Etiology of Acute Febrile Illness Among Hospitalized Adults and Children at a Public Tertiary-Care Center in Pune, India

Background: Fever is the most common symptom reported by Indians seeking medical care.  Despite the immense healthcare burden acute febrile illness (AFI) poses in India and beyond, systematic characterization of the etiology of AFI in India has been limited.

Methods: Patients admitted to Sassoon General Hospital in Pune, India from July 2013 through December 2015 with fever were enrolled.  A dedicated study team obtained a standardized clinical history and samples for influenza rapid test, blood culture, malaria rapid test, chikungunya IgM, and dengue NS1 ELISA.  Treating clinicians ordered IgM tests for leptospirosis, dengue, hepatitis A, hepatitis E, and culture of blood, urine, cerebrospinal fluid (CSF), and sputum on select patients per routine clinical care, results of which were obtained from the medical record.  Contaminant organisms were discounted.  Meningitis was defined by headache or altered mental status, with >= 10 white blood cells (WBC)/µL in CSF, pneumonia by clinical suspicion confirmed by chest radiograph, and urinary tract infection by isolation of bacteria in urine plus dysuria or urine microscopy showing > 10 WBC/high power field.

Results: Among 970 adults and 755 children under age 12, microbiologic testing within case definitions yielded a diagnosis in 528 (31%) patients.  An additional 193 (11%) patients met standardized case definitions, but did not have a positive culture.  Of the remaining patients, 658 (38%) were assigned a clinical diagnosis by their treating clinicians; no diagnosis was determined for 346 (20%) patients.  Vector-borne diseases were the most commonly identified causes of AFI in adults: dengue in 191 (20%), malaria in 72 (7%), leptospirosis in 18 (2%), and chikungunya in 16 (2%).  Pneumonia was the most common cause of AFI in children, occurring in 219 (29%) children (Fig 1 and 2).  Bacteremia was uncommon, found in 86 (5%) patients.  Central nervous system infections occurred in 59 (6%) adults and 65 (9%) children.

Conclusion: Despite comprehensive testing, the etiology of AFI defies standardized diagnosis in one half of cases and remains a mystery in one fifth.  Determining the etiology of AFI is important to provide optimal patient care, and to guide allocation of resources to high-burden diseases.