Abstract
BackgroundAvian influenza H5N1 has a high human case fatality rate, but is not yet well-adapted to human hosts. Amino acid substitutions currently circulating in avian populations may enhance viral fitness in, and thus viral adaptation to, human hosts. Substitutions which could increase the risk of a human pandemic (through changes to host specificity, virulence, replication ability, transmissibility, or drug susceptibility) are termed key substitutions (KS). Egypt represents the epicenter of human H5N1 infections, with more confirmed cases than any other country. To date, however, there have not been any spatial analyses of KS in Egypt.MethodsUsing 925 viral samples of H5N1 from Egypt, we aligned protein sequences and scanned for KS. We geocoded isolates using dasymetric mapping, then carried out geospatial hot spot analyses to identify spatial clusters of high KS detection rates. KS prevalence and spatial clusters were evaluated for all detected KS, as well as when stratified by phenotypic consequence.ResultsA total of 39 distinct KS were detected in the wild, including 17 not previously reported in Egypt. KS were detected in 874 samples (94.5%). Detection rates varied by viral protein with most KS observed in the surface hemagglutinin (HA) and neuraminidase (NA) proteins, as well as the interior non-structural 1 (NS1) protein. The most frequently detected KS were associated with increased viral binding to mammalian cells and virulence. Samples with high overall detection rates of KS exhibited statistically significant spatial clustering in two governorates in the northwestern Nile delta, Alexandria and Beheira.ConclusionsKS provide a possible mechanism by which avian influenza H5N1 could evolve into a pandemic candidate. With numerous KS circulating in Egypt, and non-random spatial clustering of KS detection rates, these findings suggest the need for increased surveillance in these areas.
Highlights
Avian influenza H5N1 has a high human case fatality rate, but is not yet well-adapted to human hosts
Geospatial hot spots were evaluated for individual Phenotypic Consequences Group (PCG), using a p-value cutoff of 0.05 to evaluate statistical significance
We detected probable hot spots based upon dasymetric adjustment for PCG1 in Alexandria and Beheira and for PCG2 only in Beheira, the remaining PCGs falling below the 9500 iterations threshold
Summary
Avian influenza H5N1 has a high human case fatality rate, but is not yet well-adapted to human hosts. Given the high pathogenicity of the virus, an H5N1 virus capable of airborne human-to-human transmission could lead to a devastating pandemic [3,4,5]. This scenario has been predicted for many years [1, 2, 6, 7]. Egypt has reported more confirmed human cases of avian H5N1 than any other country, and is regarded by many observers as the epicenter of human H5N1 infections [1, 13,14,15,16,17].
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