Chikungunya Outbreaks in India: A Prospective Study Comparing Neutralization and Sequelae during Two Outbreaks in 2010 and 2016

Abstract

Chikungunya fever (CHIKF) is a major public health concern and is caused by chikungunya virus (CHIKV). In 2005, the virus was reintroduced into India, resulting in massive outbreaks in several parts of the country. During 2010 and 2016 outbreaks, we recruited 588 patients from a tertiary care hospital in New Delhi, India, during the acute phase of CHIKF; collected their blood and clinical data; and determined their arthralgic status 12 weeks post-onset of fever. We evaluated IgM/IgG CHIKV-binding antibodies and their neutralizing capacity, sequenced complete genomes of 21 CHIKV strains, and correlated mutations with patient sequelae status. We also performed infections in murine models using representative strains from each outbreak to evaluate differences in pathogenesis. Our screening and analysis revealed that patients of the 2016 outbreak developed earlier IgM and neutralizing antibody responses that were negatively correlated with sequelae, compared with 2010 patients. Mutations that correlated with human disease progression were also correlated with enhanced murine virulence and pathogenesis. Overall, our study suggests that the development of early neutralizing antibodies and sequence variation in clinical isolates are predictors of human sequelae.

A Novel Sub-Lineage of Chikungunya Virus East/Central/South African Genotype Indian Ocean Lineage Caused Sequential Outbreaks in Bangladesh and Thailand

“…Our Bangladeshi CHIKV sequences in 2017 clustered with other Bangladeshi and Italian CHIKV strains in the same collection year. Their tMRCA was estimated to be 2015.61 (95%HPD: 2015.25–2016.01, PP = 1) at node C2.3b, and they shared a common ancestral strain with the Indian strain in 2016 (MK473624) [ 9 ]. Furthermore, consequent CHIKV sequences descended from node C2.3c, including our Thailand and other Thailand strains in 2018-2019 together with CHIKVs from Myanmar and China, formed a monophyletic clade (PP = 1), and shared a tMRCA at 2016.98 (95%HPD: 2016.73–2017.25, PP = 1).…”

“…albopictus served as the primary vector [ 48 , 49 ]. In addition, an expansion of IOL E1-226A virus was detected in northern India and was supposedly related to the outbreaks in New Delhi in 2010 and 2016 [ 9 , 50 ].…”

“…In addition to E1-K211E, E2-V264A was first detected in 2010 in India in Kerala and New Delhi, and also from Ae. aegypti in Yemen [ 9 , 45 , 51 ]. They are also specific to the new IOL sub-lineage that emerged around mid-2008.…”

“…They are also specific to the new IOL sub-lineage that emerged around mid-2008. An early appearance of these two substitutions was detected in Southern India around late 2009-2010 [ 44 ], followed by New Delhi in 2010 and 2016 [ 9 , 10 ]. Additionally, in 2010-2011, in Uttar Pradesh, a state located in northern India, a sequence determination of the E1 region in mosquitoes showed the co-existence of E1-211K and E1-211E variants in the background of E1-226A in Ae.…”

“…In 2016, another CHIKV outbreak started in northern India [ 9 , 10 ] and Pakistan, and it spread to Bangladesh in 2017 [ 11 ] and even Kenya and Italy in 2016–2017 [ 12 , 13 , 14 ]. A re-emergence of CHIKV has also been reported in Thailand since 2018 until present [ 15 ].…”