Recombinomics: H5N1 Cairo Cluster Delays Raise Transmission Concerns

Commentary

Recombinomics Commentary 22:31
April 19, 2009

Woman, age 25, 33 weeks pregnant, began experiencing symptoms of fever and cough on April 6. She was admitted to Ain Shams Hospital on April 11 and received Tamiflu April 16. Infection with avian influenza was confirmed April 17.

The above comments detail the gap between admission and the start of oseltamivir treatment for the 65th confirmed case (25F) in Egypt. This five day gap is unusual, because patients with bird flu symptoms and contact with poultry are immediately treated with Tamiflu, and a throat swab is collected for PCR analysis for H5N1.

The delay in treatment for this patient suggests she denied a poultry contact. The possibility is support by the delayed treatment of case #63 (6M), whose treatment was also delayed at the same hospital. Since she was confirmed and was in critical condition, the significance of the treatment should have been well known to the staff at Ain Shams Hospital, because case #63 was also treated there. These two cases appear to be a few miles apart (see updated map), raising concerns that this geographic cluster is signaling more efficient transmission of H5N1.

These concerns were increased by the confirmation of case #66 (2F) in Kafr El Sheik. This case followed a recent case (#64) in Kafr El Sheik in the same district (Kellin). Moreover the 8 day gap in disease onset dates raises concerns that these two cases are related, and case #64 infected case #66.

Such transmission was recent seen in Beheira where two cases from the same districts were subsequently described as next door neighbors and cousins (both 2M). Moreover the 4 day gap in disease onset dates strongly suggests that one cousin infected the other.

The presence of three distinct clusters in Egypt this month, as well as three confirmed cases in three days has raised concerns that H5N1 infections were much higher than the reported 66 cases. The latest case is the 11th toddler between the ages of 1 ½ or 2 ½ in Egypt this year, representing a significant increase in frequency and number of H5N1 confirmed toddlers. This concentration of so many cases in such as small age group (in contrast to 6 toddler cases in the three preceding years), raises concerns that many in older age groups has protective immunity due to a significant prior exposure to H5N1.

These results indicate that toddlers with bird flu symptoms, but no contact with poultry, should be tested for H5N1. Moreover, the 99% of suspect cases with poultry contact who test negative by PCR should be tested fro H5N1 antibodies.

Recent results have suggested that the 3 BP deletion (S129del) in a subset of cases produces similarities with H1N1, and phylogenetic analysis of the first two toddler cases in 2009 had this deletion, raising concerns that this change, which interacts with the receptor binding domain, has produce H5N1 which is more efficiently transmitted.

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