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More Bird Flu Monitoring Problems in Vietnam

Recombinomics Commentary
March 8, 2005

>> "It's also possible that they have a very light viral load, and Vietnamese tests may not be sensitive to pick it up," he added.

His colleague, Peter Horby, said the finding underlined the need for support for Vietnam's laboratories.

But he stressed that there had not been any problems with Vietnamese results before.

"It could just be a problem with one lab," he said. <<

Clearly if there is a sensitivity problem with the monitoring tests, the ability to identify such problems would be limited.  The data from familial clusters clearly point toward detection problems.  The most recent example was in January, which coincides with the reported false negatives.  The index case in the January Thai Binh cluster tested negative twice.  He was only positive at autopsy.  However, prior to autopsy he was contagious, because he passed the virus to his brother, who also initially tested negative for H5N1.

The false negatives were not limited to tests in January, 2005.  A year earlier in another Thai Binh cluster, both sisters initially tested as inconclusive.  Moreover, media reports indicated that the sister in the most recent Thai Binh cluster also tested negative initially.

The problem of false negatives is not limited to Vietnam.  In the cluster in Thailand, which was reported in the New England Journal of Medicine as the first clear example of human-to-human transmission, the aunt also initially tested negative.

These false negatives may be related to viral load, which may also be related to prognosis.  Two of the patients described above, the aunt in Thailand and the brother in Thai Binh, recovered, and the sister in Thai Binh is also recovering.  The WHO report indicates that the seven false negatives also recovered.

This season there has been a significant difference in outcomes in Vietnam.  All of the confirmed H5N1 patients in the south have died, while many of the patients in the north have recovered.  However, it is not clear if this difference is due to differences in the virus or patients, or is simply a sensitivity testing issue.  If the tests in the north are more sensitive, they may detect patients with lighter loads who recover, while the tests in the south only detect the most severe cases, who die.

The lack of a sensitive, reliable test severely compromises containment efforts, because the distribution of the virus is unknown.  If the virus is widespread and is being actively spread throughout the human population, then recombination in people is a major concern.  The potential for dual influenza infections in people by avian and human or avian and avian viruses is much greater.

In the 1918 pandemic, the devastating outbreak in the fall of 1918 was preceded by mild cases in the spring.  The possibility that the human population is being seeded with a milder H5N1, which can turn virulent via recombination, cannot be excluded because of the poor monitoring of avian influenza, which is still scandalously poor and incomplete.

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