BioNyt - Videnskabens Verden (Comments: bionyt@gmail.com)

Swine flu - Mexican A/H1N1 influenza - North American influenza A/H1N1 virus
Outbreak in spring 2009

Things to do if the risk is there; History of the epidemic; Assessing the severity of an influenza pandemic; Bacterial co-infections?; Information for laboratory workers; Background for the epidemic; General information; Symptoms of the Swine Flu; Overcoming the Swine Flu; Should vaccination be with live or inactivated virus?; Next generation of vaccines; Literature and references; Key words and abbreviations; Swine flu genes in China - and diagnostic means; Other flu infections; Links; The AVAAZ initiative against big unregulated pig farms.

Influenza A(H1N1) is the official name of the disease since it spreads from humans and not pigs

The Influenza A(H1N1) epidemic is not alarming because:
• It is not a good killer (this was not known in the beginning of the epidemic)

The Influenza A(H1N1) epidemic could be alarming because:
• It might change to become a better killer

• It might be a better killer next virus season (it is not uncommon that the next wave of a flu a half year later is more aggressive)

• It might spread in countries entering their flu season (Argentina etc., South Africa, New Zealand)

The Influenza A(H1N1) epidemic is alarming because:
• It can kill young healthy people just like the influenza in 1918 ("Spanish flu").
• It is a new flu virus from animals - unknown for the human immune system.
• It spreads globally
• It can infect from people to people
• It infects young and middle aged people
• It might change to a more lethal type - spontaneous or if an individual (pig or human) get two different virus types simultaneous
• We know by experience that flu - if lethal and infectious - can kill millions. The Spanish flu i 1918-1919 killed more people than World War I.
• A vaccine would take more than 6 months to produce.
• The new flu came at the beginning of the flu season for countries with poor ressources.

• The more people are infected with the new flu, the bigger is the risk that the virus will infect a cell which is already infected by another flu virus (may be a bird flu virus). Then a new, recombined virus can emerge, which might be more lethal, more infectious or both. (However the bird flu virus which has infected few people during the last 13 years and which is highly lethal has not yet recombined with a human flu virus)
• Two billion people will likely be infected if the flu becomes a pandemic (1/3 of the world 6 billion people based on experiences from earlier pandemics). It is unknown how many would die.Luckily the new virus is not very lethal, but rather similar to ordinary flu. However it may change and even a not very lethal virus could make great damage if it is highly infectious.
[7015]

Swine flu has symptoms nearly identical to regular flu — fever, cough and sore throat — and spreads like regular flu — through tiny particles in the air — when people cough or sneeze.

The reason some people die of this infection seems to be a result of the immune systems overreaction resulting in fluid in the lungs blocking oxygen uptake to the blood.

The fact that some people die means a resource problem for the hospitals - very soon there will be too few respirators and too little personel to handle all the sick people.

Around 4 May 2009 it became clear that the swine flu of April 2009 was not so dangerous if treated. The reason that people died in Mexico but not in other countries was lack of treatment. The people who died were often too poor to go to hospital (could not afford to be ill), or were not treated. This became known as "the influenza epidemic danger has disappeared". However, it might be too soon to make this conclusion. The poor countries of the world - with no treatment drugs available and no plans for such epidemics - are now going into the flu season (winter). The fact that this flu might not be containable, and still is dangerous for otherwise healthy people is a course for concern.

In the 1918 pandemic there were a four-month gap between the first, mild wave of illness and the big attack, which had a death rate that if translated into today would mean 170 million victims world wide. [6978] A pandemic today could take fewer lives - or it could take more lives. Only a few countries have vaccine plants, mainly in Europe. They may in a chaotic life-treatening situation be more or less willing to export their products. Afterall infectious diseases are the greatest enemy, even compared to war, earthquake or tsunamis. [6978]

The risk of global deadly virus infections should be taken more serious. Research in the swine flu virus has been neglected. This new type of virus emerged in USA in 1998, so we have had 11 years to study and fight it.

It became endemic on swine farms across North America. The new virus combination is so different from existing human flu virus that most people have no immunity to is and there is no existing vaccines. [6978] The new Mexican A/H1N1 swine flu virus are parcicularly worrying because the surface proteins will not be recognised and defeated by the human immune system since all surface proteins are from swine flu virus. It contains two genes from bird flu virus which are thought to make the virus spread more easily [6978]. The new virus flu spreads rather easy from human to human. The virus also containes one human flu gene - and five swine flu genes.

The further the virus spreads (one person from South Korea was infected in April 2009) the more chance it will mix, or reassort, with other flu viruses in circulation and turn into something more lethal. "The prospects for change in the virus are considerable and worrying," warns virologist Kennedy Shortridge, who is a professor emeritus at the University of Hong Kong, where he led investigations into the initial emergence of H5N1 bird influenza in 1997, when it killed six of the 18 people it infected. The city squelched that outbreak by slaughtering all 1.4 million chickens and ducks in the territory. H5N1 re-emerged in 2003 and since then has claimed 257 lives while devastating poultry flocks throughout much of Asia and parts of Africa. Kennedy Shortridge also was among the first to suggest that pigs might act as mixing vessels for new combinations of viruses. He has long advocated global cooperation in the surveillance of circulating flu viruses to spot emerging new strains so that public health officials could plan a response and drug companies could get a head start on making vaccines. [Science, 6971]

Kennedy Shortridge is concerned that this new patched-together virus - with genes likely to come from N-America, Europe and Asia - might not be stable. The virus could easily reassort with other viruses such as H5N1 virus i Asia and strains of human H1N1 resistant to Tamiflu - such resistant strains are in circulation in many areas. He speculates that swapping one or more genes among these viruses could result in a virus that is more pathogenic, more easily passed from person to person, more resistant. [Science, 6971]

If you are exhibiting flu-like symptoms prior to going abroad, it is highly recommended that you consider postponing international travel. If you are currently travelling and have become ill, seek medical attention immediately. [7038]



Things to do if the risk is there:
Do not kiss or make physical contact. Keep a distance. Stay indoor. Wear a mask. Keep hands off everything in the public. Wash your hands very often. Stay away from gatherings, such as busses, warehouses etc. (The masks do little to prevent the spread of the virus - but keep your hands away from your face - and make you recall to protect yourself). Hand washing is one of the easiest and most important things you can do to stop the spread of germs.

Always wash hands: after coughing, sneezing or blowing your nose
after using the restroom
before and after preparing food
before eating
before and after changing diapers
after touching an animal or its waste
after doing chores, such as handling garbage or doing yardwork
before and after caring for someone who is sick or hurt


Remember to wash your hands for at least twenty seconds. If you need a timer, imagine singing "Happy Birthday" two times. If you do not have soap and water nearby, use an alcohol-based hand sanitizer (at least 60% alcohol based).

Disinfecting shared objects and common areas can help kill germs on surfaces and keep people from getting infected. For example, clean countertops, sinks, doorknobs, tables, telephones and anything else that people touch often.

Don't share personal items
These include anything that has been near a person's mouth, nose or eyes, such as:
toothbrushes
drinking cups or straws
makeup
eating utensils
washcloths or towels


Practice cough and sneeze etiquette
try to stay at least 3 feet away from other people
cover your mouth and nose with a tissue, then throw the tissue away
cough or sneeze into your upper sleeve if you have no tissue (not your hand)
always wash your hands immediately afterwards


Keep your distance from family and loved ones until you are well again. If you have children who are sick, it is a good idea to keep them home from school.




Never use the hand dryer on the toilet. They spread virus. According to a British study people have 3 times more bacteria on their hands after using the hand dryer machine than if they use paper to dry their hands. The air flow also make virus to fly around you.



Swine Influenza (swine flu, pig flu) is a respiratory disease of pigs caused by type A influenza. This virus type regularly cause outbreaks of influenza among pigs. Normally, swine flu viruses do not infect humans. However, human infections with swine flu do occur. Cases of human-to-human spread of the new type of swine flu viruses have been documented. The new subtype of A/H1N1 of the spring 2009 had not previously been detected in swine or humans.

Since March 2009, a number of confirmed human cases of a new strain of swine influenza A (H1N1) virus infection have been identified in Mexico, USA (including New York and California), Canada, Portugal, Spain, Switzerland, Scotland & Britain, Germany, Austria, Holland, Israel, South Korea, Peru, and New Zealand.

The new strain of swine flu is the suspected killer of about 150 people in Mexico (April 26, 2009). 20 of these have been confirmed to have been infected by the new virus strain. Most concerning the dead were 25-45 years old, while normally only old people and very young die during influenza epidemics. During the Spanish Disease in 1918 people from 15-45 years old died.

The authorities closed schools, museums, libraries and theaters in the capital of Mexico and asked people not to go to church and other gatherings.

The authorities tried to contain the outbreak that had spurred concerns of a global flu epidemic. Do not kiss or contact. Keep a distance. Stay indoor. Wear a mask. Keep hands off everything in the public. Wash your hands very often. Stay away from gatherings, such as busses, warehouses etc.

Stay home if you get sick: Stay home from work or school and limit contact with others to keep from infecting them.

Develop a family emergency plan as a precaution. This should include storing a supply of food, medicines, facemasks, alcohol-based hand rubs and other essential supplies.


Never use the hand dryer on the toilet. They spread virus. According to a British study people have 3 times more bacteria on their hands after using the hand dryer machine than if they use paper to dry their hands. Even more: The use of the hand dryer machine INCREASED the bacteria on the hands 254%, while use of the paper for drying hands REDUCED the bacteria 77%. The air flow also make virus to fly around you. Noro-virus is known to be spread by the hand dryer machine. Do not use it.



The new virus combines genetic material from pigs, birds and humans in a way researchers have not seen before. A genetic test has shown that the new swine influenza is a combination of European swine genes and North American swine genes.



Symptoms of Swine Flu

Symptoms of the new strain are similar to regular flu symptoms: fever, cough, sore throat, headache, runny nose, and muscle aches.

The new strain give more vomiting and diarrhea than regular flu.

Those infected will show symptoms within 9 days or so, and be contagious from one day before symptoms and for up to 7 (or more) days after symptoms start.

Day 1 Infection
Day 2 no symptoms!
Day 3 no symptoms!
Day 4 no symptoms!
Day 5 no symptoms! BUT CONTAGIOUS!! (the incubation time might be up to 10 days)
Day 6 influenza symptoms CONTAGIOUS!!
Day 7 influenza symptoms CONTAGIOUS!!
Day 8 influenza symptoms CONTAGIOUS!!
Day 9 influenza symptoms CONTAGIOUS!!
Day 10 influenza symptoms CONTAGIOUS!!
Day 11 influenza symptoms CONTAGIOUS!!
Day 12-13-14-15- influenza symptoms CONTAGIOUS!!

Small children can be contagious for longer time.

The above is the disease in general for adults - not everyone show symptoms on day 9, of course.

The viruses cannot be spread through eating pork.





Assessing the severity of an influenza pandemic
The major determinant of the severity of an influenza pandemic, as measured by the number of cases of severe illness and deaths it causes, is the inherent virulence of the virus. However, many other factors influence the overall severity of a pandemic's impact. [7036]

Even a pandemic virus that initially causes mild symptoms in otherwise healthy people can be disruptive, especially under the conditions of today's highly mobile and closely interdependent societies. Moreover, the same virus that causes mild illness in one country can result in much higher morbidity and mortality in another. In addition, the inherent virulence of the virus can change over time as the pandemic goes through subsequent waves of national and international spread. [7036]

Properties of the virus
An influenza pandemic is caused by a virus that is either entirely new or has not circulated recently and widely in the human population. This creates an almost universal vulnerability to infection. While not all people ever become infected during a pandemic, nearly all people are susceptible to infection. [7036]

The occurrence of large numbers of people falling ill at or around the same time is one reason why pandemics are socially and economically disruptive. Very rapid spread can undermine the capacity of governments and health services to cope. [7036]

The contagiousness of the virus also influences the severity of a pandemic's impact, as it can increase the number of people falling ill and needing care within a short time frame in a given geographical area. On the positive side, not all parts of the world, or all parts of a country, are affected at the same time. [7036]

Pandemics usually have a concentrated adverse impact in specific age groups. Concentrated illnesses and deaths in a young, economically productive age group will be more disruptive to societies and economies than when the very young or very old are most severely affected. [7036]

Population vulnerability
The overall vulnerability of the population can play a major role. For example, people with underlying chronic conditions, such as cardiovascular disease, hypertension, asthma, diabetes, rheumatoid arthritis, and several others, are more likely to experience severe or lethal infections. The prevalence of these conditions, combined with other factors such as nutritional status, can influence the severity of a pandemic in a significant way. [7036]

Subsequent waves of spread The overall severity of a pandemic is further influenced by the tendency of pandemics to encircle the globe in at least 2, sometimes 3, waves. For many reasons, the severity of subsequent waves can differ dramatically in some or even in most countries. [7036]

A distinctive feature of influenza viruses is that mutations occur frequently and unpredictably in the 8 gene segments, and especially in the hemagglutinin gene. The emergence of an inherently more virulent virus during the course of a pandemic can never be ruled out. [7036]

Different patterns of spread can also influence the severity of subsequent waves. For example, if schoolchildren are mainly affected in the 1st wave, the elderly can bear the brunt of illness during the 2nd wave, with higher mortality seen because of the greater vulnerability of elderly people. [7036]

The 1918 pandemic began mild and returned, within 6 months, in a much more lethal form. The pandemic that began in 1957 started mild, and returned in a somewhat more severe form, though significantly less devastating than seen in 1918. The 1968 pandemic began relatively mild, with sporadic cases prior to the 1st wave, and remained mild in its 2nd wave in most, but not all, countries. [7036]

Capacity to respond
Finally, the quality of health services influences the impact of any pandemic. The same virus that causes only mild symptoms in countries with strong health systems can be devastating in other countries where health systems are weak, supplies of medicines, including antibiotics, are limited or frequently interrupted, and hospitals are crowded, poorly equipped, and understaffed. [7036]

Assessment of the current situation
To date observations specific to H1N1 are preliminary, based on limited data in only a few countries. The H1N1 virus strain causing the current outbreaks is a new virus that has not been seen previously in either humans or animals. Although firm conclusions cannot be reached at present, scientists anticipate that pre-existing immunity to the virus will be low or non-existent, or largely confined to older population groups. [7036]

H1N1 appears to be more contagious than seasonal influenza. The secondary attack rate of the common seasonal influenza ranges from 5 per cent to 15 per cent. Current estimates of the secondary attack rate of H1N1 range from 22 per cent to 33 per cent. [7036]

With the exception of the outbreak in Mexico, which is still not fully understood, the H1N1 virus tends to cause very mild illness in otherwise healthy people. Outside Mexico, nearly all cases of illness, and all deaths, have been detected in people with underlying chronic conditions. [7036]

In the two largest and best documented outbreaks to date, in Mexico and the United States of America, a younger age group has been affected than seen during seasonal epidemics of influenza. Though cases have been confirmed in all age groups, from infants to the elderly, the youth of patients with severe or lethal infections is a striking feature of these early outbreaks. [7036]

The tendency of the H1N1 virus to cause more severe and lethal infections in people with underlying conditions is of particular concern. [7036]

The prevalence of chronic diseases has risen dramatically since 1968, when the last pandemic of the previous century occurred. The geographical distribution of these diseases, once considered the close companions of wealthy societies, has likewise shifted dramatically. Today, WHO estimates that 85 per cent of the burden of chronic diseases is now concentrated in low- and middle-income countries. In these countries, chronic diseases show an earlier average age of onset than seen in more wealthy parts of the world. [7036]

Some scientists speculate that the full clinical spectrum of disease caused by H1N1 will not become apparent until the virus is more widespread. This, too, could alter the current disease picture, which is overwhelmingly mild outside Mexico. [7036]

Apart from the intrinsic mutability of influenza viruses, other factors could alter the severity of current disease patterns, though in completely unknowable ways, if the virus continues to spread. [7036]

Scientists are concerned about possible changes that could take place as the virus spreads to the southern hemisphere and encounters currently circulating human viruses as the normal influenza season in that hemisphere begins. [7036]

The fact that the H5N1 avian influenza virus is firmly established in poultry in some parts of the world is another cause for concern. No one can predict how the H5N1 virus will behave under the pressure of a pandemic. At present, H5N1 is an animal virus that does not spread easily to humans and only very rarely transmits directly from one person to another. [7036]



Overcoming the Swine Flu

The new Swine Flu virus have proved resistant to amantadine and rimantadine anti-viral drugs.

However, it is susceptible (day 1 and 2 of symptoms) to oseltamivir (= Tamiflu) and zanamivir (= Relenza), both are newer anti-viral drugs for flu. Must be given within 48 hours.



About Swine Influenza

Swine influenza (Swine flu, pig flu) refers to influenza cases that are caused by Orthomyxoviruses. These viruses are endemic to populations of pigs.

The viruses are referred to as Swine influenza viruses (SIV).

The distinction is not based on phylogeny. The SIV strains isolated have been classified either as Influenzavirus C or one of the various subtypes of the genus Influenzavirus A.

Swine influenza virus developes first in pigs and can be carried to humans. In the 2009-epidemic humans then infected other humans with the virus.

Washing hands and clothes, and cancelling big and small public events can slow the spread of the virus, giving time, but such things will not stop the virus. Antivirus drugs are limited in stocks, and only work if taken early enough like within 2 days. If diagnose is not accurate or takes too long time, there is the risk that the antivirus drugs will be spoilt on the worried but just infected by an innocent virus - or that the stocks are controlled to strict so that drugs are administered too late. [6978] Vaccine is the answer to virus infections. But vaccine production is dictated by a few companies commercial interests. If a company stop producing vaccine towards the season flu and switch to a vaccine towards the new flu, the company risk to loose the income from the standard season vaccination and that the new vaccine are not sold because the feared pandemic never actually happen. [6978] According to one study we could have 340 million doses of vaccine in four months if the companies focus on this. If the actual vaccine production is easy we might have three times more vaccine doses - but still not for all nearly 7 billion people in the world. [6978] On the long line (of political involvement in virus infection research) We could pool all our resources - making vaccines that focus on the parts of the virus that do not mutate (and therefore would be active against new virus types) - and we could made new antiinflammatory treatments (to hinder the deadly immune-overreaction of the body) - and we could make new DNA vaccines and protein vaccines - or we could base the antibody therapy on the serum of survivors. [6978]

The global preparedness for a pandemic is extremely patchy. Poorer countries are least prepared, but even in richer regions there are serious gaps: a survey in 2007 of 30 European nations found that countries had in place only half of the measures expected by the WHO [6991]. The biggest gap was in preparedness to keep society functioning beyond its health system, to ensure continued provision of electricity, transport, banking, food and policing. Only 12 of 30 nations had multisectoral planning. In Africa only 35 out of 53 countries have pandemic plans. In developing countries already struggling with malaria, HIV and TB a lethal flu during the flu season would represent a profound challenge [6991].



Discussion: Live or inactivated vaccine?
With current manufacturing capabilities, there will be enough vaccine for only a fraction of the world's population, and not before six months from now. And most of that will go to rich countries. [7040, 12 May 2009 (Nature)]

One controversial idea is to use a live attenuated vaccine, which could boost the number of doses available by 50- to 100-fold. Manufacturers are lukewarm to the idea. But some experts say the live-virus idea should be entertained. David Fedson, a pandemic-vaccine expert and retired former medical director of French vaccine development company Aventis-Pasteur, now known as Sanofi Pasteur, argues that the live-virus approach is the way to go now with H1N1. [7040]

Inactivated virus in seasonal flu
The ordinary seasonal flu vaccine uses inactivated virus. Serious regulatory barriers exist to introducing a live-virus vaccine. Demonstrating efficacy and getting regulatory approval in time would pose "quite significant difficulties", says George Kemble, vice-president of vaccine research and development at MedImmune in Gaithersburg, Maryland, which makes live flu-virus vaccine. [7040]

Time to be used for making a new vaccine
Two factors largely determine whether a vaccine can protect large numbers of people during a pandemic. Culturing vaccines in chicken eggs is the main time delay in production. The delay before substantial quantities of vaccine become available is usually around six months due to the time required to grow the virus in hens' eggs. (Cell culture and other technologies could be faster, but they are not yet ready for prime time.) [7040]

The second limiting factor is production capacity, currently at around 700 million to 900 million doses of seasonal flu vaccine annually. [7040]

Vaccine production capacity
Although still limited, production capacity is now in 2009 much better than five years ago (currently 700 - 900 million doses of seasonal flu vaccine annually – but around 2004 it was around 300 million — mainly because of measures taken by governments to prepare for a pandemic threat. [7040]

The content of the seasonal vaccine
The seasonal vaccine contains antigens against three circulating flu strains. [7040]

Switching to producing a single vaccine against just the new H1N1 virus could, in principle, mean that existing vaccine producers could make three times as many doses. [7040]

But even if global facilities switched entirely to producing an inactivated H1N1 vaccine, only about 1 billion doses at most are expected to be available by the end of the year, around the time of the Northern Hemisphere flu season. [7040]

Because the population has little to no pre-existing immunity, the vaccine will probably need to be given in two doses — reducing the actual number of vaccines to 500 million. [7040]

Live-virus vaccine would effectively increase production capacity - the virus in such a vaccine is capable of reproducing in humans, so much lower doses can be given. [7040]

Live-virus vaccines also don't require adjuvants to bolster their effectiveness, can be administered nasally — avoiding the need for syringes — and are thought to provoke a broader and stronger immune response than inactivated vaccine. [7040]

One egg yields one dose of inactive vaccine, - but for a live vaccine one egg yields somewhere from 50 to 100 doses. [7040]

Production capacity will also depend on how well the new H1N1 virus can be grown and cultivated. The news here seems to be good. [7040]

Doris Bucher, an immunologist at New York Medical College, was asked by US Centers for Disease Control and Prevention in Atlanta, Georgia, to help grow the first reference strains to be sent to manufacturers. "We've done 7 cycles, 42 hours each, and it's going very well," she said. [7040]

The immune response produced by the resultant seed vaccines will need to be tested in clinical trials; if it were, for example, to require three times as much antigen as seasonal flu to prompt an adequate immune response, that would cut theoretical production capacity to a third. [7040]

To grow live attenuated vaccines, scientists would reassort (recombine) the new flu strain with a 25°C cold-adapted strain, which will multiply in the nose but not grow in the higher temperatures of the lower respiratory tract. [7040]

Only two groups have the technology to produce live attenuated flu vaccines: MedImmune, and Nobilon, a subsidiary of Schering-Plough, which has licensed technology developed at the Institute of Experimental Medicine in St Petersburg, Russia. [7040]

MedImmune's FluMist is approved for use in the United States for those aged 2-49 years old; older people have been exposed to past pandemic viruses, and their immune systems therefore kill the live vaccine for current circulating strains. [7040]

The WHO has obtained a licence from Nobilon to allow manufacturers in developing countries to use the Russian technology. [7040]

Producers of inactivated vaccine seem sceptical about using live attenuated vaccines more widely, even in a pandemic situation. [7040]

Changing over to a live vaccine would mean introducing new production methods and possibly having to license outside technology, such as that from MedImmune. [7040]

There are also safety and liability issues, because it would be difficult to organize clinical trials of an untested vaccine quickly enough. [7040]

Jesse Goodman, acting chief scientist of the US Food and Drug Administration, notes that live attenuated vaccine is approved in the United States for children and young adults, who "may be at particular risk of infection" in the current H1N1 outbreak. Safety, however, is paramount, he adds: "It is also important to keep in mind, even in the face of a pandemic threat, the importance of doing all that is appropriate and possible to assure high vaccine quality and safety, particularly if and as new facilities, processes and products may be considered." [7040]

Memories are still vivid of the 1976 flu-vaccine fiasco. That year, a new swine flu emerged at an army barracks in New Jersey, killing one person but failing to spread further. A mass vaccination campaign ordered by president Gerald Ford caused neurological side effects in some people, and killed 25. [7040]

Initial information suggests that vaccine producers are well along in producing the seasonal H1N1 and H3N2 strains for the Northern Hemisphere, but are having difficulty growing the third influenza B strain. [7040]

One option may be drop the influenza B from next year's vaccine. Northern Hemisphere production would then be freed up faster to work on a swine-flu vaccine. [7040]

In the Southern Hemisphere vaccine production typically starts around November and continues through March. [7040]

The amounts of vaccine ordered by Southern Hemisphere countries is much lower than that by the north, meaning that northern manufacturers might then have extra time to work on a swine-flu vaccine. [7040]

One scenario, she says, is that full-scale manufacturing of swine-flu vaccine could start by July 2009 at the earliest. [7040]

The new H1N1 strain remains susceptible to the antiviral drugs oseltamivir (Tamiflu) and zanamivir (Relenza). Cheaper and more widely available antibiotics and anti-inflammatories, such as statins, could also have a role in limiting mortality in a severe pandemic. [7040]





Background
For years the scientific community has been speculating that new influenza strains might arise when an bird influenza virus infects swine that are also coinfected with human influenza viruses. This coinfection in the same host, along with a possible 3rd coinfection of a swine influenza virus, has been felt to offer the potential for reassortment of the genetic material of the viruses, that might ultimately produce a virus that is novel to humans, and can infect humans and be transmitted between humans.[6955]

Birds and humans rarely catch flu viruses which are adapted to another host. But such viruses can pass flu to pigs. Pigs also have their own strains. If a pig catches two kinds of flu at once the pig can act as a mixing vessel. Hybrid viruses can emerge with genes from both viruses. - THis is what happened
Swine are susceptible to the same influenza A virus subtypes as humans are – that is: H1N1, H3N2 and H1N2.

Many swine influenza viruses are the result of reassortment: Their genes are composed of human and bird and/or swine virus genes.

It is known that both human and bird influenza viruses occasionally transmit to pigs, and that pigs can serve as “mixing vessels” for these viruses. Thereby viruses can exchange genetic material and lead to the production of a new “hybrid” virus.

Pandemic viruses could emerge following reassortment in pigs.

Influenza is a major cause of acute respiratory disease in pigs. Subclinical infections are also common in pigs.

The symptoms and pathogenesis of influenza in pigs show remarkable similarities with those of seasonal influenza in humans. However, the epidemiology is different because of the extremely rapid turnover of the swine population with constant introduction of immunologically naïve animals into swine herds.

By the end of the six-month-long fattening period many pigs have had infections with two or even three swine influenza subtypes.

The viruses in Europe differ significantly in their antigenic and genetic make-up from those circulating in North America, even though they consist of the same H and N subtypes.

Humans in contact with pigs occasionally become infected by swine influenza viruses. But person to person transmission of pig flu appears to be rare.

Hog workers in Europe and North America are far more likely than others to be infected with potentially lethal pathogens such as MRSA (Methicillin-resistant Staphylococcus aureus), drug-resistant E. coli and Salmonella, and of course, swine influenza. Many scientists also believe that people who work inside CAFOs are more at risk of contracting and spreading these and other "zoonotic" diseases than those working in smaller-scale operations, with outdoor pens or pasture and far lower animal density.

Example: A middle-aged woman in Spain suffered a mild influenza-like illness for which few physicians would have taken a swab. However the general practitioner (GP) she consulted happened to be part of an active influenza surveillance scheme and a specimen was taken and recognised as being influenza A (H1N1) phylogenetically close to European H1N1 swine influenza viruses.

Until March-April 2009, hog workers with swine flu have rarely gone on to infect other people, save for close family members. And that is why the new strain A/H1N1 of swine influenza virus is so vexing - and alarming. It seems to spread quite easily through casual human contact.

The continual cycling of swine influenza viruses and other animal pathogens in large herds or flocks provides increased opportunity for the generation of novel viruses through mutation or recombinant events that could result in more efficient human-to-human transmission of these viruses. In addition, agricultural workers serve as a bridging population between their communities and the animals in large confinement facilities. This bridging increases the risk of novel virus generation in that human viruses may enter the herds or flocks and adapt to the animals. [6989, Pew Commission on Industrial Farm Animal Production, http://ncifap.org/]

Reassortant influenza viruses with human components have ravaged the modern swine industry. Such novel viruses potentially increase zoonotic disease transmission risk to the communities where the workers live. 64% of 63 persons exposed to humans infected with H7N7 bird influenza virus had serological evidence of H7N7 infection following the 2003 Netherlands bird influenza outbreak in poultry. The spouses of swine workers who had no direct contact with pigs had increased odds of antibodies against swine influenza virus. Among communities where a large number of workers in factory farms live, there is great potential for these workers to accelerate pandemic influenza virus transmission. Industry calls they "confined animal feeding operations," or CAFOs (KAY-fohs), though most people know them simply as "factory farms." In the last several years, U.S. hog conglomerates have opened giant swine CAFOs south of the border, including dozens around Mexico City in the neighboring states of Mexico and Puebla and in the State of Veracruz [6989]

Gregory Gray, a University of Iowa professor of international epidemiology and expert in zoonotic infections, warned that factory farm workers could serve as a "bridging population" to rural communities sharing viruses with the pigs, and vice-versa. Factory farm production could lead to another 1918-style global pandemic. May be waterfowl cross-infected pigs in USA with a new type of avian-swine super-virus that was quickly transmitted to farm workers, possibly in Iowa, who went off to military training camps for World War I, and then spread the pathogen worldwide, starting the "Spanish flu" (only called Spanish because Spain at that time was not at war - and therefore free to report about the flu). [6989]

Factory farms are not hermetically sealed environments. Pathogens can enter and exit via swine workers or flies, via waste lagoons and recycled water into the animal housing (dwindling groundwater supplies is a particular concern in parts of Mexico). Wildfowl land in the lagoons and can shed influenza virus into the water. Factory farms have high rates of ventilation - enormous number of animals that would die of heat stress unless the building was ventilated. Scientists have measured bacteria and viruses in the environment around poultry and swine houses. [6989]

Intensive operations of chickens and pigs in factory farms are contributing to speeding up viral evolution. [6989] During an ongoing epidemic Where the virus evolved is not as important as locating the virus, and stopping its spread. [6989]

• Bird-proofing - All doorways, windows and air-flow vents in swine housing units should be adequately sealed or screened to prevent entrance of birds.

• Water treatment - Do not use untreated surface water as either drinking water or water for cleaning in swine facilities. Likewise, it may be prudent to attempt to minimize waterfowl use of farm lagoons.

• Separation of pig and bird production - Do not raise pigs and domestic fowl on the same premises.

• Feed security - Keep pig feed in closed containers to prevent contamination with feces from over-flying waterfowl.

• Worker biosecurity - Provide boots for workers that are worn only within the pig housing units, thus eliminating.

Pigs don't fly, but every year more than two million wild fowl fly up to 1,500 miles or more eastward across the Arctic Ocean from Asia to North America and intersect with North American species. In October 2008 U.S. Geological Survey published a study in Molecular Ecology that found genetic evidence of (non-H5N1) flu viruses in northern pintail ducks in Alaska whose genes were more closely related to Asian bird flu strains than those in the Americas. [6989]

Wild birds can carry virus with swine components in it. A lot of bird viruses contain elements from pigs. An Asian bird virus could contain swine flu components from Eurasian pigs. A pig infected by a bird virus can come into contact with swine virus, which then could combine and be picked up by a bird again. [6989]

Pig's don't fly, but pork does. There is an active international transfer of all kinds of animal products - some of it is imported from Asia or Europe to North America." [6989]

And people fly. The human travel is the most likely way that Eurasian swine viral components made their way to Mexico. A tourist from China could have gone to Mexico City, and that Asian strain was picked up by somebody else, who then went to a swine barn. [6989]

A concern is that new strains of bird flu combining with swine flu could make the swine flu more deadly, and because viruses pass so easily between pigs and people, such a new bird component could make swine flu more virulent. [6989]

The human disease from pig flu is usually clinically similar to disease caused by infections with human influenza viruses. Pneumonia and death have occasionally been reported in the literature in otherwise healthy adults. However, human infections with swine influenza virus is normally much milder than those seen with bird influenza A (H5N1).



In 1976 an outbreak of swine influenza virus infections in humans was detected in recruits in a military camp in Fort Dix, New Jersey in the United States. The presumed link to pigs was never discovered but there was extensive human to human transmission, with over 200 infections resulting in 12 hospitalisations and one death. This was human to human transmission of a novel influenza virus which might be described as WHO Pandemic Phase 4.

The true incidence of swine influenza in humans is unknown. It is known from USA that the few reported cases of swine influenza in humans represent a larger number of undetected infections among those in contact with pigs. However, two factors are probably restricting infection of humans: limited fitness of the virus in a different host species, and immunity to human H1 or H3 influenza viruses may protect against infection with swine viruses.

Some scientists have advocated seasonal influenza vaccination to persons working with pigs to reduce their risk of getting infected. However, experience with workers with domestic poultry on this point is not encouraging. In one audit attempt in Europe uptake of the vaccine was low and those offered immunisation were confused as to what they were being protected against.

In 1998 swine H1N1 hybridised with human and bird viruses, resulting in swine-human-bird triple "reassortants". The virus emerged in Minnesota, Iowa and Texas. This triple reassortant in pigs seems to be the precursor for the Mexican flu. The virus initially had human surface proteins and internal swine proteins, with the exception of three genes that make RNA polymerase (the enzyme for virus replication). Two of these three crucial genes were from bird flu virus and one was from human flu virus. Researchers believe that the bird polymerase allows the virus to replicate faster than virus with human or swine versions, - making the virus more virulent. [6978]

The swine versions with these faster replicating bird polymerase enzymes easily outcompeted those viruses that did not have these fast polymerase enzymes, so that by 1999 these new viruses comprised the dominant flu strains in North American pigs. Unlike the swine virus they replaced, they were actively evolving and in 2009 there were many versions with different pig surface proteins or human surface proteins, - including one with H1 and N1 from the original swine virus. This is just like the Mexican flu from March-April 2009. [6978]

All these viruses still contained the same "cassette" of internal genes, including the bird and human polymerase genes. But the viruses had been actively switching their surface proteins - thereby evading the pigs' immunity. The polymerase gene sequences were of the bird-virus and human-virus type, yet these viruses were for many years only reported in pigs. [6978]

There were in 2009 so many kinds of pig flu that pig flu was no longer seasonal. One in five pig producers in USA maked their own vaccines, because the vaccine industry could not keep up with the virus changes. [6978]

This rapid evolution posed a potential for pandemic influenza. Researchers who focused on swine flu could see the threat developing, while the medical researchers who focused on human flu viruses seemed not to have been aware of this threat. Around 2004 several scientists warned that pigs in USA were an increasingly important reservoir of viruses with human pandemic potential. One in five pig workers in USA had been found to have antibodies to swine flu, showing they had been infected, but most people had no immunity to these viruses. Also the American CDC warned in 2008 that swine H1N1 would represent a pandemic threat if it started circulating in humans. [6978]

The immune response in the body makes the whole difference between a mild disease and a lethal disease. Our immune respons is mainly due to the H surface protein of the virus. The Mexican virus carries the swine version of the surface protein. Therefore, the antibodies we humans carry to human H1N1 viruses will not recognise the virus with the swine-virus type of H-proteins on the surface of the virus particle. [6978]

The bird polymerase genes are especially worrying, as similar genes are what make H5N1 bird flu very lethal in mammals and what made the 1918 human pandemic virus so lethal in people. [6978] A Russian scientist predicted the deadly swine flu pandemic back in 2004, when he said the deadly bird flu was likely to mix with the human flu virus in the organism of a pig. Professor Dmitry Lvov of the Virology Institute at the Russian Academy of Sciences said at a conference that up to one billion people could be killed within six months, and that such a the pandemic was possible in 2005 or later. The pandemic could be caused by a mutation of the H3N2 ‘bird flu’ virus, he said. Bird flu killed millions of birds in South Asia. Among 45 cases of humans catching bird flu 30 of them died. The worst thing was that the virus got into a population of pigs. The bird flu virus is not very contagious for humans, but pigs are ideal “incubators” to breed a new stem of the virus, far deadlier than H5N1 or H3N2. [6995]

The Veratect Corporation based in Kirkland, Washington, monitors world press and government reports to provide early disease warnings for clients. Their first inkling of the Mexican swine flu A/H1N1 was a 2 April 2009 report of a surge in respiratory disease in the town La Gloria (Perote Municipality, Veracruz State, Mexico), east of Mexico City, which resulted in the deaths of three young children [6978]. About 3000 inhabitants, most of the people in La Gloria, had flu symptoms. 1300 were investigated, and 450 of these treated, the news media later wrote. The swine were killed as a prevention, although the influenza was not found in the pigs. [7008, video from La Gloria].

Only on 16 April 2009 - after Easter week, when millions of Mexicans travel to visit relatives - did reports surface elsewhere in Mexico. [6978]

Local reports in La Gloria blamed pig farms about 8 km from the town in nearby Perote owned by Granjas Carroll, a subsidiary of US hog giant Smithfield Foods. The farms produce nearly a million pigs a year. Smithfield Foods, in a statement, insists there were "no clinical signs or symptoms" of swine flu in its pigs or in its workers in Mexico - but that was unsurprising since the company also said that it "routinely administers influenza virus vaccination to swine herds". (However the company would not tell New Scientist any more about recent tests). Furthermore, vaccination keeps pigs from getting sick,, but it does not block infection or shedding of the virus. [6978]

A "pandemic" is an epidemic that goes global. Technically there is a flu pandemic every year, but the term is usually reserved for bad outbreaks. The influenza virus constantly evolves. Pandemics happen every few decades when the flu virus gets new surface proteins that people have little immunity to, generally because they come from an animal strain. [6978]

The lack of immunity means the virus affects more people more severely. H5N1 bird flu is very dangerous because its H5 surface protein is totally new to humans - and because H5N1 bird flu virus has killed more than half of the people it has infected. [6978]

Bird flu virus from the H5, H7 or H9 families, which are unknown for our body, only needs to become readily contagious to go pandemic. [6978]

H1N1 has received less attention partly because a H1N1 strain already circulates in humans. However, the Mexican strain carries different versions of H1 surface proteins. [6978]

The new strain from Mexico is packing a faster virus engine than previous H1N1 strains. With its bird virus gene it has become dominant in pigs, - no one knows if this will make it dangerous in people. [6978]
Literature






Swine flu genes in China - and diagnostic means.

The HA-segment and 5 other gene segments should according to searches in gene data banks be from the previous h1.3.2 "classical" swine influenza viruses. The other 2 gene segments in the virus (NA and M) are believed to be from h1.1.3 (“bird-like”) swine influenza viruses. [6994].

The 3 clusters of H1 subtypes can be detected by a RT-PCR system (using one upper primer and 2 differentiation down primers with the sequences:

H1S-3: 5'-TAAGCAAAAGCAGGGGAAAATAAAA-3'
H1R-1143: 5'-TGGTGATAACC(G/A)TACCATCCATCT-3'
H1Rm-610: 5'-CACGAGGACTTCTTTCCCTTTATCAT-3' [6994].

It is important to detect the viral NA gene to clarify whether the virus is similar to the current A(H1N1) swine influenza virus spreading in humans. [6994].

If¤ suspicious samples through the aforementioned detection of the viral HA gene is found, the following primer to amplify and sequence the viral NA gene can be used. [6994].

NAS-5A 5'-GCAAAAGCAGGAGTTTAAAATGAA-3'¤
NAR-1108A 5'-GTTCTCCCTATCCAAACACCAT-3' [6994].

Another kit for detection of all H1 subtype swine influenza viruses:

H1-762U: 5'-TATCAACAATAAGAA-3'¤
H1-762L: 5'-CAAACATCCAGAAGA-3'¤

The upper primer H1-762U is located at a highly variable region within the targeted gene, so that the specificity of the primers cannot be guaranteed. [6994].

Another kit for detection of the current A(H1N1) swine influenza virus circulating in humans. [6994].

H1-292U: 5'-CATTAATGATAAAGG-3'¤
H1-292 L: 5'-TCCAGCATTTCTTTC-3' [6994].

Since the primers are too short the specificity of the primers and the effective combination of the primers to the corresponding regions cannot be guaranteed. [6994].

Most of the influenza viruses circulating in pigs in China have been H1N1 (cluster: h1.3.2 "classical") and H3N2 (cluster: h3.1.5) swine influenza viruses. [6994].

The viruses within cluster h1.1.3 (“bird-like”) were isolated from pigs only in 2007 in China. [6994].

H9N2 subtype bird influenza viruses have been isolated from pigs in China since 2003. [6994].

H5N1 subtype bird influenza viruses were isolated from pigs only once in 2005 and (until 2009) never after China has implemented compulsory H5 vaccination in poultry. [6994].

A few human H3N2 and H1N1 subtypes of influenza viruses have also been isolated from pigs in China. [6994]

Moreover, it seemed that re-assortment of the gene segments of influenza viruses from different origins was rather frequent in pigs in China. [6994]

A re-assortment subtype (H1N2) swine influenza virus has been isolated since 2004. [6994].

The March-April 2009¤A(H1N1) swine influenza virus spreading in humans has never been isolated in China despite surveillance by several research groups in the past decade in China. However, with the experience of the recent emergence of a dangerous human influenza virus, presumably directly from pigs in North America, it is of high significance to carry out rigid surveillance on the influenza viruses circulating in the pigs in China for a long time. The March-April 2009¤A(H1N1) influenza viruses spreading in humans are very dangerous for China, which has a very large population and limited hygiene resources. [6994].

The morbidity and mortality of the epidemic, if spreading in China, could be as high as in Mexico, since both are developing countries, and consequently, thousands of young people in China could die due to the infection. Therefore, it is rational for China to take some rigid measures to prevent the disease from spreading to China, according with International Health Regulations and the Code of the World Organisation for Animal Health (OIE). [6994].





Bacterial co-infections?

The death seen from flu influenza in Mexico could be due to the combination of virus and bakteria infections. Three observations make it highly likely that the "flu" fatalities are due to such bacterial co-infections:

1st, a study (Ramilio et al, Blood, 2007) of humans with flu-symptoms found that greater than 30 percent of the fatalities were in people with bacterial-influenza co-infections. Knowing the inadequacy of the diagnostics the number of co-infections could be much higher than 30 percent, possibly even 90 percent in fatalities. [6994].

2nd, the index case (“case zero”) in Mexico was a small boy who got severely sick, but his doctor gave him an antibiotic (usually for bacterial infections), and he survived. The fact that he got better 2 days after an antibiotic may indicate that he had a bacterial infection in addition to a flu infection. [6994].

3rd, one of the earliest Mexican deaths was a diabetic woman in her 40's. A lung biopsy contained influenza. Several people around her had respiratory diseases, but none of them were positive for influenza! This means that it is possible she too had both flu and bacterial infections that lead to her death. [6994].

¤It is well known that flu infections make it easier to maintain respiratory bacterial infections and visa versa. [6994].

To safeguard against flu-related deaths, doctors could prescribe more antibiotics. However, since the cost of antibiotics is high and since over-prescribing antibiotics is dangerous, diagnostics that discriminate between viral and bacterial infections should be used. There is already an FDA approved pregnancy-test-type device [produced by Rapid Pathogen Screening (RPS), Inc.] that determines whether teardrops from a person with conjunctivitis arise from bacterial or viral infection (it uses antibodies to MxA and C-reactive proteins, which are early host responses to either viral or bacterial infections). Molecular biologists have found¤changes in circulating H3N2 viruses as well as H1N1 and since the available diagnostics are poor, much of what was blamed on H1N1 could have been H3N2 (or another virus or bacteria or a co-infection). Much more funding should go to developing host-response diagnostics, since there are about 100 known host proteins that can discriminate acute bacterial infections from acute viral infections. Expression of those proteins in the plasma should allow to discriminate the serious cases from the light ones. However, antibiotics should be used only with probable bacterial infection. and what is also important is the use of appropriate antibiotics, e.g. anti-staphylococcal agents if staphylococcal rather than pneumococcal.pneumonia is suspected. For example in the 1957 pandemic, S. aureus was 2nd only to the pneumococcus as a cause of secondary bacterial pneumonia, but many other organisms also caused secondary bacterial pneumonia. Also an issue for discussion is the need to have an adequate supply of antibacterial agents available as well as antivirals in the presence of a pandemic. The concern of many infectious diseases experts in USA is that we do not have such a supply and that there are inadequate antibiotics in the pipeline to deal with emerging bacterial resistance. [6994].




Information for laboratory workers:
CDC guidance is for laboratory workers: Diagnostic laboratory og suspected swine influenza A (H1N1) should be conducted in a BSL2 laboratory, sample manipulations done inside a biosafety cabinet, and Viral isolation in a BSL2 laboratory with BSL3 practices (enhanced BSL2 conditions). [6955, Friday 24 April 2009]
Additional precautions include:
* recommended personal protective equipment (based on site specific risk assessment)
* respiratory protection -- fit-tested N95 respirator or higher level of protection.
* shoe covers
* closed-front gown
* double gloves
* eye protection (goggles or face shields) [6955]

Appropriate disinfectants
* 70 per cent ethanol
* 5 per cent Lysol
* 10 per cent bleach [6955]

For personnel who had unprotected exposure or a known breach in personal protective equipment to clinical material or live virus from a confirmed case of swine influenza A (H1N1), antiviral chemoprophylaxis with zanamivir (= Relenza) or oseltamivir (= Tamiflu) for 7 days after exposure can be considered. [6955]

Oseltamivir (brand name Tamiflu®, made by Roche AG) is approved to both treat and prevent influenza A and B virus infection in people one year of age and older. [6958]

Zanamivir (brand name Relenza® made by GlaxoSmithKline) is approved to treat influenza A and B virus infection in people 7 years and older and to prevent influenza A and B virus infection in people 5 years and older. [6958]

Oseltamivir (= Tamiflu, made by Roche AG) antivirus-compound reduced the disease with one day, from about 5 days to about 4 days. [TV DR1 27 Apr.2009 evening]

Oseltamivir (= Tamiflu, made by Roche AG) and Zanamivir (brand name Relenza® made by GlaxoSmithKline) are both neuraminidase inhibitors.




Detection of the virus
The virus can be detected with several means. InDevR (www.indevr.com) is a small biotech company in Boulder, CO, founded 2003, which licensed the intellectual property to the FluChip technology from the University of Colorado and CDC. The M gene version of the FluChip can detect swine-origin H1N1 influenza A viruses and clearly distinguish them from seasonal influenza viruses (A/H1N1 and A/H3N2) as well as the deadly avian A/H5N1 virus. The M-gene version of the FluChip is more robust because the diagnostic target is a stable, internal gene which codes for the virus' matrix proteins. Current qRT-PCR subtyping assays target a more highly mutable gene that codes for a protein, hemagglutinin (HA), which is subject to antigenic drift. As has happened in the past, if the HA gene changes in a critical region, qRT-PCR will fail and the researcher won't know why until the gene is re-sequenced. [7020; http://www.eurekalert.org/pub_releases/2009-05/uoca-ifd050509.php ]




Production of vaccines
6 May 2009: After the H1N1 virus was found in a Canadian swine herd an Iowa State University researcher developed an H1N1 flu vaccine for pigs, said Hank Harris, professor in animal science and veterinary diagnostic and production animal medicine. Harris' start-up company at the ISU Research Park, Harrisvaccines, Inc., uses a technology that is much faster for producing vaccines than traditional methods. The technique, called "RNA Backbone", was developed for human use by a North Carolina company called Alphavax. Harrisvaccines has adapted it for pigs. The technique uses electric current to combine the RNA Backbone material with the relevant genetic information from the active flu virus through a process called electro-poration. Harris notes that his new vaccines using the Backbone method are currently in the pipeline for approval and may have approval from the United States Department of Agriculture by 2011. Recently, Harris' new, faster method of producing vaccines was put to use during an outbreak of the disease Porcine Reproductive Respiratory Syndrome virus. Harris' Backbone method allowed vaccines to be ready within two months of the outbreak. That research was supported by the United States Department of Agriculture's Small Business Innovation Research Program. Traditional production methods require five to six months for human vaccines and 11 to 12 months for swine vaccines. "Right now, to make human or animal vaccines, you have to get the live virus and grow it in eggs or cell culture and then inactivate it," said Harris. "We don't have to do that." "That is what is really neat about this technology, you do not really need the live virus," he said. "We just need the genes from the original virus which can be made synthetically." Harris needs only the virus' genetic information, which is easily available. The new H1N1 virus, for instance, has already been genetically mapped and is already available on the Web and in the public domain. [7021; http://www.eurekalert.org/pub_releases/2009-05/isu-isu050609.php]

Check these websites for further information and updates
www.cdc.gov/swineflu and www.cdc.gov/swineflu/investigation.htm.
The Association of Public Health Laboratories (APHL) swine influenza web page can be found www.aphl.org/aphlprograms/infectious/outbreak/Pages/swineflu.aspx. [6955]




History of Swine influenza:
February 2009 - early March 2009: In February a seven-month-old baby died of pneumonia in the village La Gloria in the Veracruz state of Southern Mexico. In early March a two-month-old died in La Gloria. The parents were told both children had died of bacterial pneumonia. [6964]

18 March 2009 : Federal District of Mexico begins to pick up cases of swine flu.[6966]

21 Marts 2009: Around 21 March 2009, dozens of people in La Gloria started suffering high fevers, terrible aches and sore throats that led to trouble breathing.[6964]

Bertha Crisostomo, a woman who is a local community leader, called the authorities in the city of Perote. Doctors were sent in with antibiotics and painkillers. [6964]

In Veracruz state of Southern Mexico pig farming is a key industry in mountain hamlets. On either side of the long straight road to La Gloria scrawny horses pull ploughs across flat sandy fields, sending up clouds of dust. These places small clinics provide the only health care. [6964,6963]

Residents in La Gloria say the prevailing wind invariably blows the fetid air their way, where it gets stuck because of the hills that rise just behind the village. [6964]

28 March 2009: Earliest onset date of swine flu reaching the United States, according to the CDC.[6965]

2 April 2009: Edgar Hernández Hernández, a neat four old with a shy smile living in a little white house in La Gloria, had an illness that laid him up in bed for a week: "My head hurt a lot ... I couldn't breathe", he later told journalists, when he was well again. [6964]

3 April 2009: Local nurses took a swab from Edgar's throat on 3 April 2009 and two weeks later this was sent with a batch of other swabs to the Centres for Disease Control and Prevention in Atlanta, Georgia. The sample was testet positive for a new strain of swine flu. Edgar's was the earliest sample. (Edgar Hernández Hernández was one of a group of residents who came down with what was at the time labeled a particularly bad case of the flu. It was later reportet that only one sample from the group, that belonging to this boy, was preserved)[6964][6988]

9 April 2009: A door-to-door tax inspector, Maria Adela Gutierrez, was hospitalized 9 April 2009 with acute respiratory problems in the neighboring state of Oaxaca, infecting 16 hospital workers before she became Mexico’s first confirmed death. She also had diabetes, and she died 13 April 2009, four days after being hospitalized on the local hospital. She fell ill after pairing up with a temporary worker from Veracruz who seemed to have a very bad cold. She was a 39-year-old woman from working as a door-to-door census-taker or the tax board in Oaxaca and may have had contact with scores of people. She lived in the southern city of Oaxaca, capital of the state of the same name. Martin Vazquez Villanueva, the regional health secretary in Oaxaca, denied local news reports that said she had infected 20 people, as well as her husband and children. [6963][6988]

"Eventually we began to get better, but it was truly terrible while it lasted," Bertha Crisostomo from the village La Gloria later told journalists. "The doctors told us that it was just an atypical cold and nothing to worry about, - and that it was probably caused by the flies from the pig farms, so they sent in fumigation teams to get rid of the flies". Bertha Crisostomo got ill herself for more than a week.[6964]

"We watched what was going on in Mexico City and we said to each other that was exactly what happened to us," said Rosa Jimenez later to journalists. Many families in La Gloria have relatives who work in Mexico City but who came back to the village for the Easter week celebrations around 3-5 April 2009. "Could that be how it spread to the capital of Mexico City?" she asked [6964]. Also people from La Gloria kept going to jobs in Mexico City despite their illnesses, and could have infected people in the capital [6963].

The villagers of La Gloria believe they suffered the disease before Edgar, the 5 year old boy. They blame a huge pig farm in the area belonging to a multinational, Smithfield Foods. The pigs live in modules around the valley in long metal buildings with large rectangular tanks attached. The closest one to La Gloria is a few miles back down a paved road and then a couple more down a cactus-lined track. The tank lies open, apparently unattended, and a putrid odour is emanating from it. The company has vehemently denied that its pigs had anything to do with the outbreak. [6964]

There is much fear in La Gloria that the company will get angry at suggestions that it might have had something to do with the infection. Many people would only talk to journalists on condition of anonymity, like one man raking rubbish outside his home: "I was ill, my wife was ill, my children, my aunt. We were all in bed with exactly the same symptoms as we are now being told are swine flu," he said. "But I don't want to speak out, because I am afraid. This is a company with lots of power and lots of dollars. They have always been protected by the government and there is not much we can do about it". The Mexican health minister, José Ángel Córdova (Angel Cordoba Villalobos), insisted that Edgar, the 5 year old boy, was the only case of swine flu in La Gloria - although residents say his illness came after weeks during which most of the village fell ill.[6964]

Local health officials in Mexico gave a different account of the source of infection: The infection may have started with a migrant farmer who returned from work in the U.S. and gave the disease to his wife, who in turn passed it on to other women in the community. [6988]

Monday 8 April 2009: A 23 months old child from Mexico got the new swine flu infection. He died Monday 27 April 2009 (at a hospital in Houston, Texas). He had underlying health problems.

3-12 April2009 Semana Santa (~April 3 – 12, Palm Sunday to Easter Sunday), which is Mexico’s second largest holiday. Mexico’s population is approximately 90% Catholic, which results in substantial population migration patterns during this time period. In Ixtapalapa (in Mexico City), one million people visit for Semana Santa. Other well-known sites for the holiday include Pátzcuaro, San Cristobal de las Casas (Chiapas), and Taxco.

Sunday 12 April 2009 (Easter Sunday): Human infect pigs: A pig farm in Canada with 2200 pigs (220 sows and their piglets in 2 barns and 1800 growers in 4 barns) was infected by a human with A/H1N1. 450 pigs were infected (23%). Morbidity not significantly rised.

[6993]. A carpenter hired by a Canadian farm owner in Alberta (ALB-001) travelled to Mexico and returned to Canada on 12 Apr 2009. The carpenter, the producer and the producer's family became ill with influenza-like symptoms between 14 - 29 Apr 2009. [6983]

A Canadian Food Inspection Agency (CFIA) team later attended the premises on 28 Apr 2009 and collected samples from swine for influenza virus testing at the CFIA National Centre for Foreign Animal Diseases (NCFAD) in Winnipeg. The samples were run in conventional RT-PCR for the Matrix and the H1 gene. These results showed that 19/24 samples were positive for the M gene and 15/24 samples positive for the H1 gene. [6983]

This was immediately followed up by sequencing of these PCR products (6 samples for the Matrix and 5 for the H1 gene). The sequences of a segment of approximately 244 nucleotides of the Matrix gene from 6 samples showed that this sequence was 100 percent identical to sequences derived from the novel A/H1N1 influenza virus from the USA and Mexico and similar results (99-100 percent identity) were found for around 500 nucleotides of the H1 gene from 5 samples. [6983]

The sequences derived from the pig samples were identical to each other and for the M gene most similar to the Eurasian lineage while the H1 gene was more reminiscent of the North American lineage as would be expected for this novel virus. [6983]

Additional sequencing of part of the N gene clearly showed that this was an N1 virus and the sequence of the approximately 1400 nucleotide fragment was highly related to the novel A/H1N1 influenza virus. [6983]

It was thus confirmed that this was the novel A/H1N1 influenza virus and being very closely related to the human strains of the new Mexican Swine Flu based on the genes sequenced so far. [6983]

One can speculate that similar situations have ocurred in other countries where H1N1 infected humans have had contacts with domestic pigs. This is particularly relevant to Mexico, where the prevalence of the new virus in humans may have reached high dimensions. "Surveillance in pig farms in Mexico is thus anticipated the earliest", said FAO later, 4 May 2009. [6983]

Those involved in the surveillance activities on farms, as well as personnel of suspected pig herds, should be vaccinated against seasonal influenza virus to prevent possible mixed infections. [6983]

After the detection of the A/H1N1 virus in pigs in Canada transmitted by a human, the Food and Agriculture Organization of the United Nations (FAO) urged national authorities and farmers to carefully monitor pigs for influenza-like symptoms. [6983]

It is no surprise that influenza viruses are capable of transmitting from humans to animals, as seen in Canada. [6983]

All cases of porcine respiratory syndrome were recommended to be immediately reported to veterinary authorities. [6983]

Where A/H1N1 influenza is confirmed, movement restrictions should be in force for 7 days after the last animal has recovered. [6983]

Persons who work directly with swine should be urged not to go to work if they have any signs of respiratory disease, fever or any influenza-like illness. [6983]

Animal handlers and veterinarians should wear protective clothing to minimize the risk of being infected. [6983]

The FAO stressed (
[6984] 4 May 2009, www.fao.org/news/story/en/item/19365/icode/) that there is absolutely no need to slaughter animals in view of preventing circulation of the A/H1N1 virus. [6983]

The agency emphasized that the A/H1N1 virus cannot be transmitted to humans by pork and pork products. [6983]

ProMED [6993] wrote about this: The human-infect-pigs story clearly indicates how the zoonotic bridge between animals and humans is a 2-lane highway. Humans and animals can interface and transmit disease through many unpredictable scenarios as illustrated by the events described here. The story also highlights the need for surveillance on swine farms particularly those where the unusual chance contacts between an ill human and pigs would have occurred early in this outbreak, before awareness of this virus got disseminated. It also highlights the importance of keeping sick people off swine farms - this should be fully realized everywhere. [6993]

Swine farms in Mexico, Texas, and California near the location of early human cases should intensively evaluate any respiratory disease and include the new, novel influenza A (H1N1). [6993]

Broad efforts at surveillance in swine populations should be a definite priority at this point in the outbreak.[6993]

The decision not to cull the pigs may very well be because they had already recovered from the respiratory signs indicated but clarification would be helpful. [6993]

It is possible that the virus originated from pig populations somewhere in North America. It is also possible that the virus remains in some pig populations somewhere in North America, unknown exactly where. Since the diversity of H1 subtype influenza viruses is very complicated in pigs, it is very difficult to make a test for actual pig H1-subtypes of A/H1N1. [6994].

There are 3 main clusters of H1 subtype swine influenza viruses circulating in pigs in the world. They are called h1.3.2 "classical", h1.2.5 "human-like" and h1.1.3 "bird-like" [= "Eurasian" because almost all of the viruses within the cluster were isolated from Europe and Asia]. Another cluster h1.3.1 "old classical", corresponds to the classical swine influenza viruses circulating in the world in the 1930s and 1940s, but which largely has disappeared from the world. [6994].

The A(H1N1) swine influenza virus spreading in humans from March-April 2009 is in the cluster of h1.3.2 "classical". It is highly homogenous to some North American strains isolated after the year 1999. [6994].

There are 2 main clusters of N1 subtype swine influenza viruses circulating in pigs in the world. They are called n1.3.2 "classical" and n1.1.7. "bird-like" ("Eurasian"). [6994].

The A(H1N1) influenza of 2009 belong to the cluster n1.1.7 ("bird-like") - and highly homogenous to many Eurasian strains and at least 2 North American strains isolated in the past decade. [6994].

xxxxxxxxxxxxxxx About 15 April 2009: The virus was sequenced in full. The genetics of the virus - 14 kilobases long - include eight genes, which code for surface proteins hemagglutinin (H) and neuraminidase (N), the matrix that surrounds the nucleus, the nucleoprotein itself, and three polymerase enzymes called PA, PB1, and PB2. It had similarities of about 94% in the hemaggluttinin [H] gene to the nearest strain known - and almost equidistant to swine viruses from the United States and Eurasia. The neuraminidase gene and the matrix gene were close relatives to swine virus genes from Asia. PA (bird flu), PB1 (human flu), and PB2 (bird flu). The human flu gene had been known in swine viruses since 1998. The neuraminidase and the matrix genes had not been seen in North America swine virus before. They were two new players from Asia. Virus from Midwestern of US were exported to Asia, since Korea and many countries import swine from the U.S. So in reality the virus could come from Asia or Europe - from a person. It suggested that the mixing didn’t happen in Mexico. The hemagglutinin gene is a lonely branch - and unknown where it evolved. [6974]

The virus do not grow very well in eggs. The scientists hope the virus will improve the ability to grow in eggs so that it will be easier to produce a vaccine very quickly. However, some countries might not have the good surveillance to make proper use of such vaccines. [6974]

Tuesday day 21 April 2009: CDC laboratories confirmed two cases in California. [6965]

Wednesday 22 April 2009 In case after case, patients in Mexico have complained of being misdiagnosed, turned away by doctors and denied access to drugs.

A 32-year-old truck driver Alejandro had a bad cough when he returned to Mexico City from Veracruz and soon developed a fever and swollen tonsils. He was taken to a series of doctors and finally a large hospital. By then, he had a temperature of 102 Fahrenheit and could barely stand. They sent him away and said it was just tonsillitis. His wife, Monica Gonzalez, took him to Mexico City’s main respiratory hospital, “like dying in the taxi.” Doctors diagnosed pneumonia, but it may have been too late: He had suffered a collapsed lung and was unconscious. This was 22 April 2009 - and by that time the medical community in Mexico City was aware of a disturbing trend in respiratory infections, and Veracruz had been identified as a place of concern. [6963]

Thursday 23 April 2009: Mexico announced the epidemic 23 April 2009 [6967]. The time of the year was very late for seasonal influenza. (It was in fact a little bit easier that the epidemic was occurring in the end of the influenza season because then there was not so much noise with background influenza to look through for the investigation teams). In the coming days military personnel were seen in the streets distributing million of masks and looking for people with flu. The health authorities got authority to isolate people and search their houses for sick people. Via TV people with flu were told to contact lokal doctors and hospitals resulting in long queues outside medical houses and hospitals.

Friday 24 April 2009: In Denmark Else Smith, the director of the Center for Disease Prevention at The National Board of Health (the supreme health care authority in Denmark), was informed first time about the new disease. During the next week she was to give about 50 interviews to journalists and inform the Minister of Health five times.

Saturday 25 April 2009: WHO's Emergency Committee, called together for the first time since it was created in 2007. The committee draws on experts from around the world. The Committee agreed that the situation constituted a public health emergency of international concern. Based on this advice, the Director-General determined that the events constituted a public health emergency of international concern.

Saturday 25 April 2009: The Centers for Disease Control and Prevention (CDC) in USA: There were 11 confirmed cases in the USA with 7 in California, 2 in Texas and 2 in Kansas.

Saturday 25 April 2009: Two 16-year-old boys in Texas near San Antonio were confirmed infected. Human-to-human spread was obvious since there had been no contact with pigs. The virus contained genetic segments from four different virus sources: Some genetic segments from North American swine influenza viruses. Some gene segments from North American bird influenza viruses. One gene segment from a human influenza virus and two gene segments that are normally found from swine influenza viruses in Asia-Europe. Genetic reassortment of a virus of swine influenza from the Americas with a swine influenza virus from Eurasia had not been detected in the past. Genetic sequencing of influenza viruses isolated from a ten-year-old and a nine-year-old child (San Diego County and Imperial County, both California) were very similar but not identical to each other. [6967]

The sequence of the virus was published on the Internet http://www.gisaid.org.

Saturday 25 April 2009: The United States government declared a public health emergency as the number of identified cases of swine flu in the nation rose to 20. In New York City eight students at St. Francis Preparatory School in Queens have tested positive for swine flu.

Saturday 25 April 2009: 81 deaths in Mexico had been deemed "likely linked" to swine flu. 20 of these had by 25th April 2009 been confirmed as infections with the new virus strain.

Saturday 25 April 2009: Canada confirmed its first cases of swine flu with four people said to have the virus in the eastern province of Nova Scotia. The cases were among students who had recently traveled to Mexico. The people affected were only "mildly ill."

Saturday 25 April 2009: All 8 people infected with swine flu in California and Texas had recovered.

Saturday 25 April 2009: In New Zealand 22 students and three teachers from Auckland's Rangitoto College back home from a three-week-long language trip to Mexico may have been infected with the swine flu virus. Fourteen have shown flu-like symptoms. 10 students tested positive for influenza A. The specimens will be sent to WHO to determine whether it is H1N1 swine influenza.

Saturday 25 April 2009: Gregory Hartl of the World Health Organization said the strain of the virus seen in Mexico is worrisome because it has mutated from older strains. "Any time that there is a virus which changes ... it means perhaps the immunities the human body has built up to deal with influenza might not be adjusted well enough to deal with this new virus" Gregory Hartl said.

Saturday 25 April 2009: Russia forbid import of meat from Mexico, some states in USA and 9 Latin American countries.

Sunday 26 April 2009: A total of confirmed cases in Canada was now six, including four in Nova Scotia, all of whom presented only mild symptoms and were not hospitalized. It was the same type A, H1N1 swine flu virus that had earlier appeared in California and Mexico.

Sunday 26 April 2009: A specialist doctor in respiratory diseases and intensive care at the Mexican National Institute of Health described the severe emergency over the swine flu there: "More and more patients are being admitted to the intensive care unit. Despite the heroic efforts of doctors, nurses, specialists, etc. patients continue to inevitably die. The truth is that anti-viral treatments are not expected to have any effect, even at high doses. It is a great fear among the staff. The infection risk is very high among the doctors and health staff".[6954]

Sunday 26 April 2009: USA reported of 20 confirmed cases (8 in New York, 7 in California, 2 in Texas, 2 in Kansas, and 1 in Ohio). All had mild influenza-like illness with only one requiring brief hospitalization. [6955]

Sunday 26 April 2009: In Mexico there was now over 1400 reported cases in 19 of 32 States, with 81 (or 86 depending upon the source) reported fatalities. [6954]

Sunday 26 April 2009: A spokesman for WHO, Fukuda, said. "Right now we have cases occurring in a couple of different countries and in multiple locations - but we also know that in the modern world cases can simply move around from single locations and not really become established."

Sunday 26 April 2009: So far, WHO had only urged governments to step up their surveillance of suspicious outbreaks. However, WHO director-general Margaret Chan called the outbreak a public health emergency of "pandemic potential". Her agency was considering whether to issue nonbinding recommendations on travel and trade restrictions, and even border closures. It would in that case be up to governments to decide whether to follow the advice.

Sunday 26 April 2009: China said anyone experiencing flu-like symptoms within 2 weeks of arrival from an affected area had to report to authorities.

Sunday 26 April 2009: A Russian health agency said any passenger from North America running a fever would be quarantined until the cause of the fever is determined.

Sunday 26 April 2009: Tokyo's Narita airport installed a device to test the temperatures of passengers arriving from Mexico.

Sunday 26 April 2009: The Secretary of the Department Homeland Security in USA, Janet Napolitano, declared a public health emergency in the United States to allow funds to be released to support the public health response.

Sunday 26 April 2009: An e-mail card about handwash for sending to friends was made in USA.

Sunday 26 April 2009: Five people died of swine flu in the last 24 hours in Mexico City, bringing the total of those killed to 15 in the capital, Mexico City's mayor, Marcelo Ebrard said.

Sunday 26 April 2009: A school group from New Zealand's largest city of Auckland was being quarantined at home after returning from Mexico

Monday 27 April 2009: First confirmed case found in Europe: Spain.

Monday 27 April 2009: The first death from the outbreak outside Mexico was a Mexico City 2 year old child from Mexico who traveled to Texas with family and died Monday 27 April 2009 at a Houston hospital. He was ill since 8 April 2009 and had underlying health problems.

Monday 27 April 2009: Two confirmed cases found in United Kingdom (Scotland). Both patients, a man and a woman, recovered well. 7 other people who had been in contact with them were displaying mild symptoms. Both the Scottish patients were from the Forth Valley area of central Scotland. The pair, who had been traveling together, returned from Mexico on 21 Apr 2009.

Monday 27 April 2009: WHO's warning level 3 of 6 should be 6 (maximum), said the Guan Yi, the professor in Hong Kong, who found SARS-virus in a catlike animal in 2003 and started the initiative which forbid selling such animals. WHO are always too slow and reluctant to highten the warnings, said professor Guan Yi.

Monday 27 April 2009: Airplane companies shares fell 5-17% because of the swine flu. Drug companies like Roche which make vaccines rised.

Monday 27 April 2009: Officials in Hong Kong urged residents not to travel to Mexico. They ordered immediate detention at a hospital of anyone who arrived with a fever and symptoms of a respiratory illness after traveling in the previous seven days through a city with a laboratory-confirmed outbreak. Thomas Tsang, the controller of the Hong Kong government’s Center for Health Protection, said that until the test was proven negative the person would not be allowed out of hospital. The cutoff for having a fever would be 100.4 degrees Fahrenheit. It would take two or three days to obtain test results.

Monday 27 April 2009: There were information in the press that 145 people might have died in Mexico from the disease. Most cases were not confirmed. No lethal cases outside Mexico had been reported. [TV DR1 Denmark, evening broadcasting]

Monday 27 April 2009: All schools in the country of Mexico were ordered closed until 6th of May. Day-care centers, and universities, museums, pyramids, and the 35000 restaurants in Mexico City were closed to keep crowds from spreading contagion. Churches were closed - a big thing in a catholic country, and telling people that the situation was serious. Social and cultural activities were suspended. Public celebrations of Cinco de Mayo were banned. For the first time in decades, Mexico canceled the popular re-enactment of its May 5, 1862, victory over invading French troops in the central state of Puebla. About 2000 people might be infected. People on street were given masks by officials. Everybody had filled their kitchen with food and stay at home.

The Dutch government's Institute for Public Health and Environment had advised any traveler who returned from Mexico since April 17 and develops a fever over 101.3 degrees Fahrenheit (38.5 Celsius) within four days of arriving in the Netherlands to stay at home.

Hong Kong use infrared scanners in airport to detect people with fever: Ever since the 2003 outbreak of SARS-infection Hong Kong has used infrared scanners to measure the facial temperatures of all arrivals at its airport and at its border crossings with mainland China.

Hong Kong may be better prepared for a flu pandemic than practically anywhere else in the world. Fearing that SARS might recur each winter, the city embarked on a building program to enlarge its capacity to isolate and treat those infected with such respiratory diseases.

Hong Kong has also expanded its flu research labs, already among the best in the world and leaders in tracking the H5N1 bird flu virus (bird flu virus), which kills an unusually high share of its victims. It has periodically triggered fears about a possible pandemic, just like swine flu did in spring 2009.

Monday 27 April 2009: At least 20 cases in USA had now been confirmed in New York, Ohio, California, Kansas and Texas.

Monday 27 April 2009: At this time the case fatality rate (CFR) was still uncertain. If the number of infected in Mexico was significantly higher than the reported approximately 1500 cases by this time, it would lower the calculated case fatality rate (CFR). [6955]

Monday 27 April 2009: In USA there were now 40 confirmed cases: New York City 28 cases, California 7 cases, Kansas 2 cases, Texas 2 cases and Ohio 1 case. [http://bit.ly/KO5pA].

CDC's Division of the Strategic National Stockpile (SNS) in USA released one-quarter of its antiviral drugs, personal protective equipment, and respiratory protection devices to help states of USA respond to the outbreak.

Monday 27 April 2009: WHO raised the level of influenza pandemic alert from phase 3 to phase 4, indicating that the likelihood of a pandemic had increased. WHO Phase 4 "is characterized by verified human-to-human transmission of an animal or human-animal influenza reassortant virus able to cause 'community-level outbreaks.' ... Phase 4 indicates a significant increase in risk of a pandemic but does not necessarily mean that a pandemic is a forgone conclusion."

Given the widespread presence of the virus WHO now considered that containment of the outbreak would not be feasible. The current focus should be on mitigation measures. WHO recommended NOT to close borders and NOT to restrict international travel. It was considered prudent for ill people to delay international travel.

Monday 27 April 2009: Mexico had now reported 26 confirmed human cases of infection with the same virus, including 7 deaths (the total suspected death in Mexico toll: 149 people among 1995 people, who had been hospitalized with serious cases of pneumonia since the beginning of the epidemic). Just 2 laboratories in the country of Mexico, one in Mexico City and one in the state of Veracruz, were able to confirm this new strain. This day an earthquake happened in Mexico.

Monday 27 April 2009: Canada had reported 6 cases. Still no deaths outside Mexico.

Monday 27 April 2009: Israel's health minister updated a nervous public about the swine flu epidemic - and renamed it Mexican flu.

Monday 27 April 2009: Swiss police said a container with animal swine flu samples exploded as it was being shipped on a train from Zürich to Geneva, injuring a woman. Authorities said dry ice keeping the samples cold caused the explosion, but the incident posed no threat to humans.

Tuesday 28 April 2009: It was now obvious: The infection could not be contained. WHO flu expert Dr Keiji Fukuda said "Containment is not a feasible operation". However, WHO chief Dr Keiji Fukuda said it was not inevitable that the outbreak would develop into a global epidemic - or pandemic - but countries should "take the opportunity to prepare". WHO spokesman Gregory Hartl said experts were working on a vaccine, but said it could take five or six months to develop.

Tuesday 28 April 2009: Since the end of March 2009, Mexico had observed an unusual pattern of acute respiratory infection (SARI) cases, which increased even more in the 1st weeks of April 2009. From 17 to 28 Apr 2009, 1551 suspected cases of influenza with severe pneumonia were reported, including 84 deaths. These figures were smaller than those reported yesterday earlier due to the investigation work and clean-up of data that had being carried out in field. The suspected cases were recorded in 31 of the 32 states of Mexico. [6970]

Wednesday 29 April 2009: World Health Organization raised its pandemic alert for swine flu to the second highest level "phase 5", meaning that it believed a global outbreak of the disease was imminent. It was the first time the WHO had declared a phase 5 outbreak (phase 4 was also first time). A phase 5 alert means there is sustained transmission among people in at least two countries. Once the virus shows effective transmission in two different regions of the world, a full pandemic outbreak — phase 6 — would be declared, meaning a global epidemic of a new and deadly disease. [6963]



Wednesday 29 April 2009: There was now 3 countries (USA, Canada and Mexico) that had reporting human to human spread of the virus.[6970]

Wednesday 29 April 2009: In Canada to that date, 13 human cases of swine influenza A/H1N1 had been confirmed (2 in Alberta, 4 in the province of New Scotland, 3 in British Columbia and 4 in Ontario), some of them with recent trip history to Cancun, Mexico. None required hospitalization.[6970]

Wednesday 29 April 2009: Confirmed cases in countries outside Mexico were now: Austria (1), Canada (13), Germany (3), Israel (2), New Zealand (3), Spain (4) and the United Kingdom (5). [6970]

Wednesday 29 April 2009: The Mexican health minister, José Ángel Córdova, suddenly reduced the official number of confirmed dead by the infection from 20 to 7. On a chaotic press conference in Mexico City he contradicted himself several times. At the news conference, numerous journalists and camera operators wore masks as protection against the disease. The meeting grew hostile at points, with journalists shouting more questions than the officials seemed willing to take. However he admitted that the Mexican health system could no way handle the situation. Only 10 of the 31 states of Mexico have even one laboratory for virus. The samples must be sent to Mexico City, taking time. From all corners of the country there are report of chaos and panic in hospitals where patients wait in days for medical supervision and end going home without meeting a doctor. The hygiene of the hospital in Obregón in Mexico City is catastrophic, a blogger wrote. The hospitals are on the point of giving up. The National Institute for Respiratory Diseases need masks, surgery glasses and white coats and warn that it will stop treatment unless they got such supplies. The antiviral medicine has been in short supply, and many hospitals have no more. Corruption is the reason, the medicine is stolen and sold to higher prices before it reach the hospitals. 2009 is election year in Mexico. The Mexican health secretary, Jose Angel Cordova, has said that the country’s supply of medicine was sufficient. [6963]

Wednesday 29 April 2009: Germany's biggest tour operator suspended trips to Mexico. [6968]

Wednesday 29 April 2009: US President Barack Obama asked Congress for $1.5bn (£1bn) to help prepare for a possible outbreak. He suggested that all schools ought to be closed if the pupils had any risk of being infected. The country has 132,000 schools. USA had now 91 confirmed infected in 10 states. With 13 cases in California governor Arnold Schwarzenegger declared a state of emergency over the threat.

Wednesday 29 April 2009: In the Muslim Egypt the government decided to kill all pigs in the country, about 300.000 - 350.000. Egypt ordered the pig slaughter even though there hadn’t been a single case of swine flu in Egypt - and even though the A/H1N1 "Swine flu" infection is not spreading from pigs to humans, but from human to human. The pig owners are not Muslim but Christians. Because of bad information people in Egypt believe that the pig meat is infected - 98% of the pig meat sale collapsed. It will take a half year to kill all pigs in Egypt but the government will buy 3 machines with a capacity of killing 3000 pigs dayly. By 5 May 2009 about 1821 pigs had been killed in the pig killing campaign. To set the case in perspective Egypt is at this time infected by bird flu (H5N1). 68 people in Egypt have been infected by this flu virus and 23 of these 68 infected people have died of the infection. However, nobody talks about killing all poultry in the country (poultry is an important food supply in Egypt). [6992]

While epidemiologists kept stressing that it is humans, not pigs, who are spreading the disease, sales plunged for pork producers around the world. WHO says eating pork is safe, but Mexicans have even cut back on their beloved greasy pork tacos. Pork producers were trying to get people to stop calling the disease swine flu, and Obama notably referred to it only by its scientific name, H1N1. United Nations animal health expert Juan Lubroth noted some scientists say “Mexican flu” indicating that it would be more accurate - a suggestion which inflamed passions in Mexico. [6963]

Wednesday 29 April 2009: Lebanon discouraged traditional Arab peck-on-the-cheek greetings, even though no one has come down with the virus there. [6963]

Wednesday 29 April 2009: Peru and Ecuador joined Cuba and Argentina in banning travel either to or from Mexico.

Wednesday 29 April 2009: In England the health minister has ordered 32 million face masks.

Wednesday 29 April 2009: The European Center for Disease Control advised against unnecessary travels to Mexico. WHO did still not advise against travels to Mexico.

Wednesday 29 April 2009: The Danish health minister has ordered 40.000 doses of Relenza antivirus medicine in case the virus becomes resistant to Tamiflu, which Denmark has on stock. On a central storage in Copenhagen 300.000 pills of Tamiflu is ready for 30.000 danes for immeadiate treatment. I en freezer 1.000.000 kg pulver is stored, which can be made into antiviral medicine for one million Danes. [7014].

Wednesday 29 April 2009: Confirmed cases were by now found in Mexico, USA, Canada, Britain, Israel, New Zealand, Spain, - and this date also South Korea, Peru, Germany and Austria, bringing the number of affected countries to 11. [6963]

Wednesday 29 April 2009: Spain reported the first case in Europe of swine flu in a person who had not been to Mexico, illustrating the danger of person-to-person transmission. [6963]

Wednesday 29 April 2009: Suspected cases were being reported from many countries including Latin America (Argentina, Bolivia, Brazil, Chile, Colombia, Costa Rica, Ecuador, Guatemala, Uruguay): Colombia - 42 suspected cases after travel to Mexico ; Chile - 24 suspected cases; Brazil - 11 suspected cases; Bolivia - 2 suspected cases after travel to Mexico; Uruguay - 2nd suspected case under investigation ; Costa Rica - one "confirmed case" after travel to Mexico reported by media on 28 Apr 2009 but not confirmed according to WHO data ; Guatemala - one suspected case after travel to Mexico .
Europe: Slovakia - one suspected case after travel to Mexico ; Belgium - 7 suspected cases after travel to Mexico or USA , France - 32 suspected cases, of which 2 are considered probable (the 2 probable had a history of travel to Mexico) ; Poland - 3 suspected cases after travel to Mexico .
Australia - 91 suspected cases

Wednesday 29 April 2009: A Danish young woman brought this day's morning Influenza A H1N1 infection with her on a Continental Airlines flight CO122N flying directly Newark (New York) - Kastrup (Copenhagen) landing in Copenhagen Airport on the morning 29 April at 7.35 o'clock, where she had been on vacation. She contacted Hvidovre Hospital the same evening with influenza symptoms in the throat and muscles but no fever. A sample was taken and the person was asked to stay at home. She lived alone and had only limited contact with other people. The infection was confirmed 1 May 2009. All passengers on the flight was thereafter contacted. The passengers sitting up to 2 rows in front or back of the infected received antiviral treatment. After the case was confirmed by a quick-test the woman was treated in isolation until 6 May 2009. The press could not get information about in which hospital [7013]. The virus was similar to the type found in New York except for a mutation. It was sensitive to Tamiflu. This dane was the first European person to be infected in USA. [7012]

A Danish university team has shown that a flight seat which send out air around each passenger in an airplane can hinder infection. The system could be in production in 2-3 years if someone would invest in the system. The system could also be used to busses, concert buildings and even hospital beds. Advanced computermodels and dolls with artificial lungs have shown that the system works well. During the SARS epidemic 19 passengers were infected during a single flight. Contact bionyt@gmail.com for address to the Danish inventors.

25-29 April 2009: BBC ask people in the areas affected by the swine flu outbreak to send their accounts to the BBC to be published on http://news.bbc.co.uk/2/hi/talking_point/8018428.stm. Here are some examples from 25-29 April 2009:

"Two soccer games have been cancelled at the Olympic Stadium. A sold out game with 70,000 expected attendance will be played behind closed doors. Another game at the famous Azteca Stadium that would draw an attendance of 50,000 will also be played behind closed doors." [Juan Carlos Leon Calderon, Mexico City]

"Two of my friends at work are sick, they were sick for a couple of days, they went to the hospital and they sent them back to work. The doctor told them it was just a flu until Friday when the alarm was spread, then they were allowed to go home. I work in a call centre and I'm worried because there are no windows in the building so it cannot be ventilated and around 400 people work there. - We all have talked to our supervisor but no one has done anything not even sterilise or disinfect the area. We will be sick soon and, well, do the math - 400 can infect at least another two per day. "[Adriana, Mexico City]

"I work as a resident doctor in one of the biggest hospitals in Mexico City and sadly, the situation is far from "under control". As a doctor, I realise that the media does not report the truth. Authorities distributed vaccines among all the medical personnel with no results, because two of my partners who worked in this hospital (interns) were killed by this new virus in less than six days even though they were vaccinated as all of us were. The official number of deaths is 20, nevertheless, the true number of victims are more than 200. I understand that we must avoid to panic, but telling the truth it might be better now to prevent and avoid more deaths." [Yeny Gregorio Dávila, Mexico City]

"They say on the news that the cases that are most critical involve people aged 20 to 50." [Nallely T, State of Mexico]

"In the capital of my state, Oaxaca, there is a hospital closed because of a death related to the porcine influenza. Many friends working in hospitals or related fields say that the situation is really bad, they are talking about 19 people dead in Oaxaca, including a doctor and a nurse. Last night the local baseball stadium was full, mainly with young people. What's really happening? I know that the economic situation is not the best, and it will worsen with panic. But panic comes from a lack of information. Many people travel for pleasure or without any real need. Stopping those unjustified trips can help a lot to ease the situation. We must do something!" [Alvaro Ricardez, Oaxaca City, Oaxaca, Mexico]

"I have been trying to purchase face masks for myself and my family - my wife and two children - but haven't been able to get one anywhere. I have visited six pharmacies in the area and all are sold out." [Jorge, Mexico City, Mexico ]

"I'm a doctor responsible for managing vaccines in the northern Mexican state of Nuevo Leon. On Sunday we had our first death in the area. It was someone who came from Mexico City. But we don't have the means to confirm whether it was as a result of swine flu. We need to have the means to diagnose people. More than anything, we lack equipment and laboratory kits. All we can do is look at the symptoms and make a clinical diagnosis. In the pharmacies, there is no Tamiflu available. People here are not aware that this flu outbreak can kill people." [Dr Vicente Torres, Monterrey, Nuevo Leon, Mexico]

"I live in Mexico city...I am actually studying here! Mexico city isn't the cleanliest of places and people's attitude make it worse. Nearly half of the 20 million people are not wearing their masks and some are acting as if it's normal to have this flu with their 'I don't care' attitude." [Rachael, Mexico City ]

Thursday 30 April 2009: On a meeting between the 27 EU member states the health minister of France, Roselyne Bachelot, suggest that all flights to Mexico from Europe stop. Such travel restriction to Mexico was not adopted. One argument was, that it would still be possible to travel to another country and then to Mexico.

The U.S., the European Union and other countries have discouraged nonessential travel to Mexico. Some countries have urged their citizens to avoid the United States and Canada as well. Health officials said such bans would do little to stop the virus. WHO said total bans on travel to Mexico were questionable because the virus is already fairly widespread. “WHO does not recommend closing of borders and does not recommend restrictions of travel,” said Dr. Keiji Fukuda, the Geneva-based organization’s flu chief. “From an international perspective, closing borders or restricting travel would have very little effect, if any effect at all, at stopping the movement of this virus.” [6963]

Thursday 30 April 2009: Danish tourists in Mexico were voluntarily evacuated to Denmark.

Thursday 30 April 2009: Confirmed cases were found in Switzerland (19 year old man), Portugal and Holland (3 year old boy).

Thursday 30 April 2009: At this time 109 confirmed cases in USA; 1 death (Mexican boy treated in Texas): New York 50, Texas 26 , California 14, South Carolina 10, Kansas 2, Massachusetts 2, Michigan 1, Indiana 1, Nevada 1, Ohio 1, Arizona 1.

Thursday 30 April 2009: Lab-confirmed cases this date were up to 236 - a jump from 148 the day before. [6972]

Thursday 30 April 2009: A member of US President Barack Obama’s security team was suspected of catching swine flu during a recent visit to Mexico with the president. [6972]

Thursday 30 April 2009: Thanks to some additional testing, the number of confirmed cases in Mexico jumped to 97 from 26. The number of deaths remained at 7. [6972]

Thursday 30 April 2009: Senior health officials from different countries were attempting to coordinate disease surveillance and response with one another, spending hours on transnational conference calls even while separately quibbling over details such as travel restrictions (considered useless by CDC and WHO, but recommended by some countries), and the importance of antiviral drugs. Identifying every case was also a priority, as was determining when to limit social gatherings, as Mexico had been doing, and considering what types of businesses or government operations could briefly be shut down, such as courts, and which ones must stay open, such as the shipping of food. [6972]

Thursday 30 April 2009: U.S. Vice President Joseph Biden caused a stir when he said he wouldn’t want to travel by plane or subway, contradicting his boss’s advice. [6972]

Thursday 30 April 2009: Experts and authorities discussed whether vaccine manufacturers should shift efforts to producing a vaccine against the swine H1N1 instead of producing the seasonal flu vaccine. [6972]

Thursday 30 April 2009: At this time there was also discussions about the usefulness of ferrets for influenza research. In October 2008, researchers from Iowa State University reported about an outbreak of H1N1 swine influenza in a ferret colony on an Iowa farm about 0.4 kilometers from a swine farm. 8% of about 1000 of the minklike animals were infected. The ferret infection was not connected with the later human infection since the H1N1 differed.

Thursday 30 April 2009: Until the outbreak in April 2009, the transmission of swine flu from human to human was virtually unheard of. The CDC laboratories in US received 300 samples from Mexico covering February, March, and April. Those sample were human flu virus until the end of March. There are two or three cases up to the last days of March that are swine flu. Then in April they skyrocket. The swine virus really transmitted very efficiently in humans. [6974]

Thursday 30 April 2009: The epidemic swine flu might die out in the Northern hemisphere like USA, which were going out of the flu season, but countries on the Southern hemisphere were entering winter and flu season at this time.

Friday 1 May 2009: First confirmed case in Denmark. A dane from Sjælland was infected with Influenza A H1N1 in New York. She took the infection with her on a direct flight from New York to Copenhagen.

Saturday 2 May 2009: Canada reported the identification of the A(H1N1) virus in a swine herd in Alberta. The pigs must have been exposed to the virus from a Canadian farm worker recently returned from Mexico, who had exhibited flu-like symptoms and had contact with the pigs. (See 12 April 2009 for a description of this event).

The people who live on an Alberta pig farm where the pigs were found to be infected with swine flu were later tested negative for the virus. [7003]

A number of people living on the pig farm experienced flu-like symptoms after the pigs fell ill and were tested to see whether they too were infected. [7003]

But tests suggested the people were not infected with the H1N1 swine virus. However, blood samples from the people were taken to test for antibodies to look for a definitive answer on whether they were infected. [7003]

The carpenter also tested negative for the virus, but it was believed that that was because he was too far along in his recovery to be still shedding virus. [7003]

A nasal swab from the man was only collected after the pigs started falling sick, and that was more than 10 days after his return from Mexico. [7003]

Officials intended to test his blood too, looking for antibodies to the new H1N1 swine flu virus. [7003]

The antibody test was developed at Canada's National Microbiology Laboratory, which played a key role in the investigation into this new flu virus. [7003]

It was the Winnipeg lab that determined that an unusual outbreak of severe respiratory illness in Mexico was being caused by a new swine flu virus which U.S. researchers had found was infecting people in the United States. [7003]

It was reassuring to learn that the virus causing illness in pigs on the Albertan farm has (probably) not been transmitted to people living on the farm. [7003]

The failure of the swine virus to transmit back to people suggested that the novel H1N1 virus causing human illness did not come into the human population directly from swine. [7003]

[Report about this case; 6 May 2009]:

In Canada a pig herd in Alberta was infected by a man. Clinical signs were observed in 450 out of over 2000 pigs. 19 out of 24 samples were positive for the influenza A matrix gene and 15/24 for the H1 gene. Partial sequencing indicated 100 per cent identity of the matrix gene and 99-100 per cent identity of the H1 gene with sequences from virus isolates from humans in USA and Mexico. [7041]

This was an isolated incident of human to pig transmission by a farm worker returning from holiday in Mexico. [7041]

The worker returned from Mexico on 12 Apr 2009, and then developed flu-like symptoms. He returned to work on 14 Apr and between 14-29 Apr the worker, pig producer, and producer's family all showed symptoms. [7041]

By 24 Apr 2009 the worker had recovered and he tested negative for the flu virus. After this date, the pigs exhibited signs of inappetence, fever, and respiratory signs. [7041]

The affected animals have recovered and there was no mortality that could be directly attributed to influenza infection. [7041]

The premises came under quarantine. [7041]

Transmission of influenza in pigs is via inhalation of aerosols. Some influenza viruses have the capacity to enter the bloodstream and therefore meat and other tissues, but this has not been seen following natural infection in swine with influenza viruses. [7041]

Infection in swine does not produce viraemia and the virus is not found outside the respiratory tract and associated lymph nodes. Therefore, it would be highly unlikely that influenza viruses could be transmitted in pork or pork products or pig semen. [7041]

Surveillance for influenza in pig herds in GB and elsewhere in the EU has been carried out since 1991. Results suggest that although swine influenza of all strains remains a low level disease with occasional epizootics of new strains, this new variant of H1N1 does not appear to be present in pigs in the UK or EU. [7041]

There would be a negligible likelihood of introducing new variant influenza A (H1N1) to the UK by the legal import of pigs or pig products from Canada. The current EU trade rules for live pigs and pig products are considered appropriate to mitigate the risk of disease introduction. [7041]

EU Rules allow the export of live pigs and pig meat or pig products from Canada to the EU. [7041]

Another possible route for disease introduction into pig herds by workers on a pig farm. Livestock workers recently returning from an affected country and/or showing symptoms of an infectious disease should not have contact with pigs or pig farms. [7041]

Swine influenza virus does not produce viraemia. The virus is not found outside the respiratory tract and associated lymph nodes. The virus has not been recovered from semen. This virus could be present in semen but the disease probably would not be transmitted through artificial insemination. [7041]

Though animal influenza viruses do occasionally cause viraemia (such as HPAI H5N1 in cats, it appears that viraemia generally does not occur in cases of (classical) swine influenza. [7041]

Saturday 2 May 2009: Food and Agriculture Organization of the United Nations (FAO), the World Organisation for Animal Health (OIE), the World Health Organization (WHO) and the World Trade Organization. Influenza viruses are not known to be transmissible to people through eating processed pork or other food products derived from pigs. Heat treatments commonly used in cooking meat (e.g. 70 C/160 F core temperature) will readily inactivate any viruses potentially present in raw meat products. Africa remaining the only continent where no such information has yet become available There are still serious gaps in the knowledge about the virus, its epidemiology and pathogenicity, communicating clear, unanimously accepted and scientifically-based information and advice to the public is complex. [7002]

Sunday 3 May 2009: 18 countries have officially reported 787 + 103 ten hours later this day. cases of influenza A(H1N1) infection. Mexico has reported 506 confirmed human cases of infection, including 19 deaths. Other confirmed cases: USA (160), Austria (1), Canada (85), Colombia (1), China, Hong Kong Special Administrative Region (1), Costa Rica (1), Denmark (1), El Salvador (1), France (2), Germany (8), Ireland (1), Israel (3), Italy (1), Netherlands (1), New Zealand (4), Republic of Korea (1), Spain (40), Switzerland (1) and the United Kingdom (15). [6977]


Sunday 3 May 2009: USA had by this time confirmed a total of 226 human cases: New York (63), Texas (40), California (26), Arizona (18), Carolina del Sur (15), Delaware (10), Massachusetts (7), New Jersey (7), Colorado (4), Florida (3), Illinois (3), Indiana (3), Virginia (3), Wisconsin (3). Connecticut (2), Kansas (2), Michigan (2), Alabama (1), Iowa (1), Kentucky (1), Minnesota (1), Missouri (1), Nebraska (1), Nevada (1), New Hampshire (1), New Mexico (1), Ohio (1), Rhode Island (1), Tennessee (1), Utah (1),

Sunday 3 May 2009: Ongoing testing of previously collected specimens in Mexico gave higher number of confirmed cases: 30 Apr: 97 (7 deaths) / 1 May: 156 (9 deaths) / 2 May: 397 (16 deaths) / 3 May: 506 (19 deaths) [6977]. The 506 confirmed cases 3 May 2009 had this distribution in Mexico: Federal District: 288 (death: 13), Mexico State: 70 (death: 4), San Luis Potosi: 42, Hidalgo: 27, Tlaxcala: 19 (death: 1), Baja California: 11, Colima: 9, Chiapas: 6, Aguascalientes: 5, Chichuahua: 4, Tabasco: 4, Zacatecas: 4, Guerrero: 3, Puebla: 3, Durango: 2, Queretaro: 2, Guanajuato: 1, Michoacan: 1, Oaxaca: 1, Veracruz: 1, Quintana Roo: 1, Sonora: 1, Tamaulipas: 1.

Sunday 3 May 2009: Germany had now 8 confirmed cases, 4 of which have human-to-human transmission. In Bavaria an infection of a couple in Frankfurt/Oder in Brandenburg had been infected on a flight from Mexico likely by the confirmed case in Hamburg.

Sunday 3 May 2009: In Mexico 1498 samples had now been tested, 1280 had been tested twice, and 218 would have a second verification test. This had given 506 confirmed cases from 23 states: 272 women (53.8%) and 234 men (46.2%). 487 survivors, 19 deaths. Age breakdown of 506 confirmed cases were (population distribution according to 2005 census):
Ages 0-9 122 cases (24.1 %) (20.6 %)
Ages 10-19 120 cases (23.7 %) (20.9 %)
Ages 20-29 98 cases (19.4 %) (16.9 %)
Ages 30-39 69 cases (13.6 %) (14.9 %)
Ages 40-49 51 cases (10.1 %) (10.8 %)
Ages 50-59 34 cases (6.7 %) (7.8 %)
Ages 60+ 3 cases (0.6 %) (8.3 %)
unknown age 9 cases (1.8 %)

48 percent of confirmed cases in Mexico are less than 20 years of age and 43 percent of cases are 20-49 years of age.

Comparing the age distribution of cases with the general age distribution of the population in Mexico (based on 2005 census data), it appeared as though the young 0-20 year population was slightly over-represented proportionally and the 20-49 year group was appropriately represented (43 percent of cases, and 43 percent of the population). The elderly in Mexico appeared to be underrepresented - in contrast to seasonal influenza. It was not clear if there was an epidemiologic or immunologic explanation for this.

The 19 death in Mexico confirmed to be related with A/H1N1-virus were:
11 Apr 2009 --- 2 deaths

13 Apr 2009 --- 1 death
16 Apr 2009 --- 1 death
17 Apr 2009 --- 2 deaths
20 Apr 2009 --- 3 deaths
22 Apr 2009 --- 1 death
24 Apr 2009 --- 1 death
25 Apr 2009 --- 1 death
26 Apr 2009 --- 5 deaths
27 Apr 2009 --- 1 death
28 Apr 2009 --- 1 death

Monday 4 May 2009: In Canada the 1st serious case, a young child, was admitted to a intensive care unit (link)

Monday 4 May 2009: Spain had now 54 infected. 50 of them had returned from a visit to Mexico. (New York Times).

In Mexico the R0 (i.e. the virus reproduction number, or number of contacts of infected people that results in transmission of the virus), was estimated 1.4, with a variability ranging from 1.3 to 1.8. In the case of seasonal influenza, this rate is somewhat lower 1.3. [6986]



The reproductive ratio (R0) of 1.4 with a range of 1.3 to 1.8 whereas the observed R0 for seasonal influenza was 1.3 (the R0 refers to the expected number of secondary infections seen in a population of susceptibles from contact with a single individual during their infectious period.) This slight increase in R0 suggests that the A(H1N1) observed in Mexico is slightly more transmissible than seasonal influenza. (Global Security discussion on influenza transmission and the R0 figure).

Tuesday 5 May 2009: A Texas woman who lived near a popular border crossing was confirmed as the second outside Mexico and the first U.S. resident to die after contracting the virus. She had chronic medical conditions. The 33-year-old woman was pregnant and delivered a healthy baby while hospitalized. She was a teacher in the Mercedes Independent School District, which announced it would close its schools until May 11 2009. [6990]

Tuesday 5 May 2009: Many people in Mexico city shunned their surgical masks Tuesday 5 May 2009; a boy selling music CDs on a subway train planted a wet kiss on the unprotected cheek of a girl hawking tiny flashlights. A fruit salad vendor dished up slabs of freshly cut mango and coconut without mask and gloves. The government is requiring businesses to keep a distance of 2 meters (yards) between customers to prevent the disease from spreading. The rule seemed unlikely to survive in the overcrowded capital. "It's a little senseless, that people ride into town all jammed together on the subway, and the minute they enter a restaurant, they have to be 2 meters apart," said Nahum Navarette, manager of Yug, a vegetarian restaurant that was still serving only takeout on Tuesday, its dining room deserted. Across Mexico, people were now eagerly anticipating the reopening of businesses, restaurants, schools and parks, after a claustrophobic five-day furlough. Thousands of newspaper vendors, salesmen hawking trinkets and even panhandlers dropped their protective masks and joined the familiar din of traffic horns and blaring music on the streets of the capital with its 20 million residents. Denver's annual festival, which typically draws 400,000, was going to be held as planned next weekend. High schools and universities were being scrubbed down to reopen Tuesday 5 May 2009. Younger children were to return to school on Monday 11 MAy 2009. Only essential services like gas stations and supermarkets had been allowed to operate since April 27. Some officials were worried about a sudden rush toward normalcy. "The scientists are saying that we really need to evaluate more," said Dr. Ethel Palacios, the deputy director of the swine flu monitoring effort here. "In terms of how the virus is going to behave, we are keeping every possibility in mind. ... We can't make a prediction of what's going to happen", a journalist was told. [6990].

Tuesday 5 May 2009: The Mexican influenza epidemic might be caused by not one but two new virus types. Influenza A detections done by a laboratory in Canada between 24 Apr 2009 and 3 May 2009 found equally of the H1 or H3 subtype. During late March and early April 2009 the laboratory reported an unexpected number of late-season outbreaks due to H3 influenza in Canada, and two new H3 mutations arose in early March 2009. They also found at least one returning traveler to have likely acquired illness due to this new H3 virus in Mexico. If two new influenza viruses emerged simultaneously in Marts 2009 it might explain some unusual features with the Mexican epidemic. [6982]

5 May 2009 There had by this time been a world total of 1490 cases and 31 deaths of influenza A (H1N1) infection from 21 countries (a rise from the day before [4 May 2009], where the total figures were 1085 confirmed cases and 26 deaths from 21 countries).

Guatemala notified its first confirmed case of influenza A (H1N1) in a person that has travelled to Mexico.

A few countries reported a day-by-day increase; death in parenthesis:
Canada: 19 / 34 / 51 / 85 / 101 / 140
Mexico: 97(7) / 156 (9) / 397 (16) / 506 (19) / 590 (25) / 866 (29)
United Kingdom: 8 / 8 / 15 / 15 / 18 / 27
United States: 109 (1) / 141 (1) / 160 (1) / 226 (1) / 286 (1) / 403 (1); USA had confirmed influenza A (H1N1) in 38 States.


Mexico had by this time reported 866 laboratory confirmed human cases of infection, including 29 deaths.

In Mexico the majority of infections occurred in previously healthy young adult people, and few cases in children under 5 years old (102/822).

The 866 confirmed cases in Mexico corresponded to 32.2 % of the cases on which specimens were obtained. 50.9 % were women. With respect to confirmation of suspected cases, 47.8 % of the specimens obtained from young people between 10 and 19 years of age were positive. Of suspected cases in people older than 60 years only 16.5 % were confirmed. 73.7 % of the cases older than 60 years were women.

The graph of the 866 confirmed cases showed a downward trend by date having begun on 26 Apr and now substantially lower numbers of cases were reported on a daily basis. This trend of decreasing case reports is among confirmed cases but also among suspected cases.

There were initially 214 reported deaths attributable to acute pneumonia in Mexico. Of these were 74 definitively discarded based on clinical studies. This left 140 possible deaths due to A (H1N1). Only 29 were confirmed through molecular biologic studies. 35 laboratory studies were still pending. For 77 deaths it was not possible to obtain specimens so confirmation was impossible - they remained as suspected cases.

The mean age of the infected is 17 years. The majority of deaths in Mexico were between 20 and 39 years of age [18 of the 26 deaths were aged 20 - 39 years, whereas 273 of the confirmed cases were in this age group, with an age specific case fatality rate of 6.6 percent, when compared with an overall case fatality rate of 3.0]. So, the overall case fatality rate (CFR) for the confirmed cases in Mexico was at this time 3.0 percent, but the CFR for the 20-39 year old age group was 6.6 percent.

41.5 percent of the Mexican population in general is less than 20 years of age. 51.6 percent of confirmed cases in Mexico were less than 20 years of age - suggesting a higher representation of this age group among cases (or higher age specific attack rate). [6986]

Mexico had 810 000 antiviral treatments - each involving 10 doses. The World Health Organization said it was shipping 2.4 million treatments of antiflu drugs to 72 countries "most in need," and France sent 100,000 doses of antiflu drugs worth $1.7 million to Mexico. [6986] [6990]

Mexican Finance Secretary Agustin Carstens said the outbreak cost Mexico's economy at least $2.2 billion, and he announced a $1.3 billion stimulus package, mostly for tourism and small businesses, the sectors hardest hit by the epidemic. Mexico will temporarily reduce taxes for airlines and cruise ships and cut health insurance payments for small businesses. [6990]

About 20 Chinese businessmen and students, each wearing surgical masks, left Tijuana zon Tuesday on a Chinese government flight after being stranded when China canceled all direct flights to Mexico. Mexico, meanwhile, was collecting more than 70 Mexican nationals quarantined in China with its own charter flight. [6990]

Four U.S. citizens were quarantined in China, the U.S. Embassy in Beijing said Tuesday, and about 200 passengers who flew from the United Kingdom were under quarantine in a Brunei hospital after three of them arrived with fevers. [6990]

Wednesday 6 May 2009: Sweden report its first confirmed infection - a woman in Stockholm after a visit to USA.

Wednesday 6 May 2009: Canadian officials announced the Winnipeg lab had completed full virus sequencing of 3 sample viruses, 2 from Canadian swine flu cases and one from Mexico. The viruses were virtually identical. The full genetic sequences of viruses retrieved from the pigs have not yet been completed. That work is being done at the National Centre for Foreign Animal Diseases, the National Microbiology Laboratory's animal health counterpart. The 2 labs are co-located. Experts will be keen to study the genetic sequences of the viruses isolated from the pigs to determine whether there are any mutations that arose when the virus went back into swine. [7003]

Thursday 7 May 2009: Two new countries have confirmed cases: Brazil and Argentina [6999]

Thursday 7 May 2009. The New England Journal of Medicine bring an article about the flu: Between the 1930s and the 1990s, the most commonly circulating swine influenza virus among pigs -- classic swine influenza A (H1N1) -- underwent little change. But by the late 1990s multiple strains and subtypes (H1N1, H3N2, and H1N2) of triple-reassortant swine influenza A (H1) viruses (whose genomes included combinations of avian, human, and swine influenza virus gene segments) had became predominant among North American pig herds. Worldwide, more than 50 cases of swine influenza virus infection in humans, most due to classic swine influenza virus, have been documented in the past 35 years. People with occupational swine exposure are at highest risk for infection. Until April 2009, only limited, nonsustained human-to-human transmission of swine influenza virus had been reported. The CDC identified the 1st human infection with triple-reassortant swine influenza A (H1) viruses in the United States in December 2005. From December 2005 through February 2009, the CDC received 11 notifications of human infection with triple-reassortant swine influenza A(H1) viruses, 8 of which occurred after June 2007. Triple-reassortant swine influenza A (H1) viruses (with genes from avian, human, and swine influenza viruses) emerged and became enzootic among pig herds in North America during the late 1990s. From December 2005 until just before the current human epidemic of swine-origin influenza viruses, there was sporadic infection with triple-reassortant swine influenza A (H1) viruses in persons with exposure to pigs in the United States. Although all the patients recovered, severe illness of the lower respiratory tract and unusual influenza signs such as diarrhea were observed in some patients, including those who had been previously healthy.

Thursday 7 May 2009: The New England Journal of Medicine - wrote in another article: Triple-reassortant swine influenza viruses, which contain genes from human, swine, and avian influenza A viruses, have been identified in swine in the United States since 1998. 12 cases of human infection with such viruses were identified in the United States from 2005 through 2009. On 15 Apr 2009 and 17 Apr 2009, the Centers for Disease Control and Prevention(CDC) identified 2 cases of human infection with a swine-origin influenza A (H1N1) virus (S-OIV) characterized by a unique combination of gene segments that had not been identified among human or swine influenza A viruses. Prevention (CDC) identified 2 cases of human infection with a swine-origin influenza A (H1N1) virus (S-OIV) characterized by a unique combination of gene segments that had not been identified among human or swine influenza A viruses. From 15 Apr 2009 through 5 May 2009, a total of 642 confirmed cases of S-OIV infection were identified. The ages of patients ranged from 3 months to 81 years. The most common presenting symptoms were fever (94 percent of patients), cough (92 percent), and sore throat (66 percent); 25 percent of patients had diarrhea, and 25 percent had vomiting. Of the 399 patients for whom hospitalization status was known, 36 (9 percent) required hospitalization. Of 22 hospitalized patients with available data, 12 had characteristics that conferred an increased risk of severe seasonal influenza, 11 had pneumonia, 8 required admission to an intensive care unit, 4 had respiratory failure, and 2 died. It is likely that the number of confirmed cases underestimates the number of cases that have occurred. [7000]

Wednesday 7 May 2009: First cases in Brazil. Three persons were infected in Mexico, and one person was infected in USA. All were young adult persons. [7010]

Thursday 7 MAY 2009: The case-fatality rate of the flu was still difficult to ascertain in a rapidly evolving outbreak, because an unknown proportion of currently infected patients might die; there may be unreported cases, and groups at high risk for death from seasonal influenza (e.g., older adults and patients with chronic disease) might not yet have been exposed to the novel influenza A (H1N1) virus. Summertime influenza outbreaks in temperate climates have been reported in closed communities such as prisons, nursing homes, cruise ships, and other settings with close contact. Such outbreaks typically do not result in community-wide transmission, but they can be important indicators of viruses likely to circulate in the upcoming influenza season. The novel influenza A (H1N1) virus has been circulating in North America largely after the peak influenza transmission season. The imminent onset of the season for influenza virus transmission in the southern hemisphere, coupled with detection of confirmed cases in several countries in the southern zone, raise concern that spread of novel influenza A (H1N1) virus might result in large-scale outbreaks during upcoming months. Influenza virus can circulate year round in tropical regions.

Assessments to be made include:
Clinical progression of disease.
Rates of complications for different age and risk groups;
Types of complications for different age and risk groups.
Information on virus transmissibility.
[7003]

Thursday 7 May 2009: In the Netherlands, the 2nd laboratory confirmed human case of influenza A (H1N1) virus infection was reported. A 53-year-old woman returned on the 30 Apr 2009 from Cancun, Mexico. During the flight she developed an unproductive cough. 2 days later, on 2 May 2009, she had a temperature of 38.6C and a sore throat and consulted a general practitioner. Samples were submitted for diagnostic evaluation and both the patient and her husband were treated with oseltamivir. The patient recovered completely and uneventfully. Samples collected 4 days later tested negative. The sequence data suggested that the virus was susceptible to both oseltamivir and zanamivir. The amino acid 627 in PB2 (glutamicacid) was not human-host-adapted, similar to recent swine influenza A (H1N1) viruses. However, a glutamic acid to glycine amino acid substitution was detected at position 677 in PB2. This mutation was not observed in any of the A (H1N1) sequences submitted since 27 Apr 2009. Lam et al. (2008) [T.T. Lam et al., "Evolutionary and transmission dynamics of reassortant H5N1 influenza virus in Indonesia", PLoS Pathog. 2008 Aug 22;4(8):e1000130] postulated that this substitution could reflect adaptation to mammalian hosts of highly pathogenic avian influenza A (H5N1) viruses, as it was found to be under positive selection based on phylogenetics of Indonesian viruses. Based on the position of the mutation it might contribute to more efficient human-to-human transmission by enhanced replicative efficiency of the polymerase of the influenza A (H1N1) virus in humans [PB2 is a polymerase component]. The identification of a single mutation in the PB2 gene (encoding the major component of the viral polymerase) of the novel 2009 strain of influenza A (H1N1) virus is only previously reported in the case of avian influenza A (H5N1) virus. Such a mutation might influence the transmissibility and the host range of the virus. But it would be premature to draw such a conclusion since there appears to have been no onward transmission of the virus to any other person. [7001]

Friday 8 May 2009: 25 countries have officially reported 2500 cases of influenza A (H1N1) infection. [6999]

Friday 8 May 2009: Mexico has reported 1204 laboratory confirmed human cases of infection, including 44 deaths. The United States has reported 896 laboratory confirmed human cases, including 2 deaths. [6999]

Friday 8 May 2009: The following countries have reported laboratory confirmed cases with no deaths - Austria (1), Brazil (4), Canada (214), Hong Kong (1), Colombia (1), Costa Rica (1), Denmark (1), El Salvador (2), France (12), Germany (11), Guatemala (1), Ireland (1), Israel (7), Italy (6), Netherlands (3), New Zealand (5), Poland (1), Portugal (1), Republic of Korea (3), Spain (88), Sweden (1), Switzerland (1), United Kingdom (34). [6999]

Friday 8 May 2009: Number of cases 30 Apr 2009 / 1 May / 2 May / 3 May / 4 May / 5 May / 6 May / 7 May / 8 May in some countries: [6999]
Canada: 19 / 34 / 51 / 85 / 101 / 140 / 165 / 201 / 214
France: 0 / 0 / 2 / 2 / 4 / 4 / 5 / 5 / 12
Germany: 3 / 4 / 6 / 8 / 8 / 9 / 9 / 10 / 11
Mexico: 97(7) / 156 (9) / 397 (16) / 506 (19) / 590 (25) / 822 (29) / 942 (29) / 1112 (42) / 1204 (44)
Spain: 13 / 13 / 13 / 40 / 54 / 57 / 73 / 81 / 88
United Kingdom: 8 / 8 / 15 / 15 / 18 / 27 / 28 / 32 / 34
United States: 109 (1) / 141 (1) / 160 (1) / 226 (1) / 286 (1) / 403 (1) / 642 (2) / 896 (2)
Total No. countries reporting cases: 11 / 13 / 16 / 18 / 21 / 21 / 23 / 24 / 25
Total cases reported (death in parenthesis): 257 (8) / 367 (10) / 658 (17) / 898 (20) / 1085 (26) / 1490 (30) / 1893 (31) / 2371 (44) / 2500 (46) [6999]

Friday 8 May 2009: Novel influenza A (H1N1) activity is now being detected in 2 of CDC's routine influenza surveillance systems as reported in the [8 May 2009] FluView [see ]. FluView is a weekly report that tracks US influenza activity through multiple systems across 5 categories. The 8 May 2009 FluView found that the number of people visiting their doctors with influenza-like-illness is higher than expected in the US for this time of year. Also, laboratory data shows that regular seasonal influenza A (H1N1), (H3N2) and influenza B viruses are still circulating in the US, but novel influenza A (H1N1) and "unsubtypable"* viruses now account for a significant number of the viruses detected in the US. CDC continues to take aggressive action to respond to the outbreak. [7036]

Saturday 9 May 2009: There was now reported more cases from USA than Mexico (1364 confirmed human cases of
infection in Mexico, 1639 in USA (and number of confirmed cases rapidly growing during this day). 45 deaths in Mexico, 2 deaths in USA, Canada one death.)

There was a dramatic increase in the number of cases in USA day-by-day: 109 - 141 - 160 - 226 - 286 - 403 - 642 - 896 - 1639.

Two new countries, Argentina and Panama, have confirmed cases of
Influenza A(H1N1).

The World Health Organization maintained pandemic alert of Phase 5.
There was no evidence of sustained community level human to human
transmission outside of the Americas.

In Brazil a mother of a 29-year-old
student infected by a 21-year-old student who returned to Rio de
Janeiro from Cancun, Mexico, on 2 May, was hospitalized on Sat 9 May
as a suspect case. Test results will be known on Tue 12 May.

Arizona: 1 / 4 / 4 /18 / 17 / 17 / 48 / 48 / 131 / 182
California: 14 / 13 / 24 / 26 / 30 / 49 / 67 / 106 / 107 / 171
Colorado: 0 / 2 / 2 / 4 / 7 / 6 / 17 / 17 / 25 / 41
Connecticut: 0 / 0 / 1 / 2 / 2 / 2 / 4 / 4 / 4 / 14
Delaware: 0 / 4 / 4 / 10 / 20 / 20 / 33 / 28 / 39 / 44
Florida: 0 / 0 / 2 / 3 / 5 / 5 / 5 / 5 / 6 / 43
Illinois: 0 / 3 / 3 / 3 / 8 / 82 / 122 / 204 / 392 / 421
Iowa: 0 / 0 / 0 / 1 / 1 / 1 / 1 / 5 / 5 / 43
Maryland: 0 / 0 / 0 / 0 / 4 / 4 / 4 / 4 / 4 / 23
Massachusetts: 2 / 2 / 8 / 7 / 6 / 6 / 45 / 71 / 83 / 89
Michigan: 1 / 2 / 2 / 2 / 2 / 2 / 8 / 9 / 49 / 103
Missouri: 0 / 0 / 1 / 1 / 1 / 1 / 2 / 4 / 9 / 10
Nebraska: 0 / 1 / 0 / 1 / 1 / 1 / 4 / 4 / 4 / 13
New Mexico: 0 / 0 / 0 / 1 / 1 / 1 / 3 / 8 / 8 / 30
New York: 50 / 50 / 50 / 63 / 73 / 90 / 97 / 98 / 174 / 190
Ohio: 1 / 1 / 1 / 3 / 3 / 3 / 5 / 5 / 6 / 12
Oregon: 0 / 0 / 0 / 0 / 3 / 15 / 15 / 15 / 15 / 15
Pennsylvania: 0 / 0 / 0 / 0 / 1 / 1 / 1 / 2 / 2 / 10
South Carolina: 10 / 16 / 13 / 15 / 15 / 16 / 16 / 17 / 29 / 42
Tennessee: 0 / 0 / 0 / 1 / 1 / 2 / 2 / 2 / 36 / 46
Texas: 26 (1) / 28 (1) / 28 (1) / 40 (1) / 41 (1) / 41 (1) / 61 (2) /
91 (2) / 93 (2) / 110 (2)
Utah: 0 / 0 / 0 / 1 / 1 / 1 / 1 / 8 / 24 / 60

Virginia: 0 / 2 / 2 / 3 / 3 / 3 / 3 / 11 / 14 / 16
Washington: 0 / 0 / 0 / 0 / 0 / 0 / 9 / 23 / 33 / 83

Wisconsin: 0 / 0 / 0 / 3 / 3 / 3 / 6 / 26 / 240 / 317

A fatality has been reported
from Costa Rica: a 53 year old male with preexisting diabetes and
chronic lung disease.

A new
fatality reported in the USA: a 30-year-old male with preexisting
heart disease.

A confirmed case in Norway and
the 1st locally transmitted case in Italy.

The USA has officially reported 2254 laboratory confirmed cases
coming from 44 states (compared with 1639 cases from 43 states on 8
May 2009)
[7007]

Sunday 10 May 2009:
First confirmed cases in Norway: A man from Oslo and a woman from Skien, who both studied in Mexico, were ill Wednesday 7 May 2009 with the flu. [7009]

Sunday 10 May 2009 (morning), 29 countries have officially reported 4379 cases of influenza A (H1N1) infection. Confirmed human cases of infection (deaths): Mexico 1626 (45), USA 2254 (2), Canada 280 (1), Costa Rica 8 (1). All other countries no deaths: Spain 93, United Kingdom 39, France 12, Germany 11, Italy 9, Israel 7, New Zealand 7, Brazil 6, Japan 4, Netherlands 3, Panama 3, Republic of Korea 3, El Salvador 2, Argentina 1, Australia 1, Austria 1, Colombia 1, Denmark 1, Guatemala 1, Hong Kong 1, Ireland 1, Poland 1, Portugal 1, Sweden 1, Switzerland 1. [7023]

Sunday 10 May 2009: Day-by-day: Country: number of cases (deaths in parenthesis) 2009 Apr: 30 / May: 1 / 2 / 3 / 4 / 5 / 6 / 7 / 8 / 9 / 10:
Total cases reported: 257 (8) / 367 (10) / 658 (17) / 898 (20) / 1085 (26) / 1490 (30) / 1893 (31) / 2371 (44) / 2500 (46) / 4379 (49) [7023]

Sunday 10 May 2009: Mexico has reported 2062 confirmed cases of influenza A (H1N1), including 48 deaths, in 30 of 32 states. The states with the highest number of confirmed cases are the Federal District (Mexico City), State of Mexico, San Luis Potosi, and Hidalgo. [7023]

Sunday 10 May 2009: In Canada: 284 human cases of influenza A (H1N1) have been confirmed, including 1 death in Alberta, in 9 of 13 Provinces (48 in Alberta, 79 in British Columbia, 2 in New Brunswick, 56 in Nova Scotia, 15 in Quebec, 1 in Manitoba, 76 in Ontario, 3 in Prince Edward Island and 4 in Saskatchewan). [7023]

Sunday 10 May 2009: USA has confirmed a total of 2532 cases of influenza A (H1N1), including 3 deaths (2 in Texas and one in the state of Washington), in 44 States (including the District of Columbia): 4 in Alabama, 182 in Arizona, 282 in California, 39 in Colorado, 24 in Connecticut, 44 in Delaware, 53 in Florida, 3 in Georgia, 6 in Hawaii, 1 in Idaho, 466 in Illinois, 39 in Indiana, 43 in Iowa, 36 in Kansas, 3 in Kentucky, 9 in Louisiana, 4 in Maine, 23 in Maryland, 88 in Massachusetts, 114 in Michigan, 7 in Minnesota, 10 in Missouri, 13 in Nebraska, 9 in Nevada, 4 in New Hampshire, 7 in New Jersey, 30 in New Mexico, 190 in New York, 7 in North Carolina, 6 in Ohio, 14 in Oklahoma, 17 in Oregon, 10 in Pennsylvania, 7 in Rhode Island, 32 in South Carolina, 1 in South Dakota, 54 in Tennessee, 108 in Texas, 63 in Utah, 1 in Vermont, 16 in Virginia, 102 in Washington, 4 in Washington DC, and 357 in Wisconsin. [7023]

Graphics on the status of the epidemic: . [7023]

Sunday 10 May 2009: China-mainland report its first confirmed case. (It is also the 1st confirmed case on mainland after history of travel to USA). [7023]

Sunday 10 May 2009: Brazil, Colombia, and El Salvador each notified 2 new confirmed cases of influenza A (H1N1).

11 May 2009: Monday 11 May 2009 morning: 30 countries have officially reported 4694 cases of influenza A(H1N1) infection.

Mexico has reported 1626 laboratory confirmed human cases of infection, including 48 deaths. The United States 2532 with 3 deaths. Canada 284 with one death. Costa Rica 8 with 1 death. Other countries (with no deaths): Argentina (1), Australia (1), Austria (1), Brazil (8), China-mainland (2), Hong Kong Special Administrative Region, and 1 in mainland China), Colombia (3), Denmark (1), El Salvador (4), France (13), Germany (11), Guatemala (1), Ireland (1), Israel (7), Italy (9), Japan (4), Netherlands (3), New Zealand (7), Norway (2), Panama (15), Poland (1), Portugal (1), Republic of Korea (3), Spain (95), Sweden (2), Switzerland (1) and the United Kingdom (47). [7036]

Monday 11 May 2009 afternoon: The total of confirmed cases of influenza A (H1N1) recorded is 5029 including 61 deaths, in 10 countries of the Americas (Argentina, Brazil, Canada, Colombia, Costa Rica, El Salvador, Guatemala, Mexico, Panama, and the United States). This figure could be higher, however, because some countries are still waiting for the laboratory confirmation of samples collected in previous weeks. [7036]

To date, the United States has confirmed a total of 2600 human cases of influenza A (H1N1) including 3 deaths, in 44 states including the District of Columbia: 4 in Alabama, 182 in Arizona, 191 in California, 39 in Colorado, 24 in Connecticut, 44 in Delaware, 54 in Florida, 3 in Georgia, 6 in Hawaii, 1 in Idaho, 487 in Illinois, 39 in Indiana, 43 in Iowa, 18 in Kansas, 10 in Kentucky, 9 in Louisiana, 4 in Maine, 23 in Maryland, 88 in Massachusetts, 130 in Michigan, 7 in Minnesota, 14 in Missouri, 13 in Nebraska, 9 in Nevada, 4 in New Hampshire, 7 in New Jersey, 30 in New Mexico, 190 in New York, 11 in North Carolina, 6 in Ohio, 14 in Oklahoma, 17 in Oregon, 10 in Pennsylvania, 7 in Rhode Island, 32 in South Carolina, 1 in South Dakota, 54 in Tennessee, 179 in Texas, 63 in Utah, 1 in Vermont, 16 in Virginia, 128 in Washington, 4 in Washington, DC and 384 in Wisconsin. Other suspected cases are being investigated. [7036]

From [1 Mar 2009 to 10 May 2009], Mexico has reported 2059 confirmed cases of influenza A (H1N1), including 56 deaths, in 30 of 32 states. The states with the highest number of confirmed cases are Distrito Federal, Estado de Mexico, San Luis Potosi and Hidalgo. [7036]

In Canada, to date 330 human cases of influenza A (H1N1) have been confirmed, including a death, in 9 of 13 provinces: (52 in Alberta, 79 in British Columbia, 2 in New Brunswick, 57 in Nova Scotia, 16 in Quebec, 1 in Manitoba, 110 in Ontario, 3 in Prince Edward Island and 10 in Saskatchewan). [7036]

To date, Argentina has confirmed 1 human case of influenza A (H1N1); Brazil, 8 cases; Colombia, 3 cases; Costa Rica, 8 cases including a death; El Salvador, 4 cases, Guatemala, 1 case; and Panama, 15 cases. [7036]

Monday 11 May 2009: Judging the pandemic potential of this new flu is difficult with limited data but nevertheless is essential to inform appropriate health responses. [7024 (Science report)].

By analyzing the outbreak in Mexico estimates suggest that 23 000 (range 6000-32 000) individuals had been infected in Mexico by late April 2009, giving an estimated case fatality ratio (CFR) of 0.4 per cent (range 0.3 to 1.5 per cent) based on confirmed and suspect deaths reported up to that time. [7024 (Science report)].

In a community outbreak in the small community of La Gloria, Veracruz, no deaths were attributed to infection, giving an upper 95 per cent bound on CFR of 0.6 per cent. [7024 (Science report)].

Thus, while substantial uncertainty remains, clinical severity appears less than that seen in 1918 but comparable with that seen in 1957. [7024 (Science report)].

Clinical attack rates in children in La Gloria were twice those in adults (less than 15 years of age: 61%, 15: 29%). [7024 (Science report)].

Three different epidemiological analyses gave R0 estimates in the range 1.4-1.6, while a genetic analysis gave a central estimate of 1.2. [7024 (Science report)].

This range of values is consistent with 14 to 73 generations of human-to-human transmission having occurred in Mexico to late April 2009. ¤ [7024 (Science report)].

Transmissibility is therefore substantially higher than seasonal flu and comparable with lower estimates of R0 obtained from previous influenza pandemics. [7024; (Science)].

A UK analysis reported in Science concludes that the World Health Organization was right to raise the alert over a potential global flu pandemic. [7024b].

It says the outbreak is likely to be comparable to the pandemics of the 20th century. [7024b].

The study, led by Professor Neil Ferguson, of Imperial College, London, is published in the leading journal Science [see preceding report]. It finds that -- as suspected -- the virus is more infectious than normal. [7024b].

Seasonal flu normally infects one in 10 of the population. [7024b].

So far, swine flu has infected 1/3rd of the people that have come into contact with it in Mexico. [7024b].

Professor Fergusons study (admitting it was difficult to quantify the impact at this stage) suggests that swine flu could kill between 4 in every 1000 infected people and 14 in every 1000. [7024b].

Professor Ferguson said: "The World Health Organization was correct in its judgment that this is a virus that should not be ignored, but these figures suggest at this stage it is not going to be catastrophic." [7024b].

Four other schools in England have reopened after cases of infection. Hampton School in south west London was closed for a week starting Monday 11 May 2009 after a Year 7 pupil fell ill after traveling overseas. It is offering antiviral drugs to all children in Year 7, any staff who had close contact with the pupil, and any other children who shared school coach journeys with him. [7024b].

All infections in the UK so far had been "mild" and thanks to early diagnosis and treatment with antivirals, the spread of the virus is being limited and symptoms reduced. [7024b].

2 cases in London are both connected with Alleyn's School in Dulwich, which was closed on 4 May 2009 after 5 pupils were confirmed with the virus. The 2 latest cases were a 12 year old pupil and a parent. [7024b].

NHS East of England said the 4 cases in its area included a man from North Weald, Essex, who had close contact with an already confirmed case and a child from Canvey Island, also in Essex, who recently visited Mexico. [7024b].

Another case involved a man from Lowestoft, Suffolk, who recently visited Florida. [7024b].

The 4th case was a woman from the Huntingdonshire district in Cambridgeshire. [7024b].

Holiday companies Thomson and First Choice were cancelling all flights to the Mexican resorts of Cancun and Cozumel up to and including 18 May 2009. [7024b].

Their last holiday makers still in Mexico would be returning home to England on Monday 11 May 2009. [7024]



Tuesday 12 May 2009
The new virus, which had now infected 5,251 people in 30 countries and killed 61, has displayed great efficiency in spreading among people

This virus, which has only been around a few months, is very unstable - and we know that its presence is dramatically increasing in human population, so the chance of it meeting with H5N1 (bird flu virus) is actually increased.

Both swineorigin-H1N1 and birdflu-H5N1 are unstable so the chances of them exchanging genetic material are higher, whereas a stable (seasonal flu) virus is less likely to take on genetic material.

While swineorigin-H1N1 appears to be mild so far with many infected people recovering even without treatment, the birdflu-H5N1 has a mortality rate of between 60 to 70 percent.

Experts are fearful about the emergence of a hybrid which combines the killing power of the H5N1 with the efficient transmissibility of swineorigin-H1N1.

birdflu-H5N1 is believed to be endemic in countries like China, Indonesia, Vietnam and Egypt.

There is a huge information gap due to a lack of regular surveillance on animal disease.

Each one of the eight gene segments in the new virus has been seen in pigs in the past 10 years, but experts have no clue when this new swineorigin-H1N1 virus strain first appeared and in which animal species it had been incubating.

We know when each gene segment appeared, but we don't know when this strain first appeared, there is an information gap of about five to 10 years, from 1999 to 2009. If there was regular surveillance, we would know when this virus came about.

We don't know if this reassortment happened in pigs or human ... It's likely to have come from pigs because all the segments have been found in pigs, but we can't be 100 percent sure.

It appears to be more virulent than seasonal flu because it is killing younger people and it appears to have higher mortality than seasonal flu, so it doesn't make sense to treat this like seasonal flu.

[7033; interview with Guan Yi, a leading microbiologist with the University of Hong Kong.]



Tuesday May 12, 2009: The new H1N1 virus shows no signs of sustained person-to-person spread outside of North America and so has not yet tipped over into a pandemic, a top World Health Organization official, Dr. Keiji Fukuda, acting WHO assistant director-general, said on Monday. Things change on an almost daily basis," Fukuda said. "We are evaluating the clinical features, we are evaluating the epidemiology and the spread. [7034]

In Mexico, millions of children, many of them wearing surgical masks and clutching hand sanitizer, went back to classes for the first time in two weeks. Schools throughout Mexico were scrubbed from floor to ceiling last week and the 20 million students who returned on Monday were told to follow strict hygiene rules. Although there is no evidence to show masks protect people who have not been infected, many children wore them. [7034]

Chinese authorities were searching for 150 people who took the same flights as mainland China's first confirmed case of the new flu. State television and the Xinhau news agency said the government had tracked down and quarantined about 150 people who flew with the 30-year-old man, first from Tokyo to Beijing and then from Beijing to the Sichuan provincial capital, Chengdu. But another 150 or so were unaccounted for. The patient himself, a Chinese student in the U.S. state of Missouri, was doing well. [7034]

Thai scientists who infected piglets with the new virus said it caused flu-like symptoms in the animals before disappearing, just like many of the human cases. [7034]

Cuba reported its first confirmed case of the new flu in a student from Mexico. [7034]

In Italy 1 in 10 Italians is said to have stopped eating pork despite reassurances the virus is not food-borne - while 12 percent were actually buying more pork because prices had fallen since the outbreak. [7034]

Tuesday 12 May 2009:
During seasonal influenza epidemics and previous pandemics, pregnant women have been at increased risk for complications related to influenza infection. In addition, maternal influenza virus infection and accompanying hyperthermia place fetuses at risk for complications such as birth defects and preterm birth. [7042]

CDC initiated surveillance for pregnant women who were infected with the novel virus. As of 10 May 2009, a total of 20 cases of novel influenza A (H1N1) virus infection had been reported among pregnant women in the United States, including 15 confirmed cases and 5 probable cases. [7042]

The age was 15-39 years. 3 women were hospitalized, one of whom died. [7042]

Pregnant women with confirmed, probable, or suspected novel influenza A (H1N1) virus infection should receive antiviral treatment for 5 days. Oseltamivir is the preferred treatment for pregnant women. The drug regimen should be initiated within 48 hours of symptom onset, if possible. [7042]

Pregnant women who are in close contact with a person with confirmed, probable, or suspected novel influenza A (H1N1) infection should receive a 10 day course of chemoprophylaxis with zanamivir or oseltamivir. [7042]

On 15 Apr 2009 a woman aged 33 years at 35 weeks' gestation with a one day history of myalgias, dry cough, and low-grade fever was examined by her obstetrician. She had been in relatively good health and had been taking no medications other than prenatal vitamins, although she had a history of psoriasis and mild asthma. The patient had not recently traveled to Mexico. Rapid influenza diagnostic testing performed in the physician's office was positive. [7042]

On 19 Apr 2009, she was examined in a local emergency department, with worsening shortness of breath, fever, and productive cough. She experienced severe respiratory distress, with an oxygen saturation of about 80 per cent on room air and a respiratory rate of about 30 breaths per minute. A chest radiograph revealed bilateral nodular infiltrates. The patient required intubation and was placed on mechanical ventilation. On 19 Apr 2009, an emergency cesarean delivery was performed, resulting in a female infant with Apgar scores of 4 at 1 minute after birth and of 6 at 5 minutes after birth; the infant is healthy and has been discharged home. On 21 Apr 2009, the patient developed acute respiratory distress syndrome (ARDS). The patient began receiving oseltamivir on 28 Apr 2009. She also received broad spectrum antibiotics and remained on mechanical ventilation. The patient died on 4 May 2009. [7042]

On 30 Apr 2009, a nasopharyngeal specimen was collected, which was positive by rRT-PCR for novel influenza A (H1N1) virus at CDC. [7042]

Patient B. A previously healthy woman aged 35 years at 32 weeks' gestation was febrile 20 Apr 2009 (101.6 deg F [38.7 deg C]), with a heart rate of 128 beats per minute, respiratory rate of 22 breaths per minute. The patient received a parenteral nonsteroidal anti-inflammatory medication, acetaminophen, and inhaled albuterol and later antibiotics, antinausea medication, acetaminophen, and an inhaled corticosteroid. The patient recovered fully, and her pregnancy is proceeding normally. She had been in Mexico during the 3 days preceding her arrival at the emergency department. [7042]

Several family members in Mexico and the United States had recently been ill with influenza-like illness, and her sister had been hospitalized for pneumonia during the preceding week. [7042]

She had a confirmed infection with novel influenza A (H1N1) virus. [7042]

Patient C. On 29 Apr 2009, a woman aged 29 years at 23 weeks' gestation was experiencing cough, sore throat, chills, subjective fever, and weakness of 1 day's duration. The patient had a history of asthma but was not taking any asthma medications. Her son, aged 10 years, reportedly had similar symptoms the week before the onset of her symptoms. Another son, aged 7 years, had become ill on the same day as his mother and accompanied her to the clinic. At the clinic, the younger son was coughing vigorously and was asked to put on a mask by office staff members. The woman was prescribed oseltamivir, which she began taking later the same day. Her symptoms are resolving without complications, and her pregnancy is proceeding normally. She had a confirmed infection with novel influenza A (H1N1) virus. [7042]

The physician who evaluated patient C was also pregnant (13 weeks' gestation). The physician began chemoprophylaxis with oseltamivir and remained asymptomatic. [7042]

Previous influenza pandemics (4,5) have shown that pregnant women generally are at higher risk for influenza-associated morbidity and mortality compared with women who are not pregnant. The increased risk of complications is thought to be related to several physiologic changes that occur during pregnancy, including alterations in the cardiovascular, respiratory, and immune systems. Pregnant women with underlying medical conditions such as asthma are at particularly high risk for influenza-related complications. Because pregnant women are at increased risk for influenza complications, the Advisory Committee on Immunization Practices and the American College of Obstetricians and Gynecologists have recommended that women receive the trivalent inactivated influenza vaccine. [7042]

Limited data from observational studies among hospitalized patients with seasonal influenza indicate that oseltamivir can reduce mortality, even when started more than 48 hours after illness onset. [7042]

In addition, oseltamivir and zanamivir have been highly effective in preventing seasonal influenza if used shortly after exposure to the disease. [7042]

Little information is available on the safety or effectiveness of these medications when used during pregnancy. However, considering the limited information available and the known risks for influenza complications during pregnancy, any potential risk to a fetus likely is outweighed by the expected benefits of influenza antiviral treatment for this novel virus. Thus, CDC interim guidance indicates that pregnant women with confirmed, probable, or suspected novel influenza A (H1N1) virus infection should receive antiviral treatment for 5 days. [7042]

Although zanamivir can be used in pregnancy, oseltamivir is preferred for treatment of pregnant women because of its systemic absorption. [7042]

Theoretically, higher systemic absorption might suppress influenza viral loads more effectively in sites other than the respiratory system (such as placenta) and might provide better protection against mother-child transmission. [7042]

Any pregnant woman hospitalized with confirmed, probable, or suspected novel influenza A (H1N1) virus infection should receive oseltamivir, even if more than 48 hours have elapsed since illness onset. Beginning treatment as early as possible is critical. In addition, treating fevers in pregnant women with acetaminophen is important because maternal hyperthermia has been associated with various adverse fetal and neonatal outcomes. [7042]

Pregnant women who are in close contact with a person who has a confirmed, probable, or suspected case should receive a 10 day course of chemoprophylaxis with zanamivir or oseltamivir. [7042]

Tuesday 12 May 2009: A total of 5696 cases and 63 deaths have been reported worldwide. [7042]

Tuesday 12 May 2009: Thailand and Finland have each confirmed 2 cases after travels to Mexico. [7042]

Tuesday 12 May 2009: The USA has officially reported 3009 laboratory confirmed cases coming from 45 states and 4 deaths. Mexico has reported 2282 confirmed cases with 58 deaths [7042]

Other flu infections

The H1N1 swine flu of 2009 is seen as the biggest risk since H5N1 bird flu re-emerged in 2003, killing 257 people of 421 infected in 15 countries. [6963]

In 1968 a “Hong Kong” flu pandemic killed about 1 million people globally. [6963]

A 1957 pandemic killed about 2 million. [6963]

The ordinary seasonal flu severely affects 3-5 million people and causes 250,000 to 500,000 deaths in a normal year [7038]. Including healthy children in rich countries. In a country like Denmark 1000-3000 die of influenza in a year of an ordinary influenza type. In the U.S. alone, health officials say about 36,000 people die every year from flu-related causes. [6963]

Pandemics: [7011] 1918-1919: "The Great flu (The Spanish flu), den spanske syge", About 40-50 million dead (Denmark 14000). [7011]
1957-58 "Asian flu; Den asiatiske influenza", 2 mill. dead (Denmark 1700). [7011]
1968-70 "Hong Kong influenza", 1 mill. dead (Denmark 1300). [7011]
1997- "Bird flu, Fugleinfluenzaen", 257 dead (Denmark 0). [7011]
2003 "SARS", 774 dead (Denmark 0). [7011]


The Spanish flu 1919 (90 years ago) compared with today:
Antiviral drugs such as Tamiflu was not available.
Today effective vaccines can be produced in 6 months. Experimental vaccines can be made in one month [7032]
Antibacterial drugs against secondary bacteria infections was not available.
The health system today is much better today.
The hygiene today is much better today.
The information technology is much better today.
The nutrition standard is much better today.
The housing standard is much better today.


Follow the development of the epidemic through CDC (USA)

Follow the disease via ProMed (The global electronic reporting system for outbreaks of emerging infectious diseases). Subscribe to its email

Follow the daily updates on the WHO swine influenza website


Read more on Google



The flu that never came: President Ford's decision for a national inoculation against swine flu in 1976 is still debated by experts today.

On the cold afternoon of February 5, 1976, an Army recruit told his drill instructor at Fort Dix that he felt tired and weak but not sick enough to see military medics or skip a big training hike.

Within 24 hours, 19-year-old Pvt. David Lewis of Ashley Falls, Mass., was dead, killed by an influenza not seen since the plague of 1918-19,

government doctors knew from tests hastily conducted at Dix after Lewis' death that 500 soldiers had caught swine flu without falling ill.

Any flu able to reach that many people so fast was capable of becoming another worldwide plague,

Does America mobilize for mass inoculations in time to have everybody ready for the next flu season? Or should the country wait to see if the new virus would, as they often do, get stronger to hit harder in the second year?

The Great Plague, as it came to be called, rivaled the horrid Black Death of medieval times in its ability to strike suddenly and take lives swiftly. In addition to the half million in America, it killed 20 million people around the world.

The post-WWI flu was brought to Europe by American troops who had been based in the South before they went to war.

Medical detectives, still working on the case in the 1990s, determined that a small group of our soldiers took swine flu to Europe and that it spread to the world from there.

How the swine flu got to Fort Dix in 1976 still hasn't been tracked down.

CDC had to make a fast decision to get the immunizations manufactured by the fall.

The doctors knew they faced complaints if the epidemic broke out and vaccines weren't ready, as well as criticism if they spent millions inoculating people for a plague that didn't happen.

By mid-March 1976, CDC Director Dr. David J. Sencer had lined up most of the medical establishment behind his plan to call on president Ford to support a $135 million program of mass inoculation.

On March 24 in 1976, one day after a surprise loss to Ronald Reagan in the North Carolina Republican presidential primary, president Ford decided to make the announcement to the American public.

Congress still had to appropriate the money, and that wasn't going to be easy. Even before official congressional consideration of the plan was taken up, there were forces arguing against it.

Another big hurdle was the drug makers, who were insisting the government take liability for any harmful side effects from the vaccine.

During congressional hearings in the spring and early summer, lawmakers heard some naysayers who noted that the swine flu of last winter never got beyond Dix and that only one death had been reported.

The president and his experts prevailed, however, and on Aug. 12 Congress put up the money to get the job done.

The mighty task was put into the hands of a charismatic 33-year-old physician for the Department of Health, Education and Welfare, Dr. W. Delano Meriwether. Meriwether was given until the end of the year to get all 220 million Americans inoculated against swine flu.

By Oct. 1, 1976, the makers had the serums ready and America's public health bureaucracy had lined up thousands of doctors, nurses and paramedics to give out the shots at medical centers, schools and firehouses across the nation.

Within days, however, several people who had taken the shot fell seriously ill. On Oct. 12, three elderly people in the Pittsburgh area suffered heart attacks and died within hours of getting the shot, which led to suspension of the program in Pennsylvania.

In other states of US inoculations went on.

On Dec. 16, 1976, increasingly concerned about reports of the vaccine touching off neurological problems, especially rare Guillain-Barre syndrome, the government suspended the program, having inoculated 40 million people. The flu never came.

Hundreds of Americans later filed suit against the government on behalf of children left without a parent due to fatal side effects from the swine flu vaccine. [7005]

Scientists including Dr. Edwin Kilbourne believed at that time that pandemic flu returned periodically - they thought it came back once every eleven years or so. When a young soldier at Fort Dix (who went on a long march carrying a heavy pack despite his illness) died of a strain of influenza that seemed to be related to the 1918, flu experts were very concerned. About 40 million people were vaccinated, and a few hundred were paralyzed. At least 25 people died. It was called the Swine Flu pandemic - a flu pandemic that didn't happen.



Interview 17 October 2005 [7004] (during the [still on-going] bird flu situation) with Science writer Wendy Orent, author of "Plague: The Mysterious Past and Terrifying Future of the World's Most Dangerous Disease" (Free Press).

According to the CDC, 36,000 people die a year in the United States from flu or its complications.

Flu virus depend on mobile hosts to transmit them through coughing and sneezing. Flu just isn't that deadly a disease - the need for the virus to keep the host mobile (and not immobilised in bed) ensures that flu normally is not too dangerous.

In the 1957 pandemic, the virus killed about 70,000 in the US.

Flu is too explosive to be quarantinable. But for most bioweapons agents, smallpox and plague quarantine would work quite well.

Children may be the chief disseminators of flu according to a study in Japan.

There is about one case per million (or fewer) of paralysis from the live polio virus. Not a high number, but in the absence of wild polio, that's still too high a risk, - which is why now people in the US are given the killed virus instead.

The people who die from flu, under normal circumstances, are elderly, immuno-compromised, pregnant, people with cardiac conditions, or sometimes the very young. That's the worst-case "normal" pandemic scenario - as happened in 1957. Under non-pandemic conditions (every year) it's typically the elderly or very young.

Masks won't really help - the flu particles are too small. The mask gets charged with moisture and turns useless. Stay home as much as you can - and more important, don't go out if you get ill, pandemic or not. That's the best way to minimize transmission of even ordinary flu. If you're sick, stay home! Flu is mostly airborne. You're at the mercy of those people who think that working while they're ill is heroic. I repeat - if you're sick, stay home! Please!

Wash your hands when you get home. Soap is soap - stay away from the antibacterial stuff, which can help grow resistant strains. Alcohol-based sanitizers are useful.

Bird flu virus in autopsies of people who died because of a bird flu infection shows up only deep in lung tissues. It can't be coughed out that way. We're a long way from transmissibility!

Virulence is deadliness - how thoroughly a germ exploits a host's tissues, how likely it is to kill. Transmissibility is how it gets from one host to another. ,...it has to be shed in some way. Human flu is highly transmissible, but not very virulent. 1918 flu was both virulent and transmissible. Bird flu is virulent, at least sometimes (and very virulent for chickens) but not transmissible.

Bird flu ought really to be called "poultry flu" - the entire bird flu problem comes from the conditions in which chickens and other birds are raised. In SE Asia and China, some of the poultry farms are enormous - one farm have five million chickens packed together - that's a very good way to start growing a virulent disease. Really disease factories.

The 1918 flu virus was an extremely well-adapted virus. It was very good at spreading among people and killing them. It was a human virus, even though its genes apparently originally came from birds.

The fact remains that H5N1 is NOT spreading in long chains person to person - there have been very few instances of person-to-person infection of this bird flu. [7004]


7022; http://www.eurekalert.org/pub_releases/2009-05/l-pia050809.php

8 May 2009: An Editorial published by The Lancet says that the flu crisis in 2009 can be seen as a timely exercise in preparing health authorities for a far more devastating pandemic. [7022]

The Editorial praises the overall coverage by the media, saying: "Our impression is that mass media coverage of the H1N1 outbreak has—barring some chequebook journalism and a few unnecessary superlatives—been balanced and rational. Perhaps the media could be criticised for failing to put the outbreak into context, in that the morbidity and mortality associated with H1N1 has, until now, been inconsequential compared with the thousands of lives taken every day by—for example—AIDS, tuberculosis, malaria, pneumonia, sepsis, and even seasonal influenza. The general public seems to have passed its own judgement on the dangers of H1N1 in that there have been no signs of panic on the streets, and the story has already started to slip down the news agenda." [7022]

The Editorial concludes: "We have been fortunate in that the virus that has brought the world closest to an influenza pandemic for more than 40 years seems to cause little serious illness. This episode can be seen as a timely exercise in preparing health authorities for a far more devastating pandemic. By and large...national and international health authorities have responded to H1N1 in a measured fashion." [7022]

Science explores the limits of uncertainty. When asked to speculate on what course the H1N1 outbreak might take.for example, on number of deaths, influenza specialists have given a range of possible scenarios. [7022]

When translated into headlines, it is hardly surprising that the upper end of the possible range is emphasised. [7022]

8 May 2009 WHO reported 2384 confirmed cases in 24 countries with 44 fatalities. Among these, 1112 cases and 42 deaths were reported from Mexico. [7022]

There were at this time early indications that the epidemic peak has passed in Mexico, but WHO has accepted that the outbreak will continue to spread internationally. [7022]

Although the illness caused by H1N1 appears to be mild, this is a new form of the virus to which most human beings have little pre-existing immunity. Therefore, the potential for a pandemic has not gone away. [7022]

The virus may yet cause illness in a sufficient proportion of the population to produce economic disruption. [7022]

Since community-spread-of-infection, rather than severity-of-disease, is the criterion for determining whether a full pandemic should be declared (phase six on the WHO scale), such a decision might not be far away. [7022]

If a pandemic is declared, WHO will have to decide whether to begin manufacture of a vaccine against the pandemic virus. [7022]

The H1N1 strain will not be incorporated into the next seasonal influenza vaccine. [7022]

Therefore, manufacture of pandemic vaccine will impinge upon the capacity to make seasonal vaccine. [7022]

In the absence of a vaccine, closure of schools with infected pupils has been used by some countries as a measure to prevent spread of the H1N1 virus. [7022]

In the USA, the CDC initially supported school closures, but has since backed away from this recommendation. [7022]

The Public Health Agency of Canada does not recommend closing schools because, given the generally mild illness, the resulting disruption would outweigh any potential benefits. [7022]

The official line of the UK Health Protection Agency is that consideration should be given to temporarily closing the school. [7022]

In practice, all five schools in England with confirmed cases have been closed for several days. [7022]

Experts at the various agencies have presumably considered the same evidence on the benefit of school closures - yet reached different conclusions. This is an area that needs more research and harmonisation of guidelines. [7022]

We have been fortunate in that the virus that has brought the world closest to an influenza pandemic for more than 40 years seems to cause little serious illness. [7022]

This episode can be seen as a timely exercise in preparing health authorities for a far more devastating pandemic. [7022]

Influenza A H1N1 (swine flu) has spread around the world with what has, at times, felt like horrifying speed. [7022]

Of the first 2384 laboratory-confirmed cases reported in 24 countries, there was 44 deaths, 42 of which were in Mexico. [7022]

These numbers are far lower than the annual toll from seasonal influenza, which kills hundreds of people every day in the peak season. [7022]

Epidemiologists are still largely in the dark about how the virus will continue to spread and, ultimately, how severe the disease it causes will be. [7022]

The threats of severe acute respiratory syndrome (SARS) and H5N1 a few years ago prompted the world to set up plans to deal with the possibility that these viruses would, by developing sustained human-to-human transmission, trigger a pandemic. [7022]

The chaos caused by the outbreaks revealed just how badly countries around the world - increasingly linked by frequent international travel and growing globalisation - were prepared to deal with a worldwide infectious disease pandemic. [7022]

Pandemic preparedness has come a long way since those two viruses caused worldwide alarm, says Sandra Mounier-Jack (London School of Hygiene and Tropical Medicine, London, UK) but there are holes in many countries' plans. [7022]

In 2006, with her colleague Richard Coker, Mounier-Jack compared the strategies of Asia-Pacific countries with those in Europe. [7022]

Many of the Asia-Pacific plans, had a stronger focus on early containment of disease and social distancing. [7022]

Developing countries are likely to need this strategy more than developed ones, Mounier-Jack told TLID, because of chronic shortages of antiviral drugs and vaccines. [7022]

But the problem with focusing on surveillance and monitoring, she says, is that poor countries, especially those in Asia, do not have a plan B if the virus becomes pandemic. [7022]

Developing countries are severely underprepared for a pandemic. [7022]

Many existing plans focus somewhat short-sightedly on avian influenza in poultry. [7022]

Countries, including those in Europe, did not adequately address organisational responsibility at the local level. [7022]

Even now, these plans have only really been tested through desk-based exercises, says Mounier-Jack. [7022]

Whether strategic plans are operational is the key question, says Coker. [7022]

In southeast Asia, for example, only Thailand has evaluated its preparedness. [7022]

Despite being a relatively affluent country in the region, it would have substantial resource shortages if a pandemic is anything but mild, he says. [7022]

Without this sort of analysis, Coker adds, policy makers risk making knee-jerk decisions in their allocation of resources that may be ineffective, inefficient, and inequitable. [7022]

European preparedness is patchy too. [7022]

Many plans included only half of the WHO recommendations for dealing with pandemics. [7022]

The challenges Mounier-Jack foresees are implementational - how responsibility is divided between primary and secondary care, for example - rather than in technical or medical problems. [7022]

She also advocates a cohesive multisectoral approach between the food industry, the health-care sector, and government. [7022]

Quarantine and travel bans might seem an intuitive way to curb the spread, but the reality is more complicated. [7022]

For one thing, health officials have been at odds over the advice the public should follow. [7022]

In late April, the European Unions health commissioner Androulla Vassiliou said Europeans should avoid travelling to Mexico or the USA unless it is very urgent. [7022]

Almost immediately, Richard Besser, the acting director for the US Centers for Disease Control and Prevention, and Michael Bloomberg, New York Citys mayor, disagreed. [7022]

Apart from the fact that travel restrictions would have very little effect on stopping the virus from spreading, says Alessandro Vespignani (Indiana University, Bloomington, IN, USA), it would be highly disruptive to the global community. [7022]

Vespignani is modelling the spread of H1N1 with travel data, high-definition geo-graphical population data, and disease dynamics, including the number of people each infected person passes it on to (reproductive rate). Estimates for H1N1's reproductive rates are 1 0.1E4, which is fairly low given that seasonal influenza has a rate of 1E5.3E0. Vespignani's predictions for the rest of May point to a steady increase in the number of observed cases. [7022]

More worryingly, he told TLID that just in the USA, we could hit several thousand cases. He hopes, however, that he will soon see discrepancies between his Preparation for a pandemic: influenza A H1N1 [7022]

Although this is not a scenario scientists usually wish for, in this case it would mean that containment and mitigation measures had been successful. [7022]

H1N1fs seemingly low reproductive rate does not mean we should be complacent: a 2006 study of the rate of the 1918 pandemic influenza suggests that the rate of the first wave of the virus was about 1E5, but that of the second wave was 3E5. [7022]

Coker points out that H5N1 is still present in many countries and is endemic in southeast Asia. One concern at the back of many virologists minds is the prospect, however remote, that the H1N1 might recombine with the virulent H5N1 to form a so-called Armageddon virus. [7022]

If that happened, says Coker, antivirals would need to be rapidly distributed; the problem is that those drugs are currently being allocated to deal with the existing H1N1 virus. [7022]

For now, though, the northern hemisphere is out of its annual influenza season and there is a window for H1N1 vaccine production. [7022]

An initial idea to incorporate this strain into the vaccine against regular seasonal influenza has been dismissed, and WHO is due to talk with vaccine manufacturers about switching to production of a pandemic H1N1 vaccine. [7022]

On May 6, Marie-Paule Kieny, director of WHOs vaccine research initiative, said WHO estimated that the worlds vaccine production capacity could make 1 billion to 2 billion doses of H1N1 vaccine. [7022]

During the H5N1 outbreaks, tests indicated that, unlike seasonal influenza, people needed two doses for a vaccine to be effective. [7022]

Whether people would need two doses of H1N1 vaccine is too early to say, said Kieny. [7022]

For developing countries, these issues are less pressing than the question of whether they can get their hands on the vaccine at all. [7022]

So, on 19 May 2009, WHOs Director General Margaret Chan and UN Secretary General Ban Ki-Moon are meeting in Geneva with vaccine manufacturers to appeal to corporate responsibility and discuss avenues to ensure equitable access for developing countries to this vaccine. [7022]

If doomsayers are right, and H1N1 does become pandemic, the biggest guns in the drug arsenal are oseltamivir and zanamivir. [7022]

However, monotherapy is vulnerable to resistance. N1 genes are more prone to mutations, and oseltamivir-resistance occurrence in N1 genes is not uncommon, says Alan McNally (Nottingham Trent University, Nottingham, UK). [7022]

Indeed the vast majority of seasonal H1N1 isolates this past autumn and winter were oseltamivir resistant. [7022]

This undoubtedly poses a threat, and is something that reference labs will be monitoring extremely closely, says McNally. [7022]

WHO is at pains to stress that raising the alert to level six would not relate to the severity of the infection. [7022]

If anything, initial indications are that the virus is no more harmful than seasonal influenza. [7022]

H1N1 is a hybrid of virus genes originating in viruses of pigs, birds, and human beings. Wendy Barclay (Imperial College, London, UK) has analysed H1N1's genes and says that it has no genetic features of a highly pathogenic virus at all. [7022]

She told TLID that it looks as though this virus should target the upper respiratory tract and not the lung. This is important because viruses that bind in the lower respiratory tract, such as H5N1, cause more severe illness. [7022]

Barclay adds that the virus's NS1 protein looks normal, so we would not expect a cytokine storm. [7022]

Epidemiologists are also scrabbling to collect as much information as they can about which groups of people are the hardest hit, and to find out why some people develop more severe symptoms than others. [7022]

On 5 May 2009, WHO's assistant director-general for health security and environment, Keiji Fukuda, told reporters that the average age of infection was the mid-20s. [7022]

But he pointed out that the infections tend to be seen in travellers, so does the age reflect a characteristic of the virus or the fact that young people are most likely to travel? [7022]

Older people might have an immunity if they have been exposed to components of the virus before. [7022]

Countries worldwide will now be figuring out how to prepare for a relatively unknown quantity. [7022]

Did scientists and health officials take their eye off the ball after the initial fears of a bird flu or SARS pandemic faded? [7022]

It is understandable that pandemic fatigue set in, says Mounier-Jack, since countries have a range of health-care concerns to deal with. [7022]

But should scientists have seen this coming? [7022]

In 2004, Richard Webby and Robert Webster (St Jude Childrens Research Hospital, TN, USA) raised a note of concern that in 1998 swine H1N1 had recombined with human and bird viruses. [7022]

They warned that the growing complexity of influenza at this animal/human interface and the presence of viruses with a seemingly high affinity for reassortment makes the US swine population an increasingly important reservoir of viruses with human pandemic potential. [7022]

Knowing this potential is one thing, but it is not clear how one would prevent that from happening, says Barclay. [7022]

As Fukuda told reporters on 4 May 2009, there is no timetable for how the virus will spread. [7022]

For now, it is going to be a matter of watching and waiting to see what H1N1 does next. [7022]



Despite some resemblance to the deadly 1918 flu, the swine-origin flu of 2009 may not be so bad as first feared. [7039]

. There are certain characteristics, molecular signatures, which this virus lacks, said Peter Palese in an interview. He is a microbiologist and influenza expert at Mt. Sinai Medical Center in New York. In particular, the swine flu lacks an amino acid that appears to increase the number of virus particles in the lungs and make the disease more deadly. [7039]

. Ralph Tripp, an influenza expert at the University of Georgia, said that his early analysis of the virus' protein-making instructions suggested that people exposed to the 1957 flu pandemic--which killed up to 2 million people worldwide--may have some immunity to the new strain. That could explain why older people have been spared in Mexico, where the swine flu has been most deadly. [7039]

. At a press conference today held by the Centers for Disease Control, acting director Richard Besser said that it's premature to say anything about the virulence compared with other strains of influenza based on genetic analysis. [7039]

. If this virus keeps going through our summer, I would be very concerned," said Peter Palese, influenza expert at Mt. Sinai Medical Center in New York. [7039]

.



Next generation of vaccines
Flu shots have to be reformulated every year, thanks to the constantly mutated virus. And the annual vaccine won't protect against more deadly strains, like the H5N1 bird flu. But that may soon change: scientists have now developed antibody proteins that can neutralize different strains of the influenza virus, including the deadly H5N1 bird flu, the virus behind the 1918 epidemic, and common seasonal strains. These new antibodies target part of the virus that is shared between different strains and thus appears to be broadly effective. The research was published February 2009 in the journal Nature Structural & Molecular Biology. [7039]

. The antibodies also give researchers clues about how to develop new vaccines. "This opens up the avenue of thinking about universal influenza vaccines, which has not been realistic before", says Peter Palese, an influenza expert at Mount Sinai School of Medicine in New York who was not involved in the work. [7039]

. A vaccine using this technology could theoretically be used to protect against various types of flu, as well as to treat the virus once a person is infected. [7039]

. Scientists who developed the antibodies say that they hope to have a candidate vaccine to test in humans within the next three years. [7039]

. But not everyone is as optimistic about the possibilities. According to an article in the New York Times, Henry L. Niman, a biochemist who tracks flu mutations, was skeptical, arguing that human immune systems would have long ago eliminated flu were the virus as vulnerable in one spot as this discovery suggested. Also, he noted, protecting the mice in the study took huge doses of antibodies, which are expensive and cumbersome to infuse. [7039]

. The research began by screening a library of 27 billion antibodies, looking for some that take aim at the hemagglutinin "spikes" on the shells of flu viruses The flu virus uses the lollipop-shaped hemagglutinin spike to invade cells in the nose and lungs. There are 16 known types of spikes, H1 through H16. [7039]

. The spike's tip mutates constantly, which is why flu shots have to be reformulated each year. But the team found a way to expose the spike's neck, which apparently does not mutate, and picked antibodies that clamped onto it. Once its neck is clamped, a spike can still penetrate a human cell, but it cannot unfold to inject the genetic instructions that take over the cell's machinery to make more virus. The team then turned the antibodies into full-length immunoglobulins and tested them in mice [7039]

.

.
Words and abbreviations used in articles about swine influenza:
ILI = influenza like illness (ILI)
CFR = case fatality rate (CFR).
BMBL = Biosafety in Microbiological and Biomedical Laboratories (BMBL)
BSC = biosafety cabinet (BSC).
ISID = International Society for Infectious Diseases (ISID)

Swine Flu Keywords
The Swine Flu keywords observed on Google HotTrends include:
swine flu symptoms
swine flu more condition symptoms
cdc.gov
pig flu
swine flu san diego
pandemic
swine virus
center for disease control
swine flu mexico
swine influenza virus
swine flu in mexico
pig influenza
schweinepest
pig flu mexico
Pig flu sparks epidemic fears.

References:

6954:
here
6955: here
6958: here
6961: here
6962: here
6963: here
6964: here
6965: 6965
6966: here
6967: here
6968: here
6969: here
6971: here
6972: here
6973: here
6974: here
6975: here
6976: here
6977: here
6978: New Scientist 2. maj 2009 bd.202 nr. 2706 side 3, 6-9. (here and here)
6980: here
6982: here
6983: here
6984: here
6985: here
6986: here
6989: here
6990: here
6991: here
6992: Danish radio broadcasting: Horizont - DR1 radio 6. maj 2009 kl. 22.30
6993: here
6994: here
6995: here
7000: here
7001: here
7002: here
7003: here
7004: here
7005: here
7007: here
7008: here
7009: here
7010: here
7011: Politiken 3. maj 2009 PS s.6.
7012: here
7013: here
7014: here
7015: here
7020: here
7021: here
7022: here
7023: here
7024: Science: here [here]
7024b: here (BBC-News: here)
7025: here
7032: here
7033: here
7034: here
7038: here
7040 (Nature): here
7041: here
7042: here


The AVAAZ initiative against big unregulated pig farms: (link avaaz.org) (1) Biosurveillance report tracing the disease to the Smithfields farm: (link biosurveillance.typepad.com) Reports on the link between the Mexican factory farm and the flu: (link) (link independent.co.uk) (link scientificamerican.com) (link newscientist.com) (link huffingtonpost.com) (2) WHO pandemic information (link euro.who.int) (3) FAO, EC and CDC reports on the risks of industrial farming on public health FAO and CIWF and (link cdc.gov) (4) CIWF and PETA video reports of the disgusting conditions for animals in factory farms and the disease ridden manure swamps: CIWF and PETA (5) Reports on Smithfield's animal welfare and environmental damage (link independent.co.uk) (link foodandwaterwatch.org) (link avaazimages) (6) Reports on UK tax payers subsidising factory farms (link telegraph.co)