Is the World Prepared for a Deadly Influenza Pandemic?

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Kawaoka suggested prioritizing further scientific research into the biology of the influenza virus in order to develop more efficacious countermeasures. Anthony Fauci, director of NIAID at NIH, presented a case for the need to develop a universal influenza vaccine and sketched a pathway for making that vaccine a reality. To contextualize the need for a universal influenza vaccine, Fauci identified several challenges related to the current state of influenza vaccinology and explained how they would be ameliorated by the development of a universal influenza vaccine see Box Fauci noted that current seasonal influenza vaccines are not consistently effective.

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According to estimates by CDC, the effectiveness of seasonal influenza vaccines peaked at 60 percent in and but dipped as low as 10 percent in and see Figure CDC, d. He said that the need to improve seasonal vaccines is illustrated by the — seasonal-influenza season, which was the worst on record in recent years: There were 80, reported deaths, 2 almost 1 million hospitalizations, and around 49 million symptomatic illnesses CDC, c.

During this season, vaccine effectiveness reached only 40 percent overall and was as low as 25 percent for the circulating H3N2 strain. Fauci explained that when influenza pandemics occur, post hoc development of vaccines is often ineffective in response to the pandemic. During the H1N1 pandemic, for example, the first human outbreak occurred in March and began to spread worldwide by April.

Egg-based vaccines take approximately 6 months to develop and produce, so public health officials presumed that the vaccine would be ready by the typical peak of influenza season in December and January. The vaccine was barely available when the pandemic peaked, and by the time vaccine doses were finally ready to administer, the pandemic had waned; only 90 million doses were used out of the million doses that were produced. In , significant investment was channeled into developing, producing, and stockpiling a vaccine for the H7N9 strain.

However, the H7N9 virus circulating by had mutated, and the vaccine no longer provided adequate protection. This required developers to start chasing prepandemic influenza vaccines anew Branswell, Fauci argued that the large investments would be better invested in efforts to develop a universal vaccine rather than strain-specific ones. Furthermore, Fauci suggested that vaccine manufacturing techniques need to transition beyond traditional egg-based methods of vaccine production and toward cell-based technologies and cutting-edge platform technologies.

Once a virus is selected, egg-based vaccine development and production take about 6 months before vaccinations can begin. Given the lead time required to have a vaccine ready for winter seasonal-influenza seasons, he explained, virus selection needs to occur in February or March. However, even if the appropriate virus were selected, the virus could change during that 6-month period—which would decrease the effectiveness of the vaccine being developed. Another challenge for egg-based vaccine-production methods is that viruses can adapt within the egg environment in ways that contribute to decreased effectiveness.

For example, from to , the H3N2 virus selected was a good match for the eventual seasonal virus. However, it mutated to grow more effectively in eggs, and the effectiveness of the produced vaccine was reduced. Fauci argued that a universal influenza vaccine would provide more effective protection when the next major influenza pandemic strikes Paules and Fauci, ; Paules et al.

However, he added that producing a universal vaccine would require advanced vaccine manufacturing techniques such as cell-based production and new platform technology. Fauci explained that researchers are currently pursuing new platforms to develop a universal influenza vaccine. These include recombinant proteins, viral vectors e. Fauci sketched the pathway toward developing a universal influenza vaccine Paules et al.

The ideal universal influenza vaccine, he said, would cover all influenza strains in Group 1 and Group 2 of influenza A and potentially strains of influenza B—although this may be aspirational. He said the most practical path to a universal vaccine would be to iteratively broaden the vaccine coverage over time see Figure The penultimate iterative step in developing a universal vaccine would be developing a pan-group vaccine able to cover all strains in Group 1 or in Group 2.

He noted that a vaccine able to cover H3N2 strains and all of the H1N1 strains would be very good for seasonal influenza intervention. With the appropriate group specificity, it would also be useful against pandemic influenza.

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He explained that the influenza A HA protein consists of a head region and a stem region. To address this problem, investigators have focused on the stem region of the HA as the target of universal influenza vaccines. The stem region is similar across different influenza strains, and it is the site of relatively few mutations each season. Approaches researchers have explored. For example, a person born in an era when H1N1 circulated was probably exposed to that strain first, so subsequent exposure to any other strains would induce an immune system response to the H1N1 strain.

Although this does not prevent the immune system from mounting a response against the current strain, it does distract the immune response. This phenomenon explains why different influenza pandemics seem to spare different age cohorts. David Fidler, professor of law at Indiana University Bloomington, gave the next presentation on the role of global governance in bolstering preparedness for pandemic influenza.

He noted that the existing set of global governance mechanisms did not directly result from the pandemic. In fact, it took roughly another 90 years before the main international legal instrument for addressing infectious diseases specifically included provisions for influenza. As a consequence, contemporary global governance structures have yet to be tested by an event as catastrophic as the influenza pandemic.

Fidler described the existing global governance infrastructure for pandemic influenza as a regime complex : a set of interlinked and overlapping institutions, rules, processes, and practices. Overall, this regime complex forms and supports a web of influenza preparedness and response activities that work at both functional and strategic levels.

Functionally, governance mechanisms enable surveillance, virus sharing, scientific research, and vaccine development. Strategically, this web of activities integrates national security, economic interests, human rights, and ethical values into pandemic influenza governance. This web of governance interweaves political calculations about threats of pandemic influenza with public health capabilities to mitigate those threats. However, this regime never included influenza as a reportable disease. The revised IHR broke away from this approach by requiring countries to notify WHO about any disease events that could constitute a public health emergency of international concern.

Specifically, the revised IHR. The revised IHR were quickly subjected to its first influenza challenge in when Indonesia withheld its virus samples from WHO after an outbreak of H5N1 and asserted that the influenza virus-sharing system produced benefits such as access to vaccines that were mainly reaped by countries deemed more developed see Chapter 7 for further discussions on virus sharing and benefit sharing.

The revised IHR were not yet in force, and the question of whether they required countries to share influenza virus samples was contentious.

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According to Fidler, WHO began negotiations to address influenza virus sharing and benefit sharing once it determined the IHR did not specifically govern that issue. However, this innovative governance framework facilitates influenza virus sharing while also creating benefits that flow back to countries that share viruses. Fidler said the PIP. Framework has generally worked, but he has concerns about its future. In particular, he noted that virus sharing has declined since and that the PIP Framework has yet to be tested by a serious influenza pandemic WHO, a see Chapter 7 for a full list of concerns and challenges for the PIP Framework.

Fidler explained that the revised IHR were in full force in when the H1N1 pandemic provided its first real test. That pandemic was not as devastating as predicted, and the IHR generated overall benefits. However, a postpandemic review of the IHR revealed problems with country-level surveillance and response capacities and with questionable trade and travel measures WHO, He said various post-Ebola efforts to strengthen the IHR are under way, but governance issues during that outbreak illustrate that the current IHR have not adequately prepared the world for a dangerous strain of influenza.

Fidler concluded by reflecting on whether progress has been made in global influenza governance. Despite their problems, he suggested the IHR and the PIP Framework facilitate important contributions to existing webs of governance around influenza preparedness and response.

However, he said neither the political commitment nor the functional capacities starting at the international level currently exist to withstand a crisis. He observed that the trend represents a political dynamic that handicaps functional work to build national and international preparedness and to increase response capacities. To transcend. He also said governance efforts should be relentless about ensuring that the next severe influenza pandemic does not cause similar devastation.

Jacqueline Katz, deputy director of the Influenza Division at CDC, discussed the benefits of a One Health approach for pandemic influenza preparedness. The past three of these pandemics were caused by viruses created by reassortment—mixing genes within a common host. According to Katz, the number of novel influenza A virus infections in humans has increased sharply over the past 20 years. These zoonotic infections are caused when an influenza A virus jumps from an animal source into humans; these viruses are antigenetically and genetically distinct from the seasonal influenza A viruses that circulate in humans.

Ever-expanding virus subtypes have been derived either from avian or from swine species.

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The most recent influenza pandemic in was derived from a swine source, but that virus also contained genes of both human and avian origin. She explained that the H5N1 outbreak in Hong Kong was the first time researchers realized that a wholly avian influenza virus could infect humans, and this catalyzed the development of a One Health approach, which was able to quell the outbreak see Box She noted that the increasing number of zoonotic influenza A virus infections in humans will require ongoing laboratory and epidemiologic investigations carried out jointly by researchers from human- and animal-health sectors.

Katz said the H7N9 influenza A virus poses the greatest risk for a human pandemic. This is likely due to a confluence of factors, including a two-fold increase in the global population of poultry, a steady increase in the number of pigs farmed globally, and a steep increase in the number of people who travel globally UNWTO, She added that increased and improved surveillance contributes to the increasing number of cases detected. The emergence of highly pathogenic avian-influenza H7N9 viruses in —not seen in previous H7N9 waves—prompted the Chinese government to introduce poultry vaccination for H7 strains Shi et al.

By controlling the virus in the poultry population, the government essentially controlled the disease in humans. Another developing concern Katz identified was the emergence of variant swine influenza viruses, which have infected humans. The largest wave thus far occurred in when people were infected with H3N2 variant viruses; researchers identified a close association between these infections and children who showed swine at agricultural fairs or participated in swine events at seasonal state fairs Bowman et al.

This pattern has continued, although specific numbers vary by year.

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She emphasized that. WHO Collaboration Centers provide support for the antigenic and genetic characterization of animal viruses. This inter-sectoral collaboration creates the capacity to track viruses in animals and the emergence of zoonotic infections in humans. She noted that certain genetic markers are associated with enhanced mammal adaptation and greater transmission potential. Researchers follow these genetic markers. The collaborating groups meet twice per year to analyze data about the human epidemiology of zoonotic infections, virus distribution and ecology in animals, and the joint genetic and antigenic characterization of viruses from both human and animal sources.

Katz explained that these biannual analyses provide the scientific rationale for developing new candidate vaccine viruses CVVs against emerging and re-emerging influenza viruses that have pandemic potential. Most CVVs are egg-based, inactivated vaccines that are ready for use if needed. Many have been used to produce pilot lots for human clinical vaccine trials, which have provided information about how the vaccines work in humans, including what doses would be needed and whether adjuvants would be required.

She added that some of the CVVs have also been used by veterinary vaccine producers. Katz described how the One Health approach has been applied specifically to influenza in the United States. Samples of any associated animal infections are sent to the U. CDC and USDA collaborate by exchanging gene sequencing data and epidemiologic information about both human and animal viruses; they have also co-developed protocols for notification of and response to potential zoonotic events detected in either sector.

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Finally, CDC and USDA have jointly developed educational and guidance materials about variant influenza viruses and the outbreak-investigation process for both animal-sector producers and the public, including targeted materials for 4-H youth development and mentoring groups. According to Katz, the expansion of next-generation sequencing capacity has strengthened One Health surveillance and readiness in the United States.

Field tests of new mobile technology for influenza sequence analysis e. Real-time genetic sequencing indicated that swine viruses from the Expo were similar to human viruses detected at state fairs months later. Katz suggested that this technology could potentially allow CVVs to be prepared in advance from genetic sequences found in swine earlier in the season; it. Katz considered some global challenges for the One Health approach to influenza preparedness and response. Sharing influenza specimens and viruses with pandemic potential is a complex process that involves different regulations across multiple sectors and countries, and this sometimes delays risk assessment and response timeliness.

It is used to assess potential pandemics for the risk of novel influenza-virus emergence in humans, including human-to-human transmission, and of public health impact and its severity. It is followed closely by H5 subtype viruses. Virus-related elements are genomic variation, receptor binding, transmission in laboratory animals, and antivirals and other treatment options. Population-related elements are existing population immunity, disease severity and pathogenesis, and antigenic relationship to vaccine candidates.

Ecology-related elements are global geographic distribution, infection in animals, human risk of infection, and human infections and transmission. To start the discussion, McKinney asked Kawaoka about the current state of global readiness to identify new viruses with severe pathogenicity prior to an outbreak. Kawaoka replied that influenza pathogenicity is driven by the specific traits of each virus, but immunity in each affected population affects the size of the outbreak.

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For instance, the impact of the H1N1 pandemic is often considered to be relatively low, but the virus affected children more than it affected older people, who tended to have preexisting immunity. Kawaoka said that experimental settings can help researchers identify or predict the pathogenicity of a virus, but they cannot be used to predict the magnitude of an outbreak, which is shaped by this population-immunity factor. Keiji Fukuda, director and clinical professor, School of Public Health, The University of Hong Kong, then asked the panel about ethical and safety concerns related to research that involves dangerous viruses.

Fauci replied that oversight systems have improved during recent years. In the United States, the federal government exercises oversight only on federally funded work, but it has no control over research funded elsewhere. He suggested that difficult decisions about certain types of research—those related to naturally occurring virus mutations, for example—must be formally assessed to determine risks versus benefits to society.

Fauci asserted that creating something that would never occur in nature is the only type of experiment that should be completely disallowed.

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Katz added that federally funded scientific research is subjected to careful and thorough risk—benefit analyses to ensure that the benefits of public health research outweigh the. At the same time, FBI is charged with protecting sensitive research and ensuring its security, as well as with protecting the people who conduct that work and their related institutions.

Influenza was first noted in Australia in and reported in the Sydney Almanack of These include a series of pandemics in the s, , and The most devastating pandemic took place in — This pandemic started in , the last year of the First World War, and passed through soldiers in Western Europe in successively more virulent waves. Unusually, the Spanish flu affected healthy young adults much more than its usual targets: children, the elderly or those with weakened immune systems. The virus spread rapidly around the world as soldiers returned from active service at the end of the war.

Because of its remoteness from Europe, Australia had months to make necessary preparations. The Australian Quarantine Service monitored the spread of the pandemic and implemented maritime quarantine on 17 October after learning of outbreaks in New Zealand and South Africa. The first infected ship to enter Australian waters was the Mataram , from Singapore, which arrived in Darwin on 18 October Over the next six months the service intercepted vessels, of which carried the infection.

Of the 81, people who were checked, were infected. It held a national influenza planning conference in Melbourne on 26—27 November , at which state health ministers, the directors-general of their health departments and British Medical Association representatives met with Commonwealth personnel. The conference agreed to the federal government taking responsibility for proclaiming which states were infected along with organising maritime and land quarantine. The states would arrange emergency hospitals, vaccination depots, ambulance services, medical staff and public awareness measures.

In it developed its first, experimental vaccine in anticipation of pneumonic influenza reaching mainland Australia. Researchers did not know what caused influenza, but produced a vaccine that addressed the more serious secondary bacterial infections that were likely to cause death. It later evaluated the vaccines to be partially effective in preventing death in inoculated individuals. Maritime quarantine contained the spread of the virus until its virulence lessened, and restricted its eventual introduction into Australia to a single entry point.

The first case of pneumonic influenza appeared in Melbourne, on 9 or 10 January Early cases were so mild, however, that there was initially confusion about whether the virus was the Spanish flu, or simply a continuation of the seasonal flu virus from the previous winter. This uncertainty delayed the confirmation of an outbreak from Victorian health authorities, which allowed the infection to spread to New South Wales and South Australia by the end of January New South Wales was the first state to officially proclaim an outbreak of pneumonic influenza on 27 January , with Victoria following suit the next day.

Soon each state made their own arrangements for handling and containing outbreaks, including organising their own border controls. The Commonwealth temporarily withdrew from the November agreement on 11 February The experience of pneumonic influenza varied from place to place. The city of Sydney implemented strict measures in an attempt to limit the spread of the disease.

This included closing schools and places of entertainment and mandating the use of masks. Even so, Sydney experienced three waves of outbreaks, with many deaths and many more infections. Perth experienced a spike in infections after crowds gathered to celebrate Peace Day on 19 July Across the globe, the pandemic had had a devastating effect on a population only just beginning to recover from years of war.

Many more people died from the influenza pandemic 50— million than had died during the First World War 18 million.

Is the World Prepared for a Deadly Influenza Pandemic? Is the World Prepared for a Deadly Influenza Pandemic?
Is the World Prepared for a Deadly Influenza Pandemic? Is the World Prepared for a Deadly Influenza Pandemic?
Is the World Prepared for a Deadly Influenza Pandemic? Is the World Prepared for a Deadly Influenza Pandemic?
Is the World Prepared for a Deadly Influenza Pandemic? Is the World Prepared for a Deadly Influenza Pandemic?
Is the World Prepared for a Deadly Influenza Pandemic? Is the World Prepared for a Deadly Influenza Pandemic?
Is the World Prepared for a Deadly Influenza Pandemic? Is the World Prepared for a Deadly Influenza Pandemic?

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