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 6 publications

(4 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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“…Furthermore, the presence of other main circulating arboviruses was evaluated by RT-qPCR using GoTaq ® 1-Step RT-qPCR System (Promega, Madison, WI, USA). Specific diagnosis primers were used for Zika [30], dengue [31], chikungunya [32], Mayaro [33], West Nile [34] and Oropouche [35] viruses. Reactions were assembled following the manufacturer's instructions and were performed in a 7500 Real-Time PCR System (Applied Biosystems, USA).…”

Section: Arbovirusesmentioning

confidence: 99%

Lessons from a multilaboratorial task force for diagnosis of a fatal toxoplasmosis outbreak in captive primates in Brazil

Schiffler,

Moreira,

Pereira

et al. 2023

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As exemplified by the Coronavirus Disease 2019 (COVID-19) pandemic, infectious diseases may emerge and spread rapidly, often causing serious economic losses and public health concerns. In fact, disease outbreaks have become increasingly common, especially those of zoonotic origin. The Brazilian Ministry of Health is responsible for national epizootic surveillance. However, the system’s focus primarily on diseases affecting humans has led to the neglect of other zoonotic diseases. In this report, we present an integrated investigation of an outbreak that occurred during the first year of the COVID-19 pandemic among captive neotropical primates housed at a primatology center in Brazil. After presenting a range of non-specific clinical signs, including fever, prostration, inappetence, and abdominal pain, ten primates from five different species died within approximately four days. Despite the state of health emergency due to the pandemic, a network of volunteer researchers was established to investigate the outbreak. A wide range of high-resolution techniques was used for different pathogens, including SARS-CoV-2 (RTq-PCR, ELISA and IHC), Toxoplasma gondii (IHC and IFA) and Escherichia coli (IFA), as well as a portable Metagenomic Sequencing utilizing Nanopore Technology. Within a span of four days after necropsies, we successfully identified T. gondii as the causative agent of this outbreak. This case highlights some of the obstacles faced with the current Brazilian surveillance system, which is still limited. A cross-platform interdisciplinary investigation could be a possible model for future epizootic investigations in non-human animals.Author summaryThe Brazilian epizootic surveillance system, under the regulation of the Ministry of Health, has been established to address a national list of compulsory notifiable diseases. However, focusing mainly on the risks to humans causes other zoonoses to be neglected. Here we present an outbreak that occurred during the first year of the COVID-19 pandemic that affected eleven neotropical primates (NP) belonging to six different species. Within four days of exhibiting a range of non-specific clinical signs, including fever, prostration, inappetence, and abdominal pain, ten NPs died. Despite testing negative for pathogens included in the national surveillance policy, a collaborative group of researchers investigated the outbreak in detail. Using integrated diagnostic techniques, we identifiedToxoplasma gondiias the causative agent four days after necropsy. Toxoplasmosis causes devastating acute death outbreaks in neotropical primates and is currently absent in the national guidelines. This unified effort proved the effectiveness of a multidisciplinary collaborative surveillance network in facilitating precise diagnoses.

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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 6 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

Lessons from a multilaboratorial task force for diagnosis of a fatal toxoplasmosis outbreak in captive primates in Brazil

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