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**Genetic Diversity of Dengue Virus and** 

**Periodic Epidemics in South East Asia** 

The geographic distribution and genetic diversity of dengue virus is deeply rooted in Asia suggesting its origin from this region, with first reported out-break of DHF from Philippine in 1953 (Halstead, 1980). One of the characteristics notable in Asian regions, where the disease is endemic is that dengue hemorrhagic fever outbreaks occur in repetitive cycles of 3-5 years, (Ferguson et al, 1999). The incidence of disease and its severity varies across different dengue virus serotypes and also between primary and secondary infections of

Due to lack of in-vivo study models, there is little information about factors contributing to disease severity and its variation across dengue virus genotypes and the cyclical nature of dengue outbreaks. It is however critical to study these factors particularly in the South East Asian region where incidence of dengue cases is thought to be associated with variables such as water, sanitation, population density and rate of literacy as opposed to developed countries where ambient temperature, moisture and rainfall perhaps plays the major role. A better understanding of disease epidemiology and pathogenesis will help identify optimum control measures in the region. It will also develop systems for predicting the outcome of

The chapter has been divided in three parts: the first part will discuss the historical evolution of the dengue virus in the region its spatial and temporal distribution. It will also look at the effects of covariates such as poverty, water supply, sanitation and global

The second part of the chapter will focus on the genetic evolution of the viral isolates circulating in the region. Phylogenetic studies of dengue viruses have uncovered genetic variation within each serotypes, these variations have been organized in discrete clusters on dendograms. Analyses of such studies have broadened our horizon to relate the mutational changes with disease evolution and factors like seasonality and incidence variability. This part of chapter will focus on the common mutational variations that have been reported so

In the third and final part of the chapter an attempt has been made to relate the mutational changes of dengue genotypes with disease severity. Vast array of literature has been published investigating relationship of genetic variation with disease severity. The structure

mass vaccination when the vaccine becomes available in this region.

far and how these relate with the disease dynamics in the endemic region.

warming on expansion of the dengue endemic regions. .

**1. Introduction** 

same serotypes(Vaughn DW et al).

**Associated Clinical Severity During** 

E. Khan, R. Hasan, J. Mehraj and S. Mahmood

*Department of Pathology and Microbilogy Aga Khan University, Stadium Road, Karachi* 

*Pakistan*

World Health Organization.Dengue Haemorrhagic Fever: Diagnosis, Treatment, Prevention and Control, 2 nd ed., Geneva: WHO, 1997. **7** 
