Whither avian influenza H5N1?

H5N1 avian influenza has been headline news for a number of years. This is mainly because of the fear of mutation or recombination with a human strain to produce an infectious agent that is capable of causing an influenza pandemic. That, coupled with the high mortality rate of H5N1 in infected humans, has been a major concern. This commentary takes a look at the epidemiologic status of H5N1 circa March 1, 2009.

The first recognition of the current avian influenza H5N1 strain was in Hong Kong in 1997 with involvement of poultry and human cases. Although outbreaks in poultry continued in the Far East, human cases were not diagnosed again until December of 2003 in Vietnam when the current continuing human outbreak began.

Subsequently outbreaks in poultry and wild birds have occurred in the Far East, throughout Southeast Asia and in parts of the Middle East, Europe and Africa. Similarly, cases in humans have been reported from Indonesia, Vietnam, Egypt, China, Thailand, Turkey, Azerbaijan, Cambodia, Iraq, Pakistan, Laos, Djibouti, Nigeria, Bangladesh and Myanmar.

Cases in humans

As of 2009, the number of WHO confirmed cases in humans reported each year (deaths/cases) has been: 2003 (four/four); 2004 (32/46), 2005 (43/98), 2006 (79/115), 2007 (59/88), and 2008 (33/44). As of Feb. 27, 2009, there had been 408 cases with 256 deaths.

Most of the cases in recent years have occurred in Indonesia (121 cases in the past three years) and, to a lesser extent, Egypt, China and Vietnam (with 51, 22 and 14 cases in the past three years, respectively). Mild or asymptomatic infection is uncommon as serosurveys of contacts with poultry or patients have revealed few positives.

For reasons not understood, but perhaps related to differences in viral strains, the three-year mortality rate in Egypt has been lower than in the other three countries: 45% versus 84%, 71% and 68% for Indonesia, Vietnam and China, respectively.

Only the Egypt versus Indonesia differences achieved statistical significance. Another explanation that has been given for the lower mortality rate in Egypt, but without hard evidence, is that the cases in Egypt were treated earlier with oseltamivir than the cases in the other countries.

Unfortunately in early June 2008, Indonesia announced that it was no longer reporting cases of H5N1 on a real time basis and would only report deaths in a periodic fashion. In fact, we cannot determine what proportion of cases they are reporting.

Not commonly recognized is the fact that, as shown in the figure, the epidemiological curve of world cases peaked in 2006 and has subsequently declined. As reporting from Indonesia is suspect for the latter half of 2008, to give a worst case scenario, the numbers from Indonesia in 2007, instead of the numbers from 2008, should theoretically be added to the 2008 figures from the rest of the world to give a total for 2008. When this is done, the total for the world for 2008 would become 62. This still results in a downward trend for 2007 and 2008.

Analogies with influenza pandemic

Another major point of interest relates to the analogies that have been drawn between the influenza pandemic of 1918 and the clinical course of H5N1 infection. Many of us were taught that the typical cause of death in the 1918 pandemic was a diffuse widespread hemorrhagic pneumonia not unlike the findings in those dying from H5N1 infection.

It turns out, as pointed out in the commentary by Theodore Eickhoff, MD, in the September 2008 issue of Infectious Disease News, that, in fact, the great majority of deaths in the 1918 pandemic were related to secondary bacterial pneumonia. Thus, even if H5N1 did emerge in some form as the cause of the next pandemic, it is more than likely that the major complication to be faced would be secondary bacterial pneumonia and not viral pneumonia or cytokine storm.

It is impossible to predict what the subsequent course of the current epidemic will be. However, we have now had more than five years of geographic spread of the virus with huge numbers of birds (poultry and wild water birds) infected. There have been countless exposures of humans to the virus in the very populous areas of the world where back yard poultry are kept, and no significant spread to humans has occurred; the numbers remain small. Furthermore human to human spread has been limited and interestingly seems mainly or exclusively to occur in blood related relatives (eg mother-to-son or son-to-mother and not husband-to-wife).

Thus one could surmise that this virus in a mutated or recombined form may not be the cause of the next pandemic. As a pandemic caused by some strain of influenza will certainly occur in the future, it seems logical that vaccine development efforts should be aimed at methods of rapidly producing large amounts of influenza vaccine rather than focusing on this particular virus.

In addition the current approach of stock-piling antivirals as well as having available adequate amounts of antibiotics seems to be a clear need.

For more information:

• Morens DM, Taubenberger JK, Fauci AS. Predominant Role of Bacterial Pneumonia as a Cause of Death in Pandemic Influenza: Implications for Pandemic Influenza Preparedness. J Infect Dis. 2008:198;DOI 10.1086/591708.
• Brundage JF, Shanks,GD. Deaths from Bacterial Pneumonia during 1918-19 Influenza Pandemic. Emerg Infect Dis.2008;14:1193-99.
• Additional information is available online at www.who.int/csr/disease/avian_influenza/country and http://promedmail.org.