Estimating the dengue burden in India
Authors: Annelies Wilder-Smith, Priscilla Rupali
Journal: The Lancet Global Health (2019)

Dengue is the most rapidly spreading vector-borne viral disease globally, with an increasing number of areas at risk.1Jentes ES Lash RR Johansson MA et al.Evidence-based risk assessment and communication: a new global dengue-risk map for travellers and clinicians.J Travel Med. 2016; 23: taw062Crossref PubMed Scopus (69) Google Scholar Reliable estimates of the burden of dengue are important to inform policy and research. However, quantifying the true burden globally remains elusive because surveillance systems are notoriously poor at capturing all symptomatic dengue infections, resulting in gross under-reporting. Often higher quality health systems have better reporting. Cartographical and modelling efforts estimated the global disease burden of dengue to amount to 96 million cases in 2010.2Bhatt S Gething PW Brady OJ et al.The global distribution and burden of dengue.Nature. 2013; 496: 504-507Crossref PubMed Scopus (5303) Google Scholar Samir Bhatt and colleagues2Bhatt S Gething PW Brady OJ et al.The global distribution and burden of dengue.Nature. 2013; 496: 504-507Crossref PubMed Scopus (5303) Google Scholar showed a discrepancy between reported versus modelled dengue incidence, a discrepancy which was particularly high for India. According to their estimates,2Bhatt S Gething PW Brady OJ et al.The global distribution and burden of dengue.Nature. 2013; 496: 504-507Crossref PubMed Scopus (5303) Google Scholar India contributed 34 of 96 million apparent global dengue infections, a number which stands in stark contrast to the 12 484 reported cases from India to the WHO in the same year. Such a mismatch was also reported for India in another study,3Shepard DS Halasa YA Tyagi BK et al.Economic and disease burden of dengue illness in India.Am J Trop Med Hyg. 2014; 91: 1235-1242Crossref PubMed Scopus (105) Google Scholar in which the actual number of dengue cases were 282 times the number reported by the national vector-borne disease control programme. Furthermore, a study4Neuberger A Turgeman A Lustig Y Schwartz E Dengue fever among Israeli expatriates in Delhi, 2015: implications for dengue incidence in Delhi, India.J Travel Med. 2016; 23: taw003Crossref PubMed Scopus (21) Google Scholar of expatriates living in Delhi, India, had a very high incidence of dengue acquired in Delhi, unmasking substantial dengue transmission that was not reported as such in the local population. We therefore welcome the well designed, nationally representative survey to estimate age-specific seroprevalence of dengue infections in India by Manoj Murhekar and colleagues published in The Lancet Global Health.5Murhekar MV Kamaraj P Kumar MS Burden of dengue infection in India, 2017: a cross-sectional population based serosurvey.Lancet Glob Health. 2019; http://dx.doi.org/10.1016/S2214-109X(19)30250-5Scopus (39) Google Scholar A large study team did a community-based survey in 240 clusters (118 rural, 122 urban) selected from 60 districts of 15 Indian states from five geographical regions—a huge undertaking. 12 300 individuals aged 5–45 years were tested for IgG antibodies against the dengue virus with the use of indirect ELISA, and catalytic models were constructed to estimate force of infection. The overall seroprevalence of dengue infection in India was 48·7% (95% CI 43·5–54·0); increasing from 28·3% (21·5–36·2) among children aged 5–8 years to 41·0% (32·4–50·1) among children aged 9–17 years and to 56·2% (49·0–63·1) among individuals aged 18–45 years. The results are quite similar to neighbouring Bangladesh6Salje H Paul KK Paul R et al.Nationally-representative serostudy of dengue in Bangladesh allows generalizable disease burden estimates.Elife. 2019; 8e42869 Crossref PubMed Scopus (26) Google Scholar but are much lower than the seroprevalence in most southeast Asian countries where seroprevalence is often documented as above 70% already by the age of 9 years.7L'Azou M Moureau A Sarti E et al.Symptomatic dengue in children in 10 Asian and Latin American countries.N Engl J Med. 2016; 374: 1155-1166Crossref PubMed Scopus (84) Google Scholar The estimated number of dengue infections among individuals aged 5–45 years from 30 Indian states in 2017 was 12 991 357 (12 825 128–13 130 258) based on constant force of infection models. This number is lower than Bhatt and colleagues' modelling study (about 13 million based on real seroprevalence data vs 34 million based on modelling), but because it is based on nationally representative data, Murhekar and colleagues' number is more reliable. Given the size of and vast geographical differences within India, it is not unsurprising that seroprevalence differed greatly between regions: the highest seroprevalence was in southern regions (76·9%), followed by western (62·3%), and northern (60·3%) regions. The seroprevalence was also higher for urban (70·9%) versus rural areas (42·3%), which is in keeping with the observation that urbanisation appears to be one of the main drivers for the increase in dengue incidence.6Salje H Paul KK Paul R et al.Nationally-representative serostudy of dengue in Bangladesh allows generalizable disease burden estimates.Elife. 2019; 8e42869 Crossref PubMed Scopus (26) Google Scholar, 8Struchiner CJ Rocklov J Wilder-Smith A Massad E Increasing dengue incidence in Singapore over the past 40 years: population growth, climate and mobility.PLoS One. 2015; 10e0136286 Crossref PubMed Scopus (82) Google Scholar Urbanisation in India is occurring at a dazzling rate, and hence India is poised to see further upsurges of dengue. Evidence on age-stratified dengue seroprevalence is useful for taking informed decisions about the introduction of upcoming dengue vaccines in India. Several dengue vaccine candidates are in different phases of development. The first licensed dengue vaccine, CYD-TDV (Dengvaxia), developed by Sanofi Pasteur, was only recommended in geographical settings with high burden of disease, as indicated by dengue seroprevalence of 70% and higher by the age of 9 years;9Wilder-Smith A Hombach J Ferguson N et al.Deliberations of the strategic advisory group of experts on immunization on the use of CYD-TDV dengue vaccine.Lancet Infect Dis. 2019; 19: e31-e38Summary Full Text Full Text PDF PubMed Scopus (79) Google Scholar hence India would not meet the criteria for introduction. Given the serostatus-dependent performance of CYD-TDV,10Sridhar S Luedtke A Langevin E et al.Effect of dengue serostatus on dengue vaccine safety and efficacy.N Engl J Med. 2018; 379: 327-340Crossref PubMed Scopus (369) Google Scholar, 11Wilder-Smith A Serostatus-dependent performance of the first licensed dengue vaccine: implications for travellers.J Travel Med. 2018; 25: tay057Crossref Scopus (30) Google Scholar WHO's position was further revised in 2018 to recommend a prevaccination screening strategy whereby people are tested for past dengue exposure and only those tested seropositive would be vaccinated.9Wilder-Smith A Hombach J Ferguson N et al.Deliberations of the strategic advisory group of experts on immunization on the use of CYD-TDV dengue vaccine.Lancet Infect Dis. 2019; 19: e31-e38Summary Full Text Full Text PDF PubMed Scopus (79) Google Scholar Murhekar and colleagues provide a true novel contribution to the existing knowledge on the dengue burden in a subcontinent as vast as India. The study was well done with a state-of-the-art research design, including modelling the force of infection. Although the dengue burden in India at this stage is lower than that of most other southeast Asian countries, their data show that dengue does pose a substantial public health risk. Such evidence should act as an impetus for India to invest more in addressing the dengue burden. At the same time, it is important to study related flaviviruses, such as Zika virus, which could also potentially have a devastating effect in India.12Watts AG Huber C Bogoch II Brady OJ Kraemer MUG Khan K Potential Zika virus spread within and beyond India.J Travel Med. 2018; 25: tay132Google Scholar We declare no competing interests. Burden of dengue infection in India, 2017: a cross-sectional population based serosurveyThe burden of dengue infection in India was heterogeneous, with evidence of high transmission in northern, western, and southern regions. The survey findings will be useful in making informed decisions about introduction of upcoming dengue vaccines in India. Full-Text PDF Open Access