Addressing Acute Febrile Illness Using a Syndromic Approach During A Chikungunya Epidemic in Rio de Janeiro, Brazil: A Prospective Observational Study

BackgroundIdentifying etiologies of acute febrile illness (AFI) is challenging in settings with limited laboratory capacity. We aimed to describe the causes of AFI among non-severe patients seeking care at the primary level in Rio de Janeiro, Brazil when a large chikungunya virus (CHIKV) epidemic was ongoing. Methodology/Principal FindingsWe conducted a 10-month prospective AFI study in participants aged 2-65 seeking care at public emergency departments and outpatient clinics. Patients with fever [≤] 7 days were offered enrollment, and clinical, and laboratory data were gathered for consecutive participants. A syndrome-driven approach comprising culture, molecular and serologic tests were adopted to investigate the cause of fever. Logistic regression model determined predictors of laboratory-positive CHIKV. Follow-up visits were conducted 14-28 days after the index visit. Five hundred participants (median age 26 [15-41] years, 50.4% females) yielded 824 diagnoses, and 249/500 (49.8%) of whom had multiple diagnoses. Systemic infection (382/500, 76%), followed by acute respiratory infection (155/500, 31%), and urinary infection (23/500, 4.6%) were the most common febrile syndromes. CHIKV was the primary etiology found in 284 (56.8%) participants. Viral upper respiratory infection accounted for 40/155 (25.8%) of the respiratory infections, of which Rhinovirus and Influenza A were the main viruses commonly detected. None of the diagnostic tests were positive in 124/500 (25%). Predictors of laboratory-positive CHIKV were the absence of cough, arthralgia, rash, high temperature, and leucopenia. Of those 297/500 (59.4%) who returned for the follow-up, 120/297 (40%) persisted with symptoms. CHIKV-positive patients were more likely to experience persistent arthritis than CHIKV negative [OR: 10.18 (3.64-28.45)]. Conclusions/SignificanceUsing a syndromic approach to identify the etiology of fever during an epidemic of CHIKV in Rio, we found evidence of other pathogens associated with AFI. Clinical and laboratory markers might allow early identification and accurate distinction of patients with CHIKV from other AFI to guide proper clinical management. Future research should assess whether a syndromic approach to febrile illness in resource-limited settings improves patient outcomes and rationale antimicrobial use. Clinicaltrials.gov registration number: NCT03047642