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Purpose: Secondary opportunistic coinfections are a significant contributor to morbidity and mortality in intensive care unit (ICU) patients, but can be difficult to identify. Presently, new blood RNA biomarkers were tested in ICU patients to diagnose viral, bacterial, and biofilm coinfections. Methods: COVID-19 ICU patients had whole blood drawn in RNA preservative and stored at -80°C. Controls and subclinical infections were also studied. Droplet digital polymerase chain reaction (ddPCR) quantified 6 RNA biomarkers of host neutrophil activation to bacterial (DEFA1), biofilm (alkaline phosphatase [ALPL], IL8RB/CXCR2), and viral infections (IFI27, RSAD2). Viral titer in blood was measured by ddPCR for SARS-CoV2 (SCV2). Results: RNA biomarkers were elevated in ICU patients relative to controls. DEFA1 and ALPL RNA were significantly higher in severe versus incidental/moderate cases. SOFA score was correlated with white blood cell count (0.42), platelet count (-0.41), creatinine (0.38), and lactate dehydrogenase (0.31). ALPL RNA (0.59) showed the best correlation with SOFA score. IFI27 (0.52) and RSAD2 (0.38) were positively correlated with SCV2 viral titer. Overall, 57.8% of COVID-19 patients had a positive RNA biomarker for bacterial or biofilm infection. Conclusions: RNA biomarkers of host neutrophil activation indicate the presence of bacterial and biofilm coinfections in most COVID-19 patients. Recognizing coinfections may help to guide the treatment of ICU patients., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: TM and TJ have an equity interest in True Bearing Diagnostics, Inc., a diagnostics company developing RNA biomarkers for various diseases, including coronary artery disease and internal infections.

The COVID-19 pandemic has underscored the critical need for precise diagnostic methods to distinguish between similar respiratory infections, such as COVID-19 and Mycoplasma pneumoniae (MP). Identifying key biomarkers and utilizing machine learning techniques, such as random forest analysis, can significantly improve diagnostic accuracy. We conducted a retrospective analysis of clinical and laboratory data from 214 patients with acute respiratory infections, collected between October 2022 and October 2023 at the Second Hospital of Nanping. The study population was categorized into three groups: COVID-19 positive (n = 52), MP positive (n = 140), and co-infected (n = 22). Key biomarkers, including C-reactive protein (CRP), procalcitonin (PCT), interleukin- 6 (IL-6), and white blood cell (WBC) counts, were evaluated. Correlation analyses were conducted to assess relationships between biomarkers within each group. The random forest analysis was applied to evaluate the discriminative power of these biomarkers. The random forest model demonstrated high classification performance, with area under the ROC curve (AUC) scores of 0.86 (95% CI: 0.70-0.97) for COVID-19, 0.79 (95% CI: 0.64-0.92) for MP, 0.69 (95% CI: 0.50-0.87) for co-infections, and 0.90 (95% CI: 0.83-0.95) for the micro-average ROC. Additionally, the precision-recall curve for the random forest classifier showed a micro-average AUC of 0.80 (95% CI: 0.69-0.91). Confusion matrices highlighted the model's accuracy (0.77) and biomarker relationships. The SHAP feature importance analysis indicated that age (0.27), CRP (0.25), IL6 (0.14), and PCT (0.14) were the most significant predictors. The integration of computational methods, particularly random forest analysis, in evaluating clinical and biomarker data presents a promising approach for enhancing diagnostic processes for infectious diseases. Our findings support the use of specific biomarkers in differentiating between COVID-19 and MP, potentially leading to more targeted and effective diagnostic strategies. This study underscores the potential of machine learning techniques in improving disease classification in the era of precision medicine., (© 2024. The Author(s).)

Background: The role of ribonucleases in tuberculosis among people with human immunodeficiency virus (HIV; PWH) is unknown. We explored ribonuclease activity in plasma from PWH with and without tuberculosis., Methods: Participants were identified from a cohort of treatment-naive PWH in Ethiopia who had been classified for tuberculosis disease (HIV positive [HIV+]/tuberculosis positive [tuberculosis+] or HIV+/tuberculosis negative [tuberculosis-]). Ribonuclease activity in plasma was investigated by quantification of synthetic spike-in RNAs using sequencing and quantitative polymerase chain reaction and by a specific ribonuclease activity assay. Quantification of ribonuclease 1, 2, 3, 6, 7, and T2 proteins was performed by enzyme-linked immunosorbent assay. Ribonuclease activity and protein concentrations were correlated with markers of tuberculosis and HIV disease severity and with concentrations of inflammatory mediators., Results: Ribonuclease activity was significantly higher in plasma of HIV+/tuberculosis+ (n = 51) compared with HIV+/tuberculosis- (n = 78), causing reduced stability of synthetic spike-in RNAs. Concentrations of ribonucleases 2, 3, and T2 were also significantly increased in HIV+/tuberculosis+ compared with HIV+/tuberculosis-. Ribonuclease activity was correlated with HIV viral load, and inversely correlated with CD4 cell count, mid-upper arm circumference, and body mass index. Moreover, ribonuclease activity was correlated with concentrations of interleukin 27, procalcitonin and the kynurenine-tryptophan ratio., Conclusions: PWH with tuberculosis disease have elevated plasma ribonuclease activity, which is also associated with HIV disease severity and systemic inflammation., Competing Interests: Potential conflicts of interest. P. B. reports receiving payments for lectures and presentations for Gilead Sciences. All other authors report no potential conflicts. The authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) co-infection are significant public health issues, despite the availability of an effective HBV vaccine for nearly three decades and the great progress that has been made in preventing and treating HIV. HBV and HIV both modulate micro-ribonucleic acids (microRNA) expression to support viral replication. The aim of this study was to describe the pattern of microRNA expression in patients coinfected with chronic HBV and HIV with varying disease severity, as indicated by Hepatitis B e antigen (HBeAg) status, HBV viral load, alanine transaminase (ALT) levels, and HIV viral load., Methods: Plasma microRNAs, specific to HBV, were measured by quantitative real-time polymerase chain reaction (qRT-PCR) in HBV and HIV-negative healthy controls (n = 23) and patients coinfected with chronic HBV-HIV (n = 50). MicroRNA expression levels were compared between patients with high vs low HBV viral load, HBeAg positive vs HBeAg negative, high vs low ALT levels, and high vs low HIV viral load. Additionally, HBV viral load, ALT levels, and HIV viral load were correlated with microRNA expression levels., Results: Significantly higher expression levels of selected microRNAs were observed in chronic HBV-HIV coinfected patients compared to healthy controls. Significantly higher expression levels of hsa-miR-122-5p, hsa-miR-192-5p, and hsa-miR-193b-3p were observed in patients with high HBV viral load compared with low HBV viral load patients, and the levels of these microRNAs were correlated with HBV viral load levels. Significantly higher levels of hsa-miR-15b-5p and hsa-miR-181b-5p were observed in HBeAg-negative patients., Conclusion: This study demonstrates the potential use of hsa-miR-15b-5p, hsa-miR-122-5p, hsa-miR-181b-5p, hsa-miR-192-5p and hsa-miR-193b-3p as additional diagnostic biomarkers in chronic HBV disease progression., (© 2024. The Author(s).)

Background & objectives Despite the evidence of population differences in miRNA expression, limited information is available about the expression profile of miRNAs in Indian tuberculosis (TB) patients. The present study aimed to investigate the expression profile of candidate serum exosomal microRNAs in Indian patients with and without HIV-TB coinfection. Methods The pool samples of serum exosomes of study participants (HIV-TB coinfection, extra-pulmonary TB, HIV mono-infection, pulmonary TB) and healthy humans were processed for the isolation of total RNA followed by miRNA analysis using miRCURY LNA human focus PCR panel by real-time PCR. The significantly altered miRNAs were identified using differential expression analysis. The target genes prediction and potential functional analysis of exclusively differentially expressed miRNAs were performed using bioinformatics tools. Results The expression profile of 57, 58, 49 and 11 miRNAs was significantly altered in exosome samples of HIV-TB coinfected, extra-pulmonary TB, HIV mono-infected and pulmonary TB patients compared to healthy controls, respectively. The set of three (hsa-let-7i-5p, hsa-miR-24-3p, hsa-miR-92a-3p), three (hsa-miR-20a-5p, hsa-let-7e-5p, hsa-miR-26a-5p) and four (hsa-miR-21-5p, hsa-miR-19a-3p, hsa-miR-19b-3p, hsa-miR-146a-5p) miRNAs were exclusively significantly differentially expressed in study participants with HIV-TB coinfection, extra-pulmonary TB and pulmonary TB, respectively. Most of the target genes of exclusively differentially expressed miRNAs were enriched in pathways in cancer, MAPK signalling pathway and Ras signalling pathway. Interpretation & conclusions The present study demonstrates a distinct expression profile of miRNAs in serum exosomes of the study participants and identified crucial miRNAs which may have a significant impact on the biomarker analysis and pathogenesis of TB in Indian patients.

Objective: COVID-19 infection poses significant risks, including life-threatening consequences and fungus synchronization, making it a significant concern. This study seeks to assess the effect of concurrent infection of COVID-19 with Thrush Candida albicans on the patient's health state by measuring the proportion of immune cells and certain interleukins such as IL-8, -10, -17, and -33., Methods: The study involved 70 patients (30 patients with COVID-19, 17 patients with thrush candidiasis, and 23 patients with Thrush Candida albicans) and 50 healthy individuals as a control group. COVID-19 was identified using RT-PCR, while C. albicans were identified through culture media, biochemical testing, and oral swabs. Ruby equipment and ELISA kits were used for blood counts and interleukin detection., Results: COVID-19, thrush candidiasis, and Thrush Candida albicans infections occur in a wide range of age groups (4-80 years), with no significant differences between sexes (p>0.05). Immunologically, our study found that Thrush Candida albicans patients had the highest rate of neutrophils (89.6%) and basophils (2.01%), while corona patients had the highest percentage of lymphocytes (70.12%) and eosinophils (7.11%), and patients with thrush candidiasis had the highest percentage of monocytes. Thrush Candida albicans patients showed increased IL-8 (56.7 pg/mL) and IL-17 (101.1 pg/mL) concentrations, with the greatest concentration of IL-33 (200.5 pg/mL) in COVID-19, and a decrease in the level of IL-10 in patient groups compared with controls., Conclusion: Patient groups showed increased neutrophils, lymphocytes, monocytes, and IL-8 levels, with a significant linear association between proinflammatory interleukins and these cells.

Chronic immune activation in tuberculosis (TB) associated with human immunodeficiency virus (HIV) infection (HIV/TB) modifies their clinical course. We prospectively measured osteopontin (OPN), full-length galectin-9 (FL-Gal9), and total-Gal9 (T-Gal9) levels in 32 patients with HIV/TB coinfection treated with anti-tuberculosis and antiretroviral therapies over 6-18 months to determine the amelioration of inflammatory conditions in response to the therapies. We observed a significant time-dependent decrease in FL-Gal9 in both pulmonary TB (PTB, n = 20) and extrapulmonary TB (EPTB, n = 12) patients. The levels of T-Gal9, OPN, and CRP decreased significantly after treatment in only PTB patients. We calculated the inflammatory score (INS) indicating immunologic recovery based on the decline in OPN, FL-Gal9, T-Gal9, and CRP levels. Baseline levels of T-Gal9 and OPN positively correlated with INS in all TB and only PTB patients, respectively, indicating that their levels predict better recovery. In contrast, FL-Gal9 levels at the second visit negatively correlated with INS in EPTB patients. The decrease rate in OPN levels at the second visit also correlated positively with INS in PTB patients. Women showed a higher INS and lower levels of FL-Gal9 than men. The patients with moderate grade severity on chest X-ray had higher CD4 cell numbers than those with limited grade severity. Monitoring these markers will help to predict and assess the response to therapy as well as to devise strategies to reduce the complications caused by chronic immune activation in patients with HIV/TB coinfection.

Background: Secondary bacterial infection (SBI) occurs in a proportion of individuals with dengue and results in longer hospitalization, higher mortality, and increased health-related costs. However, the frequency, risk factors and predictive biomarkers of this comorbidity in pediatric dengue is partially known., Methods: We conducted a retrospective multicenter study in a dengue hyperendemic region of Colombia, analyzing 1597 children from two pediatric cohorts. We included children with confirmed dengue (mild to severe disease) and evaluated the rate of SBI, their clinical characteristics, diagnostic predictors and attention costs. We also assessed the diagnostic performance of plasma interleukin (IL)-6 for detecting SBI in pediatric dengue., Results: The frequency of SBI in children with dengue with warning signs in cohorts 1 and 2 was 2.4% and 7.3%, respectively, and this rate reached 30.7% and 38.2% in children with severe disease. Staphylococcus aureus and Escherichia coli were the more frequent infectious agents. Increased total leukocytes and C-reactive protein levels, as well as high IL-6 at hospital admission, in children <48 months of age were early indications of SBI in dengue. Higher rates of organ dysfunction, the requirement of a longer hospitalization and a 2.3-fold increase in attention costs were observed in SBI., Conclusions: An important proportion of children with dengue course with SBI and exhibit higher morbidity. Elevated leukocytes, C-reactive protein and IL-6 in young children are early markers of SBI. Physicians should identify children with dengue and risk factors for SBI, microbiologically confirm the bacterial infection, and rationally and timely provide antimicrobial therapy., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Visceral leishmaniasis (VL) is caused by the protozoan Leishmania spp, transmitted by sand fly bites. VL is one of the deadliest tropical infection diseases, yet the coinfection with HIV virus drastically increases relapses, treatment failure and mortality. The concomitant action of these two pathogens leads to high cellular activation independently of the progression to AIDS. In addition, microbial translocation and bacterial infections are thought to contribute worsening the clinical picture. Identifying biomarkers associated with disease severity is of interest for clinical management of patients with VL-HIV/AIDS. Thus, we analyzed in the sera several markers including interleukins (IL-1β, IL-6, IL-8, and IL-17), interferon-γ (IFN- γ), tumor necrosis factor (TNF), lipopolysaccharide (LPS), soluble CD14 (sCD14), macrophage migration inhibitory factor (MIF) and intestinal fatty acid-binding protein (IFABP). These markers were compared with disease severity in 24 patients with VL/HIV presenting different clinical outcomes. Disease severity was defined by the probability of death calculated using a score set system derived by the Kala-Cal® software. Probability of death ranged from 3.7% to 97.9%, with median of 28.8%. Five patients died (20%). At the univariate analysis, disease severity was correlated with TNF, IFN-γ and sCD14. LPS was positively correlated with sCD14 specifically in patients with low CD4 + count (CD4 + T-cell <200 cells/mL). Most importantly, the multivariate analysis including LPS, CD4 + count and sCD14 showed that sCD14 was the only independent predictor for disease severity and death. Altogether, our results indicated that sCD14 is a powerful marker of pathogenicity and death for patients with VL-HIV/AIDS., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: In resource-limited settings, the mortality rate among tuberculosis and human Immunodeficiency virus co-infected children is higher. However, there is no adequate evidence in Ethiopia in general and in the study area in particular. Hence, this study aims to estimate lifetime survival and predictors of mortality among TB with HIV co-infected children after test and treat strategies launched in Northwest Ethiopia Hospitals, 2021., Methods: Institution-based historical follow-up study was conducted in Northwest Ethiopia Hospitals among 227 Tuberculosis and Human Immunodeficiency Virus co-infected children from March 1, 2014, to January 12, 2021. The data were entered into Epi info-7 and then exported to STATA version 14 for analysis. The log-rank test was used to estimate the curve difference of the predictor variables. Bivariable cox-proportional hazard models were employed for each predictor variable. Additionally, those variables having a p-value < 0.25 in bivariate analysis were fitted into a multivariable cox-proportional hazards model. P-value < 0.05 was used to declare significance associated with the dependent variable., Results: From a total of 227 TB and HIV co-infected children, 39 died during the follow-up period. The overall mortality rate was 3.7 (95% CI (confidence interval): 2.9-4.7) per 100 person-years with a total of 1063.2-year observations. Cotrimoxazole preventive therapy (CPT) non-users [Adjusted Hazarded Ratio (AHR) = 3.8 (95% CI: 1.64-8.86)], presence of treatment failure [AHR = 3.0 (95% CI: 1.14-78.17)], and Cluster of differentiation 4(CD4) count below threshold [AHR = 2.7 (95% CI: 1.21-6.45)] were significant predictors of mortality., Conclusion: In this study, the mortality rate among TB and HIV co-infected children was found to be very high. The risk of mortality among TB and HIV co-infected children was associated with treatment failure, CD4 count below the threshold, and cotrimoxazole preventive therapy non-users. Further research should conduct to assess and improve the quality of ART service in Northwest Ethiopia Hospitals., Competing Interests: The authors have declared that no competing interests exist.

Rationale: Performance of blood transcriptomic tuberculosis (TB) signatures in longitudinal studies and effects of TB-preventive therapy and coinfection with HIV or respiratory organisms on transcriptomic signatures has not been systematically studied. Objectives: We evaluated longitudinal kinetics of an 11-gene blood transcriptomic TB signature, RISK11, and effects of TB-preventive therapy (TPT) and respiratory organisms on RISK11 signature score, in HIV-uninfected and HIV-infected individuals. Methods: RISK11 was measured in a longitudinal study of RISK11-guided TPT in HIV-uninfected adults, a cross-sectional respiratory organisms cohort, or a longitudinal study in people living with HIV (PLHIV). HIV-uninfected RISK11 +  participants were randomized to TPT or no TPT; RISK11 - participants received no TPT. PLHIV received standard-of-care antiretroviral therapy and TPT. In the cross-sectional respiratory organisms cohort, viruses and bacteria in nasopharyngeal and oropharyngeal swabs were quantified by real-time quantitative PCR. Measurements and Main Results: RISK11 +  status was transient in most of the 128 HIV-negative participants with longitudinal samples; more than 70% of RISK11 +  participants reverted to RISK11 - by 3 months, irrespective of TPT. By comparison, reversion from a RISK11 + state was less common in 645 PLHIV (42.1%). Non-HIV viral and nontuberculous bacterial organisms were detected in 7.2% and 38.9% of the 1,000 respiratory organisms cohort participants, respectively, and among those investigated for TB, 3.8% had prevalent disease. Median RISK11 scores (%) were higher in participants with viral organisms alone (46.7%), viral and bacterial organisms (42.8%), or prevalent TB (85.7%) than those with bacterial organisms other than TB (13.4%) or no organisms (14.2%). RISK11 could not discriminate between prevalent TB and viral organisms. Conclusions: Positive RISK11 signature status is often transient, possibly due to intercurrent viral infection, highlighting potentially important challenges for implementation of these biomarkers as new tools for TB control.

Background: The variability of Covid-19 severity between patients has driven efforts to identify prognosticating laboratory markers that could aid clinical decision-making. Procalcitonin is classically used as a diagnostic marker in bacterial infections, but its role in predicting Covid-19 disease severity is emerging. We aimed to identify the association between procalcitonin and Covid-19 disease severity in a critical care setting and whether bacterial co-infection is implicated., Methods: We retrospectively reviewed Covid-19 patients with procalcitonin concentrations measured in a critical care setting at our institution between February and September 2020. Laboratory markers including peak procalcitonin values and a range of bacterial culture results were analysed. Outcomes were the requirement and duration of invasive mechanical ventilation as well as inpatient mortality., Results: In total, 60 patients were included; 68% required invasive mechanical ventilation and 45% died as inpatient. Univariate analysis identified higher peak procalcitonin concentrations significantly associated with both the requirement for invasive mechanical ventilation (OR: 3.2, 95% CI 1.3-9.0, P  = 0.02) and inpatient mortality (OR: 2.6, 95% CI 1.1-6.6, P  = 0.03). Higher peak procalcitonin concentrations was an independent predictor of mortality on multivariate analysis (OR 3.7, 95% CI 1.1-12.4, P  = 0.03). There was a significant positive correlation between increased peak procalcitonin concentrations and duration on invasive mechanical ventilation. No significant difference was found between peak procalcitonin concentrations of patients with positive and negative bacterial cultures., Conclusions: Elevated procalcitonin concentrations in Covid-19 patients are associated with respiratory failure requiring prolonged invasive mechanical ventilation and inpatient mortality. This association may be independent of bacterial co-infection.

Background: Guidelines recommend maximal efforts to obtain blood and sputum cultures in patients with COVID-19, as bacterial coinfection is associated with worse outcomes. The aim of this study was to evaluate the yield of bacteriological tests, including blood and sputum cultures, and the association of multiple biomarkers and the Pneumonia Severity Index (PSI) with clinical and microbiological outcomes in patients with COVID-19 presenting to the emergency department (ED)., Methods: This is a substudy of a large observational cohort study (PredictED study). The PredictED included adult patients from whom a blood culture was drawn at the ED of Haga Teaching Hospital, The Netherlands. For this substudy, all patients who tested positive for SARS-CoV-2 by PCR in March and April 2020 were included. The primary outcome was the incidence of bacterial coinfection. We used logistic regression analysis for associations of procalcitonin, C reactive protein (CRP), ferritin, lymphocyte count and PSI score with a severe disease course, defined as intensive care unit admission and/or 30-day mortality. The area under the receiver operating characteristics curve (AUC) quantified the discriminatory performance., Results: We included 142 SARS-CoV-2 positive patients. On presentation, the median duration of symptoms was 8 days. 41 (29%) patients had a severe disease course and 24 (17%) died within 30 days. The incidence of bacterial coinfection was 2/142 (1.4%). None of the blood cultures showed pathogen growth while 6.3% was contaminated. The AUCs for predicting severe disease were 0.76 (95% CI 0.68 to 0.84), 0.70 (0.61 to 0.79), 0.62 (0.51 to 0.74), 0.62 (0.51 to 0.72) and 0.72 (0.63 to 0.81) for procalcitonin, CRP, ferritin, lymphocyte count and PSI score, respectively., Conclusion: Blood cultures appear to have limited value while procalcitonin and the PSI appear to be promising tools in helping physicians identify patients at risk for severe disease course in COVID-19 at presentation to the ED., Competing Interests: Competing interests: TO reports personal lecture fees from Gilead, outside the submitted work., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To evaluate the clinical significance of pro-inflammatory cytokines for disease severity and coagulation in septic patients with bacterial co-infection., Methods: A total of 92 patients with sepsis admitted to intensive care unit (ICU) from January 2017 to August 2020 were enrolled and their clinical data were retrospectively analyzed. Forty-seven patients (51.1%) had a single infection by Klebsiella pneumoniae or Acinetobacter baumannii (single-infection group), and 45 patients (48.9%) were infected by both species (co-infection group). We compared the clinical characteristics and disease severity among the 92 patients. Disease severity was defined as ICU stay time and 30-day mortality. Plasma concentrations of pro-inflammatory cytokines and their correlation with disease severity and blood coagulation were analyzed., Results: The 30-day mortality in the co-infection group (35.5%) was significantly higher than in the single-infection group (19.1%). The levels of IL-6 and TNF-α in the co-infection group were higher than in the single-infection group. Moreover, high levels of IL-6, IL-8, and TNF-α were positively correlated with disease severity (Spearman P value < 0.05). High levels of IL-6 and TNF-α were negatively correlated with the platelet count (Spearman P value < 0.05) and positively correlated with prothrombin time, and plasma levels of fibrin degradation product and D-dimer levels (Spearman P value < 0.05 for all)., Conclusion: Septic patients with bacterial co-infection had increased plasma levels of pro-inflammatory cytokines. Furthermore, a positive correlation between high levels of pro-inflammatory cytokines and increased disease severity and depressed blood coagulation function for septic patients with co-infection was identified., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by the Shock Society.)

Argentina exhibits low serological prevalence for Hepatitis B virus (HBV); however, occult hepatitis B infection (OBI) has been reported in blood donors, Amerindians and individuals coinfected with hepatitis C virus (HCV), and/or human immunodeficiency virus (HIV). The aim of this study was to analyze the genetic diversity of HBV and to evaluate serological marker associations and coinfections with HCV and HIV in patients attending and treated in a public hospital in the province of Buenos Aires, Argentina. A total of 189 HBV reactive samples (HBsAg and/or anti-HBc) were analyzed for HBV DNA characterization. All reactive samples were tested for anti-HCV and HIV-antigen/antibody using CMIA assays. Thirty-six samples exhibited detectable HBV DNA, 7 of which were OBI. HBV sequences were classified as subgenotypes A1, A2, B2, D3, F1b, F3 and F4. Mutations related to the ability to escape the host's immune response, resistance to antiviral therapy and progression to disease were found in patients, partly due to the variable sensitivity of HBsAg, the reverse transcriptase, the basal core promoter and the preCore. HCV and HIV prevalence was 10% and most of the genotypes found in the sequences were genotype 1 and B/F recombinant subtype, respectively. Of the total samples analyzed, 7 exhibited coinfections. This study shows the frequency of OBI, subgenotype distribution, HBV mutations and coinfections, which may have important clinical implications in public hospital patients. Planned prevention, detection and treatment adherence are needed to reduce transmission and morbidity in vulnerable populations.

Pregnant women are an important group to be monitored for infection due to the risk of transmitting infections to their babies. Both herpes simples virus (HSV) and Zika virus (ZIKV) are neurotropic viruses that can be transmitted congenitally. In this study, the prevalence and risk factors of HSV among Zika-positive and -negative pregnant women from Rio de Janeiro, Brazil, were evaluated and compared. About 167 serum samples included in our study were from pregnant women with ZIKV infection symptoms, who were attended to in different hospitals in Rio de Janeiro between November 2015 to February 2016. Blood samples collected from 167 pregnant women were used for this study. The presence of HSV antibodies and viremia were evaluated by commercial ELISA and quantitative real-time polymerase chain reaction analyses, respectively. The data obtained from medical records were statistically analyzed. The HSV-1 and HSV-2 prevalence among pregnant women was 80.2% and 12.5% for Zika-positive women and 84.5% and 5.6% for Zika-negative women, respectively. None of the pregnant women exhibited HSV viremia. Age, trimester of gestation, and skin color were associated with HSV-1 and HSV-2 prevalence among the groups studied. HSV-2 was more prevalent in Zika-positive pregnant women than in Zika-negative pregnant women, and this simultaneous infection should be better investigated in future studies., (© 2020 Wiley Periodicals LLC.)

Background: School-aged children (SAC) are a high-risk demographic group for infectious diseases and malnutrition. The objective of this study was to assess the burden and the effect of Plasmodium falciparum and Schistosoma haematobium infections on the haematological indices in SAC and the confounding influence of malnutrition on the outcomes., Methods: This cross-sectional study was conducted in SAC 4-14 years old living in Ikata, Bafia and Mile 14-Likoko in Muyuka, Cameroon. Anthropometric measures of malnutrition were obtained and blood samples collected were used for detection of malaria parasites by Giemsa-stained blood films using light microscopy and complete blood count analysis using an automated haematology analyser. Urine samples collected were used to detect micro haematuria with the aid of reagent strips and the eggs of S. haematobium by urine filtration technique. Multiple linear regression model was used to examine influence of independent variables on haematological parameters., Results: Out of the 606 SAC examined, the prevalence of single infections with Plasmodium or S. haematobium and co-infection with both parasites was 16.2, 16.3 and 8.3%, respectively. Overall, malaria parasite (MP), urogenital schistosomiasis, malnutrition, anaemia, haematuria, microcytosis and thrombocytopenia was prevalent in 24.4, 24.6, 25.9, 74.4, 12.2, 45.4 and 11.1% of SAC, respectively. A significant linear decline (P = 0.023) in prevalence of P. falciparum infection with the severity of stunting was observed. Factors that significantly influenced haematological parameters included haemoglobin: age, stunting and MP; haematocrit: age and MP; white blood cell count: age; red blood cell count; age and MP; lymphocyte counts: stunting; mean cell volume: age; mean cell haemoglobin: age and stunting; mean cell haemoglobin concentration: sex, stunting and red cell distribution width-coefficient of variation: sex, age and stunting., Conclusions: Malnutrition, Plasmodium and S. haematobium infections are common while anaemia is a severe public health problem in Muyuka, Cameroon. The interaction between haematological parameters with malaria parasites as well as linear growth index was negative and other interactions indicate systemic inflammation. While findings provide contextual intervention targets to ensure the judicious use of the limited resources, there is need for regular monitoring and proper treatment to improve the health of the underserved population.

The objective of this work was to identify predictive factors of fibrosis regression after direct antiviral agents (DAAs) in HCV-monoinfected and HIV/HCV-coinfected patients. This was a prospective study of HCV-monoinfected (n = 20), HIV/HCV-co-infected (n = 66) patients and healthy controls (n = 15). Patients had started DAAs and achieved sustained virological response. Liver stiffness (LS) and serum concentrations of profibrotic transforming growth factor (TGF)-β1 and CXC chemokine ligand 4 (CXCL4) and antifibrotic HGF hepatocyte growth factor (HGF) were analyzed at baseline (M0) and 12 months after starting DAAs (M12). A M12 LS achievement of ≤ 9.5 kPa was considered the cutoff point to discharge from a liver clinic. The LS decrease from M0 to M12 was 34%. No significant differences were observed in LS decline between HCV- and HIV/HCV-infected individuals. Changes of serum CXCL4, TGF-β1 and HGF levels did not correlate with LS improvement. 16 out from 56 patients (28%) with a baseline LS > 9.5 achieved a M12 LS ≤ 9.5. HCV-monoinfected and HIV/HCV coinfected patients experienced a significant reduction of LS after sustained virological response. This improvement did not correlate with changes in serum profibrotic or antifibrotic markers. A 29% of those with a baseline LS > 9.5 achieved a LS under this cutoff point.

Coronavirus Disease 2019 (COVID-19) is an acute respiratory infectious disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection that started in Wuhan, China in December 2019 and has spread rapidly worldwide. It's critical to take extra precautions if a person has chronic illnesses (comorbidities), such as human immunodeficiency (HIV) infection. Concerns about people living with HIV (PLHIV) having a higher risk of serious COVID-19 disease may be based on the assumption that PLHIV are more likely to be immunocompromised. On the other hand, limited information is available in such people about the characteristics of co-infection between SARS-CoV-2 and Human Immunodeficiency Virus (HIV) who are at greater risk than the general population. Our findings, is of a 32 year old patient who came to Emergency Unit of Wangaya Hospital, Medical Faculty, Udayana University in Denpasar, Bali with complaint of fever, dry cough, and shortness of breath since prior 3 days and had also the past history prolonged fever, weight loss more than 10% 4 weeks. Diagnosis of COVID-19 was confirmed by nasopharyngeal swab sample was used for RT-PCR assay and PITC to confirm HIV infection. He had prolonged hospitalized and discharge after 18 days.

The spreading of viral hepatitis among injecting drug users (IDU) is an emerging public health concern. This study explored the prevalence and the risks of hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis D virus (HDV) among IDU-dominant prisoners in Taiwan. HBV surface antigen (HBsAg), antibodies to HCV (anti-HCV) and HDV (anti-HDV), viral load and HCV genotypes were measured in 1137(67.0%) of 1697 prisoners. 89.2% of participants were IDUs and none had HIV infection. The prevalence of HBsAg, anti-HCV, dual HBsAg/anti-HCV, HBsAg/anti-HDV, and triple HBsAg/anti-HCV/anti-HDV was 13.6%, 34.8%, 4.9%, 3.4%, and 2.8%, respectively. HBV viremia rate was significantly lower in HBV/HCV-coinfected than HBV mono-infected subjects (66.1% versus 89.9%, adjusted odds ratio/95% confidence intervals [aOR/CI] = 0.27/0.10-0.73). 47.5% anti-HCV-seropositive subjects (n = 396) were non-viremic, including 23.2% subjects were antivirals-induced. The predominant HCV genotypes were genotype 6(40.9%), 1a(24.0%) and 3(11.1%). HBsAg seropositivity was negatively correlated with HCV viremia among the treatment naïve HCV subjects (44.7% versus 72.4%, aOR/CI = 0.27/0.13-0.58). Anti-HCV seropositivity significantly increased the risk of anti-HDV-seropositivity among HBsAg carriers (57.1% versus 7.1%, aOR/CI = 15.73/6.04-40.96). In conclusion, IUDs remain as reservoirs for multiple hepatitis viruses infection among HIV-uninfected prisoners in Taiwan. HCV infection increased the risk of HDV infection but suppressed HBV replication in HBsAg carriers. An effective strategy is mandatory to control the epidemic in this high-risk group.

It can be a diagnostic challenge to identify patients with coronavirus disease 2019 in whom antibiotics can be safely withheld. This study evaluated the effectiveness of a guideline implemented at Sheffield Teaching Hospitals NHS Foundation Trust that recommends withholding antibiotics in patients with low serum procalcitonin (PCT), defined as ≤0.25 ng/mL. Results showed reduced antibiotic consumption in patients with PCT ≤0.25 ng/mL with no increase in mortality, alongside a reduction in subsequent carbapenem prescriptions during admission. The results support the effectiveness of this guideline, and further research is recommended to identify the optimal cut-off value for PCT in this setting., (Crown Copyright © 2021. Published by Elsevier Ltd. All rights reserved.)

In canine leishmaniosis caused by the protozoan Leishmania infantum, little is known about how co-infections with or co-seropositivities for other pathogens can influence aggravation of this disease. Therefore, the objectives of this study were to evaluate the frequency of co-infections with or co-seropositivities for certain pathogens in dogs seropositive for L. infantum and their relationship with clinical signs, histological changes and L. infantum load. Sixty-six L. infantum-seropositive dogs were submitted to clinical examination, collection of blood and bone marrow, culling, and necropsy. Antibodies against Anaplasma spp., Borrelia burgdorferi sensu lato, Ehrlichia spp. and Toxoplasma gondii and Dirofilaria immitis antigens were investigated in serum. Samples from different tissues were submitted to histopathology and immunohistochemistry for the detection of Leishmania spp. and T. gondii. Quantitative real-time PCR was used to assess the L. infantum load in spleen samples. For detection of Coxiella burnetii, conventional PCR and nested PCR were performed using bone marrow samples. All 66 dogs tested positive for L. infantum by qPCR and/or culture. Fifty dogs (76%) were co-seropositive for at least one pathogen: T. gondii (59%), Ehrlichia spp., (41%), and Anaplasma spp. (18%). Clinical signs were observed in 15 (94%) dogs monoinfected with L. infantum and in 45 (90%) dogs co-seropositive for certain pathogens. The L. infantum load in spleen and skin did not differ significantly between monoinfected and co-seropositive dogs. The number of inflammatory cells was higher in the spleen, lung and mammary gland of co-seropositive dogs and in the mitral valve of monoinfected dogs. These results suggest that dogs infected with L. infantum and co-seropositive for certain pathogens are common in the region studied. However, co-seropositivities for certain pathogens did not aggravate clinical signs or L. infantum load, although they were associated with a more intense inflammatory reaction in some organs., Competing Interests: The authors have declared that no competing interests exist.

Background: Multidrug-resistant or rifampicin-resistant tuberculosis (MDR/RR-TB) and human immunodeficiency virus (HIV) co-infection are a deadly combination. While evidence on the effects of HIV co-infection on MDR/RR-TB treatment outcomes is well-documented, little published evidence describes the effects of MDR/RR-TB treatment on HIV disease., Methods: We conducted a review of literature published prior to June 2020. We searched Pubmed, CINAHL, and EMBASE using variations of the terms "multidrug-resistant tuberculosis," "HIV," and either "CD4" or "viral load." Two reviewers independently completed title and abstract screening, full-text screening, article evaluation, and data extraction. We also included five published articles evaluated as evidence by the World Health Organization (WHO) in preparation for the 2019 MDR/RR-TB treatment guideline update., Results: A total of 459 references were returned, with 362 remaining after duplicate removal. Following article screening, six manuscripts were included. Articles reported CD4 count and/or viral load results for MDR/RR-TB and HIV co-infected patients during and/or after MDR/RR-TB treatment. The additional five references identified from the WHO guideline revision did not report HIV disease indicators after MDR/RR-TB initiation., Conclusion: There is a paucity of evidence on HIV disease indicators following MDR/RR-TB treatment. Researchers should report longitudinal HIV disease indicators in co-infected patients in publications., Competing Interests: The authors have declared that no competing interests exist.

Background & Aims: Coronavirus disease 2019 (COVID-19) is a major global health threat. We aimed to describe the characteristics of liver function in patients with SARS-CoV-2 and chronic hepatitis B virus (HBV) coinfection., Methods: We enrolled all adult patients with SARS-CoV-2 and chronic HBV coinfection admitted to Tongji Hospital from February 1 to February 29, 2020. Data of demographic, clinical characteristics, laboratory tests, treatments, and clinical outcomes were collected. The characteristics of liver function and its association with the severity and prognosis of disease were described., Results: Of the 105 patients with SARS-CoV-2 and chronic HBV coinfection, elevated levels of liver test were observed in several patients at admission, including elevated levels of alanine aminotransferase (22, 20.95%), aspartate aminotransferase (29, 27.62%), total bilirubin (7, 6.67%), gamma-glutamyl transferase (7, 6.67%), and alkaline phosphatase (1, 0.95%). The levels of the indicators mentioned above increased substantially during hospitalization (all P < .05). Fourteen (13.33%) patients developed liver injury. Most of them (10, 71.43%) recovered after 8 (range 6-21) days. Notably the other, 4 (28.57%) patients rapidly progressed to acute-on-chronic liver failure. The proportion of severe COVID-19 was higher in patients with liver injury (P = .042). Complications including acute-on-chronic liver failure, acute cardiac injury and shock happened more frequently in patients with liver injury (all P < .05). The mortality was higher in individuals with liver injury (28.57% vs 3.30%, P = .004)., Conclusion: Liver injury in patients with SARS-CoV-2 and chronic HBV coinfection was associated with severity and poor prognosis of disease. During the treatment of COVID-19 in chronic HBV-infected patients, liver function should be taken seriously and evaluated frequently., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Originated in Wuhan, China, the coronavirus 19 disease (COVID-19) has quickly spread worldwide, reaching countries that already faced other endemics and epidemics. In Brazil, such a concerning situation includes arboviruses, among which the dengue virus stands out. Here, we determined the rate of SARS-CoV-2/dengue virus co-infection in a total of 178 patients with COVID-19 symtoms admitted into a large public hospital of the Federal District of Brazil. Furthermore, we evaluated whether prior or active dengue virus infection influenced hematological, biochemical, and clinical parameters of such patients. One hundred and twelve (63%) individuals tested positive for COVID-19, of which 43 (38.4%) were co-infected with dengue virus, and 50 (44.6%) had antibodies indicative of previous dengue infection. Co-infected patients showed lower numbers of circulating lymphocytes and monocytes, higher glucose rates, and a worse pulmonary condition. Of note, prior infections with dengue virus did not influence clinical parameters, but active dengue fever resulted in higher hospitalization rate. In conclusion, amid the current complex epidemiological scenario in Brazil, our data support the notion that SARS-CoV-2 and dengue co-infection affects an important percentage of COVID-19 patients and leads to worse clinical parameters, requiring greater attention from health authorities., (Copyright © 2020. Published by Elsevier B.V.)

Background: HIV and HCV coinfection leads to accelerated liver fibrosis, in which microbial translocation and systemic inflammation might play important roles., Objective: This study aimed to provide an extensive profile of the plasma microbial translocation and inflammation biomarkers associated with advanced liver fibrosis among HIV-HCV-coinfected patients., Methods: This cross-sectional study recruited 343 HIV-HCV-coinfected patients on combination antiretroviral therapy (cART) from a rural prefecture of Yunnan province in Southwest China. The plasma concentrations of sCD14 and 27 cytokines and chemokines were assayed and compared against advanced or mild levels of liver fibrosis., Results: Of the 343 HIV-HCV-coinfected patients, 188 (54.8%) had severe or advanced liver fibrosis (FIB-4 > 3.25). The patients with advanced liver fibrosis (FIB-4 > 3.25 vs. FIB-4 ≤ 3.25) had higher plasma levels of interleukin (IL)-1β, IL-6, IL-7, IL-9, IL-12, IL-15, IL-17, granulocyte macrophage colony stimulating factor (GM-CSF), Interferon-γ (IFN-γ), tumor necrosis factor (TNF-α), IL-4, IL-10, IL-13, fibroblast growth factor 2 (FGF-basic), and Monocyte chemoattractant protein-1 (MCP-1). Multivariable logistic regression models showed that advanced liver fibrosis was associated with an increased plasma level of IL-1β, IL-6, IL-7, IL-12, IL-17, GM-CSF, IFN-γ, IL-4, IL-10, MCP-1, Eotaxin, and FGF-basic, with FGF-basic continuing to be positively and significantly associated with advanced liver fibrosis, after Bonferroni correction for multiple comparisons (adjusted odds ratio (aOR) = 1.92; 95%CI: 1.32-2.81; p = 0.001). Plasma sCD14 was also significantly associated with advanced liver fibrosis (aOR = 1.13; 95%CI: 1.01-1.30; p = 0.049)., Conclusions: HIV-HCV-coinfected patients are living with a high prevalence of advanced liver fibrosis which coexists with a mixture of elevated plasma inflammation and microbial translocation biomarkers. The significant associations of advanced liver fibrosis with FGF-basic and sCD14 may reveal pathogenic mechanisms and potential clinical intervention targets for liver fibrosis in HCV-HIV coinfection.

Introduction: The study was carried out to determine the prevalence of and risk factors for hepatitis B and C viral co-infections in HIV infected children in Lagos., Method: A cross-sectional study conducted to determine the prevalence and risk factors for hepatitis B and C viral co-infection in children aged 2 months to 13 years. There were 187 HIV infected and 187 HIV naïve age, sex-matched controls. Blood samples of participants were assayed for the serologic markers [HBsAg, anti-HBc, and anti-HCV)] of HBV and HCV viral infections using the Enzyme-Linked Immunosorbent assay (ELISA) method., Result: The prevalence of HBV infection using HBsAg was 5.3% and 4.8% (p = 0.814), among HIV-infected and HIV naïve children respectively, while using anti-HBc the prevalence was 7.0% and 7.5% (p = 0.842) among HIV- infected and HIV naïve children respectively. The prevalence of HCV infection among HIV- infected and HIV naive children were equal to 0.5% (p = 1.000). There was also no significant association with the identifiable risk factors (sharing of a toothbrush, sharing of needles, incision marks/tattoo, hepatitis B immunization status, history of blood transfusion, previous surgical operation, sexual exposure/abuse, history of jaundice, and genital circumcision) and the HBV and or HCV status among both groups of children. History of sexual exposure/abuse and history of jaundice were however found to be predictors of the presence of HBsAg among HIV infected children only, using a binary logistic regression model., Conclusion: The prevalence of HBV and or HCV infection among HIV-infected children is similar to the prevalence among HIV naïve children, suggesting that HIV-infected children are not more predisposed to viral hepatitis than healthy children. Also, there was no significant difference in the prevalence of HBV infection irrespective of the use of HBsAg or anti-HBc., Competing Interests: The authors have declared that no competing interests exist.

Objectives: To characterise infections by HIV, Treponema pallidum, hepatitis B (HBV) and C virus (HCV) in parturients admitted to Irene Neto Maternity, Lubango city, Huíla province, Angola, namely its seropositivity rate and its association with sociodemographic factors., Methods: An observational, cross-sectional and analytical facility-based survey was conducted among 500 parturients at Irene Neto Maternity, from October 2016 to September 2017. Women in labour were screened for antibodies against HIV-1/2, T. pallidum and HCV. Antigen detection was used to diagnose HBV infections. Sociodemographic data were also collected. The seropositivity rate and respective CIs were estimated at a level of 95%. Multivariable logistic regression models were performed to explore the association between the studied infections and sociodemographic factors., Results: In 11.8% of the parturients (95% CI 9.3 to 14.9), at least one infection was detected. HBV infection was the most common (8.6%), followed by HIV infection (3.0%) and syphilis (1.0%). Coinfection with HBV and HIV was observed in two parturients (0.4%) and HBV, HIV and T. pallidum were all detected in one parturient (0.2%). No HCV infection was detected. For each additional year of formal education, pregnant women had a 10.0% lower chance of being infected with HBV (adjusted OR=0.900, 95% CI 0.816 to 0.992)., Conclusions: This study is one of the few reports contributing for the knowledge of some sexually transmitted infections epidemiology in Angola. The seropositivity rate of the studied infections is of concern, especially the high endemicity of HBV. There is a need for a stronger commitment and further research to design cost-effective public health and clinical interventions to improve the situation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Occult hepatitis B (OHB) is a major concern in HIV infected patients as it associates with a high risk of HBV reactivation and disease progression. However, data on the prevalence of OHB among HIV positive patients in Ethiopia is lacking. This study aims to determine the prevalence of OHB in HBV/HIV co-infected patients from Gondar, Ethiopia., Methods: A total of 308 consented HIV positive patients were recruited from the University of Gondar Teaching Hospital, Ethiopia. Clinical and demographic data of the participants were recorded. Plasma was tested for HBsAg and anti-HBc using commercial assays (Abbott Architect). In HBsAg negative anti-HBc positive patient samples, total DNA was isolated and amplified using nested PCR with primers specific to HBV polymerase, surface and pre-core/core regions, followed by Sanger sequencing and HBV mutational analysis using MEGA 7.0., Results: Of the total study subjects, 62.7% were female, median age 38.4 years, interquartile range (IQR): 18-68, and 208 (67.5%) had lifestyle risk factors for HBV acquisition. Two hundred and ninety-one study subjects were HIV+/HBsAg-, out of which 115 (39.5%) were positive for anti-HBc. Occult hepatitis B was detected in 19.1% (22/115) of anti-HBc positive HIV patients. HBV genotype D was the predominant genotype (81%) among OHB positive patients. Mutations associated with HBV drug resistance, HBV reactivation, and HCC risk were detected in 23% (5/22), 14% (3/22) and 45.5% (10/22) of patients, respectively., Conclusion: This study found a high rate of occult hepatitis B in HIV patients. Further, high rates of mutations associated with HBV reactivation, drug resistance, and HCC risk were detected in these patients. These data highlighted the need for integrating OHB screening for proper management of liver diseases in HIV patients., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Procalcitonin (PCT) has been proposed for differentiating viral vs. bacterial infections. In COVID-19, some preliminary results have shown that PCT testing could act as a predictor of bacterial co-infection and be a useful marker for assessment of disease severity., Methods: We studied 83 COVID-19 hospitalized patients in whom PCT was specifically ordered by attending physicians. PCT results were evaluated according to the ability to accurately predict bacterial co-infections and death in comparison with other known biomarkers of infection and with major laboratory predictors of COVID-19 severity., Results: Thirty-three (39.8%) patients suffered an in-hospital bacterial co-infection and 44 (53.0%) patients died. In predicting bacterial co-infection, PCT showed a relatively low accuracy (area under receiver-operating characteristic [ROC] curve [AUC]: 0.757; 95% confidence interval [CI]: 0.651-0.845), with a strength for detecting the outcome not significantly different from that of white blood cell count and C-reactive protein (CRP). In predicting patient death, PCT showed an AUC of 0.815 (CI: 0.714-0.892), not better than those of other more common laboratory tests, such as blood lymphocyte percentage (AUC: 0.874, p=0.19), serum lactate dehydrogenase (AUC: 0.860, p=0.47), blood neutrophil count (AUC: 0.845, p=0.59), and serum albumin (AUC: 0.839, p=0.73)., Conclusions: Procalcitonin (PCT) testing, even when appropriately ordered, did not provide a significant added value in COVID-19 patients when compared with more consolidated biomarkers of infection and poor clinical outcome. The major application of PCT in COVID-19 is its ability, associated with a negative predictive value >90%, to exclude a bacterial co-infection when a rule-out cut-off (<0.25 μg/L) is applied.

A key unsolved question in the current coronavirus disease 2019 (COVID-19) pandemic is the duration of acquired immunity. Insights from infections with the four seasonal human coronaviruses might reveal common characteristics applicable to all human coronaviruses. We monitored healthy individuals for more than 35 years and determined that reinfection with the same seasonal coronavirus occurred frequently at 12 months after infection.

Background: The morbidity in dengue fever is dependent on the dengue virus (DENV) serotypes, the patient age, predisposing immunogenic markers and the frequency of primary and secondary infections. This study aims to distinguish acute primary from secondary dengue infections of Vietnamese adults and to assess the association of viremia and anti-dengue immunoglobulin levels with clinical outcomes., Study Design: Viral RNA, dengue serotypes and levels of anti-dengue IgM and IgG of hospitalized adult cases were determined in EDTA-plasma samples prospectively collected during three consecutive years of dengue infection in Hanoi. Patients admitted to hospital within 7 days of their 1st reported fever were included. Primary infections were anti-dengue IgG enzyme-linked immunosorbent assay (ELISA) negative on both day of hospital entry (day 0) and day two or three of hospitalization (day 2 or 3) with a positive anti-dengue IgM on either day 0 or day 2 or 3 hospitalization. The secondary infections were anti-dengue IgG ELISA positive on both day 0 and day 2 or 3 with positive anti-dengue IgM ELISA on either day 0 or day 2 or 3., Results: The hospitalized dengue fever cases between October 2016 and March 2019 were predominantly secondary infections (74%, 68% and 77%, respectively) with DENV-1 (60% and 65%) and DENV-2 (22% and 26%) serotypes determined in the latter two years. The viremia in primary infection was significantly higher than that in secondary infection (P < 0.01) and positively correlated with the days of hospital stay. In secondary infections, platelet counts were lower than in primary infections (P = 0.04) and IgG levels in secondary infection negatively correlated with platelet counts (Spearman's r = -0.22, P < 0.01)., Conclusions: Our results indicate high rates of secondary infection with DENV1 and DENV2 serotypes. Anti-dengue immunoglobulins negatively correlate with hospital stay and platelet counts with few warning signs or severe disease. Further investigations of specific antibodies in adults which predict auto-inflammatory activity after the recovery from dengue infection are warranted., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Acquired immunodeficiency syndrome (AIDS) complicated with tuberculosis (TB) is a global public issue. Due to the paucity of bacteria in AIDS/TB, blood-based biomarkers that reflect disease severity are desired. Plasma levels of matricellular proteins, such as osteopontin (OPN) and galectin-9 (Gal-9), are known to be elevated in AIDS and TB. Therefore, full-length (FL)-Gal9 and FL-OPN, and their truncated forms (Tr-Gal9, Ud-OPN), and 38 cytokines/chemokines were measured in the plasma of 24 AIDS (other than TB), 49 TB, and 33 AIDS/TB patients. Receiver-operating characteristic analysis was used to screen molecules that could distinguish either between disease and normal group, among each disease group, or between deceased patients and survivors. Selected molecules were further analyzed for significant differences. Tr-Gal9 had the highest ability to differentiate TB from AIDS or AIDS/TB, while Ud-OPN distinguished multidrug resistance (MDR)-TB from non-MDR TB, and extra-pulmonary TB from pulmonary TB. Molecules significantly elevated in deceased patients included; FL-Gal9, Tr-Gal9, interleukin (IL)-1 receptor antagonist, IL-17A and transforming growth factor-α in AIDS; IL-6, granulocyte colony-stimulating factor and monocyte chemotactic protein-1 in TB; and macrophage inflammatory protein-1β in AIDS/TB. From the sensitivity, specificity, and significant elevation, Tr-Gal9 is the best biomarker of inflammation and severity in AIDS and AIDS/TB.

Introduction: the most recently discovered severe acute respiratory syndrome Coronavirus 2 (SARS-COV-2) that causes COVID-19, subjected the entire world in turmoil health-wise and economically. With higher burden of malaria in Nigeria and other sub-Saharan African countries coupled with fragile healthcare system and delivery, these may pose a threat in the diagnosis and management of COVID-19 patients co-infected with malaria. Free radicals have been implicated in the progression and pathogenesis of malaria and COVID-19 through Fenton's reaction and cytokine storm respectively., Methods: the current research comprises of seventy-four (74) participants; 20 apparently healthy controls and 54 COVID-19 patients (34 among which were co-infected with malaria). Serum levels of 8-iso PGF2α and Alphatocopherol were determined among the study participants using ELISA technique and colorimetric assay, respectively., Results: results revealed statistically significant elevation of 8-iso PGF2α in COVID-19 patients co-infected with malaria compared to COVID-19 patients only, and this may be due to increase production of free radicals. Furthermore, a significant decrease of Alphatocopherol was observed in COVID-19 co-infected with malaria compared to COVID-19 patients due to increase utilization of antioxidants in counterbalancing the negative effect of free radicals generated., Conclusion: conclusively, SARS-COV-2 patients co-infected with malaria might be predisposed to oxidative stress and low Alphatocopherol. The increase in oxidative stress is proportional to malaria parasite density and inversely related to Alphatocopherol levels. This implies that oxidative stress is notably higher and such patients may have a severer form of the COVID-19. Increased 8-iso-PGF2α in co-infection and decreased alphatocopherol levels can reflect the severity and adverse outcomes compared to COVID-19 naïve because of their tremendous involvement in the pathogenesis and progression of diseases., Competing Interests: The authors declare no competing interest., (Copyright: Yahaya Muhammad et al.)

E. granulosus is a cestode that causes Cystic Echinococcosis (CE), a zoonotic disease with worldwide presence. The immune response generated by the host against the metacestode induces a permissive Th2 response, as opposed to pro-inflammatory Th1 response. In this view, mixed Th2 and regulatory responses allow parasite survival. Overall, larval Echinococcus infections induce strong regulatory responses. Fasciola hepatica, another common helminth parasite, represents a major infection in cattle. Co-infection with different parasite species in the same host, polyparasitism, is a common occurrence involving E. granulosus and F. hepatica in cattle. 'While it is known that infection with F. hepatica also triggers a polarized Th2/Treg immune response, little is reported regarding effects on the systemic immune response of this example of polyparasitism. F. hepatica also triggers immune responses polarized to the Th2/ Treg spectrum. Serum samples from 107 animals were analyzed, and were divided according to their infection status and Echinococcal cysts fertility. Cytokines were measured utilizing a Milliplex Magnetic Bead Panel to detect IFN-γ, IL-1, IL-2, IL-4, IL-6, IL-10, IL-12 and IL-18. Cattle infected only with F. hepatica had the highest concentration of every cytokine analyzed, with both 4.24 and 3.34-fold increases in IL-10 and IL-4, respectively, compared to control animals, followed by E. granulosus and F. hepatica co-infected animals with two-fold increase in IL-10 and IL-4, compared to control animals, suggesting that E. granulosus co-infection dampens the cattle Th2/Treg immune response against F. hepatica. When considering Echinococcal cyst fertility and systemic cytokine concentrations, fertile cysts had higher IFN-γ, IL-6 and IL-18 concentrations, while infertile cysts had higher IL-10 concentrations. These results show that E. granulosus co-infection lowers Th1 and Th2 cytokine serological concentration when compared to F. hepatica infection alone. E. granulosus infections show no difference in IFN-γ, IL-1, IL-2, IL-6 and IL-18 levels compared with control animals, highlighting the immune evasion mechanisms of this cestode., Competing Interests: The authors have declared that no competing interests exist.

Background: Zika virus (ZIKV) was discovered over 70 years ago in East Africa, but little is known about its circulation and pathogenesis there., Methods: We screened 327 plasma samples collected 2-12 months after febrile illness in Western and coastal Kenya (1993-2016) for binding and neutralizing antibodies to distinguish ZIKV and dengue virus (DENV) responses, which we found were common in coastal Kenya., Results: Two cases had durable ZIKV-specific antibodies and 2 cases had ZIKV antibodies at similar levels as DENV antibodies., Conclusions: This suggests low-level ZIKV circulation in Kenya over 2 decades and sets a baseline for future surveillance efforts in East Africa., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Chronic inflammation in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfection increases cognitive impairment. With newer, direct-acting antiviral therapies for HCV, our objective was to determine whether chronic inflammation would be decreased and cognition improved with HCV sustained viral response (SVR) in coinfection., Methods: We studied 4 groups longitudinally: 7 HCV-monoinfected and 12 HIV/HCV-coinfected persons before and after treatment for HCV, 12 HIV-monoinfected persons, and 9 healthy controls. We measured monocyte activation and gene expression, monocyte-derived exosome micro-ribonucleic acid (miRNA) expression, plasma inflammation, and cognitive impairment before and after therapy., Results: Plasma soluble CD163 and neopterin were decreased in HCV mono- and coinfected persons. Blood CD16+ monocytes were decreased in coinfection after HCV treatment. Global deficit score improved 25% in coinfection with the visual learning/memory domain the most improved. Hepatitis C virus SVR decreased monocyte interferon genes MX1, IFI27, and CD169 in coinfection and MX1, LGALS3BP, and TNFAIP6 in HCV monoinfection. Monocyte exosomes from coinfected persons increased in microRNA (miR)-19a, miR-221, and miR-223, all of which were associated with decreasing inflammation and nuclear factor-κB activation., Conclusions: Hepatitis C virus cure in coinfection brings monocyte activation to levels of HIV alone. Cognitive impairment is significantly improved with cure but not better than HIV infection alone, which strong suggests that cognitive impairment was driven by both HIV and HCV.SummaryHCV cure in HIV coinfection improves monocyte and plasma activation markers and increases cognitive function in the visual learning/memory domain., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background and Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly identified pathogen that mainly spreads by droplets. Most published studies have been focused on adult patients with coronavirus disease 2019 (COVID-19), but data concerning pediatric patients are limited. In this study, we aimed to determine epidemiological characteristics and clinical features of pediatric patients with COVID-19., Methods: We reviewed and analyzed data on pediatric patients with laboratory-confirmed COVID-19, including basic information, epidemiological history, clinical manifestations, laboratory and radiologic findings, treatment, outcome, and follow-up results., Results: A total of 74 pediatric patients with COVID-19 were included in this study. Of the 68 case patients whose epidemiological data were complete, 65 (65 of 68; 95.59%) were household contacts of adults. Cough (32.43%) and fever (27.03%) were the predominant symptoms of 44 (59.46%) symptomatic patients at onset of the illness. Abnormalities in leukocyte count were found in 23 (31.08%) children, and 10 (13.51%) children presented with abnormal lymphocyte count. Of the 34 (45.95%) patients who had nucleic acid testing results for common respiratory pathogens, 19 (51.35%) showed coinfection with other pathogens other than SARS-CoV-2. Ten (13.51%) children had real-time reverse transcription polymerase chain reaction analysis for fecal specimens, and 8 of them showed prolonged existence of SARS-CoV-2 RNA., Conclusions: Pediatric patients with COVID-19 presented with distinct epidemiological, clinical, and radiologic characteristics from adult patients. Nearly one-half of the infected children had coinfection with other common respiratory pathogens. It is not uncommon for pediatric patients to have prolonged fecal shedding of SARS-CoV-2 RNA during the convalescent phase., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)

Introduction: Inflammation associated with Helicobacter pylori (H. pylori) infection is linked to the development of a gastric precancerous lesion. Helminth infections could influence the pro-inflam matory response to such infection from LTCD4+ Th1 to a less harmful LTCD4+ Th2 response. Ob jective: To characterize the polarization of the LTCD4+ Th2 immune response in co-infected pa tients with H. pylori and helminths from low-risk areas for developing gastric cancer., Patients and Method: We analyzed 63 patients infected by H. pylori (40 adults and 23 children). Through the Multiplex Analysis technology (xMAP), we determined the serum profiles of the interleukins asso ciated with the polarization of the immune response of LTCD4+ Th1 (IL-1Β, INF-γ, TNF-α) as well as the LTCD4+ Th2 (IL-4, IL-10, and IL-13). The ratio between helminths co-infection status in H. pylori-infected patients and the polarization of the immune response mediated by LTCD4+ Th1 and LTCD4+ Th2 was assessed using a Mixed Effects Logistic Regression Model., Results: The frequency of helminths was similar between adults (15%) and children (17%). The polarization of the immu ne response was more prevalent in LTCD4+ Th1. Serum values of interleukins associated with the immune response polarization of LTCD4+ Th1 (IL-1Β, INF-γ, and TNF-α) and LTCD4+ Th2 (IL-4, IL-10, and IL-13) were independent of helminths infection status., Conclusion: The prevalence of in testinal parasitic infection was high and the immune response polarization was mainly LTCD4 + Th1.

Endothelial cell dysfunction contributes to sepsis induced initiate immune response and the infiltration of immune cells into organs, resulting in organ injury. Heat shock protein A12B (HSPA12B) is predominantly expressed in endothelial cells. The present study investigated whether endothelial HSPA12B could regulate macrophage pro-inflammatory response during sepsis. Wild type (WT) and endothelial cell-specific HSPA12B deficient (HSPA12B -/- ) mice were subjected to CLP sepsis. Mortality and cardiac function were monitored. Higher mortality, worsened cardiac dysfunction, and greater infiltrated macrophages in the myocardium and spleen were observed in HSPA12B -/- septic mice compared with the WT septic mice. The serum levels of TNF-α and IL-1β were higher and the levels of IL-10 were lower in HSPA12B -/- septic mice than in WT septic mice. Importantly, endothelial exosomes contain HSPA12B which can be uptaken by macrophages. Interestingly, endothelial exosomal HSPA12B significantly increases IL-10 levels and decreases TNF-α and IL-1β production in LPS-stimulated macrophages. Mechanistic studies show that endothelial exosomal HSPA12B downregulates NF-κB activation and nuclear translocation in LPS stimulated macrophages. These data suggest that endothelial HSPA12B plays a novel role in the regulation of macrophage pro-inflammatory response via exosomes during sepsis and that sepsis induced cardiomyopathy and mortality are associated with endothelial cell deficiency of HSPA12B., (Copyright © 2020 Tu, Wang, Zhang, Ha, Wang, Fan, Yang, Gill, Ozment, Dai, Liu, Williams and Li.)

Dengue virus (DENV) co-circulation in Brazil represents a challenge for treatment and vaccine development. Despite public health impact, the occurrence of coinfections with other viruses is a common event. Increased T cell activation and altered inflammatory response are found during DENV coinfection with Human Immunodeficiency Virus (HIV) impacting HIV-pathogenesis. Even with Antiretroviral therapy (ART), HIV- treated patients had chronic immune activation and lymphocyte apoptosis. However, apoptotic mechanisms have not been investigated during coinfection with DENV. Our attention was attracted to apoptotic cell markers expressions in PBMCs from DENV and DENV/HIV coinfected patients. We found CD4/CD8 ratio inversion in most coinfected patients. CD4 T and CD8 T-cell subsets from DENV and DENV/HIV groups expressed low levels of anti-apoptotic protein Bcl-2. Furthermore, CD8 CD95 double positive cells frequency expressing low levels of Bcl-2 were significantly higher in these patients. Additionally, the density of Bcl-2 on classical monocytes (CD14 ++ CD16 - ) was significantly lower during DENV infection. Upregulation of pro-apoptotic proteins and anti-apoptotic proteins were found in DENV and DENV/HIV, while catalase, an antioxidant protein, was upregulated mainly in DENV/HIV coinfection. These findings provide evidence of apoptosis triggering during DENV/HIV coinfection, which may contribute to knowledge of immunological response during DENV acute infection in HIV-patients treated with ART.

Background: Liver disease is a leading cause of morbidity and mortality among Human Immunodeficiency virus (HIV) infected patients; however no consensus exists on HIV-related risk factors for it. The aim of this study was to identify risk factors for liver fibrosis/cirrhosis in a cohort of Greek HIV-infected patients., Methods: Patients attending the HIV outpatient clinic of Pathophysiology Department at «Laiko» General Hospital in Athens, Greece, between December 2014 and December 2017 were eligible for inclusion. Inclusion criteria were confirmed HIV infection and age > 18 years. Exclusion criteria were Body-Mass index (BMI) > 40, liver metastases of malignant diseases and concurrent or previous chemotherapy. Liver stiffness (LS) was measured using Vibration Controlled Transient Elastography (TE) and laboratory tests were acquired in all patients. Patients were classified in 2 groups: those with mild or no fibrosis (equivalent to Metavir score F0-F2) and those with significant fibrosis (equivalent to Metavir score F3-F4)., Results: A total of 187 consecutive patients were included in this study. Median TE value was 5.1 kilopascals (KPa) (range 2.8-26.3), with 92.5% (173/187) of the patients having no/mild fibrosis and 7.4% (14/187) significant fibrosis. On multivariate logistic regression analysis older patient's age, abnormal serum aspartate aminotransferase (AST) value, Hepatitis C virus (HCV) infection, alcohol abuse, CD4/CD8 ratio and an increased number of liver related events (LREs) were significantly correlated with liver fibrosis/cirrhosis., Conclusions: In our cohort of HIV-infected individuals HCV/HIV co-infection, older age, alcohol abuse and CD4/CD8 ratio seem to correlate with fibrogenesis in the liver.

Background: Rapid tests detecting both dengue virus (DENV) NS1 antigen and anti-DENV IgM and IgG antibodies facilitate diagnosis of dengue fever (DF) in resource-poor settings., Methodology/principal Findings: 92 acute phase serum samples from patients with a PCR-confirmed DENV infection collected in Lao People's Democratic Republic (Lao PDR) in 2013 and 2015 were analyzed with the SD Bioline Dengue Duo test. A subset of 74 samples was additionally tested with the Platelia NS1 antigen test, the Panbio DENV μ-capture ELISA and the Panbio DENV IgG ELISA. IgM seroconversion was assayed using follow-up samples of 35 patients collected in the convalescent phase. 57.6%, 22.8% and 44.6% of acute phase serum samples tested positive in the SD Bioline Dengue Duo NS1, IgM, and IgG test, respectively. Diagnostic sensitivity of the SD Bioline Dengue Duo NS1 test strongly correlated with viral load, decreased rapidly over the acute phase of the disease, and was significantly reduced in presence of high anti-DENV IgG antibody titers resulting from secondary DENV infection. While a good concordance (Cohen's kappa 0.78) was found between the SD Bioline Dengue Duo NS1 test and the Platelia NS1 antigen ELISA, both the SD Bioline Dengue Duo IgM and IgG test displayed a significantly lower sensitivity than the corresponding ELISA tests., Conclusions/significance: The SD Bioline Dengue Duo test is a valuable tool for diagnosis of DENV infections especially when analyzing early acute phase samples with high viral load. Nevertheless, in endemic areas, where secondary flavivirus infections are common, diagnostic sensitivity of the NS1 and IgM test components may be compromised., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: HS and PE are inventors of patent EP2492689 owned by BNITM; HS, PE, and CD are inventors of patent EP3207375 owned by BNITM. HEH is an employee of Altona Diagnostics GmbH. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Human herpesviruses (HHVs) remain latent after primary infection and can be reactivated in response to immunosuppression and chemotherapy. Little is known about their incidence, potential relationships, risk factors and clinical impact in non-transplant leukemia patients. This study investigated prospectively incidence, risk factors, clinical impact and possible association of HHVs-(1-7) infections in patients with newly diagnosed acute leukemia., Methods: Study design involved longitudinal sampling before chemotherapy and in different phases of chemotherapy: post-induction, post-remission, and post-salvage during 2016-2018. A total of 734 plasma samples from 95 patients were analyzed by a qualitative, multiplex PCR for HHVs detection and a quantitative real-time PCR was used for cytomegalovirus (CMV) quantification. HHVs-(1-6) IgG and IgM antibodies were tested using immunoassays. Risk factors were analyzed by binary logistic regression and relationships between viruses were analyzed using the Chi-square or Fisher's exact test as appropriate., Results: The overall seroprevalences of HHV-(1-6) IgG were high (> 80%). At least one herpes viral agent was detected in 60 patients (63.3%). CMV was the most commonly detected virus in the different phases of chemotherapy (19.4%), followed by HHV-6 (9.7%), HHV-7 (5.2%) and EBV (2.7%). HSV-1/2 and VZV DNA were not detected. Twenty-seven patients (28.4%) had more than one virus detected in the follow-up, with 23 who were co-infected. CMV/HHV-6 was the most frequent co-infection (69.5%, 16/23). HHV-6 infection (p = 0.008) was identified as a risk factor for CMV infection while salvage treatment (p = 0.04) and CMV infection (p = 0.007) were found to be independent risk factors for HHV-6 infection. CMV co-infection was associated with severe lymphopenia with an absolute lymphocyte count (ALC) (< 500/μL) (p = 0.009), rash (p = 0.011), pneumonia (p = 0.016) and opportunistic infections [bacteremia, p < 0.001 and invasive fungal infection, (p = 0.024)] more frequently than CMV mono-viral infections., Conclusions: Our data suggest that co-infection with HHVs, especially CMV and HHV-6, may contribute to the development of serious clinical manifestations with profound lymphopenia, pneumonia rash and increased risk for bacterial and fungal co-infections. These findings may suggest the synergistic effect of HHVs associated infection.

Representatives from academia, industry, regulatory agencies, and patient groups convened in March 2019 with the primary goal of developing agreement on chronic HBV treatment endpoints to guide clinical trials aiming to 'cure' HBV. Agreement among the conference participants was reached on some key points. 'Functional' but not sterilising cure is achievable and should be defined as sustained HBsAg loss in addition to undetectable HBV DNA 6 months post-treatment. The primary endpoint of phase III trials should be functional cure; HBsAg loss in ≥30% of patients was suggested as an acceptable rate of response in these trials. Sustained virologic suppression (undetectable serum HBV DNA) without HBsAg loss 6 months after discontinuation of treatment would be an intermediate goal. Demonstrated validity for the prediction of sustained HBsAg loss was considered the most appropriate criterion for the approval of new HBV assays to determine efficacy endpoints. Clinical trials aimed at HBV functional cure should initially focus on patients with HBeAg-positive or negative chronic hepatitis, who are treatment-naïve or virally suppressed on nucleos(t)ide analogues. A hepatitis flare associated with an increase in bilirubin or international normalised ratio should prompt temporary or permanent cessation of an investigational treatment. New treatments must be as safe as existing nucleos(t)ide analogues. The primary endpoint for phase III trials for HDV coinfection should be undetectable serum HDV RNA 6 months after stopping treatment. On treatment HDV RNA suppression associated with normalisation of alanine aminotransferase is considered an intermediate goal. In conclusion, regarding HBV 'functional cure', the primary goal is sustained HBsAg loss with undetectable HBV DNA after completion of treatment and the intermediate goal is sustained undetectable HBV DNA without HBsAg loss after stopping treatment., (Copyright © 2019 European Association for the Study of the Liver, American Association for the Study of Liver Diseases. Published by Elsevier B.V. All rights reserved.)