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Necessary pandemic milestone: first documented H5N1 human to human transmission


Indonesia has first documented H5N1 human to human transmission. While there is identifiable genetic mutation between host and victim, it is not at this time significantly adapted to human infection:

The family members in the cluster had a banquet in late April, when the vegetable merchant was already ill and coughing heavily. Some spent the night in the same small room with her. Some members also cared for their relatives when they were sick… The first five family members to fall ill had identical strains of H5N1, one that is common in animals in Indonesia. But the virus mutated slightly in the sixth victim, the 10-year-old boy, and he apparently passed the mutated virus to his father. The presence of that mutation allowed the lab to confirm the route of transmission.

Not yet a pandemic, but another signpost on the road towards its possibility.

The cross-reactive immunity (protection that a virus vaccine confers against the original virus as well as variants of the original virus) against current H5N1 recently announced by St. Jude Children's Research Hospital may be none too soon. Not yet tested in humans, this clinical trial in ferrets is a step towards the use of a human "stockpiled vaccine until a vaccine against the specific variant causing the outbreak is developed… So our success with ferrets is extremely promising news":

Scientists at St. Jude Children’s Research Hospital have announced that a vaccine they developed a few years ago against one antigenic variant of the avian influenza virus H5N1 may protect humans against future variants of the virus. Vaccines based on this model might therefore be suitable for stockpiling for use during a pandemic (worldwide epidemic) until a new vaccine could be developed specifically against the variant causing the outbreak, the researchers said. An antigen is a molecule that stimulates production of antibodies by the immune system…

The researchers showed that the vaccine completely protected ferrets from a lethal nasal infection against not only the original virus the vaccine was made to thwart, but also against a newer variant that has already proved fatal to humans. The ferrets experienced a more significant reduction of virus multiplication than otherwise would have occurred, the researchers reported. Moreover, the infections failed to spread out of the upper respiratory tract to the lungs or brain.

"These findings are especially significant because ferrets are known to be an excellent and accurate model of influenza infection and immune response in humans," said Elena Govorkova, Ph.D., a staff scientist in the Department of Infectious Diseases at St. Jude. "Restricting the infection to the upper respiratory tract is important since in humans the virus has been isolated from specimens taken from the cerebrospinal fluid, feces, throat and blood serum. Therefore, limiting the spread of virus in an infected human is crucial to saving that person’s life." Govorkova is the lead author of the JID paper and led the research team conducting the study.

Successful cross-reactive immunity for H5N1 would be a major milestone in H5N1 response. For those wishing to understand the issue, I suggest Second WHO meeting on the development of influenza vaccines that induce broad spectrum and long-lasting immune responses and Modeling Influenza Epidemics and Related Issues (text, not the equations). Other related items in the citation list below.

Indonesia is already one of the "have nots" in terms of lacking a prophylactic tripwire treatment for an H5N1 pandemic:

Richer countries facing little immediate avian-flu danger are stockpiling vast amounts of the drug needed to fight the current outbreak and possibly forestall the pandemic. Asian nations at the epicenter of the threat are seriously short of the drug. It is a familiar problem in global health care. Life-saving drugs for infectious diseases that also pose world-wide threats -- AIDS, tuberculosis, influenza -- rarely reach poorer countries where they are often needed most. The flu drug, known as Tamiflu, has shown strong results in lab tests…

A worried WHO [World Health Organization] has urged countries to prepare for the threat of a pandemic partly by stocking up on Tamiflu… Scientists believe that if Tamiflu is quickly supplied at the site of an initial pandemic outbreak, it could help to contain the bug for as long as six months or even eliminate it. Those six months are exactly what researchers would need to develop a vaccine based on the pandemic strain that emerges.

The WHO recommends that countries in the area hit by avian flu stockpile enough Tamiflu to cover 25 percent of their populations. But Asian nations have lagged behind others in ordering the drug because of its relatively high cost, about $3.90, or 3 euros, a capsule…

Continuing this imbalance, the "massive effort" to "upgrade veterinary systems, launch vaccination drives and help educate people about hygienic ways to raise animals" agreed to by developed countries in January 2006 has fallen short again, with only $286 million has been paid against pledges of near $1.9 billion:

Since that meeting in January, the H5N1 avian influenza virus has spread out of Asia, across Europe and into Africa. It has not always affected commercial poultry but has killed or forced the culling of tens of millions of more birds. In January, the virus had killed 79 people, all of them in Asia. Now it has infected at least 224 people in 10 countries, and killed 127 of them, according to the World Health Organization. Experts fear it could mutate at any time into a strain that could pass easily from one person to another, sparking a pandemic that would travel around the globe in weeks or months.

Businesses have little choice but to revisit their contingency plans as the implications for inaction and lack of preparation are astounding:

Current models, based on seasonal influenza and the three 20th-century flu pandemics, suggest that a new and highly contagious virus strain would spread across the United States in about five weeks. It would affect communities for six to eight weeks before receding. There would probably be at least two waves, separated by months.

At least a third of the population is likely to become ill in each wave, with peak absenteeism somewhat higher, about 40 percent of the workforce. Depending on the strain's virulence, 900,000 to 10 million people might be hospitalized, and 200,000 to 2 million might die.

Given this scenario, the consultants say, companies should expect that a pandemic will kill some employees, temporarily cripple workforces, sow confusion and fear, and force people to make harrowing decisions between allegiances to work or family. It would make communication difficult, threaten supply chains, and probably interrupt production of goods and delivery of services.


We are now at level 3 on the escalation hierarchy:

  1. Inter-pandemic phase: Low risk of human cases
  2. New virus in animals, no human cases: Higher risk of human cases
  3. Pandemic alert, New virus causes human cases: No or very limited human-to-human transmission
  4. Pandemic alert, New virus causes human cases: Evidence of increased human-to-human transmission
  5. Pandemic alert, New virus causes human cases: Evidence of sustained human-to-human transmission
  6. Pandemic, Efficient and sustained human-to-human transmission

The lessons of SARS have been conveniently forgotten by most; we created a hierarchy of supply chain and services collapse for avian flu based upon our SARS event monitoring. See:

Yet we remain on the cusp of a "global blizzard of potentially 12 to 18 months' duration." Here is testimony by Michael Osterholm, Director, Center for Infectious Disease Research and Policy:

I firmly believe that based on our past experiences with outbreaks such as SARS and even the post-9/11 anthrax attack, that if an influenza pandemic began today, borders will close, the global economy will shut down, pharmaceutical supplies, including drugs and very important childhood vaccines will be in extreme short supply, healthcare systems will be overwhelmed and panic will reign. Access to pandemic influenza vaccines and effective antiviral drug treatments will be limited for the entire world for years to come because of our lack of modern technology vaccines and a grossly inadequate worldwide production capability. To minimize the fallout of a pandemic during this time, the industrialized world must create a detailed response strategy far beyond just enhancing influenza vaccines and treatment drugs, and one that involves both the public and private sectors. In addition, we can no longer assume that business continuity plans for both our multinational companies and small businesses, largely based on a concept of a regional event of a limited duration, will approximate the actual impact and consequence of an influenza pandemic. Rather, I believe an influenza pandemic will be like a 12 to 18 month global blizzard that will ultimately change the world as we know it today. This will occur even if we experience a milder worldwide pandemic of millions of deaths rather than many millions of deaths.

Let's do hope that the research on cross-reactive immunity bears fruit in human tests and that the resulting vaccine can be reasonably mass produced. Alternatives beyond that of chance are few. As Deming was fond of saying, "It is not necessary to change. Survival is optional."

Bird Flu Passed From Son to Father, W.H.O. Says
New York Times
June 23, 2006

H5N1 Vaccine Could Be Basis For Life-saving Stockpile Against Possible Bird Flu Outbreak
Science Daily
Source: St. Jude Children's Research Hospital
Posted: June 20, 2006

H5N1 Avian Influenza
Overview, Prevention and Mitigation, Business Responses
Overseas Security Advisory Council (SAC)
16 June, 2006

Less than $300 mln spent on bird flu - World Bank
By Lesley Wroughton and Maggie Fox
Reuters AlertNet
04 Jun 2006 14:11:00 GMT

Rich Countries Hoard Flu Drug, Poor Run Short
World Bank Press Review []
Press Review for May 18 2005

Business Plan for a Pandemic?
Most Firms Haven't Prepared for Possibility Of a Global Outbreak
By David Brown
Washington Post
May 2, 2006

Is Business Ready for a Flu Pandemic?
New York Times
March 16, 2006

Avian Flu: Addressing the Global Threat
Michael T. Osterholm, PhD, MPH
Director, Center for Infectious Disease Research and Policy
Associate Director, DHS National Center for Food Protection and Defense
Professor, School of Public Health
Testimony Before the House Committee On International Relations
December 7, 2005

Second WHO meeting on the development of influenza vaccines that induce broad spectrum and long-lasting immune responses
Initiative for Vaccine Research (IVR)
WHO HQ Geneva
6-7 December 2005

Modeling Influenza Epidemics and Related Issues
Carlos Castillo-Chavez et al
Mathematical and Theoretical Biology Institute (MTBI)
Arizona State University

Variola Virus and Other Orthopoxviruses
Chapter 2

Mathematical Studies of Parasitic Infection and Immunity
Roy M. Anderson
Science, Vol 264
24 June, 1994

Gordon Housworth

InfoT Public  Strategic Risk Public  


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