Enteroviral central nervous system infections in patients with Lyme neuroborreliosis.

Patients with Lyme neuroborreliosis (LNB) are rarely tested for the presence of neurovirulent viruses other than tick-borne encephalitis virus (TBEV); however, such coinfections could be of clinical importance. The aim of the study was to search for the presence of neurotropic viruses in a LNB patients. Fourteen patients admitted with signs and symptoms of neuroinfection who were eventually diagnosed to have LNB (according to the guidelines of the European Federation of Neurological Societies) were subjects of the study. Sera and cerebrospinal fluid (CSF) collected at the time of initial presentation were tested for viral pathogens most common in our geographical area: human enteroviruses (EV), herpes simplex virus type 1 and 2, varicella-zoster virus, Epstein-Barr virus, cytomegalovirus, human herpesvirus type 6, human adenoviruses, and TBEV using PCR/RT-PCR and serological assays. RNA and DNA-based metagenomic next-generation sequencing (mNGS) was used to detect other viral pathogens. EV was detected in CSF from two (14 %) LNB patients and viral loads were similar (220 and 270 copies/ml). The mMGS analysis were performed on CSFs from 10 patients and generated a total 213,750,885 NGS reads, 0.05 % of which were viral. However, none of potential pathogens fulfilled the criteria for positive viral detection by mNGS. Using a number of PCR/RT-PCR assays and mNGS we identified EV infection in two out of 14 LNB patients. The possible co-occurrence of enterovirus and Lyme neuroborreliosis infections may warrant further research.

Metagenomic search of viral coinfections in herpes simplex encephalitis patients.

Little is known about concomitant central nervous system (CNS) infections by more than one virus. Current diagnostics are based on molecular tests for particular pathogens making it difficult to identify multi-viral infections. In the present study, we applied DNA- and RNA-based next-generation sequencing metagenomics (mNGS) to detect viruses in cerebrospinal fluids from 20 patients with herpes simplex encephalitis. Coinfection was detected in one patient: sequences in cerebrospinal fluids matched enterovirus A (2.660 reads; 4% of recovered genome) and enterovirus B (1.571 reads; 13% of recovered genome). Subsequent PCR combined with serotyping allowed to identify human echovirus 6, a representative of enterovirus B. Several other mNGS hits (human pegivirus, Merkel cell polyomavirus, human papillomavirus type 5) were not considered to represent a genuine signal as they could not be confirmed by specific RT-PCR/PCR. HSV DNA, while being detectable by PCR in every patient, was detected by mNGS in only one. In conclusion, contaminations and false signals may complicate mNGS interpretation; however, the method can be useful in diagnostics of viral coinfections in CNS, particularly in the case of rare pathogens.

The Clinical Course and Outcomes of Patients Hospitalized Due to COVID-19 during Three Pandemic Waves in Poland: A Single Center Observational Study.

Background: The first case of coronavirus disease 2019 (COVID-19) in Poland was reported on 4 March 2020. We aim to compare the clinical course and outcomes of patients hospitalized in the Hospital for Infectious Diseases in Warsaw due to COVID-19 during three pandemic waves. Materials and methods: The medical data were collected for all patients diagnosed with COVID-19 hospitalized in our hospital from 6 March 2020 till 30 November 2021. COVID-19 diagnosis was confirmed by nasopharyngeal swabs using real-time polymerase chain reaction assay (RT-PCR) or SARS-CoV-2 antigen test. COVID-19 waves were defined based on the number and dynamics of cases. Results: Altogether, 2138 patient medical records were analyzed. The majority of the cohort was male (1235/2138, 57.8%), and the median age was 65 years [IQR: 50−74 years]. Patients hospitalized during the third wave had lower oxygen saturation on admission (p < 0.001) and were more likely to receive oxygen supplementation (p < 0.001). Serious complications, including pneumothorax (p < 0.001) and thromboembolic complications (p < 0.001), intensive care unit admission (p = 0.034), and death (p = 0.003), occurred more often in patients of the third wave. Conclusions: During the third wave, patients in our cohort experienced a more severe course of the disease and poorer outcomes.

The effectiveness of erysipelas prophylaxis depends on the cumulative dose of benzathine penicillin G.

Erysipelas is an acute infection due to S. pyogenes and is characterized by a high risk of relapses. The number of patients suffering from one or more recurrences varied depending on the study and accounted for between 16% and 47% of the total number of those affected. Antibiotic prophylaxis with the use of penicillin can reduce the risk of recurrence by 47%. A number of 873 patients with erysipelas treated at the Hospital for Infectious Diseases in Warsaw from 2010 to 2018 was enrolled in the study. Benzathine-penicillin G was given intramuscularly at a dose of 1.2 MU or 2.4 MU or 3.6 MU. The earliest moment that prophylactic treatment was administered was the first episode of erysipelas recurrence. The decision to administer the antibiotic and the dose to use was discretionally made by the examining physician. Altogether 104 (11.9%) persons experienced at least one episode of erysipelas recurrence during the study period. A total of 2976 doses of benzathine- penicillin G (BP) were administered. The most common dose was that of 2.4 MU (2380, 80%). The dose of 1.2 MU was given 567 times (19%). The highest dose, i.e. 3.6 MU, was administered to only 5 patients (8 applications, 0.2%). No effect was shown by either the number of benzathine- penicillin G administered doses (p=0.07) or the median dose (p=0.65), whereas patients without relapse received a statistically higher cumulative dose of the antibiotic (p=0.047). Age was a risk factor of recurrence only in the group of diabetic patients (p=0.03). Benzathine penicillin G given in an appropriate cumulative dose is effective in preventing erysipelas recurrence.

Patients with Infections of The Central Nervous System Have Lowered Gut Microbiota Alpha Diversity.

There are multiple lines of evidence for the existence of communication between the central nervous system (CNS), gut, and intestinal microbiome. Despite extensive analysis conducted on various neurological disorders, the gut microbiome was not yet analyzed in neuroinfections. In the current study, we analyzed the gut microbiome in 47 consecutive patients hospitalized with neuroinfection (26 patients had viral encephalitis/meningitis; 8 patients had bacterial meningitis) and in 20 matched for age and gender health controls. Using the QIIME pipeline, 16S rRNA sequencing and classification into operational taxonomic units (OTUs) were performed on the earliest stool sample available. Bacterial taxa such as Clostridium, Anaerostipes, Lachnobacterium, Lachnospira, and Roseburia were decreased in patients with neuroinfection when compared to controls. Alpha diversity metrics showed lower within-sample diversity in patients with neuroinfections, though there were no differences in beta diversity. Furthermore, there was no significant change by short-term (1-3 days) antibiotic treatment on the gut microbiota, although alpha diversity metrics, such as Chao1 and Shannon's index, were close to being statistically significant. The cause of differences between patients with neuroinfections and controls is unclear and could be due to inflammation accompanying the disease; however, the effect of diet modification and/or hospitalization cannot be excluded.

Risk factors for complicated course and recurrence of Clostridioides Difficile infections during COVID-19 pandemic.

INTRODUCTION: The primary symptom of Clostridioides difficile infection (CDI) is diarrhea of varying severity. Both malnutrition and clinical nutrition increase the risk for contracting Clostridioides difficile (C. difficile) infection and the likelihood of relapses. Moreover, the risk for recurrence is higher if there is infection with a hypervirulent strain (NAP1/BI/027). Hypoalbuminemia predisposes to a severe course of the disease and morbidity. MATERIAL AND METHODS: Analysis was carried out of the data regarding patients hospitalized at the Regional Hospital for Infectious Diseases in Warsaw from 01 January 2020 to 31 December 2021 who were diagnosed with C. difficile infection. A severe course of infection was diagnosed when a blood test showed a leukocyte count greater than or equal to 15,000/µl and/or a creatinine concentration >1.5 mg/dl (>132.6 mmol/l). RESULTS: Clostridioides difficile infection was the reason for 185 hospitalizations (involving 108 women and 77 men), of 167 patients aged from 22 to 93 years old. There were 68 (37%) cases of recurrent infection. Seventy-five (41%) infections met the study's criteria for severe CDI, and 12 (7%) patients died. Out of the total number of hospitalizations, 41 (22%) were due SARS-CoV-2 co-infection. PCR tests detecting binary toxin revealed 34 (18%) positive results. Infection with a hypervirulent strain was an independent risk factor for the recurrence of diarrhea which had C. difficile etiology. Overall, during an episode of diarrhea, one antibacterial drug was used in 139 cases (75%), two in 27 (15%), three in 14 (8%) situations, and four - twice (1%). Among these, drugs not recommended for the treatment of CDI were used in 21 (11%) cases. The number of antibacterial drugs administered during an episode of diarrhea was an independent risk factor for the death of the infected person. Clinical nutrition was applied during 19 hospitalizations (10%), out of which 12 (63%) cases showed a severe course of C. difficile infection, while four patients (21%) died. Using clinical nutrition methods was an independent risk factor for a severe course of the disease and patient death. CONCLUSIONS: Clinical nutrition and the number of antibiotics used during an episode of diarrhea are independent risk factors for the death of a patient with CDI. Infection with a hypervirulent strain increases the risk for relapse.

Detection of Lipoprotein X (LpX): A challenge in patients with severe hypercholesterolaemia.

BACKGROUND: Lipoprotein X (LpX) is an abnormal lipoprotein fraction, which can be detected in patients with severe hypercholesterolaemia and cholestatic liver disease. LpX is composed largely of phospholipid and free cholesterol, with small amounts of triglyceride, cholesteryl ester and protein. There are no widely available methods for direct measurement of LpX in routine laboratory practice. We present the heterogeneity of clinical and laboratory manifestations of the presence of LpX, a phenomenon which hinders LpX detection. METHODS: The study was conducted on a 26-year-old female after liver transplantation (LTx) with severely elevated total cholesterol (TC) of 38 mmol/L and increased cholestatic liver enzymes. TC, free cholesterol (FC), cholesteryl esters (CE), triglycerides, phospholipids, HDL-C, LDL-C, and apolipoproteins AI and B were measured. TC/apoB and FC:CE ratios were calculated. Lipoprotein electrophoresis was performed using a commercially available kit and laboratory-prepared agarose gel. RESULTS: Commercially available electrophoresis failed to demonstrate the presence of LpX. Laboratory-prepared gel clearly revealed the presence of lipoproteins with γ mobility, characteristic of LpX. The TC/apoB ratio was elevated and the CE level was reduced, confirming the presence of LpX. Regular lipoprotein apheresis was applied as the method of choice in LpX disease and a bridge to reLTx due to chronic liver insufficiency. CONCLUSIONS: The detection of LpX is crucial as it may influence the method of treatment. As routinely available biochemical laboratory tests do not always indicate the presence of LpX, in severe hypercholesterolaemia with cholestasis, any discrepancy between electrophoresis and biochemical tests should raise suspicions of LpX disease.

Search for Viral Infections in Cerebrospinal Fluid From Patients With Autoimmune Encephalitis.

BACKGROUND: It has been reported that virus-mediated brain tissue damage can lead to autoimmune encephalitis (AE) characterized by the presence of antibodies against neuronal surface antigens. In the study, we investigate the presence of viruses in cerebrospinal fluid (CSF) from patients with AE using reverse transcription polymerase chain reaction (RT-PCR)/PCR and shotgun metagenomics. METHODS: CSF samples collected from 200 patients with encephalitis were tested for the presence of antibodies against antiglutamate receptor (NMDAR), contactin-associated protein 2 (CASPR2), glutamate receptors (type AMPA1/2), leucine-rich glioma-inactivated protein 1 (LGI1), dipeptidyl aminopeptidase-like protein 6 (DPPX), and GABA B receptor, and those found positive were further analyzed with real-time RT-PCR/PCR for common viral neuroinfections and shotgun DNA- and RNA-based metagenomics. RESULTS: Autoantibodies against neuronal cells were detected in CSF from 8 individuals (4% of all encephalitis patients): 7 (3.5%) had anti-NMDAR and 1 (0.5%) had anti-GABA B. RT-PCR/PCR identified human herpes virus type 1 (HSV-1; 300 copies/mL) and the representative of Enterovirus genus (550 copies/mL) in 1 patient each. Torque teno virus (TTV) was found in another patient using metagenomic analysis, and its presence was confirmed by specific PCR. CONCLUSIONS: We detected the presence of HSV, TTV, and Enterovirus genus in CSF samples from 3 out of 8 AE patients. These findings support the concept of viral involvement in the pathogenesis of this disease.

Differences and similarities in clinical manifestations of Listeria monocytogenes and Mycobacterium tuberculous meningitis.

INTRODUCTION: Tuberculous meningitis (TbM) and meningitis caused by Listeria monocytogenes (LM) require different treatment regimens and have grave prognosis if therapy is delayed. THE AIM OF THE STUDY: Comparison of clinical manifestations, laboratory features and outcome of TbM and LM. MATERIAL AND METHODS: We retrospectively analyzed records of 402 patients with community acquired bacterial meningitis (BM) who were hospitalized between January 2010 and September 2019. RESULTS: LM and TbM were diagnosed in 28 (7.0%) and 23 (5.7%) patients, respectively. Patients with TbM were more likely to present with hydrocephalus (p<0.001), scored lower on the Thwaites Index (TI) (p<0.001) and had longer duration of symptoms prior to hospitalization (p=0.001). Furthermore, TbM patients had lower concentration of c-reactive protein (CRP) (p<0.001) and lower white blood cells count (WBC) (p=0.035). When compared to BM patients with etiology other than LM and TbM (nLnTbM), TbM patients presented with lower concentration of CRP (p<0.001), and procalcitonin (PCT) (p<0.001), lower WBC (p<0.001), and lower granulocyte percentage of CSF cytosis (p<0.001), but were more likely to present with hydrocephalus (p<0.001), aphasia (p=0.003) and hemiparesis (p=0.008). In comparison with the nLnTbM group, LM patients had lower concentration of CRP (p=0.01), lower WBC (p<0.001), and lower granulocyte percentage of CSF cytosis (p<0.016). LM patients were also more likely to have concomitant cancer (p=0.008), receive immunosuppressive treatment (p<0.001) or be immunocompromised (p=0.015). CONCLUSIONS: TbM patients had less pronounced inflammation but more severe central nervous system complications compared to patients with LM and other etiologies. Furthermore, LM patients, but not TbM patients, were often immunocompromised.

Advanced age and increased CRP concentration are independent risk factors associated with Clostridioides difficile infection mortality.

Clostridioides difficile (C.difficile) is a Gram-positive, spore-forming, toxin-producing anaerobic bacillus, which is one of the most common causes of health-care-associated infection developed mainly by elderly patients. The objective of this study was to assess mortality among the patients of the Hospital for Infectious Diseases in Warsaw related to C.difficile infection. Analysis was conducted of 1638 records reporting the medical histories of patients hospitalized for the first time due to Clostridioides difficile infection (CDI) in the Hospital for Infectious Diseases in Warsaw from 2010 to 2017. The inclusion criteria were any (principal or secondary) discharge diagnosis code for CDI according to ICD-10 and being an adult (≥ 18 years). 108 out of 1638 (7%) of the patients died. The median age in this group was 83 years. The largest number of deaths (90%) occurred in the group of patients aged 65 years or older and 81-90 years old (53% of all the deaths). In the multivariate logistic regression model relevant only to the age groups, not to sepsis-age over 80 and over 90 were independent predictors of death, increasing the risk of death by 3.4 and 1.8 times, respectively. The result of the receiver operating curve (ROC) analysis determined the age of 77 years as the threshold value, indicating the increased risk of death (AUC 0.727, standard error 0.025, 95% CI 0.678-0.776, p < 0.0001). In addition, other quantitative variables, namely CRP, creatinine and leucocytes were studied and turned out to be independent death predictors as well. The diagnosis of sepsis increased the risk of death fourfold (OR = 4.042; 95% Cl 2.4-6.7; p < 0.001). Increased inflammatory parameters, namely CRP and white blood cell count, advanced age, particularly over the age of 80, as well as a diagnosis of sepsis are independent risk factors for death and could be used as predictive markers of poor outcome in CDI.

Clinical Course and Outcome of Community-Acquired Bacterial Meningitis in Cancer Patients.

The aim of the study was to determine the course and outcome of bacterial meningitis (BM) in patients with cancer. We retrospectively reviewed files of patients with community-acquired BM, hospitalized in a single neuroinfection center between January 2010 and December 2017. There were 209 patients included in the analysis: 28 had cancer (9 women, 19 men; median age 76, IQR 67-80 years) and 181 were cancer-free (76 women, 105 men; median age 52, IQR 33-65 years) and constituted the control group. Cancer patients, compared with controls, were more likely to present with seizures (25% vs. 8%, p = 0.019), scored higher on the Sequential Organ Failure Assessment, and had a higher mortality rate (32% vs. 13%, p = 0.025). Further, cancer patients were less likely (64% vs. 83%, p = 0.033) to present with two or more out of four clinical manifestations of BM (pyrexia, neck stiffness, altered mental status, and headache) and had a lower white blood cell (WBC) count than non-cancer controls. In multiple regression analysis, the presence of bacterial meningitis in cancer patients was independently associated only with older age (p = 0.001) and lower WBC count (p = 0.007), while mortality was associated with lower Glasgow Coma Score (p = 0.003). In conclusion, bacterial meningitis in cancer patients is characterized by atypical symptoms and high mortality, which requires physicians' vigilance and a prompt investigation of cerebrospinal fluid in suspected cases. However, multiple regression analysis suggests that differences in clinical presentation and outcomes of bacterial meningitis between cancer and cancer-free patients may also be attributable to other factors, such as age differences.

The clinical course and outcome of Listeria monocytogenes meningitis: A retrospective single center study.

BACKGROUND: The aim of the study was to determine clinical manifestations and outcome of Listeria monocytogenes meningitis (LM) and to compare with other forms of bacterial meningitis (BM). MATERIAL AND METHODS: We analyzed records of all adult patients with BM who were hospitalized between January 2010 and December 2017 in the largest neuroinfection center in Poland. RESULTS: Out of 343 analyzed patients with BM 24 were diagnosed to have LM. Patients with LM were older compared to patients with other forms of BM (62 years vs. 57 years, p=0.039), were more likely to have cancer (16.7% vs. 4.7%, p=0.045), receive immunosuppressive treatment (45.8% vs. 10.7%, p<0.001), or be immunocompromised in any way (62.5% vs. 35.5%, p=0.016). Blood tests showed lower WBC (10.7 × 103 cells/µl vs. 15.5 × 103 cells/µl, p=0.004), C-reactive protein (150 mg/L vs. 221 mg/L, p=0,019) and procalcitonin (1.27 ng/mL vs. 3.78 ng/mL, p=0.003) in LM group. Analysis of cerebrospinal fluid showed lower cell count (531.5 cells/µL vs. 1100 cells/µL, p<0.001) and lower chloride (113 mmol/L vs. 117 mmol/L, p=0.036) in patients with LM. In the multiple logistic regression analysis, immunosuppressive therapy was the only variable independently associated with LM (OR:8.72, CI 95%:1.41-64.34, p=0.024). CONCLUSIONS: LM is associated with older age, cancer and immunosuppressive therapy. However, in multivariate analysis only immunosuppressive therapy turned out to be an independent risk factor for LM.

Chronic alcohol abuse affects the clinical course and outcome of community-acquired bacterial meningitis.

The aim of the study was to determine the effect of chronic alcohol abuse on the course and outcome of bacterial meningitis (BM). We analyzed records of patients with BM who were hospitalized between January 2010 and December 2017 in the largest neuroinfection center in Poland. Out of 340 analyzed patients, 45 (13.2%) were alcoholics. Compared with non-alcoholics, alcoholics were more likely to present with seizures (p < 0.001), scored higher on the Sequential Organ Failure Assessment (SOFA) (p = 0.002) and lower on the Glasgow Coma Scale (GCS) (p < 0.001), and had worse outcome as measured by the Glasgow Outcome Score (GOS) (p < 0.001). Furthermore, alcoholics were less likely to complain of headache (p < 0.001) and nausea/vomiting (p = 0.005) and had lower concentration of glucose in cerebrospinal fluid (CSF) (p = 0.025). In the multiple logistic regression analysis, alcoholism was associated with lower GCS (p = 0.036), presence of seizures (p = 0.041), male gender (p = 0.042), and absence of nausea/vomiting (p = 0.040). Furthermore, alcoholism (p = 0.031), lower GCS score (p = 0.001), and higher blood urea concentration (p = 0.018) were independently associated with worse outcome measured by GOS. Compared with non-alcoholics, chronic alcohol abusers are more likely to present with seizures, altered mental status, and higher SOFA score and have an increased risk of unfavorable outcome. In multivariate analysis, seizures and low GCS were independently associated with alcoholism, while alcoholism was independently associated with worse outcome.

Usefulness of SOFA score and artesunate - based treatment in severe malaria ­ a single center study

INTRODUCTION: This study was conducted to assess the usefulness of the guidelines of treatment recommended in Malaria diagnosis and treatment guideline published by University College London Hospitals-NHS Foundation Trust on 26th June 2013, usefulness of artesunate-based therapy and usefulness of SOFA (sepsis-related organ failure assessment) score in treatment of severe malaria. Severe malaria is usually caused by Plasmodium falciparum and most of the time fulfills the criteria of sepsis which are specified in the new definition of sepsis. The other malaria species are commonly considered to be the cause of mild course of malaria, however more and more cases of severe malaria are reported in the course of tertian fever malaria caused by Plasmodium vivax and in the disease caused by Plasmodium knowlesi. MATERIALS AND METHODS: Fourteen patients with malaria were hospitalized in the Department of Adults' Infectious Diseases and in the Intensive Care Unit of the Hospital for Infectious Diseases in Warsaw between December 2013 and April 2017. All patients were treated according to Malaria diagnosis and treatment guideline UCLH. RESULTS: Thirteen patients in our study fulfilled the criteria of severe malaria. All fourteen patients presented with a SOFA score ≥2 points. Intravenous artesunate was administered to all patients in doses recommended in the UCLH guidelines. All patients presented with thrombocytopenia and elevated level of D-Dimers. The main factor influencing the dynamics of SOFA score was thrombocytopenia. All the patients fully recovered without any complications. CONCLUSIONS: The malaria treatment guidelines used in the Department for Infectious Diseases in Adults and in the Intensive Care Unit of the Hospital for Infectious Diseases in Warsaw in years 2013-2017 are effective. In assessing the severity of malaria SOFA score is useful especially as a warning of possibility of a severe course of the disease.

The angiotensinogen AGT p.M235T gene polymorphism may be responsible for the development of severe anaphylactic reactions to insect venom allergens.

BACKGROUND: Insect venom allergy (IVA) is present in 1-3% of the population. A group of patients with high specific IgE do not react to stings. In contrast, a proportion of patients with IVA have low specific IgE levels. These findings indicate that factors other than specific IgE may also be involved in IVA. Dysfunction of the renin-angiotensin system (RAS) has been described as a potential factor in IVA. The objective of this study was to determine the prevalence of angiotensin AGT p.M235T and angiotensin-converting enzyme ACE I/D, I/I, D/D gene polymorphisms in patients with IVA and to relate the presence of these gene variants to the course of IVA and the safety of treatment. METHODS: A total of 107 patients with IVA and 113 controls were studied. AGT p.M235T and ACE (ID, I/I, D/D) gene polymorphisms were examined, and angiotensin I levels were measured by immunoassay. RESULTS: The frequency of the AGT MM M235T variant was significantly higher in IVA patients (29.9%) than in controls (17%, p = 0.02). The presence of the MM M235T genotype increased the risk of grade IV reactions (odds ratio = 2.5 and 95% confidence interval 1.04-6.08). There were no differences in the prevalence of the ACE I/D polymorphism and angiotensin I levels between control groups and patients with different grades of anaphylactic reactions or patients with side effects of venom immunotherapy. CONCLUSION: The AGT M235T MM variant may be responsible for severe anaphylactic reactions to insect venom allergens in some patients.