Evaluating the Performance of the DPP® ZDC IgM/IgG Rapid Test for Chikungunya Virus Diagnosis in Febrile Outpatients: A Prospective, Diagnostic Accuracy Study

Objective Evaluate the performance of a novel antibody-based rapid diagnostic test (RDT) for detecting Chikungunya virus (CHIKV) infection in febrile patients in Rio de Janeiro, Brazil. Methods We prospectively enrolled non-severe febrile patients aged 2-65 years presenting as outpatients between October 2018 and July 2019. Serum samples were collected during acute and convalescent phases and tested for CHIKV antibodies using the DPP® ZDC IgM/IgG rapid test and compared against the reference test, CHIKV RT-PCR. We determined the seropositivity using ELISA IgM/IgG and evaluated the diagnostic performance of the WHO-endorsed CHIKV clinical definition against the reference test. Results Of 500 participants, 226/261 (86.5%) tested ELISA IgM positive, 45/271 (16.6%) tested ELISA IgG positive, 100/294 (34%) CHIKV RT-PCR positive, and 117/495 (23.6%) RDT-antibody positive. During the acute phase [median 3 (2-4) days post illness onset], the sensitivity of IgM, IgG, and combined IgM/IgG ranged from 14.71-34.85%, while specificity ranged from 63.32-65.61%. During the convalescent phase [mean 16.5 (±5.5) days post-illness onset], sensitivity increased from 65.75% to 77.78%, and specificity ranged from 93.33-98.11%. The WHO’s CHIKV clinical definition had a sensitivity, specificity, positive predictive value, and negative predictive value of 88 (79.9-93.6)%, 74 (68-80)%, 64.2 (58.2-69.8)%, and 92.3 (87.6-95.3)%, respectively. Conclusions The DPP® ZDC IgM/IgG accurately diagnosed CHIKV on samples collected during the convalescent phase. Field applications include investigating CHIKV in patients with sub-acute to chronic osteoarticular symptoms and conducting serosurveys to inform priority areas for CHIKV vaccine implementation. The WHO’s clinical definition of CHIKV was accurate and could be deployed, especially in regions with limited diagnostic capacity. [Clinicaltrials.gov][1] NCT03047642 ### Competing Interest Statement JM is an employee of Instituto Butantan (Sao Paulo, Brazil). SD, LC, CE are employees or formal employees of Foundation for Innovative New Diagnostics (FIND). ### Clinical Trial Clinicaltrials.gov: [NCT03047642][2] ### Funding Statement This work was funded by independent grants from Australia, the Netherlands, and the 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 National Ethics Research Committee (CONEP) approved the study (protocol number: 70984617.9.0000.5262), and written informed consent was obtained from all participants or the caregivers of participants before enrollment. 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%2F05%2F01%2F2023.04.27.23289217.atom