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H5N1 Under the Tamiflu Blanket
Recombinomics Commentary 00:33
December 29, 2007
In the meantime, six people who came from two families but were kept in one house in Serang, Banten, being stated by the bird flu negative because immediately took medicine.
They took medicine because of experiencing the sign similar to bird flu after his 17 chickens died suddenly.
"The level of the awareness that was high to immediately take medicine helped them was avoided from the risk. Earlier we suspicious happened kluster.
They could be isolated, was given medicine oseltamifir and was checked by Balitbangkes Departemen of the Health. Results of the negative," explained Nyoman Kandun.
The above translation suggest that the recent cluster in Serang, Indonesia tested negative because testing was primarily on samples collected after the start of Tamiflu treatment. Tamiflu inhibits the release of influenza from cells, so viral RNA levels in circulation decline. This decline has the potential of producing false negatives, which may account for the high case fatality rate in Indonesia. Patients treated early recover and test negative, even though they were H5N1 infected. Those who start treatment late, or have a high viral load, test positive but subsequently die.
The effect is most easily seen in clusters. One of the best examples was the Garut cluster. Although there were only three confirmed cases, the confirmed cases were in significant clusters. They were linked to earlier cases who died with bird flu symptoms, but samples were not collected for testing, so the index cases for the multiple clusters were ot confirmed.
The positive cases led to the implementation of a Tamiflu blanket over the entire village. Many contacts developed symptoms and were hospitalized. Several were into the ICU, but none tested positive. A health care worker noted that many times initial tests are negative. However, the Tamiflu makes the subsequent test negative also, so the patient recovers but the recovery doesn’t lower the case fatality rate because H5N1 is never confirmed. Confirmation could be done with follow-up test on convalescent sera collected 3-4 weeks after symptoms, but such follow-up is rare.
This type of follow-up was planned for the outbreak in Turkey. Those cases also had problems with false negatives. The four siblings which included the index case all tested negative initially. Three of the four died and tested positive, but were only positive with lung samples collected at the time of death. A Tamiflu blanket was aggressively applied, but results from follow-up testing were never reported and it is not clear that samples were ever collected.
Comments from the latest cluster in Pakistan indicate testing there is also on samples collected after the start of Tamiflu treatment. Antibody testing of the negatives has been promised, but at this time only one of the nine patients were positive in local test have been confirmed by WHO reference labs.
The false negatives can lead to a lack of follow-up on contacts and a false termination of a transmission chain, which can lead to assurances that are not supported by the true infections or spread.
Recombinomics Paper at Nature Precedings