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Epidemiology and Significance of the 2009 H1N1 Virus






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Epidemiology and Significance of the 2009 H1N1 Pandemic

The 2009 H1N1 outbreak

In April 2009, a novel virus was isolated from two unrelated human cases of influenza in California 1. The isolated virus, A/California/7/2009 (group/location/isolate number/year), was determined to be an influenza A of subtype H1N1. Genetic analysis revealed that this H1N1 virus was unrelated to seasonal human influenza viruses; instead it appeared to be a reassortment of two swine influenza A viruses1.

On April 27, 2009 the World Health Organization (WHO) reported 26 human infections of the novel H1N1 influenza  in Mexico, including 7 fatalities 2. 40, 6, and 1 human H1N1 infections were reported in the United States, Canada, and Spain respectively, with a median patient age of 16 years old. Evidence for human-to-human transmission of the virus was confirmed by April 28, 2009 2.

On June 11, 2009 the WHO declared H1N1 influenza a phase 6 pandemic of moderate severity. A phase 6 pandemic refers to a “new virus causing sustained community level outbreaks in more than one WHO region”3. The pandemic is considered moderate because most patients recover without being hospitalized 4.

            As of September 20, 2009 there have been at least 318, 925 cases of 2009 H1N1 influenza and over 3917 deaths related to 2009 H1N1 influenza in 191 countries around the globe (Table 1) 5. In northern, temperate regions of the globe, the number of reported influenza-like-illnesses is presently above seasonal baseline 5.

 

Table 1. 2009 H1N1 influenza cases and deaths worldwide5.
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Spread of influenza A

            Aquatic birds are a reservoir of influenza A 2. Aquatic birds shed influenza A virus in their feces 6. Occasionally influenza A viruses endemic in aquatic birds will spill over into other species such as marine mammals, humans, swine, horses, and poultry (Figure 1). If the influenza A virus is capable of intra-species transmission within the newly infected species, the virus may become endemic in that species 6. For example, influenza A subtypes H1N1, H3N2, and H1N2 are established in swine. Seasonal influenza A subtypes H1N1 and H3N2 are established in humans 2. A spillover of a novel strain of H1N1 from swine to humans is responsible for the 2009 H1N1 influenza (Figure 1). 2009 H1N1 influenza is unrelated to the seasonal H1N1 influenza already established in human populations 7.

spread

Figure 1. Influenza A virus spread 6

How did the 2009 H1N1 influenza virus emerge?

The 2009 H1N1 influenza virus likely arose from the reassortment of two or more swine influenza A viruses, although 2009 H1N1 has gene segments common to swine, human, and avian influenza A subtypes 1.

Pigs are considered ‘mixing vessels’ for avian, swine, and human influenza A viruses 2. Avian influenza A viruses use α2,3-galactose-linked sialic acids as a receptors, while human influenza A viruses use α2,6-galactose-linked sialic acids as receptors. Pigs have both α2,3-galactose-linked sialic acids and α2,6-galactose-linked sialic acids in their tracheal epithelium; thus pigs may be infected with both avian and human influenza A. In modern swine operations, pigs are often exposed to both birds and humans, potentiating interspecies influenza A transmission (Figure 2) 2.

reassort
Figure 2. Reassortment of avian and human influenza A in the pig 2.

Within the pig, avian, human, and swine influenza A viruses may exchange genes to produce progeny viruses with enhanced virulence 2. For this reason, it is of paramount importance that the 2009 H1N1 influenza strain circulating in humans is not re-introduced into swine populations, where the virus may acquire enhanced transmission and replication potential, and/or antiviral resistance through genetic reassortment with a highly pathogenic influenza A subtypes such as avian H5N1 1.

The 2009 H1N1 influenza has already been demonstrated to spread from humans to swine 8. On May 2, 2009, the Canadian Food Inspection Agency (CFIA) indicated that a Canadian individual infected with 2009 H1N1 influenza introduced the virus into a swine herd in Alberta. The pigs and the infected individual made a full recovery 8.

Characterisitcs of the 2009 H1N1 influenza virus

The 2009 H1N1 influenza virus has not undergone significant antigenic drift or reassortment thus far; all laboratory isolates of 2009 H1N1 have been similar to the original A/California/7/2009 isolate 5. If 2009 H1N1 influenza remains homogeneous, a vaccine developed against the A/California/7/2009 isolate will likely be protective 1.

So far, 2009 H1N1 has not acquired any of the virulence factors associated with 1918 pandemic influenza or highly pathogenic avian influenza 1. Furthermore, pandemic H1N1 has shown limited genetic resistance to the antiviral neuraminidase inhibitor oseltamivir (Tamiflu). Only 28 oseltamivir-resistant 2009 H1N1 virus isolates have been identified worldwide, while more than 10,000 2009 H1N1 virus isolates have been shown to be sensitive to oseltamivir 5.

Who is at risk for developing 2009 H1N1 influenza?

Adults under the age of 50 are at the greatest risk of severe illness or death due to 2009 H1N1 influenza 7. By comparison, seasonal H1N1 influenza typically has the most severe effects on individuals over 65 years of age 7.

H1N1 influenza viruses which circulated in humans during the early 1950s had antingenic similarity to the 2009 H1N1 virus 1. As a result, individuals over 60 years of age may possess antibodies which cross-react with 2009 H1N1, reducing their risk of developing 2009 H1N1 influenza 1.    

Individuals with underlying conditions such as asthma, diabetes, obesity, auto-immune disorders, immunosuppression or pregnancy are more likely to be hospitalized as a result of 2009 H1N1 infection 1, 7.

            2009 H1N1 influenza may be especially devastating for individuals in developing countries who have limited access to health care and sanitation services 7.

Epidemiology of 2009 H1N1 influenza in human populations

The basic reproduction number (R0) (mean number of secondary infections caused by one infected individual in a na´ve population) has been estimated to range from 1.4-1.6 or 2.2-3.1 1.

In one Mexican village, secondary attack rates for 2009 H1N1 influenza were 61% for individuals under 15 years of age and 29% for individuals over 15 years of age 1.

Thus far, pigs and other animals are not connected to the epidemiology of 2009 H1N1 influenza in human populations. Furthermore, 2009 H1N1 influenza does not pose a food safety risk to humans who consume pork products 10.

Epidemiology of 2009 H1N1 influenza in swine populations 

Infected pigs have been experimentally demonstrated to transmit 2009 H1N1 influenza to na´ve pigs, leading to virus shedding in the na´ve pigs after three days of contact 9. This evidence suggests that 2009 H1N1 influenza will spread quickly once introduced into commercial swine herds. It is of note that infected pigs were not demonstrated to transmit 2009 H1N1 influenza to na´ve chickens over a 21 day time period 9.

            If 2009 H1N1 influenza is introduced to a swine herd, herd quarantine will be ineffective in slowing the spread of the virus 11. The incubation period for swine influenza viruses is typically 3-5 days. Due to the mild symptoms associated with 2009 H1N1 influenza, herd level infection may not be detected until 7 days following the index case. Sampling and laboratory diagnosis of 2009 H1N1 influenza will not occur until at least one week after introduction of the virus. In modern swine operations, there is movement of pigs to new sites or herds multiple times each week. Thus, spread of 2009 H1N1 influenza to other herds will occur before the diagnosis of virus in the index herd 11.

            Accordingly, the Canadian Food Inspection Agency (CFIA) will not quarantine swine herds to prevent spread of 2009 H1N1 influenza in swine; instead, veterinary management and biosecurity practices are strictly enforced 10. 

Economic significance of the 2009 H1N1 influenza pandemic

            2009 H1N1 influenza is currently the dominant human influenza strain worldwide 7.

The 2009 H1N1 pandemic has had a global economic impact as a result of antiviral and vaccine stockpiling, increased health care costs, improvements in sanitation, trade and travel restrictions, and enhanced biosecurity.

Although Canadian pork products have been declared safe for human consumption 10, the Canadian swine industry has been negatively affected by the 2009 H1N1 pandemic.

Dr. David Hall, Associate Professor, Animal Health Economy, Faculty of Veterinary Medicine, University of Calgary, estimates that the Canadian swine industry has lost $400 million from April to August 22 as a result of the 2009 H1N1 pandemic. This $400 million loss includes a loss of $140 million due to a 15% drop in market price and a $240 million loss due to the multiplier effect in communities 12.

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References

1. Peiris JSM, Poon LLM, Guan Y. Emergence of a novel swine-origin influenza A virus (S-OIV) H1N1 virus in humans. Journal of Clinical Virology 2009 JUL;45(3):169-73.

2. Naffakh N, van der Werf S. April 2009: An outbreak of swine-origin influenza A(H1N1) virus with evidence for human-to-human transmission. Microb Infect 2009 JUL-AUG;11(8-9):725-8.

3. Pandemic Influenza [Internet]; c2009 [cited 2009 September 27]. Available from: http://www.euro.who.int/influenza/20080618_2.

4. What is phase 6? [Internet]; c2009 [cited 2009 September 27]. Available from: http://www.who.int/csr/disease/swineflu/frequently_asked_questions/levels_pandemic_alert/en/index.html.

5. Pandemic (H1N1) 2009 - update 67 Weekly update [Internet]; c2009 [cited 2009 September 27]. Available from: http://www.who.int/csr/don/2009_09_25/en/index.html.

6. Influenza [Internet]; c2009 [cited 2009 September 27]. Available from: http://homepage.usask.ca/~vim458/vetvirol/synopses/flu1.html.

7. Preparing for the second wave: lessons from current outbreaks [Internet]; c2009 [cited 2009 September 27]. Available from: http://www.who.int/csr/disease/swineflu/notes/h1n1_second_wave_20090828/en/index.html.

8. An Alberta Swine Herd Investigated for H1N1 Flu Virus [Internet]; c2009 [cited 2009 September 27]. Available from: http://www.inspection.gc.ca/english/corpaffr/newcom/2009/20090502e.shtml.

9. Lange E, Kalthoff D, Blohm U, Teifke JP, Breithaupt A, Maresch C, Starick E, Fereidouni S, Hoffmann B, Mettenleiter TC, Beer M, Vahlenkamp TW. Pathogenesis and transmission of the novel swine-origin influenza virus A/H1N1 after experimental infection of pigs. J Gen Virol 2009 SEP;90:2119-23.

10. Management of Pandemic H1N1 in Swine Herds [Internet]; c2009 [cited 2009 September 27]. Available from: http://www.inspection.gc.ca/english/corpaffr/newcom/2009/20090724e.shtml.

11. [Anon]. American association of swine veterinarians position statement on pandemic (H1N1) 2009 influenza. Journal of Swine Health and Production 2009 SEP-OCT;17(5):288-9.

12. Hall D. Influenza conference. September 1-2, 2009.

Figure 1, Figure 2:
Bird photo courtesy of www.tufts.edu/vet/lead/index.html
Horse photo courtesy of http://fineartamerica.com/featured/friesian-horse-in-galop-michael-mogensen.html
Cat photo courtesy of  http://www.petfinder.com/cgi-bin/mt/mt-search.cgi?blog_id=1&tag=cats&limit=20
Swine photo courtesy of www.ncbi.nlm.nih.gov/projects/genome/guide/pig/
Dog photo courtesy of www.squidoo.com/doghealthmedicines
Human photo courtesy of http://homepage.usask.ca/~vim458/lab.html
Poultry photo courtesy of http://1.bp.blogspot.com/_fw7iF68JR8k/RlZYI9tJp_I/AAAAAAAADW0/iER6ezSfCxk/s400/chicken.JPG
Seal photo courtesy of http://www.enr.gov.nt.ca/_live/pages/wpPages/ringed_seal.aspx.

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