among influenza B viruses, adamantanes have limited use in the prevention of influenza.
  • Persons who receive an antiviral medication for chemoprophylaxis might still acquire influenza virus infection and be potentially able to transmit influenza virus, even if clinical illness is prevented.[29][30]

References

  1. ↑ Brainerd, E. and M. Siegler (2003), “The Economic Effects of the 1918 Influenza Epidemic”, CEPR Discussion Paper, no. 3791.
  2. ↑ Poland G (2006). "Vaccines against avian influenza—a race against time". N Engl J Med. 354 (13): 1411–3. PMID 16571885.
  3. ↑ "CDC Flu Vaccine Effectiveness".
  4. ↑ "CDC Guidance on the Use of Influenza Antiviral Agents".
  5. ↑ Hayden FG, Osterhaus AD, Treanor JJ, Fleming DM, Aoki FY, Nicholson KG; et al. (1997). "Efficacy and safety of the neuraminidase inhibitor zanamivir in the treatment of influenzavirus infections. GG167 Influenza Study Group". N Engl J Med. 337 (13): 874–80. doi:10.1056/NEJM199709253371302. PMID 9302301.
  6. ↑ Monto AS, Fleming DM, Henry D, de Groot R, Makela M, Klein T; et al. (1999). "Efficacy and safety of the neuraminidase inhibitor zanamivirin the treatment of influenza A and B virus infections". J Infect Dis. 180 (2): 254–61. doi:10.1086/314904. PMID 10395837.
  7. ↑ Nicholson KG, Aoki FY, Osterhaus AD, Trottier S, Carewicz O, Mercier CH; et al. (2000). "Efficacy and safety of oseltamivir in treatment of acute influenza: a randomised controlled trial. Neuraminidase Inhibitor Flu Treatment Investigator Group". Lancet. 355 (9218): 1845–50. PMID 10866439.
  8. ↑ 8.0 8.1 Whitley RJ, Hayden FG, Reisinger KS, Young N, Dutkowski R, Ipe D; et al. (2001). "Oral oseltamivir treatment of influenza in children". Pediatr Infect Dis J. 20 (2): 127–33. PMID 11224828.
  9. ↑ Carrat F, Vergu E, Ferguson NM, Lemaitre M, Cauchemez S, Leach S; et al. (2008). "Time lines of infection and disease in human influenza: a review of volunteer challenge studies". Am J Epidemiol. 167 (7): 775–85. doi:10.1093/aje/kwm375. PMID 18230677.
  10. ↑ Cowling BJ, Chan KH, Fang VJ, Lau LL, So HC, Fung RO; et al. (2010). "Comparative epidemiology of pandemic and seasonal influenza A in households". N Engl J Med. 362 (23): 2175–84. doi:10.1056/NEJMoa0911530. PMC 4070281. PMID 20558368.
  11. ↑ Hayden FG, Fritz R, Lobo MC, Alvord W, Strober W, Straus SE (1998). "Local and systemic cytokine responses during experimental human influenza A virus infection. Relation to symptom formation and host defense". J Clin Invest. 101 (3): 643–9. doi:10.1172/JCI1355. PMC 508608. PMID 9449698.
  12. ↑ Hayden FG, Treanor JJ, Fritz RS, Lobo M, Betts RF, Miller M; et al. (1999). "Use of the oral neuraminidase inhibitor oseltamivir in experimental human influenza: randomized controlled trials for prevention and treatment". JAMA. 282 (13): 1240–6. PMID 10517426.
  13. ↑ Sato M, Hosoya M, Kato K, Suzuki H (2005). "Viral shedding in children with influenza virus infections treated with neuraminidase inhibitors". Pediatr Infect Dis J. 24 (10): 931–2. PMID 16220098.
  14. ↑ Jefferson T, Demicheli V, Rivetti D, Jones M, Di Pietrantonj C, Rivetti A (2006). "Antivirals for influenza in healthy adults: systematic review". Lancet. 367 (9507): 303–13. doi:10.1016/S0140-6736(06)67970-1. PMID 16443037. Review in: Evid Based Nurs. 2006 Oct;9(4):108 Review in: ACP J Club. 2006 Sep-Oct;145(2):45 Review in: Evid Based Med. 2006 Oct;11(5):141
  15. ↑ 15.0 15.1 Kaiser L, Wat C, Mills T, Mahoney P, Ward P, Hayden F (2003). "Impact of oseltamivir treatment on influenza-related lower respiratory tract complications and hospitalizations". Arch Intern Med. 163 (14): 1667–72. doi:10.1001/archinte.163.14.1667. PMID 12885681.
  16. ↑ 16.0 16.1 Heinonen S, Silvennoinen H, Lehtinen P, Vainionpää R, Vahlberg T, Ziegler T; et al. (2010). "Early oseltamivir treatment of influenza in children 1-3 years of age: a randomized controlled trial". Clin Infect Dis. 51 (8): 887–94. doi:10.1086/656408. PMID 20815736.
  17. ↑ Longini IM, Halloran ME, Nizam A, Wolff M, Mendelman PM, Fast PE; et al. (2000). "Estimation of the efficacy of live, attenuated influenza vaccine from a two-year, multi-center vaccine trial: implications for influenza epidemic control". Vaccine. 18 (18): 1902–9. PMID 10699339.
  18. ↑ Nichol KL (1999). "Influenza vaccination for healthy working adults". Minn Med. 82 (11): 24–6. PMID 10589210.
  19. ↑ Ashkenazi S, Vertruyen A, Arístegui J, Esposito S, McKeith DD, Klemola T; et al. (2006). "Superior relative efficacy of live attenuated influenza vaccine compared with inactivated influenza vaccine in young children with recurrent respiratory tract infections". Pediatr Infect Dis J. 25 (10): 870–9. doi:10.1097/01.inf.0000237829.66310.85. PMID 17006279.
  20. ↑ Fleming DM, Crovari P, Wahn U, Klemola T, Schlesinger Y, Langussis A; et al. (2006). "Comparison of the efficacy and safety of live attenuated cold-adapted influenza vaccine, trivalent, with trivalent inactivated influenza virus vaccine in children and adolescents with asthma". Pediatr Infect Dis J. 25 (10): 860–9. doi:10.1097/01.inf.0000237797.14283.cf. PMID 17006278.
  21. ↑ Belshe RB, Edwards KM, Vesikari T, Black SV, Walker RE, Hultquist M; et al. (2007). "Live attenuated versus inactivated influenza vaccine in infants and young children". N Engl J Med. 356 (7): 685–96. doi:10.1056/NEJMoa065368. PMID 17301299.
  22. ↑ Hayden FG, Atmar RL, Schilling M, Johnson C, Poretz D, Paar D; et al. (1999). "Use of the selective oral neuraminidase inhibitor oseltamivir to prevent influenza". N Engl J Med. 341 (18): 1336–43. doi:10.1056/NEJM199910283411802. PMID 10536125.
  23. ↑ Hayden FG, Gubareva LV, Monto AS, Klein TC, Elliot MJ, Hammond JM; et al. (2000). "Inhaled zanamivir for the prevention of influenza in families. Zanamivir Family Study Group". N Engl J Med. 343 (18): 1282–9. doi:10.1056/NEJM200011023431801. PMID 11058672.
  24. ↑ Eiland LS, Eiland EH (2007). "Zanamivir for the prevention of influenza in adults and children age 5 years and older". Ther Clin Risk Manag. 3 (3): 461–5. PMC 2386359. PMID 18488077.
  25. ↑ Welliver R, Monto AS, Carewicz O, Schatteman E, Hassman M, Hedrick J; et al. (2001). "Effectiveness of oseltamivir in preventing influenza in household contacts: a randomized controlled trial". JAMA. 285 (6): 748–54. PMID 11176912.
  26. ↑ Monto AS, Webster A, Keene O (1999). "Randomized, placebo-controlled studies of inhaled zanamivir in the treatment of influenza A and B: pooled efficacy analysis". J Antimicrob Chemother. 44 Suppl B: 23–9. PMID 10877459.
  27. ↑ Monto AS, Pichichero ME, Blanckenberg SJ, Ruuskanen O, Cooper C, Fleming DM; et al. (2002). "Zanamivir prophylaxis: an effective strategy for the prevention of influenza types A and B within households". J Infect Dis. 186 (11): 1582–8. doi:10.1086/345722. PMID 12447733.
  28. ↑ 28.0 28.1 "CDC. Updated interim recommendations for the use of antiviral medications in the treatment and prevention of influenza for the 2009--10 season. Atlanta, GA: US Department of Health and Human Services, CDC; 2009. Available at http://www.cdc.gov/H1N1flu/recommendations.htm". External link in |title= (help); Missing or empty |url= (help)
  29. ↑ Lee, Vernon J; Yap, Jonathan; Tay, Joshua K; Barr, Ian; Gao, Qiuhan; Ho, Hanley J; Tan, Boon; Kelly, Paul M; Tambyah, Paul A; Kelso, Anne; Chen, Mark I (2010). "Seroconversion and asymptomatic infections during oseltamivir prophylaxis against Influenza A H1N1 2009". BMC Infectious Diseases. 10 (1): 164. doi:10.1186/1471-2334-10-164. ISSN 1471-2334.
  30. ↑ Khazeni N, Bravata DM, Holty JE, Uyeki TM, Stave CD, Gould MK (2009). "Systematic review: safety and efficacy of extended-duration antiviral chemoprophylaxis against pandemic and seasonal influenza". Ann Intern Med. 151 (7): 464–73. PMID 19652173. Review in: Ann Intern Med. 2010 Mar 16;152(6):JC3-3

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