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Pandemic Bird Flu - Human to Human Transmission

Recombinomics Commentary

April 24, 2005

>>  Vietnamese and international health officials say they are confident that the mortality rate has dropped but are not sure by how much. Better screening and wider public awareness of bird flu could mean health workers are catching and recovering from milder cases that would have gone unreported a year ago. WHO officials have complained, however, that Vietnam is reluctant to provide detailed information about human cases. Senior Health Ministry officials respond that reports are provided in accord with national regulations.

The question now is whether bird flu in Vietnam has begun passing among humans. <<

The questions really center on the efficiency and extent of the transmission.  Data from last season clearly demonstrated human-to-human transmission within families.  One of the most well publicized clusters involved a groom and his two sisters in Thai Binh over a year ago.  The groom developed symptoms and died without sample collection.  However, his two sisters who cared for him developed symptoms on the same day, were hospitalized on the same day, initially tested inconclusive, subsequently were confirmed to be H5N1 positive, and died with 1 hour of each other.  However, one developed a respiratory disease and the other was gastro-intestinal, but the disease onset dates were consistent with an infection from their brother.

Since then there have been over a dozen similar clusters, and virtually all have the same bimodal distribution of onset dates.  The index case develops symptoms and then the caregiver, who is usually a female relative, develops symptoms a week or two after symptoms appear in the index case.  Monitoring and testing are poor so most of the time there is no sample collected on the index case or initial tests are negative.  The secondary cases eventually are confirmed, but frequently the index case is not an official case, even though the index case dies and the relative is lab confirmed H5N1 positive.  Last year most of the secondary cases died also.  This year, the secondary cases in the north are surviving.

Although the testing of patients remains scandalously poor, the size of the clusters are growing, so the clusters are hard to ignore, even though most of those infected with the H5N1 circulating in the north survive.  The first reported Thai Binh cluster reported this year involved an index case who died, but his bother survived.  His youngest brother was also reported to be H5N1 positive but without symptoms.  This report was not officially confirmed, but the number of unreported cases appears to be exceedingly large and dwarfs the small number of official cases.

The largest reported suspect cluster is in Quang Binh in the central highlands.  A 13 year-old died, but no sample was collected.  Her 5 year-old brother, however, subsequently developed symptoms and was H5N1 positive.  Media reports indicated 195 members of the commune had flu-like symptoms.  An investigative team found many who had already recovered.  Samples were collected from patients who still had symptoms as well as from birds in the commune.  Although these samples were collected over a month ago, test results have not been disclosed.  One media report did refer to the commune members as being positive for H5N1, which appears likely.  Thus, results from this small commune cold triple the number of cases in Vietnam.

However, there are many more signs of extensive human-to-human transmission involving milder cases in the north.  On March 22 a family of 5 was hospitalized and all 5 tested positive for H5N1.  They all recovered, and the relatively short time for the course of the disease was not very different than a case of human flu.  Thus, the number of H5N1 patients who did not go to the hospital, were not tested at the hospital, or had positive results that were not reported could be exceedingly large.

Northern Vietnam sent up to 1000 samples to the CDC on April 15 for testing.  These results have not been made public, but it is likely that most of these samples are H5N1 positive and testing will include sequencing and determining the extent of genetic variation in northern Vietnam.  Since preliminary evidence has indicated a protein contains one less amino acid, which is likely to be in the HA protein and match isolates from mainland China, the possibility of widespread human H5N1 infections with milder symptoms in China remains high.

Thus, there are several clues that H5N1 infections in humans may dwarf official numbers, yet these results go unreported and media reports continue to talk about possible human-to-human transmission.

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