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Influenza virus

Introduction

In 1918 the H1N1 influenza virus was estimated to have infected 50% of the global population and caused the deaths of approximately 50 million individuals. This was at a time when the global population stood at 1.8 billion.

There have been a number of other influenza pandemics since 1918 that involved different viral strains, however recently the world health organisation (WHO) declared a state of pandemic due to the emergence of a new strain of the H1N1 virus commonly referred to as ‘swine flu.'

This assignment will be highlighting the similarities and differences between the influenza pandemic of 1918 and the ongoing 2009 pandemic. The focus will be on influenza viruses and the conditions at the time. Furthermore details will be provided on the responses at both a UK domestic and global level.

The pandemics of 1918 and 2009 are referred to as ‘Spanish flu' and ‘swine flu' respectively. However the viruses belong to the family known as the Orthomyxovride and to the same genus of influenza A. The viruses are enveloped and contain a negative sensed RNA strand consisting of eight segments encased in a helical structure. Both viruses have extensions of glycoproteins on their surface, prominent amongst them are Haeamagglutinin (HA) and neuraminidase (NA) that play a pivotal role in infection. HA and NA are presented on the viruses in varying amounts, and changes in HA and NA are responsible for different strains of H1N1 and determine their potency to elicit a reaction at a pandemic level. Current research has suggested that the current H1N1 viral pandemic has a swine influenza viral origin that had been formed from the reassortment of two previous strains attributed to the avian and human influenza virus.

The 1918 virus is believed to have been a product of reassortment between mammalian viruses and a human influenza virus circulating within human or pigs. However there has been much conflicting research suggesting different origins of the viruses. For instance research has shown the 1918 virus to be of an avian strain. This suggests that tracing the origins of a virus is complicated and made more complicated as viruses mutate very regularly.

Mechanism of infection

Although the viruses have differences in structure, the mechanisms of infection are identical. Firstly the influenza virus spreads mainly through droplets in the air. Columnar cells of the host's respiratory tract are targeted. HA binds to galactose bound salic acid on the host cell. Viruses enter cells by endocytosis. Viral coat is removed and consequently RNA is converted to DNA by a non proof reading transcriptase. The DNA is subsequently combined with the hosts DNA. Viral DNA is expressed resulting in the production of virons.

A theory to explain host response to viral infection

Infected epithelial and immune cells release cytokines in large quantities thus causing localised and systemic inflammation. This is known as a ‘cytokine storm.' Different cytokines are released in response to different viruses. Both swine and Spanish flu causes the release of IL-1, IL-6 and TNF which are inflammatory cytokines. In addition swine flu causes another cytokine to be released IL-10. The sudden release of IL-10 interrupts the cytokine signalling, and hinders the process from inflammation to recovery, consequently the acute inflammatory responses can be life threatening.

Accumulation of fluid (due to inflammation) in the respiratory tract leads to respiratory diseases (secondary infections) e.g. pneumonia, acute respiratory syndrome etc. Individuals are also more prone to opportunistic infections, and any underlining conditions may worsen as a result. 5

Epidemiology

The mortality rates in the pandemic of 1918 and the current 2009 pandemic differ due to a number of reasons. A typical graph of age demographics in comparison to number of deaths of a viral infection would show a ‘U' shape as this would suggest the highest incidence of mortality in the elderly and the very young. However the 1918 pandemic was unusual in that it affected the adult population. Fig 2 1 shows how the mortality rates of seasonal flu compared with the pandemic of 1918 in the USA.

The trends in mortality rates in regards to the ongoing pandemic of 2009 are somewhat similar to the pandemic of 1918. Just over half the deaths are between the age groups of 20 to 49. Furthermore the deaths of individuals between the ages of 0 to 9 and 50 to 59 are relatively low in comparison to other age demographics.

An accurate comparison cannot be made on the statistical evidence provided. Firstly the current pandemic of 2009 is not over and the statistical information provided for the 1918 pandemic are estimates. This was because it could not be verified that an individual had died of Spanish flu as there was not a definite method of ascertaining the cause of death.

Theories to explain epidemiological findings.

The deaths reported from the 1918 pandemic significantly outweigh the number of mortalities, so far, for the 2009 pandemic. There are multiple theories as to why this may be the case. Firstly it can be put down to the pathogenicity of the virus. For the 1918 virus latest research suggest that the non structural protein one (NS1) is a protein which plays an integral role in the immune response. NS1 destroys a protein within the host cell called the TRIM25 protein. TRIM25 protein is involved with a mechanism which the host cell deploys in the event of an invasion of a virus. The TRIM25 aids in the signalling pathway referred to as the RIG-1 pathway which causes the release of interferon from the cells.. The H1N1 strain of 2009 has undergone an antigenic shift. Antigenic shift is the process of recombination of influenza viruses forming a new subtype. The Gene encoding for the NS1 protein in H1N1 2009 has been truncated at codon 220 thus reducing its pathogenicity in comparison to the 1918 viral pandemic.

Immunity with respect to influenza strains has had an effect on the number of deaths in both pandemics. The mortality for the elderly population is lower than expected. This suggests that the elderly had acquired a level of immunity towards the influenza virus. For instance, in the 1890 pandemic of H1N1, those that survived this pandemic and lived on to 1918 had a higher chance of survival. This is due to memory cells in their immune system. Research has shown that memory cells can live for up to 90 years in an individual.

The reaction of the immune system can also have an impact on the number of deaths. For the very young who have less exposure to antigens and the elderly who have a weaker immune system their reaction to an antigen is weak and therefore less cytokines are produced. Adults tend to have a stronger immune system and release larger quantities of cytokines and are more at risk of inducing a cytokine storm. Hence the number of adult deaths in both pandemics has been unusually high 1.

The current 2009 pandemic shows a large reduction in the number of deaths so far, in comparison. This can also be due to the actions taken by various institutions. In the UK the NHS has begun vaccination programmes and has been distributing Tamiflu (which is a NA inhibitor) to priority groups and health workers. The UK has vast stock piles of Tamiflu. There has also been a large and sustained public health promotion which has made the public more aware of the current pandemic. Furthermore the process of strategic planning has been undertaken by the NHS and other institutions such as the universities, work places, etc. The combination of these measures, undertaken in the UK, has contributed to a reduction in the number of deaths of swine flu.

However there has not been any concrete information to explain why the H1N1 seasonal flu does not replicate the trend in the number of deaths in the different age groups.

Social and economic factors

In 1918 the First World War had ended and soldiers were returning back to their homes, carrying with them the influenza virus. At this time in the pre-NHS period of the UK there was a lack of professional health care facilities and understanding of viral infection. In 1918 there was no global authority that was in place to monitor the health of the global population. Health inequalities were endemic in the UK as there was no public health care system. In contrast in the current pandemic of 2009 there is not a global war. The UK has a NHS which is free at the point of delivery, with much more health workers per head of population than in 1918. On the global level there is the WHO which is tasked to co-ordinate and direct health globally. However, health inequalities still persists, but to a lesser extent to the pre-NHS period.

On a global level there are still health inequalities. Examining fig 4 what can clearly be seen is that out of the top 5 countries that have the most cases of swine flu only one is less economically developed. Whereas out of the top five countries that have the most deaths only one is considered to be an economically developed country. A theory which could further explain this is that through globalisation there are more people moving to economically developed countries so they will have higher cases of swine flu. In developing countries there is a higher population density and so a higher level of transmission and less medical facilities, and this combination could explain why less developed countries have more deaths from swine flu.

The economic impact of the two pandemics differs in extent. In 1918 there was a global reduction in the labour force and the use of transportation across countries, and this had a very negative impact on the global economy. In contrast in the current pandemic of 2009 the impact has not been as severe. For example in the UK the main impact the H1N1 virus has had is in the number of sick days individuals are taking off from work. However due to the strategic planning undertaken by various institutions the effect of swine flu on the economy is minimal. The biggest impact swine flu has is on the NHS as it has to divert resources to prevent its spread., The NHS plays a pivotal role in the UK economy as it prevents a large proportion of its labour force from being infected.

However it is important to recognise that the effects of pandemic can not be exclusively blamed for the performance of the economy. In 1918 the economy was affected by the First World War, and in the current pandemic of 2009 economies are affected by the global recession.

Media

Media representation of both pandemics differed greatly. In 1918 the media had little reach and did not have a large effect on a population. By comparison the current pandemic of 2009, in the UK, the media allows rapid widespread communication which is easily accessible. This not only allows up-to-date communications with the public but also between institutions which aids in the development of strategic planning. On the other hand even with the current global media there has been a lack of coverage on how less developed countries are being affected by the ongoing pandemic.

The lack of media at the time of the 1918 pandemic had been exploited politically. For example the term ‘Spanish flu' came into being because it was Spain which openly discussed the pandemic. In other countries this information was not freely available and so governments took advantage as they did not want to shift public opinion from the war. Similarly in this current pandemic in the UK due to the overwhelming media coverage of the pandemic, pharmaceutical companies are exploiting the media to sell more products. Another example is how the Egyptian government has culled a large number of pigs as a precautionary measure to prevent the spread of swine flu even though there is no evidence to support this strategy.

Conclusion

In conclusion, what can be deduced is that the two pandemics each had particular characteristics and true comparisons cannot be made because the environments were substantially different. However the pandemics allow the development of future health models and a greater understanding of epidemiology. Unfortunately a striking similarity between both pandemics is the lack of involvement of populations that are unable to provide health resources for themselves. It is difficult to predict the extent of the 2009 pandemic but it is reasonable to assume that if there is not a concerted global effort to prevent future pandemics there is a high likelihood that a virus will mutate to such an extent within a certain population that it may resemble the pandemic of 1918. In the UK already the NHS resources are very limited and in the winter there is expected to be a large influx of patients into hospitals. There are already reports from Australia that the medical institutions were overwhelmed by the volume of patients. Global governments must ensure that they are adequately prepared and do not underestimate the severity of swine flu.


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