He said that the culling method recommended in Indonesia was developed from the experience of developing countries, where poultry raising is very concentrated in almost factory-type situations. But in Indonesia there are millions of chickens that live in backyards.

(text slightly edited for better understandability - original on xinhuanet)

- - - -

SCIENTIFIC AMERICAN
FEATURE ARTICLE
November 2005 issue

SPECIAL REPORT - see original here

Preparing for a Pandemic

One day a highly contagious and lethal strain of influenza will sweep across all humanity, claiming millions of lives. It may arrive in months or not for years--but the next pandemic is inevitable. Are we ready?

By W. Wayt Gibbs and Christine Soares

When the levees collapsed in New Orleans, the faith of Americans in their government's ability to protect them against natural disasters crumbled as well. Michael Chertoff, the secretary of homeland security who led the federal response, called Hurricane Katrina and the flood it spawned an "ultracatastrophe" that "exceeded the foresight of the planners."

But in truth the failure was not a lack of foresight. Federal, state and local authorities had a plan for how governments would respond if a hurricane were to hit New Orleans with 120-mile-per-hour winds, raise a storm surge that overwhelmed levees and water pumps, and strand thousands inside the flooded city. Last year they even practiced it. Yet when Katrina struck, the execution of that plan was abysmal.

The lethargic, poorly coordinated and undersized response raises concerns about how nations would cope with a much larger and more lethal kind of natural disaster that scientists warn will occur, possibly soon: a pandemic of influenza. The threat of a flu pandemic is more ominous, and its parallels to Katrina more apt, than it might first seem. The routine seasonal upsurges of flu and of hurricanes engender a familiarity that easily leads to complacency and inadequate preparations for the "big one" that experts admonish is sure to come.

The most fundamental thing to understand about serious pandemic influenza is that, except at a molecular level, the disease bears little resemblance to the flu that we all get at some time. An influenza pandemic, by definition, occurs only when the influenza virus mutates into something dangerously unfamiliar to our immune systems and yet is able to jump from person to person through a sneeze, cough or touch.

Flu pandemics emerge unpredictably every generation or so, with the last three striking in 1918, 1957 and 1968. They get their start when one of the many influenza strains that constantly circulate in wild and domestic birds evolves into a form that infects us as well. That virus then adapts further or exchanges genes with a flu strain native to humans to produce a novel germ that is highly contagious among people.

Some pandemics are mild. But some are fierce. If the virus replicates much faster than the immune system learns to defend against it, it will cause severe and sometimes fatal illness, resulting in a pestilence that could easily claim more lives in a single year than AIDS has in 25. Epidemiologists have warned that the next pandemic could sicken one in every three people on the planet, hospitalize many of those and kill tens to hundreds of millions. The disease would spare no nation, race or income group. There would be no certain way to avoid infection.

Scientists cannot predict which influenza strain will cause a pandemic or when the next one will break out. They can warn only that another is bound to come and that the conditions now seem ripe, with a fierce strain of avian flu killing people in Asia and infecting birds in a rapid westward lunge toward Europe. That strain, influenza A (H5N1) does not yet pass readily from one person to another. But the virus is evolving, and some of the affected avian species have now begun their winter migrations.

As a sense of urgency grows, governments and health experts are working to bolster four substantial lines of defense against a pandemic: surveillance, vaccines, containment measures and medical treatments. The U.S. plans to release by October a pandemic preparedness plan that surveys the strength of each of these barricades. Some failures are inevitable, but the more robust those preparations are, the less humanity will suffer. The experience of Katrina forces a question: Will authorities be able to keep to their plans even when a large fraction of their own workforce is downed by the flu?

Surveillance: What Is Influenza Up to Now?

Our first defense against a new flu is the ability to see it coming. Three international agencies are coordinating the global effort to track H5N1 and other strains of influenza. The World Health Organization (WHO), with 110 influenza centers in 83 countries, monitors human cases. The World Organization for Animal Health (OIE, formerly the Office International des …pizooties) and the Food and Agriculture Organization (FAO) collect reports on outbreaks in birds and other animals. But even the managers of these surveillance nets acknowledge that they are still too porous and too slow.

Speed is of the essence when dealing with a fast-acting airborne virus such as influenza. Authorities probably have no realistic chance of halting a nascent pandemic unless they can contain it within 30 days. The clock begins ticking the moment that the first victim of a pandemic-capable strain becomes contagious.

The only way to catch that emergence in time is to monitor constantly the spread of each outbreak and the evolution of the virus's abilities. The WHO assesses both those factors to determine where the world is in the pandemic cycle, which a new guide issued in April divides into six phases.

The self-limiting outbreaks of human H5N1 influenza seen so far bumped the alert level up to phase three, two steps removed from outright pandemic (phase six). Virologists try to obtain samples from every new H5N1 patient to scout for signs that the avian virus is adapting to infect humans more efficiently. It evolves in two ways: gradually through random mutation, and more rapidly as different strains of influenza swap genes inside a single animal or person.

The U.S. has a sophisticated flu surveillance system that funnels information on hospital visits for influenzalike illness, deaths from respiratory illness and influenza strains seen in public health laboratories to the Centers for Disease Control and Prevention in Atlanta. "But the system is not fast enough to take the isolation or quarantine action needed to manage avian flu," said Julie L. Gerberding, the CDC director, at a February conference. "So we have been broadening our networks of clinicians and veterinarians."

In several dozen cases where travelers to the U.S. from H5N1-affected Asian countries developed severe flulike symptoms, samples were rushed to the CDC, says Alexander Klimov of the CDC's influenza branch. "Within 40 hours of hospitalization we can say whether the patient has H5N1. Within another six hours we can analyze the genetic sequence of the hemagglutinin gene" to estimate the infectiousness of the strain. (The virus uses hemagglutinin to pry its way into cells.) A two-day test then reveals resistance to antiviral drugs, he says.

The next pandemic could break out anywhere, including in the U.S. But experts think it is most likely to appear first in Asia, as do most influenza strains that cause routine annual epidemics. Aquatic birds such as ducks and geese are the natural hosts for influenza, and in Asia many villagers reside cheek by bill with such animals. Surveillance in the region is still spotty, however, despite a slow trickle of assistance from the WHO, the CDC and other organizations.

A recent H5N1 outbreak in Indonesia illustrates both the problems and the progress. In a relatively wealthy suburb of Jakarta, the eight-year-old daughter of a government auditor fell ill in late June. A doctor gave her antibiotics, but her fever worsened, and she was hospitalized on June 28. A week later her father and one-year-old sister were also admitted to the hospital with fever and cough. The infant died on July 9, the father on July 12.

The next day an astute doctor alerted health authorities and sent blood and tissue samples to a U.S. Navy medical research unit in Jakarta. On July 14 the girl died; an internal report shows that on this same day Indonesian technicians in the naval laboratory determined that two of the three family members had H5N1 influenza. The government did not acknowledge this fact until July 22, however, after a WHO lab in Hong Kong definitively isolated the virus.

The health department then readied hospital wards for more flu patients, and I Nyoman Kandun, head of disease control for Indonesia, asked WHO staff to help investigate the outbreak. Had this been the onset of a pandemic, the 30-day containment window would by that time have closed. Kandun called off the investigation two weeks later. "We could not find a clue as to where these people got the infection," he says.

Local custom prohibited autopsies on the three victims. Klaus Stˆhr of the WHO Global Influenza Program has complained that the near absence of autopsies on human H5N1 cases leaves many questions unanswered. Which organs does H5N1 infect? Which does it damage most? How strongly does the immune system respond?

Virologists worry as well that they have too little information about the role of migratory birds in transmitting the disease across borders. In July domestic fowl infected with H5N1 began turning up in Siberia, then Kazakhstan, then Russia. How the birds caught the disease remains a mystery.

Frustrated with the many unanswered questions, Stˆhr and other flu scientists have urged the creation of a global task force to supervise pandemic preparations. The OIE in August appealed for more money to support surveillance programs it is setting up with the FAO and the WHO.

"We clearly need to improve our ability to detect the virus," says Bruce G. Gellin, who coordinates U.S. pandemic planning as head of the National Vaccine Program Office at the U.S. Department of Health and Human Services (HHS). "We need to invest in these countries to help them, because doing so helps everybody."

Vaccines: Who Will Get Them - and How Quickly?

Pandemics of smallpox and polio once ravaged humanity, but widespread immunization drove those diseases to the brink of extinction. Unfortunately, that strategy will not work against influenza--at least not without a major advance in vaccine technology.

Indeed, if an influenza pandemic arrives soon, vaccines against the emergent strain will be agonizingly slow to arrive and frustratingly short in supply. Biology, economics and complacency all contribute to the problem.

Many influenza strains circulate at once, and each is constantly evolving. "The better the match between the vaccine and the disease virus, the better the immune system can defend against the virus," Gellin explains. So every year manufacturers fashion a new vaccine against the three most threatening strains. Biologists first isolate the virus and then modify it using a process called reverse genetics to make a seed virus. In vaccine factories, robots inject the seed virus into fertilized eggs laid by hens bred under hygienic conditions. The pathogen replicates wildly inside the eggs.

Vaccine for flu shots is made by chemically dissecting the virus and extracting the key proteins, called antigens, that stimulate the human immune system to make the appropriate antibodies. A different kind of vaccine, one inhaled rather than injected, incorporates live virus that has been damaged enough that it can infect but not sicken. The process requires six months to transform viral isolates into initial vials of vaccine.