Search Results (166)

Coronavirus disease 2019 (COVID-19), with an increasing number of deaths worldwide, has created a tragic global health and economic emergency. The disease, caused by severe acute respiratory syndrome coronavirus 2019 (SARS-CoV-19), is a multi-system inflammatory disease with many of COVID-19-positive patients requiring intensive medical care due to multi-organ failures. Biomarkers to reliably predict the patient’s clinical cause of the virus infection, ideally, to be applied in point of care testing or through routine diagnostic approaches, are highly needed. We aimed to probe if routinely assessed clinical lab values can predict the severity of the COVID-19 course. Therefore, we have retrospectively analyzed on admission laboratory findings in 224 consecutive patients from four hospitals and show that systemic immune inflammation index (SII) is a potent marker for predicting the requirement for invasive ventilator support and for worse clinical outcome of the infected patient. Patients’ survival and severity of SARS-CoV-2 infection could reliably be predicted at admission by calculating the systemic inflammatory index of individual blood values. We advocate this approach to be a feasible and easy-to-implement assay that may be particularly useful to improve patient management during high influx crisis. We believe with this work to contribute to improving infrastructure availability and case management associated with COVID-19 pandemic hurdles. Full article

Human herpesvirus 6A (HHV-6A) is a common virus that has important immunomodulatory effects. Dendritic cells (DC) are key players in innate and adaptive immunity and are implicated in the pathogenesis of many human diseases, including infections. (1) Background: Previous studies have demonstrated suppressive effects of HHV-6A on key DC functions. (2) Methods: human monocyte derived dendritic cells were inoculated with HHV-6A and viral replication, cell viability, and release of high mobility group box 1 (HMGB1) protein from DC and of the cytokines IL-2, IL-4, IL-6, IL-10, TNF and IFN-γ after co-culture with allogenic CD4+ T cells were assessed. (3) Results: Nonproductive infection of HHV-6A in DC leads to titer-dependent cell death and the release of HMGB1 protein, and a Th2 polarization. (4) Conclusion: These immune responses aimed to clear the infection may also imply risks for inflammatory pathologies associated with HHV-6A such as multiple sclerosis. Full article

Bacterial vaginosis is characterized by an imbalance of the vaginal microbiome and a characteristic biofilm formed on the vaginal epithelium, which is initiated and dominated by Gardnerella bacteria, and is frequently refractory to antibiotic treatment. We investigated endolysins of the type 1,4-beta-N-acetylmuramidase encoded on Gardnerella prophages as an alternative treatment. When recombinantly expressed, these proteins demonstrated strong bactericidal activity against four different Gardnerella species. By domain shuffling, we generated several engineered endolysins with 10-fold higher bactericidal activity than any wild-type enzyme. When tested against a panel of 20 Gardnerella strains, the most active endolysin, called PM-477, showed minimum inhibitory concentrations of 0.13–8 µg/mL. PM-477 had no effect on beneficial lactobacilli or other species of vaginal bacteria. Furthermore, the efficacy of PM-477 was tested by fluorescence in situ hybridization on vaginal samples of fifteen patients with either first time or recurring bacterial vaginosis. In thirteen cases, PM-477 killed the Gardnerella bacteria and physically dissolved the biofilms without affecting the remaining vaginal microbiome. The high selectivity and effectiveness in eliminating Gardnerella, both in cultures of isolated strains as well as in clinically derived samples of natural polymicrobial biofilms, makes PM-477 a promising alternative to antibiotics for the treatment of bacterial vaginosis, especially in patients with frequent recurrence. Full article

(1) Background: Toxoplasma gondii is an important zoonosis and one of the major causes of abortion in sheep worldwide. (2) Methods: We performed a 2-year longitudinal serological anti-T. gondii IgG screening on a cohort of a spatially confined population of a Portuguese autochthonous sheep breed in central Portugal. (3) Results: From the screening of the 2015 and 2016 sera, an increase of seroprevalence was observed (57.7% (95% CI: 49.9–65.3%) versus 69.1% (95% CI: 61.5–75.9), from 2015 and 2016, respectively) (p = 0.031). (4) Conclusions The present study is the first to provide prospective data on the anti-T. gondii serological status of a sheep cohort in Portugal, showing an increase in the occurrence of T. gondii. There is a need to provide a clearer understanding of T. gondii epidemiology in Portugal, ideally by implementing monitoring programs on sentinel herds, not only due to the high impact of T. gondii on animal health but also for it being a zoonosis. Full article

Nowadays, apart from having to know first-line Helicobacter pylori eradication regimens well, we must also be prepared to face treatment failures. The aim of this review is to summarize the role of rifabutin in the management of H. pylori infection. Bibliographical searches were performed in PubMed. Data on resistance and efficacy of rifabutin-containing regimens on H. pylori eradication were meta-analyzed. Mean H. pylori rifabutin resistance rate (39 studies, including 9721 patients) was 0.13%; when studies only including patients naïve to H. pylori eradication treatment were considered, this figure was even lower (0.07%). Mean H. pylori eradication rate (by intention-to-treat) with rifabutin-containing regimens (3052 patients) was 73%. Respective cure rates for second-, third-, fourth- and fifth-line therapies, were 79%, 69%, 69% and 72%. Most studies administered rifabutin 300 mg/day, which seemed to be more effective than 150 mg/day. The ideal length of treatment remains unclear, but 10–12-day regimens are generally recommended. Adverse events to rifabutin treatment in H. pylori studies were relatively infrequent (15%), and severe adverse events were exceptional (myelotoxicity was the most significant, although always reversible). In summary, rifabutin-containing therapy represents an encouraging strategy generally restricted, at present, to patients where previous (usually multiple) eradication regimens have failed. Full article

Preventive chemotherapy (PC) is a WHO-recommended core intervention measures to eliminate Soil-Transmitted Helminths (STH) as a public health problem by 2020, defined as a reduction in prevalence to <1% of moderate or high-intensity infection. We conducted a cross-sectional study to investigate the prevalence, intensity, and correlates of STH after a decade of PC in Rwanda. A total of 4998 school children (5–15 years old) from four districts along Lake Kivu in the western province were screened for STH using Kato-Katz. The overall prevalence of Soil-transmitted helminths among school children was 77.7% (range between districts = 54% to 92%). Trichirus trichiura was the most common STH (66.8%, range between districts = 23% to 88.2%), followed by Ascaris lumbricoides (49.9%, range between district = 28.5% to 63.3%) and hookworms (1.9%, range between districts = 0.6% to 2.9%). The prevalence of single, double and of triple parasite coinfection were 48.6%, 50.3%, and 1.1%, respectively. The overall prevalence of moderate or high-intensity infection for Trichirus trichiura and Ascaris lumbricoides was 7.1% and 13.9, respectively. Multivariate logistic regression model revealed that male sex, district, stunting, and schistosomiasis coinfection as significant predictors of STH infection. Despite a decade of PC implementation, STH remain a significant public health problem in Rwanda. Full article

Peri-implantitis is a steadily rising disease and is caused by oral bacterial pathogens able to form biofilm on implant surfaces and peri-implant tissues, making antibiotics treatment less effective. The use of commercial probiotics against oral pathogens could serve as an alternative to prevent biofilm formation. Streptococcus intermedius is one of the early colonizers of biofilm formation in dental implants. The aim of this study was to model the interaction between S. intermedius and Streptococcus salivarius strain K12, a probiotic bacterium producing bacteriocins. S. intermedius was co-cultured with S. salivarius K12 in an in vitro model simulating the biofilm formation in a dental implant composed by a titanium cylinder system. Biofilm formation rate was assessed by Real-Time PCR quantification of bacterial count and expression levels of luxS gene, used in response to cell density in the biofilm. Biofilm formation, bacteriocin production, luxS expression patterns were found to be already expressed within the first 12 h. More importantly, S. salivarius K12 was able to counter the biofilm formation in a titanium cylinder under the tested condition. In conclusion, our dental implant model may be useful for exploring probiotic-pathogen interaction to find an alternative to antibiotics for peri-implantitis treatment. Full article

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to spread globally. Although several rapid commercial serological assays have been developed, little is known about their performance and accuracy in detecting SARS-CoV-2-specific antibodies in COVID-19 patient samples. Here, we have evaluated the performance of seven commercially available rapid lateral flow immunoassays (LFIA) obtained from different manufacturers, and compared them to in-house developed and validated ELISA assays for the detection of SARS-CoV-2-specific IgM and IgG antibodies in RT-PCR-confirmed COVID-19 patients. While all evaluated LFIA assays showed high specificity, our data showed a significant variation in sensitivity of these assays, which ranged from 0% to 54% for samples collected early during infection (3–7 days post symptoms onset) and from 54% to 88% for samples collected at later time points during infection (8–27 days post symptoms onset). Therefore, we recommend prior evaluation and validation of these assays before being routinely used to detect IgM and IgG in COVID-19 patients. Moreover, our findings suggest the use of LFIA assays in combination with other standard methods, and not as an alternative. Full article

Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer. Its development has been associated with diverse factors such as tobacco smoking and alcohol consumption. In addition, it has been suggested that microorganisms are risk factors for oral carcinogenesis. Epstein–Barr virus (EBV), which establishes lifelong persistent infections and is intermittently shed in the saliva, has been associated with several lymphomas and carcinomas that arise in the oral cavity. In particular, it has been detected in a subset of OSCCs. Moreover, its presence in patients with periodontitis has also been described. Porphyromonas gingivalis (P. gingivalis) is an oral bacterium in the development of periodontal diseases. As a keystone pathogen of periodontitis, P. gingivalis is known not only to damage local periodontal tissues but also to evade the host immune system and eventually affect systemic health. Persistent exposure to P. gingivalis promotes tumorigenic properties of oral epithelial cells, suggesting that chronic P. gingivalis infection is a potential risk factor for OSCC. Given that the oral cavity serves as the main site where EBV and P. gingivalis are harbored, and because of their oncogenic potential, we review here the current information about the participation of these microorganisms in oral carcinogenesis, describe the mechanisms by which EBV and P. gingivalis independently or synergistically can collaborate, and propose a model of interaction between both microorganisms. Full article

Aggregatibacter actinomycetemcomitans (Aa) is a keystone pathogen associated with periodontitis in adolescents. The knowledge on the prevalence of Aa and periodontitis among adolescents in Northern Europe is sparse. A total of 525 14- to 15-year-old adolescents from the municipality of Aarhus, Denmark, underwent a full-mouth clinical examination. Plaque score (PS), bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment loss (CAL) were recorded. Subgingival plaque samples (SPS) and stimulated saliva samples (SSS) were collected and analyzed for the presence of JP2 and non-JP2 genotypes of Aa using real-time PCR. A total of 70 (13.3%) individuals were positive for Aa, with 17 found in SPS, 19 in SSS, and 35 in both. The highly leukotoxic JP2 genotype of Aa was not detected. The individuals positive for Aa in both SPS and SSS had poorer periodontal outcomes (PPD and CAL) than individuals without Aa and individuals carrying Aa in either SPS or SSS only. In conclusion, 13% of 14- to 15-year-old Danish adolescents were positive for Aa, and the presence of Aa in both SPS and SSS was associated with poorer periodontal outcomes. Full article

Background: coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome—coronavirus-2 (SARS-CoV-2)—is an ongoing pandemic with high morbidity and mortality rates. Preliminary evidence suggests that acute kidney injury (AKI) is uncommon in patients with COVID-19 and associated with poor outcomes. Study aims and design: we performed a systematic review of the literature with a meta-analysis of clinical studies to evaluate the frequency of AKI and dialysis requirement in patients who underwent hospitalization due to COVID-19. The incidence of AKI according to the death risk was calculated in these patients. The random-effects model of DerSimonian and Laird was adopted, with heterogeneity and stratified analyses. Results: thirty-nine clinical studies (n = 25,566 unique patients) were retrieved. The pooled incidence of AKI was 0.154 (95% CI, 0.107; 0.201; p < 0.0001) across the studies. Significant heterogeneity was found (p = 0.0001). The overall frequency of COVID-19-positive patients who underwent renal replacement therapy (RRT) was 0.043 (95% CI, 0.031; 0.055; p < 0.0001); no publication bias was found (Egger’s test, p = 0.11). The pooled estimate of AKI incidence in patients with severe COVID-19 was 0.53 (95% CI, 0.427; 0.633) and heterogeneity occurred (Q = 621.08, I2 = 97.26, p = 0.0001). According to our meta-regression, age (p < 0.007) and arterial hypertension (p < 0.001) were associated with AKI occurrence in hospitalized COVID-19 positive patients. The odds ratio (OR) for the incidence of AKI in deceased COVID-19 positive patients was greater than among survivors, 15.4 (95% CI, 20.99; 11.4; p < 0.001). Conclusions: AKI is a common complication in hospitalized COVID-19 positive patients. Additional studies are under way to assess the risk of AKI in COVID-19 patients and to deepen the mechanisms of kidney injury. Full article

Testing HIV-1 RNA in plasma by PCR is universally accepted as the ultimate standard to confirm diagnosis of HIV-1 infection and to monitor viral load in patients under treatment. However, in some cases, this assay could either underestimate or overestimate the replication capacity of a circulating or latent virus. In the present study, we performed the assessment of evaluating the HIV-1 reverse transcriptase (RT) activity by means of a new assay for the functional screening of the status of HIV-1 patients. To this purpose, we utilized, for the first time on blood samples, an adapted version of a real-time RT quantitative PCR assay, utilized to evaluate the HIV-1-RT inhibitory activity of compounds. The study analyzed blood samples from 28 HIV-1-infected patients, exhibiting a wide range of viremia and immunological values. Results demonstrated that plasma HIV-1 RT levels, expressed as cycle threshold values obtained with the assay under appraisal, were inversely and highly significantly correlated with the plasma HIV-1-RNA levels of the patients. Thus, an HIV-1 RT quantitative PCR assay was created which we describe in this study, and it may be considered as a promising basis for an additional tool capable of furnishing information on the functional virological status of HIV-1-infected patients. Full article

Ivermectin (IVM) is a broad spectrum endectocide whose initial indication was onchocerciasis. Although loiasis is not among its indications, IVM also exhibits antiparasitic activity against Loa loa. IVM-based preventive chemotherapies (PCs), so-called community-directed treatment with ivermectin (CDTI), have led to the interruption of transmission of onchocerciasis in some foci. A cross-sectional study was conducted in the Yabassi Health District where CDTI have been implemented since 20 years to fight onchocerciasis. All volunteers aged ≥ 5 years underwent daytime calibrated thick blood smears to search for L. loa microfilariae (mf). The prevalence of loiasis was 3.7% (95% CI: 2.2–6.2), significantly lower than its baseline prevalence (12.4%; 95% CI: 10.1–15.2; Chi-Square = 21.4; df = 1; p < 0.0001). Similarly, the microfilarial density was significantly low (mean = 1.8 mf/mL; SD = 13.6; max = 73,600) compared to baseline microfilarial density (mean = 839.3 mf/mL; SD = 6447.1; max = 130,840; Wilcoxon W = 179,904.5; p < 0.0001). This study revealed that the endemicity level of loiasis was significantly low compared to its baseline value, indicating a significant impact of IVM-based PC on this filarial disease. However, transmission is still ongoing, and heavily infected individuals are still found in communities, supporting why some individuals are still experiencing severe adverse events despite > 2 decades of CDTI in this Health District. Full article

The resistance of Gram-negative bacteria to colistin, mediated by plasmid-borne mcr genes, is an emerging public health concern. The complete genome sequence (4.55 Mb) of a clinical isolate of Aeromonas veronii biovar veronii obtained from a patient with septicemia was determined using short-read and long-read platforms. This isolate (C198) was found to harbor a novel mcr-3 gene, designated mcr-3.41. Isolate C198 revealed adjacent mcr-3.41 and mcr-3-like genes. It contained one chromosome and two plasmids, both of which encoded a RepB replication protein. Other antimicrobial resistance genes, including bla_cphA3, bla_OXA-12, tetA, rsmA, and adeF, were also present. Isolate C198 was resistant to amoxicillin–clavulanate, ampicillin–sulbactam and tetracycline, and showed intermediate resistance to trimethoprim–sulfamethoxazole. The isolate was susceptible to piperacillin–tazobactam, carbapenem, third-generation cephalosporins, fluoroquinolones, chloramphenicol, and aminoglycosides. Putative virulence genes in the C198 genome encoded type II, III, and VI secretion systems; type IV Aeromonas pili; and type I fimbria, flagella, hemagglutinin, aerolysin, and hemolysins. Multilocus sequence typing revealed a novel sequence type (ST), ST720 for C198. Phylogenetic analysis of the single nucleotide polymorphisms in C198 demonstrated that the strain was closely related to A. veronii 17ISAe. The present study provides insights into the genomic characteristics of human A. veronii isolates. Full article

The extended and diverse interference of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in multiple host functions and the diverse associated symptoms implicate its involvement in fundamental cellular regulatory processes. The activity of ten-eleven translocase 2 (TET2) responsible for selective DNA demethylation, has been recently identified as a regulator of endogenous virus inactivation and viral invasion, possibly by proteasomal deregulation of the TET2/TET3 activities. In a recent report, we presented a detailed list of factors that can be affected by TET activity, including recognition of zinc finger protein binding sites and bimodal promoters, by enhancing the flexibility of adjacent sequences. In this review, we summarize the TET-associated processes and factors that could account for SARS-CoV-2 diverse symptoms. Moreover, we provide a correlation for the observed virus-induced symptoms that have been previously associated with TET activities by in vitro and in vitro studies. These include early hypoxia, neuronal regulation, smell and taste development, liver, intestinal, and cardiomyocyte differentiation. Finally, we propose that the high mortality of SARS-CoV-2 among adult patients, the different clinical symptoms of adults compared to children, the higher risk of patients with metabolic deregulation, and the low mortality rates among women can all be accounted for by the complex balance of the three enzymes with TET activity, which is developmentally regulated. This activity is age-dependent, related to telomere homeostasis and integrity, and associated with X chromosome inactivation via (de)regulation of the responsible XIST gene expression. Full article