Difficulties Diagnosing Bird Flu Patients In Vietnam
Recombinomics Commentary
January 22, 2005
>> Tests were also being conducted on a teenage boy from Bac Lieu province who had died, reports said.
Southern Vietnam's bird flu test center, the Ho Chi Minh City Pasteur Institute, dismissed reports confirming the two suspected cases had been confirmed as bird flu.
"The test results on the two deaths are not affirmative, not clear yet," institute director Nguyen Thi Kim Tien told Reuters, adding that more tests were being done. <<
The difficulty in detecting bird flu with initial detection tests in the south is another major concern. The two confirmed bothers in the north required multiple tests. Both were negative on the first attempt and the fatal case required 3 tests before scoring as a positive.
Difficulty in detecting H5N1 can be due to a changing virus. Although sequencing efforts are focusing on reassortment, which is a shuffling of existing genes, the real pandemic potential of influenza (and all viruses) is driven by recombination, which creates new genes.
The influenza receptor binding domain is on the H and right now the current H's that are easily transmitted human to human are H1 and H3. H1 is commonly found in H1N1 or H1N2 human flu viruses, while H3 is in H3N2 as is present in the widely circulating Fujian or Wellington sub-types. However, these Hs are readily detected in screening assays and most people who have either been vaccinated against the flu or actually had the human flu recently have antibodies to the H1s and H3s.
Thus, a reassortment that swapped H5 (avian) for H1 or H3 (human) would created a virus (H1N1 or H3N1) that was easily transmitted, but wouldn't have much pandemic potential because most people would have immunity. The recent isolates from grey herons have evidence of reassortment because they have an H and N that is similar to the H and N from a Canada goose from Hong Kong in 2002, but 4 of the other genes are described as "novel".
"Novel" genes are almost always recombinants, and although the description of the sequences from the grey herons only mentioned 4 novel genes that encode internal proteins, recombination can also happen on the H and N. This recombination could impact the ability to transmit human to human, as well as the ability to detect using anti-sera or sequences of earlier versions of H5N1. These recombinants would also be harder to recognize by existing antibodies in the patient population, which could lead to a more serious disease.
A number of suspect cases were mentioned about 10 days ago, and many have not been confirmed. This delay in confirmation also raises concerns about the ability of some of the quicker diagnostic tests to recognize this season's version of H5N1. Moreover, the changing of the pneumonia associated with H5N1 to something more complex is another cause for concern that the virus is genetically changing.
This season, the case fatality rate is running at 90% assuming the earlier reports of confirmation of the 8th and 9th fatalities are accurate and the middle (42M) brother in the north continues to recover. So far this season, no confirmed case of avian influenza in Vietnam has been discharged from the hospital, so technically the case fatality rate for confirmed cases with outcomes remains at 100%.
Difficulties diagnosing H5N1 infections are also increased because asymptomatic ducks increase the gene pool of H5N1 for further recombination and can easily enter the food supply. This hides risk factors that flag avian influenza cases for follow-up testing when initial tests are negative.
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