
Seasonal flu is due to antigen drift, tends to affect the elderly and at risk. Type A on the other hand exhibits antigen shift (probably by recombination between avian and human flu types in pigs, which can host either) as well as drift so attacks all sections of population equally, making epidemics/pandemics more likely, with attack rates of about 25%. Spanish flu in 1918 killed 20-50 million worldwide, almost half of whom were young, fit adults. Type B has no subtypes (although it does have neuraminidase, so susceptible to oseltamivir). Type C causes mild disease only, non epidemic.
Flu A subgrouped according to Neuraminidase and haemagglutinin (surface proteins) types.
Incubation period is short viz 1-3 days. Sudden onset fever, headache, cough/coryza, myalgia, GI upset. Benign myositis (with raised CK) esp calves can occur in type B.
Bacterial super-infection probably responsible for many deaths: good evidence for increased susceptibility to pneumococcus esp serotype 1, Hib, staph and meningococcus. So probably wrong to compare historical death rates too much given modern antibiotics and intensive care.
Other causes of death are encephalopathy, and myocarditis. A necrotizing encephalopathy (characterized by normal CSF and negative PCR) can occur - MRI shows bilateral high intensity T2 signals in thalamus, brainstem and cerebellum.
Transmission is not well understood! No good model. PCR can be positive in upper respiratory tract but not necessarily transmissible.
Prevention is by avoidance of droplets viz handwashing, masks, gloves and gowns. These are effective at preventing spread of respiratory viruses (NNT=4-6). Incremental benefit of antiseptics was uncertain. Benefit of advanced N95 mask uncertain. But most data comes from studies using drugs – only 3 looking at distancing (physical distance) or barrier methods. Annual vaccination campaigns run for people at risk - see Green book.
Oseltamivir and Zanamivir licensed for treatment and the former also for post-exposure prophylaxis. NICE recommends Oseltamivir from the age of 1yr upwards when:
Dose is twice daily for 5 days. It recommends Oseltamivir post-exposure prophylaxis where:
Dose is once daily for 10 days. Treatment for up to 6 weeks might be required during an epidemic.
WHO maintains pandemic flu surveillance. Has 6 phase alert system:
When levels of infection begin to drop, it may signify waning of the pandemic but subsequent waves are possible.
Pandemics do not necessarily start in winter. Different pandemics have exhibited different patterns of age affected, symptoms, severity. In Asian flu there was more diarrhoea, starting up to 1 week before respiratory symptoms; it also had a longer than usual incubation period. Waves of infection come every 15 weeks, of variable severity. Cumulative attack rate 25%, 1 in 200 hospitalized.
The consequences of a pandemic are:
This pandemic sneaked out before the predicted H5 pandemic appeared, starting in Mexico with large numbers of cases and deaths. Spread quickly around the world, with particular hotspots in the US, the UK, Australia, and Spain.
Because this was a strain associated with animals, apparently causing severe disease in young people, and spreading easily through communities, a pandemic stage 6 was eventually declared by WHO.
Epidemiology so far:
Severe disease usually develops on day 3-5 of illness. Sudden deterioration occurs, with progression to respiratory failure typically within 24 hours. Lung disease is mainly primary viral pneumonia, although 30% show coinfection esp pneumococcus, staph aureus. With severe disease, multiorgan involvement is common, and death is usually from respiratory failure (hence importance of ECMO) or refractory shock.
Oseltamivir does appear to be effective in severe disease.
A vaccine is now available.
In 1997 H5N1 appeared, every chicken in Hong Kong killed - spread controlled. Transmitted by respiratory route in birds whereas low pathogenicity avian influenza is faecal-oral. Since then has emerged again in mainland China, has increased virulence, and is now endemic in SE Asia poultry. Now also found in Africa. Human cases have spread as far as Turkey. Causes severe pneumonia and ARDS (also deranged LFTs, diarrhoea, ?enceph). >50% mortality. Family clustering suggests host susceptibility factors. In cats causes multisystem disease and can be spread cat to cat; but in monkeys it is almost exclusively a respiratory disease! Humans appear to be somewhere in between.
Higher viral load in throat/endotracheal cf nose unlike other influenza - suggests preference for lower respiratory tract, hence more severe respiratory disease, but equally lower transmissibility? Blood PCR positive is specific to fatal cases but not vey sensitive.
Culling is the preferred control measure but vaccination is complementary.
UK government has guidelines on avian flu - suspect if symptoms within 2 weeks of being in an affected country with contact history with birds. If mild, can be managed at home but review within 48 hours.

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