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Bird Flu False Negative for Second Nurse in Thai Binh?

Recombinomics Commentary
March 13, 2005

>> Test results provided by the Center for Tropical Diseases in Hanoi showed the nurse was free of H5N1, the deadly strain of the avian influenza, said Vietnam's Central Institution of Sanitation and Epidemiology on March 13.

The nurse, who worked in a hospital in the Red River Delta province of Thai Binh, was previously thought to be infected and hospitalized for treatment. <<

Additional tests on the nurse at Thai Binh is warranted in view of her relationship to four other H5N1 confirmed cases, and the history of false negative or inconclusive results of patients in clusters in Thai Binh.

The first cluster was in January of 2004.  The index case in the cluster was never tested, but his two sisters who cared for him were tested.  Their initial results were inconclusive, but they subsequently tested positive, and unique H5N1 sequences were obtained for each.  All three patients died.  One of the sisters had one of the first confirmed cases that did not present as a respiratory illness.

The second cluster was about a year later.  The index case had been at home for a week before going to the hospital on January 1, 2005.  The hospital had a small holiday staff, so it is not clear exactly when he was first tested, but he was tested twice while he was alive, and both tests were negative.  He died on January 9 and was positive at autopsy.  His brother developed symptoms on January 9, and he too tested negative initially.  He subsequently tested positive and recovered.

The nurse described above is linked to the third Thai Binh cluster.  She and another nurse had contact with the index case.  The index case's sister also tested positive, although some media reports indicated that she too tested negative in initial tests.

Thus, at least one confirmed positive in each of the first Thai Binh clusters initially tested negative for H5N1.

False negatives have also been reported for patients in southern Vietnam.  Seven samples that had previously given negative results at the Pasteur Institute in Ho Chi Minh City were positive when tested in Japan.  Four of these samples were then positive when retested in Vietnam.  Three however, tested negative again in Vietnam, and the assay is being replaced with one that is more sensitive.

Details on the assay in Thai Binh would be useful.  Many of the first cases in December, 2003 in Hanoi were positive on an influenza A test.  This test might help determine if the bird flu symptoms were due to influenza A.  The virus can evolve quickly, and genetic changes can reduce the sensitivity of assays.

The nurse's history of contacts with co-workers and patients raises the suspicion level and suggests that her bird flu symptoms are due to influenza A.  If the infection is due to a recombinant or reassortant, then the virus may not be detected with the standard H5N1 reagents.

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