Sat, Mar 26, 2005 page9

• Solving the riddle of H5N1

  In part 1 of a two-part story, Mark Honigsbaum went to Vietnam to talk to some of the health experts who have treated people infected with a deadly version of the avian flu virus. In part 2, he examines the growing body of evidence showing that the virus has mutated to allow for human-to-human transmission

  • By Mark Honigsbaum / THE OBSERVER
  • • 
    • 
    • 

  "My whole skull was throbbing," he told me. "I felt like I was going color blind and the walls were pressing in on me."

  Hung was still in the hospital when, on Jan. 19, a chronically backlogged lab finally sent back word that his brother had died of bird flu. Soon after, it was confirmed Hung had it, too.

  "I was quite scared at first, but by then I was starting to feel better. The fever and pain were over and I thought to myself, I'm through the worst," he said.

  

  PHOTO: MOUNTAIN PEOPLE

  Nonetheless, it was a further 10 days before Hung was well enough to be discharged.

  The story of Hung's survival is a riddle -- one that should alarm us but also provides room for comfort and hope.

  The first mystery is how he contracted the virus. Dr Nguyen Tuong Van, director of the emergency ward at Hanoi's Institute for Clinical Research into Tropical Diseases, and the Vietnamese government have taken the position that he got it from ingesting the raw duck's blood pudding. But, aside from his brother who had also slaughtered the duck, thus presumably exposing himself to a massive dose of the virus, no other family members who ate the pudding fell ill.

  Hung's symptoms also did not appear until 14 days after the meal -- far longer, say experts, than the typical three- to seven-day incubation period seen in other cases.

  On hearing of Hung's case, the World Health Organization (WHO) asked the Vietnamese government for nasal swabs and sent the specimens to a laboratory in Tokyo for analysis. But though tests confirmed Hung had H5N1, the specimens were not good enough to allow the WHO to culture the virus and conduct more precise molecular studies which would show whether or not it was identical to the avian strain or had mutated. The WHO is now conducting virulence studies in animals which may answer that.

  "For the moment," says Peter Horby, the WHO's representative in Hanoi. "We cannot rule out the possibility that this was a case of human-to-human transmission."

  The other question is, given that Hung had H5N1 and didn't receive Tamiflu, how did he manage to recover? One answer may be the speed with which he got himself to hospital. In other cases, Van said, where patients have arrived too late and she has had to intubate, only one in 10 have survived. The other key factor may have been Hung's physical fitness.

  "Most people who die of bird flu are poor and not in the best physical condition in the first place," Van said.

  Influenza, which was first recorded in Italy more than 100 years ago, takes its name from the Latin word "influentia," reflecting the then widespread belief that the illness was due to the influence of the stars. But respiratory diseases accompanied by fevers that read very much like influenza are also mentioned by ancient Greek and Roman physicians and it is likely flu has plagued mankind for as long as people have been living in close quarters with chickens and pigs.

  The virus almost certainly began as an infection of birds and in all probability has been harbored by avian populations for millennia.

  But for reasons still poorly understood, since the advent of the industrial revolution these avian viruses have shown an increasing propensity to spread to mammals and infect humans. Now and again, these viral "leaps" spark pandemics.

  The first occurred in December 1889, when the Russian flu suddenly appeared in St. Petersburg and in a matter of months spread across most of the world, killing at least 250,000 Europeans (the total global death toll is unknown, but may have been as high as 1 million).

  And it happened again at the end of World War I, when the so-called Spanish influenza sparked the Great Influenza Pandemic of 1918-1919, killing more than 50 million people worldwide. And it also happened in 1957 in China and in 1968 in Hong Kong -- outbreaks which caused 1 million deaths on each occasion.

  One reason influenza experts are so concerned now is that on average these pandemics have occurred every 27 years -- and it is 37 years since the Hong Kong flu pandemic. Statistically speaking, the next outbreak is 10 years overdue.

  A second reason is that all the signs are that the virus, which has been widespread in Asia for some time and is highly pathogenic in chickens, appears to have acquired the ability to infect new species in just the past few months.

  Indications that H5N1 might be in the process of mutating came last October, when tigers at a zoo near Bangkok who had been fed on raw chicken carcasses suddenly began dying. Prior to last year they had never been susceptible to the avian strain. Since then, vets have shown that cats can also be infected with the virus.

  The third reason for concern is the increasing incidence of concurrent infections within the same family, such as Hung's and his brother's -- what epidemiologists call "family clusters."

  During Tet 2003, Van treated a similar multiple infection involving two sisters, also from Thai Binh Province, whose brother had died of a mysterious pneumonia after slaughtering chickens for a wedding banquet. The brother's body was subsequently cremated, so Van was unable to confirm he'd had H5N1, but 10 days later the sisters fell ill and were admitted to her ward with raging fevers.

  At that point Van had yet to treat anyone with bird flu. However, she and her colleagues had treated several SARS patients the previous year. She also knew from reading about H5N1 outbreaks in Hong Kong that the disease had a rapid onset. Nonetheless, she says she was shocked by how quickly the sisters went into decline. Seven days after she admitted the sisters, Van was forced to intubate.

  Three days later they were both dead, expiring within an hour of one another on the eve of Tet. Tests confirmed they both had H5N1.

  "I was shocked at the speed of it," Van said. "It was like SARS all over again. I wore a mask and protective glasses and insisted my staff do the same."

  But the strongest evidence for human-to-human transmission so far has come from Thailand. Last September, an 11-year-old girl from a remote village, Kamphaeng Phet, fell ill with fever. A few days earlier all her pet chickens had died suddenly. Her aunt rushed her to hospital, where she was joined by the girl's mother, who lived near Bangkok. Within 16 hours the girl was dead and, in keeping with Thai custom, her body was cremated.

  Two weeks later her mother, who had had no exposure to the chickens, was admitted to hospital in Bangkok with the same symptoms. She also died. Then, days later, the aunt also developed a cough and fever. Tests showed that, like her sister, she had H5N1. Unlike her sister, however, she survived.

  The WHO concluded both had almost certainly caught the virus while nursing the sick girl.

  "The worrying thing about the Thai case," Horby said. "Is the girl and her mother lived several miles apart, so they could not have been exposed to a common poultry source. The hospital bedside was the most likely contact."

  For the final piece in the puzzle of the emerging virus, however, I had to travel to Ho Chi Minh City and speak to Jeremy Farrar. A mild-mannered Englishman, Farrar is director of the Oxford University Clinical Research Institute at the Hospital for Tropical Diseases -- a unit funded by the Wellcome Trust. Together with Dr Tran Tinh Hien, the vice-director of the hospital, he has been tracking H5N1 since its inception and has as good a grasp as anyone of how close we are to a viral Armageddon.

  In his office decorated with Vietnamese art and a huge map of the country, Farrar appears the epitome of a tropical disease expert.

  The biggest causes of infant mortality in Vietnam, he tells me, are dengue fever and malaria. But for all that he worries about mosquito-borne diseases, he will never forget his first brush with bird flu.

  As with the latest infections, it occurred during Tet and, once again, a duck was involved.

  "It was the eve of Tet, the last night in the lunar year, a hugely auspicious day in Vietnam," he recalled. "At around 8pm, Dr Hien called me and said that he'd just admitted an eight-year-old girl to hospital with acute pneumonia and could I check her nasal swab for type A influenza."

  Hien had taken a detailed clinical history from the girl and discovered that shortly before she'd fallen ill her duck had died and she'd buried it, then dug it up and reburied it. At that point, Vietnam had only reported one death from bird flu, in Hanoi, but Hien knew enough about the disease to know that ducks might be implicated.

  Farrar immediately ran a PCR (polymerase chain reaction) test. It was positive. The girl had H5N1.

  "Those two weeks over Tet were a frightening time," Farrar said. "At that point we didn't know very much about the virus's clinical pathology. Was it the same as the Hong Kong strain of H5N1 or was it like SARS? Were other family members at risk? Could we catch it?"

  Today, Farrar and Hien are in a better position to answer those questions. In the past two years, they've treated nearly 20 people for bird flu. Although Hien has had nine patients die this year, he is confident that the present strain is not particularly infectious between humans.

  "If H5N1 was like SARS then at least 10 of my staff ought to be dead by now. They're not," he told me in his office, before his ward round.

  "That isn't to say that the disease isn't dangerous. It is," he said.

  "But the main reason we are continuing to see so many deaths is the delay in referring people to hospital," he said.

  Nonetheless, Hien said we cannot afford to be sanguine. The virus could very easily mutate if Vietnam doesn't get the medicines and aid it needs to deal with its infected poultry.

  "The world has to understand it's not only Vietnam's problem, it's the world's problem," he said.

  Farrar also has a further reason for concern. Last month, he and a colleague reported on a disturbing new case of a girl and boy from Dong Thap Province in southern Vietnam, whose deaths last year had been attributed to acute encephalitis -- an inflammation of the brain.

  Neither the nine-year-old girl nor her brother, four, had shown any sign of respiratory illness or pneumonia prior to slipping into comas, but when Farrar received a sample of fluid from the boy's brain he got a big surprise. The fluid was heavily infected with H5N1. Post-mortem samples confirmed it was also in the boy's feces, blood and nose.

  Unfortunately, no tissue samples had been taken from his sister, so Farrar could not confirm whether she had also been infected with H5N1. Nor could he establish where they might have acquired the virus. The family did not keep chickens, but did have healthy fighting cocks. A more likely possibility was a canal near their home, where the girl often swam. It was teeming with ducks and wild geese.

  Although further studies will need to be done to see if H5N1 is implicated in other cases of encephalitis, the implication is clear: bird flu may be much more widespread than we realize.

  "The crucial question is, are we only seeing a small number of cases because we are only looking at patients who present with the most severe symptoms, or is the virus actually much more prevalent than that?" Farrar said. "In other words, is this just a very nasty infection in a few people, or a wide-ranging infection, one that has the potential to become a global pandemic?"

  No one knows where or when the next mutation in the virus will occur. It could be in a duck pond in the Mekong delta tomorrow or it could be a year hence in a poultry market in Thai Binh. But one thing is certain: if the virus does become -- to recall the analogy of John Oxford (a virologist at the Queen Mary and Westfield School of Medicine) -- a normal greyhound, jet travel will speed it round the globe in days.

  During my return flight to London via Bangkok, with passengers sneezing and coughing all around me, I had plenty of time to ponder what this might mean.

  In the last great pandemic in 1918, the absence of air travel and restrictions on movements during wartime meant it took two years for Spanish influenza to spread from crowded army camps in northern France -- where Oxford and other experts now postulate it first gained a foothold, in troops weakened by mustard gas -- to the rest of the world. Then, 50 million people died. Today, given the growth in the world's population, the equivalent death toll would be 175 million.

  Not surprisingly, these figures, coupled with dire warnings from the WHO, have begun to command governments' attention. Two days after I returned from Hanoi, the British Department of Health called a press conference to announce it was stockpiling more than 14 million doses of Tamiflu as part of its Influenza pandemic contingency plan. Meanwhile, the US, France and Italy have been placing advance orders for a prototype vaccine (the British government has resisted this course, pointing out that until we know which strain of H5N1 to vaccinate against such measures are a waste of resources).

  Earlier this month, I called a contact in Hanoi to check on the progress of Sy Tuan and his sister. Miraculously, both were still alive and receiving treatment. But in the meantime, a nurse who'd been with Sy Tuan had contracted the virus.

  That was not the end of the bad news. A 35-year-old sanitation worker whose job it was to clean the slops from slaughtered chickens at Hanoi's poultry market had also contracted the virus. In addition, officials in Thai Binh had belatedly reported that a 69-year-old man hospitalized locally had died from avian flu on Feb. 23 -- the 14th fatality in Vietnam this year. Like the other casualties he'd eaten infected poultry over Tet.

  I thought of Nguyen Nhung Ngoan pacing the corridor, anxiously waiting to see if her brother and 14-year-old sister would recover.

  Until such time as scientists tell us otherwise the front line is Vietnam, not the UK. But like Nhung Ngoan we have little choice but to wait and pray.

  Comments will be moderated. Keep comments relevant to the article. Remarks containing abusive and obscene language, personal attacks of any kind or promotion will be removed and the user banned. Final decision will be at the discretion of the Taipei Times.
• Most Popular

  • 1

    F-16 Block 70 jets to arrive this month, official says

  • 2

    Taiwan-Tokyo travel pass launched

  • 3

    US House passes Taiwan conflict act

  • 4

    Chinese man captured on a rubber boat

  • 5

    US military warns PLA against making ‘dangerous’ moves