Acute-phase Serum Cytokine Levels and Correlation with Clinical Outcomes in Children and Adults with Primary and Secondary Dengue Virus Infection in Myanmar between 2017 and 2019
Khine Mya Nwe,
Mya Myat Ngwe Tun,
Theingi Win Myat,
Chris Fook Sheng Ng,
Moh Moh Htun,
Htin Lin,
Nang Sarm Hom,
Aung Min Soe,
Annie Elong Ngono,
Shinjiro Hamano,
Kouichi Morita,
Kyaw Zin Thant,
Sujan Shresta,
Hlaing Myat Thu,
Meng Ling Moi
Affiliations
Khine Mya Nwe
Department of Virology, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, Japan
Mya Myat Ngwe Tun
Department of Virology, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, Japan
Theingi Win Myat
Department of Medical Research, Yangon 11191, Myanmar
Chris Fook Sheng Ng
Program for Nurturing Global Leaders in Tropical and Emerging Communicable Diseases, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8501, Japan
Moh Moh Htun
Department of Medical Research, Yangon 11191, Myanmar
Htin Lin
Department of Medical Research, Yangon 11191, Myanmar
Nang Sarm Hom
Department of Medical Research, Yangon 11191, Myanmar
Aung Min Soe
Department of Virology, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, Japan
Annie Elong Ngono
Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA
Shinjiro Hamano
Program for Nurturing Global Leaders in Tropical and Emerging Communicable Diseases, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8501, Japan
Kouichi Morita
Department of Virology, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, Japan
Kyaw Zin Thant
Department of Medical Research, Yangon 11191, Myanmar
Sujan Shresta
Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA
Hlaing Myat Thu
Department of Medical Research, Yangon 11191, Myanmar
Meng Ling Moi
Department of Virology, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, Japan
The dengue virus (DENV) has been endemic in Myanmar since 1970, causing outbreaks every 2–3 years. DENV infection symptoms range from mild fever to lethal hemorrhage. Clinical biomarkers must be identified to facilitate patient risk stratification in the early stages of infection. We analyzed 45 cytokines and other factors in serum samples from the acute phase of DENV infection (within 3–5 days of symptom onset) from 167 patients in Yangon, Myanmar, between 2017 and 2019. All of the patients tested positive for serum DENV nonstructural protein 1 antigen (NS1 Ag); 78.4% and 62.9% were positive for immunoglobulin M (IgM) and G (IgG), respectively; and 18.0%, 19.8%, and 11.9% tested positive for serotypes 1, 3, and 4, respectively. Although the DENV-4 viral load was significantly higher than those of DENV-1 or DENV-3, disease severity was not associated with viral load or serotype. Significant correlations were identified between disease severity and CCL5, SCF, PDGF-BB, IL-10, and TNF-α levels; between NS1 Ag and SCF, CCL5, IFN-α, IL-1α, and IL-22 levels; between thrombocytopenia and IL-2, TNF-α, VEGF-D, and IL-6 levels; and between primary or secondary infection and IL-2, IL-6, IL-31, IL-12p70, and MIP-1β levels. These circulating factors may represent leading signatures in acute DENV infections, reflecting the clinical outcomes in the dengue endemic region, Myanmar.
