Dengue Seroepidemiology in India. Rohit Arora, Sanofi Pasteur

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

Dengue Seroepidemiology in India 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)

Active surveillance estimates of under reporting in SEA countries

Under-reporting: Large Scale, Multi-year School based Active surveillance for Dengue in Southern Vietnam 200 400 600 800 1000 1200 1400 1600 1800 2000 ? 15 yrs >15 yrs Incidence per 100,000 Unreported Reported DF Under-reporting factor 15.6 DHF 5.1 DSS 1.1

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

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.

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

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)

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)

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)

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

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