Naturopathy always claimed that a natural process like fever should not be suppressed. A long tradition of empirical observation confirms that fever is helpful and meaningful.
More formally, the same is claimed by Darwinian or evolutionary medicine. Evolutionary medicine investigates medical topics in the light of the evolutionary development. Our function, our robustness and adaptability are the product of billions of generations.[1] Every biological function is a product of this evolutionary process.[2] Fever is one of these functions. It is produced in warm and cold-blooded vertebrates for over 600 million years. Therefore, fever must be a meaningful means of the organism to fight infections.[3] That is, fever is not a complication of a disease. The organism intentionally increases body temperature to create a better immune response.
Yet science, as we understand it today, regards empirical knowledge and theoretical reasoning not as valid. Scientific is only what studies, clinical and laboratory research say.
It is astonishing that the use of antipyretics, although it is one of the most common medical treatments, never went through a rigorous research process. Most is done by good faith, fear or out of habit. That is, the use of antipyretics is unscientific. Of course, there are quite a few small studies that investigated the effects of antipyretic therapies. Most of them agree in one point: antipyretics in infectious disease do more harm than good.
Some problems in the use of antipyretics
Taking antipyretics, people recover slower from influenza[4] or varicella.[5] The disease lasts longer and has more and more intensive symptoms. This is exactly what I have seen in my 30 years of practice. During a flu, people and especially children have continuously 39-40 degrees fever for 3 days and then it is over. Giving antipyretics the disease might last much longer, a week, or even more. Complications like otitis and pneumonia occur more easily, something hardly seen when no antipyretics are given.
The only systematic review on the use of antipyretics (at least as I know) has been conducted in animals. It shows exactly this motive: antipyretic treatment increases the risk of complications and mortality.[6] For example, the virus spreads more easily to CNS. [7]
Laboratory research supports these clinical findings. Antipyretics reduce the function of the immune system on many levels (overview).[8] They suppress the immune reaction. Lymphocyte trafficking,[9] interferon response,[10] and enzyme activity, all important for the immune response, are reduced.[11]
In the context of Covid 19 two studies are important.
- If a person has pneumonia, the higher the fever was, the less were complications.[12] The result of this study is in line with the clinical observation of Tsiodras that high fever was associated with a better outcome in Covid 19.[13]
- A study compared critically ill patients treated with and without antipyretics. The patients who took antipyretics had condiderably more complications and a worse development that the study had been stopped ahead of time out of ethical reasons. [14]
That antipyretics might increase the severity of a disease was already a topic during the Spanish flu. Aspirin, then a new and miraculous drug, had been extensively used when the pandemic raged. Aspirin contributed to the high lethality of the disease.[15]
The fear of fever
There is a tremendous and unfounded fear of fever. The following are common wrong opinions about fever (in adults and children older than 5 months)
- There is the fear that fever might harm. It does not. A disease might harm. If someone suffers from a meningitis, a pneumonia, a pericarditis or a nephritis, the person might suffer damage. But this is not because of the fever. Fever is the attempt of the body to solve the problem. Moreover, it does not destroy brain cells.
- Fever does not rise uncontrolled to a dangerously high level. It normally stops somewhere at 40. Some children might have an overshot during the first hours of an infectious disease. But then temperature goes back to lower levels of 39-40. Rarely fever remains higher than 40,5. If fever remains at 41 degrees it might be a sign of a more severe development or of a complication. But lowering the temperature even in this case is of no benefit, as the studies cited above demonstrated. In any case, there is no need to measure every half an hour body temperature as some parents do. This just disturbs and stresses the child who needs a calm and relaxed environment to get well again. (The right care for an ill child will be discussed in a future article.)
- As long as the nervous system is still unripe, until the age of 2-5 years, mostly between 12-16 months, there is a certain probability of fever cramps.[16] About 2-4% of children will suffer from such a fever cramp. Mostly it is a single event. These cramps have in general a duration of 10-30 seconds, although up to 10 min are still regarded as normal und unproblematic. Of course, parents are shocked when their child cramps, but when they realize what happens, the cramps are mostly over. Fever cramps do not damage.[17] Most cramps manifest during the first hours of fever, when the body temperature rises abruptly and it appears rarely on the second day. If there is no history of fever cramps, antipyretics should not be given to prevent them. Especially as there are indications that antipyretics might not prevent these cramps at all.[18]
- Parents don’t want their children to suffer and they do not want to suffer themselves. They cannot stand the fear and the uncertainty. Antipyretics become a tranquilizer for the parents. This is a very harmful strategy. If we compare fever with a red control lamp in a car, flashing up in case of a problem, the antipyretics would mean to cover the lamp with a band and to continue to drive normally. The disease is not changed for better when fever is suppressed. It tends to become worse.
- Children with fever are mostly quiet and sometimes lethargic. After receiving antipyretics, they feel better, play and do a lot of activities they should avoid being ill. Eating is such an activity. Anorexia during an infection is helpful and important. It is one of the meaningful evolutionary mechanisms since millions of years. The body needs all its energy to fight an infection. Digestion disturbs this fight. But there are parents even saying, “I gave antipyretics so that my child could eat at least”. This little trust they have in the function of the body.
As a result, antipyretics might be harmful for the individual taking them. But they have also a social aspect.
The social aspect of antipyretics
The suppression of fever reduces the function of the immune system. Consequently, the so-called viral load is higher, e.g. in influenza (and probably in Covid 19). That is, more viruses remain in the upper respiratory system.[19]
In every crisis we learn new terms. During the financial crisis we learned what ‘spreads’ are. Now we get used to the viral load and also to the term basic reproduction number (R0). This number R0 describes how infective a disease is, or, more exactly, represents the number of secondary infections resulting from a single primary infection into an otherwise susceptible population.[20] It played an important role in the Coronaviruse pandemic. The development of the epidemic and what kind of restrictive measures have to be taken had been based on this number.
Antipyretics increase the reproduction number. Models show that for influenza the increase might be 1 or even up to 5.[21] Antipyretics, and this is important to understand, play an important role how easily a disease is transmitted. Or to translate it into the terms of social restrictions, the difference might be light or severe restrictive measures. Some called the use of antipyretics even unsocial.[22]
[1] Lenski RE, Barrick JE, Ofria C (2006): Balancing Robustness and Evolvability. PLoS Biol 4(12): e428,
https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.0040428
[2] Weitz JS, Benfey PN, Wingreen NS (2007) Evolution, Interactions, and Biological Networks. PLoS Biol 5(1): e11,
https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.0050011
[3] Berlim MT, Abeche AM (2001): Evolutionary approaqcxh to medicine, Souther Medical Journal 94; 1: 26-32
[4] Plaisance KI, Kudaravalli S, Wassermann SS, Levine MM, Mackowiak PA (2000): Effect of antipyretic therapy on the duration of illness in experimental influenza A, Shigella sonnei, and Rickettsia rickettsii infections, Pharmacotherapy 20; 12: 1417-1422
[5] Doran DF, DeAngelis C, Baumgartner RA, Mellits ED (1989): Acetaminophen: More harm than good for chicken pox? J Pediatr 114: 1045-1048
[6] Sally Eyers, et al. The effect on mortality of antipyretics in the treatment of influenza infection: systematic review and meta-analyis. Journal of the Royal Society of Medicine 2010; 103 (10): 403-411
[7] Sunden Y, Park CH, Matsuda K, Anagawa A, Kimura T, Ochiai K, Kida H, Umemura T (2003): The effects of antipyretics on influenza virus encephalitis in mice and chicks, J Vet Med Sci. 2003 Nov;65(11):1185-8
[8] Evans, S. S., Repasky, E. A., & Fisher, D. T. (2015). Fever and the thermal regulation of immunity: the immune system feels the heat. Nature reviews. Immunology, 15(6), 335–349. https://doi.org/10.1038/nri3843
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4786079/
[9] Chen Q, Fisher DT, Clancy KA, Gauguet JM, Wang WC, Unger E, Rose-John S, von Andrian UH, Baumann H, Evans SS (2006): Fever-range thermal stress promotes lymphocyte trafficking across high endothelial venules via an interleukin 6 trans-signaling mechanism, Nature Immunology 7, 1299 – 1308
[10] John FS Crocker, et al. Effects of antipyretics on mortality due to influenza B virus in a mouse model of Reye’s syndrome. Clinical and Investigative Medicine 1998; 21 (4/5): 192
[11] Blaho VA, Buczynski MW, Dennis EA, Brown CR (2009): Cyclooxygenase-1 Orchestrates Germinal Center Formation and Antibody Class-Switch via Regulation of IL-17, J. Immunol., 183: 5644 – 5653.
[12] Barlow G, Lilie P et.al. (2010): FEVER AS NATURE’S ENGINE, BMJ 2010;340:c90
[13] Evening bulletin 19.3.20
[14] Carl I. Schulman, et al. The effect of antipyretic therapy upon outcomes in critically ill patients: a randomized, prospective study. Surgical Infections 2005; 6 (4): 369-375
[15] Starko KM (2009): Salicylates and Pandemic Influenza Mortality, Clinical Infectious Diseases, 2009; DOI: 10.1086/606060
[16] Waruiru C, Appleton R (2017): Febrile seizures: an update, Arch Dis Child 2004;89:751–756. doi: 10.1136/adc.2003.028449
[17] Leung, A. K., Hon, K. L., & Leung, T. N. (2018). Febrile seizures: an overview. Drugs in context, 7, 212536. https://doi.org/10.7573/dic.212536
[18] Mewasingh LD (2014): Febrile seizures, Clinical Evidence 2014;01:324
[19]Husseini RH, Sweet C, Collie MH, Smith H (1982): Elevation of nasal viral levels by suppression of fever in ferrets infected with influenza viruses of differing virulence, J Infect Dis 145:520-52
Stanley ED, Jackson GG, Panusarn C, Rubenis M, Dirda V. Increased Virus Shedding With Aspirin Treatment of Rhinovirus Infection. JAMA. 1975;231(12):1248–1251. doi:10.1001/jama.1975.03240240018017
[20] Perasso A (2018): AN INTRODUCTION TO THE BASIC REPRODUCTION NUMBER IN
MATHEMATICAL EPIDEMIOLOGY, PROCEEDINGS AND SURVEYS, September 2018, Vol. 62, p. 123-138
[21] Earn DJ, Bolker PW, Bolker PM (2014): Population-level effects of suppressing fever, Proc. R. Soc. B.28120132570 http://doi.org/10.1098/rspb.2013.2570
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