- Email: [email protected]
Will there ever be a new influenza pandemic and are we prepared?
Vaccine 33 (2015) 7037–7040
Contents lists available at ScienceDirect
Vaccine journal homepage: www.elsevier.com/locate/vaccine
Will there ever be a new influenza pandemic and are we prepared? Will there ever be a new influenza pandemic? The simple answer is ‘yes’. The only thing we don’t know is ‘when’. And are we prepared? Unfortunately, the answer is ‘no’ or ‘not as well as we could be’. Lessons learned from the previous pandemic must inspire our seasonal flu approach.
1. H5N1 Influenza pandemics are relatively rare: there have only been four in the last one hundred years. But the infection of humans by animal influenza viruses is relatively common. “In the last three years alone, ten different animal influenza viruses have caused infections in humans,” says Colin Russell from Cambridge University, UK. “So far, however, none of them have managed to transmit efficiently once they have infected humans. So there is a clear lesson: while infection with an animal virus is relatively easy, the further transmission is difficult. Part of the reason why transmission is difficult is related to the position in the human respiratory tract where the avian influenza viruses bind. Normal seasonal influenza viruses bind in the upper respiratory tract, basically in the throat and nose. This means that it is easy to get the virus out of your body and into someone else’s. In other words, it is easy to transmit. In comparison, avian influenza viruses predominantly bind in the lower respiratory tract, deep in the lungs and it is difficult to get something into or out of our lungs. So before we can see an avian influenza virus becoming a pandemic virus, we will first have to see its binding position switch in the human upper respiratory tract.” Human infections with avian influenza typically take place where there is a massive human–animal interface, in situations where humans are exposed to large numbers of animals or have extremely close contact with animals. Russell: “For example, the chicken population in Indonesia exceeds 5 billion new chickens per year. Indonesia has a large population of 237 million people, but with 5 billion chickens, many of which are kept in domestic settings, there is still a huge human–animal interface.” The progress of the pandemics during the last one hundred years is worth noting. The pandemic virus from 1918 entered the human population and circulated as seasonal influenza until 1957, when another animal influenza virus, the H2N2 virus, entered the population. This in turn circulated as seasonal influenza until 1968. At this point, the H3N2 virus entered the system, which still circulates as seasonal influenza to this day. The 2009 flu pandemic entered the population from pigs; hence the name ‘swine flu’. But interestingly enough, the virus itself was believed to have been introduced to pigs from humans somewhere around the time of the 1918 pandemic. It then circulated in pigs, along with a variety of other viruses, for about 90 years, before re-emerging in the 0264-410X/$ – see front matter http://dx.doi.org/10.1016/j.vaccine.2015.08.045
human population in 2009. There is one other noteworthy influenza A event that did not originate from birds: the re-introduction of the H1N1 virus in 1977, which may have been due to a laboratory release. “At the moment we have H1 to H16 circulating in birds in different parts of the world in an incredible variety of different combinations. But in spite of the fact that we have seen a variety of influenza viruses infecting humans, the viruses that cause pandemics only represent a tiny proportion of the viruses circulating in animals around the world,” says Russell. But how can we know which of these viruses should be causing us concern? According to Russell, most pandemic virus risk assessments are driven by a simple guiding principle. “Animal viruses that cause sporadic human infections are thought to pose a greater pandemic risk than viruses that have not been documented to infect humans. This is particularly true if we see large numbers of human cases contracted directly from animals, especially when those viruses are highly pathogenic.” Based on this reasoning, H5N1 is a major cause for concern. It was first observed in humans in 1997. H5N1 is a highly pathogenic avian virus. “We have been watching it and worrying about it for the last 17 years,” says Russell. “It has caused more than 600 human cases, with a mortality rate of over 50%. The fundamental question is why, with all the human cases we have observed, H5N1 has not yet caused a pandemic. Fortunately, H5N1 does not seem to transmit efficiently from human to human. The first hypothesis is that the virus is just not capable of becoming human-to-human transmissible. The second is that it might be capable, but that it requires too many mutations to happen naturally.” Two years ago, there was a major scientific controversy resulting from the publication of two different papers, one by Yoshihiro Kawaoka, University of Tokyo, Japan, and one by Ron Fouchier, Erasmus MC Rotterdam, The Netherlands, which showed it was possible to make H5N1 transmit efficiently between ferrets via aerosol. Russell: “It only takes five mutations for some of these viruses to become transmissible between ferrets. It is alarming that roughly thirty percent of the H5N1 variants that have been sequenced so far from birds already have two of the five mutations that might allow these viruses to become aerosol transmissible. Two viruses collected from birds have been found to already have three of the mutations, so that they might only need two more.” The crucial questions remain unanswered. Is five mutations a lot or a little? And is the jump from two or three to five mutations an easy or a hard one? Russell: “There are many unknowns. Further work must be done in order to better understand the problem. We need more surveillance in regions where mutations are already prevalent and where there are short chains of transmission in non-human animals. We also need to do deep sequencing in avian and other non-human virus samples and in human samples at multiple time-points, preferably from individuals with long infections. Perhaps other sets of mutations, other than the ones we know of, could activate a high-transmission capability. We
7038
Will there ever be a new influenza pandemic and are we prepared? / Vaccine 33 (2015) 7037–7040
therefore need to identify and monitor other substitutions that could have the same effect. For all these reasons, it is clear that we should continue specific investigations to better understand the workings of H5N1.”
2. H7N9 and other flu threats But what about H7N9 and other looming flu threats? Sander Herfst, from the Department of Viroscience at the Erasmus Medical Centre in Rotterdam, the Netherlands, echoes the opinions of Colin Russell. H7N9 first emerged in March 2013 in East China. “All three patients developed severe pneumonia and acute respiratory distress syndrome, ultimately resulting in death. In the following two months, more human infections were reported, although in the summer months it seemed as if the virus had disappeared. But in the 2013–2014 winter season H7N9 reappeared in humans, with the last reported infections in May of this year. This seasonal reappearance may indicate that the virus will re-emerge again soon. The human infections with H7N9 appear to be associated with exposure to infected live poultry or contaminated environments, including markets where live poultry are sold. Over 80% of human cases reported a history of exposure to birds or live poultry markets. In addition, the viruses isolated from humans are genetically similar to those isolated from birds and the environment.” In total, some 450 laboratory-confirmed cases have been reported. H7N9 is fatal in approximately 30% of cases. “Whereas H5N1 is primarily isolated from individuals younger than 50 years of age, most of the individuals who were infected with H7N9 were more than 50 years old,” says Herfst. “When we look solely at the number of cases that have been reported for both viruses, we can see that the transmissibility of the H7N9 viruses from poultry to humans may be greater than is the case with avian H5N1 viruses.” Much remains unknown about the animal reservoirs of H7N9. Herfst: “What we do know is that there is only limited airborne transmission of H7N9 between ferrets. However, when we return to humans, there was a suspected occurrence of limited human-tohuman transmission of H7N9 in some family clusters, following close, prolonged and unprotected contact. Having said this, no sustained human-to-human transmission has yet been reported. Nevertheless, some H7N9 strains already harbour mammalian adaption markers that have been associated with increased replication and transmission in mammals. The binding pattern of H7N9 is also unusual, since these viruses bind to both the upper and the lower human respiratory tract. Although binding to host cells is only the first step in the virus replication cycle, this binding pattern suggests that H7N9 viruses not only have the potential to cause severe pneumonia, but also the potential to transmit infection among humans by virtue of the virus binding position in the upper respiratory tract. In addition, some H7N9 strains already possess three of the same properties that H5N1 requires to gain airborne transmissibility.” There is currently very little knowledge about the determinants for the transmission of respiratory viruses and further research is needed to augment our understanding. “Additional studies are needed to link the mutations in various influenza subtypes, including the newly emerging subtypes, to phenotypic changes that affect within-host fitness and between-host transmissibility,” says Herfst. He also recommends the improvement of surveillance studies and epidemiological investigations by including simple virus phenotyping assays.
revised its pandemic phases. Diane Gross, from the WHO Regional Office for Europe in Denmark, explains how and why. The Review Committee on the Functioning of the International Health Regulations in relation to the H1N1 pandemic recommended that the WHO should not only include guidelines on risk assessment, but also emphasize a risk-based approach that would enable countries to adopt a more flexible response. The Committee also proposed that the revision should draw on the lessons learned at a country, regional and global level. The overall goal was to simplify the phase structure. “The revision was inspired by demands for greater flexibility from WHO member states,” says Diane Gross. “It was felt that the previous guidance was too rigid and lacked the necessary degree of risk communication. In some countries purchase agreements were linked to the WHO phases, but not all countries were affected at the same time, so that this created issues during the actual response.” The main lesson learned from the pandemic was that the linking of national actions to the different phases simply wasn’t workable. Gross: “In many states the ministry of health was not the overall agency leading the pandemic response. Communication was one of the major issues identified as being a problem and many responses were inflexible or based solely on the outbreak of a severe pandemic, with little room for manoeuvre in the event of a less severe outbreak.” The new 2013 Pandemic Influenza Risk Management Guidance outlines the essential components of a risk management system that could be used for any hazards, including the influenza-specific components. It also emphasizes a risk-based approach and uncouples global phases from national action. Gross: “The new approach is designed to align the pandemic influenza guidance with WHO’s new all-hazard approach, and to give member states the flexibility to implement activities in accordance with the situation in their own country, basing their actions on the local/national risk assessment. As pandemic viruses emerge, countries and regions face different risks at different times. For that reason, countries are strongly advised to develop their own national risk assessments based on local circumstances, taking into consideration the information contained in the global assessments provided by WHO. National risk management decisions are therefore expected to be informed by global risk assessments, but based on local risk assessments.” As far as the decision to recommend a move to a pandemic scale of vaccine production is concerned, this will be taken following collaboration and consultation with the relevant technical advisory bodies. Gross: “WHO will then announce its recommendations with regard to whether or when to switch from seasonal vaccine production to pandemic vaccine production. WHO will also decide which virus strain should be used in the pandemic vaccine. This approach is being documented and different scenarios will be tested.” The new approach encourages countries to base their individual national actions – for example, school closures – on their own risk assessments, resources and needs. A major component of the risk assessment is measurement of severity. Yet at the same time, the individual countries also remain dependent on WHO’s overall risk assessment. Some of the mechanisms remain unclear. For example, there is still considerable doubt whether the vaccines will be ready on time if there is no agreed mechanism for informing companies of the need to switch production from seasonal vaccines to pandemic vaccines. Clarity in this and several other areas is urgently needed.
4. The advantage of using familiar systems 3. Revised pandemic phases How well are we prepared for the next pandemic? In the aftermath of the H1N1 pandemic, the World Health Organization (WHO)
One thing is certain: good seasonal flu preparedness leads to a better pandemic preparedness and vice versa. Chloe Sellwood is the Pandemic Influenza Resilience Manager for the National Health Service in England, with particular focus on the London region.
Will there ever be a new influenza pandemic and are we prepared? / Vaccine 33 (2015) 7037–7040
“With 8 million inhabitants and 1 million commuters every day, we have quite a large population to look after,” says Sellwood. “The NHS is well embedded in society. We engage with different health organizations: acute, specialist and mental hospitals, community providers and general practitioners, not to mention opticians, dentists etc. All these people play a role in our seasonal flu response and would, of course, also be closely involved in our response to a pandemic. The NHS also works with non-medical partners, such as the local authorities, police and fire brigade.” There are, of course, differences between the approach to regular seasonal flu and what was seen during the previous pandemic. Sellwood: “Different characteristics are typically indicative of a pandemic. But some of them can also be applied to a seasonal epidemic. In seasonal flu we also see sudden increases in the demand for services, with numerous cases in a short period of time. We know that the higher the impact, the greater the potential shortage in facilities becomes, not only in things like beds, but also staff, because of their own sickness or the need for carer’s leave. All of these things apply equally to a pandemic. In 2009–2010, the pandemic had two recognized waves and in the UK we had a third very significant wave the following winter. Potentially, there is a similarity here with the return of seasonal influenza. There are two things, however, that we do not see during a seasonal epidemic but would need to be considered during a pandemic: the disruption to national infrastructure and the possibility of mass casualties, with the need for extra body storage facilities.” It is important to build pandemic preparedness on pre-existing systems. “There is little point in developing a whole new system during a pandemic, which would be strange and unfamiliar. Even during a pandemic, we need to deliver the vaccine in a way that patients are familiar with. Where possible, we have to use systems that are already well embedded. Even so, the need for certain pandemic-specific schemes is unavoidable,” says Sellwood. In the UK, the First Few 100 database aims to pick up key information on initial influenza cases and the Pandemic Influenza Triage in the Emergency Department (PAINTED) study attempted to identify the most accurate triage method for predicting severe illness among patients attending emergency departments with suspected pandemic influenza. Sellwood: “The message that comes back from people on front line is that they want to be part of this, they want to know, they want to be trained to do things that can have a meaningful impact on the care of patients. The importance of cross-team management is one element from the pandemic that we now apply in our seasonal flu management. We have instigated command and coordination practices throughout the health service. We try to have a consistent level of service and a consistent level of messages going out to people. We work with GP practices, so that they can ‘buddy together’ and support each other. This standard approach to business continuity all leads to increased capacity across the whole organisation. In order to get the antivirals into patients very quickly – national policy states that patients should receive them within 12 to 48 h – we work together with community pharmacists, because we have learned that patients want to go somewhere that they are familiar with.” During the pandemic, clinical countermeasure distribution arrangements in the UK were multi-channelled. Tamiflu was distributed in various ways; through pharmacies, but also in town halls and schools. “What we learned – and this applies to the response as a whole – is that you should use points of contact that are as close to people’s normal way of life as possible,” says Sellwood. “We have also worked very hard to increase vaccine uptake in health care workers. Vaccine uptake in NHS workers is very low, but there are huge variations in the different health care organizations. We have been collaborating with these different organizations to understand what works and what doesn’t work. We have learned
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to tailor vaccine delivery to the individual person or the organization where it is being delivered. It is no good saying to people that they have to come to one specific place to get their vaccine. You have to take the vaccine to the people.”
5. Pandemic threat on the agenda What is necessary to put the pandemic threat back on the agenda? Robert Dingwall from Dingwall Enterprises Ltd, UK, has investigated the obstacles to influenza preparedness from a sociological point of view. “A pandemic is not just a public health problem,” says Dingwall. It represents a risk to the entire social, economic and political system, and should therefore be dealt with at the highest levels of government. The threat of a pandemic lies in disruption ‘to our everyday assumptions, in the potential fragility of human social structure and interaction, and in the huge diversity and elaboration of human thought, morality and technology’. Based on this theorem, first developed by medical sociologist Philip M. Strong, Dingwall distinguishes three psycho-social pandemics. The first is a pandemic of fear, making people distrust human and environmental contact; “The unknown nature of a pandemic destabilizes our trust in human contact in a way that is independent of the actual risk,” says Dingwall. As a result, the sick may be left uncared for and those felt to be carriers may be shunned or persecuted. The second is a pandemic of explanation, where different explanations for the disease will compete and moralists will attempt to seize the moral high ground. Dingwall: “What will happen when biomedical science cannot deliver immediate certainty? And will the resultant moralising help or hinder public measures?” During a pandemic, many suggestions for limiting the contagion may cut across or even threaten conventional codes and practices. The third pandemic is one of action. When planning for the preservation of public order, it may not be automatically possible to rely on coercion; the security forces will also be sick. Plans to maintain trust in government and institutions therefore need to focus on clear communication and the principled allocation of resources. “Pandemics can only be managed when new routines and assumptions that deal directly with the crisis are firmly in place, a process that requires collective as well as individual action,” says Dingwall.
6. SPI lessons learned It is clear that there is a need for further specific investigations to allow a better understanding of possible pandemic viruses. Roughly thirty percent of the H5N1 variants that have so far been sequenced from birds already have two of the five sequences necessary to become aerosol transmissible. Two of these variants only need two further mutations. H7N9 viruses are likely to have the potential to transmit among humans, because the virus binds to cells in the upper respiratory tract. In addition, some H7N9 strains already possess three of the properties that H5N1 needs to gain airborne transmissibility. WHO has revised its pandemic phases. The new approach encourages countries to base national actions on their own risk assessments, resources and needs. However, some key mechanisms still remain unclear. It is important to build pandemic preparedness on pre-existing, embedded systems. It is no use centralising vaccine distribution at a single location. You have to take the vaccine to the people. A pandemic is not just a public health problem. It represents a risk to the entire social, economic and political system, and should therefore be dealt with at the highest levels of government.
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Will there ever be a new influenza pandemic and are we prepared? / Vaccine 33 (2015) 7037–7040
Conflict of interest statement
b NHS England, London, UK University of Cambridge, Cambridge, UK d Erasmus MC, Rotterdam, The Netherlands e World Health Organization Europe, Copenhagen, Denmark f Dingwall Enterprises Ltd., Nottingham, UK c
Sellwood: none declared; Russel: none; Herfst: none; Gross: none and Dingwall: none declared. Larisa Rudenko a,∗ Chloe Sellwood b Colin Russell c Sander Herfst d Diane Gross e Robert Dingwall f a Dept. of Virology, Institute of Experimental Medicine, akad. Pavlov str., 12, 197376 St. Petersburg, Russia
∗ Corresponding author. E-mail address: [email protected] (L. Rudenko)
Available online 26 September 2015
Contents lists available at ScienceDirect
Vaccine journal homepage: www.elsevier.com/locate/vaccine
Will there ever be a new influenza pandemic and are we prepared? Will there ever be a new influenza pandemic? The simple answer is ‘yes’. The only thing we don’t know is ‘when’. And are we prepared? Unfortunately, the answer is ‘no’ or ‘not as well as we could be’. Lessons learned from the previous pandemic must inspire our seasonal flu approach.
1. H5N1 Influenza pandemics are relatively rare: there have only been four in the last one hundred years. But the infection of humans by animal influenza viruses is relatively common. “In the last three years alone, ten different animal influenza viruses have caused infections in humans,” says Colin Russell from Cambridge University, UK. “So far, however, none of them have managed to transmit efficiently once they have infected humans. So there is a clear lesson: while infection with an animal virus is relatively easy, the further transmission is difficult. Part of the reason why transmission is difficult is related to the position in the human respiratory tract where the avian influenza viruses bind. Normal seasonal influenza viruses bind in the upper respiratory tract, basically in the throat and nose. This means that it is easy to get the virus out of your body and into someone else’s. In other words, it is easy to transmit. In comparison, avian influenza viruses predominantly bind in the lower respiratory tract, deep in the lungs and it is difficult to get something into or out of our lungs. So before we can see an avian influenza virus becoming a pandemic virus, we will first have to see its binding position switch in the human upper respiratory tract.” Human infections with avian influenza typically take place where there is a massive human–animal interface, in situations where humans are exposed to large numbers of animals or have extremely close contact with animals. Russell: “For example, the chicken population in Indonesia exceeds 5 billion new chickens per year. Indonesia has a large population of 237 million people, but with 5 billion chickens, many of which are kept in domestic settings, there is still a huge human–animal interface.” The progress of the pandemics during the last one hundred years is worth noting. The pandemic virus from 1918 entered the human population and circulated as seasonal influenza until 1957, when another animal influenza virus, the H2N2 virus, entered the population. This in turn circulated as seasonal influenza until 1968. At this point, the H3N2 virus entered the system, which still circulates as seasonal influenza to this day. The 2009 flu pandemic entered the population from pigs; hence the name ‘swine flu’. But interestingly enough, the virus itself was believed to have been introduced to pigs from humans somewhere around the time of the 1918 pandemic. It then circulated in pigs, along with a variety of other viruses, for about 90 years, before re-emerging in the 0264-410X/$ – see front matter http://dx.doi.org/10.1016/j.vaccine.2015.08.045
human population in 2009. There is one other noteworthy influenza A event that did not originate from birds: the re-introduction of the H1N1 virus in 1977, which may have been due to a laboratory release. “At the moment we have H1 to H16 circulating in birds in different parts of the world in an incredible variety of different combinations. But in spite of the fact that we have seen a variety of influenza viruses infecting humans, the viruses that cause pandemics only represent a tiny proportion of the viruses circulating in animals around the world,” says Russell. But how can we know which of these viruses should be causing us concern? According to Russell, most pandemic virus risk assessments are driven by a simple guiding principle. “Animal viruses that cause sporadic human infections are thought to pose a greater pandemic risk than viruses that have not been documented to infect humans. This is particularly true if we see large numbers of human cases contracted directly from animals, especially when those viruses are highly pathogenic.” Based on this reasoning, H5N1 is a major cause for concern. It was first observed in humans in 1997. H5N1 is a highly pathogenic avian virus. “We have been watching it and worrying about it for the last 17 years,” says Russell. “It has caused more than 600 human cases, with a mortality rate of over 50%. The fundamental question is why, with all the human cases we have observed, H5N1 has not yet caused a pandemic. Fortunately, H5N1 does not seem to transmit efficiently from human to human. The first hypothesis is that the virus is just not capable of becoming human-to-human transmissible. The second is that it might be capable, but that it requires too many mutations to happen naturally.” Two years ago, there was a major scientific controversy resulting from the publication of two different papers, one by Yoshihiro Kawaoka, University of Tokyo, Japan, and one by Ron Fouchier, Erasmus MC Rotterdam, The Netherlands, which showed it was possible to make H5N1 transmit efficiently between ferrets via aerosol. Russell: “It only takes five mutations for some of these viruses to become transmissible between ferrets. It is alarming that roughly thirty percent of the H5N1 variants that have been sequenced so far from birds already have two of the five mutations that might allow these viruses to become aerosol transmissible. Two viruses collected from birds have been found to already have three of the mutations, so that they might only need two more.” The crucial questions remain unanswered. Is five mutations a lot or a little? And is the jump from two or three to five mutations an easy or a hard one? Russell: “There are many unknowns. Further work must be done in order to better understand the problem. We need more surveillance in regions where mutations are already prevalent and where there are short chains of transmission in non-human animals. We also need to do deep sequencing in avian and other non-human virus samples and in human samples at multiple time-points, preferably from individuals with long infections. Perhaps other sets of mutations, other than the ones we know of, could activate a high-transmission capability. We
7038
Will there ever be a new influenza pandemic and are we prepared? / Vaccine 33 (2015) 7037–7040
therefore need to identify and monitor other substitutions that could have the same effect. For all these reasons, it is clear that we should continue specific investigations to better understand the workings of H5N1.”
2. H7N9 and other flu threats But what about H7N9 and other looming flu threats? Sander Herfst, from the Department of Viroscience at the Erasmus Medical Centre in Rotterdam, the Netherlands, echoes the opinions of Colin Russell. H7N9 first emerged in March 2013 in East China. “All three patients developed severe pneumonia and acute respiratory distress syndrome, ultimately resulting in death. In the following two months, more human infections were reported, although in the summer months it seemed as if the virus had disappeared. But in the 2013–2014 winter season H7N9 reappeared in humans, with the last reported infections in May of this year. This seasonal reappearance may indicate that the virus will re-emerge again soon. The human infections with H7N9 appear to be associated with exposure to infected live poultry or contaminated environments, including markets where live poultry are sold. Over 80% of human cases reported a history of exposure to birds or live poultry markets. In addition, the viruses isolated from humans are genetically similar to those isolated from birds and the environment.” In total, some 450 laboratory-confirmed cases have been reported. H7N9 is fatal in approximately 30% of cases. “Whereas H5N1 is primarily isolated from individuals younger than 50 years of age, most of the individuals who were infected with H7N9 were more than 50 years old,” says Herfst. “When we look solely at the number of cases that have been reported for both viruses, we can see that the transmissibility of the H7N9 viruses from poultry to humans may be greater than is the case with avian H5N1 viruses.” Much remains unknown about the animal reservoirs of H7N9. Herfst: “What we do know is that there is only limited airborne transmission of H7N9 between ferrets. However, when we return to humans, there was a suspected occurrence of limited human-tohuman transmission of H7N9 in some family clusters, following close, prolonged and unprotected contact. Having said this, no sustained human-to-human transmission has yet been reported. Nevertheless, some H7N9 strains already harbour mammalian adaption markers that have been associated with increased replication and transmission in mammals. The binding pattern of H7N9 is also unusual, since these viruses bind to both the upper and the lower human respiratory tract. Although binding to host cells is only the first step in the virus replication cycle, this binding pattern suggests that H7N9 viruses not only have the potential to cause severe pneumonia, but also the potential to transmit infection among humans by virtue of the virus binding position in the upper respiratory tract. In addition, some H7N9 strains already possess three of the same properties that H5N1 requires to gain airborne transmissibility.” There is currently very little knowledge about the determinants for the transmission of respiratory viruses and further research is needed to augment our understanding. “Additional studies are needed to link the mutations in various influenza subtypes, including the newly emerging subtypes, to phenotypic changes that affect within-host fitness and between-host transmissibility,” says Herfst. He also recommends the improvement of surveillance studies and epidemiological investigations by including simple virus phenotyping assays.
revised its pandemic phases. Diane Gross, from the WHO Regional Office for Europe in Denmark, explains how and why. The Review Committee on the Functioning of the International Health Regulations in relation to the H1N1 pandemic recommended that the WHO should not only include guidelines on risk assessment, but also emphasize a risk-based approach that would enable countries to adopt a more flexible response. The Committee also proposed that the revision should draw on the lessons learned at a country, regional and global level. The overall goal was to simplify the phase structure. “The revision was inspired by demands for greater flexibility from WHO member states,” says Diane Gross. “It was felt that the previous guidance was too rigid and lacked the necessary degree of risk communication. In some countries purchase agreements were linked to the WHO phases, but not all countries were affected at the same time, so that this created issues during the actual response.” The main lesson learned from the pandemic was that the linking of national actions to the different phases simply wasn’t workable. Gross: “In many states the ministry of health was not the overall agency leading the pandemic response. Communication was one of the major issues identified as being a problem and many responses were inflexible or based solely on the outbreak of a severe pandemic, with little room for manoeuvre in the event of a less severe outbreak.” The new 2013 Pandemic Influenza Risk Management Guidance outlines the essential components of a risk management system that could be used for any hazards, including the influenza-specific components. It also emphasizes a risk-based approach and uncouples global phases from national action. Gross: “The new approach is designed to align the pandemic influenza guidance with WHO’s new all-hazard approach, and to give member states the flexibility to implement activities in accordance with the situation in their own country, basing their actions on the local/national risk assessment. As pandemic viruses emerge, countries and regions face different risks at different times. For that reason, countries are strongly advised to develop their own national risk assessments based on local circumstances, taking into consideration the information contained in the global assessments provided by WHO. National risk management decisions are therefore expected to be informed by global risk assessments, but based on local risk assessments.” As far as the decision to recommend a move to a pandemic scale of vaccine production is concerned, this will be taken following collaboration and consultation with the relevant technical advisory bodies. Gross: “WHO will then announce its recommendations with regard to whether or when to switch from seasonal vaccine production to pandemic vaccine production. WHO will also decide which virus strain should be used in the pandemic vaccine. This approach is being documented and different scenarios will be tested.” The new approach encourages countries to base their individual national actions – for example, school closures – on their own risk assessments, resources and needs. A major component of the risk assessment is measurement of severity. Yet at the same time, the individual countries also remain dependent on WHO’s overall risk assessment. Some of the mechanisms remain unclear. For example, there is still considerable doubt whether the vaccines will be ready on time if there is no agreed mechanism for informing companies of the need to switch production from seasonal vaccines to pandemic vaccines. Clarity in this and several other areas is urgently needed.
4. The advantage of using familiar systems 3. Revised pandemic phases How well are we prepared for the next pandemic? In the aftermath of the H1N1 pandemic, the World Health Organization (WHO)
One thing is certain: good seasonal flu preparedness leads to a better pandemic preparedness and vice versa. Chloe Sellwood is the Pandemic Influenza Resilience Manager for the National Health Service in England, with particular focus on the London region.
Will there ever be a new influenza pandemic and are we prepared? / Vaccine 33 (2015) 7037–7040
“With 8 million inhabitants and 1 million commuters every day, we have quite a large population to look after,” says Sellwood. “The NHS is well embedded in society. We engage with different health organizations: acute, specialist and mental hospitals, community providers and general practitioners, not to mention opticians, dentists etc. All these people play a role in our seasonal flu response and would, of course, also be closely involved in our response to a pandemic. The NHS also works with non-medical partners, such as the local authorities, police and fire brigade.” There are, of course, differences between the approach to regular seasonal flu and what was seen during the previous pandemic. Sellwood: “Different characteristics are typically indicative of a pandemic. But some of them can also be applied to a seasonal epidemic. In seasonal flu we also see sudden increases in the demand for services, with numerous cases in a short period of time. We know that the higher the impact, the greater the potential shortage in facilities becomes, not only in things like beds, but also staff, because of their own sickness or the need for carer’s leave. All of these things apply equally to a pandemic. In 2009–2010, the pandemic had two recognized waves and in the UK we had a third very significant wave the following winter. Potentially, there is a similarity here with the return of seasonal influenza. There are two things, however, that we do not see during a seasonal epidemic but would need to be considered during a pandemic: the disruption to national infrastructure and the possibility of mass casualties, with the need for extra body storage facilities.” It is important to build pandemic preparedness on pre-existing systems. “There is little point in developing a whole new system during a pandemic, which would be strange and unfamiliar. Even during a pandemic, we need to deliver the vaccine in a way that patients are familiar with. Where possible, we have to use systems that are already well embedded. Even so, the need for certain pandemic-specific schemes is unavoidable,” says Sellwood. In the UK, the First Few 100 database aims to pick up key information on initial influenza cases and the Pandemic Influenza Triage in the Emergency Department (PAINTED) study attempted to identify the most accurate triage method for predicting severe illness among patients attending emergency departments with suspected pandemic influenza. Sellwood: “The message that comes back from people on front line is that they want to be part of this, they want to know, they want to be trained to do things that can have a meaningful impact on the care of patients. The importance of cross-team management is one element from the pandemic that we now apply in our seasonal flu management. We have instigated command and coordination practices throughout the health service. We try to have a consistent level of service and a consistent level of messages going out to people. We work with GP practices, so that they can ‘buddy together’ and support each other. This standard approach to business continuity all leads to increased capacity across the whole organisation. In order to get the antivirals into patients very quickly – national policy states that patients should receive them within 12 to 48 h – we work together with community pharmacists, because we have learned that patients want to go somewhere that they are familiar with.” During the pandemic, clinical countermeasure distribution arrangements in the UK were multi-channelled. Tamiflu was distributed in various ways; through pharmacies, but also in town halls and schools. “What we learned – and this applies to the response as a whole – is that you should use points of contact that are as close to people’s normal way of life as possible,” says Sellwood. “We have also worked very hard to increase vaccine uptake in health care workers. Vaccine uptake in NHS workers is very low, but there are huge variations in the different health care organizations. We have been collaborating with these different organizations to understand what works and what doesn’t work. We have learned
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to tailor vaccine delivery to the individual person or the organization where it is being delivered. It is no good saying to people that they have to come to one specific place to get their vaccine. You have to take the vaccine to the people.”
5. Pandemic threat on the agenda What is necessary to put the pandemic threat back on the agenda? Robert Dingwall from Dingwall Enterprises Ltd, UK, has investigated the obstacles to influenza preparedness from a sociological point of view. “A pandemic is not just a public health problem,” says Dingwall. It represents a risk to the entire social, economic and political system, and should therefore be dealt with at the highest levels of government. The threat of a pandemic lies in disruption ‘to our everyday assumptions, in the potential fragility of human social structure and interaction, and in the huge diversity and elaboration of human thought, morality and technology’. Based on this theorem, first developed by medical sociologist Philip M. Strong, Dingwall distinguishes three psycho-social pandemics. The first is a pandemic of fear, making people distrust human and environmental contact; “The unknown nature of a pandemic destabilizes our trust in human contact in a way that is independent of the actual risk,” says Dingwall. As a result, the sick may be left uncared for and those felt to be carriers may be shunned or persecuted. The second is a pandemic of explanation, where different explanations for the disease will compete and moralists will attempt to seize the moral high ground. Dingwall: “What will happen when biomedical science cannot deliver immediate certainty? And will the resultant moralising help or hinder public measures?” During a pandemic, many suggestions for limiting the contagion may cut across or even threaten conventional codes and practices. The third pandemic is one of action. When planning for the preservation of public order, it may not be automatically possible to rely on coercion; the security forces will also be sick. Plans to maintain trust in government and institutions therefore need to focus on clear communication and the principled allocation of resources. “Pandemics can only be managed when new routines and assumptions that deal directly with the crisis are firmly in place, a process that requires collective as well as individual action,” says Dingwall.
6. SPI lessons learned It is clear that there is a need for further specific investigations to allow a better understanding of possible pandemic viruses. Roughly thirty percent of the H5N1 variants that have so far been sequenced from birds already have two of the five sequences necessary to become aerosol transmissible. Two of these variants only need two further mutations. H7N9 viruses are likely to have the potential to transmit among humans, because the virus binds to cells in the upper respiratory tract. In addition, some H7N9 strains already possess three of the properties that H5N1 needs to gain airborne transmissibility. WHO has revised its pandemic phases. The new approach encourages countries to base national actions on their own risk assessments, resources and needs. However, some key mechanisms still remain unclear. It is important to build pandemic preparedness on pre-existing, embedded systems. It is no use centralising vaccine distribution at a single location. You have to take the vaccine to the people. A pandemic is not just a public health problem. It represents a risk to the entire social, economic and political system, and should therefore be dealt with at the highest levels of government.
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Will there ever be a new influenza pandemic and are we prepared? / Vaccine 33 (2015) 7037–7040
Conflict of interest statement
b NHS England, London, UK University of Cambridge, Cambridge, UK d Erasmus MC, Rotterdam, The Netherlands e World Health Organization Europe, Copenhagen, Denmark f Dingwall Enterprises Ltd., Nottingham, UK c
Sellwood: none declared; Russel: none; Herfst: none; Gross: none and Dingwall: none declared. Larisa Rudenko a,∗ Chloe Sellwood b Colin Russell c Sander Herfst d Diane Gross e Robert Dingwall f a Dept. of Virology, Institute of Experimental Medicine, akad. Pavlov str., 12, 197376 St. Petersburg, Russia
∗ Corresponding author. E-mail address: [email protected] (L. Rudenko)
Available online 26 September 2015