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Influenza pandemic

Encyclopedia : I : IN : INF : Influenza pandemic

 H5N1

WHO pandemic phases
1. Low risk
2. New virus
3. Self limiting
4. Person to person
5. Epidemic exists
6. Pandemic exists
Flu

An influenza pandemic is a large scale epidemic of the influenza virus, such as the 1918 Spanish flu. The World Health Organization (WHO) warns that there is a substantial risk of an influenza pandemic within the next few years. One of the strongest candidates is a highly pathogenic variation of the H5N1 subtype of Influenza A virus which is rapidly mutating and could mutate into a variation that transmits easily human to human causing a pandemic. If such a mutation occurs, it might remain an H5N1 subtype or could shift subtypes as did H2N2 when it evolved into the Hong Kong Flu strain of H3N2.

Contents

Nature of a pandemic

Some pandemics are relatively minor and can be contained quickly such as the one in 1957 which "only" killed around a million people throughout the world. The mutation in the virus that causes the high infection rate may also cause the virus to be less deadly as it needs to pass between host to host and replicate itself.

In a bad pandemic, some communities attempt to cut themselves off totally while others have half (or more) of their population die, and others may not feel many of the effects but may still be affected due to the high degree of illness and the bereavement felt by the members of the community. Desperate people try anything to cure or prevent the illness. [New York Times] article Turning to Chickens in Fight With Bird Flu published May 2, 2006. "Desperate times call for desperate measures. In the worst months of the 1918 Spanish flu pandemic, doctors flailing to save patients tried all sorts of outlandish 'cures'. Cupping and bleeding made comebacks. Intravenous hydrogen peroxide was tried, sometimes fatally. One doctor injected a mix of blister fluid, morphine, strychnine and caffeine. Typhoid vaccine was given, since it prompts immune reactions; so was quinine, because it breaks malarial fevers."

The 1918 pandemic killed around 150 000 people in the UK, but even the loss of this relatively small number of people in the population caused upheaval and psychological damage to many people. [Nap Book] There are not enough doctors, hospital rooms, or medical supplies for the living due to their contracting the disease and dead bodies often lie unburied as few people are available to deal with them. There is great social disruption and a sense of fear and efforts to deal with the pandemic always leave a great deal to be desired due to selfishness, lack of trust, illegal behavior, and ignorance. For example in the 1918 pandemic "This horrific disconnect between reassurances and reality destroyed the credibility of those in authority. People felt they had no one to turn to, no one to rely on, no one to trust." [Book]

A letter from a physician at one U.S. Army camp in the 1918 pandemic said:

It is only a matter of a few hours then until death comes [...]. It is horrible. One can stand it to see one, two or twenty men die, but to see these poor devils dropping like flies [...]. We have been averaging about 100 deaths per day [...]. Pneumonia means in about all cases death [...]. We have lost an outrageous number of Nurses and Drs. It takes special trains to carry away the dead. For several days there were no coffins and the bodies piled up something fierce [...]. [NAP Book]

H5N1

To have a flu pandemic several distinct phases must happen. H5N1's next phase is easy person to person transmission. After that occurs, it is theoretically possible to stop it before it becomes an epidemic, or if that opportunity is missed, to stop the epidemic before it becomes a pandemic. It is widely believed by the experts that it will not be possible to prevent any of these phases from occurring with H5N1, but if we are lucky enough to delay it for a few years, we might come up with a solution such as a flu vaccine.

H5N1 is just one of the many subtypes of the species Influenza A virus. Any one of them can combine with each other or with different variant genotypes within its own subtype creating new varients, any one of which could become a pandemic strain. We know enough about the genetics to know what strains to fear most (H5 and H7 subtypes) and we know what genetic factors make a flu virus a human virus (i.e. easily passed human to human); so we know H5N1 is the biggest pandemic threat of all the strains in circulation and we know it is only one antigenic shift mutation or a couple of antigenic drift mutations from being an avian flu virus to being a human flu virus. If it does this it may or may not still be in the H5N1 subtype. Both the drift and the shift can happen in any infected animal and then be passed to a human and spread like wildfire. Possible shift scenarios include the shift occurring in humans, pigs, or cats. To acquire the needed mutation through drift, it simply has to continue being an epidemic in birds long enough for the mutations to occur and then be passed to a human.

Comes in waves

Flu pandemics typically come in waves. The 1889–1890 and the 1918-1919 flu pandemics each came in three or four waves of increasing lethality. [NAP Book page 60] But within a wave, mortality was greater at the beginning of the wave. [NAP Book page 63]

Variable mortality

Mortality varies widely in a pandemic. In the 1918 pandemic:

In U.S. Army camps where reasonably reliable statistics were kept, case mortality often exceeded 5 percent, and in some circumstances exceeded 10 percent. In the British Army in India, case mortality for white troops was 9.6 percent, for Indian troops 21.9 percent. In isolated human populations, the virus killed at even higher rates. In the Fiji islands, it killed 14 percent of the entire population in 16 days. In Labrador and Alaska, it killed at least one-third of the entire native population. [NAP Book page 61]

Strategies to prevent a pandemic

If influenza remains an animal problem with limited human-to-human transmission it is not a pandemic, though it continues to pose a risk.

To prevent the situation from progressing to a pandemic, the following short-term strategies have been put forward:

The rationale for vaccinating poultry workers against common flu is that it reduces the probability of common influenza virus recombining with avian H5N1 virus in the bloodstream of poultry workers to form a pandemic strain.

Longer term strategies proposed for regions where highly pathogenic H5N1 is endemic in wild birds have included:

Strategies to slow down a pandemic

Vaccines

A vaccine probably would not be available in the initial stages of population infection [CDC]. Once a potential virus is identified, it normally takes at least several months before a vaccine becomes widely available, as it must be developed, tested and authorized. The capability to produce vaccines varies widely from country to country; in fact, only 15 countries are listed as "Influenza vaccine manufacturers" according to the World Health Organization [WHO]. It is estimated that, in a best scenario situation, 750 million doses could be produced each year, whereas it is likely that each individual would need two doses of the vaccine in order to become inmuno-competent. Distribution to and inside countries would probably be problematic [phacilitate.co.uk]. Several countries, however, have well-developed plans for producing large quantities of vaccine. For example, Canadian health authorities say that they are developing the capacity to produce 32 million doses within four months, enough vaccine to inoculate every person in the country. [Canada TV News]

There are two serious technical problems associated with the development of a vaccine against H5N1. The first problem is this: seasonal influenza vaccines require a single injection of 15 μg haemagluttinin in order to give protection; H5 seems to evoke only a weak immune response and a large multicentre trial found that two injections of 90 µg H5 given 28 days apart provided protection in only 54% of people . Even if it is considered that 54% is an acceptable level of protection, the world is currently capable of producing only 900 million doses at a strength of 15 μg (assuming that all production were immediately converted to manufacturing H5 vaccine); if two injections of 90 μg are needed then this capacity drops to only 70 million . Trials using adjuvants such as alum or MF59 to try and lower the dose of vaccine are urgently needed. The second problem is this: there are two circulating clades of virus, clade 1 is the virus originally isolated in Vietnam, clade 2 is the virus isolated in Indonesia. Current vaccine research is focussed on clade 1 viruses, but the clade 2 virus is antigenically distinct and a clade 1 vaccine will probably not protect against a pandemic caused by clade 2 virus.

Anti-viral drugs

Many nations, as well as the World Health Organization, are working to stockpile anti-viral drugs in preparation for a possible pandemic. Oseltamivir (trade name Tamiflu) is the most commonly sought drug, since it is available in pill form. Zanamivir (trade name Relenza) is also considered for use, but it must be inhaled. Other anti-viral drugs are less likely to be effective against pandemic influenza.

Both Tamiflu and Relenza are in short supply, and production capabilities are limited in the medium term. Some doctors say that co-administration of Tamiflu with probenecid could double supplies [Nature].

There also is the potential of viruses to evolve drug resistance. Some H5N1-infected persons treated with oseltamivir have developed resistant strains of that virus.

Tamiflu was originally discovered by Gilead Sciences and licensed to Roche for late-phase development and marketing.

Donald Rumsfeld, the major shareholder in Gilead Sciences, has profited from the US government stockpiling of oseltamivir in case of an influenza pandemic. [Forbes] Critics have used this fact to question both government stockpiling policies and the H5N1 potential pandemic itself.

Global response

Individual response

(The World Health Organization published a [compendium of non-pharmaceutical interventions] in November 2005. The following list is not identical to the WHO recommendations.) [compendium of non-pharmaceutical interventions]

Strategies for individuals in a pandemic

In the case of a flu pandemic, to avoid the risk of contracting H5N1 (or indeed, any other strain of the flu virus) people may have to take certain precautions, and make changes to their routine, to minimize the risk of infection. They may also have to prepare for the possibility of their lives being disrupted in a significant way, even if they do not actually become ill.

Social disruption

A flu pandemic could cause major disruption to everyday life, with footpaths and the countryside being partially or even totally off-limits, and even restrictions on public gatherings (such as public meetings, parties, services at places of worship), quarantine, and bans on individuals travelling to certain locations. However, there are a number of things people could do to prepare themselves:

Work

Education

Transport

Organizing

Food storage

Keep a supply of water and food. During a pandemic you may not be able to get to a store. Even if you can get to a store, it may be out of supplies or it may not be safe to enter it. Public waterworks services may also be interrupted. Stocking supplies can be useful in other types of emergencies. Store foods that:

Personal health and hygiene

Will the seasonal flu shot protect me against pandemic influenza?

Take common-sense steps to limit the spread of germs. Make good hygiene a habit.

It is always a good idea to practice good health habits.

Being informed during a pandemic

Knowing the facts is the best preparation. Identify sources you can count on for reliable information. If a pandemic occurs, having accurate and reliable information will be critical. Listen to local and national radio, watch news reports on television, and read your newspaper and other sources of printed and Web-based information. Talk to your local health care providers and public health officials. Read your government Web sites. As you begin your individual or family planning, you may want to review your state's planning efforts and those of your local public health and emergency preparedness officials.

Australia
Brazil
Canada
Finland (FI)
France (FR)
Germany
Hong Kong
India
Ireland
New Zealand (NZ)
Singapore
South Africa
Spain
Switzerland
United Kingdom (UK)
United States (US)

Stocks / Investments

Experts agree that a lethal pandemic will have a negative effect on the world and local economies.

Phases of an influenza pandemic

The World Health Organization (WHO) has developed a global influenza preparedness plan, which defines the stages of a pandemic, outlines WHO's role and makes recommendations for national measures before and during a pandemic. The World Health Organization announces the current phase of the pandemic alert [here].

See "Assessing the pandemic threat" at [link]. WHO published a first edition of the Global Influenza Preparedness Plan in 1999, and updated it in April 2005. See [link] and [link] which define the responsibilities of WHO and national authorities in case of an influenza pandemic. This is the first time a pandemic has been anticipated and is being prepared for.

The aims of such plans are, broadly speaking, the following:

  • Before a pandemic, attempt to prevent it and prepare for it in case prevention fails.
  • If a pandemic does occur, to slow its spread and allow societies to function as normally as possible.

Investigations of small clusters of cases are currently ongoing in southeast Asia, particularly Vietnam, to rule out limited human-to-human spread (which would signify Phase 4). The phases are defined as:

Interpandemic period

Pandemic alert period

Pandemic period

Notes

The distinction between phase 1 and phase 2 is based on the risk of human infection or disease resulting from circulating strains in animals. The distinction is based on various factors and their relative importance according to current scientific knowledge. Factors may include pathogenicity in animals and humans, occurrence in domesticated animals and livestock or only in wildlife, whether the virus is enzootic or epizootic, geographically localized or widespread, and/or other scientific parameters.

The distinction between phase 3, phase 4 and phase 5 is based on an assessment of the risk of a pandemic. Various factors and their relative importance according to current scientific knowledge may be considered. Factors may include rate of transmission, geographical location and spread, severity of illness, presence of genes from human strains (if derived from an animal strain), and/or other scientific parameters.

The pandemic stage 6 may be marked by two or more waves. For example, the initial wave of the Spanish Influenza pandemic in the spring of 1918 was so mild in its effects that it received the dismissive nickname of the "three day flu." But when the second wave hit North America a few months later in the summer of 1918, it was lethal. Apparently in the interim the novel H1N1 pandemic strain had added the gene or genes that made the final wave a killer. Perhaps the effects of the lethal second wave would have been even more devastating if the innocuous first wave had not already passed through the population, leaving in its wake at least some immune response to the surface antigens presented by the H1N1 in both waves.

CIDRAP provides a thoroughgoing overview, which has its roots in materials from the U.S. HHS National Vaccine Program Office. CIDRAP's overview originally set forth a model listing five numbered stages for the pandemic itself, preceded by four additional pre-pandemic stages, each numbered as zero, that overlapped the WHO's first five stages of a pandemic. CIDRAP's overview has since adopted the WHO's 6-stage model. [CIDRAP's Pandemic Influenza]

Preparations for a potential influenza pandemic

According to the New York Times as of March 2006, "governments worldwide have spent billions planning for a potential influenza pandemic: buying medicines, running disaster drills, [and] developing strategies for tighter border controls" due to the H5N1 threat [New York Times].

"[T]he United States is collaborating closely with eight international organizations, including the World Health Organization (WHO), the Food and Agriculture Organization of the United Nations (FAO), the World Organization for Animal Health (OIE), and 88 foreign governments to address the situation through planning, greater monitoring, and full transparency in reporting and investigating avian influenza occurrences. The United States and these international partners have led global efforts to encourage countries to heighten surveillance for outbreaks in poultry and significant numbers of deaths in migratory birds and to rapidly introduce containment measures. The U.S. Agency for International Development (USAID) and the U.S. Department of State, the U.S. Department of Health and Human Services (HHS), and Agriculture (USDA) are coordinating future international response measures on behalf of the White House with departments and agencies across the federal government." [US AID]

Together steps are being taken to "minimize the risk of further spread in animal populations", "reduce the risk of human infections", and "further support pandemic planning and preparedness". [US AID]

Ongoing detailed mutually coordinated onsite surveillance and analysis of human and animal H5N1 avian flu outbreaks are being conducted and reported by the USGS National Wildlife Health Center, the Centers for Disease Control and Prevention, the World Health Organization, the European Commission, the National Influenza Centers, and others. [pandemicflu.gov]

International government sponsored scientific seminars on H5N1 pandemic prevention

AEWA MOP-3: The third Meeting of the Parties to AEWA met from 23-27 October 2005 in Dakar, Senegal. Participants adopted Resolution 3.18, which calls for, inter alia: urgent responses to the spread of HPAI including the development of national surveillance schemes and contingency planning, involving immediate and long-term measures; increased focus on education and awareness programmes and capacity building, particularly in Africa; increased cooperation between relevant bodies; and additional scientific research.

MEETING ON AVIAN INFLUENZA AND HUMAN PANDEMIC INFLUENZA: This meeting was held from 7-9 November 2005 in Geneva, Switzerland and was co-sponsored by WHO, FAO and OIE. Participants identified key steps to be taken to contain the spread of HPAI, including source control, surveillance, rapid containment, pandemic preparedness, integrated country plans, and communications.

RAMSAR COP-9: The ninth Conference of the Parties to the Ramsar Convention was held from 8-15 November 2005 in Kampala, Uganda. Participants adopted Resolution IX.23, which calls for fully integrated approaches, at both national and international levels, to address HPAI by bringing ornithological, wildlife, and wetland management expertise together with those traditionally responsible for public health and zoonoses. It emphasizes that destruction or substantive modification of wetland habitats with the objective of reducing contact between domesticated and wild birds may exacerbate the problem by causing further dispersal of infected birds.

CMS COP-8: The eighth Conference of the Parties to CMS convened from 20-25 November 2005 in Nairobi, Kenya. Participants adopted Resolution 8.27, which calls for support and capacity building for research related to disease processes in migratory bird species, long-term monitoring of their movements and populations, and rapid development of surveillance programmes for HPAI in populations of wild birds. An Annex to the Resolution lists key research needs related to the spread of HPAI in relation to migratory birds and their habitats.

INTERNATIONAL PLEDGING CONFERENCE ON AVIAN AND HUMAN INFLUENZA: This event, held from 17-18 January 2006 in Beijing, China, was co-sponsored by the Government of China, the European Commission and the World Bank. During this event the international community pledged US$ 1.9 billion in financial support and discussed coordination mechanisms. Participants adopted the Beijing Declaration, in which they commit themselves to effective development and implementation of integrated national action plans, long-term strategic partnerships, information sharing, increased cooperation on global research, and periodic evaluation of national pandemic influenza preparedness and action plans.

CBD COP-8: The eighth Conference of the Parties to the Convention on Biological Diversity (CBD) was held in Curitiba, Brazil from 20-31 March 2006. A brainstorming session on HPAI preceded the meeting. Participants at this session: highlighted threats to migratory species and wetlands, knowledge gaps and the need for capacity building; welcomed the participation of the CBD in the Scientific Task Force on Avian Influenza; and suggested that CBD’s Subsidiary Body on Scientific, Technical and Technological Advice (SBSTTA) further assess the interlinkages between ecosystems and health on matters including climate change and avian flu. Participants adopted a Decision on Avian Flu (UNEP/CBD/COP/8/L.35), in which they take note of the brainstorming meeting report and encourage similar consultations as and when emerging issues that may impact CBD implementation arise.

6TH INTERNATIONAL SYMPOSIUM ON AVIAN INFLUENZA: This event was held from 3-6 April 2006 in Cambridge, UK. Participants addressed lessons learned from recent outbreaks in Asia, Africa and Europe and recent epidemiological and virological information. They identified short- and long-term needs, including enhanced scientific information, cross-sectoral and international cooperation, and improved awareness among decision makers and the general public.

UPCOMING MEETINGS

INTERNATIONAL SCIENTIFIC CONFERENCE ON AVIAN INFLUENZA AND WILD BIRDS: This meeting, organized by FAO and OIE, will take place from 30-31 May 2006 in Rome, Italy. The meeting aims to exchange scientific information on AI and the role of wild birds, to assess the risk of the introduction of the HPAI virus to as yet uninfected areas as well as to propose mitigation and preventive measures. For more information, contact: Maria Zampaglione, OIE; tel: +33 (0) 1 44 15 18 88; fax: 33 (0) 1 42 67 09 87; e-mail: m.zampaglione@oie.int; internet: http://www.oie.int or http://www.fao.org/AG/AGAInfo/subjects/en/health/diseases-cards/special_avian.html

2ND BIRD FLU SUMMIT: During this meeting, which will be held from 28-29 June 2006 in Washington DC, USA, business, government, public and private sector leaders interact with avian influenza experts from around the world to address the issues of pandemic prevention, preparedness, response and recovery. For more information, contact: Nancy Lane, New Fields; tel: +1-202-536-5850; fax: +1-202-478-2989; e-mail: nancy@new-fields.com; internet: http://www.new-fields.com/birdflu2/index.asp

BIOSAFETY PROTOCOL COP/MOP-4 AND CBD COP-9: The fourth Meeting of the Parties to the Cartagena Protocol on Biosafety and the ninth Conference of the Parties to CBD are expected to be held back-to-back in 2008, in Germany. For more information, contact: CBD Secretariat; tel: +1-514-288-2220; fax: +1-514-288-6588; e-mail: secretariat@biodiv.org; internet: http://www.biodiv.org

United Nations

In September 2005, David Nabarro, a lead UN health official warned that a bird flu outbreak could happen anytime and had the potential to kill 5-150 million people. [BBC News]

United States

"[E]fforts by the federal government to prepare for pandemic influenza at the national level include a $100 million DHHS initiative in 2003 to build U.S. vaccine production. Several agencies within Department of Health and Human Services (DHHS) — including the Office of the Secretary, the Food and Drug Administration (FDA), CDC, and the National Institute of Allergy and Infectious Diseases (NIAID) — are in the process of working with vaccine manufacturers to facilitate production of pilot vaccine lots for both H5N1 and H9N2 strains as well as contracting for the manufacturing of 2 million doses of an H5N1 vaccine. This H5N1 vaccine production will provide a critical pilot test of the pandemic vaccine system; it will also be used for clinical trials to evaluate dose and immunogenicity and can provide initial vaccine for early use in the event of an emerging pandemic." [NAP Book]

On August 26, 2004, Secretary of Health and Human Services, Tommy Thompson released a draft Pandemic Influenza Response and Preparedness Plan [draft Pandemic Influenza Response and Preparedness Plan], which outlined a coordinated national strategy to prepare for and respond to an influenza pandemic. Public comments were accepted for 60 days.

In a speech before the United Nations General Assembly on September 14, 2005, President George W. Bush announced the creation of the International Partnership on Avian and Pandemic Influenza. The Partnership brings together nations and international organizations to improve global readiness by:

On October 5, 2005, Democratic Senators Harry Reid, Evan Bayh, Dick Durbin, Ted Kennedy, Barack Obama, and Tom Harkin introduced the Pandemic Preparedness and Response Act as a proposal to deal with a possible outbreak. [Senate.gov]

On October 27, 2005, the Department of Health and Human Services awarded a $62.5 million contract to Chiron Corporation to manufacture an avian influenza vaccine designed to protect against the H5N1 influenza virus strain. This followed a previous awarded $100 million contract to sanofi pasteur, the vaccines business of the sanofi-aventis Group, for avian flu vaccine.

In October 2005, President Bush urged bird flu vaccine manufacturers to increase their production. [BBC News]

On November 1, 2005 President Bush unveiled the National Strategy To Safeguard Against The Danger of Pandemic Influenza [Whitehouse.gov]. He also submitted a request to Congress for $7.1 billion to begin implementing the plan. The request includes $251 million to detect and contain outbreaks before they spread around the world; $2.8 billion to accelerate development of cell-culture technology; $800 million for development of new treatments and vaccines; $1.519 billion for the Departments of Health and Human Services (HHS) and Defense to purchase influenza vaccines; $1.029 billion to stockpile antiviral medications; and $644 million to ensure that all levels of government are prepared to respond to a pandemic outbreak. [State.gov]

On 06 March 2006, Mike Leavitt, Secretary of Health and Human Services, said U.S. health agencies are continuing to develop vaccine alternatives that will protect against the evolving avian influenza virus. [State.gov]

The U.S. government, bracing for the possibility that migrating birds could carry a deadly strain of bird flu to North America, plans to test nearly eight times as many wild birds starting in April 2006 as have been tested in the past decade. [USA Today]

On 08 March 2006, Dr. David Nabarro, senior U.N. coordinator for avian and human influenza, said that given the flight patterns of wild birds that have been spreading avian influenza (bird flu) from Asia to Europe and Africa, birds infected with the H5N1 virus could reach the Americas within the next six to 12 months. [State.gov]

"Jul 5, 2006 (CIDRAP News) – In an update on pandemic influenza preparedness efforts, the federal government said last week it had stockpiled enough vaccine against H5N1 avian influenza virus to inoculate about 4 million people and enough antiviral medication to treat about 6.3 million." [CIDRAP] article '' HHS has enough H5N1 vaccine for 4 million people'' published July 5, 2006

Further reading

Sources and notes

 

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