INFECTIOUS DISEASE EPIDEMIOLOGY

Emerging Vector-borne Diseases

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

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. Aedes albopictus into the Americas)

Climate change could also amplify endemic transmission

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

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

Flaviviridae

Single-stranded, linear, (+) sense, RNA genome

Icosohedral capsid structure Enveloped Replicates in cytoplasm of the host

cell Virus transmitted by bite of infected

arthropod

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

Dengue

4 separate serotypes: dengue 1, dengue 2, dengue 3, and

dengue 4 Infection with multiple serotypes is

most relevant to severity of disease

Dengue

Dengue fever: Transmission Virus is transmitted by the bite of the

Aedes aegypti or Aedes albopictus mosquitos

Ae. aegypti is a much more efficient vector because it much prefers humans

Dengue

Reservoir: Humans

Dengue

Dengue fever: signs and symptoms Flu-like illness (but not respiratory) Fever Intense headache Myalgia and arthralgia, also usually

intense…nicknamed break bone fever Maculopapular rash Some minor bleeding is possible, gums

and petechiae, during the febrile phase

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)

Dengue

Because of the large number of dengue infections each year…

Billions of people are at risk for DHF/DSS

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 Aedes aegypti 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

Dengue – the vector

Aedes albopictus 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

Mosquito distribution in US

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

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

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

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