Morbidity and mortality rates from febrile illnesses vary dramatically with age. Younger adults with fever usually have benign self-limited disease with low mortality. The challenge in this group is to identify rare causes of fever such as meningitis or sepsis when confronted with a predominance of self-limited viral and focal bacterial diseases. Patients older than 65 years, or those with chronic disease who have fever, represent a group at higher risk for serious disease with higher rates of morbidity and mortality. For example, the incidence of community-acquired pneumonia is 2.6 times greater in adults 65 to 79 compared with younger adults, and in those over 79 years, it is seven times greater. The relative mortality and morbidity rates for any given infection are much higher in the geriatric population; more than 50% of sepsis cases occur in patients older than 65 years, with a resultant mortality up to 26%. Even viral illnesses that are generally not fatal, such as influenza or COVID-19, can be lethal in older adults. Three body systems—the respiratory tract, urinary tract, and skin and soft tissue—are the target for more than 80% of these infections.

Body temperature is normally controlled within a narrow range by the preoptic area of the hypothalamus. In the anterior hypothalamus, neurons directly sense the blood temperature. Temperature is subsequently controlled by a combination of vasomotor changes, shivering, changes in metabolic heat production, and behavioral changes. Normal temperature range is usually 36.0°C to 37.8°C (96.8°F to 100.0°F). There is a circadian rhythm within this range, with lower temperatures in the morning and higher temperatures in the late afternoon. Fever occurs when this normal range is reset to a higher value.

There is no consensus on the threshold core temperature that defines fever. The Centers for Disease Control and Prevention define fever as a core temperature greater than 38.0°C (100.4°F) in the absence of fever-reducing medication. However, most authorities agree that a core body temperature of 38.3°C (100.9°F) represents a significant fever. Fever is distinct from hyperthermia. Hyperthermia is an elevation of the temperature related to the inability of the body to dissipate heat; fever is the elevation of body temperature caused by thermoregulatory pathways in response to infections and certain other medical circumstances ( Box 8.1 ). Most cases of temperatures higher than 41.0°C (105.8°F) are a result of hyperthermia, but febrile illness may also be considered.

Fever may be produced by a number of endogenous and exogenous substances termed pyrogens . Endogenous pyrogens include a variety of cytokines released by leukocytes in response to infectious, inflammatory, and neoplastic processes. Exogenous pyrogens include a large number of bacterial and viral products and toxins. Toxins induce fever by stimulating cells of the immune system to release endogenous pyrogens. These cytokines, such as interleukin-1 (IL-1), IL-6, tumor necrosis factor, and interferon, travel to the hypothalamus and induce the production of prostaglandin E ₂ (PGE ₂ ).

PGE ₂ raises the set point of the temperature range by a combination of effects, including peripheral vasoconstriction, increased metabolic heat production, shivering, and behavioral changes that conserve heat. Fever is maintained as long as the levels of endogenous pyrogens and PGE ₂ are high. There is also a variety of other humoral and neural pathways that modulate this basic response. Cyclooxygenase inhibitors, such as aspirin, decrease fever by blocking the production of PGE ₂ . Age, malnutrition, immunosuppression, and chronic disease may also blunt the febrile response.

Moderate elevations of the body temperature may serve to aid host defenses by increasing chemotaxis, decreasing microbial replication, and improving lymphocyte function. Elevated temperatures may directly inhibit the growth of certain bacteria and viruses. Fever also results in certain increased physiologic effects to the host, including increased oxygen consumption, metabolic demands, protein breakdown, and gluconeogenesis. These effects are particularly problematic in older adults who typically have a smaller margin of reserve for any given body system. Older adults have a blunted febrile response and a lower baseline temperature than younger adults. Some authorities therefore suggest that the threshold for the definition of fever should be considered lower (i.e., 100.4°F) in frail older adults than in younger persons.

The therapeutic benefit of treating febrile patients with antipyretics is controversial and may depend on individual patient factors. For example, some studies indicate that febrile intensive care unit (ICU) patients with sepsis have reduced mortality if allowed to maintain an elevated temperature but that this may not be the case for febrile ICU patients without sepsis. A recent meta-analysis of antipyretic treatment of septic patients showed no mortality benefit at 28 days, but early mortality (14 days) was significantly lower in febrile patients treated with antipyretic therapies. Treatment of fevers makes patients feel more comfortable, however, and because of the detrimental effects of the increased metabolic demands caused by high fevers, it is recommended that patients with temperatures greater than 41°C be treated with antipyretics.

The initial step in the process of fever is resetting the thermostatic set point in the hypothalamus to a higher temperature while the actual body temperature remains normal. This mismatch of the thermostat with the “sensed” body temperature causes the patient to feel chilled (chills). The patient remains chilled until the body temperature rises to near the (elevated) hypothalamic set point. At this point, the patient no longer experiences chills and feels euthermic—but may feel fatigued or ill—but, to the caregiver, the skin temperature or thermometer reading is now elevated. The sequence of chills followed by febrile illness is the basis of the (incorrect) popular belief that getting chilled leads to infection, such as pneumonia. When the thermostatic set point is reduced to normal, the patient suddenly feels hot and sweats until the body temperature falls to match the set point, now normal.