Combining anti‐IgM and IgG immunoassays for comprehensive chikungunya virus diagnostic testing

Mendoza, Emelissa J; Robinson, Alyssia; Dimitrova, Kristina; Mueller, Nicole; Holloway, Kimberly; Makowski, Kai; Wood, Heidi

doi:10.1111/zph.12641

Cited by 6 publications

(8 citation statements)

References 35 publications

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“…The commercial kit studies mostly use cohort or partial cohort partial case-control study designs. Case-control study design was used in only two of the studies [39,41].…”

Section: Subgroup Analysis Of Commercial Serological Tests For Chikvmentioning

confidence: 99%

“…4.4.2 Quality assessment of bias and application. The high risk of bias in the patient selection domain was mainly contributed by studies that applied case-control study design [23,30,38,39,41,45,46,52,54]. As mentioned previously, the case-control study design could exaggerate the test accuracy and thus may not reflect the actual accuracy.…”

Section: Plos Neglected Tropical Diseasesmentioning

confidence: 99%

“…The ELISA-based test results were categorised into positive, borderline (or equivocal), and negative based on the obtained OD (absorbance) or a ratio. To simplify the analysis, some studies coded the borderline or equivocal samples as positive [41] and negative [13,50]. A study coded equivocal results for the immunochromatographic test as negative [31].…”

Section: Plos Neglected Tropical Diseasesmentioning

confidence: 99%

“…This meta-analysis specifies direct detection methods such as virus isolation and molecular-based method as the reference standard for antigen detection tests to ensure that the samples were collected during the viral stage. Some studies used molecular tests as the reference standards [36,41], and subsequent samples collected from the same patient were used for IgM or IgG accuracy studies. Although not wrong, each patient's immune response can be varied against CHIKV.…”

Section: Plos Neglected Tropical Diseasesmentioning

confidence: 99%

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Diagnostic accuracy of serological tests for the diagnosis of Chikungunya virus infection: A systematic review and meta-analysis

et al. 2022

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Background Chikungunya virus (CHIKV) causes febrile illnesses and has always been misdiagnosed as other viral infections, such as dengue and Zika; thus, a laboratory test is needed. Serological tests are commonly used to diagnose CHIKV infection, but their accuracy is questionable due to varying degrees of reported sensitivities and specificities. Herein, we conducted a systematic review and meta-analysis to evaluate the diagnostic accuracy of serological tests currently available for CHIKV. Methodology and principal findings A literature search was performed in PubMed, CINAHL Complete, and Scopus databases from the 1st December 2020 until 22nd April 2021. Studies reporting sensitivity and specificity of serological tests against CHIKV that used whole blood, serum, or plasma were included. QUADAS-2 tool was used to assess the risk of bias and applicability, while R software was used for statistical analyses. Thirty-five studies were included in this meta-analysis; 72 index test data were extracted and analysed. Rapid and ELISA-based antigen tests had a pooled sensitivity of 85.8% and 82.2%, respectively, and a pooled specificity of 96.1% and 96.0%, respectively. According to our meta-analysis, antigen detection tests serve as a good diagnostic test for acute-phase samples. The IgM detection tests had more than 90% diagnostic accuracy for ELISA-based tests, immunofluorescence assays, in-house developed tests, and samples collected after seven days of symptom onset. Conversely, low sensitivity was found for the IgM rapid test (42.3%), commercial test (78.6%), and for samples collected less than seven of symptom onset (26.2%). Although IgM antibodies start to develop on day 2 of CHIKV infection, our meta-analysis revealed that the IgM detection test is not recommended for acute-phase samples. The diagnostic performance of the IgG detection tests was more than 93% regardless of the test formats and whether the test was commercially available or developed in-house. The use of samples collected after seven days of symptom onset for the IgG detection test suggests that IgG antibodies can be detected in the convalescent-phase samples. Additionally, we evaluated commercial IgM and IgG tests for CHIKV and found that ELISA-based and IFA commercial tests manufactured by Euroimmun (Lübeck, Germany), Abcam (Cambridge, UK), and Inbios (Seattle, WA) had diagnostic accuracy of above 90%, which was similar to the manufacturers’ claim. Conclusion Based on our meta-analysis, antigen or antibody-based serological tests can be used to diagnose CHIKV reliably, depending on the time of sample collection. The antigen detection tests serve as a good diagnostic test for samples collected during the acute phase (≤7 days post symptom onset) of CHIKV infection. Likewise, IgM and IgG detection tests can be used for samples collected in the convalescent phase (>7 days post symptom onset). In correlation to the clinical presentation of the patients, the combination of the IgM and IgG tests can differentiate recent and past infections.

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“…The commercial kit studies mostly use cohort or partial cohort partial case-control study designs. Case-control study design was used in only two of the studies [39,41].…”

Section: Subgroup Analysis Of Commercial Serological Tests For Chikvmentioning

confidence: 99%

Section: Plos Neglected Tropical Diseasesmentioning

confidence: 99%

Section: Plos Neglected Tropical Diseasesmentioning

confidence: 99%

Section: Plos Neglected Tropical Diseasesmentioning

confidence: 99%

See 2 more Smart Citations

Diagnostic accuracy of serological tests for the diagnosis of Chikungunya virus infection: A systematic review and meta-analysis

et al. 2022

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“…Additionally, it has been associated with cases of meningoencephalitis, Guillain–Barré syndrome, and hemorrhagic disease [ 1 ]. The combination of IgM and IgG ELISAs may provide evidence for both recent and past exposures to the virus [ 2 ]. Several commercial tests are available for anti-CHIKV antibody detection.…”

Section: Introductionmentioning

confidence: 99%

Chikungunya E2 Protein Produced in E. coli and HEK293-T Cells—Comparison of Their Performances in ELISA

Bagno

Godói

Figueiredo

et al. 2020

Viruses

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Chikungunya virus (CHIKV) is a mosquito-borne pathogen that causes a disease characterized by the acute onset of fever accompanied by arthralgia and intense joint pain. Clinical similarities and cocirculation of this and other arboviruses in many tropical countries highlight the necessity for efficient and accessible diagnostic tools. CHIKV envelope proteins are highly conserved among alphaviruses and, particularly, the envelope 2 glycoprotein (CHIKV-E2) appears to be immunodominant and has a considerable serodiagnosis potential. Here, we investigate how glycosylation of CHIKV-E2 affects antigen/antibody interaction and how this affects the performance of CHIKV-E2-based Indirect ELISA tests. We compare two CHIKV-E2 recombinant antigens produced in different expression systems: prokaryotic-versus eukaryotic-made recombinant proteins. CHIKV-E2 antigens are expressed either in E. coli BL21(DE3)—a prokaryotic system unable to produce post-translational modifications—or in HEK-293T mammalian cells—a eukaryotic system able to add post-translational modifications, including glycosylation sites. Both prokaryotic and eukaryotic recombinant CHIKV-E2 react strongly to anti-CHIKV IgG antibodies, showing accuracy levels that are higher than 90%. However, the glycan-added viral antigen presents better sensitivity and specificity (85 and 98%) than the non-glycosylated antigen (81 and 71%, respectively) in anti-CHIKV IgM ELISA assays.

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Desenvolvimento de plataformas de diagnóstico uniplex e multiplex para infecção com arbovírus utilizando proteínas recombinantes.

Santos¹

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Os vírus Dengue (DENV), Zika (ZIKV) e Chikungunya (CHIKV) são arbovírus evidentes no cenário internacional atual que apresentam dificuldade na geração de dados epidemiológicos acurados. Tal fato ocorre devido à grande semelhança dos sintomas clínicos compartilhados pelas doenças, além da elevada reação cruzada observada entre alguns desses vírus quando avaliados em testes de diagnóstico sorológico. A disponibilidade de testes sorológicos sensíveis, específicos e de baixo custo contra esses vírus ainda é limitada no país. Diante disso, o presente projeto teve por objetivo desenvolver plataformas de diagnóstico sorológico uniplex (ELISA) e multiplex (Luminex), baseadas em formas recombinantes de proteínas DENV, ZIKV e CHIKV. Após avaliação in silico, porções da proteína não estrutural 1 (NS1) de DENV e ZIKV (denominadas ∆NS1 ZIKV e ∆NS1 DENV1-4), e da proteína 2 do envelope (E2) de CHIKV (denominada E2.1 CHIKV) apresentaram baixa homologia entre si e com as mesmas regiões de vírus próximos a DENV, ZIKV e CHIKV, sendo escolhidas como antígenos de diagnóstico. As proteínas foram implementadas nas plataformas de sorodiagnóstico, as quais foram otimizadas e validadas com a utilização de painéis de soros humanos fornecidos por colabores. Todos os testes gerados na plataforma de ELISA apresentaram valores de sensibilidade e especificidade iguais ou superiores aos testes atualmente disponíveis no mercado, com destaque para o teste ELISA ZIKV, o qual proporcionou uma parceria público privada que culminou na aprovação da sua comercialização pela ANVISA. Resultados similares foram observados com a implementação dos antígenos à plataforma Luminex, corroborando o potencial dos antígenos desenvolvidos. O sucesso do desenvolvimento do presente projeto salienta a importância do estudo e do desenvolvimento de metodologias diagnósticas, bem como ilustra de forma clara como a pesquisa acadêmica pode ser feita em sintonia com empresas voltadas para o desenvolvimento de tecnologias na área da saúde.

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Combining anti‐IgM and IgG immunoassays for comprehensive chikungunya virus diagnostic testing

Cited by 6 publications

References 35 publications

Diagnostic accuracy of serological tests for the diagnosis of Chikungunya virus infection: A systematic review and meta-analysis

Diagnostic accuracy of serological tests for the diagnosis of Chikungunya virus infection: A systematic review and meta-analysis

Chikungunya E2 Protein Produced in E. coli and HEK293-T Cells—Comparison of Their Performances in ELISA

Desenvolvimento de plataformas de diagnóstico uniplex e multiplex para infecção com arbovírus utilizando proteínas recombinantes.

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