2017 GH Sesi 8 RAA Dengue Fever
3/9/17
Dengue Fever
What is Dengue?
Is an acute fever producing infectious disease
Mostly found in the tropics
Complications can be fatal
It is also known as Dengue fever , breakbone fever or
Dengue hemorrhagic fever
Bauman, R., (2006). Microbiology disease by systems. San Francisco , CA: Pearson Benjamin
Cumming Publishers
1
3/9/17
Dengue Virus
• Flavivirus (single-stranded RNA virus)
• Spherical, 40-50 nm (dia.) viral particle
– 3 Structural (E, C, M) proteins
– 7 Nonstructural (NS1, NS2A, NS2B, NS3, NS4A, NS4B,
NS5)
• 5 serotypes
– DENV 1 through 5
– Multiple genotypes per serotype
• Common progenitor 1,000 years ago
• Serotypes have further divergence
– 62 to 67% homology based on amino acid sequence
• Varying pathogenicity based on serotype
History of Dengue
• Clinical descriptions date as far back as 992 AD
in China
• David Bylon (Batavia) in 1779
– knokkelkoorts --- joint fever
• Benjamin Rush
– Termed breakbone fever
– Comes from Swahili ka dinga pepo
meaning a sudden cramp like seizure
and plague
Thomas S Advances in Virus Research 2003.
Kyle J Annu Rev Microbiol 2008. 62:71-92.
http://www91.homepage.villanova.edu/eli.greenbaum/peru.htm
2
3/9/17
History of Dengue
• Viral etiology suggested in early 1900’s by
Ashburn and Craig
• DENV-1 and 2 isolated during World War II
• 1956 outbreak in Manila led to identification of
DENV-3 and DENV-4
• Dengue hemorrhagic fever recognized since
1950’s
• DENV-5 discovered in Sarawak 2013
Thomas S Advances in Virus Research 2003.
Kyle J Annu Rev Microbiol 2008. 62:71-92.
Transmission of Dengue
A mosquito is the biological vector
This mosquito is the obligate intermediate
host for some viruses
Aedes albopictus/aegypti are generally
associated with the spread of dengue fever
Akram, W., (n.d.). Aedes as a vector of Dengue: a possible threat to our lives. Khwarzimig Science Society.
University of Agriculture, Faisalabad. Retrieved April 19, 2010 from
http://www.khwarzimic.org/takveen/dengue_kss.pdf
3
3/9/17
Aedes albopictus
Aedes aegypti
4
3/9/17
Aedes aegypti behaviors
5
3/9/17
Aedes aegypti life cycle
2-7 days
>4 days
days
2
Classification of Dengue
Old WHO classification
Classical Dengue Fever
Dengue Fever with hemorrhagic
manifestations
DHF grade one
DHF grade two
DHF grade three
DHF grade four
DHF with unusual manifestations
New WHO classification
Probable dengue ( group A - OPD
management)
Dengue with warning signs (
Group B - inward observation and
management)
( patients are admitted for social reasons and
when they are in high risk category)
Severe Dengue ( Group C resuscitation and management)
1. With compensated shock
2. With hypotensive shock
3. With severe organ impairment
6
3/9/17
Diagnosis for Dengue
Travel history and symptom profile
Detection of antibodies against the virus: IgM, IgG
Complete blood count
Chemistry panel
Liver function test
Occult blood in stool
DIC panel
Dengue rapid test NS1
PCR
Price, D.D., Wilson, S.R., (2009). Dengue fever: differential diagnoses and workout. Medscape. Retrieved
April 19, 2010 from http://emedicine.medscape.com/article/781961-diagnosis
Immune Response & Dengue diagnosis
NS-1: Effective days 1-5
post onset of symptoms
Acute
Acute
Convalescent
Day 0
IgM/IgG: Effective after
day 5
Convalescent
A diagnostic capable of
detecting both is
desirable
7
Slide courtesy of Dr. Subhamoy Pal
7
3/9/17
Rapid Diagnostic Tests (RDT’s)
Current RDT’s
Future RDT’s
Important for:
• Quick diagnosis (lab results take time
and require labs)
• In resource-limited settings
• Alerts a unit to ID threats
• Helpful for triage during outbreaks
• Curtail geographic spread of
infectious diseases
• Stability operations and
infrastructure building
Worldwide demand for better diagnostics to
manage treatment and prevention
Slide courtesy of Dr. Subhamoy Pal
Product Introduction
#1: IgG/IgM Dengue Duo Cassette
10μL of serum, plasma, or whole
blood
15 minute (time to result)
Wu et. al. CDLI 2000, pp 106-109
10 uL of serum
1.5 hours
Slide courtesy of Dr. Subhamoy Pal
8
3/9/17
Product Introduction cont'd
#2: NS-1/IgG/IgM Dengue Duo
Cassette
120μL of serum or plasma
15 minute (time to result)
Osorio et al. Virology Journal 2010, 7:361
Slide courtesy of Dr. Subhamoy Pal
Standard Diagnostics Dengue Duo (NS-1) RDT
NS1 Ag
IgG/IgM Ab
3 drops (110 μl) of plasma or serum
for early acute phase samples (day 1 ~5)
10 μl of plasma or serum for early convalescence phase
samples (after day 5 ~ 14)
IgG
Ag/Ab level
Ag/Ab level
IgG
IgM
NS1 Ag
1 2 3
5
7
10
12 Day
IgM
NS1 Ag
1 2 3
5
7
10
12 Day
Slide courtesy of Dr. Subhamoy Pal
9
3/9/17
Treatment for Dengue
No specific therapeutic agents exist for dengue
infections
Bed rest and hydration therapy
Fever control with acetaminophen. Narcotics may be
necessary if headaches are very severe
Aspirin should be avoid because of anticoagulant
properties, children should avoid aspirin when a viral
infection is suspected
Monitoring of signs and symptoms for warning signs of
DHF or DSS
Price, D.D., Wilson, S.R., (2009). Dengue fever: differential diagnoses and workout. Medscape. Retrieved April 19, 2010 from
http://emedicine.medscape.com/article/781961-diagnosis
Geographic distribution of Dengue
• Dengue disease occurs in tropical and subtropical
areas
• Endemic in over 100 countries in the Caribbean,
South, Central and North America, Africa, the
Pacific Islands, Hawaii, Asia, Eastern
Mediterranean and Australia
• Before 1970 only nine countries had experience
dengue hemorrhagic fever epidemics, a number
that had increased more than four-fold by 1995
•
World Health Organization, (2009). Dengue and Dengue haemorrhagic fever. Retrieved April 19, 2010 from
http://www.who.int/mediacentre/factsheets/fs117/en/
10
3/9/17
Geography distribution of Dengue
Blue dot: Geographic extension of dengue 2000-2007
Blue shaded areas: Risk of dengue transmission
Lines: Lines demarcate the area where the vector for dengue exists
Global geographic distribution of DENV
(1940 – 2013)
11
3/9/17
Suitability for Dengue
Transmission
High suitability
Low suitability
Unsuitable or nonendemic
Estimated Burden of Dengue by
continent (2010)
Bhatt et.al 2013)
12
3/9/17
Dengue episodes and economic burden in
12 SE Asia countries (2001-2010)
13
3/9/17
Estimated annual economic burden in
SE Asia (in million USD 2010)
Economic burden of dengue
• Significant Economic Burden
– Direct and Indirect costs
– SE Asia: 1,300 disability-adjusted life years
• DHF in Thailand: $19 to $51 (US) Million/year
– Similar to TB, other childhood and tropical diseases
– 1981 Cuban DF/DHF/DSS epidemic
• $103 Million (US), including control measures ($43 Million)
and medical services ($41 Million)
– Puerto Rico DF/DHF/DSS annual
• $150-$200 Million (US)
14
3/9/17
Figure 1. Average number of dengue and severe dengue cases reported to WHO annually
in 1955–2007 and number of cases reported in recent years, 2008–2010
2500000
2204516
Number of cases
2000000
1451083
1500000
1279668
1000000
925896
479848
500000
295554
122174
0
908
15497
55–59
60–69
70–79
80–89
90–99
00–07
2008
2009
2010
Period of year
Dengue control strategy
15
3/9/17
Natural history of Dengue
Natural history of Dengue
16
3/9/17
Natural history of Dengue
Time
Infected
Death
Clinical horizon
Susceptible host
Cure
Non infected
Incubation period
Latent
Non-infectious
Infectious
Exposure
Onset
Global Strategy
TREATMENT, PREVENTION AND CONTROL
GOAL:
TO REDUCE THE BURDEN OF DENGUE
OBJECTIVES:
2O12–2O2O
GLOBAL STRATEGY
FOR DENGUE PREVENTION AND CONTROL
UÊ /ÊÀi`ÕViÊ`i}ÕiÊÀÌ>ÌÞÊLÞÊ>ÌÊi>ÃÌÊxä¯ÊLÞÊÓäÓäI
UÊ /ÊÀi`ÕViÊ`i}ÕiÊÀL`ÌÞÊLÞÊ>ÌÊi>ÃÌÊÓx¯ÊLÞÊÓäÓäI
UÊ /ÊiÃÌ>ÌiÊÌ iÊÌÀÕiÊLÕÀ`iÊvÊÌ iÊ`Ãi>ÃiÊLÞÊÓä£x
IÊ/ iÊÞi>ÀÊÓä£äÊÃÊÕÃi`Ê>ÃÊÌ iÊL>Ãii°
Technical element 1:
Technical element 2:
Technical element 3:
Technical element 4:
Technical element 5:
Diagnosis and case
management
Integrated surveillance
and outbreak
preparedness
Sustainable vector
control
Future vaccine
implementation
Basic operational
and implementation
research
ENABLING FACTORS FOR EFFECTIVE IMPLEMENTATION OF THE GLOBAL STRATEGY:
UÊ
UÊ
UÊ
UÊ
UÊ
>`ÛV>VÞÊ>`ÊÀiÃÕÀViÊLâ>ÌÊ
«>ÀÌiÀÃ «]ÊVÀ`>ÌÊ>`ÊV>LÀ>ÌÊ
VÕV>ÌÊÌÊ>V iÛiÊLi >ÛÕÀ>ÊÕÌViÃ
V>«>VÌÞLÕ`}Ê
ÌÀ}Ê>`ÊiÛ>Õ>Ì
17
3/9/17
Case management
• Improve case management and diagnosis to prevent deaths
from dengue
– Improve early clinical case detection for dengue with
warning signs and severe dengue;
– Improve management of severe cases.
• Improve capacities to facilitate a reduction in the burden of
the disease
– Improve access health care services;
– Reorganization of health service for better managing
outbreak situations;
– Establish QA in both the private and the public sector;
Surveillance and outbreak preparedness
• Improve surveillance to enhance reporting,
prevention and control of dengue
– Surveillance indicators – for clinical reasons, a minimum
set of indicators should be reported;
– Risk indicators:
• Mosquito breeding sites (i.e. household water storage containers, poor
urban water drainage)
• Environmental control measures (i.e. tightly fitting water storage lids,
presence of fish or other biological control measures, and regular cleaning
containers)
– sentinel sites for age- stratified seroprevalence and burden
of disease (including economic costs).
– Serotype changes should be monitored continuously.
18
3/9/17
Surveillance and outbreak preparedness
• Outbreak preparedness (10 priority area)
1.
2.
3.
4.
5.
6.
7.
8.
Establish a multisectoral dengue action committee
Formalize an emergency action plan
Enhance disease surveillance
Perform diagnostic laboratory testing
Enhance vector surveillance and control
Protect special populations and reduce the impact
Ensure appropriate patient care
Engage the community in dengue control and ensure
participation in dengue prevention and control
9. Investigate the epidemic
10. Manage the mass media.
Sustainable vector control
• Combination of:
– Environmental management
– Biological control
– Chemical control
19
3/9/17
New vaccine
DENGVAXIA® (Sanofi Pasteur)
Phase&3&Trials&of&CYD.TDV&
Adapted!from!Guy%(2015)%
5!
20
3/9/17
DENGVAXIA® (Sanofi Pasteur)
VE&against&DENV1.4&by&serostatus&before&
vaccinaXon&(ITT&–&M0.M25)&
Study&
PopulaXon&
SeroposiXve&at&
baseline&
CYD14&
CYD15&
Pooled&
Pooled&&
(2.14&years)& (9.16&years)& (2.16&years)& (9.16&years)&
74.3%&
83.7%&
78.2%&
81.9%&
(53.2F86.3)!
(62.2F93.7)!
(65.4F86.3)!
(67.2F90.0)!
38.1%&
52.5%&
(F3.4F62.9)!
(5.9F76.1)!
43.2%&
35.5%&
SeronegaXve&at&
baseline&
(F27.0F66.6)! (F61.6F80.0)!
DENGVAXIA® (Sanofi Pasteur)
VE&against&DENV1.4&by&age&(ITT&–&M0.M25)&
Study&PopulaXon&
All&ages&
2.5&years&
6.11&years&
12.16&years&
CYD14&
(2.14&years)&
CYD15&
(9.16&years)&
54.8%&
64.7%&
(46.8F61.7)!
(58.7F69.8)!
%&seroposiXve&before&
vaccinaXon&
CYD&14& CYD15&
68%&
79%&
NA!
51%&
NA&
59.5%&
61.7%&
72%&
75%&
(48.9F68.0)!
(52.3F69.3)!
74.4%&
67.6%&
81%&
84%&
(59.2F84.3)!
(59.3F74.3)!
33.7%&
(11.7F50.0)!
15!
21
3/9/17
Fig. 1 Model fit to publicly available data from the Asian phase 3 clinical trial.
Neil M. Ferguson et al. Science 2016;353:1033-1036
Published by AAAS
New discovery (Research arm)
• Wolbachia
22
3/9/17
Frekuensi Wolbachia dan kasus dengue di Nogotirto
and Kronggahan (Sleman)
Wolbachia frequency in Jomblangan and
Singosaren (Bantul)
23
Dengue Fever
What is Dengue?
Is an acute fever producing infectious disease
Mostly found in the tropics
Complications can be fatal
It is also known as Dengue fever , breakbone fever or
Dengue hemorrhagic fever
Bauman, R., (2006). Microbiology disease by systems. San Francisco , CA: Pearson Benjamin
Cumming Publishers
1
3/9/17
Dengue Virus
• Flavivirus (single-stranded RNA virus)
• Spherical, 40-50 nm (dia.) viral particle
– 3 Structural (E, C, M) proteins
– 7 Nonstructural (NS1, NS2A, NS2B, NS3, NS4A, NS4B,
NS5)
• 5 serotypes
– DENV 1 through 5
– Multiple genotypes per serotype
• Common progenitor 1,000 years ago
• Serotypes have further divergence
– 62 to 67% homology based on amino acid sequence
• Varying pathogenicity based on serotype
History of Dengue
• Clinical descriptions date as far back as 992 AD
in China
• David Bylon (Batavia) in 1779
– knokkelkoorts --- joint fever
• Benjamin Rush
– Termed breakbone fever
– Comes from Swahili ka dinga pepo
meaning a sudden cramp like seizure
and plague
Thomas S Advances in Virus Research 2003.
Kyle J Annu Rev Microbiol 2008. 62:71-92.
http://www91.homepage.villanova.edu/eli.greenbaum/peru.htm
2
3/9/17
History of Dengue
• Viral etiology suggested in early 1900’s by
Ashburn and Craig
• DENV-1 and 2 isolated during World War II
• 1956 outbreak in Manila led to identification of
DENV-3 and DENV-4
• Dengue hemorrhagic fever recognized since
1950’s
• DENV-5 discovered in Sarawak 2013
Thomas S Advances in Virus Research 2003.
Kyle J Annu Rev Microbiol 2008. 62:71-92.
Transmission of Dengue
A mosquito is the biological vector
This mosquito is the obligate intermediate
host for some viruses
Aedes albopictus/aegypti are generally
associated with the spread of dengue fever
Akram, W., (n.d.). Aedes as a vector of Dengue: a possible threat to our lives. Khwarzimig Science Society.
University of Agriculture, Faisalabad. Retrieved April 19, 2010 from
http://www.khwarzimic.org/takveen/dengue_kss.pdf
3
3/9/17
Aedes albopictus
Aedes aegypti
4
3/9/17
Aedes aegypti behaviors
5
3/9/17
Aedes aegypti life cycle
2-7 days
>4 days
days
2
Classification of Dengue
Old WHO classification
Classical Dengue Fever
Dengue Fever with hemorrhagic
manifestations
DHF grade one
DHF grade two
DHF grade three
DHF grade four
DHF with unusual manifestations
New WHO classification
Probable dengue ( group A - OPD
management)
Dengue with warning signs (
Group B - inward observation and
management)
( patients are admitted for social reasons and
when they are in high risk category)
Severe Dengue ( Group C resuscitation and management)
1. With compensated shock
2. With hypotensive shock
3. With severe organ impairment
6
3/9/17
Diagnosis for Dengue
Travel history and symptom profile
Detection of antibodies against the virus: IgM, IgG
Complete blood count
Chemistry panel
Liver function test
Occult blood in stool
DIC panel
Dengue rapid test NS1
PCR
Price, D.D., Wilson, S.R., (2009). Dengue fever: differential diagnoses and workout. Medscape. Retrieved
April 19, 2010 from http://emedicine.medscape.com/article/781961-diagnosis
Immune Response & Dengue diagnosis
NS-1: Effective days 1-5
post onset of symptoms
Acute
Acute
Convalescent
Day 0
IgM/IgG: Effective after
day 5
Convalescent
A diagnostic capable of
detecting both is
desirable
7
Slide courtesy of Dr. Subhamoy Pal
7
3/9/17
Rapid Diagnostic Tests (RDT’s)
Current RDT’s
Future RDT’s
Important for:
• Quick diagnosis (lab results take time
and require labs)
• In resource-limited settings
• Alerts a unit to ID threats
• Helpful for triage during outbreaks
• Curtail geographic spread of
infectious diseases
• Stability operations and
infrastructure building
Worldwide demand for better diagnostics to
manage treatment and prevention
Slide courtesy of Dr. Subhamoy Pal
Product Introduction
#1: IgG/IgM Dengue Duo Cassette
10μL of serum, plasma, or whole
blood
15 minute (time to result)
Wu et. al. CDLI 2000, pp 106-109
10 uL of serum
1.5 hours
Slide courtesy of Dr. Subhamoy Pal
8
3/9/17
Product Introduction cont'd
#2: NS-1/IgG/IgM Dengue Duo
Cassette
120μL of serum or plasma
15 minute (time to result)
Osorio et al. Virology Journal 2010, 7:361
Slide courtesy of Dr. Subhamoy Pal
Standard Diagnostics Dengue Duo (NS-1) RDT
NS1 Ag
IgG/IgM Ab
3 drops (110 μl) of plasma or serum
for early acute phase samples (day 1 ~5)
10 μl of plasma or serum for early convalescence phase
samples (after day 5 ~ 14)
IgG
Ag/Ab level
Ag/Ab level
IgG
IgM
NS1 Ag
1 2 3
5
7
10
12 Day
IgM
NS1 Ag
1 2 3
5
7
10
12 Day
Slide courtesy of Dr. Subhamoy Pal
9
3/9/17
Treatment for Dengue
No specific therapeutic agents exist for dengue
infections
Bed rest and hydration therapy
Fever control with acetaminophen. Narcotics may be
necessary if headaches are very severe
Aspirin should be avoid because of anticoagulant
properties, children should avoid aspirin when a viral
infection is suspected
Monitoring of signs and symptoms for warning signs of
DHF or DSS
Price, D.D., Wilson, S.R., (2009). Dengue fever: differential diagnoses and workout. Medscape. Retrieved April 19, 2010 from
http://emedicine.medscape.com/article/781961-diagnosis
Geographic distribution of Dengue
• Dengue disease occurs in tropical and subtropical
areas
• Endemic in over 100 countries in the Caribbean,
South, Central and North America, Africa, the
Pacific Islands, Hawaii, Asia, Eastern
Mediterranean and Australia
• Before 1970 only nine countries had experience
dengue hemorrhagic fever epidemics, a number
that had increased more than four-fold by 1995
•
World Health Organization, (2009). Dengue and Dengue haemorrhagic fever. Retrieved April 19, 2010 from
http://www.who.int/mediacentre/factsheets/fs117/en/
10
3/9/17
Geography distribution of Dengue
Blue dot: Geographic extension of dengue 2000-2007
Blue shaded areas: Risk of dengue transmission
Lines: Lines demarcate the area where the vector for dengue exists
Global geographic distribution of DENV
(1940 – 2013)
11
3/9/17
Suitability for Dengue
Transmission
High suitability
Low suitability
Unsuitable or nonendemic
Estimated Burden of Dengue by
continent (2010)
Bhatt et.al 2013)
12
3/9/17
Dengue episodes and economic burden in
12 SE Asia countries (2001-2010)
13
3/9/17
Estimated annual economic burden in
SE Asia (in million USD 2010)
Economic burden of dengue
• Significant Economic Burden
– Direct and Indirect costs
– SE Asia: 1,300 disability-adjusted life years
• DHF in Thailand: $19 to $51 (US) Million/year
– Similar to TB, other childhood and tropical diseases
– 1981 Cuban DF/DHF/DSS epidemic
• $103 Million (US), including control measures ($43 Million)
and medical services ($41 Million)
– Puerto Rico DF/DHF/DSS annual
• $150-$200 Million (US)
14
3/9/17
Figure 1. Average number of dengue and severe dengue cases reported to WHO annually
in 1955–2007 and number of cases reported in recent years, 2008–2010
2500000
2204516
Number of cases
2000000
1451083
1500000
1279668
1000000
925896
479848
500000
295554
122174
0
908
15497
55–59
60–69
70–79
80–89
90–99
00–07
2008
2009
2010
Period of year
Dengue control strategy
15
3/9/17
Natural history of Dengue
Natural history of Dengue
16
3/9/17
Natural history of Dengue
Time
Infected
Death
Clinical horizon
Susceptible host
Cure
Non infected
Incubation period
Latent
Non-infectious
Infectious
Exposure
Onset
Global Strategy
TREATMENT, PREVENTION AND CONTROL
GOAL:
TO REDUCE THE BURDEN OF DENGUE
OBJECTIVES:
2O12–2O2O
GLOBAL STRATEGY
FOR DENGUE PREVENTION AND CONTROL
UÊ /ÊÀi`ÕViÊ`i}ÕiÊÀÌ>ÌÞÊLÞÊ>ÌÊi>ÃÌÊxä¯ÊLÞÊÓäÓäI
UÊ /ÊÀi`ÕViÊ`i}ÕiÊÀL`ÌÞÊLÞÊ>ÌÊi>ÃÌÊÓx¯ÊLÞÊÓäÓäI
UÊ /ÊiÃÌ>ÌiÊÌ iÊÌÀÕiÊLÕÀ`iÊvÊÌ iÊ`Ãi>ÃiÊLÞÊÓä£x
IÊ/ iÊÞi>ÀÊÓä£äÊÃÊÕÃi`Ê>ÃÊÌ iÊL>Ãii°
Technical element 1:
Technical element 2:
Technical element 3:
Technical element 4:
Technical element 5:
Diagnosis and case
management
Integrated surveillance
and outbreak
preparedness
Sustainable vector
control
Future vaccine
implementation
Basic operational
and implementation
research
ENABLING FACTORS FOR EFFECTIVE IMPLEMENTATION OF THE GLOBAL STRATEGY:
UÊ
UÊ
UÊ
UÊ
UÊ
>`ÛV>VÞÊ>`ÊÀiÃÕÀViÊLâ>ÌÊ
«>ÀÌiÀÃ «]ÊVÀ`>ÌÊ>`ÊV>LÀ>ÌÊ
VÕV>ÌÊÌÊ>V iÛiÊLi >ÛÕÀ>ÊÕÌViÃ
V>«>VÌÞLÕ`}Ê
ÌÀ}Ê>`ÊiÛ>Õ>Ì
17
3/9/17
Case management
• Improve case management and diagnosis to prevent deaths
from dengue
– Improve early clinical case detection for dengue with
warning signs and severe dengue;
– Improve management of severe cases.
• Improve capacities to facilitate a reduction in the burden of
the disease
– Improve access health care services;
– Reorganization of health service for better managing
outbreak situations;
– Establish QA in both the private and the public sector;
Surveillance and outbreak preparedness
• Improve surveillance to enhance reporting,
prevention and control of dengue
– Surveillance indicators – for clinical reasons, a minimum
set of indicators should be reported;
– Risk indicators:
• Mosquito breeding sites (i.e. household water storage containers, poor
urban water drainage)
• Environmental control measures (i.e. tightly fitting water storage lids,
presence of fish or other biological control measures, and regular cleaning
containers)
– sentinel sites for age- stratified seroprevalence and burden
of disease (including economic costs).
– Serotype changes should be monitored continuously.
18
3/9/17
Surveillance and outbreak preparedness
• Outbreak preparedness (10 priority area)
1.
2.
3.
4.
5.
6.
7.
8.
Establish a multisectoral dengue action committee
Formalize an emergency action plan
Enhance disease surveillance
Perform diagnostic laboratory testing
Enhance vector surveillance and control
Protect special populations and reduce the impact
Ensure appropriate patient care
Engage the community in dengue control and ensure
participation in dengue prevention and control
9. Investigate the epidemic
10. Manage the mass media.
Sustainable vector control
• Combination of:
– Environmental management
– Biological control
– Chemical control
19
3/9/17
New vaccine
DENGVAXIA® (Sanofi Pasteur)
Phase&3&Trials&of&CYD.TDV&
Adapted!from!Guy%(2015)%
5!
20
3/9/17
DENGVAXIA® (Sanofi Pasteur)
VE&against&DENV1.4&by&serostatus&before&
vaccinaXon&(ITT&–&M0.M25)&
Study&
PopulaXon&
SeroposiXve&at&
baseline&
CYD14&
CYD15&
Pooled&
Pooled&&
(2.14&years)& (9.16&years)& (2.16&years)& (9.16&years)&
74.3%&
83.7%&
78.2%&
81.9%&
(53.2F86.3)!
(62.2F93.7)!
(65.4F86.3)!
(67.2F90.0)!
38.1%&
52.5%&
(F3.4F62.9)!
(5.9F76.1)!
43.2%&
35.5%&
SeronegaXve&at&
baseline&
(F27.0F66.6)! (F61.6F80.0)!
DENGVAXIA® (Sanofi Pasteur)
VE&against&DENV1.4&by&age&(ITT&–&M0.M25)&
Study&PopulaXon&
All&ages&
2.5&years&
6.11&years&
12.16&years&
CYD14&
(2.14&years)&
CYD15&
(9.16&years)&
54.8%&
64.7%&
(46.8F61.7)!
(58.7F69.8)!
%&seroposiXve&before&
vaccinaXon&
CYD&14& CYD15&
68%&
79%&
NA!
51%&
NA&
59.5%&
61.7%&
72%&
75%&
(48.9F68.0)!
(52.3F69.3)!
74.4%&
67.6%&
81%&
84%&
(59.2F84.3)!
(59.3F74.3)!
33.7%&
(11.7F50.0)!
15!
21
3/9/17
Fig. 1 Model fit to publicly available data from the Asian phase 3 clinical trial.
Neil M. Ferguson et al. Science 2016;353:1033-1036
Published by AAAS
New discovery (Research arm)
• Wolbachia
22
3/9/17
Frekuensi Wolbachia dan kasus dengue di Nogotirto
and Kronggahan (Sleman)
Wolbachia frequency in Jomblangan and
Singosaren (Bantul)
23