Wen-Hung Wang1, Chih-Yen Lin2, Ko Chang3, Aspiro Nayim Urbina4, Wanchai Assavalapsakul5, Arunee Thitithanyanont6, Po-Liang Lu7, Yen-Hsu Chen8, Sheng-Fan Wang9. 1. Division of Infectious Disease, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan; Center for Tropical Medicine and Infectious Disease, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan. Electronic address: bole0918@gmail.com. 2. Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan. Electronic address: pigpipi831205@gmail.com. 3. Division of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, 81276, Taiwan. Electronic address: johnsonckk@yahoo.com.tw. 4. Center for Tropical Medicine and Infectious Disease, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan. Electronic address: aspiro.urbina@hotmail.com. 5. Department of Microbiology, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand. Electronic address: Wanchai.A@chula.ac.th. 6. Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand. Electronic address: arunee.thi@mahidol.ac.th. 7. Division of Infectious Disease, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan. Electronic address: d830166@kmu.edu.tw. 8. Division of Infectious Disease, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan; Center for Tropical Medicine and Infectious Disease, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan. Electronic address: d810070@kmu.edu.tw. 9. Center for Tropical Medicine and Infectious Disease, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan; Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan; Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, 80708, Taiwan. Electronic address: wasf1234@kmu.edu.tw.
Abstract
OBJECTIVES: This study examined the epidemiological, clinical, and immunological characteristics of the 2015 dengue outbreak in Taiwan. METHODS: Clinical data were collected from dengue fever (DF) and dengue hemorrhagic fever (DHF) patients. A phylogenetic tree was used to analyze the source of the outbreak strain. Paired plasma samples from DF/DHF patients were used for antibody-dependent enhancement (ADE) assay and cytokine multiplex biometric immunoassay to validate the immunological mechanism. RESULTS: This outbreak mainly occurred in two of the southern cities of Taiwan: Tainan (n=22 777; 52%) and Kaohsiung (n=19 784; 45%). A high DHF death rate was noted (34.6%). The case (DHF) and control (DF) study indicated that older age (>60 years), type II diabetes, and hypertension were risk factors correlated with the development of DHF (p< 0.0001). The phylogenetic tree results suggested that the outbreak-associated strain was dengue virus serotype 2 and cosmopolitan genotype, forming a stable cluster with the isolates from Thailand and Indonesia (bootstrap value of 99%). Cytokine analyses demonstrated that levels of interleukin (IL)-6, IL-4, IL-13, IL-1β, interferon gamma (IFN-γ), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were significantly higher in DHF patients compared to DF patients (p< 0.001). The ADE assay showed that diluted plasma containing preexisting dengue antibodies from DHF patients significantly enhanced dengue infection (p< 0.05). CONCLUSION: The results suggest that older age, type II diabetes, hypertension, immunological cytokine dysregulation, and preexisting dengue antibodies inducing ADE infection are correlated with dengue severity. This study also indicates that the largest dengue outbreak in Taiwan might have been a result of imported DF from dengue epidemic regions.
OBJECTIVES: This study examined the epidemiological, clinical, and immunological characteristics of the 2015 dengue outbreak in Taiwan. METHODS: Clinical data were collected from dengue fever (DF) and dengue hemorrhagic fever (DHF) patients. A phylogenetic tree was used to analyze the source of the outbreak strain. Paired plasma samples from DF/DHF patients were used for antibody-dependent enhancement (ADE) assay and cytokine multiplex biometric immunoassay to validate the immunological mechanism. RESULTS: This outbreak mainly occurred in two of the southern cities of Taiwan: Tainan (n=22 777; 52%) and Kaohsiung (n=19 784; 45%). A high DHF death rate was noted (34.6%). The case (DHF) and control (DF) study indicated that older age (>60 years), type II diabetes, and hypertension were risk factors correlated with the development of DHF (p< 0.0001). The phylogenetic tree results suggested that the outbreak-associated strain was dengue virus serotype 2 and cosmopolitan genotype, forming a stable cluster with the isolates from Thailand and Indonesia (bootstrap value of 99%). Cytokine analyses demonstrated that levels of interleukin (IL)-6, IL-4, IL-13, IL-1β, interferon gamma (IFN-γ), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were significantly higher in DHF patients compared to DF patients (p< 0.001). The ADE assay showed that diluted plasma containing preexisting dengue antibodies from DHF patients significantly enhanced dengue infection (p< 0.05). CONCLUSION: The results suggest that older age, type II diabetes, hypertension, immunological cytokine dysregulation, and preexisting dengue antibodies inducing ADE infection are correlated with dengue severity. This study also indicates that the largest dengue outbreak in Taiwan might have been a result of imported DF from dengue epidemic regions.
Authors: N L Ajantha Shyamali; Sameera D Mahapatuna; Laksiri Gomes; Ananda Wijewickrama; Graham S Ogg; Gathsaurie Neelika Malavige Journal: Trop Med Infect Dis Date: 2020-11-16