Analytical and clinical performance of molecular assay used by the Brazilian public laboratory network to detect and discriminate Zika, Dengue and Chikungunya viruses in blood

Ribeiro, Marisa; Godoy, Daniela Tupy de; Fontana-Maurell, Marcela; Costa, Elaine; Andrade, Elisabete; Rocha, Daniele; Ferreira, Antônio G. P.; Brindeiro, Rodrigo M.; Tanuri, Amílcar; Álvarez, Patrícia

doi:10.1016/j.bjid.2021.101542

Cited by 8 publications

(12 citation statements)

References 14 publications

(25 reference statements)

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“…Another strength of this study was the RT-qPCR gold standard applied to all suspected cases, with most serum samples collected within three days of onset of symptoms and after clinical evaluation. The RT-qPCR of the ZDC Molecular kit has shown 100% sensitivity and specificity [31], similar to the Trioplex kit of CDC [47]. Consistent with our results, joint pain, joint edema, skin rash, and muscle, bone, or back pain were significant predictors of chikungunya when compared to dengue or other acute febrile illnesses in a large sample from Puerto Rico using the same gold standard [40].…”

Section: Plos Onesupporting

confidence: 86%

“…Biological samples were referred within 24 hours to reference laboratories of two institutions, the Evandro Chagas National Institute of Infectious Diseases of the Oswaldo Cruz Foundation (2016-2018) and the Noel Nutels Central Laboratory of Rio de Janeiro State (2018-2019). One-step realtime polymerase chain reaction (RT-PCR) was the gold standard for defining chikungunya, dengue (serotypes DENV-1 to DENV-4), Zika (in serum and urine), or negative status, following the manufacturer's instructions (ZDC Molecular Kit, BioManguinhos, Fiocruz) [31].…”

Section: Methodsmentioning

confidence: 99%

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Development and validation of a clinical rule for the diagnosis of chikungunya fever in a dengue-endemic area

et al. 2023

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Rio de Janeiro is a dengue-endemic city that experienced Zika and chikungunya epidemics between 2015 and 2019. Differential diagnosis is crucial for indicating adequate treatment and assessing prognosis and risk of death. This study aims to derive and validate a clinical rule for diagnosing chikungunya based on 3,214 suspected cases consecutively treated at primary and secondary health units of the sentinel surveillance system (up to 7 days from onset of symptoms) in Rio de Janeiro, Brazil. Of the total sample, 624 were chikungunya, 88 Zika, 51 dengue, and 2,451 were negative for all these arboviruses according to real-time polymerase chain reaction (RT-qPCR). The derived rule included fever (1 point), exanthema (1 point), myalgia (2 points), arthralgia or arthritis (2 points), and joint edema (2 points), providing an AUC (area under the receiver operator curve) = 0.695 (95% CI: 0.662–0.725). Scores of 4 points or more (validation sample) showed 74.3% sensitivity (69.0% - 79.2%) and 51.5% specificity (48.8% - 54.3%). Adding more symptoms improved the specificity at the expense of a lower sensitivity compared to definitions proposed by government agencies based on fever alone (European Center for Disease Control) or in combination with arthralgia (World Health Organization) or arthritis (Pan American Health Organization, Brazilian Ministry of Health). The proposed clinical rule offers a rapid, low-cost, easy-to-apply strategy to differentiate chikungunya fever from other arbovirus infections during epidemics.

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Section: Plos Onesupporting

confidence: 86%

Section: Methodsmentioning

confidence: 99%

Development and validation of a clinical rule for the diagnosis of chikungunya fever in a dengue-endemic area

et al. 2023

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“…CHIKV RNA detection was performed by RT-PCR using a commercially available kit, ZDC molecular assay (Bio-Manguinhos, Brazil) and seric anti-CHIKV IgM antibodies were measured using commercial ELISA (Euroimmun, Germany), both according to the manufacturer’s instructions [ 15 , 16 ].…”

Section: Methodsmentioning

confidence: 99%

Clinical markers of post-Chikungunya chronic inflammatory joint disease: A Brazilian cohort

et al. 2023

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Background Chikungunya-fever (CHIKF) remains a public health major issue. It is clinically divided into three phases: acute, post-acute and chronic. Chronic cases correspond to 25–40% individuals and, though most of them are characterized by long-lasting arthralgia alone, many of them exhibit persistent or recurrent inflammatory signs that define post-Chikungunya chronic inflammatory joint disease (pCHIKV-CIJD). We aimed to identify early clinical markers of evolution to pCHIKV-CIJD during acute and post-acute phases. Methodology/Principal findings We studied a prospective cohort of CHIKF-confirmed volunteers with longitudinal clinical data collection from symptoms onset up to 90 days, including a 21-day visit (D21). Of 169 patients with CHIKF, 86 (50.9%) completed the follow-up, from whom 39 met clinical criteria for pCHIKV-CIJD (45.3%). The relative risk of chronification was higher in women compared to men (RR = 1.52; 95% CI = 1.15–1.99; FDR = 0.03). None of the symptoms or signs presented at D0 behaved as an early predictor of pCHIKV-CIJD, while being symptomatic at D21 was a risk factor for chronification (RR = 1.31; 95% CI = 1.09–1.55; FDR = 0.03). Significance was also observed for joint pain (RR = 1.35; 95% CI = 1.12–1.61; FDR = 0.02), reported edema (RR = 3.61; 95% CI = 1.44–9.06; FDR = 0.03), reported hand and/or feet small joints edema (RR = 4.22; 95% CI = 1.51–11.78; FDR = 0.02), and peri-articular edema observed during physical examination (RR = 2.89; 95% CI = 1.58–5.28; FDR = 0.002). Furthermore, patients with no findings in physical examination at D21 were at lower risk of chronic evolution (RR = 0.41, 95% CI = 0.24–0.70, FDR = 0.01). Twenty-nine pCHIKV-CIJD patients had abnormal articular ultrasonography (90.6% of the examined). The most common indings were synovitis (65.5%) and joint effusion (58.6%). Conclusion This cohort has provided important insights into the prognostic evaluation of CHIKF. Symptomatic sub-acute disease is a relevant predictor of evolution to chronic arthritis with synovitis, drawing attention to joint pain, edema, multiple articular involvement including small hand and feet joints as risk factors for chronification beyond three months, especially in women. Future studies are needed to accomplish the identification of accurate and early biomarkers of poor clinical prognosis, which would allow better understanding of the disease’s evolution and improve patients’ management, modifying CHIKF burden on global public health.

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“…Other regions including C-prM, E gene, capsid, NS5 and combinations of these with 3′ and 5′ UTR are used for serotyping [105]. Minimum analytical specificity is<=100 copies/reaction and diagnostic sensitivity and specificity compared with composite clinical reference standards are as high as 100 and 100 %, though varied between 85-100 % sensitive depending on comparator assay and clinical stage of illness [100,102,[104][105][106][107][108][109][110][111][112][113]. Many described assays use TaqMan hydrolysis probes, one variant of which has been shown to be less sensitive for DENV4, though a remedial modification is available [114].…”

Section: Pcr Methodsmentioning

confidence: 99%

Dengue: A review of laboratory diagnostics in the vaccine age

Frazer,

Norton

2024

Journal of Medical Microbiology

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Background. Dengue is an important arboviral infection of considerable public health significance. It occurs in a wide global belt within a variety of tropical regions. The timely laboratory diagnosis of Dengue infection is critical to inform both clinical management and an appropriate public health response. Vaccination against Dengue virus is being introduced in some areas. Discussion. Appropriate diagnostic strategies will vary between laboratories depending on the available resources and skills. Diagnostic methods available include viral culture, the serological detection of Dengue-specific antibodies in using enzyme immunoassays (EIAs), microsphere immunoassays, haemagglutination inhibition or in lateral flow point of care tests. The results of antibody tests may be influenced by prior vaccination and exposure to other flaviviruses. The detection of non-structural protein 1 in serum (NS1) has improved the early diagnosis of Dengue and is available in point-of-care assays in addition to EIAs. Direct detection of viral RNA from blood by PCR is more sensitive than NS1 antigen detection but requires molecular skills and resources. An increasing variety of isothermal nucleic acid detection methods are in development. Timing of specimen collection and choice of test is critical to optimize diagnostic accuracy. Metagenomics and the direct detection by sequencing of viral RNA from blood offers the ability to rapidly type isolates for epidemiologic purposes. Conclusion. The impact of vaccination on immune response must be recognized as it will impact test interpretation and diagnostic algorithms.

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Analytical and clinical performance of molecular assay used by the Brazilian public laboratory network to detect and discriminate Zika, Dengue and Chikungunya viruses in blood

Cited by 8 publications

References 14 publications

Development and validation of a clinical rule for the diagnosis of chikungunya fever in a dengue-endemic area

Development and validation of a clinical rule for the diagnosis of chikungunya fever in a dengue-endemic area

Clinical markers of post-Chikungunya chronic inflammatory joint disease: A Brazilian cohort

Dengue: A review of laboratory diagnostics in the vaccine age

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