Causes of Secondary and Prolonged Fever During Treatment of Bacterial Meningitis and Viral Encephalitis

Fever is a common symptom in both viral encephalitis and bacterial meningitis. However, in some patients, fever may persist or recure during the course of treatment. This can be concerning and may indicate unresolved infection, secondary infections, inflammatory responses, or treatment complications. Understanding the underlying causes and adopting a structured approach to management is crucial for improving patient care. Prolonged fever means fever persisting beyond 8-10 days despite appropriate treatment. Secondary fever means fever occurring after an initial period of defervescence, meaning the fever had initially subsided for at least 48 hours before recurring or a new fever spike following an apparent resolution. The common and established causes of secondary and prolonged fever in pediatrics patients during the treatment of bacterial meningitis and viral encephalitis include, nosocomial infections, subdural effusion, phlebitis, pneumonia , drug fever, otitis media, gastroenteritis and urinary tract infection . Subdural effusion prolongs fever in patients with meningitis. It occurs as a complication due to persistent inflammation, secondary infection, or inadequate resolution of the infection within the subdural space. Urinary tract infections (especially in catheterized patients) is nosocomial or superimposed infections that cause secondary or prolonged fever in pediatric patients during the treatment of meningitis or encephalitis. Otitis media can cause secondary or prolonged fever during the treatment of meningitis and encephalitis in pediatric patients. This can occur due to persistent infection, suppurative complications (such as mastoiditis or subdural empyema), or an inadequate response to initial antimicrobial therapy. Pneumonia, including hospital-acquired pneumonia, can cause secondary or prolonged fever during the treatment of CNS infections in pediatric patients. This occurs due to superimposed bacterial infections, ventilator-associated pneumonia in critically ill children, or aspiration pneumonia in patients with neurological compromise. Gastro-entritis can occur in hospitalized children undergoing treatment for CNS infections due to concurrent infections, dehydration-related metabolic disturbances, or systemic inflammatory responses. Enteric pathogens such asRotavirus, Norovirus, or bacterial causes like Salmonella and Clostridioides difficile can contribute to prolonged fever in hospitalized children undergoing treatment for CNS infections. Phlebitis can cause secondary fever during the treatment of encephalitis and meningitis in pediatric patients. It is often associated with intravenous catheter use, leading to localized or systemic infections, including catheterrelated bloodstream infections, which can contribute to persistent or recurrent fever.

Drug fever is a well-recognized phenomenon where fever arises as an adverse reaction to medications, often without an identifiable infectious source. It typically resolves upon discontinuation of the offending drug. In the context of meningitis and encephalitis treatment, antibiotics (e.g., beta-lactams, sulfonamides, vancomycin), anticonvulsants, and antipyretics have been implicated. A relapse of encephalitis or meningitis occurs due to incomplete eradication of the infection, emergence of resistant pathogens, or host immune deficiencies. This can lead to persistent inflammation, ongoing infection, or secondary complications such as subdural effusion or vasculitis, which contribute to prolonged or recurrent fever.

Inclusion criteria

• Children from one month to 18 years.
• Who were diagnosed with bacterial meningitis or viral encephalitis and admitted to neurological department at Assiut University Children's Hospital (AUCH).
• Develop secondary or prolonged fever despite appropriate treatment.

Exclusion criteria

• Pediatric patients with suspected autoimmune encephalitis.
• Patient on immunosuppressive therapy (e.g., post-organ transplant, chemotherapy).
• Pediatric patients suspected metabolic disorders.
• Those with suspected endocrine dysfunction.