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Avery Lee, MS
Rennie Ferguson, MHS
Susan Henderson, MD, MPH
Outline
• Dengue• Virus
• Vector
• Clinical Manifestation
• Immunity
• Epidemiology
• Intervention
• Results• Dengue Incidence among PCVs
• Peace Corps vs. WHO data
• Explanation• Increased risk among travelers
• Underreporting
• Other explanations
• Dengue is caused by four serologically related but antigenically distinct
viruses, known as DENV-1, DENV-2, DENV-3, and DENV-4
• Dengue viruses are single-stranded, positive-sense, and composed of
RNA
• DENV-1 was first isolated in 1943 from the blood of a Japanese patient
The Virus
• The four dengue viruses originated in monkeys and independently
jumped to humans between 100 and 800 years ago (9)
• The record of a disease outbreak in Philadelphia in 1780 points to
dengue fever
• Dengue was geographically limited until the middle of the 20th Century
• The first known epidemic of severe dengue occurred in the Philippines in
1953
The Virus
• Aedes aegypti mosquitoes are the principal vector of dengue
• They can also transmit chikungunya, yellow fever, and zika virus
• Females preferentially feed indoors during the daytime and bite multiple
people in a single feeding period
The Vector
• Eggs are commonly deposited in man-
made water containers and can survive
drying for up to several months
• Female mosquitoes acquire the virus by biting an infected human
• The virus incubates for 8 to 12 days inside the mosquito before it
can be transmitted
• The virus is introduced into the blood stream of a human from the
mosquito salivary glands when the female takes a blood meal
• Symptoms generally last for 2 to 7 days, during which time the virus
can be taken up by mosquitos
Transmission
• Dengue infections are often asymptomatic in children younger than 15,
but symptomatic in adults
• Clinical disease can present as dengue or severe dengue
• Dengue is a milder, generally self-limiting infection
• Severe dengue is characterized by complications
such as plasma leakage or severe bleeding
Clinical Manifestations
• Chikungunya presents with
similar symptoms to dengue
fever
• Clinical distinction: severe joint
pain accompanies most
chikungunya infections but is
rare among dengue patients
• Laboratory distinction: elevated
hematocrit occurs in 40-69% of
dengue patients but does not
occur in patients with
chikungunya (23)
PAHO and CDC (2011) Preparedness and
Response for Chikungunya Virus Introduction in
the Americas
• Dengue infection provides long-term immunity to the infecting serotype
and 2 to 3 months immunity to the three non-infecting serotypes
• Secondary infection with a different serotype increases the risk of severe
disease
– Improved clinical management has resulted in a decline in case fatality
among hospitalized severe dengue cases from 20% to less than 0.5%
• Antibody-dependent enhancement
– Explains the increased risk for severe disease among dengue patients with a
secondary infection
Immunity
Antibody-Dependent Enhancement
• Dengue infections occur in more than 100 countries in the Asia-Pacific
region, the Americas, the Middle East and Africa
• Incidence, distribution, and clinical severity of dengue has increased
globally over the last 60 years
Epidemiology
• The WHO currently estimates that there are 390 million dengue
infections per year, of which 96 million manifest apparently (24)
• Roughly 2.5 billion people live in areas potentially at risk for dengue
transmission
• 5 vaccines are in the clinical
stages of development
• CYD-TDV vaccine
– The only vaccine to enter Phase
III clinical trials
– Tetravalent live-attenuated
vaccine developed by Sanofi
Pasteur Group
Clinical Interventions
• Asia CYD-TDV Vaccine Phase III Trial
– 10,275 subjects aged 2 to 14 years old
– 56.5% overall efficacy
– 88.5% efficacy against severe dengue
• Latin America CYD-TDV Vaccine Phase III Trial
– 20,869 subjects aged 9 to 16 years old
– 60.8% overall efficacy
– 91.7% efficacy against severe dengue
• December 2015: market approval in Mexico,
Brazil, and the Philippines
Clinical Interventions
• Environmental management and modification
• Chemical control interventions
• Biological interventions
• Integrated vector management involves
a combination of interventions as well as
community education and involvement (11)
Environmental Interventions
• Personal protection can be an important barrier to Aedes aegypti
mosquitoes and other disease-carrying vectors
• Insecticides
– The CDC recommends using products with 20% to 50% DEET
concentration
• Clothing
– Permethrin-treated clothing repels mosquitoes and kills insects that come in
contact with the cloth (28)
Individual-Level Interventions
• Created by President JFK in 1961
• To help the people of interested countries in meeting their need for
trained men and women
• To help promote a better understanding of Americans on the part of
the peoples served
• To help promote a better understanding
of other peoples on the part of Americans
United States Peace Corps
• Americans who have served: nearly 220,000
• Host countries served to date: 141
• Gender: 63% female, 37% male
• Minorities: 28% of Volunteers
• Average age: 28
• Volunteers over 50: 7% of Volunteers
Peace Corps Demographics
Carolyn Hessler-Radelet,
Peace Corps Director
• Percentage of total Volunteers serving, by geographic region, in 2015
– Africa: 45%
– Latin America: 22%
– Eastern Europe/
Central Asia: 10%
– Asia 13%
– The Caribbean: 4%
– North Africa/ Middle East: 3%
– Pacific Islands: 3%
Peace Corps Location of Service
• Peace Corps Volunteers (PCVs) commit to a 27-month assignment
abroad
• Work at the grass-roots level around the world, primarily in low- and
middle-income countries
• Generally young and healthy individuals
• PCVs have a unique risk of dengue due
to long-term travel to endemic countries as
as well as in-country living conditions
Peace Corps Volunteers
• Monthly Epidemiological Surveillance System (ESS) reports submitted
to the PC Epidemiology Unit by Peace Corps Medical Officers (PCMOs)
• ESS reports include the number of laboratory confirmed dengue cases
• Peace Corps countries divided into the following regions: Europe and
Central Asia, East and South Asia, Africa, Caribbean, Central America,
South America, and Pacific Islands
Methods
• Dengue incidence rates calculated using the yearly total of dengue
cases and Volunteer/Trainee years (VT years)
– All rates reported in cases per 1,000 VT Months
• Data analyzed using SAS 9.3 (Cary, NC), OpenEpi 3 (Atlanta, GA), and
ArcGIS 10.3.1 (Redlands, CA)
Methods
Results
1.2
0.9
0.6
1.2
1.0
1.2 1.2
1.7
0.7
1.2
1.5
0.7
1.4
1.6
0.8
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014
Case
s p
er
1,000 V
T M
on
ths
Overall Incidence Rates of Dengue among PCVs, 2000-2014
Results
0.03 0.12
1.16
2.302.55
3.34
5.51
0.0
1.0
2.0
3.0
4.0
5.0
6.0
Europe andCentral Asia
Africa South America Pacific Islands Central America East and SouthAsia
Caribbean
Case
s p
er
1,000 V
T M
on
ths
Cumulative Incidence Rates of Dengue Among PCVs by Region, 2000-2014
Results
Europe and Central Asia0.5%
East and South Asia19.8%
Africa4.3%
Central America31.6%
Caribbean25.8%
South America9.8%
Pacific Islands8.2%
Percentage of Dengue Cases by Region, 2000-2014
Results
0.0
2.0
4.0
6.0
8.0
10.0
12.0
14.0
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014
Case
s p
er
1,000 V
T M
on
ths
Incidence Rates of Dengue Among PCVs, 2000-2014
Results
0.0
2.0
4.0
6.0
8.0
10.0
12.0
14.0
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014
Case
s p
er
1,000 V
T M
on
ths
Incidence Rates of Dengue Among PCVs, 2000-2014
Results
0.0
2.0
4.0
6.0
8.0
10.0
12.0
14.0
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014
Case
s p
er
1,000 V
T M
on
ths
Incidence Rates of Dengue Among PCVs, 2000-2014
Results
0.0
2.0
4.0
6.0
8.0
10.0
12.0
14.0
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014
Case
s p
er
1,000 V
T M
on
ths
Incidence Rates of Dengue Among PCVs, 2000-2014
Results
0.0
2.0
4.0
6.0
8.0
10.0
12.0
14.0
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014
Case
s p
er
1,000 V
T M
on
ths
Incidence Rates of Dengue Among PCVs, 2000-2014
Results
0
100
200
300
400
500
600
700
800
900
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014
Rati
o
Ratio of Dengue Incidence Among PCVs Compared to WHO Reported Dengue Incidence
Domincan Republic
Nicaragua
Philippines
Risk Among Travelers
• A cohort study of Dutch travelers to Asia in 2002 reported an dengue
incidence rate of 30.0 cases per 1,000 person-months (7)
• A study conducted in 2013 among long-term aid workers from New
Zealand reported a dengue incidence
rate of 3.4 cases per 1,000
person-months (31)
Risk Among Travelers
• Bhatt et al. compiled data from 27 cohort studies and determined a
mean dengue incidence rate of 129.7 cases per 1,000 person-years
(10.8 per 1,000 person-months) (2)
• Multiple cohort studies involving short-term American missionary trips to
the Caribbean have reported dengue infection in 25% or more of
travelers (20, 21, 26)
Risk Among Travelers
• The increased risk among PCVs could potentially be explained by their
lack of previous exposure
• A study conducted in 2006 in Nicaragua found that the overall
seroprevalence of dengue antibodies among school-aged children was
91% (1)
• A similar study in the Dominican Republic reported that 98% of adults
and 56% of children under 10 were positive for dengue IgG anitbodies
(35)
Underreporting
• Underreporting is a major issue in
dengue surveillance
• In 2010, there were an estimated
96 million clinically apparent
dengue cases globally; only 2.2
million cases were reported to the
WHO
Underreporting
• Most dengue surveillance is passive and many countries do not require
reporting of dengue cases in adults
• The Nicaraguan Pediatric Dengue Cohort Study identified an average of
21.3 times more dengue cases per 100,000 persons per year than the
Nicaraguan Ministry of Health (27)
• Vong et al. estimated that there was as high as a 30-fold degree of
under-recognition and underreporting of dengue in Cambodia between
2006 and 2008 (32)
Other Explanations
• Differences in treatment seeking behavior
• Demographic and genetic differences between PCVs and host country
nationals
• Differences in use of personal protection to avoid mosquito bites
• Dengue testing may be more readily available to PCVs
• PCMOs may be more inclined to test for dengue than other physicians
Conclusions
• The incidence rate of dengue among PCVs globally appears to follow a
3-year cyclical pattern
• Each region demonstrated a unique pattern in dengue incidence rates
over the 15-year study period
• Peace Corps Volunteers serving in the Caribbean appear to be at the
highest risk for contracting dengue
• Countries with the highest cumulative incidence rates appear to be
geographically clustered within each region
Conclusions
• The rate of dengue infection among PCVs appears to be higher than
the rate reported among host country nationals in high-incidence
countries. Explanations:
– Lack of previous exposure to dengue
– Underreporting
• The distribution of dengue is ever-changing
• Continued surveillance is critical for understanding transitions in
disease patterns and informing public health decision making
• Continued monitoring of dengue incidence among PCVs in order to
inform decision making when a vaccine becomes available
• PCMEDICS
– Information about demographics, comorbidities, and hospitalization of
dengue patients
• Education for PCVs
– Adherence to mosquito control is currently the only way to reduce dengue
incidence
– This data may eventually be available for prospective Peace Corps
Volunteers
Next Steps
Questions?
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doi:10.1038/nature12060
3. Blamont M and Mennella N (2015) Sanofi wins first dengue vaccine market approval in Mexico. Reuters.
http://www.reuters.com/article/us-sanofi-dengue-idUSKBN0TS1ZK20151209
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