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The Next Influenza Pandemic: Will we be Ready to Care for Our Children?

2005; Elsevier BV; Volume: 147; Issue: 2 Linguagem: Inglês

10.1016/j.jpeds.2005.04.066

1097-6833

Charles R. Woods, Jon S. Abramson,

Viral Infections and Vectors

In October 2004, we were struck with another influenza surprise—almost half of the expected influenza vaccine supply for the United States was not available because of contamination during the manufacturing process. The Centers for Disease Control and Prevention (CDC) responded quickly to recommend that high-risk groups be given first priority for vaccine and to reroute existing vaccine stocks to areas experiencing short supplies.1Centers for Disease Control. Interim influenza vaccination recommendation, 2004-05 Influenza Season. October 5, 2004. MMWR 2004. URL: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm53d1005al.htm.Google Scholar This event occurred against the backdrop of a widespread avian influenza epidemic in Southeast Asia, described as the largest recognized to date, which re-emerged after a brief respite attributable in part to the culling of at least 100 million fowl in early 2004.2Centers for Disease Control. Update on avian influenza A (H5N1). URL: http://www.who.int/csr/don/2004_08_12/en/. August 12, 2004.Google Scholar, 3Tran T.H. Nguyen T.L. Nguyen T.D. Luong T.S. Pham P.M. Nguyen V.C. et al.Avian influenza A (H5N1) in 10 patients in Vietnam.N Engl J Med. 2004; 350: 1179-1188Crossref PubMed Scopus (747) Google Scholar, 4Centers for Disease Control Outbreaks of avian influenza A (H5N1) in Asia and interim recommendations for evaluation and reporting of suspected cases—United States, 2004.MMWR. 2004; 53: 97-100PubMed Google Scholar, 5Peiris J.S. Yu W.C. Leung C.W. Cheung C.Y. Ng W.F. Nicholis J.M. et al.Re-emergence of fatal human influenza A subtype H5N1 disease.Lancet. 2004; 363: 617-619Abstract Full Text Full Text PDF PubMed Scopus (696) Google Scholar The current H5N1 avian flu strain has spread among wild birds and also has evolved since 1997 to become more lethal to mice and more capable of spread among poultry.6Li K.S. Guan Y. Wang J. Smith G.J. Xu K.M. Duan L. et al.Genesis of a highly pathogenic and potentially pandemic H5N1 influenza virus in eastern Asia.Nature. 2004; 430: 209-213Crossref PubMed Scopus (1133) Google Scholar The bird-to-human transmissions that have occurred resulted in a high mortality rate (42 deaths among 55 patients with confirmed infection in Cambodia, Vietnam, and Thailand from January 2004–January 2005).7World Health Organization. Cumulative number of confirmed humancases of avian influenza A (H5N1). October 4, 2004 URL: http://www.who.int/csr/disease/avian_influenza/country/cases_table_2005_02_05/en/.Google Scholar Human-to-human spread of the H5N1 virus outside household contact has not been seen, but transmission within households has occurred.8World Health Organization. Avian influenza - situation in Thailand. September 28, 2004. URL: http://www.who.int/csr/don/2004_09_28a/en.Google Scholar There is concern that this strain of virus is just a point mutation—or more likely a single recombination event—away from causing the next pandemic.9Klempner M.S. Shapiro D.S. Crossing the species barrier—one small step to man, one giant leap to mankind.N Engl J Med. 2004; 350: 1171-1172Crossref PubMed Scopus (50) Google Scholar If the worldwide influenza monitoring system of the World Health Organization (WHO) and CDC had an alert system similar to that for terrorism events in the United States, the color probably would be orange. The primary focus of this commentary is to explore our preparedness to care for children and to suggest what further steps need to be taken. The news of a vaccine shortage and rampant bird flu came on the heels of an annual epidemic in 2003–2004 that was moderately severe, especially among children. It began earlier than usual (October) and continued into January 2004, with widespread disease occurring in 45 states. To deal with the volume of queries and issues that arose, the CDC activated its Emergency Operating Center and reassigned staff on a 24-hour, 7-day-per-week basis. The CDC prospectively monitored mortality rates in U.S. children for the first time during this outbreak, and 152 deaths among U.S. residents 1 day with onset of neurologic symptoms within 5 days of fever onset), with more than 40% having severe outcomes (death or neurologic sequelae).11Centers for Disease Control and Prevention. Record of the meeting of the Advisory Committee on Immunization Practices. June 23-23, 2004. URL: http://www.cdc.gov/nip/.Google Scholar Influenza A viruses accounted for 99.0% of cases in the United States in 2003–2004. H3N2 strains accounted for 99.9% of the influenza A viruses, and 89% of these were antigenically similar to the drift variant A/Fujian/411/2002. Compared with the A/Panama/2007/99 H3N2 strain (which accounted for 11% of influenza cases) that was included in the 2003–2004 vaccine, A/Fujian has 13 amino acid changes involving several antigenic sites.10Center for Disease Control Update: Influenza activity—United States and worldwide, 2003-04 Season, and composition of the 2004-05 influenza vaccine.MMWR. 2004; 53: 547-552PubMed Google Scholar, 12Treanor J. Influenza vaccine—outmaneuvering antigenic shift and drift.N Engl J Med. 2004; 350: 218-220Crossref PubMed Scopus (174) Google Scholar Although early reports raised concerns that the 2003–2004 vaccine provided minimal, if any, effectiveness against the predominant A/Fujian strain, there was some protection: vaccine efficacy was estimated to be 25% and 49%, respectively, in 2 analyses among children, and 38% and 52%, respectively, among adults with and without an underlying high-risk condition in a case-control study.13Centers for Disease Control and Prevention Assessment of the effectiveness of the 2003-04 influenza vaccine among children and adults—Colorado, 2003.MMWR. 2004; 53: 707-710PubMed Google Scholar The CDC conducted a convenience survey of 221 hospitals throughout the U.S. and found that the following types of shortages occurred during the 2003–2004 influenza season: (1) 40% had inadequate vaccine supply, (2) 58% ran out of diagnostic influenza test kits, (3) 28% and 43% had too few general inpatient and intensive care beds, respectively, (4) 35% had insufficient numbers of health care workers (HCWs), and (5) 9% needed to divert patients because of bed or HCW shortages.14Centers for Disease Control and Prevention. Record of the meeting of the Advisory Committee on Immunization Practices. February 24-25, 2004. URL: http://www.cdc.gov/nip/.Google Scholar This survey did not ask about shortages of anti-influenza drugs or hospital supplies (eg, masks), but these types of shortages occurred at our hospital, as well as other health care centers. The severity of the 2003–2004 flu season will pale in comparison with that of the next pandemic. There were 3 pandemics in the last century: the 1918 Spanish A/H1N1 influenza strain that killed at least 20 million and perhaps more than 50 million people worldwide, including many young adults, the 1957 Asian A/H2N2 influenza strain where ∼70,000 persons died in the U.S. over a 2-year period, and the 1968 Hong Kong A/H3N2 influenza strain that caused the death of ∼34,000 people in the U.S. in the first year.15Johnson N.P.A.S. Mueller J. Updating the accounts: global mortality of the 1918-1920 "Spanish" influenza pandemic.Bull Hist Med. 2002; 76: 105-115Crossref PubMed Google Scholar, 16Patriarca P.A. Cox N.J. Influenza pandemic preparedness plan for the United States.J Infect Dis. 1997; 176: S4-S7Crossref PubMed Scopus (64) Google Scholar, 17Centers for Disease Control National Vaccine Program Office. Pandemic influenza. URL: http://www.hhs.gov/nvpo/pandemics/fluprint.htm. Accessed June 10, 2005.Google Scholar The potential impact of the next influenza pandemic in the U.S. was modeled in 1999 by the CDC.18Meltzer M.I. Cox N.J. Fukuda K. The economic impact of pandemic influenza in the United States: priorities for intervention.Emerging Infect Dis. 1999; 5: 659-671Crossref PubMed Scopus (551) Google Scholar These estimates projected 89,000 to 207,000 deaths, 314,000 to 734,000 hospitalizations, 18,000,000 to 42,000,000 outpatient visits, and 20,000,000 to 47,000,000 additional illnesses. Estimates of medical costs, in 1999 dollars, ranged from $71 billion to $167 billion and did not include the indirect costs associated with disruptions to commerce and society. On August 26, 2004, the U.S. Department of Health and Human Services, via the National Vaccine Program Office, put forth the first public draft of the National Pandemic Influenza Preparedness Plan (N-PIPP) for the beginning of a 60-day public comment period.19National Vaccine Program Office. United States Department of Health & Human Services. Pandemic influenza response and preparedness plan. URL: http://www.hhs.gov/nvpo/pandemicplan/index.html. Accessed October 20, 2004.Google Scholar This planning and guidance is founded on efforts first undertaken in 1978 and then renewed in 1993.16Patriarca P.A. Cox N.J. Influenza pandemic preparedness plan for the United States.J Infect Dis. 1997; 176: S4-S7Crossref PubMed Scopus (64) Google Scholar, 20Simonsen L. Clarke M.J. Schonberger L.B. Arden N.H. Cox N.J. Fukuda K. Pandemic versus epidemic influenza mortality: a pattern of changing age distribution.J Infect Dis. 1998; 178: 53-60Crossref PubMed Scopus (579) Google Scholar, 21Misegades L. Preparedness planning for state health officials: nature's terrorist attack, pandemic influenza [monograph on the internet]. Washington: Association of State and Territorial Health Officials; 2002. URL: http://www.astho.org/pubs/PandemicInfluenza.pdf. Accessed June 10, 2005.Google Scholar This document, when finalized, will not be the completion of preparation (and was never intended to be such) but rather a major step forward in the process of (1) identifying issues that must be addressed at federal, state, and local levels—in both the public and private sectors and (2) providing guidance for planning and response to a pandemic. The need for federal, state, and local public health preparation and involvement is well recognized, but public health planning efforts in the past few years, especially at the local level, have been distracted by issues surrounding bioterrorism (eg, smallpox) and emerging infections (eg, severe acute respiratory syndrome [SARS]). The N-PIPP recognizes that it is time to refocus public health efforts toward preparation for pandemic influenza and in some circumstances even to merge these efforts with those for bioterrorism and emerging infections. At the local level particularly, individuals from the multiple public agencies that will need to work together in response to each of these types of events are largely the same, and the types of issues they will be facing are highly similar, and in many instances identical (Figure).21Misegades L. Preparedness planning for state health officials: nature's terrorist attack, pandemic influenza [monograph on the internet]. Washington: Association of State and Territorial Health Officials; 2002. URL: http://www.astho.org/pubs/PandemicInfluenza.pdf. Accessed June 10, 2005.Google Scholar, 22Gensheimer K.F. Meltzer M.I. Postema A.S. Strikas R.A. Influenza pandemic preparedness.Emerg Infect Dis. 2003; 12: 1645-1648Crossref Scopus (34) Google Scholar, 23Schoch-Spana M. Implications of pandemic influenza for bioterrorism response.Clin Infect Dis. 2000; 31: 1409-1413Crossref PubMed Scopus (71) Google Scholar, 24Hopkins R.S. Misegades L. Ransom J. Lipson L. Brink E.W. SARS preparedness checklist for state and local health officials.Emerg Infect Dis. 2004; 10: 369-372Crossref PubMed Scopus (11) Google Scholar The various problems that need to be addressed before arrival of a pandemic are broad in scope. The draft of the N-PIPP begins to address many of these issues, but as welcome and detailed as it is, there is little discussion or guidance for addressing the varying needs of infants and young children (or the very elderly). Table I provides a selected list of problems that are important for the care of children (and for adults in some cases) and potential solutions.Table IIssues that must be addressed before the next influenza pandemic∗This table includes a broad range of topics but is not considered all-inclusive by the authors. Established planning groups throughout the world have identified other problems, as well as many of the above, and are making progress toward delineation and implementation of solutions to these.CategoryProblemPotential solutionsComments1. Prediction and detection of the next pandemicDifficulty in predicting which virus will cause the next pandemicIncreased research funding to better understand (1) which influenza virus genetic sequences and other factors predict virulence and (2) which virus strain(s) will circulate in a given year.A large amount of funding currently is directed to the area of bioterrorism. Influenza causes many deaths due to natural disease and has the potential to be made into a bioterrorist weapon. Influenza research and planning should receive more funding even if it causes reprioritization of funding for other potential bioterrorism agents.32Cohen H. Gould R. Sidel V. The pitfalls of bioterrorism preparedness: the anthrax and smallpox experiences.Am J Public Health. 2004; 94: 1667-1671Crossref PubMed Scopus (58) Google ScholarSee also the WHO Consultation on Priority Public Health Interventions Before and During an Influenza Pandemic.†WHO consultation on priority public health interventions before and during an influenza pandemic. April 27, 2004. http://www.who.int/csr/disease/avian_influenza/consultation/en/.2. Response coordinationInadequate numbers of trained public health staffIncreased public health funding to hire, train, and retain additional staff at the national, state, and local levelsAdditional personnel resources can be drawn from academic medical centers. Establishing networks among such persons and providing stable funding support for them for their efforts in ongoing planning efforts would be helpful. This is especially important for pediatric pandemic preparedness.Enhanced collaboration between bioterrorism defense, emerging infections work groups, and influenza pandemic planners.The draft U.S. N-PIPP was released August 26, 2004, for 60 days of public comment.19National Vaccine Program Office. United States Department of Health & Human Services. Pandemic influenza response and preparedness plan. URL: http://www.hhs.gov/nvpo/pandemicplan/index.html. Accessed October 20, 2004.Google Scholar This plan overall represents an excellent blueprint for the next stages of preparation. Greater collaboration between the various threat-response working groups is envisioned for adults, but there is little consideration of the specific needs of children in any of these arenas.Further development of the Incident Command System, or similar approaches, to facilitate interagency communications, is needed.21Misegades L. Preparedness planning for state health officials: nature's terrorist attack, pandemic influenza [monograph on the internet]. Washington: Association of State and Territorial Health Officials; 2002. URL: http://www.astho.org/pubs/PandemicInfluenza.pdf. Accessed June 10, 2005.Google Scholar3. Early control effortsA. Isolation and quarantine of ill or exposed travelers from countries with initial outbreaks.Development of protocols for travel industry, health care systems, public health departments, etc. Consideration of closing schools and limiting other places where large numbers of people congregate.36Heymann A. Ghodick G. Reichman B. Kokia E. Laufer J. Influence of school closure on the incidence of viral respiratory diseases among children and on health care utilization.Ped Infec Dis J. 2004; 23: 675-677Crossref PubMed Scopus (116) Google ScholarUse of the precautionary principle with regard to the public health obligation to protect populations against foreseeable threats,34Applegate J. The precautionary preference: an American perspective on the precautionary principle.Hum Ecol Risk Assess. 2000; 6: 413-443Crossref Scopus (78) Google Scholar even under conditions of uncertainty, will be necessary. This application must be balanced by the principles of choosing the least restrictive/intrusive alternative, fairness and justice (both procedural and substantive).35Gostin L.O. Bayer R. Fairchild A.L. Ethical and legal challenges posed by severe acute respiratory syndrome. Implications for control of severe infectious disease threats.JAMA. 2003; 290: 3229-3237Crossref PubMed Scopus (143) Google Scholar Issues of child care for quarantined traveling families have received little discussion to date. Studies that assess the impact of school children on spread of influenza in the community are underway in the U.S. Additional epidemiologic studies assessing impact of other more crowded situations such as child care centers, shopping malls, and sports venues would be helpful.B. Prioritization plan to determine who should be the first to receive the vaccine because of the likelihood that only limited vaccine supplies will be available initially.Rationale for vaccination prioritization plan that is transparent (eg, HCW and first responders receive high priority so that they can care for patients) Completion of a logistical plan for vaccine distribution, from sites of manufacture to sites of administration.Federal legislation may be necessary to allow such prioritization plans to proceed unimpeded by legal challenges that might arise during the early stages of a pandemic with limited vaccine supply. Issues of children vs the elderly could arise and should be discussed. Legal provisions should be enacted before arrival of a pandemic to reduce appearances of favoritism during peak times of irrationality.A plan will need to involve all levels of public health infrastructure in collaboration with the private health sector at the local level.4. Vaccine productionA. Current production methods requiring an egg-based system to grow virus, with a production time of about 4 months.Use of tissue culture methods and other technology that allow for more rapid production of large quantities of influenza vaccine. Streamlining of the FDA process for influenza vaccine licensing and manufacturing.Research funding also should be provided for efforts toward (1) improved efficacy in young children, (2) vaccination of children 6 mos of age.Movement toward routine annual universal vaccination in the U.S.Routine annual universal vaccination would provide a foundation to ensure that adequate manufacturing capacity exists to make the needed number of vaccine doses and that the logistics needed to vaccinate the entire population are in place. Further studies of "half-doses" for healthy adults, as well as high-risk groups as a means of extending supplies and increasing capacity should be initiated.Requirement for mandatory vaccination of everyone >6 mos of age during a pandemic.A mandatory vaccination policy to be instituted during a pandemic will likely require federal legislation because of likely legal challenges and should be undertaken before the pandemic. Issues surrounding the swine flu vaccine effort in 1976 will need to be revisited and thought through.37Dowdle W.R. The 1976 experience.J Infect Dis. 1997; 176: S69-S72Crossref PubMed Scopus (25) Google ScholarB. Potential need for 2 doses for effective immunity against a pandemic strain.Additional clinical studies of influenza vaccines in young children.Much more needs to be learned about this issue. A second dose would be even more costly and logistically more difficult to accomplish.6. Rapid diagnosis of influenzaShortage of diagnostic kits.Stockpiling and increased production capacity for diagnostic kits.Shelf-life issues may require rotation of stocks. Stockpiling may require federal subsidy for manufacturers and reimbursement for expired products.7. Antiviral agentsA. Lack of prioritization for distribution of limited supplies of antiviral agents.Stockpiling and increased production capacity for antiviral agents. Promotion of correct use (vs overuse) of antiviral agents (beginning in first 48 hrs of illness)Shelf-life and stock-rotation issues need to be determined. Stockpiling may require subsidy for manufacturers and reimbursement for expired product.B. Lack of availability of antiviral agents for use in infants. (This problem is compounded by the lack of an effective influenza vaccine in infants <6 mos of age.)Government-funded studies to determine pharmacokinetics, safety, and efficacy of anti-influenza agents in infants.Efficacy of antiviral agents against potential pandemic strains should be ascertained, and new drugs may need to be developed. Under pandemic conditions, use of antibacterial agents for suspected or real secondary bacterial infections could lead to unanticipated shortages of some agents. Rapid production and stockpiling issues also may need to be considered for selected antibacterial agents.8. Hospital resourcesA. Shortage of hospital bedsUse of nontraditional in-house placements (short-stay suites, treatment rooms) as inpatient rooms.Procedures to permit use of "non-approved" beds or facilities under emergency conditions may need to be developed, and potentially approved by legislative bodies, at state and local levels. Cooperation among local and regional institutions likely will be essential (see below).Plan for off-site care (eg, schools) for people requiring minimal intervention (eg, oxygen, fluids etc). Postpone elective admissions.The national pandemic plan prefers use of nontraditional hospital beds and home health care first, but these resources could quickly be exhausted for adults and may not exist for young children. Protocols for temporary "wards" still need to be developed that address needs of young children, as well as adults and that include basic infection control procedures and mechanisms of handling medical waste.B. Shortage of supplies and equipmentStockpile of supplies (eg, masks, oxygen delivery materials, IV fluids) and equipment (ventilators, IV pumps).Programs to store "retired" ventilators and other equipment in central locations would be helpful. Protocols for sterilization/reuse of normally disposed items such as face masks and plastic tubing may need to be developed. Pediatric ventilators likely would be in very short supply.C. Long waiting periods in emergency departments and difficulties in triage.Develop protocols that facilitate collaboration between local health care providers and news media to provide instructions to the public as to when and where to seek help for varying degrees of illness. Those for children will differ from those for adults.Involvement of institutional public relations and marketing personnel may be useful in development and implementation of local and regional triage plans. Points of triage may need to be moved to other sites (eg, private offices) in some communities, with expertise required for both pediatric and adult patients.D. Nosocomial outbreaksScreening protocols for HCWs, family members and other visitors should be developed to help prevent nosocomial infections.Hospital visitation policies have been greatly liberalized in recent years. Involvement of local news media may be essential to deal effectively with potential restrictions.9. Public and private health care systemsA. Communication, coordination and collaboration between local and regional health care systems or institutions (even those competing in normal circumstances)‡This was reasonably well accomplished in North Carolina during the 2003–2004 influenza epidemic, although the system stresses were far less than what would be present during pandemic conditions.Establish or improve collaborations to coordinate private/public and private/private efforts, including plans to manage hospital beds and critical supplies in a collective manner.Collaborative efforts in working with news media and responding to the public also will be critical in lessening impacts on societal functions. Tabletop exercises similar to those used in preparation for bioterrorism events may be useful planning exercises for pandemic influenza.38Henning K.J. Brennan P.J. Hoegg C. O'Rourke E. Dyer B.D. Grace T.L. Health system preparedness for bioterrorism: bringing the tabletop to the hospital.Infect Control Hosp Epidemiol. 2004; 25: 146-155Crossref PubMed Scopus (24) Google Scholar, 39Doxtator L.A. Gardner C.E. Medves J.M. Responding to pandemic influenza: a local perspective.Can J Public Health. 2004; 95: 27-31PubMed Google Scholar N-PIPP provides excellent initial guidance in this area.B. Shortage of staff to meet increased patient demands for health careDevelopment of strategies to call up retired or part-time health care workers and expand hours of care provided by existing staff. Development of mechanisms for sharing of employees across systems or from outpatient to inpatient facilities at the local level (which may need to be done at the regional or state level for children).Legislation or other administrative procedures may be required to allow for temporary circumvention of licensing requirements of various professional boards during emergency conditions. Off-service clinical faculty in medical schools, medical students, residents on nonessential rotations, nursing students, and students in other health care profession training programs represent an additional HCW resource pool.10. InsurersIncreased patient volume stressing ability of office and insurer personnel to conduct "business as usual" and hinder efficient administrative responses‖This was not a major problem in short-lived influenza epidemic of 2003–2004, but this is anticipated to be a major issue under pandemic conditions of longer duration.Suspension of approval processes to free up hospital and insurance company personnel to deal with the other administrative demands of a pandemic.Federal indemnification of a proportion of pandemic-related costs may be necessary for financial survival of some health care systems, as well as for some insurers. Health insurers may need to explore how other insurers manage payments to those affected by large local natural disasters.∗ This table includes a broad range of topics but is not considered all-inclusive by the authors. Established planning groups throughout the world have identified other problems, as well as many of the above, and are making progress toward delineation and implementation of solutions to these.† WHO consultation on priority public health interventions before and during an influenza pandemic. April 27, 2004. http://www.who.int/csr/disease/avian_influenza/consultation/en/.‡ This was reasonably well accomplished in North Carolina during the 2003–2004 influenza epidemic, although the system stresses were far less than what would be present during pandemic conditions.∥ This was not a major problem in short-lived influenza epidemic of 2003–2004, but this is anticipated to be a major issue under pandemic conditions of longer duration. Open table in a new tab In terms of children's care issues, the N-PIPP does list the development of "regional surge capacity in providing care for children and adults including facilities and personnel, both in the hospital and in the community" as a priority area for upgrading the nation's health care system "to respond to bioterrorist and naturally occurring outbreaks of infectious diseases." Communities also are urged to develop real-time tracking of the number of available intensive care unit beds and medical beds for adults and children. Health care systems are encouraged to offer or expand hospital-sponsored sick care services for children of hospital staff to reduce absenteeism during pandemic conditions.25National Vaccine Program Office. United States Department of Health & Human Services. Pandemic influenza response and preparedness plan. Annex 2. URL: http://www.hhs.gov/nvpo/pandemicplan/index.html. Accessed October 20, 2004.Google Scholar The planning for specific needs of children currently is largely left to the local level. The CDC has developed 2 simple computer software modules for use as planning tools at local levels: FluAid 2.0 and FluSurge. FluAid uses p