Outline

1. Outline • Overview: What is Dengue? • DENV • Diseases Characteristics • Transmission cycle • Treatment and Control • Dengue, a global treat: cases and possible mechanisms • The first locally acquired Dengue in Key West, Florida, 2009-2010 • Epidemic in Hawai’i, 2001-2002 • Emergence of DHF/DSS in Sri Lanka, 1989 • Rising DHF/DSS cases in Singapore • Human immune status factor • Ecological and climatic factors

2. What is Dengue • A mosquito-borne infection that causes a severe flu-like illness, and sometimes potentially lethal complications called dengue haemorrhagic fever and dengue shock syndrome (DHF and DSS) • Caused by a virus (DENV1-4) • Endemic in all tropical and sub-tropical parts of the world, predominantly in urban and semi-urban areas.

3. STRUCTURAL GENES NON-STRUCTURAL GENES NS1, 2A, 2B, 4B, 5 DENV • genus Flavivirus, family Flaviviridae • comprised of four antigenically-distict serotypes (DENV1-4) • In human, an infection with a particular serotype • confer a lifelong immunity to that type. • confer a transient immunity to other three types. • ADE: antibody-dependent enhancement • After the transient protective period, infections with different serotypes are associated with more severe diseases (DHF/DSS). • Antiviral antibodies enhances viral entry into cells, leading to increased infectivity in the host. DENGUE VIRUS PARTICLE Rossmann & Kuhn, Purdue University Single, positive strand RNA genome of ~11 kb in length

4. Disease Manifestration • Inapparent infections • Undifferentiated febrile illness • Dengue fever self-limited febrile illness associated with headache, myalgia, arthralgia and rash. • Dengue Hemorrhagic Fever overt plasma leakage and extravasation of fluid. • Dengue shock syndrome severe plasma leakage.

5. SYLVATIC CYCLE URBAN CYCLE Transmission • Aedes aegypti and Aedes albopictus • No animal reservoir

6. Treatment and Control • No specific treatment/drug • No vaccine (not yet!). Developing a vaccine is challenging • four serotypes • limited understanding • no animal models • Control: Combat the vector mosquitoes • environmental management • chemical method

9. Dengue, a Global Treat increase in number of case increase in severity spread to new areas

10. The outbreak represents the first dengue cases acquired in the cotinental US outside of the Texas-Mexico border since 1945 The environmental and social conditions for dengue transmission have long been present in south Florida The abundant presence of a competent mosquito vectors Rapid urbanization Sufficient opportunity for mosquitoes to bite humans Increased international travel A largely nonimmune population Potential introduction of virus from returning travelers and visitors Locally acquired Dengue--Key West, Florida, 2009-2010

11. Mosquito-Viral adaptation • Emergence of DHF/DSS in Sri Lanka • Prior to 1989, DHF/DSS was uncommon in Sri Lanka. • 1989, a dramatically increase in number of cases was experienced and persist until now. • result from the displacement of the group A DENV3 (native) strain by the group B DENV3 (invasive) strain (Messer, 2003) • Where is the invasive strain from? • Evolved from the native strain via genetic drift? (Lanciotti,1994) • Introduced from India or East Africa? (Messer,2003) • Have been present as a minor population that increased in abundance due to some unidentified change in the selective environment? (Messer,2003)

12. Host Immune Status • Endemic stability: The state of low incidence of DF under intense transmission • Under more intense transmission, infections occur at earlier ages which result in no symptoms or mild illness, and consequently, the incidence of DF decreases. • A mathematical model recently predicted that the incidence of DHF and transmission intensity will be negatively correlated at high transmission intensities • At very intense transmission (i.e. each serotype inoculation event occurs within 6 months period of cross-protection), the individual would acquire immunity to nearly all serotypes while being cross-protected form severe illness • But the correlation is positive at low levels of transmission

13. Possible mechanisms Low herd immunity of the population Rising population density Aedes aegypti mosquito exploits hard-to-find habitats in the urban environment The predominant dengue serotype was changed from DEN-2 (2001-2003) to DEN-1 (2004) Temperature (the significant correlation between temperature and dengue incidence) Change in disease Paradox in Singapore

14. Virologic and epidemiologic data strongly suggest that the Hawaii dengue outbreak was directly linked to the one in French Polynesia. Travelers are a potential source for Hawai’i 2001dengue outbreaks DENV may have been introduced to Maui when a group of >30 persons from Hana visited Tahiti during April–May 2001. One of the travelers became ill after returning and later tested positive for anti-DENV IgM and IgG. Hawai’i dengue outbreak in 2001-2002 Confirmed dengue infections by week of illness onset and island, Hawaii, May 20, 2001, to February 17, 2002. Not only mosquito can fly!the effect of human movement on dengue spread

15. Ecological Changes

16. What about climate change? • The association between climatic variables and dengue fever has also been documented in south China, Malaysia, South Pacific, Puerto Rico, and Australia • Recently, a series of papers studying the association between climatic factors and dengue in Thailand have been published, which suggest a nonstationary influence of climatic situation on dengue epidemics in Thailand.

17. References