Case Report: Late Reactivation of Herpes B Virus After a Monkey Bite: A Case of Severe Meningoencephalitis.

Macacine alphaherpesvirus 1, also known as herpes B virus (BV), is an alphaherpesvirus endemic to several macaque species, capable of causing zoonotic infections in humans, with high mortality rates. Evidence of reactivation in humans has rarely been reported. Here we depict a case of BV reactivation after 54 years, leading to severe meningoencephalitis. This case supports the use of antiviral prophylaxis in patients surviving a confirmed BV central nervous system infection. We sequenced DNA from BV obtained from the patient's cerebrospinal fluid. Phylogenetic analysis showed significant divergence in the clustering of this particular BV strain compared with other known BVs. Therefore, additional efforts are needed to obtain a broader sequence landscape from BVs circulating in monkeys.

[Climate change and infectious diseases]. / Klimaatverandering en infectieziekten wereldwijd.

Climate change can contribute to a global increase in the burden of infectious diseases. Both the number of geographical areas as well as the number of yearly days that are suitable for transmission of certain infectious diseases can increase due to global warming. At the same time, increased 'suitability' does not always lead to a factual increase in disease burden and economic development and public health measures have resulted in marked reductions in the burden of several important infectious diseases in recent years. The net effect of global environmental change on infectious disease burden will be determined by a multitude of factors, including unpredictable outbreaks of pathogens and the extent to which public health programs can effectively function and adjust to changing health risks.

Evidence of cat-to-human transmission of Staphylococcus felis.

Introduction. Staphylococcus felis is a coagulase-negative staphylococcal species that is commonly isolated from healthy cats. Like other commensal staphylococci, S. felis can cause opportunistic infections, e.g. otitis externa, skin and urinary tract infections, in cats.Gap Statement. Several studies have reported within-household transmission between humans and pets and human infections caused by coagulase-positive staphylococci. However, human infections with coagulase-negative staphylococci of zoonotic origin are relatively rare.Methodology. Culture of a surgical site infection in a 58-year-old woman who underwent a laminectomy revealed dominant growth of S. felis. The three cats owned by the patient were sampled to investigate potential within-household transmission. S. felis isolates were sequenced to investigate the relatedness of the isolates and to look for virulence factors and host specific genes.Results. All cats were colonized with S. felis. Comparative genomics of the isolates showed that each cat was colonized with a distinct genotype. The patient's isolate clustered with isolates of one of the cats. Sequence analysis of the studied isolates together with 29 publicly available S. felis genomes detected putative virulence factors that can be crucial in potential interspecies transmission.Conclusion. The current case is the first reported human infection caused by S. felis and highlights the zoonotic potential of this bacterial species. Evidence of cat-to-human transmission was shown by comparative genomics of isolates from the patient with isolates of her cats.

Detection of intrathecal antibodies to diagnose enterovirus infections of the central nervous system.

BACKGROUND: Enterovirus-D68 (EV-D68) predominantly causes respiratory disease. However, EV-D68 infections also have been associated with central nervous system (CNS) complications, most specifically acute flaccid myelitis (AFM). Diagnosing EV-D68-associated CNS disease is challenging since viral RNA is rarely detected in cerebrospinal fluid (CSF). OBJECTIVE: In order to determine an EV antibody index (AI), we evaluated the value of a commercially available quantitative ELISA to detect EV-specific antibodies in paired CSF and blood. STUDY DESIGN: Nine paired CSF and blood samples were obtained from patients with EV-D68-associated AFM or from patients with a confirmed EV-associated CNS disease. EV-specific antibodies were detected using a quantitative ELISA. A Reiber diagram analysis was performed, by which the AI was calculated. Subsequently, EV ELISA results were compared with an EV-D68 virus neutralization test. RESULTS: ELISA detected EV-specific antibodies in 1 out of the 3 patients with EV-D68-associated AFM and in 3 out of the 6 patients with confirmed EV-associated CNS disease. In these patients, the AI was indicative for intrathecal antibody production against enterovirus. Assay comparison showed that EV-D68 neutralizing antibody detection increased the sensitivity of EV-D68 antibody detection. CONCLUSIONS: A quantitative EV IgG ELISA in combination with Reiber diagram analysis and AI-calculation can be used as a diagnostic tool for EV-associated CNS disease, including EV-D68. An EV-D68 specific ELISA will improve the sensitivity of the tool. With the growing awareness that the detection of non-polio enteroviruses needs to be improved, diagnostic laboratories should consider implementation of EV serology.

Targeting tight junctions to fight against viral neuroinvasion.

The clinical impact of viral neuroinvasion on the central nervous system (CNS) ranges from barely detectable to deadly, including acute and chronic outcomes. Developing innovative therapeutic strategies is important to mitigate virus-induced neurological and psychiatric disorders. A key gatekeeper to the CNS is the neurovascular unit (NVU), a major obstacle to viral neuroinvasion and antiviral therapies. The NVU isolates the brain from the blood through firm sealing operated by the tight junctions (TJs) of endothelial cells. Here, we make the thought-provoking assumption that TJs can be targets to prevent or treat viral neuroinvasion and resulting disorders. This review aims at defining the conceptual diverse mode of actions of such approaches, evaluates their feasibility, and discusses future challenges in the field.

Absence of Host-Specific Genes in Canine and Human Staphylococcus pseudintermedius as Inferred from Comparative Genomics.

Staphylococcus pseudintermedius is an important pathogen in dogs that occasionally causes infections in humans as an opportunistic pathogen of elderly and immunocompromised people. This study compared the genomic relatedness and antimicrobial resistance genes using genome-wide association study (GWAS) to examine host association of canine and human S. pseudintermedius isolates. Canine (n = 25) and human (n = 32) methicillin-susceptible S. pseudintermedius (MSSP) isolates showed a high level of genetic diversity with an overrepresentation of clonal complex CC241 in human isolates. This clonal complex was associated with carriage of a plasmid containing a bacteriocin with cytotoxic properties, a CRISPR-cas domain and a pRE25-like mobile element containing five antimicrobial resistance genes. Multi-drug resistance (MDR) was predicted in 13 (41%) of human isolates and 14 (56%) of canine isolates. CC241 represented 54% of predicted MDR isolates from humans and 21% of predicted MDR canine isolates. While it had previously been suggested that certain host-specific genes were present the current GWAS analysis did not identify any genes that were significantly associated with human or canine isolates. In conclusion, this is the first genomic study showing that MSSP is genetically diverse in both hosts and that multidrug resistance is important in dog and human-associated S. pseudintermedius isolates.

Diagnostic accuracy of rapid antigen tests in asymptomatic and presymptomatic close contacts of individuals with confirmed SARS-CoV-2 infection: cross sectional study.

OBJECTIVE: To assess the diagnostic test accuracy of two rapid antigen tests in asymptomatic and presymptomatic close contacts of people with SARS-CoV-2 infection on day 5 after exposure. DESIGN: Prospective cross sectional study. SETTING: Four public health service covid-19 test sites in the Netherlands. PARTICIPANTS: 4274 consecutively included close contacts (identified through test-and-trace programme or contact tracing app) aged 16 years or older and asymptomatic for covid-19 when requesting a test. MAIN OUTCOME MEASURES: Sensitivity, specificity, and positive and negative predictive values of Veritor System (Beckton Dickinson) and Biosensor (Roche Diagnostics) rapid antigen tests, with reverse-transcriptase polymerase chain reaction (RT-PCR) testing as reference standard. The viral load cut-off above which 95% of people with a positive RT-PCR test result were virus culture positive was used as a proxy of infectiousness. RESULTS: Of 2678 participants tested with Veritor, 233 (8.7%) had a RT-PCR confirmed SARS-CoV-2 infection of whom 149 were also detected by the rapid antigen test (sensitivity 63.9%, 95% confidence interval 57.4% to 70.1%). Of 1596 participants tested with Biosensor, 132 (8.3%) had a RT-PCR confirmed SARS-CoV-2 infection of whom 83 were detected by the rapid antigen test (sensitivity 62.9%, 54.0% to 71.1%). In those who were still asymptomatic at the time of sampling, sensitivity was 58.7% (51.1% to 66.0%) for Veritor (n=2317) and 59.4% (49.2% to 69.1%) for Biosensor (n=1414), and in those who developed symptoms were 84.2% (68.7% to 94.0%; n=219) for Veritor and 73.3% (54.1% to 87.7%; n=158) for Biosensor. When a viral load cut-off was applied for infectiouness (≥5.2 log10 SARS-CoV-2 E gene copies/mL), the overall sensitivity was 90.1% (84.2% to 94.4%) for Veritor and 86.8% (78.1% to 93.0%) for Biosensor, and 88.1% (80.5% to 93.5%) for Veritor and 85.1% (74.3% to 92.6%) for Biosensor, among those who remained asymptomatic throughout. Specificities were >99%, and positive and negative predictive values were >90% and >95%, for both rapid antigen tests in all analyses. CONCLUSIONS: The sensitivities of both rapid antigen tests in asymptomatic and presymptomatic close contacts tested on day 5 onwards after close contact with an index case were more than 60%, increasing to more than 85% after a viral load cut-off was applied as a proxy for infectiousness.

Temporal Kinetics of RNAemia and Associated Systemic Cytokines in Hospitalized COVID-19 Patients.

COVID-19 is associated with a wide range of extrarespiratory complications, of which the pathogenesis is currently not fully understood. However, both systemic spread and systemic inflammatory responses are thought to contribute to the systemic pathogenesis. In this study, we determined the temporal kinetics of viral RNA in serum (RNAemia) and the associated inflammatory cytokines and chemokines during the course of COVID-19 in hospitalized patients. We show that RNAemia can be detected in 90% of the patients who develop critical disease, compared to 50% of the patients who develop moderate or severe disease. Furthermore, RNAemia lasts longer in patients who develop critical disease. Elevated levels of interleukin-10 (IL-10) and MCP-1-but not IL-6-are associated with viral load in serum, whereas higher levels of IL-6 in serum were associated with the development of critical disease. In conclusion, RNAemia is common in hospitalized patients, with the highest frequency and duration in patients who develop critical disease. The fact that several cytokines or chemokines are directly associated with the presence of viral RNA in the circulation suggests that the development of RNAemia is an important factor in the systemic pathogenesis of COVID-19. IMPORTANCE Severe COVID-19 can be considered a systemic disease as many extrarespiratory complications occur. However, the systemic pathogenesis is poorly understood. Here, we show that the presence of viral RNA in the blood (RNAemia) occurs more frequently in patients who develop critical disease, compared to patients with moderate or severe disease. In addition, RNAemia is associated with increased levels of inflammatory cytokines and chemokines, like MCP-1 and IL-10, in serum during the course of disease. This suggests that extrarespiratory spread of SARS-CoV-2 contributes to systemic inflammatory responses, which are an important factor in the systemic pathogenesis of COVID-19.

Frequency of Positive Aspergillus Tests in COVID-19 Patients in Comparison to Other Patients with Pulmonary Infections Admitted to the Intensive Care Unit.

The aim of this study was to describe the frequency of positive Aspergillus tests in COVID-19 patients and investigate the association between COVID-19 and a positive Aspergillus test result. We compared the proportion of positive Aspergillus tests in COVID-19 patients admitted to the intensive care unit (ICU) for >24 h with two control groups: patients with community-acquired pneumonia with (i) a PCR-confirmed influenza infection (considered a positive control since the link between influenza and invasive aspergillosis has been established) and (ii) Streptococcus pneumoniae pneumonia (in whom positive Aspergillus tests are mostly considered as colonization). During the study period, 92 COVID-19 patients (mean [standard deviation] age, 62 [14] years; 76.1% males), 48 influenza patients (55 [14]; 56.2% males), and 65 pneumococcal pneumonia patients (58 [15], 63,1% males) were identified. Any positive Aspergillus test from any respiratory sample was found in 10.9% of the COVID-19 patients, 6.2% of the patients with pneumococcal pneumonia, and 22.9% of those infected with influenza. A positive culture or PCR or galactomannan test on bronchoalveolar lavage (BAL) fluid only was found in 5.4% of COVID-19 patients, which was lower than in patients with influenza (18.8%) and comparable to that in the pneumococcal pneumonia group (4.6%). Using logistic regression analysis, the odds ratio (OR) (95% confidence interval) for a positive Aspergillus test on BAL fluid for COVID-19 patients was 1.2 (0.3 to 5.1; P = 0.8) compared to the pneumococcal pneumonia group, while it was 0.2 (0.1 to 0.8; P = 0.02) compared to the influenza group. This difference remained significant when corrected for age and sex. In conclusion, in COVID-19 patients, the prevalence of a positive Aspergillus test was comparable to that in patients admitted for pneumococcal pneumonia but substantially lower than what we observed in patients with influenza.

Norovirus outbreak in a natural playground: A One Health approach.

Norovirus constitutes the most frequently identified infectious cause of disease outbreaks associated with untreated recreational water. When investigating outbreaks related to surface water, a One Health approach is insightful. Historically, there has been a focus on potential contamination of recreational water by bird droppings and a recent publication demonstrating human noroviruses in bird faeces suggested this should be investigated in future water-related norovirus outbreaks. Here, we describe a One Health approach investigating a norovirus outbreak in a natural playground. On social media, a large amount of waterfowl were reported to defecate near these playground premises leading to speculations about their potential involvement. Surface water, as well as human and bird faecal specimens, was tested for human noroviruses. Norovirus was found to be the most likely cause of the outbreak but there was no evidence for transmission via waterfowl. Cases had become known on social media prior to notification to the public health service underscoring the potential of online media as an early warning system. In view of known risk factors, advice was given for future outbreak investigations and natural playground design.

Neuroinvasive flavivirus infections.

Flaviviruses, including Dengue, West Nile, Japanese encephalitis, and Tick-borne encephalitis virus, are major emerging human pathogens, affecting millions of individuals worldwide. Many clinically important flaviviruses elicit CNS diseases in infected hosts, including traditional "hemorrhagic" viruses, such as Dengue. This review focuses on the epidemiology, symptomatology, neuropathology, and, specifically, neuropathogenesis of flavivirus-induced human CNS disease. A detailed insight into specific factors priming towards neuroinvasive disease is of clear clinical significance, as well as importance to the development of antiviral therapies and identification of key mechanisms involved in the (re)emergence of specific flaviviruses, including potentially novel or previously unrecognized ones, as neuroinvasive pathogens.

Intravascular lymphomatosis of the brain in a patient with myelodysplastic syndrome.

BACKGROUND: A 77-year-old retired research pharmacologist with a long-standing history of anemia and a recent pathologically confirmed diagnosis of myelodysplastic syndrome was referred to a stroke unit for evaluation of slowly progressive cognitive deterioration, confusion and paroxysmal stroke-like episodes. A previous neurological work-up had revealed no noteworthy abnormalities except for chronic bilateral caudate infarctions seen on MRI and CT examinations of the brain. INVESTIGATIONS: Physical examination, laboratory testing, brain MRI scanning, EEG, transesophageal echocardiography, cerebral angiography, CT scanning, and brain biopsy. DIAGNOSIS: Intravascular lymphomatosis of the brain. MANAGEMENT: Combined chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) and rituximab.