Evolutionary Approach to Medicine

Marcelo Turkienicz Berlim, MD, Alberto Mantovani Abeche, MD, Department of Gynecology and Obstetrics, Federal University of Rio Grande do Sul, School of Medicine, Porto Alegre, RS, Brazil

South Med J. 2001;94(1) 

In This Article

Why Fever?

Several recent studies have shown that fever and its direct consequences are adaptations of natural selection specifically to fight infections,[8,9] both by increasing the phagocytic and bacterial activity of neutrophils and by optimizing the cytotoxic activity of lymphocytes.[10] According to Kluger et al,[8] current evidence indicates that fever is a primitive immunologic response, with a long phylogenetic history. Fish, for instance, when inoculated with bacterial endotoxins or gram-negative bacteria, instinctively raise their body temperature by swimming toward regions where water is warmer. When lizards are inoculated with pyrogens or bacteria, they expose themselves to the sun to increase their body temperature up to feverish levels by means of the irradiated heat. Moreover, fever inhibition in rabbits infected with type III pneumococci increases their death rate.[9] Finally, for his work with artificial fever production, Wagner-Jauregg won the 1927 Nobel Prize in Medicine and Physiology. He treated syphilitic patients by inoculating Plasmodium spp (responsible for malaria).[9]

In an early study with rhinovirus-infected volunteers, Stanley et al[11] reported that aspirin therapy was associated with a significant increase in virus shedding when compared with placebo. In a subsequent study, Mogabgab et al[12] found no differences in this parameter between placebo-treated and aspirin-treated individuals. In a more recent placebo-controlled study done by Doran et al,[13] 68 children infected by varicella alternatively received acetaminophen or placebo for 4 days. The outcome was surprising: children who had taken placebo recovered 1.1 day faster (ie, time to total crusting) than those who had taken acetaminophen (P < .05) and even presented fewer clinical symptoms on the fourth day. The researchers' conclusion was that besides not having relieved varicella symptoms, acetaminophen extended the course of the disease. In another double-blind, controlled study done by Graham et al,[14] 56 volunteers were intentionally infected with type II rhinovirus, and variables such as antibody levels and clinical symptoms were monitored. It was observed that the use of aspirin and acetaminophen was associated with the suppression of the neutralizing humoral immune response (P < .05) and that aspirin was associated with an increase of nasal symptoms such as nasal obstruction (P < .05).

However, an evolutionary perspective offered by Darwinian Medicine calls attention to the costs and benefits of an adaptation such as fever. If there were no disadvantages in having a 38°C body temperature, the body would always remain at this temperature to prevent infection from emerging.[1,2] Nevertheless, even this moderate fever has its costs: for each 1°C rise in body temperature, there is an increase of 13% in oxygen consumption, besides an increase in caloric needs and the induction of a temporary infertile state in men. Episodes of even higher fever may cause delirium and stupor and accelerate muscular catabolism.[10]

Antipyretics are frequently administered without a compelling medical reason.[15] In most febrile illnessess, there is no evidence that fever is detrimental or that antipyretic therapy offers any benefit.[9] Likely exceptions to this principle may include pregnant women, patients for whom a hypermetabolic state could be dangerous, children with a history of febrile seizures, and patients who cannot tolerate a rise in intracranial pressure.[9,10,16,17]

Keeping in mind that bringing fever down by using medication possibly postpones recovery, increases the probability of a secondary infection, deprives one of clues as to the need for further examination or for changes in the therapeutic approach, and may provoke widespread side effects, physicians should treat feverish patients only when the expected benefits outweigh the possible risks.[1,2,9,10,16]

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