Aggressive H5N1 in Egyptian Patients
Recombinomics Commentary 12:38
March 3, 2008
The Ministry of Health and Population has declared a new AI H5N1 human case, a female 25 years old from Sennoris district, Fayum governorate. The symptoms started on 24 February 2008 and hospitalized in Fayoum Fever Hospital on the 27th of the same month. The case was referred to Giza chest hospital on 28 February 2008. The field investigation is still ongoing to indicate the source of infection. The general condition of the patient is critical and she is on ventilator.
The above comments are from the WHO Eastern Mediterranean report on the most recent confirmed case in Egypt. The above dates suggest that the H5N1 was very aggressive, even though the patient was hospitalized three days after disease onset. The patient has pneumonia in both lungs and is in critical condition.
This rapid progression may reflect genetic changes in the H5N1. Last season the case fatality rate was markedly different in the fall than the spring. In late 2006, early 2007, the first seven confirmed H5N1 cases died. In contrast, there was only one fatality in the following seventeen case, which peaked in the spring. Many of the spring cases were in central or southern Egypt and patients did not develop pneumonia.
There were clear genetic differences between the cases in the fall, which were primarily in northern Egypt, and the spring cases. Three of the fatalities were family members of the Gharbiya cluster. Sequences from this group had two receptor binding domain changes, V223I and M230I, and were Tamiflu resistant due to N294S.
Subsequently, poultry sequences similar to the human sequences were found in Gharbiya, A/chicken/Egypt/1892NAMRU-3 HK-49/2007, or Beni Suef, A/chicken/Egypt/F6/2007. Although both HA sequences had V223I and M230I, the Gharbiya chicken did not have N296S and the NA sequence from the Beni Suef chicken has not been released.
This season, NAMRU-3 released another series of sequences which were similar to the Gharbiya sequence from last season, including V223I and M230I, but there were also a large number of additional non synonymous changes raising concerns that H5N1 in Egypt was being driven in part by the vaccination program.
The concern over mismatched vaccines is also increased due to recent sequences released by the national veterinary lab in Egypt. Sequences from vaccinated farms also had a large number of newly acquired polymorphisms, which were predominantly non synonymous. Similar sequences were found at additional locations in the Nile Delta in isolates from December, 2007 and January, 2008.
Last season, all reported H5N1 infections with M230I were fatal. This season, four of the five confirmed cases in late 2007 were fatal, but sequences from these cases have not been released. The recent sequences released from the National labs had M230V, which may also be linked to a higher case fatality rate.
The two confirmed patients in the past week have developed pneumonia, and the most recent cases is in critical condition.
Release of the human H5N1 sequences from the seven confirmed cases this season would be useful.
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