Use of Cerebrospinal Fluid for the Diagnosis of Neuroinvasive Dengue, Zika, and Chikungunya: A 19-year systematic review

Mello, Cíntia da Silva; Cabral‐Castro, Mauro Jorge; Faria, Luiz Claudio Silva de; Peralta, José Mauro; Puccioni-Sohler, Márzia

doi:10.1590/0037-8682-0891-2020

Cited by 7 publications

(5 citation statements)

References 25 publications

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“…Several reports have shown that CHIKV RNA can be detected in body fluids other than serum, such as saliva [ 26 , 28 , 29 ], urine [ 24 , 28 , 29 , 34 ], sperm [ 24 , 29 ], vaginal secretions [ 29 ], placenta or amniotic fluid [ 35 ], breast milk [ 36 ], synovial liquid [ 37 ] and cerebrospinal fluid [ 38 , 39 ]. Infectious CHIKV has also been detected in the saliva of mice, monkeys and humans [ 27 ], raising concerns about the potential for non-vector-borne transmission [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Detection of Chikungunya Virus RNA in Oral Fluid and Urine: An Alternative Approach to Diagnosis?

Jacob-Nascimento,

Portilho,

Anjos

et al. 2024

Viruses

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To evaluate whether oral fluids (OF) and urine can serve as alternative, non-invasive samples to diagnose chikungunya virus (CHIKV) infection via RT-qPCR, we employed the same RNA extraction and RT-qPCR protocols on paired serum, OF and urine samples collected from 51 patients with chikungunya during the acute phase of the illness. Chikungunya patients were confirmed through RT-qPCR in acute-phase sera (N = 19), IgM seroconversion between acute- and convalescent-phase sera (N = 12), or IgM detection in acute-phase sera (N = 20). The controls included paired serum, OF and urine samples from patients with non-arbovirus acute febrile illness (N = 28) and RT-PCR-confirmed dengue (N = 16). Nine (47%) of the patients with positive RT-qPCR for CHIKV in sera and two (17%) of those with CHIKV infection confirmed solely via IgM seroconversion had OF positive for CHIKV in RT-qPCR. One (5%) patient with CHIKV infection confirmed via serum RT-qPCR was positive in the RT-qPCR performed on urine. None of the negative control group samples were positive. Although OF may serve as an alternative sample for diagnosing acute chikungunya in specific settings, a negative result cannot rule out an infection. Further research is needed to investigate whether OF and urine collected later in the disease course when serum becomes RT-qPCR-negative may be helpful in CHIKV diagnosis and surveillance, as well as to determine whether urine and OF pose any risk of CHIKV transmission.

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Section: Discussionmentioning

confidence: 99%

Detection of Chikungunya Virus RNA in Oral Fluid and Urine: An Alternative Approach to Diagnosis?

Jacob-Nascimento,

Portilho,

Anjos

et al. 2024

Viruses

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“…Data relating to prolonged excretion are potentially not generalizable to endemic settings where viremia is shorter, particularly in the setting of reinfection. PCR is used less frequently on CSF than serologic tests (though it is unclear whether this relates to access or better diagnostic sensitivity) [37]. Mosquitos and both fresh and formalin-fixed paraffin-embedded human tissues are also described [89,95,96].…”

Section: Specimens For Molecular Diagnosismentioning

confidence: 99%

“…Antibody detection is the commonest diagnostic modality requested to support the clinical diagnosis of DENV infection. It is generally performed on serum or plasma, though dried blood spots of venous or capillary blood, saliva and CSF can be used [37,84,86,87,[141][142][143]. Use in diagnosis is hampered by the degree of cross-reactivity between flaviviruses of the viral E protein in serologic assays, against which most IgG and IgM antibodies used in diagnosis are directed [67].…”

Section: Antibody Detectionmentioning

confidence: 99%

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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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“…The detection of inflammatory biomarkers in the CSF can provide valuable information about the immune response in the neuroinvasive arboviruses DENV and CHIKV [10]. In addition, neurological symptoms are not specific for neuroarboviruses, and the routine CSF analysis is frequently normal, making diagnosis difficult [18,19]. This study aims to evaluate neopterin and CXCL-10 biomarkers in CSF samples for the diagnosis of neuroinvasive DENV and CHIKV.…”

Section: Introductionmentioning

confidence: 99%

Neopterin and CXCL-10 in Cerebrospinal Fluid as Potential Biomarkers of Neuroinvasive Dengue and Chikungunya

et al. 2021

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Dengue (DENV) and chikungunya viruses (CHIKV) cause severe neurological complications, sometimes undiagnosed. Therefore, the use of more accessible neuroinflammatory biomarkers can be advantageous considering their diagnostic and prognostic potential for aggravated clinical outcomes. In this study, we aimed to evaluate neopterin and C-X-C motif chemokine ligand 10 (CXCL-10) in cerebrospinal fluid (CSF) for the diagnosis of neuroinvasive DENV and CHIKV. We analyzed the CSF of 66 patients with neurological disorders, comprising 12 neuroinvasive DENV/CHIKV, 20 inflammatory control (viral, bacterial, and fungal meningitis, and autoimmune disorders), and 24 noninflammatory control (cerebrovascular disease, dementia, neoplasm). There was no difference between the concentration of CSF neopterin in the neuroinvasive DENV/CHIKV and control groups. However, there was a significant difference in the CXCL-10 level when comparing the neuroinvasive DENV/CHIKV group and the non-inflammatory control (p < 0.05). Furthermore, we found a linear correlation between neopterin and CXCL-10 CSF levels in the three groups. For the DENV/CHIKV neuroinvasive diagnosis, the ROC curve showed the best cut-off values for CSF neopterin at 11.23 nmol/L (sensitivity of 67% and specificity of 63%), and for CSF CXCL-10 at 156.5 pg/mL (91.7% sensitivity and specificity). These results show that CXCL-10 in CSF represents an accurate neuroinflammatory biomarker that may contribute to neuroinvasive DENV/CHIKV diagnosis.

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Use of Cerebrospinal Fluid for the Diagnosis of Neuroinvasive Dengue, Zika, and Chikungunya: A 19-year systematic review

Cited by 7 publications

References 25 publications

Detection of Chikungunya Virus RNA in Oral Fluid and Urine: An Alternative Approach to Diagnosis?

Detection of Chikungunya Virus RNA in Oral Fluid and Urine: An Alternative Approach to Diagnosis?

Dengue: A review of laboratory diagnostics in the vaccine age

Neopterin and CXCL-10 in Cerebrospinal Fluid as Potential Biomarkers of Neuroinvasive Dengue and Chikungunya

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