Genetic Risk From Bird Flu?
From ProMed Mail
ProMED-mail is a program of the
International Society for Infectious Diseases
[A woman's teenage daughter] lay sprawled on a hospital bed, under observation for avian influenza. In an adjacent room, her haggard husband was sitting wrapped in a gray blanket, also under treatment for the virus. 2 of her other children had already died from it. "I don't know exactly why I'm healthy," she admitted from a cot where she was keeping vigil late last month for her family. "I don't have a fever, a cough or other symptoms. I really don't know why not."
In the weeks before the family became sick, the virus raced through their small flock of chickens. When the last 6 birds developed symptoms, the woman's husband helped his brother slit their throats beside a large palm in the front yard. The chickens were plucked and cooked in coconut milk for a family feast.
With 4 cases confirmed or suspected, her family represents one of the largest clusters of bird flu among humans in the world. It is also notable in sharing a characteristic with nearly all the other family clusters: Those infected by the virus were related to each other by blood and not by marriage. This raises the possibility that genetics play a role in determining who among those exposed contracts the often-lethal disease.
"It's intriguing," said Sonja J. Olsen of the Centers for Disease Control and Prevention in Bangkok, who has studied family clusters of avian influenza. If a biological explanation were ultimately proved, she added, "perhaps we could identify people at genetic risk."
Since H5N1 avian influenza began spreading across Asia in 2003, there have been 25 recorded family clusters involving confirmed or suspected cases. In the overwhelming majority, these have involved blood relations such as siblings, parent and child, children and grandfather, or niece and aunt. In only 3 instances did both husband and wife test positive.
Worldwide, bird flu has infected at least 165 people and killed 91, according to the World Health Organization. Health experts warn that the notoriously changeable influenza virus could develop into a form more easily transmitted among people and spark a global pandemic.
Outside the isolation ward in Hasan Sadikin hospital, a facility designated to treat bird flu in Bandung, the capital of West Java province, the young woman's relatives were camped on the lobby floor, spending nights on thin woven mats, wondering, like the experts, why she was spared while the rest of the family fell sick.
"It's a mystery. It's really incomprehensible to us," said the father's cousin. "Everyone in the family had the same contact with chickens." There is no evidence that properly cooked poultry or eggs can be a source of infection, according to the CDC. Most cases of bird flu in humans have resulted from direct or close contact with infected live or uncooked poultry or surfaces contaminated with secretions and excretions from infected birds.
The family lives about 100 miles east of Jakarta in the village of Cipedung, in the modest dwelling of a meatball peddler, with dirt floors, flimsy bamboo walls and a ramshackle roof that leaks in the rain. Chickens often wandered inside, sleeping beneath the platform beds. Health investigators have attributed the outbreak to infected poultry, reporting that avian influenza has been identified in chickens across much of the village.
2 days after the family killed and ate the infected birds, the 13-year-old daughter, the 1st to fall sick, began coughing and developed a high fever. By the time she was taken to a district hospital 6 days later, she was gravely ill. The medical staff recommended she be moved to a better hospital, but she died as the ambulance was coming to transport her. The day she died, the young woman brought their son, 4, to the district hospital after he came down with the same symptoms. The boy was urgently transferred to the provincial hospital, but he survived for only 2 days. Another daughter, 14, was next to become ill, with a slight fever, not enough to keep her out of school. But health workers urged that she too be admitted to the hospital. Her father joined her 3 days later after he began complaining of trouble breathing while overseeing the funeral for another of the children.
Tests confirmed that the 13-year-old girl and the 4-year-old boy died of bird flu. Initial results were inconclusive for the father and older daughter. But international health experts said they expected that further testing would show all 4 had contracted the disease. The father and daughter recovered and left the hospital 2 weeks ago.
The question of how the mother eluded the virus is part of a puzzle now stumping global influenza experts. Researchers acknowledge that they know little about why some people become ill while others, with even greater exposure to the infection, remain healthy.
For instance, thousands of agricultural workers, officials and soldiers have been culling poultry across Asia in an effort to contain the spread of bird flu, at times lacking even basic protection such as gloves, masks and goggles. Yet according to WHO records, not one has fallen sick. This finding has reinforced the suspicion that some people are more susceptible than others.
"We've discussed how it's always likely there's some genetic component going on," Keiji Fukuda, WHO's influenza chief, said in a telephone interview from Geneva. He cautioned that it was too soon to conclude that there is genetic susceptibility. Although the family pattern is suggestive, Fukuda said the size and number of clusters remain small. Moreover, even if research proves that some people are more susceptible, he said this information may have little practical benefit if the virus mutates into a form that spreads faster than people can be tested for genetic risk.
Olsen and other researchers have noted that behavior and not genetics might be the determining factor in who in a family gets sick. Could the rest of the family have had more contact with sick chickens than the mother did? That's doubtful, relatives and local agriculture officials said, reporting that as a rural homemaker, she was in daily contact with livestock.
Perhaps the 3 children contracted the virus by playing with chickens. Could they have then passed it to their father but not their mother? Relatives said the mother was the parent who usually looked after the children and who carried her ailing son in a sling across her chest for days.
When pressed by a reporter, the mother suggested she was spared because she did not eat chicken when the rest of the family feasted on the sick birds. She said she had high blood pressure and avoided meat. But back in the village, next door to the family's home, her mother-in-law dismissed that explanation. "Many people ate that chicken. I ate the chicken," recalled [the mother-in-law], 70, sitting cross-legged on the porch. Beside her in the rain- soaked yard were the abruptly abandoned reminders of her family: her son's rickety meatball pushcart and her grandson's plastic tricycle. "The rest of us didn't get sick," she continued, eyes reddening. "So that can't be the reason."
[Byline: Alan Sipress]
Mary Marshall
[On the basis of the predominance of blood relatives (siblings, parent and child, children and grandfather, or niece and aunt -- rather than husband and wife -- among those infected in so-called "clusters" of avian influenza virus infection, it is reasonable to suggest that genetic constitution may play a role in the susceptibility and resistance of individuals to infection. However, the numbers are small and other factors such as age, nature of exposure, and behavior cannot be discounted. A compounding factor is that there is little published information on the immune status of the population in the affected communities. The observation that none of those employed in commercial poultry operations and in the culling of diseased fowl have been victims of H5N1 avian influenza may indicate that asymptomatic infection and development of immunity is widespread. Also the predominance of children and younger people among the victims of infection could indicate protection of older people by development of immune responses. Comprehensive data on seroprevalence are still lacking. - Mod.CP] AR2006021401973.html
Patricia A. Doyle, DVM, PhD- Bus Admin, Tropical Agricultural
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