Patricia Daly MD, FRCPC, Reka Gustafson MD, FRCPC, Perry Kendall, MBBS, FRCPC Introduction to pandemic influenza We cannot predict when the next pandemic will occur or how severe it will be, but we can estimate overall impact using our knowledge of past pandemics. ABSTRACT: Influenza pandemics nfluenza pandemics can cause sig- headache, myalgias, and cough. Com- are global outbreaks that result from nificant morbidity, mortality, and plications can include viral or bacteri- the emergence of new subtypes of social disruption worldwide. The al pneumonia, exacerbation of under- the influenza A virus. A pandemic Ihistory of pandemics shows that a lying conditions such as congestive can occur if a new subtype causes pandemic has occurred every 10 to 40 heart failure, and, occasionally, death. significant human illness and is eas- years over the last 400 years. Recent During seasonal influenza, complica- ily transmitted from person to per- concerns about widespread outbreaks tions affect mostly the elderly, the very son. New subtypes may arise from of avian influenza H5N1 among poul- young, and those with underlying car- strains of avian or swine influenza A, 1 try (accompanied by more than 290 diac and respiratory conditions. which can occasionally cause hu- reported and confirmed human cases) Influenza viruses are part of the man illness but rarely precipitate have renewed pandemic planning Orthomyxoviridae family and are pandemics. H5N1 avian influenza, efforts from governments and public madeup of three types—A, B, andC— first identified a decade ago, has health officials. Since influenza pan- all of which can infect humans. Type caused widespread outbreaks among demics spread primarily in communi- A influenza viruses can also infect poultry since 2003 (beginning in Asia ty settings, community physicians birds as well as pigs and other mam- and then spreading to Europe and will provide much of mals, andare responsible for most sea- Africa) and rare but severe human the health care response during the sonal influenza epidemics. InfluenzaA illness. Concern that H5N1 may mu- next pandemic. However, community viruses also cause influenza pan- tate to produce a pandemic strain physicians’ involvement in pandemic demics. Influenza A viruses are nega- has prompted increased pandemic planning has been limited to date— tively stranded RNA viruses surround- planning among public health offi- something that must be addressed so ed by protein coats. During infection cials worldwide. that the needs of physicians and their Dr Daly is a medical health officer and the contribution to pandemic response can medical director of Communicable Disease be well defined. This will not only Control, Vancouver Coastal Health. She is help physicians to prepare for the next also a clinical associate professor in the influenza pandemic, it will provide a Department of Health Care and Epidemiol- good platform for considering the ogy at the University of British Columbia. issues facing physicians in other pub- Dr Gustafson is a clinical assistant profes- lic health emergencies. sor with Vancouver Coastal Health, and an Influenza A viruses instructor in the Department of Health Care and Epidemiology at UBC. Dr Kendall is Physicians are very familiar with in- BC’s Provincial Health Officer and a clinical fluenza, which in most otherwise professor in the Department of Health Care healthy children and adults causes a and Epidemiology at UBC. self-limiting febrile illness with fever, 240 BC MEDICAL JOURNAL VOL. 49 NO. 5, JUNE 2007 Introduction to pandemic influenza tion of hemagglutinins and neu- from the three pandemics that occurred raminidases (e.g., H1N1 shifts to in the 20th century: the 1918–19 neuraminidase H2N2). There are a number of possi- “Spanish flu,” the 1957 “Asian flu,” ble mechanisms for antigenic shift, and the 1968 “Hong Kong flu.” The hemagglutinin including the reassortment of human 1918–19 pandemic was due to an glycan chain of influenza viruses with avian or swine H1N1 virus, and caused as many as 50 host cell viruses, or significant point muta- million deaths worldwide during three membrane of 2 host cell tions of avian or swine viruses. distinct waves of illness over a 2-year protein Past pandemics period. The case fatality rate (i.e., the proportion of those infected who died) Influenza pandemics are global out- has been estimated to have been less Figure. Influenza A virus infects a host cell. 3 breaks of influenza that occur with the than 5%. No antivirals or antibiotics Source: US National Institute of General Medical Sciences. appearance of a new influenza A sub- were available at the time to treat pri- type, or re-emergence of a subtype that mary or secondary pneumonia. The has not been in circulation for many 1918–19 pandemic was unique not Figure ( ), aprotein on theviral sur- years. If a new subtype has either never only in its virulence but in its high face, hemagglutinin (H), attaches the circulated among humans, or has not mortality rate among young adults. virus to epithelial receptors in the res- done so for some time, the entire pop- The 1957 pandemic, caused by an piratory tract. Viral RNA then repli- ulation is naive and susceptible to H2N2 virus, was milder, resulting in cates in the host cell nucleus, and infection. In order for a new subtype to an estimated 1 million deaths world- another surface protein, neraminidase result in a pandemic, it must also cause wideanda case fatality rate of less than 4 (N), allows the newly formedviral par- significant human illness and be easi- 0.1%. The mortality rate was highest 2 ticles to be releasedfrom the host cell. ly transmissible from person to per- among traditional high-risk groups for Type A influenza viruses are fur- son. influenza (e.g., the elderly). The 1968 ther subtyped by their surface pro- teins—16 distinct hemagglutinins (H) and 9 distinct neuraminidases (N) are known, the combination of which is used to designate the subtype (e.g., H1N1, H3N2). All 16 hemagglutinins Although no expert can predict when the next and 9 neuraminidases can infect birds, causing avian influenza, but only a pandemic will occur or how severe it will be, subset (H1, H2, and H3; N1 and N2) 2 we can attempt to estimate overall impact typically circulate among humans. Influenza A viruses lack a mecha- using knowledge of previous pandemics. nism for correcting mistakes that oc- cur during viral replication, which can result in changes to the surface pro- teins. The continuous and relatively small changes that occur, known as “antigenic drift,” produce new strains of virus within the same virus sub- The first clearly documented hu- pandemic, caused by an H3N2 virus, 2 type. Since influenza vaccines induce man influenza pandemic was described was milder still. antibodies to surface viral proteins, in 1580, andhistorians have since doc- After each pandemic of the 20th influenza vaccines change yearly to umented 31 influenza pandemics in century, the new subtypes of influen- reflect the change in circulating total—suggesting that the appearance za A continued to circulate, causing strains. More substantial antigenic of new influenza A subtypes that can predictable annual seasonal influenza changes, known as “antigenic shift,” circulate among humans is inevitable. outbreaks. The H1N1 subtype remain- occur more rarely and result in new Most of our current understanding of edin circulation from 1918 until 1957, subtypes by switching the combina- influenza pandemics has been derived when it was replacedby the H2N2 sub- VOL. 49 NO. 5, JUNE 2007 BC MEDICAL JOURNAL 241 Introduction to pandemic influenza Estimating the impact of pandemic influenza on the BC explains why young infants experi- health care system ence greater morbidity from influenza infection than older children and During an influenza pandemic, the BC health care system will not continue to function in the adults—this is their first exposure to usual fashion. Health care deliverers, planners, and managers are being encouraged to use the virus. scenarios and planning assumptions to develop mitigating strategies that address issues Although no expert can predict such as determining if elective surgeries will continue at the usual rates, and ensuring there when the next pandemic will occur or are triage protocols for clinical care resources developed with the aid and assistance of bio- how severe it will be, we can attempt ethicists. To reduce the burden on primary care, health authorities will also provide self-care information to the public during a pandemic, including details on how to stay healthy, what to estimate overall impact using our symptoms to look for, how to take care of your own illness, and when to seek medical care. knowledge of previous pandemics. One estimate of the potential impact The BC Ministry of Health has used the pandemic parameters included in FluSurge (the of a pandemic on morbidity, mortali- 5 pandemic estimation tool developed by the US Centers for Disease Control and Prevention) ty, and health care demand is described to predict the demand on the BC health care system. The basic assumptions from this 5,6 model are: in the accompanying box, “Estima- • There will be a 35% clinical attack rate. ting the impact of pandemic influenza • Half of those infected will seek ambulatory care. on the BC health care system.” This is • 1.3% of the 35% infected will require hospitalization. a rough estimate, based on the 1957 and 1968 pandemics, and should there- Epidemics in populous areas will have sharper peaks than those in less populous areas. The peak period of the epidemic curves will likely be between 3 and 5 weeks in duration. In the fore be interpreted only as an indica- absence of mitigating antiviral strategy or a pandemic vaccine, both of which are being tion of the order of magnitude of mor- planned for at the provincial and national levels, the following scenarios could be anticipat- bidity and mortality we could see in a ed during a peak epidemic week: pandemic of the severity of those two • A 40% increase in GP visits over the average of 377 651 weekly fee-for-service pandemics.