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

Background Identifying 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 Findings We 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/Significance Using 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][1] registration number: [NCT03047642][2] ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial Clinicaltrials.gov registration number: [NCT03047642][2] ### Funding Statement This work was supported by independent grants from Australia, the Netherlands, and UK aid from the British people. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Brazilian Institution Review Board (Comissao Nacional de Etica em Pesquisa) and the local Institution Review Board (CEP do Instituto Nacional de Infectologia Evandro Chagas) gave ethical approval for this work (protocol number 70984617900005262). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present work are contained in the manuscript. [1]: http://Clinicaltrials.gov [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT03047642&atom=%2Fmedrxiv%2Fearly%2F2023%2F04%2F19%2F2023.04.15.23288370.atom