Volume 79, Issue 2
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645


High prevalence of hepatitis B virus (HBV) infection in China offers a unique setting to examine HBV’s influence on the presentation of dengue fever. In 398 patients admitted for suspected dengue fever, 89% (353/398) were positive for dengue IgM antibodies. Among dengue-infected patients, 8% (29/353) had chronic HBV co-infection. Only dengue virus serotype 1 was identified by virus isolation and reverse transcriptase-polymerase chain reaction assays. No case of dengue hemorrhagic fever/dengue shock syndrome was diagnosed. In addition to routine clinical tests, inter-leukin 2 (IL-2), IL-4, IL-6, IL-10, interferon γ (IFNγ), and tumor necrosis factor α (TNFα) levels were measured in the sera of 95% (334/353) of dengue-infected subjects as well as controls. Surprisingly, HBV/dengue co-infected patients made less IL-6 ( < 0.05) and TNFα ( < 0.05) than patients with only dengue infection. Similar levels of IL-4, IL-10, and IFNγ were found in both groups. Thus, HBV co-infection seems to alter the cytokine production pattern when patients contract dengue infection.


Article metrics loading...

The graphs shown below represent data from March 2017
Loading full text...

Full text loading...



  1. Wilder-Smith A, Schwartz E, 2005. Dengue in travelers. N Engl J Med 353 : 924–932. [Google Scholar]
  2. Mackenzie JS, Gubler DJ, Petersen LR, 2004. Emerging flaviviruses: the spread and resurgence of Japanese encephalitis, West Nile and dengue viruses. Nat Med 10 : S98–S109. [Google Scholar]
  3. Halstead SB, Heinz FX, Barrett AD, Roehrig JT, 2005. Dengue virus: molecular basis of cell entry and pathogenesis, 25–27 June 2003, Vienna, Austria. Vaccine 23 : 849–856. [Google Scholar]
  4. Green S, Rothman A, 2006. Immunopathological mechanisms in dengue and dengue hemorrhagic fever. Curr Opin Infect Dis 19 : 429–436. [Google Scholar]
  5. Russell PK, Nisalak A, 1967. Dengue virus identification by the plaque reduction neutralization test. J Immunol 99 : 291–296. [Google Scholar]
  6. Porterfield JS, 1980. The Togaviruses—Biology, Structure, Replication. New York: Academic Press.
  7. Halstead SB, 1988. Pathogenesis of dengue: challenges to molecular biology. Science 239 : 476–481. [Google Scholar]
  8. Halstead SB, 1970. Observations related to pathogensis of dengue hemorrhagic fever. VI. Hypotheses and discussion. Yale J Biol Med 42 : 350–362. [Google Scholar]
  9. Xu G, Dong H, Shi N, Liu S, Zhou A, Cheng Z, Chen G, Liu J, Fang T, Zhang H, Gu C, Tan X, Ye J, Xie S, Cao G, 2007. An outbreak of dengue virus serotype 1 infection in Cixi, Ningbo, People’s Republic of China, 2004, associated with a traveler from Thailand and high density of Aedes albopictus. Am J Trop Med Hyg 76 : 1182–1188. [Google Scholar]
  10. Qiu FX, Gubler DJ, Liu JC, Chen QQ, 1993. Dengue in China: a clinical review. Bull World Health Organ 71 : 349–359. [Google Scholar]
  11. Qiu FX, Chen QQ, Ho QY, Chen WZ, Zhao ZG, Zhao BW, 1991. The first epidemic of dengue hemorrhagic fever in the People’s Republic of China. Am J Trop Med Hyg 44 : 364–370. [Google Scholar]
  12. Li FS, Yang FR, Song JC, Gao H, Tang JQ, Zou CH, Hu BN, Wen SR, Qiu FX, 1986. Etiologic and serologic investigations of the 1980 epidemic of dengue fever on Hainan Island, China. Am J Trop Med Hyg 35 : 1051–1054. [Google Scholar]
  13. Luo H, He J, Zheng K, Li L, Jiang L, 2002. Analysis on the epidemiologic features of Dengue fever in Guangdong province, 1990–2000. Zhonghua Liu Xing Bing Xue Za Zhi 23 : 427–430. [Google Scholar]
  14. Zhang FC, Chen YQ, Lu YC, Wang J, Chen WS, Hong WX, 2005. Analysis on clinical and epidemiological characteristics of 1032 patients with Dengue fever in Guangzhou. Zhonghua Liu Xing Bing Xue Za Zhi 26 : 421–423. [Google Scholar]
  15. CDC, 2007. Progress in hepatitis B prevention through universal infant vaccination–China, 1997–2006. Morb Mortal Wkly Rep 56 : 441–445. [Google Scholar]
  16. WHO, 1996. Dengue Haemorrhagic Fever: Diagnosis, Treatment, Prevention and Control. Geneva: World Heath Organization.
  17. Vazquez S, Hafner G, Ruiz D, Calzada N, Guzman MG, 2007. Evaluation of immunoglobulin M and G capture enzyme-linked immunosorbent assay Panbio kits for diagnostic dengue infections. J Clin Virol 39 : 194–198. [Google Scholar]
  18. Fang DY, Zhou JJ, Huang JB, Han YP, Jiang LF, 2006. Identification and analysis of virulence of dengue virus isolated from patient serum. Biotechnology (NY) 16 : 26. [Google Scholar]
  19. Zhou JJ, Fang DY, Yan HJ, Huang JB, Jiang LF, 2007. Gene sequencing and analysis of the whole length of E gene from dengue virus type 1 isolated in Guangzhou area. Chin J Zoonoses 23 : 48. [Google Scholar]
  20. Halstead SB, 2007. Dengue. Lancet 370 : 1644–1652. [Google Scholar]
  21. Lee MS, Hwang KP, Chen TC, Lu PL, Chen TP, 2006. Clinical characteristics of dengue and dengue hemorrhagic fever in a medical center of southern Taiwan during the 2002 epidemic. J Microbiol Immunol Infect 39 : 121–129. [Google Scholar]
  22. Nguyen TL, Nguyen TH, Tieu NT, 1997. The impact of dengue haemorrhagic fever on liver function. Res Virol 148 : 273–277. [Google Scholar]
  23. Kuo CH, Tai DI, Chang-Chien CS, Lan CK, Chiou SS, Liaw YF, 1992. Liver biochemical tests and dengue fever. Am J Trop Med Hyg 47 : 265–270. [Google Scholar]
  24. Vaughn DW, Green S, Kalayanarooj S, Innis BL, Nimmannitya S, Suntayakorn S, Endy TP, Raengsakulrach B, Rothman AL, Ennis FA, Nisalak A, 2000. Dengue viremia titer, antibody response pattern, and virus serotype correlate with disease severity. J Infect Dis 181 : 2–9. [Google Scholar]
  25. Balmaseda A, Hammond SN, Perez L, Tellez Y, Saborio SI, Mercado JC, Cuadra R, Rocha J, Perez MA, Silva S, Rocha C, Harris E, 2006. Serotype-specific differences in clinical manifestations of dengue. Am J Trop Med Hyg 74 : 449–456. [Google Scholar]
  26. Corwin AL, Larasati RP, Bangs MJ, Wuryadi S, Arjoso S, Sukri N, Listyaningsih E, Hartati S, Namursa R, Anwar Z, Chandra S, Loho B, Ahmad H, Campbell JR, Porter KR, 2001. Epidemic dengue transmission in southern Sumatra, Indonesia. Trans R Soc Trop Med Hyg 95 : 257–265. [Google Scholar]
  27. Egger JR, Coleman PG, 2007. Age and clinical dengue illness. Emerg Infect Dis 13 : 924–925. [Google Scholar]
  28. Nguyen TH, Nguyen TL, Lei HY, Lin YS, Le BL, Huang KJ, Lin CF, Do QH, Vu TQ, Lam TM, Yeh TM, Huang JH, Liu CC, Halstead SB, 2005. Association between sex, nutritional status, severity of dengue hemorrhagic fever, and immune status in infants with dengue hemorrhagic fever. Am J Trop Med Hyg 72 : 370–374. [Google Scholar]
  29. Nguyen TH, Lei HY, Nguyen TL, Lin YS, Huang KJ, Le BL, Lin CF, Yeh TM, Do QH, Vu TQ, Chen LC, Huang JH, Lam TM, Liu CC, Halstead SB, 2004. Dengue hemorrhagic fever in infants: a study of clinical and cytokine profiles. J Infect Dis 189 : 221–232. [Google Scholar]
  30. Hober D, Poli L, Roblin B, Gestas P, Chungue E, Granic G, Imbert P, Pecarere JL, Vergez-Pascal R, Wattre P, Maniez-Montreuil M, 1993. Serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-1 beta (IL-1 beta) in dengue-infected patients. Am J Trop Med Hyg 48 : 324–331. [Google Scholar]
  31. Libraty DH, Endy TP, Houng HS, Green S, Kalayanarooj S, Suntayakorn S, Chansiriwongs W, Vaughn DW, Nisalak A, Ennis FA, Rothman AL, 2002. Differing influences of virus burden and immune activation on disease severity in secondary dengue-3 virus infections. J Infect Dis 185 : 1213–1221. [Google Scholar]
  32. Dunn C, Brunetto M, Reynolds G, Christophides T, Kennedy PT, Lampertico P, Das A, Lopes AR, Borrow P, Williams K, Humphreys E, Afford S, Adams DH, Bertoletti A, Maini MK, 2007. Cytokines induced during chronic hepatitis B virus infection promote a pathway for NK cell-mediated liver damage. J Exp Med 204 : 667–680. [Google Scholar]
  33. Tilg H, Vogel W, Tratkiewicz J, Aulitzky WE, Herold M, Gruber M, Geissler D, Umlauft F, Judmaier G, Schwulera U, Thrun A, Huber C, 1993. Pilot study of natural human interleukin-2 in patients with chronic hepatitis B. Immunomodulatory and antiviral effects. J Hepatol 19 : 259–267. [Google Scholar]
  34. Zhang W, Yue B, Wang GQ, Lu SL, 2002. Serum and ascites levels of macrophage migration inhibitory factor, TNF-alpha and IL-6 in patients with chronic virus hepatitis B and hepatitis cirrhosis. Hepatobiliary Pancreat Dis Int 1 : 577–580. [Google Scholar]
  35. Akpolat N, Yahsi S, Godekmerdan A, Demirbag K, Yalniz M, 2005. Relationship between serum cytokine levels and histopathological changes of liver in patients with hepatitis B. World J Gastroenterol 11 : 3260–3263. [Google Scholar]
  36. Halstead SB, 1981. The Alexander D. Langmuir Lecture. The pathogenesis of dengue. Molecular epidemiology in infectious disease. Am J Epidemiol 114 : 632–648. [Google Scholar]
  37. Rothman AL, 2004. Dengue: defining protective versus pathologic immunity. J Clin Invest 113 : 946–951. [Google Scholar]

Data & Media loading...

  • Received : 17 Oct 2007
  • Accepted : 10 Apr 2008

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error