Bird flu: neurotropic and underestimated?

This week's New England Journal of Medicine reports on two Vietnamese bird flu cases of a year ago. What was unusual was the initial presentation was not fever and respiratory symptoms but gastrointestinal (diarrhea) and coma. The deaths of the two children, a boy and a girl, were first classified as encephalitis. H5N1 was recovered from the boy's feces, giving rise to another route of person-to-person transmission not previously contemplated. As noted in press reports, the authors warned (via Bloomberg):

"Clinical surveillance of influenza H5N1 should focus not only on respiratory illness, but also on clusters of unexplained deaths or severe illnesses of any kind,'' Menno de Jong, a virology researcher who led the study, wrote with colleagues. "These cases have important clinical, scientific and public health implications.''

The NEJM report is also highlighted in a news article from the Center for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota:

"These cases emphasize that avian influenza A(H5N1) should be included in the differential diagnosis of a much wider clinical spectrum of disease than previously considered and that clinical surveillance of influenza H5N1 should focus not only on respiratory illnesses, but also on clusters of unexplained deaths or severe illnesses of any kind," the [NEJM] report states. "Awareness of the full clinical spectrum is essential to appropriate management of the illness, since treatment with antiviral agents is likely to be beneficial only when it is started early in the course of illness."

CIDRAP goes on to give some details from the NEJM report (which is subscription only):

Both children died in hospitals in southern Vietnam in February 2004, the article says. The 9-year-old girl arrived on Feb 1 with a 4-day history of fever, watery diarrhea without blood or mucus, and increasing drowsiness. She had no respiratory symptoms, and her chest radiograph was clear. She became comatose and died the following day; acute encephalitis of unknown origin was listed as the cause. Her body was not autopsied.

The girl's little brother was admitted to the same hospital in Dong Thap province on Feb 12, 2004, having suffered fever, headache, vomiting, and severe diarrhea for 2 days. A chest radiograph was normal.

Within days, his diarrhea and stupor worsened. He was transferred to a hospital in Ho Chi Minh City on Feb 15 but fell into a coma within 12 hours of the transfer. By Feb 16, a chest radiograph showed bilateral infiltrates. He died the next day, with acute encephalitis reported as the cause. No autopsy was performed, but samples were taken for an ongoing study of the causes of acute encephalitis.

When researchers examined those samples at different times over the succeeding months, they ruled out several possible causes before they found the H5N1 virus in the boy's throat, rectal swabs, serum, and cerebrospinal fluid.

It is reported WHO is now in the process of changing its case definition of bird flu to take into account the new findings. The lead researcher in the NEJM paper, Dr. Menno de Jong, said that

"[i]t appears this virus is progressively adapting to an increasing range of mammals in which it can cause infection, and the range of disease in humans is wide and clearly includes encephalitis." [snip]

Dr Jeremy Farrar, director of the Wellcome Trust's Vietnam unit, said [to the BBC]: "This latest work underlines the possibility that avian influenza can present itself in different ways.

"The main focus has been on patients with respiratory illnesses but clearly that's not the only thing we should be looking for.

"Therefore the number of cases of H5N1 may have been underestimated."

This is confirmation of the warnings that Henry Niman at Recombinomics has been sounding for some time, reiterated yesterday here, here and here.

It is also the kind of development we called on WHO to acknowledge with some public information regarding the Philippine meningo-like cases they investigated and the definition of person-to-person transmission in case clusters in our Open Letter of February 16, 2005.

We are still waiting for a response.