1. ¹Department of Research Policy and Cooperation, World Health Organization, Geneva, Switzerland
2. ²Institute of Health and Community Medicine, Universiti Malaysia Sarawak, Kuching, Malaysia
3. ³Department of Virology, PAHO/WHO Collaborating Center for the Study of Dengue and its Vectors, Instituto de Medicina Tropical Pedro Kouri, Havana, Cuba

Correspondence: Dr T Pang, Department of Research Policy and Cooperation, World Health Organization, Ave Appia 20, Geneva 1211, Switzerland. E-mail: pangt@who.int

Received 19 September 2006; Accepted 26 September 2006; Published online 28 November 2006.

Abstract

The past four decades has witnessed a consolidation of the original observations made in the 1970s that dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS) have an immunological basis. Following reinfection with a dengue virus of different serotype, severe disease is linked to high levels of antibody-enhanced viral replication early in illness which is followed by a cascade of memory T-cell activation and a 'storm' of inflammatory cytokines and other chemical mediators. These compounds are released mainly from T cells, monocytes/macrophages and endothelial cells, and ultimately cause an increase in vascular permeability. The consolidation of the evidence has been largely due to several important prospective sero-epidemiological studies in areas endemic for DHF/DSS, which have shown that risk of severe disease is significantly higher in secondary dengue infections. These advances have underscored the fact that DHF/DSS pathogenesis is a complex, multifactorial process involving cocirculation of various dengue virus serotypes and the interplay of host and viral factors that influence disease severity. The continued search to define risk factors in susceptible populations must be combined with the new techniques of molecular virology and innovative approaches in vaccine design to achieve the ultimate objective of developing a safe and effective vaccine.