Study profiles human H5N1 burden in Egypt

Mar 22, 2011 (CIDRAP News) – A study of human H5N1 influenza cases in Egypt, including a genetic analysis of some of the isolates, shows that most cases have occurred in children and females but does not explain why the fatality rate there is significantly lower than in other countries.

Writing in PLoS One, a team of US and Egyptian scientists says Egypt became the epicenter of human H5N1 cases in 2009 and 2010, with 68 of the 121 cases reported worldwide. But the country's H5N1 case-fatality rate (CFR) is 34%, versus 60% for other countries with human cases.

Because the H5N1 viruses in Egypt seem to be less virulent than those elsewhere, there is concern that they are becoming more adapted to humans, say the authors, who are from St. Jude Children's Hospital in Memphis and the Egypt's National Research Center in Cairo. Their report was published yesterday.

119 cases in 5 years
Egypt had 119 human H5N1 cases from 2006 through 2010, with 40 deaths (CFR, 34%), the report says. In 2006 the cases peaked in the spring, and in the ensuing 4 years they peaked in the winter and spring. There were three family clusters totaling seven cases during that time.

Sixty-two percent of the patients were under age 18, and 60% were female. The mean age for all patients was 10.0 years, with a range of 1 to 75 years. The young age distribution could reflect Egypt's demographics or children's level of contact with poultry, the authors say. They also note that women typically play the lead role in tending backyard poultry, perhaps explaining the burden of cases in females, but this needs corroboration.

The fatality rate increased with age and was three times as high in females as in males, the investigators found. The CFR ranged from 4% for children under 5 to 10% for 5- to 9-year-olds and 53% for 10- to 18-year olds. Adults up to age 49 had a 61% CFR, and the rate was 75% for older adults. The rate for females was 47%, versus 15% for males, a significant difference.

The CFR also varied considerably by year and was particularly low in 2009, at 10%, before bouncing up to 45% in 2010, the authors note. Most of the cases in 2009 were in children under age 5, but a regression analysis showed that mortality was significantly lower in 2009 than in other years even when the different age distribution was taken into account.

The time from illness onset to hospitalization was found to be a key factor in risk of death. The CFR for patients who were hospitalized within the first 2 days was 8%, versus 54% for those who were hospitalized later, a significant difference.

The authors caution that the overall 34% CFR may be an overestimate, because the rate of unrecognized cases is unknown.

The team found that the pattern of H5N1 cases in humans tends to mirror the pattern in poultry, both in frequency and severity. "Milder disease among poultry leads to mild human infection," the report says. "For instance, a decrease in human case-fatality rate in 2009 was accompanied by an observed decrease in mortality among poultry."

No host-adaptation mutation
On the genetic front, the scientists say several sublineages of H5N1 clade 2.2.1 have been reported in Egypt, of which at least three are still circulating. They identified what they believe is a new sublineage, which they call Egypt-G, represented by four isolates. But they found no specific lineages that seemed to circulate in humans but not in birds or vice versa, and thus no "host-adaptation mutation."

Similarly, they couldn't find particular changes in the virus that seemed linked to changes in the fatality rate: "We were not able to confirm that lower pathogenicity of the viruses is the main reason for increase or decrease in the mortality rate among humans in Egypt."

The virus appeared "in its most virulent form in 2006," and any significant mutation may be expected to lead to lower virulence, they add. But they caution that other host and environmental factors that may affect disease severity must be properly studied before concluding that any decrease in mortality is due to mutations.

The study was limited to lab-confirmed cases reported to the World Health Organization, and a lack of data for many variables forbade an in-depth epidemiologic investigation, the authors say.

They say experts are concerned about "the potential of H5N1 viruses circulating in Egypt to become more adapted to human-to-human transmission," because the viruses are less virulent and may be causing asymptomatic infections, especially in adults. Consequently there is an urgent need for more epidemiologic studies in Egypt, they conclude.

Kayali G, Webby RJ, Ducatez MR, et al. The epidemiological and molecular aspects of influenza H5N1 viruses at the human-animal interface in Egypt. PLoS One 2011 Mar 21;6(3):e17730 [Full text]

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