H5N1 Human Clusters Continue To Cause Concern
Recombinomics Commentary 14:01
February 13, 2008
The recent familial cluster in Indonesia adds yet another H5N1 genetic background to the list of recently reported clusters. The recent clusters all had large gaps between disease onset dates, indicating they represented human to human (H2H) transmission, and these clusters involved all three major H5N1 sub-clades in circulation, clade 2.1 in Indonesia, clade 2.2 in Pakistan, and clade 2.3 in China.
Clusters have been reported about this time of the year for the past four years, but the increasing diversity of H5N1, coupled with milder infections that may not be reported, increases pandemic concerns.
Four years ago in early 2004, the clusters were limited to Clade 1 outbreaks in Vietnam. The clusters were small and involved two or three family members.
In early 2005, the clusters were larger in northern Vietnam. The expansion in numbers and size were linked to a decrease in case fatality rates. The vast majority of cases in northern Vietnam recovered, but these clusters represented a significant percentage of reported cases. Although these cases still involved clade 1, the cases in the north had acquired a novel HA cleavage site via recombination with clade 2 H5N1 circulating in China. Later in the year there were additional clusters in Indonesia (clade 2.1) and China (clade 2.3).
In early 2006, the focus shifted to the Middle East and adjacent countries. The first clade 2.2 human cases were reported in Turkey, which was followed by clusters in Iraq and Azerbaijan. All involved clade 2.2 and had receptor binding domain changes associated with increased affinity for human receptors.
In early 2007 these was a lull in clusters. The cluster in late 2006 in Egypt captured the most attention because the cluster of three was the largest reported to date in Egypt, and the cluster had two receptor binding domain changes and was oseltamivir resistant.
Now in earlier 2008 there is a cluster in Indonesia, which comes on the heals of the large cluster in Pakistan and small cluster in China.
Like earlier clusters, these cases are somewhat milder than earlier cases. In Pakistan there were two deaths among approximately 10 cases which were lab confirmed in Pakistan. In China both family members recovered, and in Indonesia the index is no longer in critical condition.
The milder cases however, raise concerns regarding undetected clusters. Last spring in Egypt, only one in 17 H5N1 confirmed patients died. Most cases were children who did not develop pneumonia. Such cases would be easily missed in most countries. In West Bengal India approximately 4 million birds have been culled. Many villagers engaged in high risk activity, including eating dead birds. However, there have been no confirmed cases in India or in adjacent Bangladesh, in spite of widespread infections in domestic and wild birds. Similarly, clusters have been reported in Indonesia that were not lab confirmed.
The possibility that the confirmed clusters, which almost certainly represent H2H, also signal mild undetected spread of H5N1 in human populations, continue to cause concern.
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