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Pandemic Flu Fever Failure Fuels School Cluster Explosions
Recombinomics Commentary 17:06
August 21, 2009

The standard definition of influenza includes a fever. But an odd feature of the new virus is the lack of fever in a significant proportion of documented cases, even after some patients become seriously ill. In Chile, it was about half, in Mexico City about a third and elsewhere, less, Dr. Wenzel said. Lack of fever has been noted by other observers in several Canadian cases.

Analysis of data from specimens yet to be tested may shed light on how often infected individuals who have no fever spread the virus.

The above comments from the NY Times pandemic influenza report suggest that H1N1 infections are markedly higher than confirmed cases, and the absence of fever can lead to significant silent spread (see map).  As noted, most associate fever with influenza, so the initial observations in Mexico on the percentage of patients infected without fever were low.  Milder cases would probably not seek medical treatment, and those who did would probably be mis-diagnosed, because of the absence of a fever.  Even the 50% of H1N1 fever failures in Chile is likely to be an under-estimate.

Sequences have been published worldwide, including those from Mexico and Chile.  All isolates are closely related and it is likely that differences in the frequency of infected patients without fever are tightly linked to testing.  In the US, fever is used in the case definition, so the official numbers show that 93% of lab confirmed cases have a fever.  However, this is almost certainly linked to the case definition.  Thus, patients without a fever do not meet the case definition and are not tested.

The high frequency of infections without fever may be linked to the pandemic H1N1 PB2 gene, which is avian.  The avian PB2 has optimal activity at 41 C, the body temperature of birds.  In mammals, a high fever is usually detrimental to an infectious agent, but in influenza with avian PB2, the higher temperature may lead to an increased level of virus.  Therefore some hosts may have a feedback mechanism that keeps the patient's temperature low, which may limit viral replication.

However, these patients may still be infectious, and the absence of a fever may lead to increased exposures because the patient may assume that there is no swine flu infection.  The lack of fever likely had a serious effect on border checks which used fever as a diagnostic tool.  Consequently the 50% of infections with no fever would pass through border fever scans undetected.

The absence of fever can also seriously impact students.  Current policy is to keep schools open and monitor infections, which are largely linked to the presence or absence of a fever.  A fever is included in instructions to parents for keep ill students at home, and is also used to determine when the student can return.

The emphasis on fevers will likely keep students in school, because they will assume that an absence of fever will mean that they do not have swine flu and are not infectious.  Since serious cases have no fever, the absence of a fever is not likely to be linked to an absence of transmissible virus, and therefore these students are likely to silently spread pandemic H1N1.

A serious testing program of student with symptoms, but lack a fever is long overdue.  The current approach, of using fever in the H1N1 case definition is likely to increase spread of H1N1 in schools in the upcoming weeks.

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