Table of Contents  
REVIEW ARTICLE
Year : 2018  |  Volume : 20  |  Issue : 2  |  Page : 79-82

Fever: A friend or a foe


1 Medicine Department, Jos University Teaching Hospital, Jos, Plateau State, Nigeria
2 Medicine Department, Federal Medical Centre, Abeokuta, Nigeria

Date of Web Publication17-Jul-2019

Correspondence Address:
A S Omololu
Medicine Department, Federal Medical Centre, Abeokuta
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jomt.jomt_4_18

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  Abstract 


The concept of fever is an interesting subject that has intrigued clinicians for centuries. As pain is an important stimuli to withdraw from a noxious stimuli that may be potentially harmful, so is fever an important sign of a possible microbial invasion. Back and forth, there has been arguments and debates about whether fever is deleterious, a foe, or actually beneficial. There has also been question about whether or not to treat it, and when to treat it. This review article tries to paint a broad picture of both sides of this coin.

Keywords: Benefits, fever, harmful


How to cite this article:
Shehu N Y, Omololu A S. Fever: A friend or a foe. J Med Trop 2018;20:79-82

How to cite this URL:
Shehu N Y, Omololu A S. Fever: A friend or a foe. J Med Trop [serial online] 2018 [cited 2020 Jul 11];20:79-82. Available from: http://www.jmedtropics.org/text.asp?2018/20/2/79/262756




  Introduction Top


Fever has been with man since the beginning of time, as is well documented in many ancient manuscripts of Egyptian, Greek, and Bible origins.[1],[2] Fever is one of the most common clinical feature that prompts people to seek medical care, and it is estimated that globally, there are millions of annual consultations for fever-related complaints.[3] In 2015, infectious diseases that largely presents with fever accounted for three out of the 10 global causes of deaths.[4] Furthermore, even the noninfectious diseases cause of death are frequently complicated by infections, and as such manifest with fever. In developing countries including Nigeria, infectious diseases still account for one of the major leading causes of morbidity and mortality.[5],[6],[7] Fever is clearly the most significant clinical early sign of infectious diseases.[8] In Nigeria, fever accounts for about 20% to 40% of general consultations.[9]

As pain is an important stimuli to withdraw from a noxious stimuli that may be potentially harmful, so is fever an important alarm sign of a possible microbial invasion. Microbial invasion without this alarm sign would progress unknowingly unabated without this critical “flag.” The overwhelming weight of medical opinion for many centuries has been that fever is a deleterious phenomenon, which must be treated. However, the febrile response is being subjected to an increasing scientific scrutiny, which is causing a reevaluation of our approach toward its treatment.[10] It is pertinent to review the beneficial and harmful effects of fever so that fever would always be seen and evaluated in the right perspective.


  Definition of fever Top


According to the International Union of Physiological Sciences Thermal Commission Glossary of terms for thermal physiology, fever is defined as a state of elevated core temperature, which is often, but not necessarily, part of the defensive response of multicellular organisms (hosts) to the invasion of live (microorganisms) or inanimate matter recognized as pathogenic or alien by the host.[11] Although fever is recognized clinically by its thermal characteristics, it is in fact a complex physiological reaction to disease involving a cytokine-mediated rise in body core temperature, generation of acute-phase reactants, and activation of numerous physiological, endocrinologic, and immunologic systems.[10] There are differing views about the range of normal body temperature, and the upper cutoff value for fever,[12],[13] but a temperature reading of >37.2 °C is to a large extent accepted as being febrile in adults.[14] However, ambient temperature affects the cutoff point for fever. A temperature of 37.7°C in the morning may be considered as fever, but in the evening may be considered normal.[14] Readings may also differ depending on the part of the body where they are taken. Lower esophageal/tympanic membrane (TM) temperature readings reflect core temperature. Rectal temperature is 0.4°C higher than oral, whereas temperature of the TM is 0.8°C higher than oral.. Maximum normal oral temperature is 37.2°C at 6:00 am and 37.7°C at 4:00 pm.[15] It is also important for the instrument, the clinical thermometer, to be accurate for determining temperature. This could be the mercury, digital, or infrared thermometers.

An important consideration in discriminating the presence or absence of fever is to rule out factitious fever. Temperature may be increased by physical activity, strong emotion, eating, heavy clothing, medications, high room temperature, high humidity, and during menstrual period. Conversely, it may be reduced by uremia, severe sepsis, corticosteroids in the elderly, and significantly malnourished individual.[15]

Fever may be broadly classified as undifferentiated or differentiated. Undifferentiated fever means fever without specific symptoms or localizing signs. It is a common early feature of many infections and clinical clues to the cause of illness are likely to emerge as time progresses. The common causes of undifferentiated fever following tropical exposure are malaria, dengue, rickettsial infections, leptospirosis, and enteric fever. Differentiated fever, on the other hand, means fever with specific symptoms and localizing signs that can help in quick diagnosis of the cause of the fever.[16]


  Pathogenesis of fever Top


From current concepts, we understand that exogenous and/or endogenous stimuli initiate the febrile response by being presented to specialized host cells, which in turn respond by synthesizing and releasing specific quantities of various pyrogenic cytokines into the circulation.[10],[14] Currently recognized endogenous pyrogenic cytokines include interleukin (IL)-1, IL-6, tumor necrosis factor (TNF)-α, and interferon.[17],[18],[19] Under normal conditions in healthy individuals, these cytokines are undetectable and are produced in a wide range of tissues in response to diverse stimuli. They have short intravascular half-lives and are pleiotropic, recognizing receptors on multiple host target tissue. After release, they can be found in virtually all body fluids and exert local as well as systemic effects.[10] In a given host, a particular exogenous pyrogen (e.g., Lipopolysaccharide (LPS) or a virus) promotes release of its own characteristic pattern and concentration of cytokines. Ultimately, each cytokine recognizes and binds to its own specific receptors, the most important of which, at least in terms of their thermoregulatory effects, are located on neurons in close proximity to the preoptic region of the anterior hypothalamus. Here, the cytokine–receptor interaction activates phospholipase A2, resulting in liberation of plasma arachidonic acid as a substrate for the cyclooxegenase (COX) pathway.[20] COX expression can be directly increased by some cytokines, leading to release of prostaglandin E2, an arachidonate metabolite. Prostaglandin E2 diffuses across the blood–brain barrier, where it influences the responsiveness of the thermosensitive neurons that the thermoregulatory center comprises, perhaps in combination with other pyrogenic factors.[10]


  Beneficial effects of fever Top


It seems unlikely that an energy-dependent process, such as fever, would have been retained for hundreds of millions of years, in so many groups of organisms, if it provided no selective advantage. Fever may represent a leukocyte-based amplification mechanism to affect host challenge: enhanced motility of leukocytes, enhanced lymphocyte response to mitogens, increased production of interferon, and enhanced immune response to viral antigens.[21] Fever has had a long phylogenetic history; it occurs not only in infected birds and mammals but also in infected reptiles, amphibians, fish, and even insects. These animals have been shown to manifest fever when exposed to microorganisms and also to show enhanced resistance to infection when increases in body temperature occur within their physiological range.[22],[23] Mammalian experimental models have shown that an enhanced febrile response is able to increase the resistance of different animals to a variety of viral, fungal, and bacterial infections.[24],[25],[26] Clinical data supporting an adaptive role for fever, although sparse, include evidence of both the beneficial effects of fever and the adverse effects of antipyretics on the outcome of infection.[26] Human studies show that there is slower healing of varicella,[27] and longer duration of malarial infections,[28] if antipyretics are used. Adults infected with rhinovirus exhibit more nasal viral shedding when given aspirin than when given placebo.[29] Studies have also shown that all four of the major pyrogenic cytokines have immune-potentiating capabilities, which might theoretically enhance resistance to infection.[30]

Additionally, fever is an important clinical sign without which microbial invasion may progress unnoticed, as it serves as an alarm to seek medical care. Individuals that have been on nonsteroidal antiinflammatory drugs and who develop an infectious disease may not seek therapeutic interventions. Fever is also critical in evaluating the possible etiologies. Consideration of the onset, progression, pattern, type, and associated clinical feature would help in the determination of the possible cause of the fever and the initial empiric therapy. Furthermore, fever is an important factor in monitoring response to therapeutic intervention, and this is why many authorities strongly discourage administering antipyretics in patients with infectious diseases until fever goes beyond a certain threshold.[26]


  Adverse effects of fever Top


The adverse effects of fever cannot be overemphasized, with its effects being multisystemic in humans. In the central nervous system, a temperature of 41°C will lead to adverse effects like delirium and seizures. At 42°C, patients could present with coma, whereas a temperature of 41.6°C to 42°C could lead to death. Other consequences include an increase in basal metabolic rate by 15%, and pulse by 15 beats/min for every degree rise in temperature. This could cause febrile convulsions in children, and tilt those with underlying predisposing conditions into heart failure. There is also an increase in muscle proteolysis for acute-phase reactant synthesis, and an increase in bone resorption, leading to hypercalciuria.[31] Fever may also increase insensible water loss to about 300 to 500 mL/m2/day, which may be significant, especially in patients that have some form of dehydration, whereas it may also increase oxygen consumption by 13%. Report from recent studies have shown that pyrogenic cytokines play a role in mediating the physiological abnormalities of at least some infections, suggesting that fever’s mediators may, at times, exert a detrimental effect.[32] In experimental animals, challenge with LPS causes TNF-α and IL-1 to be released into the bloodstream coincident with the appearance of signs of sepsis.[33] IL-1, alone or in combination with other cytokines, induces many of the same physiological abnormalities (e.g., fever, hypoglycemia, shock, and death) seen after administration of purified LPS,[34] observations which have led to a growing conviction that pyrogenic cytokines are central mediators of the clinical and humoral manifestations of gram-negative bacterial sepsis.[26]


  Conclusion Top


Review of the foregoing shows that fever has both beneficial and detrimental effects. Overall, fever is not generally a foe in itself, if it is identified, evaluated, and managed appropriately, except it goes beyond a certain threshold. As has been previously stated, it is highly unlikely that such an energy-dependent process would have been preserved for such a long time in diverse groups of animals, if it did not offer a selective advantage, whereas on the other hand, a lot of its deleterious effects have also been discussed. Like a coin, fever has two sides, a good and a bad side, and the good side must be appreciated and utilized appropriately to get the best out of this awesome phenomenon.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Abstract
Introduction
Definition of fever
Pathogenesis of ...
Beneficial effec...
Adverse effects ...
Conclusion
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