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WHO Analysis of H5N1 Transmission in Egypt
But a W.H.O. spokesman said privately that the agency was just helping the Egyptians with a long-planned study and the article had “jumped the gun.”
Gregory Hartl, a spokesman for the WHO, told CIDRAP News that because of holiday observances in Egypt, the WHO team just left for that country today.
The above comments suggests there are two distinct WHO investigations of H5N1 in Egypt, which are related to mild cases in children in the spring of 2007, as well as mild cases in toddlers in 2009. The initial comments above reported in the Donald McNeil New York Times piece on the mild cases in toddlers are in reference to the 2007 data and such antibody studies have been previously planned for the summer.
The latter comments are with regard to WHO officials who are en route to Egypt, which are linked to the 2009 toddler cases and clusters. This week’s trip is also supported by a report from the European Centre for Disease Prevention and Control as well as local media in Egypt, which are focused on the high incidence of mild toddler cases this year.
In the spring of 2007, 16/17 H5N1 cases recovered, and 16/17 cases were in children between the ages of 3-10. The vast majority of these cases not only recovered, but did not develop pneumonia and the cases presented much like seasonal flu. In addition, sequences from cases that were not epidemiologically linked were virtually identical, and the one cluster that was epidemiologically linked involved siblings in Qena, whose sequences match each other and had a deletion, S129del. The identity of the sequences, and the four day spread in admission dates strongly supported human to human transmission. Moreover, additional contacts had symptoms, but tested negative. These data raised concerns that the H5N1 was silently spreading because many patients with symptoms would not seek treatment or would be treated for seasonal flu and would not be tested for H5N1.
Such spread could be identified by tests fro H5 antibodies. However, recent data on immune responses in recovered H5N1 patients in southeast Asia indicates that antibody levels are largely not maintained over time, and therefore such patients may return false negatives if tested weeks, months, or years after exposure. Thus, such testing may not identify asymptomatic or mild cases because of delays in testing and reductions in antibody levels over time.
This year there were mild cases in Egypt again, except the demographics had changed. Instead of involvement of children between the ages of 3-10, almost all confirmed cases were toddlers. Previously, infections in toddlers were rare. In the 51 confirmed cases in 2006-2008, only six were toddlers. In contrast, 10 of the first 11 cases in 2009 were toddlers and the current count is 11 of 15 cases. Only one of the older cases was a child, so 11/12 children were toddlers between the ages of 1 ½ and 2 ½. This new demographers increased concerns that the mild cases in 2007 were widespread in children providing protective immunity, which limited the number of confirmed cases in 2009 to one child.
The data in 2009 was characterized as “something strange” as noted above and increased concerns that the number of human H5N1 cases in Egypt was orders of magnitude higher than the current 66 confirmed cases. Evidence for additional cases comes from test results as well as the mild nature of confirmed cases. In Egypt, suspect cases with a history of exposure to dead or dying poultry leads to rapid treatment and testing. However, more than 99% of hospitalized and suspect cases are PCR negative. Moreover, cases without a poultry connection are not tested, so cases without a stated connection could be silently spreading H5N1, even if symptomatic.
Thus, there is concern that the mild cases in the toddler demographic may signal a broad spectrum of testing failures and the recent cases should be tested for antibodies, which are at peak levels 3-4 weeks after disease onset. Therefore the symptomatic cases that are PCR negative should be tested for antibody now, not at some future date when antibody levels decline. Similarly, toddlers, which are the current major at risk population, should be PCR tested, and those who have recently recovered should be tested for antibodies.
Repeating failed experimental protocols of the past is not useful.
Serious testing for H5N1 in Egypt is long overdue as is the release of H5N1 sequences, which are expected to contain the same deletion seen in the Qena cluster in 2007.