title: Clinical and immunological markers of dengue progression in a study cohort from a hyperendemic area in Malaysia.
abstract: BACKGROUND
  With its elusive pathogenesis, dengue imposes serious healthcare, economic and social burden on endemic countries. This study describes the clinical and immunological parameters of a dengue cohort in a Malaysian city, the first according to the WHO 2009 dengue classification.
  
  
  RESULTS
  This longitudinal descriptive study was conducted in two Malaysian hospitals where patients aged 14 and above with clinical symptoms suggestive of dengue were recruited with informed consent. Among the 504 participants, 9.3% were classified as non-dengue, 12.7% without warning signs, 77.0% with warning signs and 1.0% with severe dengue based on clinical diagnosis. Of these, 37% were misdiagnosed as non-dengue, highlighting the importance of both clinical diagnosis and laboratory findings. Thrombocytopenia, prolonged clotting time, liver enzymes, ALT and AST served as good markers for dengue progression but could not distinguish between patients with and without warning signs. HLA-A*24 and -B*57 were positively associated with Chinese and Indians patients with warning signs, respectively, whereas A*03 may be protective in the Malays. HLA-A*33 was also positively associated in patients with warning signs when compared to those without. Dengue NS1, NS2A, NS4A and NS4B were found to be important T cell epitopes; however with no apparent difference between with and without warning signs patients. Distinction between the 2 groups of patients was also not observed in any of the cytokines analyzed; nevertheless, 12 were significantly differentially expressed at the different phases of illness.
  
  
  CONCLUSIONS
  The new dengue classification system has allowed more specific detection of dengue patients, however, none of the clinical parameters allowed distinction of patients with and without warning signs. While the HLA-A*33 may be predictive marker for development of warning signs; larger studies will be needed to support this findings.
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Anusyah
authors.initials: A
authors.lastname: Rathakrishnan
authors.affiliation: Department of Global Health, College of Public Health, University of South Florida, Tampa, Florida, United States of America.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Klekamp
authors.affiliation: Institute of Medical Molecular Biotechnology, Faculty of Medicine, University Technology Mara, Selangor, Malaysia.
authors.forename: Seok Mui
authors.initials: SM
authors.lastname: Wang
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Thamil Vaani
authors.initials: TV
authors.lastname: Komarasamy
authors.affiliation: Hospital Tengku Ampuan Rahimah, Persiaran Tengku Ampuan Rahimah, Klang, Selangor.
authors.forename: Santha Kumari
authors.initials: SK
authors.lastname: Natkunam
authors.affiliation: Clinical Hematology Laboratory, Department of Hematology, Hospital Ampang, Ampang, Selangor, Malaysia.
authors.forename: Jameela
authors.initials: J
authors.lastname: Sathar
authors.affiliation: Department of Global Health, College of Public Health, University of South Florida, Tampa, Florida, United States of America.
authors.forename: Azliyati
authors.initials: A
authors.lastname: Azizan
authors.affiliation: Department of Global Health, College of Public Health, University of South Florida, Tampa, Florida, United States of America.
authors.forename: Aurora
authors.initials: A
authors.lastname: Sanchez-Anguiano
authors.affiliation: Department of Trauma and Emergency Medicine, University Malaya Medical Centre, Kuala Lumpur, Malaysia.
authors.forename: Rishya
authors.initials: R
authors.lastname: Manikam
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Shamala Devi
authors.initials: SD
authors.lastname: Sekaran
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism*; D016022:Case-Control Studies; D015331:Cohort Studies; D015897:Comorbidity; D003710:Demography; D003715:Dengue / Q000175:diagnosis / Q000453:epidemiology* / Q000276:immunology* / Q000821:virology; D003716:Dengue Virus / Q000502:physiology; D018450:Disease Progression; D019353:Endemic Diseases / Q000706:statistics & numerical data*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D015234:HLA-A Antigens / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D008296:Malaysia / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D013601:T-Lymphocytes / Q000276:immunology; D055815:Young Adult
chemical_list: D015415:Biomarkers; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D007075:Immunoglobulin M; D007371:Interferon-gamma