What causes a fever?

How Someone Gets a Fever

Fever occurs when exogenous or endogenous pyrogens trigger the body's thermoregulatory response, causing a regulated increase in body temperature above normal. 1

Causes of Fever

Infectious Causes

• Bacterial Infections: Common sources include respiratory tract (34.5%), urinary tract (23.8%), and other sites (12.2%) 2
• Viral Infections: Respiratory viruses like adenovirus, influenza A and B, parainfluenza, and respiratory syncytial virus can cause high fevers that may last 2.5-5.2 days 3
• Parasitic Infections: Various parasites can trigger fever as part of the body's immune response 1

Pathophysiological Mechanism

• Pyrogen Recognition: The innate immune system recognizes infectious pathogens (bacteria, viruses, parasites) 4
• Mediator Release: This recognition triggers hepatic and pulmonary macrophages to release lipid mediators and cytokines 4
• Prostaglandin E2 (PGE2) Production: PGE2 is synthesized by cyclooxygenase-2 and microsomal PGE2 synthase-1 4
• Hypothalamic Reset: PGE2 enters the brain and acts on the hypothalamus, which serves as the body's thermostat, raising the temperature set point 4
• Temperature Elevation: The body responds by increasing heat production and decreasing heat loss until the new higher temperature set point is reached 4

Fever vs. Hypothermia in Systemic Inflammation

• Fever: Associated with mild forms of systemic inflammation 4
• Hypothermia: Corresponds to more severe forms of systemic inflammation 4
• Both responses are beneficial host defense mechanisms: Fever helps fight mild infections, while hypothermia may be beneficial in severe systemic inflammation 4

Special Considerations

Age-Related Differences

• Neonates and Young Infants: More susceptible to serious bacterial infections due to immature immune systems 5
• Elderly Patients: May not always present with fever despite having infections; approximately 70% of febrile episodes in hospitalized elderly are caused by nosocomial infections 2

Fever Patterns

• High Fever: Temperatures ≥39.0°C (102.2°F) are common in adenovirus (68%), influenza A (84%), and influenza B (65%) infections 3
• Duration: Mean duration varies by pathogen, with 37% of children with respiratory viral infections experiencing fever for five days or longer 3
• Response to Antipyretics: There is no significant difference in fever response to acetaminophen between bacterial and viral infections, making this an unreliable method to distinguish between infection types 6

Clinical Implications

• Fever is a symptom, not a disease itself, and represents the body's natural defense mechanism 1
• Laboratory tests including complete blood count, C-reactive protein, and procalcitonin lack sufficient sensitivity and specificity to definitively determine if fever is caused by bacterial, viral, or parasitic infections 1
• Blood cultures should be obtained when bacteremic or septic illness is suspected 1
• Core temperature measurements (rectal, oral, or invasive) are most accurate for detecting true fever 1

Common Pitfalls

• Assuming fever always indicates infection; non-infectious causes like drug reactions, malignancies, and autoimmune disorders can also cause fever 5
• Relying solely on temperature response to antipyretics to differentiate between viral and bacterial infections 6
• Failing to recognize that fever may be absent in older or immunocompromised patients despite serious infection 1
• Overlooking "silent" sources of infection such as otitis media, decubitus ulcers, or perineal abscesses when evaluating fever 5