Chikungunya is a disease caused by Aedes mosquito-borne chikungunya virus infection. This disease is becoming one of the emerging/re-emerging viral diseases in tropical and subtropical countries but is neglected by public health systems. This study assessed the seroprevalence of chikungunya virus infection among patients with acute febrile illness seeking healthcare in a malaria-endemic area in the Afar Region, Northeast Ethiopia. An institution-based cross-sectional study was employed from September 2022 to March 2023 to assess the seroprevalence of chikungunya virus infection among malaria-suspected febrile patients attending health institutes in the Afar Region. Sociodemographic, clinical features, and venous blood were collected from each study participant. Blood films were prepared and examined for plasmodium infection using microscopy. Sera were separated and screened for anti-chikungunya virus IgM and IgG antibodies using an enzyme-linked immunosorbent assay. Data were entered into Epi Data 3.1 and analyzed using Stata/SE 14.2. In this study, 368 malaria-suspected febrile patients (55.4% female, aged 5-80 years old, mean ± SD = 27.28 ± 14.0) participated. The prevalence of anti-chikungunya virus IgM antibodies, indicating acute infection, was 47.8%, while the prevalence of IgG antibodies, indicating previous exposure, was 6.3%. Nonmarried participants were found to be more likely to have acute chikungunya virus infection (AOR = 2.34, 95% CI: 1.141-4.964), and back pain was associated with higher likelihood of acute infection (AOR = 1.785; 95% CI: 1.078-2.954). About 10.6% of the participants tested positive for Plasmodium parasite infection, with P. falciparum (84.6%) being the most common, followed by P. vivax (10.3%) and mixed (5.1%) infections. The study revealed a high seroprevalence of acute chikungunya virus infection among febrile patients in the Afar Region, highlighting the importance of regular screening for arbovirus infection in febrile patients to control and mitigate chikungunya spread.
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