Effect of Antipyretic Therapy on the Duration of Illness in Experimental Influenza A, <i>Shigella sonnei</i>, and <i>Rickettsia rickettsii</i> Infections

Plaisance, Karen I.; Kudaravalli, Suneel; Wasserman, Steven S.; Levine, Myron M.; Mackowiak, Philip A.

doi:10.1592/phco.20.19.1417.34865

Cited by 47 publications

(42 citation statements)

References 20 publications

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“…The results are consistent with other studies showing that antipyretic treatment increases viral shedding in human volunteers infected with rhinovirus [36] and lengthens the infectious period in children with chickenpox [37]. Moreover, in a study of human volunteers infected with influenza A, the number of antipyretic doses received was positively correlated with the duration of illness [38]. Some cytokines reduce viral shedding, so a likely mechanism by which antipyresis increases viral shedding is the suppression of temperature-dependent cytokine responses to influenza infection (see the electronic supplementary material, §3.2).…”

Section: Estimating the Effect For Influenzasupporting

confidence: 91%

Population-level effects of suppressing fever

Earn

Andrews

2014

Proc. R. Soc. B.

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Fever is commonly attenuated with antipyretic medication as a means to treat unpleasant symptoms of infectious diseases. We highlight a potentially important negative effect of fever suppression that becomes evident at the population level: reducing fever may increase transmission of associated infections. A higher transmission rate implies that a larger proportion of the population will be infected, so widespread antipyretic drug use is likely to lead to more illness and death than would be expected in a population that was not exposed to antipyretic pharmacotherapies. We assembled the published data available for estimating the magnitudes of these individual effects for seasonal influenza. While the data are incomplete and heterogeneous, they suggest that, overall, fever suppression increases the expected number of influenza cases and deaths in the US: for pandemic influenza with reproduction number R 1:8, the estimated increase is 1% (95% CI: 0.0-2.7%), whereas for seasonal influenza with R 1:2, the estimated increase is 5% (95% CI: 0.2-12.1%).

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Section: Estimating the Effect For Influenzasupporting

confidence: 91%

Population-level effects of suppressing fever

Earn

Andrews

2014

Proc. R. Soc. B.

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“…15 Data show beneficial effects on certain components of the immune system in fever, and limited data have revealed that fever actually helps the body recover more quickly from viral infections, although the fever may result in discomfort in children. 11,[16][17][18] Evidence is inconclusive as to whether treating with antipyretics, particularly ibuprofen alone or in combination with acetaminophen, increases the risks of complications with certain types of infections. 19,20 Potential benefits of fever reduction include relief of patient discomfort and reduction of insensible water loss, which may decrease the occurrence of dehydration.…”

Section: Physiology Of Fevermentioning

confidence: 99%

Fever and Antipyretic Use in Children

Sullivan¹,

Farrar²

2011

Pediatrics

366

313

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Fever in a child is one of the most common clinical symptoms managed by pediatricians and other health care providers and a frequent cause of parental concern. Many parents administer antipyretics even when there is minimal or no fever, because they are concerned that the child must maintain a “normal” temperature. Fever, however, is not the primary illness but is a physiologic mechanism that has beneficial effects in fighting infection. There is no evidence that fever itself worsens the course of an illness or that it causes long-term neurologic complications. Thus, the primary goal of treating the febrile child should be to improve the child's overall comfort rather than focus on the normalization of body temperature. When counseling the parents or caregivers of a febrile child, the general well-being of the child, the importance of monitoring activity, observing for signs of serious illness, encouraging appropriate fluid intake, and the safe storage of antipyretics should be emphasized. Current evidence suggests that there is no substantial difference in the safety and effectiveness of acetaminophen and ibuprofen in the care of a generally healthy child with fever. There is evidence that combining these 2 products is more effective than the use of a single agent alone; however, there are concerns that combined treatment may be more complicated and contribute to the unsafe use of these drugs. Pediatricians should also promote patient safety by advocating for simplified formulations, dosing instructions, and dosing devices.

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“…13 However, it is very important to point out that hyperthermia (as used here) differs in several important ways from an actual fever and that further study is needed to establish how activation thresholds are influenced during actual infections or tissue damage in which inflammatory signals may alter the signals that lymphocytes and other immune cells receive. Further study may lead to new strategies by which mild heating could be used therapeutically to improve pathologies, such as immunosenescence, that are linked to deficiencies in CD28 expression.…”

Section: Discussionmentioning

confidence: 99%

“…There is intriguing evidence that sustained increases in temperature associated with fever result in significant survival benefits following infection in multiple vertebrate species, 12 including humans. [13][14][15] Therefore, thermal shifts which exist during the early stages of infection, when optimal co-stimulatory signals may not yet be generated, might help to improve, or speed, the host immune response. While previous research on the relationship between physiological temperature shifts and specific T cell receptors during activation is sparse, several studies using non-specific activators point strongly to the hypothesis that thermal signals may help to calibrate the requirements for activation.…”

Section: Introductionmentioning

confidence: 99%

A role for the thermal environment in defining co-stimulation requirements for CD4⁺T cell activation

et al. 2015

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Abbreviations: APC, antigen-presenting cell; CD28, cluster of differentiation 28; CD3, cluster of differentiation 3; CD4, cluster of differentiation 4; CD8, cluster of differentiation 8; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; CTxB, cholera toxin B subunit; Ct, cycle threshold; ELISA, enzyme-linked immunosorbant assay; EtOH, ethanol; FITC, fluoroisothiocyanate; GM1, monosialotetrahexosylganglioside; IDEAS, imagestream data exploration and analysis software; IL-2, interleukin 2; LA, latrunculin A;MbCD, methyl-b-cyclodextrin; PD-1, Programmed cell death-1; PMA, phorbol 12-myristate 13-acetate; pMHC, peptide-major histocompatibility complexes; qRT-PCR, quantitative reverse transcription polymerase chain reaction; TCR, T cell receptor; TDI, time delay integration; TMA-DPH, trimethylammonium diphenylhexatriene; WBH, whole body hyperthermia.Maintenance of normal core body temperature is vigorously defended by long conserved, neurovascular homeostatic mechanisms that assist in heat dissipation during prolonged, heat generating exercise or exposure to warm environments. Moreover, during febrile episodes, body temperature can be significantly elevated for at least several hours at a time. Thus, as blood cells circulate throughout the body, physiologically relevant variations in surrounding tissue temperature can occur; moreover, shifts in core temperature occur during daily circadian cycles. This study has addressed the fundamental question of whether the threshold of stimulation needed to activate lymphocytes is influenced by temperature increases associated with physiologically relevant increases in temperature. We report that the need for co-stimulation of CD4C T cells via CD28 ligation for the production of IL-2 is significantly reduced when cells are exposed to fever-range temperature. Moreover, even in the presence of sufficient CD28 ligation, provision of extra heat further increases IL-2 production. Additional in vivo and in vitro data (using both thermal and chemical modulation of membrane fluidity) support the hypothesis that the mechanism by which temperature modulates co-stimulation is linked to increases in membrane fluidity and membrane macromolecular clustering in the plasma membrane. Thermally-regulated changes in plasma membrane organization in response to physiological increases in temperature may assist in the geographical control of lymphocyte activation, i.e., stimulating activation in lymph nodes rather than in cooler surface regions, and further, may temporarily and reversibly enable CD4C T cells to become more quickly and easily activated during times of infection during fever.

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Effect of Antipyretic Therapy on the Duration of Illness in Experimental Influenza A, Shigella sonnei, and Rickettsia rickettsii Infections

Cited by 47 publications

References 20 publications

Population-level effects of suppressing fever

Population-level effects of suppressing fever

Fever and Antipyretic Use in Children

A role for the thermal environment in defining co-stimulation requirements for CD4⁺T cell activation

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Effect of Antipyretic Therapy on the Duration of Illness in Experimental Influenza A, Shigella sonnei, and Rickettsia rickettsii Infections

Cited by 47 publications

References 20 publications

Population-level effects of suppressing fever

Population-level effects of suppressing fever

Fever and Antipyretic Use in Children

A role for the thermal environment in defining co-stimulation requirements for CD4+T cell activation

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A role for the thermal environment in defining co-stimulation requirements for CD4⁺T cell activation