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Silent Spread of Human H5N1 in Egypt?
Recombinomics Commentary 11:36
April 4, 2009

The reports of two more H5N1 confirmations in toddlers in Behiera, Egypt increase concerns that H5N1 is silently spreading in Egypt.  This year there have been 11 confirmed cases in Egypt, and 10 have been toddlers.  These cases appear to be mild, and none have died.  This situation is similar to the spring of 2007, where there was a spike in mild cases (16/17 survived) and the demographic had changed.  Instead of female teenagers and young adults, almost all case were children between the ages of 3 and 10.  In addition, most of the cases were from central or southern Egypt, while the more severe cases that preceded and followed the mild cases were in the north.  However, the cases this year are spread throughout the country (see updated map).

The cases in 2007 raised concerns that the number of cases was markedly higher than the confirmed cases because they could easily be misdiagnosed as seasonal flu, and like seasonal flu, could resolve with or without medical attention or anti-virals.  Thus, many of the children would recover and not be tested because a seasonal flu etiology would be assumed.  Moreover, the children could spread the H5N1 to playmates or classmates, which would produce protective immunity in this population.
Protective immunity in children would help explain why the mild cases this year are almost exclusively in toddlers.  The toddlers either were not born, or were infants in the summer of 2007, which would limit exposure.  This year, they would be more active and more likely to come into contact with H5N1.  Confirmed cases would be limited to this age group because the prior at risk groups would have some level of immunity, which would keep viral loads below detection limits.

In addition, the high number of toddler cases would signal a more efficient spread of the virus to humans, which may be linked to prior silent spreading in individuals who had developed some protective immunity.

The silent spread could have significant consequences.  H1N1 has now become Tamiflu resistant, so co-infections involving H1N1 and H5N1 could lead to H274Y jumping to H5N1, conferring resistance.  Similarly, increased spread in human hosts could make transmission more efficient due to H5N1 picking up additional changes from H1N1. 

Moreover, the milder, efficiently spread, Tamiflu resistant H5N1 could recombine with more virulent H5N1 to increase virulence, similar to the high CFR in Egypt between the two milder outbreaks, as well as infections preceding the milder cases in the spring of 2007.

Therefore, aggressive testing of toddlers who have no clear link to poultry is necessary, as is aggressive screening of prior at risk groups for detectable H5N1 antibodies, such as children in southern and central Egypt who accounted for the vast majority of confirmed cases in the spring of 2007.

The silent spread of H5N1 in human populations sets the stage for increased transmission efficiencies and a serious, if not catastrophic, pandemic.

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