Recombinomics Commentary

Rehab Mahmoud Helmi Abul Magd, and it reaches its age “6 years”, she entered the hospital of Nag Hamadi fevers last Sunday and she suffers from a rise in the temperature after its mixing the birds.

Also the hospital of Nag Hamadi fevers yesterday detained, Ahmed Rehab’s brother, and her uncle’s wife, Mona Hashem, and its neighbour named Fouad, for their injury by symptoms similar to the bird flu.

The above translation, from the spring of 2007, describes the Qena cluster.  At the time the index case (6F) had been confirmed and her brother, who developed symptoms after his sister’s admission, was also confirmed.  The HA sequences from the two siblings were identical and contained the 3 BP deletion that codes for S129del, a position in the receptor binding domain.  The wife of the index case’s uncle tested negative as did the neighbor, although both had symptoms.

The WHO reporting on this cluster was curious.  The disease onset date of the index case was not stated in the WHO update from Geneva.  The admission date, March 25, 2007, matches the above description.  The WHO Mediterranean office also issue a description of the index case and stated that osletamivir treatment began on the day of admission, which was one day after the start of symptoms, indicating the sister sought treatment immediately.

However, her brother was said to have developed symptoms on March 26, but was not hospitalized until March 29, raising the possibility that his case was even milder and he would not have sought medical treatment if his sister was not confirmed.  Similarly, the failure to detect H5N1 in the two symptomatic contacts raises concerns that the PCR testing lacks sensitivity.  The lack of sensitivity is support by the failure to detect H5N1 in more than 99% of the hospitalized patients in Egypt who have symptoms and stated contact with dead or dying poultry.

The confirmation of H5N1 in two siblings hospitalized four days apart suggests human to human transmission.  However, even if the two siblings were infected independently from a common source, the clustering signals more efficient transmission.  The deletion produces an antigenic profile that is similar to seasonal flu, H1N1, which is efficiently transmitted human to human.  The siblings were also among a spate of mild cases in the spring of 2007.  Only one of the 17 confirmed cases died, and the vast majority of cases were children between the ages of 3-10, who not only survived, but didn’t develop pneumonia.  Some had the 3 BP deletion, as seen in the siblings, while others had a novel HA cleavage site, first reported in H5N1 in wild birds in Mongolia.  The NA sequences of both sets of patients were similar, suggesting a common origin.

In 2009, the cases are again mild (no fatalities in the first 12 confirmed cases), except the target population is toddlers between the ages of 1 ½ and 2 ½ (10/12), raising concerns that the spread of H5N1 in 2007 extended well beyond the confirmed cases.  As noted above, the contacts of two confirmed cases had symptoms, but tested negative for H5N1.  These symptomatic contacts were not mentioned in the global or regional WHO updates and their final diagnosis is unclear.  They were likely given oseltamivir and recovered, which is the case for the vast majority of the hospitalized suspect patients who are PCR negative. The patients who were treated and recovered, including the 99% of recently hospitalized patients in Qena should be the first tested for convalescent H5N1 antibodies (3-4 weeks after disease onset).  However, symptomatic toddlers who lack a poultry contact should also be tested, initially by PCR and subsequently for antibodies.

The Qena cluster in 2007 was a clear warning, which was actively ignored.  The return of mild H5N1 in a target population raises serious pandemic concerns.