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Dengue Seroepidemiology in India.

Rohit Arora, Sanofi Pasteur

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Dengue in the Past Quarter

This map may be used as a guide for the assessment of dengue risk throughout the world. The blue regions represent areas of ongoing transmission risk as defined by the Centers for Disease Control and Prevention (CDC) based on data from Ministries of Health, international health organizations, journals, and knowledgeable experts (last updated in 2010 for the 2012 CDC Yellow Book). Recent reports (e.g., official, newspaper, other media) of local and regional dengue or imported cases of dengue collected by HealthMap are shown as red markers linked to the respective reports.

http://www.healthmap.org/dengue/index.php . Accessed on 22/1/2012

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Dengue Seroepidemiology in India

1960s 1970s 1980s 1990s 2000s

DENV-1 DENV-2 DENV-3 DENV-4

Decade wise circulation of various serotypes of Dengue in published literature

All 4 serotypes of Dengue have been known to circulate in the country since many decades.

Chakravarti A,, Arora R, Luxemberger S. Fifty years of dengue in India. Transactions of the Royal Society of Tropical Medicine (Under Review)

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Active surveillance estimates of under reporting in SEA countries

Study Country Expansion factors Period

E.F. dengue: 2.86

E.F. dengue: 4.81

E.F. dengue: 3.42

E.F. hospitalized dengue: 6

E.F. DHF: 4.27

EXPANSION FACTORS BASED ON EMPIRICAL ESTIMATES

Endy et a l . 20022 Thai land 1998-2000

Burke et a l . 19881 Bangkok, Tha i land

1980-1981

Anderson et a l . 20073 Thai land 1988-2002

E.F. dengue : 4

Kongs in et a l 20105 Thai land 2004-2006E.F. dengue: 3.3Hals tead et a l .2007 4 Thai land 1988-2002

Vong et a l . 20077 Cambodia n/a

Chairul fatah et a l .

20018

Bendung, Indones ia

1994-1995

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Under-reporting: Large Scale, Multi-year School based Active surveillance for Dengue in Southern Vietnam

0

200

400

600

800

1000

1200

1400

1600

1800

2000

? 15 yrs >15 yrs ? 15 yrs >15 yrs ? 15 yrs >15 yrs

Incid

en

ce p

er

10

0,0

00

Unreported

Reported

DFUnder-reporting factor

15.6

DHFUnder-reporting factor

5.1

DSSUnder-reporting factor

1.1

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Surveillance estimates of under reporting of Dengue in India

● Although Dengue is a notifiable disease, but there is still a significant factor of under-reporting.

● It is often difficult to estimate the true factor of under-reporting which may hugely vary due to differential access to healthcare infrastructure.

● This is compounded further by the non-regulated private healthcare setup where a substantial number of cases go unreported.

Transactions of the Royal Society of Tropical Medicine and Hygiene (2008) 102, 570—577

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Community-based dengue surveillance in India (DNG09)

● Principal Objectives● To estimate the population-based incidence of symptomatic laboratory-

confirmed dengue infections in the catchment population of selected cohorts across India (associated with community centers)

● Study design● Prospective epidemiological study.

● Sample size● During the determined period of data collection, all patients presenting to

the study sites and fulfilling the inclusion criteria described below will be enrolled.

● Dengue Confirmation● Detection of dengue viral RNA by reverse-transcriptase polymerase chain

reaction (RT-PCR) will be performed in acute blood sample.● Serology by (ELISA) for IgG and IgM dengue antibody.

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The Challenges….

● Significant lack of population-based estimates of incidence of laboratory confirmed dengue infection.

● Even areas with confirmed dengue reports and high risk levels based on socio-demographic factors have no documented data.

● A retrospective investigation of morbidity data in GIS mapped outbreak area revealed that dengue was never diagnosed in any of the health centres.

● Given this lack of previous accurate documentation of dengue, a seroprevalence study was planned● to assess the prevalence of dengue-specific

antibodies which will allow assessing if there has been dengue transmission in the community in recent years.

2007

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Prospective dengue seroprevalence study in 5 to 10 year-old children in India.

● Most frequent diagnosis in these centres has been of ● Acute Respiratory Infection (ARI), and except the respiratory signs, the

other ARI symptoms (e.g. fever, muscle aches, headache) are compatible with a possible diagnosis of dengue.

● A seroprevalence study was proposed, in a sample of children registered in the health centres● to assess the prevalence of dengue‐specific antibodies which will allow

assessing if there has been dengue transmission in the community in recent years (5 years).

● Seroprevalence in children age between the age of 5 to10 shall be able to provide insight into approximate average annual incidence of new dengue infection over the last 5-10 years.

● It was thought to additionally analyze JE-specific antibodies in this population● To determine exposure of the Japanese Encephalitis Virus (Flavivirus) in

this non-endemic area with close migratory connections with endemic zones (eastern UP)

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Prospective dengue seroprevalence study in 5 to 10 year-old children in India.

● Primary Objective● To determine the prevalence of specific antibodies (IgG) against dengue

in healthy 5 to 10 year old children in India through IgG testing using the commercially available kit "EL1500G" from Focus Diagnostics (California, US)

● Secondary Objective(s)● To determine the dengue virus serotype (DENV-1,2,3 and/or 4) specific to

the antibodies in positive (IgG) samples through PRNT50● To estimate the prevalence of specific antibodies (IgG) against Japanese

encephalitis in healthy 5 to 10 year-old children in India through JE IgG antibodies testing though Indirect ELISA using commercial available kits (InBios, USA)

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Prospective dengue seroprevalence study in 5 to 10 year-old children in India.

Source and study population● Children, 5 to 10 years of age, in India.

● Initially 2 study sites in Delhi. Is being progressively be expanded to 10 sites across India

● For the two study site in Delhi, the population is being drawn from children registered in health centres invited to participate during household visits performed by social workers of the health centres.● Delhi Gate (Centre 001)

● Balmiki Basti (Centre 002)

● Dengue and JE antibodies testing is being conducted in Department of Microbiology at Maulana Azad Medical College, Delhi (Dr. Anita Chakravarti)

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Sample size and power calculation

● This study is descriptive and therefore no hypothesis is being tested. The sample has been arbitrarily set at 323 subjects in each site.

● Assuming a prevalence rate of 30%, a sample of 323 subjects will ensure a precision of 5% for the 2-sided 95% confidence interval around the seroprevalence point estimate.

Prospective dengue seroprevalence study in 5 to 10 year-old children in India.

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THANKS