1. Infectious disease epidemiology Emerging Vector-borne Diseases

2. Vector-borne Infection Cross-cutting factors related to emergence: Increase in and ease of global travel – infected travelers can spread infection to new geographies Rapid urbanization in major cities in the tropics – corresponding hyper-densities of urban slums Ubiquity and abundance of non-degradable containers – has created breading sites for many important mosquito vectors close to large human populations Vector control programs have largely been abandoned due to failing public health infrastructure and external economic pressures to “privatize” traditionally state-provided services

3. Vector-borne Infection Other factors: Building large dams Deforestation and changes in land use in combination with expanded human habitation Introduction of new virus-amplifying hosts or efficient vectors into new areas (e.g. Aedesalbopictus into the Americas) Climate change could also amplify endemic transmission

4. Arboviruses Viruses which are transmitted by an arthropod-borne vector are called arboviruses They are important causes of encephalitis and hemorrhagic fever in many parts of the world including the United States Only specific species of mosquitoes or ticks in specific ecologic systems can transmit these viruses Because the viruses depend on the vector for transmission, the diseases are seasonal in temperate climates, but remain year-round in tropical climates How the viruses overwinter in temperate climates is unknown

5. Arboviruses Abroviruses are classified into four families: Togaviridae, Flaviviridae, Bunyaviridae, and Reoviridae All are relevant to human disease, but we will focus on the Flaviviruses, which are of greatest consequence globally and in the United States, and especially with respect to emergent infection

6. Flaviviridae Single-stranded, linear, (+) sense, RNA genome Icosohedralcapsid structure Enveloped Replicates in cytoplasm of the host cell Virus transmitted by bite of infected arthropod

7. Dengue Known as a human disease for hundreds of years Over the last 20 years dengue fever, dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS) have emerged as the most important arthropod-born viral infection worldwide ~ 100 million cases of dengue fever per year, with ~ 250,000 cases of DHF per year This is what is reported, actual numbers likely much higher

11. Dengue 4 separate serotypes: dengue 1, dengue 2, dengue 3, and dengue 4 Infection with multiple serotypes is most relevant to severity of disease

12. Dengue Dengue fever: Transmission Virus is transmitted by the bite of the Aedesaegypti or Aedesalbopictusmosquitos Ae. aegypti is a much more efficient vector because it much prefers humans

13. Dengue Reservoir: Humans

14. Dengue Dengue fever: signs and symptoms Flu-like illness (but not respiratory) Fever Intense headache Myalgiaand arthralgia, also usually intense…nicknamed break bone fever Maculopapular rash Some minor bleeding is possible, gums and petechiae, during the febrile phase

15. Dengue DHF is much more severe form of dengue: Carries a case-fatality rate of 5% to 15% Associated with a second infection with a new serotype following a previous infection with a different serotype The first infection sensitizes Fc receptors on vascular endothelial cells to virus-associated antibodies The formation of immune complexes associated with a subsequent infection with a new serotype in a sensitized host leads to vascular damage and associated leakage of the vascular beds This vascular pathology results in hemorrhage and/or fluid accumulation in tissues (DHF/DSS)

17. Dengue Because of the large number of dengue infections each year… Billions of people are at risk for DHF/DSS

18. Dengue – The vector General mosquito biology: Purpose of the blood meal? Production of eggs by the female How do they find mammals? They follow CO2 and heat gradients Aedesaegypti is the main vector for dengue virus Small water containing objects Transition from forest to human household environments Bite during the day Cohabitate with humans

19. Dengue – the vector Aedesalbopictus Another vector for dengue that has been introduced into exotic environments across the globe including the United States How? The tire industry Tires are stacked in large quantities on large ships and circulated throughout the world The tires catch and retain rainwater These have served as the sites for oviposition for Ae. albopictus

20. Mosquito distribution in US

21. Dengue Factors favoring dengue emergence: Increases in the use and disposal of non-degradable containers and peridomestic storage has led to more A. aegypti breeding sites Encroachment on tropical forest

22. Dengue PAHO program to eliminate A. aegypti from the Americas in 1947 …Why? Yellow fever By 1972, A. aegypti had been eliminated from 73% of the areas previously occupied by the mosquito However, the identification of a jungle cycle of yellow fever resulted in the end of the campaign By 1998, A.aegypti had colonized more geographic area in the Americas than it had prior to 1947, as well as a much greater global geography

23. Dengue Prevention and control: Very difficult to prevent because mosquitoes live in and around the home and bite at all times, especially during the day, so residual insecticide spraying is ineffective Vaccines have not progressed because they need to be effective against all serotypes and immunity must be very long-lived, otherwise the host may be placed at greater risk of DHF/DSS following vaccination

24. Dengue Prevention and control: Most effective means of prevention is destroying larval development sites Must target water filled containers in and around the home This strategy is remarkably effective at controlling the mosquito, but is also labor intensive This was the singular approach used in the 1947 PAHO campaign