Since inflammation is the body’s natural response to help …

  • Culture often trumps science even when it’s to the detriment of health. Unnecessary and even harmful suppression of certain types of inflammation falls in such a category. The cultural aspect here perhaps started with fever phobia (1). Fever is after all one of the most commonly recognized signs of generalized, widespread inflammation in the body. Thus this answer focuses on how as an example of inflammation it’s become common practice to reduce fever even though doing so may often be counter-productive in more than one way.

    Fever phobia is exaggerated fear of its potentially serious, irreversible consequences, such as febrile seizures, brain damage, coma, convulsions, dehydration and even death, especially in children (2). Coined in 1980 (3), even today careful meta-analyses of studies probing the public’s, and in particular parents’, attitude to fever find that this exaggerated fear of fever has hardly abated (2), meaning it’s stably entrenched as a cultural attribute.

    So what was the source or impetus for fever phobia in recent times? Quite plausibly, reports of higher risks of death from pediatric febrile seizures helped imprint a cultural fear of fever. For example, as far back as 1950 a study reported a 11% mortality risk for children with febrile seizures (4). Since most parents have limited knowledge of fever especially its many benefits (5, 6), fear of febrile seizures quickly permeated and became embedded culturally. This even when studies find up to a third of children brought to clinics aren’t truly febrile (1, 7, 8, 9). Some examples of fever phobia:

    • 85% of surveyed US parents reported they’d wake a child to administer antipyretics (10) even though pediatricians recommend against it (11).
    • 33 to 65% of surveyed UAE and Israeli parents reported giving acetaminophen for temperatures <38oC, i.e., for temperatures not likely to be fever (12, 13).
    • 74% of surveyed Canadian parents considered fever to be dangerous and 90% always attempted to treat it (14).

    Multiple other sources including but not limited to pharmaceutical companies, the media and pediatricians further helped embed the cultural fear of fever. For example, studies frequently find that pediatricians widely perceive fever to be dangerous (15) and advocate treating even mild fevers with antipyretics. For e.g., a 1992 survey found 65% of pediatricians perceived fevers to be dangerous and 72% often or always recommended antipyretic Rx (11).

    It’s only much more recently that much larger, much more thorough studies found that long-term mortality risk isn’t increased in children with febrile seizures. For e.g., a Danish study on 1675643 children (yes, a study with >1 million children!) born between 1977 and 2004 found 132 of 100000 children died within 2 years of a febrile seizure compared to 67 among those who didn’t (16), i.e., ~2X increased risk. However, more careful analysis showed short-term mortality risk among children with simple febrile seizure, i.e., no recurrence, was similar to those without. The short-term mortality risk was only increased among those with recurrent febrile seizures, which ‘was partly explained by pre-existing neurological abnormalities and subsequent epilepsy‘ (16). More importantly, long-term mortality rates were similar among children who either experienced febrile seizures or didn’t. Moreover recent studies suggest a strong influence of genetic risk factors for recurrent, familial febrile seizures (17, 18). Since such recurrent febrile seizures are much more rare, specific genetic risk factors thus imply vast majority of fevers, especially in children, have low risk for them and for their recurrence.

    At least four problems ensue from widespread exaggerated perception of the danger of fever and the knee-jerk response to immediately reduce it.

    • One, studies suggest antipyretics don’t prevent febrile seizures (19, 20, 21, 22).
    • Two, antipyretics themselves can have severe, though rare, side-effects such as liver or renal failure, GI tract ulcers (1) and even Stevens-Johnson syndrome (23) or asthma (24, 25).
    • Three, often parents inadvertently compound such risks by giving incorrect doses of antipyretics (12). For e.g., a study found as many as 50% of US parents did so (26).
    • Four, antipyretics such as paracetamol may delay recovery from infections or impede generation of effective immune responses to vaccines.
      • Antipyretics delay malaria parasite clearance for example (27).
      • Widespread antipyretic use may even help spread infectious diseases such as flu (28), perhaps because patients stay sick and retain higher infectious viral titers longer.
      • In recent years, it’s become more commonplace for pediatricians (29, 30, 31, 32) and even the US Advisory Committee on Immunization Practices (ACIP) (33) to recommend prophylactic antipyretic Rx prior to vaccinations to minimize the febrile response even though this is counter-productive. For e.g., individuals pre-treated with antipyretics have decreased immune responses to vaccines. This is seen not just in children (to DTaP + HBV + IPV/Hib*) (34) but also in adults (to HBV) (35).

    DTaP = Diphtheria-Tetanus-acellular Pertussis vaccine; HBV = Hepatitis B vaccine; IPV = Inactivated Polio vaccine; Hib = Haemophilus influenzae vaccine.

    Bottomline, such a state of affairs suggests scientists communicate poorly with medical doctors and both communicate poorly with the general public. As a result, both doctors and the general public are less well aware of the more recently discovered myriad benefits of inflammation and fever. This has allowed older cultural beliefs to stay entrenched and thus trump science in the optimal management of inflammation in general and of fever in particular.


    1. Wallenstein, Matthew B., et al. “Fever literacy and fever phobia.” Clinical pediatrics 52.3 (2013): 254-259.

    2. Purssell, Edward, and Jacqueline Collin. “Fever phobia: The impact of time and mortality–A systematic review and meta-analysis.” International journal of nursing studies (2015).

    3. Schmitt, Barton D. “Fever phobia: misconceptions of parents about fevers.” Archives of Pediatrics & Adolescent Medicine 134.2 (1980): 176.

    4. Ekholm, Erik, and Kalevi Niemineva. “On Convulsions in Early Childhood and Their Prognosis An investigation with follow‐up examinations of patients treated for convulsions at the Children’s Clinic of Helsinki University.” Acta paediatrica 39.1 (1950): 481-501.

    5. Evans, Sharon S., Elizabeth A. Repasky, and Daniel T. Fisher. “Fever and the thermal regulation of immunity: the immune system feels the heat.” Nature Reviews Immunology 15.6 (2015): 335-349.

    6. Harden, L. M., et al. “Fever and sickness behavior: Friend or foe?.” Brain, behavior, and immunity 50 (2015): 322-333.

    7. Casey, Rosemary, et al. “Fever Therapy: An Educational Intervention for Parents.” Pediatrics 73.5 (1984): 600-603.

    8. Wammanda, R. D., and S. O. Onazi. “Ability of mothers to assess the presence of fever in their children: Implication for the treatment of fever under the IMCI guidelines.” Annals of African medicine 8.3 (2009).

    9. Graneto, JOHN W., and DAVID F. Soglin. “Maternal screening of childhood fever by palpation.” Pediatric emergency care 12.3 (1996): 183-184.

    10. Crocetti, Michael, Nooshi Moghbeli, and Janet Serwint. “Fever phobia revisited: have parental misconceptions about fever changed in 20 years?.” Pediatrics 107.6 (2001): 1241-1246.

    11. May, Ariane, and Howard Bauchner. “Fever phobia: the pediatrician’s contribution.” Pediatrics 90.6 (1992): 851-854.

    12. Betz, Martin G., and Anton F. Grunfeld. “‘Fever phobia’ in the emergency department: a survey of children’s caregivers.” European Journal of Emergency Medicine 13.3 (2006): 129-133.

    13. Bilenko, Natalya, et al. “Determinants of antipyretic misuse in children up to 5 years of age: a cross-sectional study.” Clinical therapeutics 28.5 (2006): 783-793.

    14. Enarson, Mark C., et al. “Beliefs and Expectations of Canadian Parents Who Bring Febrile Children for Medical Care.” Pediatrics (2012): peds-2011.

    15. El-Radhi, A. S. “Fever management: Evidence vs current practice.” World J Clin Pediatr 1 (2012): 29-33.

    16. Vestergaard, Mogens, et al. “Death in children with febrile seizures: a population-based cohort study.” The Lancet 372.9637 (2008): 457-463.

    17. Saghazadeh, Amene, Mario Mastrangelo, and Nima Rezaei. “Genetic background of febrile seizures.” Reviews in the Neurosciences 25.1 (2014): 129-161. Genetic background of febrile seizures

    18. Boillot, Morgane, et al. “Novel GABRG2 mutations cause familial febrile seizures.” Neurology Genetics 1.4 (2015): e35.

    19. Schnaiderman, D., et al. “Antipyretic effectiveness of acetaminophen in febrile seizures: ongoing prophylaxis versus sporadic usage.” European journal of pediatrics 152.9 (1993): 747-749.

    20. van Stuijvenberg, Margriet, et al. “Randomized, controlled trial of ibuprofen syrup administered during febrile illnesses to prevent febrile seizure recurrences.” Pediatrics 102.5 (1998): e51-e51.

    21. Esch, Adrianus van, et al. “A study of the efficacy of antipyretic drugs in the prevention of febrile seizure recurrence.” Ambulatory Child Health 6.1 (2000): 19-25.

    22. El-Radhi, A., and W. Barry. “Do antipyretics prevent febrile convulsions?.” Archives of disease in childhood 88.7 (2003): 641.

    23. Maggio, Maria Cristina, et al. “Stevens–Johnson syndrome and cholestatic hepatitis induced by acute Epstein–Barr virus infection.” European journal of gastroenterology & hepatology 23.3 (2011): 289.

    24. El-Radhi, A. Sahib M. “Why is the evidence not affecting the practice of fever management?.” Archives of disease in childhood 93.11 (2008): 918-920.

    25. McBride, John T. “The association of acetaminophen and asthma prevalence and severity.” Pediatrics 128.6 (2011): 1181-1185.

    26. LI, SIU FAI, BRITT LACHER, and ELLEN F. CRAIN. “Acetaminophen and ibuprofen dosing by parents.” Pediatric emergency care 16.6 (2000): 394-397.

    27. Brandts, Christian H., et al. “Effect of paracetamol on parasite clearance time in Plasmodium falciparum malaria.” The Lancet 350.9079 (1997): 704-709.

    28. Earn, David JD, Paul W. Andrews, and Benjamin M. Bolker. “Population-level effects of suppressing fever.” Proceedings of the Royal Society of London B: Biological Sciences 281.1778 (2014): 20132570.

    29. Kohl, Katrin S., et al. “Fever after immunization: current concepts and improved future scientific understanding.” Clinical infectious diseases 39.3 (2004): 389-394. Current Concepts and Improved Future Scientific Understanding

    30. Marcy, S. Michael, et al. “Fever as an adverse event following immunization: case definition and guidelines of data collection, analysis, and presentation.” Vaccine 22.5 (2004): 551-556.

    31. Lewis, Karen, et al. “The effect of prophylactic acetaminophen administration on reactions to DTP vaccination.” American Journal of Diseases of Children 142.1 (1988): 62-65.

    32. Moshe, M., et al. “Acetaminophen prophylaxis of adverse reactions following vaccination of infants with diphtheria-pertussis-tetanus toxoids-polio vaccine.” The Pediatric infectious disease journal 6.8 (1987): 721-724.

    33. Centers for Disease Control and Prevention. Pertussis vaccination: use of acellular pertussis vaccines among infants and children recommendations of the Advisory Committee on Immunization Practices (ACIP). Pertussis Vaccination: Use of Acellular Pertussis Vaccines Among Infants and Young Children Recommendations of the Advisory Committee on Immunization Practices (ACIP)

    34. Prymula, Roman, et al. “Effect of prophylactic paracetamol administration at time of vaccination on febrile reactions and antibody responses in children: two open-label, randomised controlled trials.” The Lancet 374.9698 (2009): 1339-1350.

    35. Doedée, Anne MCM, et al. “Effects of prophylactic and therapeutic paracetamol treatment during vaccination on hepatitis B antibody levels in adults: two open-label, randomized controlled trials.” PloS one 9.6 (2014): e98175.

    Thanks for the R2A, Adriana Heguy.

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