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BACKGROUND: There is interest in lingering non-specific symptoms after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, referred to as Long coronavirus disease 2019 (Long COVID-19). It remains unknown whether the risk of Long COVID-19 is associated with pre-existing comorbidities or initial COVID-19 severity, including infections due to new Omicron lineages which predominated in 2023. OBJECTIVES: The aim of this case report was to characterize the clinical features of acute XBB.1.5 infection followed by Long COVID-19. METHODS: We followed a 73-year old female resident of Rio de Janeiro with laboratory-confirmed SARS-CoV-2 during acute infection and subsequent months. The SARS-CoV-2 lineage was determined by genome sequencing. FINDINGS: The participant denied comorbidities and had completed a two-dose vaccination schedule followed by two booster doses eight months prior to SARS-CoV-2 infection. Primary infection by viral lineage XBB.1.5. was clinically mild, but the participant subsequently reported persistent fatigue. MAIN CONCLUSIONS: This case demonstrates that Long COVID-19 may develop even after mild disease due to SARS-CoV-2 in fully vaccinated and boosted individuals without comorbidities. Continued monitoring of new SARS-CoV-2 lineages and associated clinical outcomes is warranted. Measures to prevent infection should continue to be implemented including development of new vaccines and antivirals effective against novel variants.
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COVID-19 , Femenino , Humanos , Anciano , COVID-19/complicaciones , SARS-CoV-2 , Síndrome Post Agudo de COVID-19 , Brasil , Mapeo CromosómicoRESUMEN
This was a household-based prospective cohort study conducted in Rio de Janeiro, in which people with laboratory-confirmed coronavirus disease 2019 (COVID-19) and their household contacts were followed from April 2020 through June 2022. Ninety-eight reinfections were identified, with 71 (72.5%) confirmed by genomic analyses and lineage definition in both infections. During the pre-Omicron period, 1 dose of any COVID-19 vaccine was associated with a reduced risk of reinfection, but during the Omicron period not even booster vaccines had this effect. Most reinfections were asymptomatic or milder in comparison with primary infections, a justification for continuing active surveillance to detect infections in vaccinated individuals. Our findings demonstrated that vaccination may not prevent infection or reinfection with severe acute respiratory syndrome coronavirus 2 (SARS CoV-2). Therefore we highlight the need to continuously update the antigenic target of SARS CoV-2 vaccines and administer booster doses to the population regularly, a strategy well established in the development of vaccines for influenza immunization programs.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Estudios Prospectivos , Reinfección/epidemiología , Vacunas contra la COVID-19 , Brasil/epidemiologíaRESUMEN
Introduction: Infection with human T cell lymphotropic virus type 1 (HTLV-1) is endemic in Brazil and is linked with pro-inflammatory conditions including HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a chronic neuroinflammatory incapacitating disease that culminates in loss of motor functions. The mechanisms underlying the onset and progression of HAM/TSP are incompletely understood. Previous studies have demonstrated that inflammation and infectious agents can affect the expression of cellular prion protein (PrPC) in immune cells. Methods: Here, we investigated whether HTLV-1 infection affected PrPC content in cell lines and primary CD4+cells in vitro using flow cytometry and western blot assays. Results: We found that HTLV-1 infection decreased the expression levels of PrPC and HTLV-1 Orf I encoded p12, an endoplasmic reticulum resident protein also known to affect post-transcriptionally cellular proteins such as MHC-class I and the IL-2 receptor. In addition, we observed a reduced percentage of CD4+ T cells from infected individuals expressing PrPC, which was reflected by IFN type II but not IL-17 expression. Discussion: These results suggested that PrPC downregulation, linked to both HTLV-1 p12 and IFN-γ expression in CD4+ cells, may play a role in the neuropathogenesis of HTLV-1 infection.
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COVID-19 vaccines have dramatically reduced rates of severe infection requiring hospitalization. However, SARS-CoV-2 variants have reduced vaccine effectiveness at preventing any symptomatic infection. This real-world study analyzed binding and neutralizing antibodies generated after complete vaccination and boosting across three vaccine platforms. Binding antibodies decayed most slowly in people under 60 with hybrid immunity. Neutralizing antibodies against Omicron BA.1 were reduced compared to other variants. The anamnestic anti-spike IgG response to the first boost was more pronounced than after the second boost. Monitoring of the effects of SARS-CoV-2 mutations on disease severity and the effectiveness of therapeutics is warranted.
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Vacunas contra la COVID-19 , COVID-19 , Adulto , Humanos , Vacuna BNT162 , COVID-19/prevención & control , SARS-CoV-2/genética , Vacunación , Anticuerpos Neutralizantes , Anticuerpos AntiviralesRESUMEN
BACKGROUND: While nasopharyngeal (NP) swabs are considered the gold standard for severe acute respiratory coronavirus 2 (SARS-CoV-2) real-time reverse transcriptase-polymerase chain reaction (RT-PCR) detection, several studies have shown that saliva is an alternative specimen for COVID-19 diagnosis and screening. METHODS: To analyze the utility of saliva for the diagnosis of COVID-19 during the circulation of the Omicron variant, participants were enrolled in an ongoing cohort designed to assess the natural history of SARS-CoV-2 infection in adults and children. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Cohen's kappa coefficient were calculated to assess diagnostic performance. RESULTS: Overall, 818 samples were collected from 365 outpatients from January 3 to February 2, 2022. The median age was 32.8 years (range: 3-94 years). RT-PCR for SARS-CoV-2 was confirmed in 97/121 symptomatic patients (80.2%) and 62/244 (25.4%) asymptomatic patients. Substantial agreement between saliva and combined nasopharyngeal/oropharyngeal samples was observed with a Cohen's kappa value of 0.74 [95% confidence interval (CI): 0.67-0.81]. Sensitivity was 77% (95% CI: 70.9-82.2), specificity 95% (95% CI: 91.9-97), PPV 89.8% (95% CI: 83.1-94.4), NPV 87.9% (95% CI: 83.6-91.5), and accuracy 88.5% (95% CI: 85.0-91.4). Sensitivity was higher among samples collected from symptomatic children aged three years and older and adolescents [84% (95% CI: 70.5-92)] with a Cohen's kappa value of 0.63 (95% CI: 0.35-0.91). CONCLUSIONS: Saliva is a reliable fluid for detecting SARS-CoV-2, especially in symptomatic children and adolescents during the circulation of the Omicron variant.
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COVID-19 , Pacientes Ambulatorios , Adolescente , Adulto , Niño , Humanos , Saliva , Prueba de COVID-19 , SARS-CoV-2/genética , COVID-19/diagnóstico , Nasofaringe , Manejo de EspecímenesRESUMEN
BACKGROUND There is interest in lingering non-specific symptoms after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, referred to as Long coronavirus disease 2019 (Long COVID-19). It remains unknown whether the risk of Long COVID-19 is associated with pre-existing comorbidities or initial COVID-19 severity, including infections due to new Omicron lineages which predominated in 2023. OBJECTIVES The aim of this case report was to characterize the clinical features of acute XBB.1.5 infection followed by Long COVID-19. METHODS We followed a 73-year old female resident of Rio de Janeiro with laboratory-confirmed SARS-CoV-2 during acute infection and subsequent months. The SARS-CoV-2 lineage was determined by genome sequencing. FINDINGS The participant denied comorbidities and had completed a two-dose vaccination schedule followed by two booster doses eight months prior to SARS-CoV-2 infection. Primary infection by viral lineage XBB.1.5. was clinically mild, but the participant subsequently reported persistent fatigue. MAIN CONCLUSIONS This case demonstrates that Long COVID-19 may develop even after mild disease due to SARS-CoV-2 in fully vaccinated and boosted individuals without comorbidities. Continued monitoring of new SARS-CoV-2 lineages and associated clinical outcomes is warranted. Measures to prevent infection should continue to be implemented including development of new vaccines and antivirals effective against novel variants.
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HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neurodegenerative disease that leads to motor impairment due to a chronic inflammatory process in the central nervous system (CNS). However, the HAM/TSP pathogenesis is not completely clear, and biomarkers to define the disease prognosis are still necessary. Thus, we aimed to identify biomarkers for HAM/TSP and potential mechanisms involved in disease development. To that end, the concentrations of VILIP-1, BDNF, VEGF, ß-NGF, TGF-ß1, fractalkine/CX3CL1, IL-6, IL-18, and TNF-α, and the soluble forms of TREM-1, TREM-2, and RAGE, were assessed using a multiplex bead-based immunoassay in paired cerebrospinal fluid (CSF) and serum samples from HAM/TSP patients (n = 20), asymptomatic HTLV-1 carriers (AC) (n = 13), and HTLV-1-seronegative individuals (n = 9), with the results analyzed according to the speed of HAM/TSP progression. HAM/TSP patients had elevated fractalkine in the serum but not in the CSF, particularly those with low neuroinflammatory activity (CSF/serum ratio of neopterin <1 and of CXCL10 < 2). HAM/TSP patients with normal CSF levels of neurofilament light chain (NfL) showed elevated ß-NGF in serum, and serum BDNF levels were increased in HTLV-1-infected individuals, particularly in HTLV-1 AC. Both HTLV-1 AC and HAM/TSP patients had lower TGF-ß1 levels in CSF compared to uninfected individuals, and HAM/TSP patients with active CNS inflammation showed higher CSF levels of IL-18, which correlated with markers of inflammation, neuronal death, and blood−brain-barrier permeability. Although none of the factors evaluated were associated with the speed of HAM/TSP progression, reduced TGF-ß1 levels in CSF suggest that suppressive responses to control subclinical and/or active neurodegeneration are impaired, while increased CSF IL-18 indicates the involvement of inflammasome-mediated mechanisms in HAM/TSP development.
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Infecciones por HTLV-I , Virus Linfotrópico T Tipo 1 Humano , Enfermedades Neurodegenerativas , Paraparesia Espástica Tropical , Humanos , Quimiocina CX3CL1 , Interleucina-18 , Factor de Crecimiento Transformador beta1 , Factor de Crecimiento Nervioso , Neopterin/líquido cefalorraquídeo , Factor de Necrosis Tumoral alfa , Inflamasomas , Factor Neurotrófico Derivado del Encéfalo , Interleucina-6 , Receptor Activador Expresado en Células Mieloides 1 , Factor A de Crecimiento Endotelial Vascular , Biomarcadores , Inflamación , Infecciones por HTLV-I/patologíaRESUMEN
Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an inflammatory neurodegenerative disease that affects motor, urinary, intestinal, and sensory functions. Typically, HAM/TSP is slowly progressive, but it may vary from limited motor disability after decades (very slow progression) to loss of motor function in a few years from disease onset (rapid). In this study, we aimed to identify prognostic biomarkers for HAM/TSP to support patient management. Thus, proteomic analysis of the cerebrospinal fluid (CSF) was performed with samples from HTLV-1 asymptomatic carriers (AC) (n=13) and HAM/TSP patients (n=21) with rapid, typical, and very slow progression using quantitative label-free liquid chromatography/tandem mass spectrometry. Enrichment analyses were also carried out to identify key biological processes associated with distinct neurological conditions in HTLV-1 infection. Candidate biomarkers were validated by ELISA in paired CSF and serum samples, and samples from HTLV-1-seronegative individuals (n=9) were used as controls. CSF analysis identified 602 proteins. Leukocyte/cell activation, immune response processes and neurodegeneration pathways were enriched in rapid progressors. Conversely, HTLV-1 AC and HAM/TSP patients with typical and very slow progression had enriched processes for nervous system development. Differential expression analysis showed that soluble vascular cell adhesion molecule 1 (sVCAM-1), chitotriosidase 1 (CHIT1), and cathepsin C (CTSC) were upregulated in HAM/TSP. However, only CHIT1 was significantly elevated after validation, particularly in HAM/TSP rapid progressors. In contrast, none of these biomarkers were altered in serum. Additionally, CSF CHIT1 levels in HAM/TSP patients positively correlated with the speed of HAM/TSP progression, defined as points in the IPEC-2 HAM/TSP disability scale per year of disease, and with CSF levels of phosphorylated neurofilament heavy chain, neopterin, CXCL5, CXCL10, and CXCL11. In conclusion, higher CSF levels of CHIT1 were associated with HAM/TSP rapid progression and correlated with other biomarkers of neuroinflammation and neurodegeneration. Therefore, we propose CHIT1 as an additional or alternative CSF biomarker to identify HAM/TSP patients with a worse prognosis.
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Personas con Discapacidad , Virus Linfotrópico T Tipo 1 Humano , Trastornos Motores , Enfermedades Neurodegenerativas , Paraparesia Espástica Tropical , Biomarcadores , Hexosaminidasas , Humanos , Paraparesia Espástica Tropical/diagnóstico , ProteómicaRESUMEN
We describe a case of prolonged COVID-19 caused by the SARS-CoV-2 Gamma variant in a fully vaccinated healthcare worker, 387 days after an infection caused by lineage B.1.1.33. Infections were confirmed by whole-genome sequencing and corroborated by the detection of neutralizing antibodies in convalescent serum samples. Considering the permanent exposure of this healthcare worker to SARS-CoV-2, the waning immunity after the first infection, the low efficacy of the inactivated vaccine at preventing COVID-19, the immune escape of the Gamma variant (VOC), and the burden of post-COVID syndrome, this individual would have benefited from an additional dose of a heterologous vaccine.
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COVID-19 , SARS-CoV-2 , Brasil , COVID-19/complicaciones , COVID-19/terapia , Humanos , Inmunización Pasiva , Reinfección , Vacunas de Productos Inactivados , Sueroterapia para COVID-19 , Síndrome Post Agudo de COVID-19RESUMEN
Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neurodegenerative disease due to axonal damage of the corticospinal secondary to an inflammatory response against infected T-cells. In the present work, we aimed to evaluate biomarkers of neurodegeneration and neuroinflammation in the definition of HAM/TSP prognosis. Neurofilament light (NfL) and phosphorylated heavy (pNfH) chains, total Tau protein, cellular prion protein (PrPc), inflammatory chemokines, and neopterin were quantified in paired cerebrospinal fluid (CSF) and serum samples from HAM/TSP patients (n=21), HTLV-1 asymptomatic carriers (AC) (n=13), and HTLV-1 seronegative individuals with non-inflammatory non-degenerative neurological disease (normal-pressure hydrocephalus) (n=9) as a control group. HTLV-1 proviral load in peripheral blood mononuclear cells and the expression of chemokine receptors CCR4, CCR5, and CXCR3 in infected CD4+ T-cells (HTLV-1 Tax+ cells) were also assessed. CSF levels of Tau, NfL, and pNfH were similar between groups, but PrPc and neopterin were elevated in HAM/TSP patients. Most individuals in the control group and all HTLV-1 AC had CSF/serum neopterin ratio < 1.0, and two-thirds of HAM/TSP patients had ratio values > 1.0, which positively correlated with the speed of disease progression and pNfH levels, indicating active neuroinflammation. HAM/TSP patients showed high serum levels of CXCR3-binding chemokines (CXCL9, CXCL10, and CXCL11) and elevated CSF levels of CCL2, CCL3, CCL4, CCL17, CXCL5, CXCL10, and CXCL11. Indeed, CXCL10 concentration in CSF of HAM/TSP patients was 5.8-fold and 8.7-fold higher in than in HTLV-1 AC and controls, respectively, and correlated with CSF cell counts. HAM/TSP patients with typical/rapid disease progression had CSF/serum CXCL10 ratio > 1.0 and a higher frequency of CXCR3+Tax+CD4+ T-cells in blood, which indicated a positive gradient for the migration of infected cells and infiltration into the central nervous system. In conclusion, the slow progression of HAM/TSP abrogates the usefulness of biomarkers of neuronal injury for the disease prognosis. Thus, markers of inflammation provide stronger evidence for HAM/TSP progression, particularly the CSF/serum neopterin ratio, which may contribute to overcome differences between laboratory assays.
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Citocinas , Virus Linfotrópico T Tipo 1 Humano/patogenicidad , Mediadores de Inflamación , Degeneración Nerviosa , Proteínas del Tejido Nervioso , Enfermedades Neurodegenerativas/diagnóstico , Paraparesia Espástica Tropical/diagnóstico , Adulto , Anciano , Biomarcadores/sangre , Biomarcadores/líquido cefalorraquídeo , Estudios de Casos y Controles , Estudios Transversales , Citocinas/sangre , Citocinas/líquido cefalorraquídeo , Progresión de la Enfermedad , Femenino , Interacciones Huésped-Patógeno , Humanos , Mediadores de Inflamación/sangre , Mediadores de Inflamación/líquido cefalorraquídeo , Masculino , Persona de Mediana Edad , Neopterin/sangre , Neopterin/líquido cefalorraquídeo , Proteínas del Tejido Nervioso/sangre , Proteínas del Tejido Nervioso/líquido cefalorraquídeo , Enfermedades Neurodegenerativas/sangre , Enfermedades Neurodegenerativas/líquido cefalorraquídeo , Enfermedades Neurodegenerativas/virología , Paraparesia Espástica Tropical/sangre , Paraparesia Espástica Tropical/líquido cefalorraquídeo , Paraparesia Espástica Tropical/virología , Valor Predictivo de las Pruebas , PronósticoRESUMEN
Adult T-cell leukemia/lymphoma (ATLL) is an aggressive malignancy of CD4+ T-cells associated with HTLV-1 infection. In this study, we used the model of immunodeficient NSG mice reconstituted with a functional human immune system (HIS) to investigate early events in HTLV-1 pathogenesis. Upon infection, human T-cells rapidly increased in the blood and lymphoid tissues, particularly CD4+CD25+ T-cells. Proliferation of CD4+ T-cells in the spleen and mesenteric lymph nodes (MLN) correlated with HTLV-1 proviral load and CD25 expression. In addition, splenomegaly, a common feature of ATLL in humans, was also observed. CD4+ and CD8+ T-cells predominantly displayed an effector memory phenotype (CD45RA-CCR7-) and expressed CXCR3 and CCR5 chemokine receptors, suggesting the polarization into a Th1 phenotype. Activated CD8+ T-cells expressed granzyme B and perforin; however, the interferon-γ response by these cells was limited, possibly due to elevated PD-1 expression and increased frequency of CD4+FoxP3+ regulatory T-cells in MLN. Thus, HTLV-1-infected HIS-NSG mice reproduced several characteristics of infection in humans, and it may be helpful to investigate ATLL-related events and to perform preclinical studies. Moreover, aspects of chronic infection were already present at early stages in this experimental model. Collectively, we suggest that HTLV-1 infection modulates host immune responses to favor viral persistence.
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Linfocitos T CD8-positivos/inmunología , Diferenciación Celular/inmunología , Infecciones por HTLV-I/virología , Virus Linfotrópico T Tipo 1 Humano/inmunología , Animales , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/virología , Infecciones por HTLV-I/inmunología , Virus Linfotrópico T Tipo 1 Humano/metabolismo , Humanos , Leucemia-Linfoma de Células T del Adulto/inmunología , Leucemia-Linfoma de Células T del Adulto/patología , Leucemia-Linfoma de Células T del Adulto/virología , Antígenos Comunes de Leucocito/metabolismo , Ratones , Infección Persistente/inmunología , Infección Persistente/virologíaRESUMEN
Human T-lymphotropic virus type 1 (HTLV-1) provirus expression is mainly directed by Tax-responsive elements (TRE) within the long terminal repeats (LTR). Mutations in TRE can reduce provirus expression and since a high proviral load (PVL) is a risk factor for the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), we evaluated polymorphisms in the 5' LTR and the association with PVL and disease progression. HTLV-1 LTR and tax sequences derived from asymptomatic carriers (AC) and HAM/TSP patients followed in a longitudinal study were analysed according to PVL and clinical severity. Individuals infected with HTLV-1 presenting the canonical TRE, considering strain ATK-1 as the consensus, displayed sustained higher PVL. By contrast, an LTR A125G mutation in TRE was associated with slightly reduced PVL only in HAM/TSP patients, although it did not influence the speed of disease progression. Moreover, this polymorphism was frequent in Latin American strains of the HTLV-1 Cosmopolitan Transcontinental subtype. Therefore, polymorphisms in the 5' TRE of HTLV-1 may represent one of the factors influencing PVL in HAM/TSP patients, especially in the Latin American population. Indeed, higher PVL in the peripheral blood has been associated with an increased inflammatory activity in the spinal cord and to a poorer prognosis in HAM/TSP. However, this event was not associated with TRE polymorphisms.
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Productos del Gen tax , Virus Linfotrópico T Tipo 1 Humano/genética , Virus Linfotrópico T Tipo 1 Humano/fisiología , Paraparesia Espástica Tropical/virología , Polimorfismo Genético , Secuencias Repetidas Terminales , Carga Viral , Anciano , Enfermedades Asintomáticas , Portador Sano/virología , Progresión de la Enfermedad , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Mutación , Filogenia , Provirus/genética , Provirus/fisiologíaRESUMEN
BACKGROUND: Zika virus (ZIKV) is associated with severe congenital abnormalities and laboratory diagnosis of antenatal infection is difficult. Here we evaluated ZIKV neutralizing antibody (nAb) kinetics in infants born to mothers with PCR-confirmed ZIKV infection during pregnancy. METHODS: Neonates (nâ =â 98) had serum specimens tested repeatedly for ZIKV nAb over the first 2 years of life using virus neutralization test (VNT). ZIKV neonatal infection was confirmed by RT-PCR in blood or urine and/or presence of ZIKV IgM antibodies, and results were correlated with infant clinical features. RESULTS: Postnatal laboratory evidence of ZIKV vertical transmission was obtained for 60.2% of children, while 32.7% exhibited clinical abnormalities. Congenital abnormalities were found in 37.3% of children with confirmed ZIKV infection and 31.0% of children without confirmed infection (Pâ =â .734). All but 1 child displayed a physiologic decline in ZIKV nAb, reflecting maternal antibody decay, despite an early ZIKV-IgM response in one-third of infants. CONCLUSIONS: Infants with antenatal ZIKV exposure do not develop ZIKV nAb despite an early IgM response. Therefore, ZIKV VNT in children is not useful for diagnosis of congenital infection. In light of these findings, it remains to be determined if children infected in utero are potentially susceptible to reinfection.
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Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Transmisión Vertical de Enfermedad Infecciosa , Complicaciones Infecciosas del Embarazo , Infección por el Virus Zika/diagnóstico , Virus Zika/inmunología , Biomarcadores , Femenino , Humanos , Inmunoglobulina M , Lactante , Recién Nacido , Cinética , Masculino , Reacción en Cadena de la Polimerasa , Embarazo , Virus Zika/genética , Virus Zika/aislamiento & purificación , Infección por el Virus Zika/congénitoRESUMEN
Patients with coronavirus disease 2019 (COVID-19) can present with distinct neurological manifestations. This study shows that inflammatory neurological diseases were associated with increased levels of interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12, chemokine (C-X-C motif) ligand 8 (CXCL8), and CXCL10 in the cerebrospinal fluid. Conversely, encephalopathy was associated with high serum levels of IL-6, CXCL8, and active tumor growth factor ß1. Inflammatory syndromes of the central nervous system in COVID-19 can appear early, as a parainfectious process without significant systemic involvement, or without direct evidence of severe acute respiratory syndrome coronavirus 2 neuroinvasion. At the same time, encephalopathy is mainly influenced by peripheral events, including inflammatory cytokines. ANN NEUROL 2021;89:1041-1045.
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COVID-19/sangre , COVID-19/líquido cefalorraquídeo , Mediadores de Inflamación/sangre , Mediadores de Inflamación/líquido cefalorraquídeo , Enfermedades del Sistema Nervioso/sangre , Enfermedades del Sistema Nervioso/líquido cefalorraquídeo , Biomarcadores/sangre , Biomarcadores/líquido cefalorraquídeo , COVID-19/epidemiología , Citocinas/sangre , Citocinas/líquido cefalorraquídeo , Humanos , Enfermedades del Sistema Nervioso/epidemiologíaRESUMEN
Toxoplasmosis is the most prevalent zoonosis in the world and is associated with a large spectrum of diseases. Acute acquired toxoplasmosis (AAT) is considered a benign and self-limiting disease but severe postnatal infections have been reported, particularly in South America. Laboratory diagnosis is based on the detection of anti-Toxoplasma gondii IgM, IgG, and presence of low IgG avidity. However, these assays present limitations, and therefore, PCR has been suggested as an alternative diagnostic tool. In this study, we performed real-time and nested PCR in DNA blood samples from 59 individuals with AAT lasting less than 80 days. None of the patients had parasitic DNA detected by PCR, even in the more severe cases or when blood was collected early after disease onset. These negative results indicate that the parasitemia kinetics needs investigation to determine the best time for blood sampling, especially in immunocompetent individuals. Thus, we emphasize that a negative PCR result does not exclude recent T. gondii infection, and serological criteria are still decisive for the laboratory diagnosis of AAT.
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Técnicas de Diagnóstico Molecular , Reacción en Cadena de la Polimerasa , Toxoplasma/aislamiento & purificación , Toxoplasmosis/diagnóstico , Enfermedad Aguda , Adolescente , Adulto , Niño , ADN Protozoario/sangre , ADN Protozoario/genética , Femenino , Humanos , Persona de Mediana Edad , Resultados Negativos , Toxoplasma/genética , Toxoplasmosis/sangre , Toxoplasmosis/parasitología , Adulto JovenRESUMEN
BACKGROUND: Cutaneous leishmaniasis (CL) is an infectious vector-borne disease caused by protozoa of the Leishmania genus that affects humans and animals. The distribution of parasites in the lesion is not uniform, and there are divergences in the literature about the choice of the better sampling site for diagnosis-inner or outer edge of the ulcerated skin lesion. In this context, determining the region of the lesion with the highest parasite density and, consequently, the appropriate site for collecting samples can define the success of the laboratory diagnosis. Hence, this study aims to comparatively evaluate the parasite load by qPCR, quantification of amastigotes forms in the direct exam, and the histopathological profile on the inner and outer edges of ulcerated CL lesions. METHODS: Samples from ulcerated skin lesions from 39 patients with confirmed CL were examined. We performed scraping of the ulcer inner edge (base) and outer edge (raised border) and lesion biopsy for imprint and histopathological examination. Slides smears were stained by Giemsa and observed in optical microscopy, the material contained on the smears was used to determine parasite load by quantitative real-time PCR (qPCR) with primers directed to the Leishmania (Viannia) minicircle kinetoplast DNA. The histopathological exam was performed to evaluate cell profile, tissue alterations and semi-quantitative assessment of amastigote forms in inner and outer edges. PRINCIPAL FINDINGS: Parasite loads were higher on the inner edge compared to the outer edge of the lesions, either by qPCR technique (P<0.001) and histopathological examination (P< 0.003). There was no significant difference in the parasite load between the imprint and scraping on the outer edge (P = 1.0000). CONCLUSION/SIGNIFICANCE: The results suggest that clinical specimens from the inner edge of the ulcerated CL lesions are the most suitable for both molecular diagnosis and direct parasitological examination.
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ADN de Cinetoplasto/análisis , Leishmania braziliensis , Leishmaniasis Cutánea/parasitología , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Úlcera/parasitología , Adulto , Femenino , Humanos , Leishmania braziliensis/genética , Leishmania braziliensis/aislamiento & purificación , Masculino , Persona de Mediana Edad , Carga de ParásitosRESUMEN
OBJECTIVES: To analyze the cerebrospinal fluid (CSF) of patients with SARS-CoV-2 infection and neurological manifestations to provide evidence for the understanding of mechanisms associated with central nervous system (CNS) involvement in COVID-19. METHODS: Patients (n = 58) were grouped according to their main neurological presentation: headache (n = 14); encephalopathy (n = 24); inflammatory neurological diseases, including meningoencephalitis (n = 4), acute myelitis (n = 3), meningitis (n = 2), acute disseminated encephalomyelitis (ADEM) (n = 2), encephalitis (n = 2), and neuromyelitis optica (n = 1); and Guillain-Barré syndrome (n = 6). Data regarding age, sex, cerebrovascular disease, and intracranial pressure were evaluated in combination with CSF profiles defined by cell counts, total protein and glucose levels, concentration of total Tau and neurofilament light chain (NfL) proteins, oligoclonal band patterns, and detection of SARS-CoV-2 RNA. RESULTS: CSF of patients with inflammatory neurological diseases was characterized by pleocytosis and elevated total protein and NfL levels. Patients with encephalopathy were mostly older men (mean age of 61.0 ± 17.6 years) with evidence of cerebrovascular disease. SARS-CoV-2 RNA in CSF was detected in 2 of 58 cases: a patient with refractory headache, and another patient who developed ADEM four days after onset of COVID-19 symptoms. Three patients presented intrathecal IgG synthesis, and four had identical oligoclonal bands in CSF and serum, indicating systemic inflammation. CONCLUSION: Patients with neurological manifestations associated with COVID-19 had diverse CSF profiles, even within the same clinical condition. Our findings indicate a possible contribution of viral replication on triggering CNS infiltration by immune cells and the subsequent inflammation promoting neuronal injury.
Asunto(s)
COVID-19/complicaciones , Enfermedades del Sistema Nervioso/líquido cefalorraquídeo , SARS-CoV-2 , Adulto , Anciano , COVID-19/líquido cefalorraquídeo , Femenino , Humanos , Inflamación/diagnóstico , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/etiologíaRESUMEN
BACKGROUND: Headache is a frequent complaint in COVID-19 patients. However, no detailed information on headache characteristics is provided in these reports. Our objective is to describe the characteristics of headache and the cerebrospinal fluid (CSF) profile in COVID-19 patients, highlighting the cases of isolated intracranial hypertension. METHODS: In this cross-sectional study, we selected COVID-19 patients who underwent lumbar puncture due to neurological complaints from April to May 2020. We reviewed clinical, imaging, and laboratory data of patients with refractory headache in the absence of other encephalitic or meningitic features. CSF opening pressures higher than 250 mmH2O were considered elevated, and from 200 to 250 mmH2O equivocal. RESULTS: Fifty-six COVID-19 patients underwent lumbar puncture for different neurological conditions. A new, persistent headache that prompted a CSF analysis was diagnosed in 13 (23.2%). The pain was throbbing, holocranial or bilateral in the majority of patients. All patients had normal CSF analysis and RT-qPCR for SARS-CoV-2 was negative in all samples. Opening pressure >200 mmH2O was present in 11 patients and, in six of these, > 250 mmH2O. 6/13 patients had complete improvement of the pain, five had partial improvement, and two were left with a daily persistent headache. CONCLUSIONS: In a significant proportion of COVID-19 patients, headache was associated to intracranial hypertension in the absence of meningitic or encephalitic features. Coagulopathy associated with COVID-19 could be an explanation, but further studies including post-mortem analysis of areas of production and CSF absorption (choroid plexuses and arachnoid granulations) are necessary to clarify this issue.