False Negatives Delay WHO Update on H5N1 Clusters in Pakistan
Recombinomics Commentary 23:02
December 27, 2007
Dr. Frederick Hayden said confirmatory tests on specimens taken from a number of other members of the family were not positive. But that shouldn't be taken as a sign that they were never infected, he cautioned.
"I think that there's a probability that other individuals in this family were in fact H5N1-infected," said Hayden, adding that blood testing on surviving members of the family holds the key to fleshing out how many infections actually occurred in this cluster.
The negative results may be the product of degradation of specimens that were shipped to a WHO collaborating lab in London for confirmatory testing, Hayden said. Other factors could also have affected the results, including when in the course of infection the specimens were taken or whether suspect cases were started on antiviral drugs before a sample was taken.
A fourth brother was also hospitalized for illness around the same time. He survived. Several other members of the family tested negative for infection, including a brother and his son who live on Long Island, N.Y. They had travelled to Pakistan to attend at least one of the funerals and suffered mild respiratory symptoms on their return to the United States.
The above comments provide updated details on the testing of Pakistan samples by the mobile unit of NAMRU-3 and Mill Hill in London. Most of the initial confirmatory tests were negative, but the negatives are likely to be false because of the patient’s symptoms and earlier positive results by Pakistani labs.
Serum samples from these patients, as well as at least one health care worker, will be tested for H5 antibodies, which can be used to confirm H5N1 infections.
The above comments contradict the report by New York, which stated that the son of the New York resident had not been exposed to H5N1, implying he did not travel to Pakistan. It is not clear if the New York residents will also be tested for H5 antibodies.
The negative data does demonstrate that many factors can produce false negative, including sample degradation and suppression of RNA levels by Tamiflu treatment. The above detail helps explain the delays in the WHO update.
Details on disease onset dates, relationships of confirmed positives, and sequence data would be useful.
Media Links
Recombinomics Presentations
Recombinomics Publications
Recombinomics Paper at Nature Precedings