content.nejm.org/cgi/content/full/352/18/1839
Find Similar Articles Annual influenza epidemics are like Minnesota winters ^ all are challeng es, but some are worse than others. No matter^ how well we prepare, some blizzards take quite a toll. Each^ year, despite our efforts to increas e the rates of influenza^ vaccination in our most vulnerable populations , unpredictable^ factors largely determine the burden of influenza disea se and^ related deaths. During a typical year in the United States,^ 30, 000 to 50,000 persons die as a result of influenzavirus infection,^ and the global death toll is about 20 to 30 times as high as^ the toll in th is country. We usually accept this outcome as^ part of the cycle of life . Only when a vaccine shortage occurs^ or young children die suddenly do es the public demand that someone^ step forward to change the course of the epidemic.
Technician Working on Egg-Based Production of Influenza Vaccine. An influenza pandemic has always been a great global infectious-disease^ threat. There have been 10 pandemics of influenza A in the past^ 300 yea rs.
Will it be caused by H5N1, the avian influenzavirus^ stra in currently circulating in Asia? Will its effect rival^ that of 1918 or be more muted, as was the case in the pandemics^ of 1957 and 1968? One key step is to rapidly ramp up research^ relat ed to the production of an effective vaccine, as the Department^ of Heal th and Human Services is doing. In addition to clinical^ research on the immunogenicity of influenza vaccines, urgent^ needs include basic resea rch on the ecology and biology of influenzaviruses,^ studies of the epid emiologic role of various animal and bird^ species, and work on early in terventions and risk assessment.
Today, making the 300 million dos es of influenza vaccine^ needed annually worldwide requires more than 35 0 million chicken^ eggs and six or more months; a cell-culture approach may produce^ much higher antigen yields and be faster.
Microcarriers with Vero cells are shown before (top) and after (bottom) i nfection with influenzavirus. Beyond research and development, we need a public health approach^ that i ncludes far more than drafting of general plans, as several^ countries a nd states have done. For example, in the United^ States today, we have on ly 105,000 mechanical ventilators, 75,000^ to 80,000 of which are in use at any given time for everyday^ medical care; during a garden-variety i nfluenza season, more^ than 100,000 are required. In a pandemic, most pa tients with^ influenza who needed ventilation would not have access to i t^ We have no detailed plans for staffing the temporary hospitals^ that woul d have to be set up in high-school gymnasiums and community^ centers a nd that might need to remain in operation for^ one or two years. Health care workers would become ill and die^ at rates similar to, or even high er than, those in the general^ public. Judging by our experience with th e severe acute respiratory^ syndrome (SARS), some health care workers wo uld not show up^ for duty. Who, for instance,^ would receive the extremely limited antiviral agents that will^ be available? We need to develop a national, and even an international,^ consensus on the priorit ies for the use of antiviral drugs well^ before the pandemic begins. In addition, we have no way of urgently^ increasing production of critical items such as antiviral drugs,^ masks for respiratory protection, or ant ibiotics for the treatment^ of secondary bacterial infections. Even unde r today's relatively^ stable operating conditions, eight different antii nfective agents^ are in short supply because of manufacturing problems. We would still need to plan with fervor for local^ nonmedical as well as m edical preparedness. Planning for a pandemic^ must be on the agenda of e very public health agency, school^ board, manufacturing plant, investmen t firm, mortuary, state^ legislature, and food distributor. Health profe ssionals must^ become much more proficient in "risk communication," so t hat^ they can effectively provide the facts and acknowledge^ the unkno wns to a frightened population.
Although the manufacturing capacity would^ still be limi ted, strategies such as developing antigen-sparing^ formulations that is, intradermal formulations that^ take advantage of copious numbers of dendritic cells for antigen^ processing or formulations including adjuva nts to boost the^ immune response might extend the vaccine supply. Urg ent^ planning efforts are required to ensure that we have the syringes^ and other essential equipment, as well as the workforce, for^ effective delivery. The belief that^ we can greatly advance manufacturing technology and expand capacity^ in the normal cour se of increasing our annual vaccination coverage^ is flawed. At our curr ent pace, it will take generations for^ meaningful advances to be made. Our goal should be to develop^ a new cell-culturebased vaccine that inc ludes antigens^ that are present in all subtypes of influenzavirus, that do^ not change from year to year, and that can be made available^ to th e entire world population. Similar changes have occurred in the human and^ animal populations of other Asian countries, creating an incredible^ mixing vessel for viruses.
Clinical,^ epide miologic, and laboratory evidence suggests that a pandemic^ caused by th e current H5N1 strain would be more likely to mimic^ the 1918 pandemic t han those that occurred more recently.
Proposed Mechanism of the Cytokine Storm Evoked by Influenzavirus. The key element in generating the storm is an uncontrolled exuberant immu ne response to the virus, in which there is an outpouring of proinflamma tory cytokines and chemoattractants.
The answer^ is a qualif ied yes that depends on how everyone, from world^ leaders to local elect ed officials, decides to respond. We need^ bold and timely leadership at the highest levels of the governments^ in the developed world; these go vernments must recognize the^ economic, security, and health threats pos ed by the next influenza^ pandemic and invest accordingly. The resources needed must be^ considered in the light of the eventual costs of failin g to^ invest in such an effort.
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