Dengue virus is a mosquito-borne virus that causes dengue fever and its more severe forms, dengue hemorrhagic fever and dengue shock syndrome. It is transmitted by Aedes aegypti and Aedes albopictus mosquitoes. There are four distinct serotypes of the virus. Infection with one serotype provides lifelong immunity to that serotype but only short-term immunity to the others. Dengue is widespread in tropical and subtropical parts of the world, with severe dengue being a leading cause of hospitalization and death among children in some Asian and Latin American countries. There is no vaccine available for dengue prevention, so control of the mosquito vector through environmental management and insect

1. DENGUE VIRUS
Speakers:
“End Dengue: Starts With Me”
@Zahirul Islam
@Mujahed Islam
Organized By:Pharma Club,University of Rajshahi
Department of Pharmacy,RU
@Masud Rana

2. Objectives
What is Dengue fever?
Sign and Symptoms
History of Dengue
Dengue on the globe
Epidemiology and Overview of Dengue in Bangladesh
 Dengue Transmission
Pathophysiology and Pathogenesis
Treatment and Preventative approaches

3. What is Dengue Fever?
Dengue is a mosquito borne tropical disease caused by the virus.
• It occurs in 3 forms: Dengue fever(DF) ,Dengue Haemorrhagic
fever(DHF) and Dengue Shock Syndrome (DSS).
•Dengue Fever is an illness caused by infection with a virus
transmitted by the Aedes mosquito.
The word dengue is derived from African word denga: meaning fever
with hemorrhage .
Alternative Names
Onyong- Nyang Fever,West Nile Fever,Break Bone Fever,Dengue like
Disease,Asian Tigher

6. …and become a MAJOR pandemic in
the last 50 years
Endemic in more than 1oo countries
2.5 billion people at risk

7. History-Dengue
This disease was first described 1780, and the
virus was isolated by Sabin 1944. Dengue virus
infection disease worldwide with an increasing
incidence in the tropical regions of Asia, Africa,
and Central and South America. There are four
serotypes of the virus.

8. DENGUE REGIONS OF THE WORLD
2018

9. Dengue on the Globe
Recently acquiredHighly endemic

10. Dengue on the Globe

11. Epidemiology and Overview of
Dengue in Bangladesh

12. Dengue Facts-1
 Arbo-viral disease
 Virus-Genus: Flavivirus
 Four serotypes: Den 1, Den 2, Den 3, Den 4. Infection with one
serotype confers life long immunity to that serotype and cross
immunity to other serotypes for 2-3 months only.
 All four serotypes are associated with epidemic and DHF.

13. Dengue Facts-2
 Aedes mosquitoes transmit dengue from person to person
 25 species of Aedes are recorded globally
 Incriminated vectors are Ae. aegypti, Ae. Albopictus , Ae.
polynesiensis and Ae.niveus (In Bangladesh only Ae. aegypti)
 Ae. aegypti – most important epidemic (primary) vector.

14. The most common epidemic vector of dengue in the world is the Aedes aegypti mosquito. It can be identified by
the white bands or scale patterns on its legs and thorax.

15. Dengue Transmission
 Female Aedes aegypti is the
principal vector (Aedes
albopictus is suspected vector)
 Extrinsic incubation period 8-
10 days
 Infective mosquito transmit
dengue through salivary fluid
to a susceptible person
 Intrinsic incubation period 3-
14 days (4-6 days average)

16. Habits of Aedes aegypti
Breeding habit:
 It breeds almost entire in domestic man made water receptacles or
artificial breeding sources
 The common breeding sources: Plastic pots, water storage jars,
Food containers, flower vases, cement baths, unused tyres, bottles,
tin cans, over head tanks(open), discarded wet cell batteries, ant
traps, freeze, A/C etc.

17. Habits of Aedes aegypti
Feeding habit:
 Two periods of biting, in the morning and in the afternoon
 May feed on more than 1 person in interrupted feeding- can infect
several members of a family if the mosquito is infective
 Generally does not feed at night but may feed in well lighted rooms at
night.

18. Habits of Aedes aegypti
Resting habit:
 Prefer to rest in dark, humid, secluded places inside houses
 Preferred indoor resting places are the underside of
furniture, hanging cloths, curtains and other articles.

19. Breeding Sources

20. Breeding Sources

21. Breeding Sources

22. TRANSMISSION CYCLE OF DENGUE

23. Virology
Flavivirus family
 Small enveloped viruses
containing single stranded
positive RNA
 Four distinct viral serotypes
(Den-1, Den-2,Den-3, Den-4)

25. Virology
Dengue virion are spherical
particles approximately 50 nm
in diameter contains a single
plus strand of RNA.
Surrounded by a lipid bilayer.
Because of the lipid envelope,
flavviviruses are readily
inactivated by organic solvents
and detergents

26. Dengue Outbreak in Bangladesh
 First outbreak of dengue fever (Dhaka fever) was documented in 1964 in Dhaka
followedby few
 Scattered cases of DF during 1977-78
 In 1996-97 dengue infections were confirmed in 13.7% of 255 fever patients
screened at Chittagong Medical College
• The reemergence started in 2000 with 5551 cases and 93 death
 The worst outbreak was in 2002 with 6,104 cases and 58 deaths. This year, a
total of 9,657 dengue patients were reported to have been hospitalized until Friday
since January 1, according to the Directorate General of Health Services (DGHS)

29. Dengue Cases and Deaths in Bangladesh (2000-2019,July)
Year Cases Death
2000 5551 93
2001 2430 44
2002 6132 58
2003 486 10
2004 3934 13
2005 1048 04
2006 2200 11
2007 466 0
2008 1153 0
2009 474 0
2010 409 0
2011 1362 06
2012 671 01
2013 1749 02
2014 168 0
2018 10000 26
2019 7766 20

30. Pathophysiology
After an infective mosquito bite in subcutaneous or intradermal
space, the virus replicates locally at the site of inoculation, in
cells of reticuloedothelial system or fibroblast or both.
Then it is detected in local lymph nodes and within 2 to 3 days,
disseminates via blood to various tissues.
The virus circulates in the blood typically for 4 to 5 days during
the febrile phase and is cleared within a day of defervescence.
Dengue virus can be detected in monocytes, hepatocytes but
not in T cells or endothelial cells.

31. Pathophysiology
Primary dengue infection develops serum antibodies that can
neutralize the homologous serotype.
In a secondary infection, the pre-existing heterologous antibodies
form complexes with the new infecting virus serotype, but do not
neutralize the new virus.
Secondary infections have been shown to lead to higher viral loads
and the manifestations of severe dengue are believed to be due to
virus replication which induces infected monocytes to release
vasoactive mediators.
Excessive release of vasoactive mediators results in increased
vascular permeability and hemorrhagic manifestations that
characterizes DHF and DSS.

32. Pathophysiology and cytokine
The pathogenesis of severe disease is not well understood. Various mechanisms
of severe disease have been suggested, including:
(a) Antibody-dependent enhancement or ADE,
(b) Complement activation by virus-antibody complexes and
(c) T-cell mediated immunopathology
(d) Cytokine abundance.
Dengue infected monocytes act as antigen presenting cells (APCs) to induce
release of lymphokines and other factors from activated T cells.Tumour Necrosis
Factor- a,Interleukin(IL) IL-1b, IL-2, IL-6, IL-8,Interferon (IFN)-g, RANTES etc. are
the cytokines that are released from these cells.
These cytokines along with complement breakdown products (C3a,C5a)
activated in DHF/DSS, increases vascular permeability of vascular endothelial cells
leading to DSS.

34. Pathophysiology of DF/DHF

35. Causes of bleeding in DF/DHF

36. Management:
1.Dengue Fever
2.Dengue Haemorrhagic Fever
3.Dengue Shock Syndrome
4.Expanded dengue syndrome

37. Revised case classification by severity
1.Dengue without warning signs (May be send home):GroupA
2.Dengue with warning signs( Referred for in hospital
care):GroupB
3.Severe dengue( Require emergency treatment):GroupC

39. New clinical case classification

40. Laboratory Diagnosis
• Complete Blood Counts
• Hematocrit
• Platelet Count
• Serum GOT, GPT
• Blood urea, serum creatinine, serum electrolyte
• Serum Albumin
• Immunological Tests : Dengue serology, dengue virus isolation or
antigen detection test.
• Chest X-Ray
• USG of Abdomen

41. Treatment of Dengue Fever
• Antipyretics (Acetaminophen) preparations to manage the pain
and fever.
• Avoid Aspirin and non-steroidal anti-inflammatory.
• Rest and drink plenty of fluids
• Monitor blood pressure, hematocrit, platelet count,...
• Keep patient in screened sickroom or under a mosquito net
• Mosquito barriers are only needed until fever subsides,to
prevent Aedes aegypti mosquitoes from biting patients and
acquiring virus.

42. Prevention
• Primary prevention of dengue is currently possible only with vector
control and personal protection from the bites of infected mosquitoes.
However, the development of vaccines and drugs has the potential to
change this

43. Vaccine
The development of vaccine for dengue fever began as early as 1929,
But has been hindered
first, by incomplete knowledge of the disease pathogenesis,
later, by the need to simultaneously create a stable immunity against all
four dengue serotypes.
Several vaccine candidates are in development including live attenuated,
inactivated, DNA and subunit vaccines. Live attenuated vaccine candidates are
the furthest along in development.

44. CYD-TDV
• CYD-TDV, sold under the brand name Dengvaxia and made by Sanofi Pasteur, is a live
attenuated tetravalent chimeric vaccine made using recombinant DNA technology by
replacing the PrM (preCYD-TDV membrane) and E (envelope) structural genes of the yellow
fever attenuated 17D strain vaccine with those from the four dengue serotypes.
• The vaccination series consists of three injections at 0, 6 and 12 months. The vaccine was
approved in Mexico, Philippines, and Brazil in December 2015, El Salvador, Costa Rica,
Paraguay, Guatemala, Peru, Indonesia, Thailand and Singapore in 2016. Tradenamed
Dengvaxia, it is approved for use for those aged nine and older and can prevent all four
serotypes.
In November 2017 Sanofi acknowledged that some participants were put at risk of severe
dengue if they had no prior exposure to the infection and recommended that the vaccine only
be used in people who have previously had a dengue infection

45. Upcoming Vaccine : DENVax or TAK-003
• DENVax or TAK-003 is a recombinant chimeric vaccine with
DENV1, DENV3, and DENV4 components on a dengue virus type 2
(DENV2) backbone originally developed at Mahidol University in
Bangkok and now funded by Inviragen (DENVax) and Takeda (TAK-
003).
• Phase I and II trials are ongoing in the United States, Colombia,
Puerto Rico, Singapore and Thailand. Based on the latest 18-month
data published in the journal Lancet Infectious Diseases, indicated that
TAK-003 produced sustained antibody responses against all four virus
strains, regardless of previous dengue exposure and dosing schedule.

46. Upcoming vaccine : TetraVax-DV
• TetraVax-DV is a tetravalent admixture of monovalent vaccines that
were tested separately for safety and immunogenicity. The vaccine
passed phase I trials and is being tested in phase II studies in Thailand
and Brazil. In Brazil, the studies are being done in collaboration with
the Instituto Butantan.

47. Upcoming vaccine : TDEND PIV
• TDEN PIV is inactivated tetravalent vaccine undergoing phase I trials
as part of a collaboration between GSK and the Walter Reed Army
Institute of Research. A synergistic formulation with another live
attenuated candidate vaccine (prime-boost strategy) is also being
evaluated in a phase II study. In prime-boosting, one type of vaccine is
followed by a boost with another type in an attempt to improve
immunogenicity.[

48. DNA Vaccine
• The Naval Medical Research Center attempted to develop a
monovalent DNA plasmid vaccine, but early results showed it to be
only moderately immunogenic

49. Complexity Of Developing A Dengue Vaccine
• Need for a tetravalent vaccine with not just one but four immunogens that
will give a balanced immune response whereby a protective long-lasting
immunity is induced against all four viruses simultaneously (balancing viral
interference, immunogenicity, and reactogenicity).
• Lack of immune correlate of protection since the mechanism of protective
immunity against DEN infection is only partially understood. It is assumed
that neutralizing antibodies are the main effector of protection against DEN
infection.
• Lack of a suitable animal model that recapitulates human disease and can be
used to evaluate candidate vaccines.
• Potentia immunopathogenesis, including antibody-dependent
enhancement…….

50. Implementation
•Needfor long-term follow-up.
•Needfor testing in both Asia and the Americas.
•Ideally, can be tested against all four DEN serotypes.
•The exact location, timing and serotype/genotype composition of
dengue epidemics varies from year to year and is somewhat
unpredictable.

51. Dengue Antiviral drugs
• No antiviral drugs for Dengue has been yet developed commercially.
• Lots of researches are performing by thousands of genius scientists
around the globe.
• According to their recent researches, they are targeting the RNA of the
virus.

52. Prevention and control of Dengue Transmission
 No vaccine against virus is available
 No specific drug against dengue virus
 No way to differentiate infective and un-infective vector
bite.
 No way to differentiate vector and non-vector bite.
 Viraemia starts one or two days before on set of clinical
symptoms an transovarian transmission are there.

53. What to do ????????
• The only way to prevent and control and control Dengue
transmission is the prevention and control of
infective/infectious vector bite.How to prevent infective bite
• May be by keeping dengue viraemic patient under
mosquito net specially during day or in mosquito free
house/word to avoid vector contact

54. Prevention & control of Dengue
Transmission by vector control
 By Chemical method:
 By application of insecticides in the form
of residual spray, aerosol spray, fog
spray ( Thermal or cold) and ULV spray
(Aerial/vehicle mounted)
 By application of insecticides in the form
of larvicides–1% temephos (Abate)
granules
 Scope is very limited and not judicious in
all situation because of adult resting
behaviour and breeding habits.

55. Some Remedial Agents
• Natural home remedies such as
papaya leaves, kiwi and other
• food items also helps in increasing
the platelet count which gets
affected during dengue.
• Acetogenin
• Vit k & C
• Minerals
• Flavonoids

56. Preparation of Papaya Juice
• Raw papaya leaves, 2 pcs just cleaned and pound and squeeze with
filter cloth.
• You will only get one tablespoon per leaf.
• So two tablespoon per serving once a day.
• Do not boil or cook or rinse with hot water, it will loose its strength.
• Only the leafy part and no stem or sap.
• It is very bitter and you have to swallow it like Won Low Kat. But it
works.

57. Prevention & control of Dengue
Transmission by vector control
 By biological methods:
 By predators( Adult and Larvae)
 By larvivorus fish (larva)
 By bacteria (larva)
 By insect growth regulator (IGR)
 The scope is also very limited and not judicious because of
adult resting behaviour and breeding habit.

58. Prevention & control of Dengue
Transmission by vector control
By physical / Environmental Method:
 By modification of environment – permanent in nature but need
carrying maintenance (house with mosquito netting,Insecticide
treated sheet and covering of breeding sources.)
 By environmental manipulation – temporary in nature but needs
periodic replenishment (detection and destruction,cleaning and
draining, Personal protection, use of repellants, use of
protective clothes, treating doors and window’s curtains with
insecticides, use of mosquito net at day time sleeping etc.

60. Integrated Vector Management
Integrated Vector Management (IVM) is a decision making
process that anticipates and prevents vector activity and
infestation by several strategies to achieve long term solutions.
Components of IVM may include education, proper waste
management, structural repair, biological and mechanical
control techniques, and pesticide application.

61. Integrated Vector Management
 Larval source reduction is the main tool for vector
control. Effective control requires a concerted
effort among the government agencies, NGOs and
communities.
 Community understanding and involvement
remains the key for implementation of preventive
and control activities. The control measures should
be implemented at personal, community and
institutional levels.

62. Household Level Action
 Wearing protective clothing such as full sleeved shirts and full
pants during day time
 Use of mosquito coils, aerosols, mats etc
 Use of mosquito net (preferably insecticidetreated) even during
day time
 Use of repellents and creams during the day
 Placing tight-fitting screens/wire mesh on doors and windows
 Water in containers (earthen jars, cement tanks, jerry can, tyre
etc.) should not be allowed to bestored for more than five days

63. Community Level Action
 Raising awareness regarding community involvement and
participation about prevention and control of dengue.
 Cleaning and covering water storage, keeping surroundings
clean, improving basic sanitation measures
 Promoting use of insecticide treated nets andcurtains
 Mobilizing households to cooperate during spraying / fogging

64. Institutional Level Action
 Hospitalized patients should be kept under mosquito net during
febrile phase even during day time
 Cleaning of larval habitats like overhead tanks, ground water
storage tanks, air coolers, planters,flower pots etc every five
days
 Carrying out indoor and outdoor space spraying (fogging, ULV
etc.)
 Promoting personal protection measures
 Notification of fever cases to health authorities

69. Questions
If you ask a question,
you are a fool for a minute.
but if you don’t,
are a fool for life.