Flaviviral infections in Nepal

Aedes aegypti and Aedes albopictus, the two most important mosquito vectors for flaviviruses including dengue and the closely related Zika virus, are quickly spreading from tropical to temperate zones and with them the viruses they carry. Currently, no anti-dengue drugs are available, and the latest clinical trials of a dengue vaccine have shown limited protection depending on dengue serotype and host immune status. More worryingly, certain vaccinated groups became more susceptible to dengue disease than unvaccinated individuals.

However, there is a dearth of scientific data connecting climatic shift and virus-mosquito interactions relevant to the spread of flaviviruses. In addition, transmission of dengue and most likely Zika virus can be modulated by host immunity, and little is known about the effect of pre-existing immunity to other flaviviruses on dengue transmission and disease severity.

Nepal with its varied terrain within a small geographical area provides an ideal setting to study how dengue transmission and disease severity are influenced by pre-existing immunity, climate shift and virus-mosquito interactions: All four dengue serotypes currently circulate in the country; both dengue and its mosquito vectors are present from the plains regions (tropical) to the highlands (temperate) and Japanese encephalitis virus, another member of the flavivirus family, has been continually circulating for the past 70 years and vaccination coverage against this virus is very high.

Dr. McCauley plans to evaluate the geographic distribution of dengue virus in Nepal by isolating dengue virus strains from hospital-based studies and classifying dengue cases by demographic and clinical data, laboratory findings and host immune status, including pre-existing immunity to Japanese encephalitis. She will also investigate the epidemiology of dengue virus spread in Nepal in the context of climatic shift by defining the molecular characteristics of dengue strains circulating in two different climatic regions of Nepal (Chitwan and Kathmandu) to identify the mutations that are unique in virus strains isolated from two different locations and by comparing the full genome sequences of Nepalese dengue virus isolates to virus strains from Southeast Asia and the Pacific.

A better understanding of links between viruses, their vectors and climate is a prerequisite to develop efficient control and vaccine strategies and could shed light on the epidemiology of other flaviviruses, such as a potential interaction between dengue and Zika virus as well as the spread of Zika.

6-month Update