Dengue severity – Institut Pasteur de Nouvelle-Calédonie

2017 Dengue outbreak, Investigations of severe cases : Dengue Severity
Principal investigator	M. Dupont-Rouzeyrol
IPNC main investigator	M. Dupont-Rouzeyrol
IPNC collaborators	A. Tarantola, C. Inizan, M. Minier, O. O’Connor
Other collaborators	E. Simon-Lorière, A. Sakuntabhai (IPP), E. Descloux, M. Sérié, M.-A. Goujart,, A.-C. Gourinat (CHT), C. Forfait, A. Pfannstiel (DASS-NC).
Budget		Budget devoted to IPNC
Financial supports	IPNC, IPP, CHT, NC
Timeline	Start date: Sept.2017		End date : Sept. 2018
Context
With 4,401 dengue cases (2,548 biologically confirmed), 579 hospitalized cases and 11 deaths between Jan 1^st and Oct 8^th 2017, the 2016-2017 dengue epidemic in New Caledonia (NC) was sizeable. More importantly, it was associated with a higher percentage of hospital admissions and severe clinical presentations (liver injury, ophthalmic complications…). The higher occurrence of deaths and heretofore rare hepatic forms observed during this epidemic may be linked with specific characteristics of viruses, patients, or host-pathogen response.
Objectives
To determine whether severe presentations of dengue infections were associated with specific characteristics such as virus genotype and hepatic tropism, patient comorbidities or earlier infection by dengue or Zika viruses.
Methods
Patients already included in the ArboVirtuess study will be asked to continue their participation and contribute an additional blood sample. – Selection of 50 sera from 2017 and previous years available for analysis: 1/3 severe forms versus 2/3 non-severe – Phylodynamic studies based on whole-genome sequencing. Search for variations in viral quasi-species. – Comparative analysis of the hepatic tropism of viral strains representative of 2016-2017 epidemic versus previous years – Sera characterization: history of previous arbovirus infections, impact of pre-existing humoral immunity on DENV replication in human monocytes (ADE)
Preliminary results
Ethical approval for patient recall have been obtained and sera have been selected and collected. Viral RNAs have been extracted from the sera and whole-genome sequencing is in progress. In parallel, viruses from this year’s epidemic are currently being isolated on mosquito C6/36 cells and will be titrated. Experimental conditions for human hepatic cell line infection as well as for ADE have been set up and are currently being validated. Characterization of viruses’ hepatic tropism and sera inhibition/enhancement capacity will soon be initiated.
Perspectives
First, this study may shed light on a potential evolution of viruses involved in severe cases compared to non-severe dengue cases, in link with a modification in virus hepatic tropism. Second, this project will provide an unprecedented characterization of the impact of anti-Zika antibodies on DENV infection. Overall, this study is expected to further the understanding of the unusual severity of DENV epidemic in 2017. Such documentation of the influence of a pre-existing anti-Zika humoral immunity on dengue severity would be useful for territories displaying an epidemiological situation similar to NC, thus suggesting a new indicator to estimate the risk of progression towards severe dengue.