Dengue – a rising public health problem

Dr. Vikas GuptaPostgraduate

Dept. of Community Medicine

History

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.

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.

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.

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%.

Burden of dengue• India: In Year 2013- highest number of cases

from Kerala state (7911) and lowest from state of Maharashtra (48).

2008 2009 2010 2011 2012 20130

20000

40000

60000

80000

12561 1553528292 18860

50222

75454

Cases(India)

Cases

2008 2009 2010 2011 2012 20130

500

1000

1500

2000

1137

125

866

267

768

1784

Cases (Haryana)

Cases

2008 2009 2010 2011 2012 20130

50100150200250300

80 96 110169

242167

Mortality (India)

Mortality

2008 2009 2010 2011 2012 20130

5

10

15

20

25

9

1

20

3 25

Mortality (Haryana)

Mortality

2008 2009 2010 2011 2012 20130

0.10.20.30.40.50.60.70.80.9

1

0.630.61

0.38

0.89

0.48

0.22

case fatality ratio

case fatality ratio

2008 2009 2010 2011 2012 20130.00

0.50

1.00

1.50

2.00

2.50

0.790.80

2.31

1.120.26

0.28

CFR

CFR

Dengue- Rohtak

2008 2009 2010 2011 20120

10

20

30

40

50

60

70

8075

6

2011

15

2 0 2 0 1

Sum of casesSum of mortality

Modes of transmission1. 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.

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.

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, vomiting2. Rash3. Aches and pains4. Leukopenia5. Positive tourniquet test

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).

Case definitions (WHO 2009)• Dengue with Warning Signs Dengue as defined above with any of the following:1. Abdominal pain or tenderness2. Persistent vomiting3. Clinical fluid accumulation (ascites, pleural effusion)4. Mucosal bleeding5. Lethargy, restlessness6. Liver enlargement >2 cm7. Laboratory: increase in HCT (hematocrit) concurrent with

rapid decrease in platelet count

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.

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 clinician3. Severe organ involvement

– Liver: AST or ALT ≥ 1000– CNS: impaired consciousness– Failure of heart and other organs

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.

Case definitions

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.

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

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)

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.

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)

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

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)

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.

Global strategy for dengue prevention and control, 2012–2020 Five technical elements:1. Diagnosis and case management2. Integrated surveillance and outbreak

preparedness3. Sustainable vector control4. Future vaccine implementation5. Basic, operational and implementation

research

Global strategy for dengue prevention and control, 2012–2020

Enabling factors for effective implementation:1. Advocacy and resource mobilization2. Partnership, coordination and collaboration3. Communication to achieve behavioural

impact(COMBI)4. Capacity building5. Monitoring and evaluation

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

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

Mid Term Plan 2011-20134. Outbreak response– Epidemic preparedness– Media management

5. Capacity building– Training– Infrastructure development– Operational research

6. Behavior Change Communication– Social mobilization,– IEC

Mid Term Plan 2011-20137. Inter-sectoral coordination– Health & non health sector

8. Monitoring & Supervision– Review, field visit , feedback– Analysis of reports

Epidemiological surveillance1. 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 surveillanceII. Enhanced surveillance – mainly during epidemic

response

Epidemiological surveillance3. 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

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.

Entomological Surveillance• PUPAL INDEX: intensity of transmission• For larvae:

1. House Index: extent of breeding2. Container Index: intensity of breeding3. Breteau Index: yardstick for

evaluation of the control strategy

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

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

COLOR CODES for Entomological Surveillance

• CODE INTERPRETATION – Red – HOUSE INDEX is >5% and/or – BRETEAU INDEX is >20%

• What to do1. Intensify IEC campaign on prevention & control 2. Mobilize residents of affected area to start clean-up campaign3. 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.

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.

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

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

months)

VECTOR MANAGEMENT1. Environmental Management2. Personal Protection3. Biological Control4. Chemical Control5. Legislation

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.

VECTOR MANAGEMENT Personal protection1. Protective clothing2. Mats, coils and aerosols3. Repellents: DEET (N, N-Diethyl-m

Toluamide)4. Insecticide-treated materials: Mosquito nets

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 /yearBoth internal and external walls of container should

be sprayed and up to 60cm of height in case of non potable water containers.

Chemical control• Adulticides1. 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

Indoor space sprayingCommercial 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.

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

Outdoor space spraying2. 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.

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.

Biological control• Larvivorous guppy fish (Poecilia reticulata) • Endotoxin-producing bacteria, Bacillus

thuringiensis serotype H-14 (Bt H-14)

Legislation1. 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

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.

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.

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.

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

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.

In Rohtak • Rapid response team:1. Dr. Ved Pal- District malaria officer2. Dr. Amarjit Rathi- Deputy civil surgeon3. Dr. Kuldeep- D.F.W.O4. Dr. Kulpratibha- SMO GH(Ped)5. Dr. Kunal- MO GH(Med)6. Dr. Arun- MO GH(Micro)7. Epidemiologist post vacant since September 2014

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

Sanofi Pasteur(CYD-TDV) vaccine

• Schedule : three doses at 6 months interval• In Asia: follow up after 28 days of 3rd dose for 1 year1. 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)

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)

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 advocacy3. Legislative advocacy(Building Constn Regulation)4. Legal advocacy(fine)5. Media advocacy

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.

Behavior Change Communication

IEC- its specific objectives are:1. Increase the visibility of the problem2. Increase levels of political commitment3. Enhance mobilization of resources4. Community Mobilization5. SustainabilityEffective communication should be SMART (specific, measurable, appropriate, realistic and time-bound) especially in outbreaks.

Intersectoral co-ordination1. Public sector

a. Ministry of Urban Development / Construction Agencies

b. Local Governments/ Corporations/ Municipality.c. Ministry of Rural Developmentd. Ministry of Science and Technologye. Ministry of HRD, etc.

2. Private sector(tyre industries) 3. NGO’s

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.