Magnitude of Antibody Cross-Reactivity in Medically Important Mosquito-Borne Flaviviruses: A Systematic Review

Adugna Endale,1,2 Girmay Medhin,1 Koyamo Darfiro,3 Nigatu Kebede,1 Mengistu Legesse1 1Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia; 2School of Medicine, College of Medicine and Health Sciences, Dire Dawa University, Dire Dawa, Ethiopia; 3Department of External Quality Assessment, Hossaena Public Health Institute Laboratory, Hossaena, EthiopiaCorrespondence: Adugna Endale Email adugnaendale73@gmail.comIntroduction: Flaviviruses are a genus of enveloped single-stranded RNA viruses that include dengue virus (DENV), yellow fever virus, West Nile virus (WNV), Japanese encephalitis virus, and Zika virus. Nowadays, diverse serological assays are available to diagnose flaviviruses. However, infection with flaviviruses induces cross-reactive antibodies, which are a challenge for serological diagnosis.Objective: This systematic review aimed to assess the magnitude of medically important mosquito-borne flavivirus–induced antibody cross-reactivity and its influence on serological test outcomes.Methods: This study was designed based on the PRISMA guidelines. It includes original research articles published between 1994 and 2019 that reported serological cross-reactions between medically important mosquito-borne flaviviruses. Articles were searched on PubMed using controlled vocabulary. Eligibility was assessed by title, abstract, and finally by reading the full paper. The articles included are compared, evaluated, and summarized narratively.Results: A total of 2,911 articles were identified, and finally 14 were included. About 15.4%– 84% of antibodies produced against non-DENV flaviviruses were cross-reactive with DENV on different assays. Up to 30% IgM and up to 60% IgG antibodies produced against non-WNV flaviviruses were cross-reactive with WNV on EIA assays. The magnitude of antibodies produced against flaviviruses that are cross-reactive with chikungunya virus (Alphavirus) was minimal (only about 7%). The highest antibody cross-reactivity of flaviviruses was reported in ...