Dengue Fever

Dengue fever is a mosquito borne disease caused by dengue virus which is usually self limiting in
most cases.

However, in some people it can present with life threatening complications such Dengue Shock
Syndrome and Dengue Haemorrhagic Fever.

Dengue is not contagious and does not spread from person to person by physical contact.

The most effective way of preventing dengue fever is by taking precautions to avoid being bitten by
mosquitoes.

Dengue fever is caused by a virus which is transmitted by an infected Aedes mosquito - Aedes
aegypti and Aedes albopictus.

Mosquitoes become infected when they bite infected humans, and later transmit infection to other
people they bite.

The disease usually is self-limiting but in some people can present with life-threatening
complications such as Dengue Haemorrhagic Fever and Dengue Shock Syndrome.

Symptoms
The symptoms usually develop within 4-7 days after being bitten by an infected mosquito. Symptoms
of classic dengue include:

 High fever (up to 40.6 C)

 Severe headache with retro-orbital (behind the eye) pain
 Severe joint and muscle pain
 Nausea and vomiting
 Body rash which appears on day 3 or 4

Dengue Hemorrhagic Fever is a severe form of dengue fever which can result in death and is
characterized by:

 Severe bleeding from the nose, gums, or under the skin causing purplish bruises

Dengue Shock Syndrome is the most severe form which usually occurs in children having a re-
infection and is sometimes fatal. It often presents with:
  Massive bleeding
 Shock (very low blood pressure)

Treatment
There is no specific treatment for dengue fever and most people recover within 2 weeks. To help
with recovery, general measures include:

 Getting plenty of bed rest

 Drinking lots of fluids
 Taking medicine to reduce fever. Avoid aspirin but paracetamol is considered safe

For severe dengue symptoms including shock and coma, hospitalisation and aggressive emergency
treatment with fluid and electrolyte replacement may be necessary to save lives.

Complications
Most people with dengue fever recover completely within 2 weeks. The more clinically severe
dengue hemorrhagic fever and dengue shock syndromes can result in vascular (blood vessel) and
liver damage, and can be life-threatening.

Prevention
The best way to prevent dengue fever is by taking precautions to avoid being bitten by mosquitoes
which include:

 Using a mosquito repellent containing DEET, or oil of lemon eucalyptus

 Dressing in protective clothing during the day-long-sleeved shirts, long pants, socks, and
shoes especially in early morning hours before day break and in late afternoon after dark.
 Keeping unscreened windows and doors closed
 Getting rid of areas where mosquitoes breed, such as standing water in flower pots,
containers, and bamboos etc

Dengue vaccine research

Dengue is a mosquito-borne flavivirus disease that has spread to most tropical and many subtropical areas. The
disease is caused by four closely related viruses, the Dengue viruses 1-4. There are no specific dengue
therapeutics and prevention is currently limited to vector control measures. A dengue vaccine would therefore
represent a major advance in the control of the disease.
Status of vaccine development
 The first dengue vaccine, Dengvaxia (CYD-TDV) by Sanofi Pasteur, was first registered in Mexico in
December, 2015. CYD-TDV is a live recombinant tetravalent dengue vaccine that has been evaluated as a 3-
dose series on a 0/6/12 month schedule in Phase III clinical studies. It has been registered for use in individuals
9-45 years of age living in endemic areas.
 Questions and answers on CYD dengue vaccine
WHO recommends that countries should consider introduction of the dengue vaccine CYD-TDV only in
geographic settings (national or subnational) where epidemiological data indicate a high burden of disease.
Complete recommendations may be found in the WHO position paper on dengue.
 WHO position paper on dengue
pdf, 437kb
 Tools to support decision-making for the addition of the licensed dengue vaccine into a public immunization
programme
There are approximately five additional vaccine candidates under evaluation in clinical trials, including other
live-attenuated vaccines, as well as subunit, DNA and purified inactivated vaccine candidates. Additional
technological approaches, such as virus-vectored and VLP-based vaccines, are under evaluation in preclinical
studies.
The growing global epidemic of dengue is of mounting concern, and a safe and effective vaccine is urgently
needed. WHO expects vaccines to be an integrated part of the Global dengue prevention and control strategy
(2012-2020).
 WHO report: global strategy for dengue prevention and control, 2012–2020
Advisory groups
 SAGE Working Group on Dengue Vaccines and Vaccination
Challenges to vaccine development
Infection by one of the four dengue virus serotypes has been shown to confer lasting protection against
homotypic re-infection, but only transient protection against a secondary heterotypic infection. Moreover,
secondary heterotypic infection is associated with an increased risk of severe disease. This and other
observations suggest an immunopathological component in dengue pathogenesis, which is referred to as immune
enhancement of disease. Due to these dengue-specific complexities, vaccine development focuses on the
generation of a tetravalent vaccine aimed at providing long-term protection against all virus serotypes.
Additional challenges are posed by the lack of an adequate animal disease model and the resulting uncertainty
around correlates of protection. In spite of these challenges, vaccine development has made remarkable progress
in recent years, and the current dengue vaccine pipeline is advanced, diverse and overall promising.

Questions and Answers on Dengue Vaccines

What is the current status of dengue vaccine development?
There is a growing public health need for effective preventive interventions against dengue, a disease caused by
four viruses, termed serotypes 1-4. A safe, effective and affordable dengue vaccine against the four strains would
represent a major advance for the control of the disease and could be an important tool for reaching the WHO
goal of reducing dengue morbidity by at least 25% and mortality by at least 50% by 2020. One dengue vaccine
has been licensed, Dengvaxia® (CYD-TDV), developed by Sanofi Pasteur. Approximately five additional
dengue vaccine candidates are in clinical development, with two candidates (developed by Butantan and Takeda)
expected to begin Phase III trials in early 2016.
What is Dengvaxia® (CYD-TDV)?
 CYD-TDV is the first dengue vaccine to be licensed. It was first licensed in Mexico in December 2015 for use in
individuals 9-45 years of age living in endemic areas. CYD-TDV is a live recombinant tetravalent dengue
vaccine developed by Sanofi Pasteur (CYD-TDV), given as a 3-dose series on a 0/6/12 month schedule.
What are the results from the Phase 3 trials?
CYD-TDV has been evaluated in two Phase 3 clinical trials (CYD14 in five countries in Asia and CYD15 in five
countries in Latin America). Together, these trials included over 35,000 participants aged 2 to 16 years: ages at
first vaccination were 2 to 14 years in CYD14, 9 to 16 years in CYD15. In each of these trials, participants were
randomized to vaccine and placebo in a 2:1 ratio. The study protocols included an active phase of follow-up for
one year after the last dose of vaccine in the series (25 months from dose 1) and include a hospital-based follow-
up period of four additional years, which is ongoing.
Results have been published for each trial separately, as well as pooled. Trial results include children aged <9
years old, which is an age group that is not included in the current indication. This is due to results that were
observed during the Phase 3 trials in the youngest age group in the CYD14 Phase 3 trial.
Vaccine efficacy against confirmed dengue pooled across both trials was 59.2% in the year following the
primary series (per protocol analysis). During this initial time period, pooled vaccine efficacy against severe
dengue was 79.1%. Efficacy varied by serotype: vaccine efficacy was higher against serotypes 3 and 4 (71.6%
and 76.9%, respectively) than for serotypes 1 and 2 (54.7% and 43.0%). Vaccine efficacy also varied by age at
vaccination and serostatus at baseline (i.e., previous exposure to dengue prior to vaccination).
When limited to older age groups (ages included in the current licensure), pooled vaccine efficacy amongst all
participants aged 9 years or over was 65.6%, and in participants aged <9 years it was 44%.
Within the randomized subset of participants for whom pre-vaccination blood samples were collected, pooled
vaccine efficacy against VCD in those seropositive for a prior exposure to dengue virus was 78.2%, while in
those seronegative at baseline it was 38.1% (not statistically significant). In a post-hoc analysis in those ≥9 years
of age, vaccine efficacy in those seronegative at baseline was 52.5% (95% CI 5.9%, 76.1%).
While efficacy was reported against hospitalized and severe dengue in Years 1 and 2 post-dose 1, an excess of
cases of hospitalized and severe dengue cases in those receiving CYD-TDV was seen in Year 3 in some
subgroups, although it is based on relatively small numbers of cases. The excess was mostly observed in those
vaccinated aged 2-5 years in CYD14 in Asia, for which the relative risk of hospitalized dengue in vaccinees was
7.45 (95% CI 1.15, 313.80) in Year 3, based on 15 cases in the CYD-TDV group and 1 case in the control group.
This younger age group has not been included in the age indication of the vaccine. No safety signals were
reported in the older age groups.
What are WHO’s recommendations related to CYD-TDV?
WHO recommends that countries should consider introduction of the dengue vaccine CYD-TDV only in
geographic settings (national or subnational) where epidemiological data indicate a high burden of disease.
Complete recommendations may be found in the WHO position paper on dengue vaccines.
 WHO position paper on dengue vaccines
pdf, 437kb
Has the vaccine been prequalified by WHO?
CYD-TDV is currently not prequalified. Prequalification requires an NRA of record, which is typically the NRA
in the manufacturing country (in this case, EMA). WHO is awaiting a submission of an application from the
manufacturer for prequalification of this vaccine.
What other interventions exist for dengue control?
Vector control has been the key strategy to control or prevent the transmission of dengue virus. Strategies
include:
 preventing mosquitoes from accessing egg-laying habitats by environmental management and modification;
 disposing of solid waste properly and removing artificial man-made habitats;
 covering, emptying and cleaning of domestic water storage containers on a weekly basis;
 applying appropriate insecticides to water storage outdoor containers;
 using of personal household protection such as window screens, long-sleeved clothes, insecticide treated
materials, coils and vaporizers;
 improving community participation and mobilization for sustained vector control;
 applying insecticides as space spraying during outbreaks as one of the emergency vector-control measures
 active monitoring and surveillance of vectors should be carried out to determine effectiveness of control
interventions.

 FIRST DENGUE VACCINE

APPROVED IN MORE THAN 10
COUNTRIES
 - Recent approvals for Dengvaxia® granted by
health authorities in Indonesia, Thailand and
Singapore -
 - First dengue vaccine continues to get growing
support from regional and national medical
societies -

Lyon, October 4, 2016 - Sanofi Pasteur, the vaccines global
business unit of Sanofi, announced today that Dengvaxia dengue ®

vaccine has now received its 11 marketing approval, four of

th

which granted from Regulatory Authorities recognized by the

World Health Organization (WHO). To date the vaccine is
approved in Mexico, The Philippines, Brazil, El Salvador, Costa
Rica, Paraguay, Guatemala, Peru, Indonesia, Thailand and
Singapore.

The vaccine is also receiving endorsements from key medical
societies at national and regional level. Notably, the Latin
American Society for Pediatric Infectious Diseases (SLIPE for
Sociedad Latino Americana de Infectología Pediátrica)
just published its support for dengue vaccination. National
medical societies in Indonesia, Brazil and Mexico have recently
also recommended vaccination with Dengvaxia . These ®

recommendations are consistent with the World Health

 Organization position paper issued on July 29th recommending
that countries with high burden of disease should consider
introduction of Dengvaxia as part of an integrated dengue
®

management program. 1


“We’re pleased to see the growing medical and public health
recognition for the vaccine,” notes Su Peing Ng, MD, Head of
Global Medical Affairs for Sanofi Pasteur. “With this new tool in
hand, public health communities in dengue-endemic countries
now have additional means to achieve the WHO objectives for
50% reduction in mortality and 25% reduction in morbidity due
to dengue by 2020.”

Parana State in Brazil has administered first doses in its public
vaccination campaign and the Philippines have just initiated 2nd
dose administration to students in public schools in three highly
endemic areas of the country. The vaccine is also being launched
through private clinics.

In the clinical study population 9 years old and older, the dengue
vaccine has been documented to prevent two-thirds of dengue
cases due to all four serotypes of dengue. The dengue vaccine
also prevented 8 of 10 hospitalizations due to dengue and 93%
of serious dengue cases like the deadly hemorrhagic form of the
disease, over the 25-month study follow-up period of the large-
scale efficacy studies conducted in 10 endemic countries in Latin
America and Asia. 2


An integrated safety analysis was recently published
documenting Dengvaxia ’s satisfactory safety profile comparable
®

to placebo during the late stage clinical study program involving

around 30,000 participants from 15 countries. In addition, the
results of this analysis documented that the vaccine provided
beneficial protection against hospitalization due to dengue and
severe dengue for up to 4 years post dose 1 of vaccination
compared to placebo in the study population 9 years and older. 3


About Sanofi Pasteur Dengue Vaccine
 Sanofi Pasteur’s vaccine is the culmination of over two decades
of scientific innovation and collaboration, as well as 25 clinical
studies in 15 countries around the world. Over 40,000 volunteers
participated in the Sanofi Pasteur dengue vaccine clinical study
program (phase I, II and III), of whom, 29,000 volunteers
received the vaccine.

A summary of the efficacy documentation on Dengvaxia for the
®

study population 9 years and older was published in The New

England Journal of Medicine on July 27th 2015. These findings
affirm the vaccine’s consistent efficacy in reducing dengue due to
all four serotypes in twothirds of the study participants 9 years
and older and also documents the ability of the vaccine to
prevent 8 out of 10 hospitalizations and up to 93% of severe
dengue cases in this age group during the 25 month follow-up
phase of the studies.4


An integrated safety analysis was recently published
documenting Dengvaxia ’s satisfactory safety profile comparable
®

to placebo during the late stage clinical study program involving

around 30,000 participants from 15 countries. In addition, the
results of this analysis documented that the vaccine provided
beneficial protection against hospitalization due to dengue and
severe dengue for up to 4 years post dose 1 of vaccination
compared to placebo in the study population 9 years and older. 5


Sanofi Pasteur’s Dengue Vaccine is the first vaccine licensed for
the prevention of dengue in the world. The vaccine is supplied
from a dedicated production site in France.

Additional information about Sanofi Pasteur’s dengue vaccine is
available on the web at www.dengue.info.

 About Sanofi
 Sanofi, a global healthcare leader, discovers, develops and
distributes therapeutic solutions focused on patients' needs.
Sanofi is organized into five global business units: Diabetes and
 Cardiovascular, General Medicines and Emerging Markets, Sanofi
Genzyme, Sanofi Pasteur and Merial. Sanofi is listed in Paris
(EURONEXT: SAN) and in New York (NYSE: SNY).

Sanofi Pasteur, the vaccines division of Sanofi, provides more
than 1 billion doses of vaccines each year, making it possible to
immunize more than 500 million people across the globe. A world
leader in the vaccine industry, Sanofi Pasteur produces a
portfolio of high quality vaccines that matches its areas of
expertise and meets public-health demand. The company's
heritage, to create vaccines that protect life, dates back more
than a century. Sanofi Pasteur is the largest company entirely
dedicated to vaccines. Every day, the company invests more than
EUR 1 million in research and development. For more
information, please
visit: www.sanofipasteur.com or www.sanofipasteur.us
JUNE IS DENGUE AWARENESS MONTH
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dengue_fp.jpg

The Department of Health (DOH) today reported a total of 22,903 dengue cases nationwide from
January to May 7 this year as it prepares to observe June as “Dengue Awareness Month”. The total number
of dengue cases is 8% higher compared to the same period last year. There were 141 deaths recorded
(Case FatalityRate-0.62%).

This year’s theme, “Eskwelahan, Simbahan, Barangay, Palengke at Buong Komunidad, Sama-Sama
Nating Sugpuin ang Dengue”, aims to heighten awareness of the strategy to fight dengue by adopting the
4S Kontra Dengue. The Centers for Health Development (CHDs) are directed to coordinate with their LGU
counterparts to encourage them to conduct a simultaneous activity with the CHDs.

The DOH 4S Kontra Dengue strategy is composed of Search and Destroy, Seek early consultation,
Self-protective measures and Say no to indiscriminate fogging.
 Most of the cases came from the National Capital Region (6,732), Central Luzon (4,181),
andCALABARZON (3,555).

At the National Capital Region, Quezon City had the most (1,694) number of cases followed
by Manila(824), Kalookan City (775), Pasig (592), Valenzuela (466), and Paranaque City (407).
“Dengue cases surge during the months of June until August,” Health Assistant Secretary Enrique
Tayag said, adding that Aedes Aegypti mosquitoes can breed even in very small receptacles like coconut
husks or empty bottles.

Ages of cases ranged from less than a month to 89 years old. Majority (53%) of the cases were males.
Most (39.9%) affected cases belonged to the 1-10 years age group.

Clustering of cases was observed in some parts of La Union, Pangasinan, Bataan, Nueva Ecija,
Pampanga, Tarlac, Batangas, Laguna, Rizal, Cebu, Negros Oriental, Zamboanga del Sur,
Misamis Oriental, Davao City, General Santos City, South Cotabato, Kalinga, and Metro Manila.
In Metro Manila, there were clustering of cases in Kalookan, Makati, Muntinlupa, Navotas, Paranaque,
Pasig, Quezon City and Valenzuela.

Meanwhile, Tayag disclosed that June 15 and every year thereafter will be observed as ASEAN Dengue
Day to foster more awareness about the disease. This pronouncement was made during the 10th ASEAN
Health Ministers Meeting held in Singapore last 22 July 2010.The theme for
the coming ASEAN Dengue Day is “Dengue is Everybody’s Concern, Causing Socio-economic Burden,
but it’s Preventable.

Tayag reminded the public that dengue, already an all-year round disease, is more common during
rainy days when there are more mosquito breeding sites. To prevent dengue, he advised the public to
destroy all possible mosquito breeding sites like old tires and tin cans, clean roof gutters, replace water in
flower vases regularly, and to use mosquito nets or protective clothing. He also stressed that fogging may
be done only in outbreak areas.

“The people, especially schoolchildren, can protect themselves from day bites by using topical insect
repellents or by wearing long-sleeved shirts. Suspected cases are urged to seek treatment if there are
persistently high fever, appearance of skin rashes or any signs of bleeding,” Tayag concluded.
 1624 reads