Friday, November 24, 2006

Tell Us Something We Didn't Know

#221


While I'm away for a few days, I'm still watching the flu news, and this article showed up this morning. It confirms something that flubies have known for nearly a year . . . that our current tests for the H5N1 avian flu virus in humans are woefully inadequate. The most common tests, the throat and nasal swabs, which have been repeatedly used to `rule out' bird flu, are all but useless.

Rapid tests for bird flu are flawed, studies find
Quick results are key to halting spread
By Donald G. McNeil Jr. / The New York Times
Published: November 24, 2006


Avian flu is extremely hard to detect with standard tests, but waiting for laboratory confirmation of an outbreak would cause dangerous treatment delays, according to new studies of two flu outbreaks.

The studies, published Thursday in The New England Journal of Medicine, were of family clusters of flu cases in Turkey and Indonesia.

Rapid tests on nose and throat swabs failed every time, and in Turkey, so did all follow-up tests, known as Elisas. The only tests that consistently did work were polymerase chain reaction tests, or PCRs, which can only be done in advanced laboratories and take several hours.

"It'll be a disaster if we have to use PCRs for everybody," said Dr. Anne Moscona, a professor of pediatrics and immunology at Weill Cornell Medical College. "It just isn't available at a whole lot of places."

If the H5N1 virus mutates into a pandemic strain, rapid tests "will be really key," she said.
The studies followed clusters in three separate families in Indonesia in 2005 and in what appears to have been one extended family near Dogubayazit, in eastern Turkey, in January.
Case clusters particularly worry public health authorities because they raise the possibility that the flu is mutating to spread faster between people.


In the Indonesian cases, the authors, a mix of experts from Indonesia, the World Health Organization and the Centers for Disease Control and Prevention in Atlanta, concluded that human-to-human transmission had probably taken place in two of the three family clusters.
In one case, a 38-year-old government auditor appeared to have caught the flu from his 8-year-old daughter or her 1-year-old sister. All three died; his wife and two sons did not become ill.
No one in the family had any known contact with poultry, wild birds, animals or sick people, so the source was a mystery.


"But you can't always tell what a young child has done," said Dr. Tim Uyeki, a CDC flu specialist and an author of the study. "There's no magical test, and you don't always get a perfect explanation."

The Dogubayazit cluster was a cause célèbre for some Internet flu-watchers following Turkish media reports in January. They argued that widespread human-to-human transmission seemed to be taking place, and that it may have begun at a banquet in late December attended by members of two related families named Ozcan and Kocyigit. The Turkish government and the WHO did not link the cases or families and tentatively blamed all transmission on birds.
The study showed how wide a net was cast: 290 people were tested at one hospital because they either had flu symptoms and/or contact with dying birds. All were given the antiviral drug oseltamivir, which is also sold as Tamiflu, and about half were hospitalized.


That accorded with WHO recommendations: widespread testing and prophylactic use of antivirals, both to save lives and to snuff out any suspected outbreak of a mutant strain.
Ultimately, only 10 came up positive on PCR tests, and only 8 of those were confirmed by a WHO laboratory. All were children; four died and four survived.


The study confirmed early suspicions that the families were linked; 7 of the 8 children were related or lived near each other. The December banquet was not mentioned.

It was impossible to tell whether the other argument made by the Internet flu-watchers was correct: that poor testing and the oseltamivir had disguised the real extent of the outbreak.

http://tinyurl.com/ybrkmn


We hear constantly about hundreds of suspected avian flu patients testing negative for the virus. Sometimes, after repeated tests, a positive result is finally produced. Ealier this year in Thailand, it required 9 tests on one patient before a positive test was achieved. But most of the time authorities are happy enough with an initial negative test, and never look any deeper.

It is telling that authorities will dismiss a suspected avian flu patient with a single negative test, but require independent confirmatory tests before a positive result is accepted.

While none of this comes as a shock to veteran flubies, perhaps now that the NEJM has said it, we will see the issue of false negatives taken seriously.

The sad thing is that it has taken this long to acknowledge a problem that was perfectly obvious nearly a year ago.