Logo Cirion

Cirion Foundation

the impact of infectious diseases

Dengue and sepsis research by PhD student Cox van de Weg

Dengue

According to a recent publication in top rank scientific journal ‘Nature’ (Bhatt et al. 2013) an estimated 390 million dengue virus infections occurred in 2010 and therefore dengue virus can be considered as a major threat for the global public health.

Dengue virus is transmitted by the bite of a tiger mosquito, which lives in tropical and subtropical areas of the globe. People living in these areas are at risk of getting infected. Fortunately, the majority of dengue virus infections will only cause an uncomplicated febrile illness. After an average period of two weeks patients will recover completely.

However, some patients can develop very severe symptoms, such as shock or severe bleeding and organ impairment. Usually severe disease develops after 3-5 days after the onset of fever. Interestingly, the highest virus titres in the blood are usually detected early in the infection and often the virus is no longer detectable at the onset of severe symptoms. This suggests that severe symptoms are caused by a highly activated immune system of the host and not directly by the virus itself.

In order to investigate the immune response of dengue virus infected patients we have set up a prospective cohort in Jakarta. Patients with a positive test for dengue virus infection were admitted to the hospital within 48 hours after the onset of fever. They were followed up for one week and blood was withdrawn to investigate the gene expression of the host in response to the virus.


Sepsis

Another disease in which the immune system plays an important role in pathogenesis is sepsis. In sepsis it has been investigated that bacterial components from the intestine translocate into the blood circulation and can stimulate the immune system.

We have investigated this mechanism in a cohort in Semarang, Indonesia and in a cohort in São Paolo, Brazil. In both settings we have found evidence of microbial translocation. Moreover, in the Brazilian cohort we could correlate microbial translocation to extensive immune activation, suggesting that this mechanism may play a role in pathogenesis.

 

Plasma leakage

One hallmark of dengue virus infection is the occurrence of plasma leakage. This symptom occurs through increased vascular permeability. In order to investigate this mechanism we use an in vitro model with human umbilical vein endothelial cells (HUVECs). In this model we can investigate the impact of dengue virus infection on vascular permeability and cytokine production.


Patient studies and cell models

Altogether, using patient studies and cell models we try to get a better insight in which factors may contribute to severe disease in patients with dengue virus infection.

 

Collaborations

  • Augustinus Soemantri and Mohamad Supriatna. Dr. Kariadi Hospital, Semarang Indonesia
  • Leonard Nainggolan and Beti Ernawati Dewi. Universitas Indonesia, Jakarta, Indonesia
  • Esper Kallas and Claudio Pannuti, University of São Paolo, São Paolo, Brazil
  • Ralph Huits, Montsy Brouns and Riem van den Berg. Dr. Horacio Oduber Hospitaal, Aruba
  • Joost Meijers, AMC, Amsterdam, Nederland
  • Mihai Netea, Universiteit van Nijmegen, Nederland
  • Anita Rijneveld, Erasmus MC, Rotterdam, Nederland

 
Publications

  1. van de Weg CA, Koraka P, van Gorp EC, et al. Lipopolysaccharide levels are elevated in dengue virus infected patients and correlate with disease severity. J Clin Virol 2012; 53:38-42.
  2. van de Weg CA, van Gorp EC, Supriatna M, Soemantri A, Osterhaus AD, Martina BE. Evaluation of the 2009 WHO dengue case classification in an Indonesian pediatric cohort. Am J Trop Med Hyg 2012; 86:166-70.
  3. van de Weg CA, Pannuti CS, de Araújo ES, et al.  Microbial translocation is associated with extensive immune activation in dengue virus infected patients with severe disease. Plos Neglected Tropical Diseases. 2013. In press.