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Antibody Confounds Clinical Trial
September 22, 2009
At baseline, 76 of 240 subjects (31.7%)
had antibody titers of 1:40 or more on hemagglutination-inhibition assay
The above comments are from the recently completed clinical
trial for H1N1 in healthy adults in Australia. Although cases
with confirmed pandemic H1N1 were excluded from the study, over 31% of
the participants had protective antibody prior to the first infection,
signaling widespread influenza in undiagnosed adults. This high
level is likely linked to limited testing, as well as the use of fever
in the case definition. Thus, those without fever are not tested
and are significantly under-represented in confirmed cases.
Data on symptomatic patients without fever suggests the frequency of
infection without fever is above 50%. 30% of initial lab
confirmed patients in Mexico, who were hospitalized because of
breathing difficulties, did not have a fever. In Chile, the
frequency of confirmed patients without fever was 50%. A recent
study of transmission during a plane flight found that 36% of lab
confirmed cases did not have a fever.
However, these figures are likely to be higher in the general
population, because mild cases with no fever will not seek medical
attention, or will not be tested because they do not meet the case
definition, which includes fever.
Similarly, students without
fever will be largely missed because guidelines cite fever AND a
subset of additional symptoms, so those without fever are not
considered to be infected patients. Thus, they are misdiagnosed
as having colds, allergies, strep throat, bronchitis, or stomach flu,
and such students frequently remain in school,
infecting other students (see map).
This leads to a high percentage of infected cases in clusters that are
not tested in general, and those that are tested are almost exclusively
cases with fever.
Thus, the inclusion of fever in the case definition ensures significant
spread by patients without fever as well as a major undercount of
infections. This selective testing limits surveillance, and
creates a large reservoir of virus in patients who have not been
at Nature Precedings