STANDARDIZED METHODOLOGY FOR IDENTIFYNG FEVER ETIOLOGY IN NON-SEVERE PATIENTS IN RIO DE JANEIRO, BRAZIL: A PROSPECTIVE OBSERVATIONAL STUDY

Abstract

Identifyng the etiologies of acute febrile illness (AFI) is challenging in settings with limited laboratory capacity. Healthcare professionals often presume that AFI is bacterial in origin potentially resulting in inappropriate antibiotic use. We aimed to identify the etiology of fever among non-severe patients seeking primary care in urban Rio de Janeiro, using a standardized methodological approach. We conducted a prospective AFI study between October 25, 2018-July 31, 2019, involving participants aged 2-65 years. Patients with fever < 7 days were offered enrollment, and clinical and laboratory data were gathered for consecutive participants. A standardized methodological approach was employed to investigate the etiology of fever, classifying patients with bacterial and non-bacterial causes of fever. A two-step approach was adopted: initially, an electronic classification was applied, followed by an independent review by a panel of three experts, blinded to each others´s assessments, who assigned patients to one of three categories: bacterial, non-bacterial, or undetermined cause of fever. The electronic classification was based on predefined and widely accepted laboratory parameters (i.e., direct pathogen detection, a fourfold increase in antibody titer, or a positive PCR or RDT). Follow-up visits were conducted 14-28 days after initial visit. Five hundred participants (median age 26 years, 50.4% female) were recruited. Besides fever, the most frequently reported complaints were headache (76.4%), arthralgia (54.4%), and cough (35.8%). Recent antibiotic use was reported in 8.8%, and comorbidities were present in 24.8%, including HIV infection in 7 participants (1.4%). Chikungunya virus (CHIKV) was the main arbovirus detected, confirmed by RT-PCR in 100/194 (51.5%) participants of those with undifferentiated illness. In patients with acute respiratory infection, nasal and throat swabs were collected for Streptococcus pyogenes and respiratory pathogen detection, with a positivity rate of 28.9% and 57.3%, respectively. . Blood cultures were positive in 3.6% (18/500). Among those who returned for follow-up, 6.1% had a fever relapse, while 93.9% reported fever resolution. The predominant etiology of fever was non-bacterial (62.8%), followed by bacterial (20%), and undetermined causes (9.4%). Using a standardized approach to classify fever etiology in non-severe patients seeking care in Rio de Janeiro, we found that non-bacterial infections predominated. Keywords: Chikungunya, Acute Febrile Illness, Antimicrobial Resistance, Fever etiology, Rio de Janeiro. Conflicts of interest: There was no conflicts of interest. Ethics and financing: This work was funded by the Foundation for Innovative New Diagnostics.