Indumal was barely conscious at the Lady Ridgeway Children's Hospital in Sri Lanka.  The year was 1997 and Colombo, the capital of Sri Lanka, was in the middle of a dengue epidemic.  Indumal's parents recounted how their 5-year-old son had been perfectly healthy until 5 days ago when he developed a fever. On the fourth day he had started to vomit blood and became extremely lethargic at which point they rushed him to the hospital.  The child's condition worsened and he died the following day in the intensive care unit.  Analysis of his blood revealed that the cause of death was dengue hemorrhagic fever.  Globally there are  2.5 billion people at risk of dengue virus infection.   Each year there are an estimated 100 million cases of dengue viral infection worldwide with 250,000 people developing the more severe dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), which is often fatal as in the case of this child in Sri Lanka.

Dengue is caused by  4 closely related viruses transmitted by Aedes aegypti mosquitoes.  These viruses are widespread and found in almost all tropical parts of the world, where they mainly thrive in urban areas.  A large proportion of  infected people develop no symptoms at all and clear the virus on their own.  Others develop dengue fever, which is a flu like illness that is not life threatening.  A minority of infected people, mostly children, develop a severe life threatening form of the disease known as dengue hemorrhagic fever (DHF).  Typically less than five percent of people infected with dengue viruses develop DHF. 

Although scientists are still far from understanding why only some dengue infections lead to hemorrhagic disease, it is clear that factors such as age of the person and previous exposure to dengue infections increase risk of severe disease.  It is also clear that all dengue viruses are not identical, and some variants of the virus are more likely to cause severe disease than others.  Therefore, the unfortunate few who develop DHF happen to be especially susceptible to the disease and/or infected with a more harmful variant of the virus.  Our group is has been conducting collaborative studies with the Genetech Research Foundation and the Medical Research Institute (MRI) in Sri Lanka and the Centers for Disease Control and prevention in the USA to better understand the epidemiology and pathogenesis of dengue.

Dengue viruses are transmitted throughout the year in Southwest Sri Lanka, although in some years an increase in the number of  cases has been observed in the middle of the year (June-August) and/or towards the end of the year (Dec- Feb).   Studies carried out by the MRI demonstrated the presence of dengue virus in Colombo as far back as the early 1960s.  However,  DHF was a very rare disease in Sri Lanka in the period between 1960-1988.  This benign state of affairs  took an abrupt turn in 1989 when the MRI reported approximately 200 DHF cases from in and around Colombo.  The 1989 DHF epidemic was not an isolated event, and every year after that hundreds to thousands of cases of DHF have been reported.  The year 2004 was one of the worst years on record with over 10,000 cases of hemorrhagic fever.

  Despite intense transmission of DVs in Sri Lanka over the period 1980-1988, DHF was very rare.  In contrast, between the period 1989-2004 DHF epidemics occurred every year and the magnitude of the epidemics increased over time (Based on data reported by the WHO and the Epidemiology Unit, Ministry of Health Sri Lanka).

 We still do not have a satisfactory explanation for why DHF suddenly appeared in Sri Lanka.   The leading theory is one that was originally proposed by Professor Tissa Vitarana at the MRI and Dr. Duane Gubler at the CDC.  They proposed that DHF has emerged because a mild strain of dengue serotype 3 has been replaced by a more virulent strain capable for causing DHF.  We are currently engaged in studies to test this idea.