Effect of Antipyretic Drugs in Children with Malaria - Clinical ...

at febrile temperatures [6]. The time spent with febrile temperatures
may not have been long enough for a visible effect.
Our in vitro studies showed that a 6-h exposure to temperatures
of 40�C at late stages leads to significant growth inhibition.
Longer exposure is needed to inhibit parasite growth at 39�C.
In the present study, however, only 6 patients (7%) had a
cumulative exposure to temperatures of 140�C for at least 6 h,
and 20 (22%) had an exposure to temperatures of 139�C for
this period of time. One reason for the small numbers of patients
exposed to these temperatures might have been the exclusion
of patients with severe malaria, who presumably would
have higher temperatures or prolonged fever. Furthermore, an
effect of fever on the course of parasitemia would be masked
by the effect of quinine, which is undoubtedly much more
effective against P. falciparum than are febrile temperatures;
thus, a beneficial effect of fever on parasitemia perhaps could
be seen in yet untreated malaria.
Antipyretics are commonly given to children with infectious
diseases, to prevent febrile convulsions. However, with P. falciparum
malaria, in which convulsions are common, more than
one-half of convulsions occur at rectal temperatures of !38�C,
suggesting that the infection, not the fever, induces convulsions
(which thus cannot be prevented by reducing fever) [19].
Plasma levels of TNF and IFN-g were, not surprisingly, associated
with fever. In addition, we found a high correlation
between plasma levels of IL-10 and body temperature. TNF
leads to the production of IL-10, which suggests a rapid
counterregulatory response to inflammatory and pyrogenic cytokines
in these children with mild malaria [20].
Our earlier study showed decreased production of radical
oxygen intermediates after acetaminophen treatment [7]. Treatment
with naproxen or metamizol did not lead to a comparable
phenomenon.
The positive correlation between temperature and parasitemia
that we found at admission has been described earlier
for a large population [21]. The initial drop in parasitemia was
faster in the mechanical antipyretic treatment group than in
the other treatment groups. The reason for this finding remains
unexplained; however, the effect was not due to fever or production
of cytokines or oxygen radicals, since there was no
significant difference in these parameters between the treatment
groups during the first 6 h of therapy. An effect of the drugs
themselves was excluded by in vitro studies showing no effect
of metamizol or naproxen treatment on the growth of P. falciparum
(authors’ unpublished data).
Taken together, the benefits from not taking antipyretics do
not seem large. However, the relative ineffectiveness of commonly
used antipyretics, the high risk of overdosing [22], and
the need to reduce drug interactions strongly argue against the
widespread practice of giving adjuvant antipyretic drugs indiscriminately
to every child with P. falciparum malaria.
Acknowledgments
We thank the children and their parents or guardians for
their participation in this study and the staff of Albert Schweitzer
Hospital (Lambaréné, Gabon) for their support.
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