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About viruses and viral disease

pandemic

Swine influenza, seasonality, and the northern hemisphere

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camp-funstonI have received several questions about my assertion that the northern hemisphere is safe, at least until the fall, from an epidemic of A/California/09/2009 influenza virus. Here are two representative questions:

If I recall correctly, Spanish flu hit hardest during the summer and fall.

As for the swine flu, is it impossible (and why?) to see the current contagion spreading in the northern hemisphere over the following months?

Influenza is a seasonal infection in temperate climates. The flu season in the northern hemisphere is between January and April, although infections have been observed in December and May. In the southern hemisphere the flu season extends from May to September. May is almost upon us, and based on past observations this signals the end of influenza in the northern hemisphere. As flu season begins in the southern hemisphere, it is quite possible that A/California/09/2009 virus will circulate extensively.

Let’s see if we learn anything from the timing of two past pandemics. The 1918-19 pandemic began in the spring of 1918 with an outbreak of mild respiratory disease in soldiers at Fort Funston, Kansas. The infection spread to other military bases in the US and eventually to Europe. These infections were mild and did not receive much attention from the press. At the end of August 1918 a more virulent H1N1 virus emerged which caused high mortality (2.5% in the US, compared to 0.1% for typical influenza). The disease peaked in September and November. In the spring of 1919 a second disastrous wave of infections took place.

The H3N2 strain of influenza virus was responsible for a pandemic in 1968-1970. This virus originated in Southern Asia in the summer of 1968 and was responsible for sporadic cases of disease from September through December in the US, England, and Japan. Epidemic spread in these and other northern hemisphere countries began in December and ceased at the end of April 1969. In Australia epidemic spread of the H3N2 virus began in January 1969, ended in October, and recommenced in June 1970.

This history demonstrates the seasonality of pandemic influenza, and suggesta that spread of A/California/09/2009 in the northern hemisphere is not imminent. Based on this regularity, the epidemic in Mexico should be over no later than the end of May. While it is not ‘impossible to see the current contagion spreading in the northern hemisphere over the following months’, it would be unprecedented.

Viboud, C., Grais, R., Lafont, B., Miller, M., Simonsen, L., & , . (2005). Multinational Impact of the 1968 Hong Kong Influenza Pandemic: Evidence for a Smoldering Pandemic The Journal of Infectious Diseases, 192 (2), 233-248 DOI: 10.1086/431150

Swine influenza H1N1 update

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pandemic-phase-42Here are some updates on the global status of swine influenza H1N1.

As of Monday, 27 April, the US has reported 40 laboratory confirmed cases of swine influenza H1N1 infection in California, Kansas, New York City, Ohio, and Texas. Mexico has confirmed 26 human cases with seven deaths,  Canada reports six cases, and Spain one case. The first two cases of the illness in the UK were reported in Scotland. These statistics were obtained from ProMED-mail, WHO, and CDC.

You might find higher numbers from other sources. The difference is that the numbers in the preceding paragraph are laboratory confirmed cases – meaning that the virus has been isolated from the patient and identified as swine influenza H1N1 (or A/California/07/2009 (H1N1), in the influenza virus nomenclature). Many suspected cases are being reported – in these the disease appears to be influenza, but confirmation of infection with A/California/07/2009 (H1N1) has not been confirmed by laboratory tests. For example, the suspected death toll in Mexico is 149, with 1995 hospitalizations. There are also suspected cases in England and Australia.

As a consequence of the continuing spread of the virus, the WHO Director-General has raised the level of influenza pandemic alert from phase 3 to phase 4. According to WHO, “This phase is characterized by verified human-to-human transmission of an animal or human-animal influenza reassortant virus able to cause community-level outbreaks.” A complete explanation of pandemic alert phases can be found at the WHO website. In Mexico, health authorities have closed schools in the entire country until 6 May. In the US, CDC activated its Emergency Operations Center to coordinate the agency’s response, and the Secretary of the Department Homeland Security has declared a public health emergency. These actions will allow the release of funds to support the public health response.

Because a vaccine is not yet available for A/California/07/2009 (H1N1), antiviral compounds (Tamiflu and Relenza) must be used to curb epidemics. The use of such compounds may save many lives at the expense of selecting for drug resistant viruses. If such variants emerge before immunization can be carried out they will limit our ability to control the infection.

Here are my answers to some questions posted to virology blog:

Q: Do you have any theories as to why the mortality rate (apparently) is higher in Mexico than it is elsewhere?

A: I have two theories. One involves the possibility that infection with the current circulating human H1N1 strain might confer some protection, in the form of milder disease, to infection with the swine H1N1 virus. If this is true – and it might not be – then one could speculate that individuals in Mexico City were less immune to human H1N1, and consequently experienced more severe disease when infected with the swine strain.

The other theory is more vague – because Mexico City is extremely densely populated, the virus may spread more quickly, infecting more people, leading to selection of more virulent viral variants.

Q: Are viruses more likely to get more or less pathogenic as time goes on?

A: It could go either way. Viruses need living hosts in which to multiply – if they kill the host quickly, or debilitate the host so it cannot interact with others (to spread the infection), then the virus will not endure. On the other hand, you can imagine how increased virulence leading to more coughing and sneezing could help spread the infection. This topic is hotly argued among virologists, which means that both sides probably are correct.

Q: Should we be saving our Relenza and Tamiflu if this does become highly pathogenic?

A: Save them for the fall, in case the virus returns then. Flu season is basically over in the US, and with the increasing heat and humidity (over 90° today in NYC) virus transmission should soon stop. However, if A/California/07/2009 (H1N1) takes hold in the southern hemisphere in the coming months – their flu season is still beginning – it is likely to return to the northern hemisphere in the fall. Unfortunately, by then extensive antiviral use in the southern hemisphere is likely to have produced drug-resistant variants.

Q: I keep thinking about the Great Influenza book – that in an era with no planes, the virus traveled around the world three times. Given our capacity for travel now, is quarantine even possible?

A: No. The CDC has already said quarantine is futile. Check out the transcripts of their press conferences; they are a good read (or listen).

Q: Will our over vigilance in treating this lead to its becoming resistant quicker?

A: If you mean treating the infection with antivirals, then the answer is a resounding yes. Many people have likely been saving Relenza and Tamiflu, and they will take them at the first sign of a respiratory illness.

Q: Should this be considered a prime candidate for next winters flu season?

A: It depends on what happens in the southern hemisphere. In the next week or two we will know whether A/California/07/2009 (H1N1) spreads in the lower half of the globe and causes epidemics of disease. If it does, then it is highly likely that the virus will return here in the fall. If the virus fails to spread, then everyone can go back to worrying about H5N1.

Send your questions to virology blog (virology@virology.ws) and I will post my answers each day.

Swine flu returns

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swineA novel strain of H1N1 swine influenza virus has now also been isolated from cases of respiratory disease in Mexico City, New York City, and two locations in Canada. Clearly I was wrong in hypothesizing that the five mild cases in Texas and California reported last week were not a cause for alarm.

In Mexico City there have been over 1,000 cases of respiratory illness, with 86 fatalities. The influenza virus isolated from these individuals is similar to the H1N1 virus found in the American children last week. This virus has caused four cases of influenza in Nova Scotia, and two in British Columbia, Canada. It has also been isolated in Kansas and New York City. All American and Canadian infections have so far been mild.

There isn’t much information yet available about the genetic and antigenic composition of the virus, but CDC has said that it contains genetic material from North American swine and avian influenza viruses, human influenza virus, and swine influenza viruses found in Asia and Europe. The specific combination of viral RNA segments has not been observed previously.

The extent of spread of the swine virus has sent news organizations, governments, and health agencies into a full-tilt pandemic preparedness mode. It’s certainly advisable to be cautious when dealing with a potentially lethal virus, but is it likely that this is the next pandemic strain?

The influenza season is nearly over in the northern hemisphere – it usually does not continue beyond May. Increasing temperature and humidity are likely to curtail transmission of the virus very rapidly. The same virus could return in the fall, but by then a vaccine could be produced and distributed.

The southern hemisphere is another story – the influenza season there is just starting. It is certainly possible that this swine virus might cause extensive epidemics.

Remember that the virus that is scaring everyone is of the H1 subtype. One of the currently circulating human influenza viruses is also of the H1 subtype – the human H1N1 virus. Although the swine H1N1 virus is antigenically different from the human H1N1 virus, it is possible that those who have been infected with the human strain could be partially protected from the swine strain. Such individuals might experience less severe disease than those with no immunological memory of an H1 virus. I have not seen immunological data that would allow assessment of this possibility.

Pandemic influenza has always been a consequence of viruses of a new subtype – for example the 1968 pandemic was caused by a virus of the H3N2 subtype, which replaced the H2N2 virus. The swine virus is of the same subtype as the currently circulating human H1N1 strain. Of course, if the swine H1 HA protein is sufficiently different from the human H1 HA protein it could lead to a pandemic despite being of the same subtype.

Infection of a Spanish woman with a swine H1N1 virus was reported in February of 2009. That virus appears to be phylogenetically close to European swine influenza viruses. Such infections have been reported from time to time, and most likely represent dead-end transmission of a pig virus to a human. The H1N1 swine influenza virus circulating in the Americas has acquired the ability to be transmitted among humans. Within the next few weeks we should learn whether it has the capability of spreading throughout the entire southern hemisphere.

Van Reeth, K, & Nicoll, A (2009). A human case of swine influenza virus infection in Europe – Implications for human health and research Eurosurveillance, 14 (7), 19124-19125

New swine influenza viruses in humans

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swineA new strain of swine influenza virus has been recently isolated from seven persons in the US. Is it time to break out the swine flu vaccine of 1976?

Last week the CDC reported that swine influenza virus had been isolated from two children with respiratory illness in California. The cases were not linked and the children recovered from the illness. The virus was identified as a swine influenza H1N1 strain, similar to viruses that have circulated in American pigs for the past ten years. However some of the viral genes are derived from Eurasian swine influenza viruses. The isolates are new because this particular combination of swine influenza virus RNAs has not been observed before among swine or human viruses.

A similar virus was subsequently identified in five additional individuals in Texas. It’s curious that one of the California children had traveled to Texas before becoming ill, but whether or not the cases are related has not been revealed.

What is the origin of these new swine viruses? None of the people who were infected had known contact with pigs. Others must have acquired the virus from pigs, who then passed it on – demonstrating that the virus can be transmitted among humans.

At the moment these infections don’t seem to be cause for alarm. Because influenza virus surveillance is more intense than ever before, it is likely that new viruses will always be detected. Furthermore, respiratory disease caused by these new viruses has not been very severe. Another mitigating factor is that the influenza season is nearly over – viral transmission wanes when the weather becomes warmer and more humid.

It is believed that swine influenza originated in 1918-19, when pigs became infected with the pandemic influenza virus strain. Since that time, the H1N1 swine virus has been transmitted back to humans. The hypothesis for the origin of swine influenza is supported by the finding that pigs can be experimentally infected with the human 1918 pandemic influenza virus strain. Furthermore, other human influenza virus strains are known to infect pigs. For example, in the early 1970s, a human H3N2 subtype entered the European swine population.

Pigs can be infected with both human and avian influenza virus strains because the cells of their respiratory tract bear receptors for both kinds of viruses. Based on this observation, it has been suggested that influenza viruses pass from birds through pigs on their way to infecting people. For example, if a pig is infected with avian and human influenza A viruses, reassortment of the viral RNAs occurs, leading to new virus strains to which humans are not immune. The 1957 and 1968 human pandemic viruses were reassortants of human and bird strains, although there is no evidence that these viruses arose in pigs. The role of pigs as a ‘mixing vessel’ for influenza virus has been questioned in view of the recent transmission of avian influenza viruses directly to humans.

Swine influenza viruses probably routinely pass among humans and swine; in this case they were detected as a consequence of heightened surveillance. Gerald Ford won’t be rolling over in his grave over this incident.

Weingartl, H., Albrecht, R., Lager, K., Babiuk, S., Marszal, P., Neufeld, J., Embury-Hyatt, C., Lekcharoensuk, P., Tumpey, T., Garcia-Sastre, A., & Richt, J. (2009). Experimental Infection of Pigs with the Human 1918 Pandemic Influenza Virus Journal of Virology, 83 (9), 4287-4296 DOI: 10.1128/JVI.02399-08

de Jong, J., Smith, D., Lapedes, A., Donatelli, I., Campitelli, L., Barigazzi, G., Van Reeth, K., Jones, T., Rimmelzwaan, G., Osterhaus, A., & Fouchier, R. (2007). Antigenic and Genetic Evolution of Swine Influenza A (H3N2) Viruses in Europe Journal of Virology, 81 (8), 4315-4322 DOI: 10.1128/JVI.02458-06

Van Reeth, K. (2007). Avian and swine influenza viruses: our current understanding of the zoonotic risk Veterinary Research, 38 (2), 243-260 DOI: 10.1051/vetres:2006062

Swine flu at Fort Dix

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swineThe death of a dozen pigs from swine influenza last week in the Philippines reminded me of an incident at Fort Dix, NJ in 1976. The infection of humans with a strain of swine influenza lead to a nationwide immunization campaign to curb a pandemic that never occurred.

An explosive outbreak of febrile respiratory disease raced through the 19,000 personnel at Fort Dix in January 1976. Virological laboratory studies revealed the presence of a new swine influenza strain which was named A/New Jersey/76 (Hsw1N1). The virus infected 230 soldiers and caused severe respiratory disease in 13, including one death.

At the time it was believed that a swine virus had caused the 1918-19 influenza pandemic. Therefore scientists were concerned that the virus had returned to Fort Dix and would soon cause another catastrophic outbreak. Dr. Edwin Kilbourne, a noted influenza researcher, and others convinced the US Public Health Service to contract for the production of 150 million doses of vaccine. In March of 1976 President Gerald Ford announced a program to inoculate every man, woman and child in the United States against swine flu. Immunizations began in October, but only 45 million doses had been distributed when the program was halted in December. By then it was clear that A/New Jersey/76 was going nowhere. An unfortunate consequence was that many individuals developed Guillain-Barré syndrome, a neurological disease involving muscle weakness, paralysis, and sometimes death.

Why didn’t A/New Jersey/76 spread to the general population? One factor was the limited contact between basic trainees and others who more frequently travel outside the facility. Older personnel may have been immune, because military influenza vaccine formulations from 1955 through 1969 contained a swine influenza component. Competition with concurrent circulating influenza virus strain, A/Victoria, might have  limited the impact of A/New Jersey virus which is believed to transmit poorly among humans.

In retrospect, the swine flu program had many flaws. The vaccine should have been stockpiled until it was clear that an epidemic was taking place. Today we realize that the 1918 influenza virus is derived from an avian strain, not a swine strain – had this information been available in 1976, the immunization campaign would not have taken place. Presumably these and many other errors will not be repeated when the time comes to immunize against the next pandemic strain.

To this day the origin of A/New Jersey/76 virus is an enigma. One theory is that a swine virus was brought to Fort Dix early in 1976 as recruits returned after the holidays. However, none of the personnel who were interviewed admitted to having contact with pigs. The virus seems to have circulated at Fort Dix for about a month, then disappeared.