Monday, June 20, 2005

The body yields some evidence on bird flu

The online version of CDC's scientific journal Emerging Infectious Diseases has just put up a paper detailing laboratory and autopsy findings in a little 6 year old Thai boy who died last year. The patient died of a primary viral pneumonia and acute respiratory distress 17 days after onset of his illness. One of the first entries in the forthcoming Flu Wiki will explain a bit about primary viral pneumonias but for now think of it as an infection of the delicate cells in the part of the lower respiratory tract where gas exchange takes place. Intensive oseltamivir therapy was not started until day 15 because of unavailability of the drug in Thailand.

Using a variety of techniques to verify that the infection was from H5N1 virus and to locate those organs and tissues where the virus could be found and replicating, the authors obtained surprising findings in this tragic case (I feel compelled to keep reminding myself that this object of medical inquiry in a scientific journal was somebody's little boy, an older or younger brother or a best friend).

Of particular interest was evidence that the virus was present and replicating in the intestinal tract, although evidence of viral proteins weren't detected there. In addition, the pathologic damage was more or less confined to the extremities of the respiratory tree (the Wiki will also explain this). In other influenza infections (like the common H1 and H3 infections) there is evident damage to the upper respiratory tract, giving rise to the symptoms of running nose and hacking cough we associate with the disease. In this case it was just the areas where gas exchange takes place that were infected (the type II pneumocytes), with fluid in the spaces between the gas exchange sacs (interstitial pneumonia). There was also sign of a secondary fungal infection of the lungs, possibly a terminal event. While there was evidence of replicating virus in the intestines, the tissues looked normal. In keeping with other findings, there were increased levels of certain cytokines (chemical signalling substances induced by infection). While only suggestive, this is consistent with a role for a dysregulated defense reaction playing a part in making the infection more severe.

The presence of the virus in the intestinal tract raises the question of whether stool is infective in these patients, an important point for transmission. The localization of the virus to the lower respiratory tract also suggests that the usual nose and throat specimen swabs may be less reliable for H5 infection than for other influenza viral subtypes.

This report is one of very few autopsy reports in the scientific literature, despite the fact that 59 deaths have occurred from this disease in southeast asia. Cultural reasons clearly play a part (as they do in the current low autopsy rate in the US). While we continually seek important viral gene sequence information, this case reminds us we have much to learn from examining the damage done to real people.

More surprises are clearly in store.