By Donald G. McNeil Jr., The New York Times – Last year, for the first time since avian flu emerged as a global threat, the number of human cases was down from the year before. As the illness receded, the scary headlines — with their warnings of a pandemic that could kill 150 million people — all but vanished.

But avian flu has not gone away. Nor has it become less lethal or less widespread in birds. Experts argue that preparations against it have to continue, even if the virus’s failure to mutate into a pandemic strain has given the world more breathing room.

There were 86 confirmed human cases last year compared with 115 in 2006, according to the World Health Organization, and 59 deaths compared with 79. Experts assume that the real numbers are several times larger, because many cases are missed, but that is still a far cry from a pandemic.

Dr. David Nabarro, the senior United Nations coordinator for human and avian flu, recently conceded that he worried somewhat less than he did three years ago. “Not because I think the threat has changed,” he quickly added, but because the response to it has gotten so much better.”

The world is clearly more prepared. Vaccines have been developed. Stockpiles of Tamiflu and masks have grown. Many countries, cities, companies and schools have written pandemic plans. The European Center for Disease Prevention and Control, created in Stockholm in 2005, just estimated that the European Union needed “another two to three years of hard work and investment” to be ready for a pandemic, but that is improving because previous estimates were for five years.

In the worst-hit countries — all poor — laboratories have become faster at flu tests. Government veterinarians now move more quickly to cull chickens. Hospitals have wards for suspect patients, and epidemiologists trace contacts and treat all with Tamiflu — a tactic meant to encircle and snuff outbreaks before the virus can adapt itself to humans.

Bernard Vallat, director general of the World Organization for Animal Health, recently called the virus “extremely stable” and, thus, less likely to mutate into a pandemic form. Many prominent virologists would vehemently disagree. But others who argued three years ago that H5N1 would not “go pandemic” are feeling a bit smug.

Dr. Paul A. Offit, a vaccine specialist at Children’s Hospital in Philadelphia, was one of those who, he jokes, “dared to be stupid” by bucking the alarmist trend in 2005.

“H5 viruses have been around for 100 years and never caused a pandemic and probably never will,” he said.

But Dr. Offit said he backed all preparedness efforts because he expected another pandemic from an H1, H2 or H3, the subtypes responsible for six previous epidemics, including the catastrophic one in 1918.

“What I worry is that this has been a ‘boy who cried wolf’ phenomenon,” he said. “When the next pandemic comes, people will say, ‘Yeah, yeah, we heard that last time.’ ”

Some who were Cassandras in 2005 still are.

The fact that human cases fell slightly last year is “pretty much meaningless,” argued Michael T. Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota. The virus is still circulating and has evolved 10 clades and hundreds of variants.

World preparations thus far are “incremental,” he said, “like sending 10 troops to a war when you need 10,000.”

He noted that the H3N8 flu found in horses in the 1960s took 40 years to adapt to dogs, but that since 2004 it has spread to kennels all over the country.

The most worrisome aspect of H5N1, virtually all scientists agree, is that it persists in birds without becoming less lethal to them.

“This is the most serious bird flu virus that has ever been known,” Dr. Nabarro said. “By 2007, it was in 60 countries. It must be dealt with.”

Despite the culling of hundreds of millions of birds and the injection of billions of doses of poultry vaccine, the virus is out of control in some of the most populous countries — though exactly which ones are in dispute, because some are touchy about conceding that they cannot rid their flocks of it.

Dr. Vallat has named three countries where it is now endemic in local birds: Egypt, Indonesia and Nigeria.

Dr. Nabarro added Bangladesh, Vietnam and parts of China. Reports of recurrent outbreaks also persist in parts of India, Myanmar and Pakistan. Last week, villagers in India were reported to be killing and eating their flocks before government cullers, who paid less than a third of market value, could seize them.

Dr. Henry L. Niman, a biochemist in Pittsburgh whose Web site tracks mutations, argues that there is a separate reservoir in wild birds that extends across Eurasia. Late each fall, fresh outbreaks appear across Europe and down into the Middle East as geese and swans migrate from Asia toward Africa.

In December, dying birds were found in Poland and Russia, in Saudi Arabia and even in a kindergarten petting zoo in Israel.

On Jan. 8, it reached one of England’s most famous swan-breeding grounds, the Abbotsbury Swannery, which has been around since the 11th century.

The Western Hemisphere is in less danger, according to a study published in the journal PloS Pathogens, which analyzed viruses found in migratory birds sampled from 2001 to 2006 in Alberta and along the Jersey Shore. It found that none carried whole viruses from Eurasian bird pathways.

Therefore, the authors argued, it is more likely that any importation of the virus would be in “birds moved legally or illegally by humans.”

It may be even more likely that a human will be the first carrier. There was a close call in early December, when six members of one family in northern Pakistan fell ill, probably infected by a brother who had culled sick poultry.

Another brother, who lived on Long Island, went to Pakistan for the funeral and felt sick when he returned home. He turned out not to have H5N1, but it showed how easily the virus could have reached the Western Hemisphere.
Pakistan had its first human cases last year, as did Laos, Myanmar and Nigeria.

Many small mutations have been recorded that seem to make the virus more adaptable to humans and more resistant to known drugs, but no combination of those producing a superstrain has yet emerged.

Ninety percent of cluster cases have been among blood relatives, and Dr. Arnold S. Monto, an avian flu expert at the University of Michigan School of Public Health, said that suggested a genetic susceptibility that has not yet been defined.

It has long been known that the virus has difficulty attaching to receptors in human noses. A team at M.I.T. has refined that, showing that those receptors come in two shapes, cones and umbrellas, and that avian viruses attach more easily to the cones.

Rapid progress has been made in vaccines. The newest, Dr. Monto said, need just small amounts of antigen — 4 micrograms an injection instead of 90 micrograms — making them much more practical to produce.

Some scientists argue for vaccinating millions of people as a precaution. One dose, even if it is based on a three-year-old strain, might protect against death, if not infection. A second, fully protective dose could be made up from whatever strain has gone pandemic.

Right now, said Dr. Klaus Stöhr, who was chief of flu vaccines for the W.H.O. and now does the same for Novartis, it would take manufacturers about one year to produce a billion doses of any vaccine based on a new pandemic strain. But the pandemic would have circled the globe within three months.

“The peak would be over, and, principally, you’d be vaccinating survivors,” Dr. Stöhr said. Switzerland, he added, has a vaccine stockpile and plans to test it on soldiers, police officers and health care workers before deciding whether to offer it to all Swiss.

Because of the American swine flu debacle of 1976, in which a vaccine made against a pandemic that never emerged harmed more people than the flu did, experts say they think it is unlikely that many Americans would be willing to take such precautions.

By Donald G. McNeil Jr., The New York Times – Avian flu in Pakistan nearly touched the United States this month when a 38-year-old Nassau County resident returned from visiting family members who were later confirmed to be part of Pakistan’s first cluster of human infections.

But the resident, who landed at Kennedy International Airport on Dec. 5 and visited his family doctor the next day, tested negative for flu, both at a state laboratory and at the Centers for Disease Control and Prevention, the New York State Health Department and the C.D.C. said.

The cluster of human cases in Pakistan — which apparently began in November — was described last week in Pakistani press reports, which were picked up by flu-watcher Web sites.

But only on Saturday did the World Health Organization say that Pakistan had detected H5N1 virus in eight people, two of whom had died. The H5N1 virus is the strain of avian flu that has international health officials most worried about the threat of a pandemic.

All the cases occurred in the remote North-West Frontier Province, near the Afghan border, where outbreaks of H5N1 in poultry have been reported for months.

Exactly how the Long Island resident was connected to the cluster was vague.

Pakistani media reports said a man who had attended the funerals of his two brothers in late November had returned to the United States. State and federal officials could not confirm that on Monday.

While some reports said he visited his doctor because he felt ill, a State Health Department spokeswoman said he had not.
Another family member on Long Island had flu symptoms even before his relative returned from Pakistan, but both tested negative, the spokeswoman said.

Early local reports of avian flu clusters have routinely been confusing.

The Pakistani cluster appears to be the largest to be detected since May 2006, when seven confirmed cases in one family were found in Karo, a village in Indonesia. Others have occurred in Egypt, Turkey and Azerbaijan. In some cases, limited human-to-human transmission has appeared likely because relatives fell sick well after others had contact with birds.
There have been 340 confirmed cases of H5N1 flu in the world since 2003, 208 of which have been fatal, according to the World Health Organization. There have been fewer cases this year than in 2006, but the flu season has just begun.

The Pakistan press reported that the first case was in a veterinarian in Abbottabad who culled sick birds. He recovered but was reported to have infected two of his brothers, who died. However, the Pakistan government denied that human-to-human transmission had occurred.

India: Bird Flu Spread ‘Alarming’

By Donald G. McNeil Jr., January 19, 2008, The New York Times – India’s third outbreak of avian flu among poultry is the worst it has faced, the World Health Organization said. The chief minister of West Bengal State, which is trying to cull 400,000 birds, called the virus’s spread “alarming.” Uncooperative villagers, angry at being offered only 75 cents a chicken by the government, have been selling off their flocks and throwing dead birds into waterways, increasing the risk. New outbreaks were also reported this week in Iran and Ukraine.

Avian influenza – situation in Indonesia – update 32
21 January 2008

The Ministry of Health of Indonesia has announced a new case of human infection of H5N1 avian influenza. An 8-year-old male from Tangerang District, Banten Province developed symptoms on 7 January 2008, was hospitalized on 16 January and died in an AI referral hospital on 18 January. Investigations into the source of his infection are ongoing, however initial reports indicate the case lived in close proximity to a chicken slaughter house.

Of the 119 cases confirmed to date in Indonesia, 97 have been fatal.

Avian influenza – situation in Egypt – update 3
3 January 2008

The Ministry of Health and Population of Egypt has announced the death of a previously confirmed case of H5N1 infection. The 50 years old female from Domiatt governorate died on 31 December.

Of the 43 cases confirmed to date in Egypt, 19 have been fatal.

Avian influenza – situation in Pakistan – update
27 December 2007

The first case of human infection with H5N1 avian influenza has been confirmed in Pakistan. Laboratory tests conducted by the WHO H5 Reference Laboratory in Cairo, Egypt and WHO Collaborating Center for Reference and Research on Influenza, in London, United Kingdom have confirmed the presence of avian influenza virus strain A(H5N1) in samples collected from one case in an affected family. The H5N1 positive case was a 25 year old male from the Peshawar area who developed febrile respiratory illness on 21 November, was hospitalized on 23 November, and died on 28 November. Additional laboratory analysis, including gene sequencing, is ongoing.

At the request of the Pakistan Government, a WHO team traveled to Pakistan to participate with national authorities in the ongoing investigations of several suspected cases of human H5N1 infections. The following conclusions have been made accordingly:

The preliminary risk assessment found no evidence of sustained or community human to human transmission.
All identified close contacts including the other members of the affected family and involved health care workers remain asymptomatic and have been removed from close medical observation.

The Ministry of Health in Pakistan has taken timely steps to investigate and contain this event including case isolation, contact tracing and monitoring, detailed epidemiological investigations, increasing the availability of personal protective equipment, dedicating hospital facilities for any new suspected cases, and other infection control measures. In addition, agricultural authorities, including the Ministry of Food, Agriculture and Livestock and FAO, have been active technical partners for the effective control of this limited outbreak.

Avian influenza – situation in Myanmar
14 December 2007

The Ministry of Health in Myanmar has confirmed the country’s first case of human infection with the H5N1 avian influenza virus. The case is a 7-year-old female from Kyaing Tone Township, Shan State (East).

The case was detected through routine surveillance following an outbreak of H5N1 in poultry in the area in mid-November. She developed symptoms of fever and headache on 21 November 2007 and was hospitalized on 27 November. She has now recovered. Samples taken from the case tested positive for H5N1 at the National Health Laboratory in Yangon, and the National Institute of Health in Thailand. The diagnosis was further confirmed at the WHO Collaborating Centre for Reference and Research on Influenza, National Institute of Infectious Diseases in Tokyo, Japan.

A team from the Ministry of Health, the Ministry of Livestock and Fisheries and the WHO Country Office are conducting investigations to confirm the source of her infection. Initial findings indicate poultry die off in the vicinity of the case’s home in the week prior to the onset of illness. To date, all identified contacts of the case remain healthy and ongoing surveillance activities in the area have not detected any further cases.

Avian influenza – situation in China – update 5
9 December 2007

The Ministry of Health in China has reported a new case of human infection with the H5N1 avian influenza virus in Jiangsu Province. The case was confirmed by the national laboratory on 6 December.

The 52-year old male is the father of the 24-year old man who died from H5N1 infection on 2 December 2007. He is one of the close contacts placed under medical observation by national authorities. He developed symptoms on 3 December and was sent immediately to hospital for treatment.

Of the 27 cases confirmed to date in China, 17 have been fatal.