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Background: Interferon-y Release Assays (IGRA) reversions have been reported in different clinical scenarios for the diagnosis of tuberculosis (TB) infection. This study aimed to determine the rate of QuantiFERON-TB Gold Plus (QFT-Plus) reversions during contact investigation as a potential strategy to reduce the number of preventive treatments. Methods: Prospective, multicentre cohort study of immunocompetent adult contacts of patients with pulmonary TB tested with QFT-Plus. Contacts with an initial positive QFT-Plus (QFT-i) underwent a second test within 4 weeks (QFT-1), and if negative, underwent a repeat test 4 weeks later (QFT-2). Based on the QFT-2 result, we classified cases as sustained reversion if they remained negative and as temporary reversion if they turned positive. Results: We included 415 contacts, of whom 96 (23.1%) had an initial positive test (QFT-i). Following this, 10 had negative QFT-1 results and 4 (4.2%) of these persisted with a negative result in the QFT-2 (sustained reversions). All four sustained reversions occurred in contacts with IFN-γ concentrations between ≥0.35 and ≤0.99 IU•mL-1 in one or both QFT-i tubes. Conclusion: In this study, TB contact investigations rarely reveal QFT-Plus reversion. These results do not support retesting cases with an initial positive result to reduce the number of preventive treatments. [ABSTRACT FROM AUTHOR]

Introduction: Prognostic markers for fetal transmission of Cytomegalovirus (CMV) infection during pregnancy are poorly understood. Maternal CMV-specific T-cell responses may help prevent fetal transmission and thus, we set out to assess whether this may be the case in pregnant women who develop a primary CMV infection. Methods: A multicenter prospective study was carried out at 8 hospitals in Spain, from January 2017 to April 2020. Blood samples were collected from pregnant women at the time the primary CMV infection was diagnosed to assess the T-cell response. Quantitative analysis of interferon producing specific CMV-CD8+/CD4+ cells was performed by intracellular cytokine flow cytometry. Results: In this study, 135 pregnant women with a suspected CMV infection were evaluated, 60 of whom had a primary CMV infection and samples available. Of these, 24 mothers transmitted the infection to the fetus and 36 did not. No association was found between the presence of specific CD4 or CD8 responses against CMV at the time maternal infection was diagnosed and the risk of fetal transmission. There was no transmission among women with an undetectable CMV viral load in blood at diagnosis. Conclusions: In this cohort of pregnant women with a primary CMV infection, no association was found between the presence of a CMV T-cell response at the time of maternal infection and the risk of intrauterine transmission. A detectable CMV viral load in the maternal blood at diagnosis of the primary maternal infection may represent a relevant biomarker associated with fetal transmission. [ABSTRACT FROM AUTHOR]

Logistic regression (LR) is the most common prediction model in medicine. In recent years, supervised machine learning (ML) methods have gained popularity. However, there are many concerns about ML utility for small sample sizes. In this study, we aim to compare the performance of 7 algorithms in the prediction of 1-year mortality and clinical progression to AIDS in a small cohort of infants living with HIV from South Africa and Mozambique. The data set (n = 100) was randomly split into 70% training and 30% validation set. Seven algorithms (LR, Random Forest (RF), Support Vector Machine (SVM), K-Nearest Neighbor (KNN), Naïve Bayes (NB), Artificial Neural Network (ANN), and Elastic Net) were compared. The variables included as predictors were the same across the models including sociodemographic, virologic, immunologic, and maternal status features. For each of the models, a parameter tuning was performed to select the best-performing hyperparameters using 5 times repeated 10-fold cross-validation. A confusion-matrix was built to assess their accuracy, sensitivity, and specificity. RF ranked as the best algorithm in terms of accuracy (82,8%), sensitivity (78%), and AUC (0,73). Regarding specificity and sensitivity, RF showed better performance than the other algorithms in the external validation and the highest AUC. LR showed lower performance compared with RF, SVM, or KNN. The outcome of children living with perinatally acquired HIV can be predicted with considerable accuracy using ML algorithms. Better models would benefit less specialized staff in limited resources countries to improve prompt referral in case of high-risk clinical progression. [ABSTRACT FROM AUTHOR]

The size of the latent HIV reservoir is associated with the timing of therapeutic interventions and overall health of the immune system. Here, we demonstrate that T cell phenotypic signatures associate with viral reservoir size in a cohort of HIV vertically infected children and young adults under durable viral control, and who initiated anti-retroviral therapy (ART) <2 years old. Flow cytometry was used to measure expression of immune activation (IA), immune checkpoint (ICP) markers, and intracellular cytokine production after stimulation with GAG peptides in CD4 and CD8 T cells from cross-sectional peripheral blood samples. We also evaluated the expression of 96 genes in sort-purified total CD4 and CD8 T cells along with HIV-specific CD4 and CD8 T cells using a multiplexed RT-PCR approach. As a measure of HIV reservoir, total HIV-DNA quantification by real-time PCR was performed. Poisson regression modeling for predicting reservoir size using phenotypic markers revealed a signature that featured frequencies of PD-1+CD4 T cells, TIGIT+CD4 T cells and HIV-specific (CD40L+) CD4 T cells as important predictors and it also shows that time of ART initiation strongly affects their association with HIV-DNA. Further, gene expression analysis showed that the frequencies of PD-1+CD4 T cells associated with a CD4 T cell molecular profile skewed toward an exhausted Th1 profile. Our data provide a link between immune checkpoint molecules and HIV persistence in a pediatric cohort as has been demonstrated in adults. Frequencies of PD-1+ and TIGIT+CD4 T cells along with the frequency of HIV-specific CD4 T cells could be associated with the mechanism of viral persistence and may provide insight into potential targets for therapeutic intervention. Author summary: Low HIV reservoir size is associated with positive outcomes of therapeutic approaches and better immune function. Here, we identified a 9-marker T cell immune signature based on phenotypic flow cytometry data that associated with total HIV DNA measurements in a pediatric cohort of 34 perinatally infected participants with sustained viral control. Notably, frequencies of PD-1+ CD4 T cells and TIGIT+ CD4 T cells were positively correlated and HIV-specific (CD40L+) CD4 T cells were negatively correlated with HIV DNA, and were impacted by time of ART initiation. Gene expression analysis by multiplex RT-PCR showed that the frequencies of PD-1+ CD4 T cells associated with an exhausted Th1 molecular profile in CD4 T cells. This signature could inform future therapeutic studies and provide mechanistic insight on HIV persistence in perinatally infected HIV. [ABSTRACT FROM AUTHOR]

Background: Maternal HIV coinfection is a key factor for mother-to-child transmission (MTCT) of HCV. However, data about HCV MTCT in HIV/HCV-coinfected pregnant women on combined antiretroviral treatment (ART) are scarce. This study assessed the HCV MTCT rate in the Madrid Cohort of HIV-infected women. Methods: Retrospective study within the Madrid Cohort of HIV-infected pregnant women (2000–2012). Epidemiological, clinical and treatment related variables were analysed for the mother and infant pairs. HCV MTCT rate was determined. Results: Three hundred thirty-nine HIV/HCV-coinfected women and their exposed infants were recorded. A total of 227 (67%) paired mother-children had available data of HCV follow-up and were included for the analysis. Sixteen children (rate 7.0%, 95%CI 3.7–10.4%) were HCV infected by 18 months of age, none of them coinfected with HIV. HIV/HCV-coinfected pregnant women were mostly of Spanish origin with a background of previous injection drug use. HCV-genotype 1 was predominant. The characteristics of mothers that transmitted HCV were similar to those that did not transmit HCV with respect to sociodemographic and clinical features. A high rate (50%) of preterm deliveries was observed. Infants infected with HCV were similar at birth in weight, length and head circumference than those uninfected. Conclusion: MTCT rates of HCV among HIV/HCV-coinfected women on ART within the Madrid cohort were lower than previously described. However, rates are still significant and strategies to eliminate any HCV transmission from mother to child are needed. [ABSTRACT FROM AUTHOR]

Background: Kawasaki disease (KD) is an acute self-limited systemic vasculitis of unknown etiology affecting mainly children less than 5 years of age. Risk factors for cardiac involvement and resistance to treatment are insufficiently studied in non-Japanese children. Objective: This study aimed to investigate the epidemiology, clinical features and risk factors for resistance to treatment and coronary artery lesions (CAL) in KD in Spain. Methods: Retrospective study (May 2011-June 2016) of all patients less than 16 years of age diagnosed with KD included in KAWA-RACE network (84 Spanish hospitals). Results: A total of 625 cases were analyzed, 63% were males, 79% under 5 year-olds and 16.8% younger than 12 months. On echocardiographic examination CAL were the most frequent findings (23%) being ectasia the most common (12%). Coronary aneurysms were diagnosed in 9.6%, reaching 20% in infants under 12 months (p<0.001). A total of 97% of the patients received intravenous immunoglobulin (IVIG) with a median number of days from fever onset to IVIG administration of 7.2. A second dose was given to 15.7% and steroids to 14.5% patients. Only 1.4% patients received infliximab. No deaths were reported. A multivariate analysis identified anemia, hypoalbuminemia, hyponatremia, higher creatinine and procalcitonin as independent risk factors for treatment failure and length under 103 cm, hemoglobin < 10.2 mg/dL, platelets > 900,000 cells/mm3, maximum temperature < 39.5°C, total duration of fever > 10 days and fever before treatment ≥ 8 days as independent risk factors for developing coronary aneurysms. Conclusions: In our population, children under 12 months develop coronary aneurysms more frequently and children with KD with anemia and leukocytosis have high risk of cardiac involvement. Adding steroids early should be considered in those patients, especially if the treatment is not started before 8 days of fever. A score applicable to non-Japanese children able to predict the risk of aneurysm development and IVIG resistance is necessary. [ABSTRACT FROM AUTHOR]

One of the main technological trends in the last five years is mass data analysis. This trend is due in part to the emergence of concepts such as social networks, which generate a large volume of data that can provide added value through their analysis. This article is focused on a business and employment-oriented social network. More specifically, it focuses on the analysis of information provided by different users in image form. The images are analyzed to detect whether other existing users have posted or talked about the same image, even if the image has undergone some type of modification such as watermarks or color filters. This makes it possible to establish new connections among unknown users by detecting what they are posting or whether they are talking about the same images. The proposed solution consists of an image matching algorithm, which is based on the rapid calculation and comparison of hashes. However, there is a computationally expensive aspect in charge of revoking possible image transformations. As a result, the image matching process is supported by a distributed forecasting system that enables or disables nodes to serve all the possible requests. The proposed system has shown promising results for matching modified images, especially when compared with other existing systems. [ABSTRACT FROM AUTHOR]