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1.
Age Ageing ; 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33620381

RESUMO

BACKGROUND: Frail older persons may have an atypical presentation of COVID-19. The value of rRT-PCR testing for identifying SARS-CoV-2 nursing homes (NH) residents is not known. OBJECTIVE: To determine whether (i) atypical symptoms may predict rRT-PCR results and (ii) rRT-PCR results may predict immunization against SARS-CoV-2 in NH residents. DESIGN: A retrospective longitudinal study. SETTING: eight NHs with at least ten rRT-PCR-positive residents. SUBJECTS: 456 residents. METHODS: Typical and atypical symptoms recorded in residents' files during the 14 days before and after rRT-PCR testing were analyzed. Residents underwent blood testing for IgG-SARS-CoV-2 nucleocapsid protein 6 to 8 weeks after testing. Univariate and multivariate analyses compared symptoms and immunization rates in rRT-PCR-positive and negative residents. RESULTS: 161 residents had a positive rRT-PCR (35.3%), 17.4% of whom were asymptomatic before testing. Temperature > 37.8°C, oxygen saturation < 90%, unexplained anorexia, behavioural change, exhaustion, malaise, and falls before testing were independent predictors of a further positive rRT-PCR. Among the rRT-PCR-positive residents, 95.2% developed SARS-CoV-2 antibodies vs 7.6% in the rRT-PCR-negative residents. Among the residents with a negative rRT-PCR, those who developed SARS-CoV-2 antibodies more often had typical or atypical symptoms (p = 0.02 and < 0.01, respectively). CONCLUSION: This study supports a strategy based on (i) testing residents with typical or unexplained atypical symptoms for an early identification of the first SARS-CoV-2 cases, (ii) rT-PCR testing for identifying COVID-19 residents, (iii) repeated wide-facility testing (including asymptomatic cases) as soon as a resident is tested positive for SARS-CoV-2, and (iv) implementing SARS-CoV-2 infection control measures in rRT-PCR-negative residents when they have unexplained typical or atypical symptoms.

2.
J Med Virol ; 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33554363

RESUMO

The implementation of rapid diagnostic tests (RDTs) may enhance the efficiency of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing, as RDTs are widely accessible and easy to use. The aim of this study was to evaluate the performance of a diagnosis strategy based on a combination of antigen and immunoglobulin M (IgM) or immunoglobulin G (IgG) serological RDTs. Plasma and nasopharyngeal samples were collected between 14 March and 11 April 2020 at hospital admission from 45 patients with reverse transcription polymerase chain reaction (RT-PCR) confirmed COVID-19 and 20 negative controls. SARS-CoV-2 antigen (Ag) was assessed in nasopharyngeal swabs using the Coris Respi-Strip. For IgM/IgG detection, SureScreen Diagnostics and Szybio Biotech RDTs were used in addition to laboratory assays (Abbott Alinity i SARS-CoV-2 IgG and Theradiag COVID-19 IgM enzyme-linked immunosorbent assay). Using the Ag RDT, 13 out of 45 (29.0%) specimens tested positive, the sensitivity was 87.0% for cycle threshold (Ct ) values ≤25% and 0% for Ct values greater than 25. IgG detection was associated with high Ct values and the amount of time after the onset of symptoms. The profile of isolated IgM on RDTs was more frequently observed during the first and second week after the onset of symptoms. The combination of Ag and IgM/IgG RDTs enabled the detection of up to 84.0% of COVID-19 confirmed cases at hospital admission. Antigen and antibody-based RDTs showed suboptimal performances when used alone. However when used in combination, they are able to identify most COVID-19 patients admitted in an emergency department.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33594740

RESUMO

As breastfeeding is of utmost importance for child development and survival, identifying whether breast milk is a route of transmission for human viruses is critical. Based on the principle of Koch's postulate, we propose an analytical framework to determine the plausibility of viral transmission by breast milk. This framework is based on five criteria: viral infection in children receiving breastmilk from infected mothers; the presence of virus, viral antigen or viral genome in the breast milk of infected mothers; the evidence for the virus in breast milk being infectious; the attempts to rule out other transmission modalities; and the reproduction of viral transmission by oral inoculation in an animal model. We searched for evidence in published reports to determine whether the 5 criteria are fulfilled for 16 human viruses that are suspected to be transmissible by breast milk. We considered breast milk transmission is proven if all 5 criteria are fulfilled, as probable if 4 of the 5 criteria are met, as possible if 3 of the 5 criteria are fulfilled and as unlikely if less than 3 criteria are met. Only five viruses have proven transmission through breast milk: human T-cell lymphotropic virus 1, human immunodeficiency virus, human cytomegalovirus, dengue virus and Zika virus. The other 11 viruses fulfilled some but not all criteria and were categorized accordingly. Our framework analysis is useful for guiding public health recommendations and for identifying knowledge gaps amenable to original experiments.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33410887

RESUMO

Importance: Recent studies have suggested that olfactory dysfunction and gustatory dysfunction are associated with coronavirus disease 2019 (COVID-19). However, olfaction has been evaluated solely on reported symptoms, after COVID-19 diagnosis, and in both mild and severe COVID-19 cases, but rarely has it been assessed in prospectively unselected populations. Objective: To evaluate the diagnostic value of a semiobjective olfactory test developed to assess patient-reported chemosensory dysfunction prior to testing for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients attending a COVID-19 screening facility. Design, Setting, and Participants: This prospective diagnostic study with participants and observers blinded to COVID-19 status was conducted in a COVID-19 screening center of a tertiary university hospital in France from March 23 to April 22, 2020. Participants were 854 consecutively included health care workers or outpatients with symptoms or with close contact with an index case. Exclusion criteria were prior chemosensory dysfunction, testing inability, or contraindications (n = 45). Main Outcomes and Measures: Participants were interviewed to ascertain their symptoms and then underwent Clinical Olfactory Dysfunction Assessment (CODA), an ad hoc test developed for a simple and fast evaluation of olfactory function. This assessment followed a standardized procedure in which participants identified and rated the intensity of 3 scents (lavender, lemongrass, and mint) to achieve a summed score ranging from 0 to 6. The COVID-19 status was assessed using reverse transcriptase-polymerase chain reaction to detect the presence of SARS-CoV-2 in samples collected via nasopharyngeal swab (reference standard) to calculate the diagnostic values of patient-reported chemosensory dysfunction and CODA. Results: Of 809 participants, the female to male sex ratio was 2.8, and the mean (SD) age was 41.8 (13.0) years (range, 18-94 years). All participants, if symptomatic, had mild disease at the time of testing, and 58 (7.2%) tested positive for SARS-CoV-2. Chemosensory dysfunction was reported by 20 of 58 participants (34.5%) with confirmed COVID-19 vs 29 of 751 participants (3.9%) who tested negative for COVID-19 (absolute difference, 30.6% [95% CI, 18.3%-42.9%]). Olfactory dysfunction, either self-reported or clinically ascertained (CODA score ≤3), yielded similar sensitivity (0.31 [95% CI, 0.20-0.45] vs 0.34 [95% CI, 0.22-0.48]) and specificity (0.97 [95% CI, 0.96-0.98) vs 0.98 [95% CI, 0.96-0.99]) for COVID-19 diagnosis. Concordance was high between reported and clinically tested olfactory dysfunction, with a Gwet AC1 of 0.95 (95% CI, 0.93-0.97). Of 19 participants, 15 (78.9%) with both reported olfactory dysfunction and a CODA score of 3 or lower were confirmed to have COVID-19. The CODA score also revealed 5 of 19 participants (26.3%) with confirmed COVID-19 who had previously unperceived olfactory dysfunction. Conclusions and Relevance: In this prospective diagnostic study of outpatients with asymptomatic or mild to moderate COVID-19, systematically assessed anamnesis and clinical testing with the newly developed CODA were complementary and specific for chemosensory dysfunction. Olfactory dysfunction was suggestive of COVID-19, particularly when clinical testing confirmed anamnesis. However, normal olfaction was most common among patients with COVID-19.

5.
Sex Transm Infect ; 97(2): 134-140, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33397802

RESUMO

OBJECTIVES: In 2017, to reduce the proportion of men who have sex with men (MSM) in the undiagnosed HIV population in France (38%), HIV screening is advised each 3 months and STI screening is advised each year in multipartner MSM. Despite the range of testing solutions, over 40% of MSM were not tested for HIV and over 50% for STIs in the past year. Based on international experiments that offer screening solutions via online advertising, the French National Health Agency launched a programme (MemoDepistages) to provide a free self-sampling kit (SSK) for HIV and STIs. This article analyses the sociodemographic and behavioural characteristics of MSM in terms of kit acceptance and sample return. METHODS: Participants were registered for the programme online after ordering an SSK. The study included men aged over 18 years, living in one of the four selected French regions, and willing to disclose their postal and email address; they had health insurance, acknowledged more than one male partner in the past year, indicated a seronegative or unknown HIV status and were not taking medically prescribed pre-exposure prophylaxis drugs. Samples were collected by users and posted directly to the laboratory. Characteristics associated with kit acceptance and sample return were analysed using logistic regression. RESULTS: Overall, 7158 eligible MSM were offered to participate in the programme, with 3428 ordering the kit (47.9%) and 1948 returning their sample, leading to a return rate of 56.8% and an overall participation rate of 27.2%. Acceptance and return rates were strongly associated with sociodemographic characteristics, mainly education level but not with behavioural characteristics. Non-college graduates had lower acceptance (44.2%) and return rates (47.7%). CONCLUSION: The programme rapidly recruited a large number of MSM. It removed geographical inequalities related to screening access.

6.
J Infect Dis ; 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33206973

RESUMO

We assessed the expression of CD169, a type I interferon-inducible receptor, on monocytes (mCD169) in 53 adult patients admitted to the hospital during the COVID-19 outbreak for a suspicion of SARS-CoV-2 infection. mCD169 was strongly overexpressed in 30 out of 32 (93.7%) confirmed COVID-19 cases, compared to three out of 21 (14.3%) patients in whom the diagnosis of COVID-19 was finally ruled out. mCD169 was associated with the plasma interferon alpha level and thrombocytopenia. mCD169 testing may be helpful for the rapid triage of suspected COVID-19 patients during an outbreak.

7.
Front Cell Infect Microbiol ; 10: 546189, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33102251

RESUMO

Human milk is a significant source of different CD133+ and/or CD34+ stem/progenitor-like cell subsets in healthy women but their cell distribution and percentages in this compartment of HIV-positive women have not been explored. To date, a decrease of CD34+ hematopoietic stem and progenitor cell frequencies in peripheral blood and bone marrow of HIV-positive patients has been reported. Herein, human milk and peripheral blood samples were collected between day 2-15 post-partum from HIV-positive and HIV-negative women, and cells were stained with stem cell markers and analyzed by flow cytometry. We report that the median percentage of CD45+/highCD34-CD133+ cell subset from milk and blood was significantly higher in HIV-positive than in HIV-negative women. The percentage of CD45dimCD34-CD133+ cell subset from blood was significantly higher in HIV-positive than HIV-negative women. Moreover, percentages of CD45dimCD34+, CD45dimCD34+CD133-, and CD45+highCD34+CD133- cell subsets from blood were significantly lower in HIV-positive than HIV-negative women. The CD133+ stem/progenitor-like cell subsets are increased in early human milk and blood of HIV-positive women and are differentially distributed to CD34+ cell subset frequencies which are decreased in blood.

8.
mBio ; 11(4)2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32753493

RESUMO

The blood-brain barrier (BBB) largely prevents toxins and pathogens from accessing the brain. Some viruses have the ability to cross this barrier and replicate in the central nervous system (CNS). Zika virus (ZIKV) was responsible in 2015 to 2016 for a major epidemic in South America and was associated in some cases with neurological impairments. Here, we characterized some of the mechanisms behind its neuroinvasion using an innovative in vitro human BBB model. ZIKV efficiently replicated, was released on the BBB parenchyma side, and triggered subtle modulation of BBB integrity as well as an upregulation of inflammatory and cell adhesion molecules (CAMs), which in turn favored leukocyte recruitment. Finally, we showed that ZIKV-infected mouse models displayed similar CAM upregulation and that soluble CAMs were increased in plasma samples from ZIKV-infected patients. Our observations suggest a complex interplay between ZIKV and the BBB, which may trigger local inflammation, leukocyte recruitment, and possible cerebral vasculature impairment.IMPORTANCE Zika virus (ZIKV) can be associated with neurological impairment in children and adults. To reach the central nervous system, viruses have to cross the blood-brain barrier (BBB), a multicellular system allowing a tight separation between the bloodstream and the brain. Here, we show that ZIKV infects cells of the BBB and triggers a subtle change in its permeability. Moreover, ZIKV infection leads to the production of inflammatory molecules known to modulate BBB integrity and participate in immune cell attraction. The virus also led to the upregulation of cellular adhesion molecules (CAMs), which in turn favored immune cell binding to the BBB and potentially increased infiltration into the brain. These results were also observed in a mouse model of ZIKV infection. Furthermore, plasma samples from ZIKV-infected patients displayed an increase in CAMs, suggesting that this mechanism could be involved in neuroinflammation triggered by ZIKV.

9.
Lancet Infect Dis ; 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32805201

RESUMO

BACKGROUND: Prevention of mother-to-child transmission (MTCT) of hepatitis B virus (HBV) involves neonatal immunoprophylaxis, with a birth dose of hepatitis B vaccine and immune globulin, and provision of peripartum antiviral prophylaxis in highly viraemic women. However, access to assays to quantify HBV DNA levels remains inadequate in resource-poor settings. This study was commissioned by WHO and aimed to identify the HBV DNA threshold for MTCT, to assess the sensitivity and specificity of hepatitis B e antigen (HBeAg) testing to identify pregnant women with HBV DNA levels above this threshold, and to predict MTCT of HBV infection on the basis of HBeAg testing. METHODS: For this systematic review and meta-analysis, we searched the PubMed, EMBASE, Scopus, CENTRAL, CNKI, and Wanfang databases for studies of pregnant women with chronic HBV infection without concurrent antiviral therapy, published between Jan 1, 2000, and April 3, 2019. Studies were eligible for inclusion if MTCT in mother-child pairs could be stratified by different levels of maternal HBV DNA during pregnancy, if maternal HBeAg status could be stratified by HBV DNA level, and if the MTCT status of infants could be stratified by maternal HBeAg status during pregnancy. Studies that selected pregnant women on the basis of HBeAg serostatus or HBV DNA levels were excluded. Aggregate data were extracted from eligible studies by use of a pre-piloted form; study authors were contacted to clarify any uncertainties about potential duplication or if crucial information was missing. To pool sensitivities and specificities of maternal HBeAg to identify highly viraemic women and to predict MTCT events, we used the DerSimonian-Laird bivariate random effects model. This study is registered with PROSPERO, CRD42019138227. FINDINGS: Of 9007 articles identified, 67 articles (comprising 66 studies) met the inclusion criteria. The risk of MTCT despite infant immunoprophylaxis was negligible (0·04%, 95% CI 0·00-0·25) below a maternal HBV DNA level of 5·30 log10 IU/mL (200 000 IU/mL) and increased above this threshold. The pooled sensitivity of HBeAg testing to identify HBV DNA levels of 5·30 log10 IU/mL or greater in pregnant women was 88·2% (83·9-91·5) and pooled specificity was 92·6% (90·0-94·5). The pooled sensitivity of HBeAg testing in predicting MTCT of HBV infection despite infant immunoprophylaxis was 99·5% (95% CI 91·7-100) and pooled specificity was 62·2% (55·2-68·7). INTERPRETATION: Maternal HBV DNA of 5·30 log10 IU/mL or greater appears to be the optimal threshold for MTCT of HBV infection despite infant immunoprophylaxis. HBeAg is accurate to identify women with HBV DNA levels above this threshold and has high sensitivity to predict cases of immunoprophylaxis failure. In areas where HBV DNA assays are unavailable, HBeAg can be used as an alternative to assess eligibility for antiviral prophylaxis. FUNDING: World Health Organization.

10.
Liver Int ; 40(10): 2367-2376, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32633864

RESUMO

BACKGROUND: Prevention of mother-to-child transmission (PMTCT) is a challenge for controlling the hepatitis B epidemic. In Sub-Saharan countries, pilot interventions including the screening of pregnant women for HBsAg, implementation of anti-HBV therapy and infant immunization within 24 hours of life are initiated and need to be evaluated. This pilot study aimed to describe the cascade of care for hepatitis B PMTCT in a real life situation, and to identify sociodemographic factors associated with adequate management of pregnant women and infants. METHOD: The study was conducted from October 1st, 2014 to February 28th, 2016 in the antenatal clinics (ANCV) of Baskuy district which comprises nine first-level public health centres. Univariate and multivariate logistic regression analysis were used to identify sociodemographic factors associated with the likelihood of retention in the cohort, HBV DNA testing, birth dose delivery and HBsAg testing of the children at 6 months of age; P ˂ .05 was selected as cut off for significance. RESULTS: In this prospective cohort study, of 5200 pregnant women consulting for the antenatal visit, 2261 (43.5%) were proposed pre-test counselling and HBsAg screening and 2220 (98.2%) have agreed to screening. Among 1580 (71.2%) women that came back for the post-counselling interview, 75 were positive for HBsAg (4.8%), 73 (97.3% of the women provided HBsAg result) consented to medical consultation with hepatogastroenterologists and 53 (72.6%); performed the HBV DNA testing. Forty-seven out of 60 (78.3%; 65.8-87.9) children born alive were immunized for HBV within 24 hours of life. Retention in care was associated with the level of education of the infant's father, secondary school or higher was associated with a better retention in care of the women (OR: 6.6; P = .03). CONCLUSION: Our study shows large gaps in HBV PMTCT. Resources for hepatitis B screening, care and prevention including universal access to the vaccine birth dose should be allocated to reduce infection in HBV exposed infants born in Burkina Faso.

11.
J Clin Virol ; 129: 104521, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32623350

RESUMO

BACKGROUND: Knowledge of the COVID-19 epidemic extent and the level of herd immunity is urgently needed to help manage this pandemic. METHODS: We used a panel of 167 samples (77 pre-epidemic and 90 COVID-19 seroconverters) and SARS-CoV1, SARS-CoV2 and MERS-CoV Spike and/or Nucleopcapsid (NC) proteins to develop a high throughput multiplex screening assay to detect IgG antibodies in human plasma. Assay performances were determined by ROC curves analysis. A subset of the COVID-19+ samples (n = 36) were also tested by a commercial NC-based ELISA test and the results compared with those of the novel assay. RESULTS: On samples collected ≥14 days after symptoms onset, the accuracy of the assay is 100 % (95 % CI: 100-100) for the Spike antigen and 99.9 % (95 % CI:99.7-100) for NC. By logistic regression, we estimated that 50 % of the patients have seroconverted at 5.7 ± 1.6; 5.7 ± 1.8 and 7.9 ± 1.0 days after symptoms onset against Spike, NC or both antigens, respectively and all have seroconverted two weeks after symptoms onset. IgG titration in a subset of samples showed that early phase samples present lower IgG titers than those from later phase. IgG to SARS-CoV2 NC cross-reacted at 100 % with SARS-CoV1 NC. Twenty-nine of the 36 (80.5 %) samples tested were positive by the commercial ELISA while 31/36 (86.1 %) were positive by the novel assay. CONCLUSIONS: Our assay is highly sensitive and specific for the detection of IgG antibodies to SARS-CoV2 proteins, suitable for high throughput epidemiological surveys. The novel assay is more sensitive than a commercial ELISA.


Assuntos
Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Imunoglobulina G/sangue , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Vírus da SARS/imunologia , Testes Sorológicos/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos Virais/imunologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas do Nucleocapsídeo/imunologia , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Curva ROC , Sensibilidade e Especificidade , Síndrome Respiratória Aguda Grave/diagnóstico , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/virologia , Glicoproteína da Espícula de Coronavírus/imunologia , Fatores de Tempo
12.
J Am Med Dir Assoc ; 21(7): 933-936, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32674822

RESUMO

OBJECTIVE: To assess the American Testing Guidance for Nursing Homes (NHs)-updated May 19, 2020-with a new COVID-19 case. DESIGN: Case investigation. SETTING AND SUBJECTS: All 79 residents and 34 health care personnel (HCP) of an NH. METHODS: Seven days after identification of a COVID-19 resident, all residents and HCP underwent real-time reverse-transcriptase polymerase chain reaction (rRT-PCR) testing for SARS-CoV-2 with nasopharyngeal swabs. This was repeated weekly in all previously negative subjects until the testing identified no new cases, and in all positive subjects until the testing was negative. COVID-19 infection prevention and control (IPC) measures were implemented in all residents and HCP with positive testing or with COVID-19 symptoms. Standard IPC was also implemented in all HCP. Six weeks after initial testing, all residents underwent testing for enzyme-linked immunosorbent assay-based IgG antibodies directed against the SARS-CoV-2. Symptoms were serially recorded in residents and HCP. RESULTS: A total of 36 residents had a positive rRT-PCR at baseline and 2 at day 7. Six HCP had a positive rRT-PCR at baseline and 2 at day 7. No new COVID-19 cases were diagnosed later. Among the SARS-CoV-2-positive cases, 6 residents (16%) and 3 HCP (37%) were asymptomatic during the 14 days before testing. Twenty-five residents (92.3%) and all 8 HCP (100%) with a positive rRT-PCR developed IgG antibodies against SARS-CoV-2. Among the residents and HCP always having tested negative, 2 (5%) and 5 (11.5%), respectively, developed IgG antibodies against SARS-CoV-2. These 2 residents had typical COVID-19 symptoms before and after testing and 2/5 HCP were asymptomatic before and after testing. CONCLUSIONS AND IMPLICATIONS: This study shows the validity of the updated American Testing Guidance for Nursing Homes (NHs). It suggests implementing COVID-19 IPC in both residents and HCP with positive testing or COVID-19 symptoms and warns that asymptomatic HCP with repeated negative rRT-PCR testing can develop antibodies against SARS-CoV-2.


Assuntos
Técnicas de Laboratório Clínico/métodos , Busca de Comunicante/estatística & dados numéricos , Surtos de Doenças/prevenção & controle , Pessoal de Saúde/estatística & dados numéricos , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Casas de Saúde/organização & administração , Anticorpos Antivirais/análise , Técnicas de Laboratório Clínico/estatística & dados numéricos , Busca de Comunicante/métodos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , DNA Viral/análise , Feminino , Humanos , Masculino , Saúde do Trabalhador/estatística & dados numéricos , Avaliação de Resultados em Cuidados de Saúde , Pandemias , Segurança do Paciente/estatística & dados numéricos , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Reação em Cadeia da Polimerase em Tempo Real/métodos , Instituições de Cuidados Especializados de Enfermagem/organização & administração , Estados Unidos/epidemiologia
13.
Neuroscience ; 441: 142-160, 2020 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-32502571

RESUMO

The present study examined if repeated bouts of micro- and hypergravity during parabolic flight (PF) alter structural integrity of the neurovascular unit (NVU) subsequent to free radical-mediated changes in regional cerebral perfusion. Six participants (5♂, 1♀) aged 29 ±â€¯11 years were examined before, during and after a 3 h PF and compared to six sex and age-matched (27 ±â€¯6 years) normogravity controls. Blood flow was measured in the anterior (middle cerebral artery, MCA; internal carotid artery, ICA) and posterior (vertebral artery, VA) circulation (duplex ultrasound) in-flight over the course of 15 parabolas. Venous blood was assayed for free radicals (electron paramagnetic resonance spectroscopy), nitric oxide (NO, ozone-based chemiluminescence) and NVU integrity (chemiluminescence/ELISA) in normogravity before and after exposure to 31 parabolas. While MCA velocity did not change (P > 0.05), a selective increase in VA flow was observed during the most marked gravitational transition from micro- to hypergravity (P < 0.05). Increased oxidative-nitrosative stress defined by a free radical-mediated reduction in NO and elevations in glio-vascular GFAP and S100ß were observed after PF (P < 0.05), the latter proportional to the increase in VA flow (r = 0.908, P < 0.05). In contrast, biomarkers of neuronal-axonal damage (neuron-specific enolase, neurofilament light-chain, ubiquitin carboxy-terminal hydrolase L1 and tau) did not change (P > 0.05). Collectively, these findings suggest that the cumulative effects of repeated gravitational transitions may promote minor blood-brain barrier disruption, potentially related to the combined effects of haemodynamic (posterior cerebral hyperperfusion) and molecular (systemic oxidative-nitrosative) stress.

15.
PLoS Negl Trop Dis ; 14(4): e0008223, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32324736

RESUMO

Usutu virus (USUV), an African mosquito-borne flavivirus closely related to West Nile virus, was first isolated in South Africa in 1959. USUV emerged in Europe two decades ago, causing notably massive mortality in Eurasian blackbirds. USUV is attracting increasing attention due to its potential for emergence and its rapid spread in Europe in recent years. Although mainly asymptomatic or responsible for mild clinical signs, USUV was recently described as being associated with neurological disorders in humans such as encephalitis and meningoencephalitis, highlighting the potential health threat posed by the virus. Despite this, USUV pathogenesis remains largely unexplored. The aim of this study was to evaluate USUV neuropathogenicity using in vivo and in vitro approaches. Our results indicate that USUV efficiently replicates in the murine central nervous system. Replication in the spinal cord and brain is associated with recruitment of inflammatory cells and the release of inflammatory molecules as well as induction of antiviral-responses without major modulation of blood-brain barrier integrity. Endothelial cells integrity is also maintained in a human model of the blood-brain barrier despite USUV replication and release of pro-inflammatory cytokines. Furthermore, USUV-inoculated mice developed major ocular defects associated with inflammation. Moreover, USUV efficiently replicates in human retinal pigment epithelium. Our results will help to better characterize the physiopathology related to USUV infection in order to anticipate the potential threat of USUV emergence.


Assuntos
Flavivirus/patogenicidade , Modelos Biológicos , Sistema Nervoso/virologia , Animais , Encéfalo/virologia , Modelos Animais de Doenças , Células Endoteliais/virologia , Células Epiteliais/virologia , Flavivirus/crescimento & desenvolvimento , Humanos , Camundongos , Epitélio Pigmentado Ocular/virologia , Medula Espinal/virologia
16.
Front Microbiol ; 11: 20, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32117090

RESUMO

The existence of an antisense Open Reading Frame (ORF) that encodes a putative AntiSense Protein (ASP) on the proviral genome of Human Immunodeficiency Virus type 1 (HIV-1) was a source of debate for 30 years. During the last years, some progresses have been made to characterize the cellular immune response against ASP in HIV-1 seropositive patients. However, no tools were available for the detection of antibodies to ASP in the plasma of HIV-1-infected patients during the natural course of the infection. The aim of our study was to develop a Luciferase Immuno-Precipitation System (LIPS) to monitor the quantitative detection of ASP-specific antibodies in the plasma of HIV-1-infected patients [antiretroviral therapy (ART) naive-patients, patients under ART and HIV-1 controllers], patients who discontinued antiretroviral drugs (ARV). We further used this approach to delineate the epitopes of ASP targeted by antibodies. Antibodies directed against ASP were detected in 3 out of 19 patients who discontinued ARV (15%) and in 1 out of 10 ART-naive patients (10%), but were neither detected in HIV-1 infected patients under ART nor in HIV-1 controllers. Individual variations in levels of ASP-specific antibodies were detected overtime. Both the conserved prolin-rich motif and the core 60-189 region of ASP were found to be essential for antibody recognition in the four patients tested positive for anti-ASP antibodies, who were all untreated at the time of sampling. Moreover, for two of these patients, increased levels of ASP-specific antibodies were observed concomitantly to viremia declines. Overall, our method may represent a useful tool to detect a humoral response to ASP in HIV-1-infected patients, which allowed us to confirm the expression of ASP during the course of HIV-1 infection. Further studies will be needed to fully characterize the humoral response to ASP in HIV-1-infected patients.

17.
Front Microbiol ; 11: 373, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32210946

RESUMO

Blood collected and dried on a paper card - dried blood spot (DBS) - knows a growing interest as a sampling method that can be performed outside care facilities by capillary puncture, and transported in a simple and safe manner by mail. The benefits of this method for blood collection and transport has recently led the World Health Organization to recommend DBS for HIV and hepatitis B and C diagnosis. The clinical utility of DBS sampling to improve diagnostics and care of HIV and hepatitis B and C infection in hard to reach populations, key populations and people living in low-income settings was highlighted. Literature about usefulness of DBS specimens in the therapeutic cascade of care - screening, confirmation, quantification of nucleic acids, and resistance genotyping -, was reviewed. DBS samples are suitable for testing antibodies, antigens, or nucleic acids using most laboratory methods. Good sensibility and specificity have been reported for infant HIV diagnosis and diagnosis of hepatitis B and C. The performance of HIV RNA testing on DBS to identified virological failure on antiretroviral therapy is also high but not optimal because of the dilution of dried blood in the elution buffer, reducing the analytical sensitivity, and because of the contamination by intracellular HIV DNA. Standardized protocols are needed for inter-laboratory comparisons, and manufacturers should pursue regulatory approval for in vitro diagnostics using DBS specimens. Despite these limitations, DBS sampling is a clinically relevant tool to improve access to infectious disease diagnosis worldwide.

18.
Clin Infect Dis ; 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32067040

RESUMO

BACKGROUND: Immune control of Epstein-Barr virus (EBV) infection is impaired in HIV-infected individuals. We explored maternal factors associated with EBV acquisition in HIV-exposed uninfected (HEU) infants and the relationship between EBV infection and serious adverse events (SAE) during the first year of life. METHODS: Two hundred and one HEU infants from Uganda enrolled in the ANRS12174 trial were tested for anti-viral capsid antigen (VCA) antibodies at week 50 of life. The date of infection was estimated by testing of EBV DNA at weeks 1, 6, 14, 26, 38 and 50 postpartum on dried blood spot (DBS). RESULTS: Eighty-seven (43%) infants were tested positive for anti-VCA IgG at week 50. Among the 59 infants positive for EBV DNA, 25% were infected within the first 26 weeks. Almost half of them (12%) were infected before week 14. Shedding of EBV in breast milk was associated with EBV DNA in maternal plasma (P=.009), HIV RNA detection (P=.039), lower CD4 count (P=.001) and was correlated with plasma EBV DNA levels (P=.002). EBV infant infection at week 50 was associated with shedding of EBV in breast milk (P=.009) and young maternal age (P=.029). Occurrence of a clinical SAE, including malaria and pneumonia, was associated with higher levels of EBV DNA in infants (P=.010). CONCLUSIONS: By assessing EBV infection in HEU infants we observed that infection during the first year of life is determined by HIV and EBV maternal factors and that EBV DNA levels was higher among infants with clinical SAE.

19.
J Viral Hepat ; 27(5): 540-543, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31895489

RESUMO

Diagnostic of acute hepatitis A virus (HAV) infection is based on the detection of anti-HAV IgM without testing for the pathogen itself. We evaluated the usefulness of HAV RNA testing for confirmation of acute hepatitis A and to provide indications about the level of HAV replication in HIV-positive and HIV-negative subjects during an unprecedented outbreak of HAV observed in France in 2017. HAV RNA was detected in 38 out of 41 (92.6%) subjects with a clinical diagnosis of acute hepatitis A, whereas nine cases tested positive for anti-HAV IgM in whom the diagnosis of acute hepatitis A was not retained were found negative for HAV RNA. All subjects in the control group were also tested negative for HAV RNA. HAV viremia was correlated to ALT peak (r = .64; P < .0001). HIV-infected patients have similar HAV RNA levels but were less likely to have prolonged international normalized ratio of prothrombin time when compared to the HIV-uninfected group (P = .016), suggesting a less severe course of acute hepatitis. HAV RNA was detected in the serum of most of the patients with acute hepatitis A, indicating that the direct detection of HAV can be used to confirm hepatitis A in patients tested positive for anti-HAV IgM antibodies. Nucleic acid tests should serve more broadly during the diagnosis workup of acute hepatitis A to improve the predictive values of HAV in vitro diagnostic tests and to confirm acute hepatitis A in patients tested positive with IgM with moderate or low S/CO values.

20.
Liver Int ; 40(3): 514-521, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31778282

RESUMO

BACKGROUND: Although novel hepatitis C virus (HCV) RNA point-of-care technology has the potential to enhance the diagnosis in resource-limited settings, very little real-world validation of their utility exists. We evaluate the performance of HCV RNA quantification using the Xpert® HCV viral load Fingerstick assay (Xpert® HCV VL Fingerstick assay) as compared to the World Health Organisation pre-qualified plasma Xpert® HCV VL assay among people who inject drugs (PWID) attending an opioid agonist therapy (OAT) clinic in Dar-es-Salaam, Tanzania. METHODS: Between December 2018 and February 2019, consecutive HCV seropositive PWID attending the OAT clinic provided paired venous and Fingerstick samples for HCV RNA quantification. These were processed onsite using the GeneXpert® platform located at the Central tuberculosis reference laboratory. RESULTS: A total of 208 out of 220 anti-HCV-positive participants recruited (94.5%) had a valid Xpert® HCV VL result available; 126 (61%; 95% CI 53.8-67.0) had detectable and quantifiable HCV RNA. About 188 (85%) participants had paired plasma and Fingerstick whole blood samples; the sensitivity and specificity for the quantification of HCV RNA levels were 99.1% and 98.7% respectively. There was an excellent correlation (R2  = .95) and concordance (mean difference 0.13 IU/mL, (95% CI -0.9 to 0.16 IU/mL) in HCV RNA levels between plasma samples and Fingerstick samples. CONCLUSION: This study found excellent performance of the Xpert® HCV VL Fingerstick assay for HCV RNA detection and quantification in an African-field setting. Its clinical utility represents an important watershed in overcoming existing challenges to HCV diagnosis, which should play a crucial role in HCV elimination in Africa.

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