this presentation deals mainly with dengue as there has been multiple outbreaks in 2015 and etiological factors involved, current scenario in India, preventive and control measures for dengue, recent strains of dengue and recent vaccine trials of dengue vaccine.

1. Dengue – a rising public
health problem
Dr. Vikas Gupta
Postgraduate
Dept. of Community Medicine

2. History

3. Introduction
• Basically the word Dengue is spanish.
• But its origin is from Swahili phrase Ka-
denga-pepo which means disease caused by
an evil spirit.
• Other names: Dandy fever, Break-bone
fever.

4. Introduction
• Dengue fever virus (DENV) is an RNA
virus(ss) of the family Flaviviridae.
• There are five strains of the virus, called
serotypes, of which the first four are referred
to as DENV-1, DENV-2, DENV-3 and DENV-
4. The fifth type was announced in 20131.

5. Burden of dengue
• Global: It infects 50 to 500 million people
worldwide a year, leading to half a million
hospitalizations and approximately 25,000
deaths.
• 75% of the global population exposed to
dengue are in the Asia-Pacific region.

7. Burden of dengue
• The fatality rate is 1–5% and less than 1% with
adequate treatment, however those who
develop significantly low blood pressure may
have a fatality rate of up to 26%.

8. Burden of dengue
• India: In Year 2013- highest number of cases
from Kerala state (7911) and lowest from
state of Maharashtra (48).

9. 12561
15535
28292
18860
50222
75454
0
20000
40000
60000
80000
2008 2009 2010 2011 2012 2013
Cases(India)
Cases
1137
125
866
267
768
1784
0
500
1000
1500
2000
2008 2009 2010 2011 2012 2013
Cases (Haryana)
Cases

10. 80 96 110
169
242
167
0
100
200
300
2008 2009 2010 2011 2012 2013
Mortality (India)
Mortality
9
1
20
3 2
5
0
5
10
15
20
25
2008 2009 2010 2011 2012 2013
Mortality (Haryana)
Mortality

11. 0.63
0.61
0.38
0.89
0.48
0.22
0
0.2
0.4
0.6
0.8
1
2008 2009 2010 2011 2012 2013
case fatality ratio
case fatality ratio
0.79
0.80
2.31
1.12
0.26
0.28
0.00
0.50
1.00
1.50
2.00
2.50
2008 2009 2010 2011 2012 2013
CFR
CFR

12. Dengue- Rohtak
75
6
20
11
15
2 0 2 0 10
10
20
30
40
50
60
70
80
2008 2009 2010 2011 2012
Sum of cases
Sum of mortality

13. Modes of transmission
1. Aedes aegypti (m/c)
2. Infected blood products and through organ
donation. In countries such as Singapore,
where dengue is endemic, the risk is
estimated to be between 1.6 to 6 per 1,000
transfusions.
3. Vertical transmission (from mother to child)
during pregnancy or at birth has been
reported.

14. Associated risk factors
• Generally dengue affect both age groups and
sex equally.
• Severe disease is more common in babies
and young children, and in contrast to many
other infections it is more common in children
that are relatively well nourished.
• Other risk factors for severe disease include
female sex, high body mass index, and viral
load.

15. Case definitions (WHO 2009)
• Uncomplicated dengue (Dengue without and
with warning sign) and severe dengue
• Dengue without Warning Signs
Fever and two of the following:
1. Nausea, vomiting
2. Rash
3. Aches and pains
4. Leukopenia
5. Positive tourniquet test

16. Tourniquet test
• Tourniquet test involves the application of a
blood pressure cuff at between the diastolic
and systolic pressure for five minutes,
followed by the counting of any petechial
hemorrhages;
• A higher number makes a diagnosis of dengue
more likely with the cut off being between 10
to 20 per 1 inch2(6.25 cm2).

17. Case definitions (WHO 2009)
• Dengue with Warning Signs
Dengue as defined above with any of the following:
1. Abdominal pain or tenderness
2. Persistent vomiting
3. Clinical fluid accumulation (ascites, pleural effusion)
4. Mucosal bleeding
5. Lethargy, restlessness
6. Liver enlargement >2 cm
7. Laboratory: increase in HCT (hematocrit) concurrent
with rapid decrease in platelet count

18. Case definitions (WHO 2009)
• Severe dengue is defined as that associated
with severe bleeding, severe organ
dysfunction, or severe plasma leakage while
all other cases are uncomplicated.

19. Case definitions (WHO 2009)
• Severe Dengue
Dengue with at least one of the following
criteria:
1. Severe Plasma Leakage leading to:
–Shock(DSS)
– Fluid accumulation with respiratory distress
2. Severe Bleeding as evaluated by clinician
3. Severe organ involvement
– Liver: AST or ALT ≥ 1000
– CNS: impaired consciousness
– Failure of heart and other organs

20. Case definitions (WHO 1997)
Dengue fever: An acute febrile illness of 2-7
days duration with two or more of the
following manifestations:
• Headache, retro-orbital pain, myalgia,
arthralgia, rash, hemorrhagic manifestations.

21. Case definitions

22. Case definitions (WHO 1997)
Dengue Shock Syndrome :
• All the above criteria for DHF plus evidence of
circulatory failure manifested by rapid and
weak pulse or hypotension for age, cold and
clammy skin and restlessness.

23. Case classification
• Suspected : A case compatible with the clinical description
• Probable : A case compatible with the clinical description
with one or more of the following:
- Supportive serology (reciprocal haemagglutination)
- Occurrence at same location and time as other confirmed
cases of dengue fever
• Confirmed : A case compatible with the clinical description
that is laboratory confirmed

24. Laboratory criteria for diagnosis
One or more of the following:
1. Isolation of Dengue virus from serum, plasma,
leucocytes or autopsy samples.
2. Demonstration of a fourfold or greater rise in
IgM antibody titers to one or more dengue virus
antigen in paired sera samples.
3. Detection of dengue virus antigen in serum
samples by NS1 ELISA or in autopsy tissue by
immunohistochemistry or immunofluorescence.
4. Detection of viral genomic sequences in autopsy
tissue, serum or CSF sample by PCR (Polymerase
Chain Reaction)

25. Recommended tests
• GoI recommends use of ELISA based antigen
detection test (NS1) for diagnosing the cases from 1st
day onwards and
• Antibody detection test IgM Capture ELISA (MAC
ELISA) for diagnosing the cases after 5th day of onset
of disease for confirmation of Dengue infection.
• NVBDCP had been using MAC- ELISA for
diagnosis of dengue infection in the network of
Diagnostic Centers established/ identified in the
Sentinel Surveillance Hospitals (SSHs) and Apex
Referral Laboratories (ARLs) across the country.

27. Sentinel Surveillance Hospitals for
dengue in Haryana
Total 14 (2012):
• 1 B.K. Hospital, Faridabad.
• 2 General Hospital, Ambala
• 3 State Bacteriological Laboratory, Karnal,
• 4 General Hospital, Gurgaon
• 5 General Hospital, Panchkula
• 6 Medical College, Agroha
• 7 Civil Hospital, Hissar
• 8 PGIMS, Rohtak
• 9 District Hospital, Kaithal
• 10 District Hospital, Kurukshetra
• 11 Mukandi lal Hospital, Yamuna Nagar
• 12 Civil Hospital, Sonipat
• 13 New Hospital, Sector-10, Gurgaon
• 14 Civil Hospital, Bahadurgarh (Jhajjar)

28. APEX REFERRAL LABORATORIES
Total 14 (2012):
• 1. National Institute of Virology, Pune.
• 2. National Center for Disease Control (former NICD), Delhi.
• 3. National Institute of Mental Health & Neuro-Sciences, Bangalore.
• 4. Sanjay Gandhi Post-Graduate Institute of Medical Sciences, Lucknow.
• 5. Post- Graduate Institute of Medical Sciences, Chandigarh.
• 6. All India Institute of Medical Sciences, Delhi.
• 7. ICMR Virus Unit, National Institute of Cholera & Enteric Diseases, Kolkata.
• 8. Regional Medical Research Centre (ICMR), Dibrugarh, Assam.
• 9. King’s Institute of Preventive Medicine, Chennai.
• 10. Institute of Preventive Medicine, Hyderabad.
• 11. B J Medical College, Ahmedabad.
• 12. State Public Health Laboratory, Thiruvananthapuram, Kerala
• 13. Defence Research Development and Establishment, Gwalior
• 14. Regional Medical Research Centre for Tribals, (ICMR) Jabalpur, Madhya
Pradesh

29. Blood sample collection
• As soon as possible after the onset of illness, hospital
admission or attendance at a clinic (acute serum,
S1).
• Shortly before discharge from the hospital or, in
the event of a fatality, at the time of death
(convalescent serum, S2).
• In the event if hospital discharge occurs within 1-2
days of the subsidence of fever collect a third
sample 7-21 days after the acute serum(S1)was
drawn (late convalescent serum, S3)

30. Global strategy for dengue
prevention and control, 2012–2020
• GOAL: TO REDUCE THE BURDEN OF
DENGUE
• OBJECTIVES:
1. To reduce mortality from dengue by at least
50% by 2020.
2. To reduce morbidity from dengue by at least
25% by 2020 (using 2010 as the baseline).
3. To estimate the true burden of dengue till
2015.

31. Global strategy for dengue
prevention and control, 2012–2020
Five technical elements:
1. Diagnosis and case management
2. Integrated surveillance and outbreak
preparedness
3. Sustainable vector control
4. Future vaccine implementation
5. Basic, operational and implementation
research

32. Global strategy for dengue
prevention and control, 2012–2020
Enabling factors for effective implementation:
1. Advocacy and resource mobilization
2. Partnership, coordination and collaboration
3. Communication to achieve behavioural
impact(COMBI)
4. Capacity building
5. Monitoring and evaluation

33. Mid Term Plan 2011-2013
• Objectives:
1. To reduce the incidence of dengue
(to bring down the disease burden)
2. To reduce the case fatality rate due
to dengue

34. Mid Term Plan 2011-2013
Elements: (8)
1. Surveillance
– Disease/Epidemiological Surveillance
– Entomological Surveillance
2. Case management
– Laboratory diagnosis
– Clinical management
3. Vector management
– Environmental management for Source Reduction
– Chemical control
– Biological control
– Personal protection
– Legislation

35. Mid Term Plan 2011-2013
4. Outbreak response
– Epidemic preparedness
– Media management
5. Capacity building
– Training
– Infrastructure development
– Operational research
6. Behavior Change Communication
– Social mobilization,
– IEC

36. Mid Term Plan 2011-2013
7. Inter-sectoral coordination
– Health & non health sector
8. Monitoring & Supervision
– Review, field visit , feedback
– Analysis of reports

37. Epidemiological surveillance
1. Event-based surveillance: uses reports
generated by the media and other open
sources of information
2. Routine surveillance:
A. Passive ( It is only surveillance active in India)
B. Active
I. Sentinel surveillance
II. Enhanced surveillance – mainly during epidemic
response

38. Epidemiological surveillance
3. Proactive surveillance:
• serological surveillance designed to monitor
dengue virus transmission, especially during
inter-epidemic periods and provide
information on:
1. where transmission is occurring,
2. what virus serotype or serotypes are
involved and
3. what type of illness is associated with the
dengue

39. Epidemiological surveillance
• Reporting :
1. During transmission period (monsoon and post
Monsoon reporting will be on daily basis by
email or by fax.
2. In non or low transmission period reporting
will be on weekly basis. Report of the previous
week (Monday to Saturday) should be compiled
by the States and send to NVBDCP by every
Monday.

43. Entomological Surveillance
• PUPAL INDEX: intensity of
transmission
• For larvae:
1. House Index: extent of breeding
2. Container Index: intensity of
breeding
3. Breteau Index: yardstick for
evaluation of the control strategy

44. Entomological Surveillance
• ADULT BITING INDEX (ABI) or HUMAN
LANDING RATE (HBR)( not done in
endemic areas as adult may be
infected with virus)
• LARVITRAP INDEX
• OVITRAP DENSITY INDEX (ODI)
• Funnel traps in sites with poor access

46. COLOR CODES for Entomological
Surveillance
• CODE INTERPRETATION= WHITE
– HOUSE INDEX is<5% and/or
– BRETEAU INDEX is <20%
• What to do:
1. Continue IEC campaign on prevention & control
2. Continue clean-up activities
3. Continue monthly entomological survey by local
health authorities
4. Maintain the Code WHITE in the community

47. COLOR CODES for Entomological
Surveillance
• CODE INTERPRETATION – Red
– HOUSE INDEX is >5% and/or
– BRETEAU INDEX is >20%
• What to do
1. Intensify IEC campaign on prevention & control
2. Mobilize residents of affected area to start clean-up campaign
3. Continue monthly entomological survey by local health
authorities
4. Improve environmental sanitation
5. Start community vigilance; search for more areas with HI >5%
and/or BI >20%
6. Apply larvicide.

48. Priority area based on
epidemiological and entomological
surveys
• Priority 1 - localities where an outbreak of
DF/DHF had occurred
• Priority 2 - localities with high larval indices
HI >5% and/or BI >20%
• Priority 3 - localities with relatively low larval
indices HI <5% and/or BI <20%
• Priority 4 - localities where there are no
dengue cases and low Aedes densities.

49. When to Conduct Entomological
Surveys
Basically it should be throughout the year.
1. With in 24 hrs. of the 1st case from an
outbreak locality .Following an outbreak
based on priority classification of the locality
1. high risk areas (Priority 1 & 2) = monthly/
quarterly in 100% of houses
2. low risk areas (Priority 3 & 4) = monthly/ quarterly
in at least 20% of houses
2. Before and after interventions
3. When there is suspect of insecticide resistance

50. Entomological team
• District biologist
• Insect collector
• Health inspector regular post
• Health worker
• Breeding checkers – temporary post(4-5
months)

51. VECTOR MANAGEMENT
1. Environmental Management
2. Personal Protection
3. Biological Control
4. Chemical Control
5. Legislation

52. Environmental management for
source reduction
• Environmental modification: physical
transformation of land, water and vegetation to
reduce vector habitats without causing any adverse
effects on the environment.
• Environmental manipulation: activities aimed at
producing temporary changes in vector habitats that
involve the management of “essential” and “non-
essential” containers, and the management or removal
of natural” breeding sites.
• Changes in human habitations: Efforts are made to
reduce man-virus contact by mosquito proofing of
houses with screens on doors/windows.

56. VECTOR MANAGEMENT
Personal protection
1. Protective clothing
2. Mats, coils and aerosols
3. Repellents: DEET (N, N-Diethyl-m
Toluamide)
4. Insecticide-treated materials: Mosquito nets

57. Chemical control
Larvicides:
1. For non potable water containers (perifocal
treatment): temephos(1mg/L),
methoprene(1mg/L), priproxyfen(0.05mg/L)
2. For potable water containers: temephos,
Bacillus thuringiensis israelensis(1-5mg/L)
 Cycle : 2-3rounds /year
 Both internal and external walls of container should
be sprayed and up to 60cm of height in case of non
potable water containers.

58. Chemical control
• Adulticides
1. Residual treatment- perifocal treatment(for tyres)
2. Space spray- recommended for control only in emergency
situations with help of:
– vehicle-mounted equipment
– portable equipment
– low-flying aircraft types (60m above ground and 180m
swath)
Types
– Indoor : with pyrethrum(deltamethrin, cyfluthrin)
– Outdoor:
• cold aerosols (ULV spray)
• thermal fogs

59. Indoor space spraying
Commercial formulation of 2% pyrethrum
(deltamethrin) extract is diluted with kerosene in the
ratio one part of 2% pyrethrum extract with 19 parts of
kerosene (volume/volume).
Thus, one liter of 2% pyrethrum extract is diluted by
kerosene into 20 liters of 0.1% pyrethrum extract
ready-to-spray formulation’.(Baygon, hit)
One liter of ‘ready-to-spray formulation is sufficient to
cover 20 households, each household having 100 cubic
meters of indoor space.

61. Outdoor space spraying
• Usually carried out in early morning or late afternoon
• For narrow roads: the spray should be directed backwards
from the vehicle.
• For wide roads: the spray should be directed at a right angle
(downwind) to the road.
1. Ultra Low Volume (ULV) Spray(cold fog):
– Technical malathion is the insecticide used for this purpose.
– Remain suspended in air for an appreciable time and driven
under the influence of wind.
– Since no diluent is used, the technique is more cost-
effective than thermal fogging
– But it does not generate a visible fog

63. Outdoor space spraying
2. Thermal Fogging
– Water based
– Oil based(m/c used)
• Technique is based on the principle that insecticide is
vaporized, which condenses to form a fine cloud of
droplets on contact with cooler air when it comes out
of the machine.
• Insecticide of choice for fogging is
malathion/pyrethrum
• Easily visible fog resulting sense of satisfaction.
• Operator exposure to insecticide is less.

66. Outdoor space spraying
• Target area: where people congregate (e.g. high-
density housing, schools, hospitals) and where dengue
cases have been reported or vectors are abundant.
• Selective space treatment up to 400 meters ( 50 houses
surrounding, 1-1.5km circumferential area in
Rohtak) from houses in which dengue cases have been
reported is commonly practiced
• Treatment cycle: initially carried out every 2–3 days
for 10 days and then be made once or twice a week to
sustain suppression of the adult vector population.

67. Biological control
• Larvivorous guppy fish (Poecilia reticulata)
• Endotoxin-producing bacteria, Bacillus
thuringiensis serotype H-14 (Bt H-14)

68. Legislation
1. Model civic byelaws: fine/punishment is
imparted, if breeding is detected. (Rs 20-200
fine). In cities Rohtak, Delhi, Mumbai,
Chandigarh.
2. Building Construction Regulation Act: In
Mumbai, prior to any construction activity, the
owners/builders deposit a fee for controlling
mosquitogenic conditions at site by the
Municipal Corporation.
3. Environmental Health Act (HIA)
4. Health Impact Assessments

69. Newer Approach for vector
management
• Insecticide-treated materials:
– Insecticide-treated window curtains
– Long-lasting insecticidal fabric covers for domestic
water-storage . Mexico and Venezuela
• Oviposition traps:
– Lethal ovitraps - Brazil
– Autocidal ovitraps
– Sticky ovitraps
• To infect mosquito population with bacteria
(Wolbachia genus), which make the mosquitoes
partially resistant to dengue virus.

70. When to call it as an outbreak
• One such approach is to track the occurrence of
current (probable) cases and compare them with
the average number of cases by week (or
month) of the preceding 5–7 years, with
confidence interval set at two standard deviations
above and below the average (±2 SD). This is
sometimes referred to as the “endemic channel”.
(WHO 2009)
• If the number of cases reported exceeds 2 SDs
above the “endemic channel” in weekly or
monthly reporting, an outbreak alert is triggered.

71. When to call it as an outbreak
• But for dengue we call outbreak even if there
is reporting of single confirmed case of
dengue fever in community or
• Even single case of suspected DHF in a
community with rising number of fever cases
for previous three weeks.

72. Outbreak Response
• Two major components:
• Early diagnosis and appropriate clinical
case management of dengue to minimize the
number of dengue-associated deaths.
• Emergency vector control to curtail
transmission of the dengue virus as rapidly
as possible

73. Local health authorities in Outbreak
• Emergency Action Committee (EAC): to co-
ordinate activities aimed at emergency vector
control measures and management of
serious cases. Mainly administrative function.
• Rapid response team: aim to undertake
urgent epidemiological investigations and
provide on the spot technical guidance
required and logistic support.

74. In Rohtak
• Rapid response team:
1. Dr. Ved Pal- District malaria officer
2. Dr. Amarjit Rathi- Deputy civil surgeon
3. Dr. Kuldeep- D.F.W.O
4. Dr. Kulpratibha- SMO GH(Ped)
5. Dr. Kunal- MO GH(Med)
6. Dr. Arun- MO GH(Micro)
7. Epidemiologist post vacant since September
2014

75. Dengue vaccines - a hope to drop
dengue count
Vaccine Type Phase
Sanofi Pasteur(CYF-TDV) Live attenuated chimeric
tetravalent
III
Naval medical research
center
Plasmid DNA
Vaccine(DEN1)
I
U.S NIH Monovalent I
Biologicale Live attenuated tetravalent preclinical
Butantan Live attenuated tetravalent II
Panacea Live attenuated tetravalent preclinical
Vabiotech Live attenuated tetravalent preclinical
Invirogen Live attenuated tetravalent II
MERCK Subunit protein I
GlaxoSmithKline Purified inactivated I

76. Sanofi Pasteur(CYD-TDV) vaccine
• Schedule : three doses at 6 months interval
• In Asia: follow up after 28 days of 3rd dose for 1 year
1. Study population consisted of 10,275 children aged 2 to 14
years in five countries Indonesia, Malaysia, the
Philippines, Thailand, and Vietnam.
2. Vaccine efficacy against dengue of any one of the four
dengue virus (DENV) serotypes in this period was
estimated as 57%, DENV1 50%, DENV2 was 35%,
DENV3 was 78%, DENV4 was 75%.
3. Vaccine efficacy was higher in those vaccinated at older
ages: 74% in participants aged 12-14 years, 60% in
participants aged 6-11 years, and 34% in participants aged
2-5 years. (WHO 2012)

77. Sanofi Pasteur(CYD-TDV) vaccine
• In Latin America : A total of 20,875 children
aged 9 to 16 years from dengue endemic areas of
countries Brazil, Colombia, Mexico, Honduras
and Puerto Rico participated.
• Large-scale phase III study successfully meets
primary endpoint with overall vaccine efficacy of
60.8 %
• Additional observation of the results shows a
significant reduction of the risk of
hospitalization by 80.3%. (WHO September
2014)

78. Advocacy
• Advocacy is a process through which groups of
stakeholders can be influenced to gain support for and
reduce barriers to specific initiatives or programmes.
Examples:
1. Social mobilization(Dengue month in July)
2. Administrative advocacy
3. Legislative advocacy(Building Constn Regulation)
4. Legal advocacy(fine)
5. Media advocacy

79. Behavior Change Communication
• Communication for Behavioural Impact (COMBI) is a
systematic planning methodology adopted by WHO to
design and implement behaviourally-focused
communication strategies for modifying behaviours
associated with dengue and other vector-borne diseases.
• Example:
– enhancing community mobilization for source reduction,
– appropriate use of household insecticides,
– appropriate and timely use of health services,
– diagnosis and reporting of dengue cases.

80. Behavior Change Communication
IEC- its specific objectives are:
1. Increase the visibility of the problem
2. Increase levels of political commitment
3. Enhance mobilization of resources
4. Community Mobilization
5. Sustainability
Effective communication should be SMART
(specific, measurable, appropriate, realistic and time-
bound) especially in outbreaks.

82. Intersectoral co-ordination
1. Public sector
a. Ministry of Urban Development / Construction
Agencies
b. Local Governments/ Corporations/ Municipality.
c. Ministry of Rural Development
d. Ministry of Science and Technology
e. Ministry of HRD, etc.
2. Private sector(tyre industries)
3. NGO’s

83. References
• Normile D (2013). “Surprising new dengue virus
throws a spanner in disease control efforts”. Science
342 (6157): 415. doi:10.1126/science.342.6157.415.
PMID 24159024.
• WHO 2009 pg.3
• Nvbdcp.in
• World Health Organization. Dengue: guidelines for
diagnosis, treatment, prevention and control -- New
edition. WHO/HTM/NTD/DEN/2009.
• World Health Organization. Global strategy for dengue
prevention and control 2012-2020.
• Mid Term Plan for Dengue & Chikungunya.