Wednesday, March 09, 2005

Open questions remain open

It has been evident for some time that there are many missed cases of influenza A/H5N1 (bird flu) in southeast asia (newstory from AFP; for a good summary with some acerbic commentary, see Henry Niman's Recombinomics site). Most confirmed cases have come from Vietnam, which has the best developed public health and medical care infrastructure, but Thailand, Cambodia and Laos all have endemic poultry problems and very likely human cases as well. It is also likely that not all of the reporting failure relates to infrastructure. Civil authorities are often reluctant to admit the existence of cases for economic or political reasons.

The implications for public health of this missing information are hard to judge. On the one hand, it might mean that there is more widespread human infection and thus evidence that the disease is more easily transmissible between people than believed to this point. Evidence from last year's Japanese studies of bird cull workers and the experience of the H7N2 outbreak in The Netherlands certainly point in this direction. Thus we are missing early warnings of an impending pandemic. On the other hand, it might mean the disease is less virulent than the recognized cases suggest, which would be good news. At this point either or both could be true.

It is past time when the international community should insist upon and support intensive and urgent case finding and seroprevalence studies in the southeast Asian region and other areas where bird flu is a plausible explanation for unexplained illness. Henry Niman's suggestion that the Baguio, Philippines meningo-like disease should be ruled out as avian influenza is a case in point.

The uncertainty and confusion caused by the missed cases is now part of the public discourse. It is very hard to understand WHO's failure to make public statements about what they know or don't know about these questions, as we asked in our Open Letter of February 16. It would cost them nothing to respond. Failure to respond will only encourage further the speculation which always rushes in to fill information vacuums.

We repeat the summary questions from our Open Letter here:
i. What are the criteria by which statements regarding possible person-to-person transmission of H5N1 are made in the face of evidence that initial testing produces some false negatives? In particular, what does WHO know about the negative predictive value of the diagnostic tests now in use in Thailand and Vietnam where time-space clusters of cases have been reported?

ii. The Recombinomics website ( raised the possibility that in a number of instances certain events could conceivably represent H5N1 infections. These include the meningo-like outbreak in the Philippines and reports of sudden bird deaths in North America. There was no claim these were H5N1 infections, only the reasonable question whether anyone had thought of the possibility and bothered to verify it or not. It was announced that WHO sent a team to the Philippines to investigate the outbreak there. Given the level of concern regarding an H5N1 event, a response from WHO would be useful.

iii. Recently there has been some discussion, both on the Recombinomics site and via email, about influenza A/H1N1/WSN/33 sequences in Korean swine influenza A/H9N2 reported to GenBank in October 2004. There are rumors that WHO has looked into this and resolved the issue. If this is true, a statement to that effect is necessary. Because of the gravity of the implications, we believe some public explanation is required.

We urge WHO to recognize the new setting regarding public health information generation and dissemination and act accordingly. Failure to do so will only create confusion where clarity is desperately needed.

The Editors (
Effect Measure