Flight Paths of Death

On Nov. 1, President Bush asked Congress for $7.1 billion to prepare the United States for an avian flu pandemic.

But is that too little too late?

While the US Department of Health and Human Services revealed plans for possible travel restrictions and closing of schools to limit the spread of the virus should there be a widespread outbreak in the US, the kind of travel that can't be controlled may bring avian flu here.

"The president's announcement is a first step in the right direction. However, the administration has been slow to react. Knowledge of this virus and the dire potential has been in the scientific community for years,” Dr. David J. Moriarty, a Cal Poly Pomona biology professor, wrote in an email.

“The last plan that I saw was for vaccine for 20 million people, and we have about 300 million in the United States,” Moriarty continued. “The plan also places a large burden on state government, which will be difficult for states to meet, particularly those states already devastated by hurricanes. A problem at this level requires an aggressive, comprehensive response at the federal level."

Caltech microbiologist Alice Huang also expressed dismay at the president's current plan.

"To focus the nation on one disease and provide money to stockpile drugs and vaccines is a good start. Unfortunately, only 20 million individuals out of a country of some 300 million will be protected. That leaves out the question of control and distribution,” Huang noted. “Moreover, the production of drugs and vaccines will need to be ramped up considerably."

Huang explained, “When resources are limited, it becomes clear that not all individuals will have equal access to the resource. In the case of the flu vaccine, it will have to be decided by someone as to where, when and with whom the vaccine would do the most good. If the deployment is not carefully considered, having 20 million doses of the vaccine may not do any good at all."

How, indeed, when last year flu shot supplies fell short and this year the flu shot isn't readily available either? In both cases, the viruses targeted are less deadly than severe acute respiratory syndrome, SARS, or the avian flu.

Historic warnings

Recent signs of dangerous bird flu came before 1997, when an outbreak in Hong Kong poultry infected 18 people there, killing six. But the first warnings came earlier than that.

Professor Jim Strauss, a virologist at Caltech, wrote via email that it was learned years ago that the world’s reservoir of influenza was waterfowl, with birds being the ultimate source of the disease. Strauss explained that there are 15 types of hemagglutinin (H1 to H15) and nine of neuraminidase (N1 to N9). These are the surface glycoproteins of flu, and all are present in waterfowl.

Until recently it was thought that only H1, H2, or H3 strains were capable of causing disease in humans. “What has changed are the recent fatal cases of H5N1 flu in Asia showing that H5 virus is capable of causing severe disease in humans, and the recent spread of H5N1 virus over very wide areas that increases the probability that mutant viruses capable of spreading in humans might arise,” Strauss wrote.

“Further, the recent determination of the complete sequence of the 1918 flu showing how a bird flu can mutate to spread in humans has told us that some of the mutations required to adapt to humans have already occurred in the H5N1 strain currently spreading in birds," he wrote.

Dr. Robert G. Webster discovered in 1957 that the Asian flu virus was the strain of virus that had been carried by certain birds years before. That was four decades ago, when not many people thought much of his conclusions.

More recently, Huang, wife of Caltech President Dr. David Baltimore, wrote in a November 2004 letter to Merck Vaccines President Dr. Adel Mahmoud, that “particularly with the increasing regularity of the avian H5 and H7 strains crossing into humans and pigs, I feel I have the responsibility to support Rob Webster.

“Nature is giving us ample warnings with these crossovers; the first was given in 1997. It is time to act and to take the multiple avian influenza threats seriously."

Webster, a microbiologist originally from New Zealand, is currently at St. Jude's Children's Research Hospital in Memphis. If people weren't listening before, they are listening now.

"The virus can infect people," Moriarty stated, "but at this point, transmission to people requires close contact with birds for a prolonged time period. The real danger comes when the virus in an infected person either mutates and/or combines with a human virus into a form that can easily be transmitted from person to person."

According to the Centers for Disease Control, CDC, birds become infected by contact with contaminated saliva, nasal secretions and feces from other birds.

But, "how the H5N1 virus is spreading is still unknown,” Strauss said. “Migratory birds may be responsible in whole or in part. But some believe this is it being spread by the movement of infected domestic fowl."

SARS and avian flu

SARS may have served as a major warning sign in 1997, but SARS and avian flu differ in several significant ways.
First, "SARS virus and influenza belong to different virus families,” Strauss explained. “SARS is a coronavirus and is in the same family as human coronavirus that causes about 25 percent of common colds. It has a very large RNA genome, about 30,000 nucleotides, in one piece that is a messenger RNA. The many strains of influenza comprise a different family. The genome is in eight pieces of RNA that sum to about 14,000 nucleotides of anti-messenger sense RNA. Perhaps this is more than you want to know about the details of these viruses but the fact that one virus has messenger sense RNA, called plus sense, and the other anti-messenger sense, called minus sense, means that the details of their replication inside cells differ in many fundamental ways. Further, the reservoir of SARS virus is bats, whereas that of flu is birds."

Bats aren't known for great migratory paths. Birds are. SARS may have been our 1997 wake-up call, but, Huang stated, "There were very few SARS deaths compared to the annual influenza virus-caused deaths worldwide, even when we do not have a pandemic. So the media did indeed create hysteria surrounding the SARS cases. In the case of the avian flu, I think the warnings in the media have been warranted."

The current avian flu that everyone is so worried about has shown ability to cross over to both pigs and humans with mortality rates that are as high as 50 percent, Huang said.

"The avian flu is carried by wild migrating birds that can distribute over thousands of miles,” Huang observed. “When the virus adapts to transmission from humans to humans [which has not occurred to any great extent yet], it will become more easily transmitted than SARS and is already more deadly in humans than the SARS coronavirus."
Because of this communicability, proposed travel restrictions might be futile. "Travel should not be limited until there is an indication that the pandemic has started in a localized area or country. If it is not localized due to wide distribution of the virus by migratory birds, then limiting travel will do little good."

Moriarty, who was part of a study of bird species seen in the wild lands of Cal Poly Pomona, including some species that use it as a part of their migratory flights, stated that “Avian flu is a real threat.”

The virus is already found in Asia and parts of Europe, “and it is highly likely that birds in the New World will become infected soon, if they aren't already infected,” Moriarty wrote.

Reports in Asia pinpoint Cambodia, Tibet, Indonesia, Kazakhastan, Malaysia, Mongolia, Siberia, Thailand and Vietnam. In Europe, Turkey and Romania are major hotspots.

There are no regular migratory birds that cross in large numbers from those areas to North America. But Moriarty noted migrants from Asia occasionally appear in North America, primarily in the far north, across the Bering Sea.

“Migrant [birds] from Europe/Africa also occasionally cross the Atlantic,” Moriarty said. “These events are not large in number, but they happen regularly.”

Pirates of the New Millennium

In its official online statement regarding avian flu, the US Fish and Wildlife Service warns that although no wild bird samples in Alaska showed signs of H5N1 from 1998 to 2004, it is likely H5N1 will come to Alaska as early as this fall or winter via birds migrating from Asia.

What the USFWS doesn't say is this might not be the biggest threat, especially to Los Angeles County.
"In my view," Moriarty wrote, "a bigger threat is the substantial illegal trade of birds. Birds are smuggled into North America from all over the world."

United Press International, UPI, reported customs officials blame Great Britain’s first avian flu on an alleged $7 million bird smuggling operation. An orange-winged Amazon parrot died and by Oct. 30 was confirmed as having the H5N1 strain of avian flu. Far worse, 32 birds had died before that particular bird and others showed sings of the virus.

A year to the day before that, US Border Patrol agents stopped a Los Angeles resident who later pleaded guilty to federal charges related to the smuggling of 45 parrots, including lilac-crowned and red-headed Amazons.

Such parrots could carry psittacosis, which can transmit to humans, or Exotic Newcastle Disease, a fatal viral disease affecting all species of bird and considered one of the most infectious diseases of poultry in the world. END is so virulent that many birds die without showing any clinical signs, and a death rate of nearly 100 percent can occur, according to the California Department of Food and Agriculture. California, which is the nation's third-largest egg producer (Southern California having a major stake in that industry), declared a state of emergency in January 2003 because of Newcastle, resulting in the destruction of thousands of birds in California and Baja California.

The quarantine zone included Santa Barbara, Ventura, Los Angeles, Orange, Riverside, San Bernardino, Imperial and San Diego counties and the southeastern part of Kern County. The US Department of Agriculture lifted the nationwide ban in September 2003.

Will we be prepared?

Huang cautioned that the planning for, production of and distribution of vaccines "takes time, and we may or may not have this time. Luckily this focus has made many local municipalities more aware of the necessity for making plans for distribution of drugs and vaccines, as well as maintaining hospital resources and personnel in case of an actual flu pandemic. It will also be important to develop some quarantine procedures and to educate the population about dealing with the pandemic on an individual basis.”

Huang added that first responders and hospital personnel should know exactly what their responsibilities should be and prepare for them before a pandemic hits. “Personally,” she noted, “individuals should not handle sick or dead birds without wearing gloves and masks. The animals should be promptly disposed of in a plastic bag or handed over to public health officials for diagnosis. During a pandemic, it would be wise to wash hands often, avoid large crowds and crowded environments, and to wear masks. In caring for an influenza-stricken person, it would be wise to be gowned, masked and gloved."

Strauss acknowledged that a vaccine can be made quickly since there has been much experience in producing flu vaccines every year. But, he wrote, there exist problems in capacity, in regulations and in legal liability.

“To make a vaccine that could be made available to almost 300 million Americans is an enormous undertaking,” Strauss stressed. “Because of the legal system in this country, our capacity to make vaccines is quite limited because vaccine manufacturers have been driven away, and manufacturing vaccine in Europe, for example, as is done with most of the flu vaccine today, will not protect Americans if there is a big epidemic because those countries will want to protect their own population first.

“The Bush administration wants to contract out vaccine manufacturing to American companies, but capacity is limited,” Strauss continued. “There is the further problem that no vaccine manufacturer will agree to make such a vaccine unless there is a ready market for it [the government will have to pay upfront and may even have to pay for expansion of facilities] and they are protected from legal liability [which the Bush administration has proposed to Congress]. There is even one silly regulatory problem. The Bush administration has proposed that American companies manufacture vaccine and store it until such time as it might be needed and have agreed to pay upfront for the vaccine, which we hope will never be needed. But SEC regulations decree that revenue from vaccine manufacture cannot be recognized until the product is shipped to the doctors that administer it. This will have to be changed before companies will manufacture such a contingent vaccine."

Avian flu H5N1 will come to North America soon and not all the pieces have been put into place.

As was the case with Hurricane Katrina, the avian flu is a disaster waiting to happen.