Commentary
H5N1
False Negatives in Egypt Raise Serious Concerns
Recombinomics Commentary
20:31
April 2, 2009
The above translation describes the hospitalized suspect H5N1 patients that tested negative in Egypt. Since the number of confirmed cases is 61, over 99% of suspect hospitalized patients test negative. Although these negatives may simply signal active testing, the recent concentration of confirmed cases in toddlers raises concerns that the number of true infections in Egypt is orders or magnitude higher than confirmed cases, and the absence of recent confirmed older cases is linked to immunity due to prior exposures to H5N1.
Although no H5N1 sequences have been released from human cases this season, prior sequences are available for almost all prior confirmed cases. In other countries, such as Indonesia, the vast majority of H5N1 isolates are from fatal cases. Although recovered cases are rare in Indonesia, the number of isolates from survivors is zero, or very close to zero. In contrast, most of the confirmed cases in Egypt are not fatal. In the spring of 2007, 16/17 patients survived, but isolates were obtained from all cases.
This high isolation rate raises concerns that only patients with high viral loads test PCR positive, which leads to an isolation rate approaching 100% regardless of outcome. Those patients with lower viral loads test negative and therefore virus isolation is not attempted.
Data supporting the lack of sensitivity in the PCR detection is the Gharbiya cluster. All three cases were fatal, but only two of the three members were PCR positive. The two that were positive were positive twice, once on samples collected prior to the start of Tamiflu treatment, and again in samples collected 48 hours after the start of Tamiflu treatment. The failure to register a PCR positive for the third fatal infection suggests false negative rates in milder cases may be significant.
In the past, H5N1 positives were concentrated in young women and girls, which was attributed to poultry contact, which was largely limited to females in Egypt. However, many of the cases in the summer of 2007 were children, and most of those cases were mild.
Thus, prior to this year, two major groups were represent in H5N1 outbreaks. Mild cases with lower viral loads may have tested negative, but may have generated protective immunity.
Therefore, the current spate of cases is limited to toddlers, who have not been previously exposed to H5N1.
Aggressive antibody testing of prior at risk populations would be useful.
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