Big Picture on Influenza - Wellcome Trust

<strong>Big</strong><strong>Picture</strong>Hit and runA flu infection can be unpleasant or deadly.The difference depends on both the virusand the person infected.© Sandy Huffaker/CorbisVirus genomesThe influenza genome is in constant flux.The influenza virus can survive and spread so wellbecause of its ever-changing genome. Two key processesshape its genome: reassortment (gene swapping) andmutation (gene change).Reassortment refers to the mixing of RNA in thevirus genome, which can occur if more than onetype of influenza virus infects a single cell,as seen in the emergence of S-OIV froma mix of different ancestors. In effect,influenza viruses have an enormousglobal pool of genetic material that cancome together in different combinations.Changes in the genome by reassortment maychange significantly the proteins on the surfaceof the virus, a process known as antigenic shift.Mutations are smaller-scale changes that occur in thegenetic material of an individual virus. However, thesemutations can lead to changes in the surface-proteinencodinggenes, resulting in new variants through theprocess of ‘antigenic drift’. Changes may arise because ofselective pressures (e.g. from the host’s immune system)or the accumulation of random changes over time.Shifts can be the earthquakes that unleash newpandemics, but drift is a constant nuisance, as newvariants evade immune responses and render vaccinesineffective within a year or so.Body of evidenceWhat happens when the influenza virus invades?When agroup ofMexicanslanded in Chinashortly after the start of the H1N1 swineflu pandemic they were in for a surprise.They were immediately placed inquarantine.However, preventing a disease suchas flu from entering a country is almostimpossible: in early stages of infection,people may show few if any symptoms.The number of places that an infectioncan enter a country is so large thatcontrol would be next to impossiblewithout bringing the country to a virtualstandstill.To date, public health has focusedon encouraging good infectioncontrol practices among the public.Is there a case for a more coerciveapproach? Certainly, if swine flu were toCivil libertiesDo human rights go out of the window whena pandemic strikes?become more severe, more draconianmeasures might be considered, suchas preventing certain large gatherings,restricting the movement of infectedpeople or enforcing vaccination.Given the political consequences ofsuch actions, they are likely to be madeonly after very careful considerationand when there is a substantial threat topublic health.It has been argued that part of thesuccess in controlling SARS wasbecause governments in the Eastwere able to impose public restrictionsrapidly and effectively. However, thisvirus has a different pattern of spreadfrom influenza.Politicians have the unenviable taskof safeguarding public liberties andpublic health, and a country’s economicwellbeing, in situations characterised byconsiderable uncertainty.The impact of an influenza virus depends on viral and hostfactors. Previous infection or vaccination should provide someprotection. If the virus is novel, the severity of an infection willdepend on its haemagglutinin and neuraminidase, and other viralproteins, which enable the virus to reproduce better in human cells.In fact, tissue damage has two origins – cells killed by the virusand the damage caused to the body’s own cells by the immunesystem. Both Spanish flu and H5N1 avian flu replicate to highlevels and provoke exceptionally powerful immune responses,which run away out of control in the lungs. Influenza viruses alsoleave patients at risk of secondary bacterial infections.To date, S-OIV has caused comparatively mild symptomsin most people. Those who have died have usually but notalways had underlying health problems, such as asthma orother respiratory ailments, morbid obesity or diabetes. Pregnantwomen are also at higher risk.Flu pandemics typically affect younger age groups thanseasonal flu. To date, H1N1 swine flu has had less impact onolder groups, possibly because they retain immunity from earlierH1N1 epidemics or benefit from some crossover immunity fromvaccination.Infants and young children may be at risk because theirimmune systems are immature. Paradoxically, young adults maybe at risk because they have the strongest immune systems.Who is doing what?International and national bodies are implementingpandemic plans.The international response to swine flu is coordinated by the World HealthOrganization, which decides pandemic levels (see page 3) and can act as aglobal coordinating body, particularly to support less developed countries. Ithas limited enforcement powers, however, so usually can only recommendparticular courses of action.The UK’s response to swine flu is led by the Department of Health (inpartnership with the devolved administrations), which receives input froma wide range of experts. Coordination across government and other keyservices is achieved through the high-level ‘COBR’ emergencies committee.The Department of Health has a pandemic plan, which has been adapted andimplemented for swine flu; it includes stockpiling of drugs and commitments topurchase vaccines.Monitoring of the pandemic has been the responsibility of the UK’s HealthProtection Agency, which has collected and disseminated data on theprevalence and spread of S-OIV.6 <strong>Big</strong> <strong>Picture</strong>: Special Issue