dc.contributor.author
Fischer, Carlo
dc.contributor.author
Bozza, Fernando
dc.contributor.author
Merino Merino, Xiomara Jeanleny
dc.contributor.author
Pedroso, Celia
dc.contributor.author
Oliveira Filho, Edmilson F. de
dc.contributor.author
Moreira-Soto, Andrés
dc.contributor.author
Schwalb, Alvaro
dc.contributor.author
Lamballerie, Xavier de
dc.contributor.author
Netto, Eduardo Martins
dc.contributor.author
Bozza, Patrícia T.
dc.contributor.author
Sarno, Manoel
dc.contributor.author
Brites, Carlos
dc.contributor.author
Talledo, Michael
dc.contributor.author
Drexlera, Jan Felix
dc.date.accessioned
2020-07-03T11:28:24Z
dc.date.available
2020-07-03T11:28:24Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/27453
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-27209
dc.description.abstract
Since 2013, the arthropod-borne Chikungunya virus (CHIKV) has cocirculated with the autochthonous Mayaro virus (MAYV) in Latin America. Both belong to the same alphavirus serocomplex, termed the Semliki Forest serocomplex. The extent of antibody cross-reactivity due to the antigenic relatedness of CHIKV and MAYV in commonly used serologic tests remains unclear. By testing 64 CHIKV- and 37 MAYV-specific sera from cohort studies conducted in Peru and Brazil, we demonstrate about 50% false-positive test results using commercially available enzyme-linked immunosorbent assays (ELISAs) based on structural antigens. In contrast, combining ELISAs for CHIKV and MAYV significantly increased positive predictive values (PPV) among all cohorts from 35.3% to 88.2% for IgM and from 61.3% to 96.8% for IgG (P < 0.0001). Testing of longitudinally collected CHIKV-specific patient sera indicated that ELISA specificity is highest for IgM testing at 5 to 9 days post-onset of symptoms (dpo) and for IgG testing at 10 to 14 dpo. IgG cross-reactivity in ELISA was asymmetric, occurring in 57.9% of MAYV-specific sera compared to 29.5% of CHIKV-specific sera. Parallel plaque reduction neutralization testing (PRNT) for CHIKV and MAYV increased the PPV from 80.0% to 100% (P = 0.0053). However, labor-intense procedures and delayed seroconversion limit PRNT for patient diagnostics. In sum, individual testing for CHIKV or MAYV only is prone to misclassifications that dramatically impact patient diagnostics and sero-epidemiologic investigation. Parallel ELISAs for both CHIKV and MAYV provide an easy and efficient solution to differentiate CHIKV from MAYV infections. This approach may provide a template globally for settings in which alphavirus coemergence imposes similar problems.IMPORTANCE Geographically overlapping transmission of Chikungunya virus (CHIKV) and Mayaro virus (MAYV) in Latin America challenges serologic diagnostics and epidemiologic surveillance, as antibodies against the antigenically related viruses can be cross-reactive, potentially causing false-positive test results. We examined whether widely used ELISAs and plaque reduction neutralization testing allow specific antibody detection in the scenario of CHIKV and MAYV coemergence. For this purpose, we used 37 patient-derived MAYV-specific sera from Peru and 64 patient-derived CHIKV-specific sera from Brazil, including longitudinally collected samples. Extensive testing of those samples revealed strong antibody cross-reactivity in ELISAs, particularly for IgM, which is commonly used for patient diagnostics. Cross-neutralization was also observed, albeit at lower frequencies. Parallel testing for both viruses and comparison of ELISA reactivities and neutralizing antibody titers significantly increased diagnostic specificity. Our data provide a convenient and practicable solution to ensure robust differentiation of CHIKV- and MAYV-specific antibodies.
en
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
cross-reactivity
en
dc.subject
arbovirus diagnostics
en
dc.subject
mosquito-borne disease
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
Robustness of Serologic Investigations for Chikungunya and Mayaro Viruses Following Coemergence
dc.type
Wissenschaftlicher Artikel
dcterms.isPartOf
2379-5042
dcterms.bibliographicCitation.articlenumber
e00915-19
dcterms.bibliographicCitation.doi
10.1128/mSphere.00915-19
dcterms.bibliographicCitation.journaltitle
mSphere
dcterms.bibliographicCitation.number
1
dcterms.bibliographicCitation.originalpublishername
American Society for Microbiology
dcterms.bibliographicCitation.volume
5
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
32024703
dcterms.isPartOf.eissn
2379-5042