Epidemics: Reading #2


Influenza: Past and Future


The Epidemic on the Way: Why Winter Flu Is So Bad This Year

Debora MacKenzie

New Scientist | January 2, 2018


Flu is an underestimated killer, taking more than a million lives around the globe annually. This time, the mutated virus seems to be hitting even harder.


What is flu?

Flu is a small virus with just 11 genes made of RNA. One type, influenza B, infects only humans, and two strains of it are circulating this year: Yamagata and Victoria. The other common type of flu is influenza A. Its many strains mostly, and in large part harmlessly, infect waterfowl, but three varieties have adapted to humans. Those three plus a few more infect other mammals, notably pigs.


Influenza A strains are named after their two main surface proteins, haemagglutinin (H) and neuraminidase (N). There are 18 types of H and 11 of N in bird viruses, and immune-system antibodies that attack one type don’t recognise another. Only viruses H1N1, H2N2 and H3N2 have fully adapted to humans, and only H1N1 and H3N2 currently circulate in us. People sometimes catch other strains of bird flu, for example H5N6, but they cannot spread.


Dominant strains of both A and B circulate together in the northern and southern hemisphere winters, infecting up to half of all people and causing disease in between 10 and 15 per cent. Influenza A is of extra concern because new viruses, or just viral genes, sometimes jump from birds to humans and the novel virus can cause an especially severe pandemic flu.



[1] Why does flu keep coming back?

Flu is unique among human diseases. It circulates constantly in cool, dry areas of east Asia, conditions the virus prefers, but when temperatures drop during the winters, it breaks out and begins a tour of the relevant hemisphere. Because it spreads from person to person efficiently in exhaled droplets, and can be picked up from contaminated surfaces, nearly everyone is exposed.


[2] And unlike, say, measles, having flu once doesn’t make you immune to catching it. The virus is uniquely talented at dodging our immune systems. The big haemagglutinin protein on its surface gets most of your immune system’s attention, and this protein constantly mutates at seven hotspots. Every few years it racks up such a number of mutations that many antibodies you made to your last infection don’t recognise the virus, and you get sick again. You still have some immunity to kinds of flu that are only a little different from viruses you have seen before, which is why much winter flu isn’t as severe as flu can be. The strains best able to evade this kind of prior immunity dominate the annual epidemic in each hemisphere, so we only need one vaccine per season— but a new one each year.


Why are people worried this year?

[3] A record number of flu strains are currently circulating, two in the influenza B group and two influenza A strains, H1N1 and H3N2. H3N2 is the real problem. Our strongest immunity is to the first kind of flu we caught. Between 1918 and 1968, no H3N2 viruses circulated as winter flu, so people born before 1968 have weaker immunity to it. That includes elderly people, whose faltering immune systems make them more vulnerable. There are more than four times more deaths in seasons dominated by H3N2, amounting to 220,000 last winter in Europe. This year’s H3N2 seems to be especially severe: in Australia in the winter just past, it caused more than three-quarters of all flu cases (see diagram), and more than 2.5 times more people than usual sought medical help. The likelihood of dying was relatively high, with most deaths among elderly people— but not all.


[4] “We don’t really know what makes some winter flu viruses more severe than others,” says Colin Russell at the University of Amsterdam. It’s a mix of the virus’s inbuilt weaponry to defeat our immune system and our system’s ability to recognise and respond to it fast enough. With this year’s H3N2, it could be either or both, says Derek Smith at the University of Cambridge— virologists can’t yet tease all the variables apart.


Waiting for the Big One: A New Flu Pandemic Is a Matter of Time

Debora MacKenzie

New Scientist | January 2, 2018


[1] The Spanish flu of 1918 remains the worst flu pandemic on record, but there have been several milder ones since (see chart, below). A pandemic is a global epidemic and, in theory, flu does that every year in the northern and southern winters. But with flu, the term is reserved for when an influenza A virus emerges that isn’t just a slightly mutated version of last winter’s flu, but a complete novelty, with surface proteins most people have no immunity to.


[2] Novel flu viruses are constantly evolving in the birds, pigs and other animals that also carry influenza A, and they can shuffle their genes with human strains, or just adapt to mammals directly. Virologists consider flu pandemics inevitable. The World Bank says a bad one “could cost $3 trillion… and cause misery, economic decline, and societal disruptions on a global scale“.


[3] Like winter flu, the impact of pandemic flu depends on both the virus’s abilities and people’s immunity. The swine flu that went pandemic in 2009 was already adapted to causing only relatively mild illness in mammals. It still killed some 300,000 people. For once, older people were better protected: many people over 52 had immunity thanks to a related winter flu that circulated before 1957.


[4] In 1918, many people over 71 were also protected, since a related winter virus seems to have circulated before 1847. But the Spanish flu was a bird flu that learned to transmit between mammals, and was equipped with fast gene-replicating enzymes that were adapted well to birds, but deadly in mammals. Young adults especially died in droves.


[5] Our knowledge of the flu strains circulating in the past century means we are pretty sure almost no one will have encountered relatives of the next bird flu to go pandemic. Virologists sounded the alarm in 1997 when H5N1 bird flu jumped to people, but so far it has not acquired the mutations that would let it spread from human to human, a necessary condition for going pandemic. H7N9, which started infecting people in China in 2013, seems to have the required mutations already: a strain isolated recently spread readily, and lethally, among experimental mammals, and was evolving resistance to Tamiflu, an antiviral drug crucial in saving severely ill people in 2009.


[6] If a pandemic strikes, what could we do? The world’s single-strain vaccine production capacity has grown from 1.8 to 6.4 billion potential doses since 2006, with World Health Organization backing. But most producers grow vaccines in eggs, which takes months. In 2009, there was no vaccine before the first wave of swine flu was nearly over. Also, manufacturers have only the egg supplies for each hemisphere’s yearly production. There may not be enough eggs when everyone wants pandemic vaccine at once– especially if the emerging flu also kills chickens.


[7] “A technological jump is required— either a universal flu vaccine or a rapid production platform”, such as insect cells or plants, says Martin Friede of the WHO. Facilities designed to combat pandemic flu will have to stay fighting fit by making other vaccines when there is no pandemic— not impossible, but commercially unprecedented. Both efforts could use a lot more funding. “The Manhattan project is an overused metaphor, but that is really what we need for flu vaccine,” says Osterholm.


[8] Yet the world has flu fatigue. A decade ago, the emergence of H5N1 caused widespread panic. Now public investment has fallen, partly because the relatively mild 2009 pandemic wasn’t the disaster feared. The real problem, say epidemiologists, is that flu is so familiar. It can be mild– except when it isn’t. Until we recognise flu for the killer it is, we won’t do better at stopping it.


Center for Infectious Disease Research and Policy (=CIDRAP) | Jun 27, 2012

CDC Estimate of 2009 Global H1N1 Pandemic Deaths: 284,000

Robert Roos



[1]  (CIDRAP News) – Working with admittedly sparse data, a research team led by the US Centers for Disease Control and Prevention (CDC) has estimated the global death toll from the 2009 H1N1 influenza pandemic at more than 284,000, about 15 times the number of laboratory-confirmed cases. The World Health Organization (WHO) has put the number of deaths from confirmed 2009 H1N1 flu at a minimum of 18,449, but that number is regarded as well below the true total, mainly because many people who die of flu-related causes are not tested for the disease.


[2]  The CDC-led team, which included researchers from several other countries, based its estimates on H1N1 case data from 12 countries and case-fatality ratios (CFRs) reported from five countries. Their report was published online yesterday in the Lancet Infectious Diseases. The researchers estimate that the pandemic virus caused 201,200 respiratory deaths and another 83,300 deaths from cardiovascular disease associated with H1N1 infections. They also calculate that Africa and Southeast Asia, which have 38% of the world's population, accounted for a disproportionate 51% of the deaths. The team estimated that 80% of those who died were younger than 65, which is in accord with previous observations that the pandemic H1N1 burden fell heavily on younger people, unlike the pattern for seasonal flu.


[3]  The team, with the CDC's Fatimah S. Dawood, MD, as first author, set out to estimate H1N1 deaths in the period April 2009 through August 2010, focusing on the first 12 months of H1N1 circulation in each country. Their general approach was to estimate the cumulative symptomatic-case attack rate (sAR) with data from high-income, middle-income, and low-income countries and multiply it by the estimated symptomatic case-fatality ratio (sCFR) derived from data from certain high-income countries. The authors stratified their estimates of SAR into three age-groups: 0 to 17 years, 18 to 64, and over 64. They obtained estimates of the attack rates in those groups from 12 countries: Bangladesh, Denmark, Germany, India, Kenya, the Netherlands, New Zealand, Nicaragua, Peru, the United Kingdom, the United States, and Vietnam. The SAR estimates ranged from 4% to 33% for the pediatric group, 0 to 22% for 18- to 64-year-olds, and 0 to 4% for those over 65.


[4]  The authors devised a way to adjust for differences in the risk of respiratory-disease death between high- and low-income countries. They used the WHO's country-specific mortality rates for lower respiratory tract infections and the agency's classification of countries into five mortality strata to come up with a "respiratory risk multiplier." As part of steps to minimize distortions related to the use of data of uneven quality, they assigned countries to one of three mortality risk groups: African countries, non-African countries with high child and adult mortality, and all other countries. The estimation process yielded thousands of mortality estimates for each age-group and risk group.


[5]  The team also devised a way to estimate deaths due to cardiovascular complications of H1N1 infections. This involved using estimates of excess circulatory and respiratory deaths attributed to the virus in Argentina, Brazil, Chile, Mexico, and the United States and the base respiratory mortality rate in each country. The total of median estimates of country-specific respiratory deaths was 201,200, with a range of 105,700 to 395,600, calculated on the basis of the 25th- and 75th-percentile estimates for each age-group and country. Another 83,300 deaths (range, 46,000 to 179,900) were attributed to cardiovascular complications, for a total of 284,400 (range, 151,700 to 575,400). (Because of rounding of regional estimates, the totals don't add up precisely.)


[6]  Twenty-nine percent of the respiratory deaths were ascribed to African countries, where the estimated mortality rate was about two to four times as high as in countries elsewhere. The addition of cardiovascular deaths reduced regional disparities in deaths, but African mortality still was two to three times higher than elsewhere, the report says. Overall, only 20% of the deaths were in people older than 64. In contrast, about 90% of seasonal flu deaths are in seniors. . . . 


[7] The authors say their estimate of 151,700 to 575,400 deaths represents 0.001% to 0.011% of the world population. For comparison, they observe, the WHO estimates that 250,000 to 500,000 people (0.004% to 0.008% of the population) die of seasonal flu annually, and flu deaths in past pandemics ranged from 0.03% of the population in 1968 to 1% to 3% in 1918. However, the team says its numbers are not directly comparable to the WHO seasonal flu estimate and the past pandemic numbers for various methodologic reasons. For example, the estimates for the earlier pandemics include data from several years of virus circulation, not just the first year. The estimation approach used by the authors received a general endorsement from Marc Lipsitch, PhD, an epidemiologist and director of the Center for Communicable Disease Dynamics at the Harvard School of Public Health.


[8]  Lipsitch told CIDRAP News via e-mail that he was not completely independent from the study because he served on a WHO working group that gave the authors some advice, and he cautioned that he had not yet read the full report. But he said, "I know the broad outlines of their method and think it is a plausible approach to a very difficult problem of making estimates with extremely limited data, where even the available data are really very uncertain. "I don't know if the number is right, but certainly any reasonable estimate would be far above the WHO number of confirmed deaths," he added. "Confirming flu deaths is not routine (and much less than 100% sensitive) in the richest countries, and would be exceptional rather than likely in much of the world. Thus the disparity from the WHO confirmed number is a good sign, not a red flag."


[9]  In a commentary accompanying the study, Cecile Viboud, PhD, and Lone Simonsen, PhD, write, "Future research should focus on obtaining additional country-specific estimates of the burden of seasonal and pandemic influenza in understudied locations through traditional excess mortality approaches or innovative surveys of mortality, and address the lack of estimates of case fatality rates from middle-income and low-income regions." Viboud works at the National Institutes of Health's Fogarty International Center, and Simonsen is with George Washington University's School of Public Health. The two were part of a team that in March 2010 estimated years of life lost because of the 2009 H1N1 pandemic in the United States. The authors of the study say their findings point up the need to expand delivery of flu vaccines to Africa and Southeast Asia, since those regions may have borne a disproportionate share of the pandemic mortality burden.


Mystery of 1918 Flu That Killed 50 Million Solved?

Children born in the 1800s lacked exposure to influenza before the pandemic of the early 20th century.

Dan Vergano

National Geographic | APRIL 28, 2014



Scientists announced Monday that they may have solved one of history's biggest biomedical mysteries— why the deadly 1918 "Spanish flu" pandemic, which killed perhaps 50 million people worldwide, largely targeted healthy young adults.


[1]  The explanation turns out to be surprisingly simple: People born after 1889 were not exposed as kids to the kind of flu that struck in 1918, leaving them uniquely vulnerable. Older people, meanwhile, had been exposed to flu strains more closely related to the 1918 flu, offering some immunity. Simply put, the Spanish flu owed its ferocity to a switch in dominant influenza varieties that had occurred a generation earlier. "All a matter of timing," says virologist Vincent Racaniello of Columbia University in New York, who was not part of the study. Researchers involved in the study looked at the evolutionary history of the components of the 1918 flu, which was built of genes from human and avian flu strains. They unraveled the history of dominant flu strains stretching back to 1830.


[2]  The evolutionary biologists found that a worldwide 1889 outbreak of the so-called Russian flu, the H3N8 flu virus, left a generation of children that had not been exposed to anything resembling the Spanish flu, which was an H1N1 strain. (The H and N in the flu designation stand for proteins called hemagglutinin and  neuraminidase, respectively). The spread of a more closely related H1 flu variety after 1900 provided partial immunity to children born after that time. That closed the window of vulnerability.


[3]  "You have the most deadly flu pandemic in history essentially leaving the elderly, its most frequent victims, completely alone," says biologist Michael Worobey of the University of Arizona in Tucson, who led the Proceedings of the National Academy of Sciences report. Instead, people aged 18 to 29 died in droves during the outbreak, which killed about 1 in 200 of victims.


[4]  Experts have suggested that such a window of vulnerability partly explained the 1918 pandemic, Racaniello notes. But the new study provides computational evidence that the 1918 flu's precursor originated around 1907, he says, and explains how the window of vulnerability opened and closed for the disease. The new finding may help public health officials deal with future pandemics, amid current worries about deadly avian flu strains jumping to humans. It may also alter how we vaccinate against future flu outbreaks, keying vaccines not to current seasonal flavor, but to strains that people didn't gain immunity to as children.


Flu Fluctuations

[5]  Seasonal flu strains typically enjoy decades of dominance in the human population. These periods are often capped by outbreaks of new flu varieties, such as the 2009 H1N1 flu pandemic that led to the current reign of this strain of flu, which killed perhaps 284,000 people worldwide, according to the U.S. Centers for Disease Control and Prevention. "The seasonal drift is normal and is the reason why we have yearly vaccines produced to protect against these seasonal changes," says immunologist Michael Gale, Jr., of the University of Washington in Seattle.


[6]  The key to the team's reconstruction was the realization that flu genes evolve at different speeds in birds, pigs, and people, Worobey says (it's faster in chickens, for example). Once the evolution of flu strains is reset with timing tuned to each carrier species, "the picture came clear," he says. Rather than a sudden movement of avian flu genes in 1918 explaining the Spanish flu, the study suggests that many of them moved into seasonal flu after 1900. A change in the kind of hemagglutinin used by an already-existent flu strain likely led to the pandemic around 1918.


Universal Vaccine

[7]  The overall message of the study is a hopeful one, say the researchers, because the bacterial pneumonia secondary to the 1918 flu that killed most of its victims is treatable with modern antibiotics. "If there was something particularly deadly about the 1918 strain, then you are out of luck when something like it happens again," Worobey says. "But if this is just the effect of lack of exposure, then we can be more confident of treatment."


[8]  If that's the case, the makers of future flu vaccines may want to tune their ingredients to people's ages, aiming to arm them against flu strains they likely missed exposure to during childhood, the prime age for getting the flu. "It really offers a lot of support for a 'universal' flu vaccine that aims to prevent all varieties of flu," Worobey says. Such a vaccine would be aimed at all strains of flu viruses, not just the current dominant seasonal ones.


Influenza: A Killer Cold?

National Geographic



[1]  For most people flu is a seasonal nuisance, announced by a fever, a headache, and a sore throat. A few days to a week and you're over it. However, the virus can be a lot more serious. Influenza, as it's properly known, causes up to half a million deaths a year worldwide. And less than a century ago it became a global catastrophe, striking a fifth of the planet's population and claiming more than 50 million lives. Experts say we can expect a similar outbreak in the future.


[2]  Among the most common contagious human diseases, influenza usually strikes in winter, spreading through airborne droplets and particles emitted in coughs or sneezes. Between 5 and 15 percent of the population are affected by these annual epidemics. Human influenzas are divided into two groups, A and B. Influenza A contains the key strains, which are distinguished by spikelike features known as antigens. The genetic makeup of these viruses allows for frequent mutations. That's how they keep managing to sneak past our immune systems and why new flu vaccines are needed each year.


[3]  These vaccines are important for the elderly and sick, who have a much higher risk of flu-related health complications such as pneumonia, a potentially fatal lung infection. More than 90 percent of deaths linked to influenza are in people over 65. We can blame birds— particularly waterfowl— for that's where flu first originated. These birds act as reservoirs for Influenza A and are thought to be its source in all other animals. Human influenzas, once established, are usually familiar enough for our bodies to deal with, despite their mutations. But occasionally something totally new comes along— and finds us sitting ducks.


Historic Outbreak

[4]  It happened, infamously, in 1918, with the outbreak of Spanish flu (so named because Spanish newspapers were among the first to report it). Known as a pandemic because of its global reach, Spanish flu spread as far as the Arctic and remote Pacific islands. It killed more than 10,000 people a week in some cities. The victims, many of them young adults, suffocated as their lungs drowned in bloody fluids. About 5 percent of those infected died. Current estimates suggest between 60 million and 100 million people died worldwide.


[5]  Today scientists think Spanish flu was a bird flu, or avian influenza. In two subsequent lesser flu outbreaks in 1957 and 1968, an avian flu combined with a human flu to create a hybrid strain that was able to infect people. For this to happen, the two viruses needed to coexist in the same animal species. Pigs are seen as the likeliest candidates. Studies suggest that Spanish flu was so lethal because it somehow crossed into people as an animal virus, without the genes from human strains that our immune systems were expecting. The same happened with the latest bird flu to affect humans. Spread by wild birds, the H5N1 virus jumped from chickens to people in 1997. First recorded in Hong Kong, nearly all infections to date have come through close contact with poultry.


Swine Flu Outbreak

[6]  In spring 2009, an outbreak of swine flu (officially called H1N1) killed more than a hundred people in Mexico, raising fears of a possible pandemic. Cases were soon reported across North America, and in October 2009 the first H1N1 vaccines became available. Swine flu is caused by an Influenza A virus and affects pigs year-round. The disease is able to jump to humans when a strain develops that is a mixture of animal and human versions of the virus. It is usually spread by people who are in close contact with pigs, such as farmers.