Neurosyphilis with Concomitant Cryptococcal Meningitis in a Patient with AIDS after COVID-19: a case report (preprint)

Background The common infections agents causing meningitis in patients with human immunodeficiency virus (HIV) include Cryptococcus neoformans and Treponema pallidum. Furthermore, there is an elevated risk of meningitis in patients with HIV concomitantly infected with SARS-CoV-2.Case presentation: A 38-year-old male presented with headache and dizziness. After hospitalization, polymerase chain reaction test for SARS-CoV-2 in nasopharyngeal swab was positive, and lumbar puncture revealed neurosyphilis with concomitant cryptococcal meningitis. He underwent Paxlovid, penicillin, antifungal and antiretroviral treatment. The patient had no other neurological symptoms and was stable during the 6-month follow-up period.Conclusions During the COVID-19 pandemic, patients with HIV, particularly those not underwent antiretroviral therapy, are at higher risk for severe infections, including central nervous system complications, due to their compromised immune systems.

Cryptococcosis in the Immunocompetent Host: Incidence and Outcomes (preprint)

Cryptococcosis is an invasive fungal infection that typically affects immunocompromised individuals. There is limited research comparing the incidence and clinical outcomes of cryptococcosis in immunocompetent versus immunocompromised patients. Retrospective analysis was performed on patients with a confirmed positive CSF PCR, CSF antigen, or serum cryptococcal antigen tests from 5 hospitals in New York from 2017–2022. Patients were classified as immunocompromised if they had a diagnosis of HIV or active cancer, received an organ transplant, or were on immunosuppressive medications at the time of diagnosis. Baseline demographic information, comorbidities, and clinical outcomes were analyzed. 29 cases of cryptococcosis were identified with 8 cases (27.6%) occurring in immunocompetent patients. Immunocompetent patients with cryptococcosis were more likely to have a prior history of cardiac disease compared to immunocompromised patients (25% vs. 4.76%, p = 0.02). After the beginning of the COVID-19 pandemic, the proportion of immunocompetent cases increased (12% vs 35%, p = 0.03). Despite presenting with meningitis more frequently (75% vs 47.6% p = 0.08), immunocompetent patients demonstrated decreased rates of fungemia (25% vs. 33.3%, p = 0.06) and a significant decrease in mortality (12.5% vs. 23.8%, p = 0.04). Immunocompetent patients presented with meningitis more frequently and demonstrated better outcomes with decreased mortality. The proportion of immunocompetent patients increased over the study period after the beginning of the COVID-19 pandemic. Additional information about cryptococcosis in immunocompetent patients, as well as the role of cardiac disease, diabetes and COVID-19 infection as potential risk factors, warrants further study. Cryptococcosis in the Immunocompetent Host: Incidence and Outcomes

Paediatric Meningitis in the Conjugate Vaccine Era and Development of a Novel Clinical Decision Model to Predict Bacterial Aetiology in 3,002 Children with Suspected Meningitis (preprint)

Background: Implementation of bacterial conjugate vaccines have resulted in dramatic reductions in bacterial meningitis globally. The aetiology of childhood meningitis in the conjugate vaccine era is not well-defined, and differentiating bacterial meningitis from other similar childhood illnesses is a major challenge. The aims of this study were to assess aetiology and clinical characteristics in childhood meningitis, and develop clinical decision rules to distinguish bacterial meningitis from other similar clinical syndromes.Methods: Children aged <16 years hospitalised with suspected meningitis/encephalitis were included. Meningitis was defined as identification of bacteria/viruses from CSF and/or a CSF WBC>5/μL. Aetiology and clinical and laboratory features were analysed. Two new clinical decision rules were developed to distinguish bacterial meningitis from aseptic or suspected meningitis.Findings: 3,002 children (median age 2·4 months, IQR: 1·0-12·7) were prospectively recruited at 31 UK hospitals. Overall 1,101/3,002 (36·7%) had meningitis, including 203 with a bacterial aetiology, 423 viral and 280 with no pathogen identified. Enterovirus was the most common pathogen in those aged < six months and 10-16 years, with N. meningitidis and/or S. pneumoniae commonest at age six months–nine years. The Bacterial Meningitis Score had a negative predictive value of 95·3%. We developed two clinical decision rules, that could be used either before (sensitivity 82%, specificity 71%) or after LP (sensitivity 84%, specificity 93%), to determine risk of bacterial meningitis.Interpretation: Bacterial meningitis comprised only 6% of children presenting to hospital with suspected meningitis/encephalitis. Our clinical decision rules provide important novel approaches to identify the children with bacterial meningitis.Funding: This independent research was supported by the UK Meningitis Research Foundation, Pfizer, and the National Institute for Health Research Programme Grants for Applied Research Programme (Understanding and improving the outcome of viral encephalitis, RP-PG-0108- 10048). MS is supported via salary awards from the BC Children’s Hospital Foundation and Michael Smith Health Research BC. TS is supported by the National Institute for Health and Care Research (NIHR) Health Protection Research Unit in Emerging and Zoonotic Infections (Grant Nos. IS-HPU- 1112-10117 and NIHR200907).Declaration of Interest: MS has been an investigator on projects funded by GlaxoSmithKline, Merck, Moderna, Pfizer, Sanofi-Pasteur, Seqirus, Symvivo and VBI Vaccines. All funds have been paid to his institute, and he has not received any personal payments. AJP was a member of the World Health Organization’s Strategic Advisory Group of Experts on Immunization until January 2022 and remains chair of the UK Department of Health and Social Care's Joint Committee on Vaccination and Immunisation (JCVI). AJP also reports providing advice to Shionogi on COVID-19, and funding from the National Institute for Health Research (NIHR), AstraZeneca, the Bill & Melinda Gates Foundation, Wellcome, the Medical Research Council, and the Coalition for Epidemic Preparedness Innovations (CEPI). Oxford University has entered into a partnership with AstraZeneca for the development of COVID-19 vaccines. TS is Director of The Pandemic Institute, which has received funding from Innova, CSL Seqirus, Aviva and DAM Health; was an advisor to the GSK Ebola Vaccine programme and the Siemens Diagnostic Programme; Co-Chaired the WHO Neuro-COVID task force and sat on the UK Government’s Advisory Committee on Dangerous Pathogens, and the Medicines and Healthcare Products Regulatory Agency (MHRA) Expert Working Group on Covid-19 vaccines. PH has been an investigator on projects funded by GlaxoSmithKline, Merck, Moderna, Pfizer, Sanofi- Pasteur, Novavax, Valneva, Minervax and AZ. All funds have been paid to his institute, and he has not received any personal payments. He is a member of the UK JCVI. All other authors have no COI to disclose.Ethical Approval: The study was approved by NRES Committee East Midlands - Nottingham 1 (Ref: 11/EM/0442).

Newly discovered Pituitary Adenoma in the Emergency Center during the COVID-19 Pandemic in Serbia: Treatment and Early Postoperative Outcome (preprint)

Introduction:Pituitary tumors represent 10-15% of all intracranial tumors. Clinical manifestations depend on the size of the tumor such as microadenoma, macroadenoma or giant adenoma, and type of the tumor (secreting or non-secreting). Surgical treatment of pituitary adenoma can be managed via transcranial or transsphenoidal approach. Depending on the approach, there is a possibillity of postoperative complications such as meningitis, pneumocephalus, liquorrhea, transient diabetes insipidus and ect. Aim:The aim of this study was to establish the frequency of newly discovered pituitary tumors in the Emergency Center, University Clinical Center Of Serbia, during the COVID-19 pandemic in Serbia, and early postoperative complications in patients treated with an endoscopic and microscope transsphenoidal approach. Material and methods: During the time period during the pandemic, the study contains 119 patients, from January 1, 2020 to March 1, 2023, of which 64 are male (53.8%) and 55 are female (46.2%), age range is 14 to 85 years with a mean of 52.10. As for statistical analysis, assessment of frequency rate and relative numbers were used as methods of descriptive statistics. Results:Macroadenoma was present in 95 patients (79.83%), microadenoma in 22 patients (18.49%), and giant adenoma in 2 patients (1.69%). Transient DI developed postoperatively in 11 patients (9.24%). The average duration of hospitalization after surgery was 8 days. Conclusion: The duration of hospitalization depends on numerous factors where the COVID-19 pandemic can serve as an example for future similar crisis situations so that better organization and preoperative preparation of patients can be implemented.

Saudi Healthcare Students' Perceptions and Beliefs About Immunizations: a Descriptive, Cross-Sectional Study.

Background: Immunization has been one of the most successful public health measures ever undertaken. However, a degree of hesitancy about vaccine use still exists. Healthcare professionals are in a unique position to provide advice and education to the public and may influence the decision to undergo immunization. Objective: The aim of this study was to explore perceptions and beliefs regarding immunizations and immunization-preventable diseases. Methods: A descriptive cross-sectional study was undertaken at the Imam Abdulrahman bin Faisal University, located in Dammam, Saudi Arabia. In the Kingdom of Saudi Arabia, a survey of 564 Saudi undergraduate healthcare students was conducted. 77.8% of participants replied (439). Information was collected regarding perceptions of; severity of immunization-preventable diseases, contracting these diseases, immunization safety, and immunization beliefs. The statistical analysis was performed using the Statistical Package for the Social Sciences (IBM SPSS v25). Non-parametric analyses were utilized. Descriptive data were generated as appropriate, including frequencies, median, and inter-quartile range. Statistical relationships of demographic variables were explored using Kruskal Wallis H-Test and Spearman's Rank-Order Correlation. A p-value < 0.05 was considered statistically significant. Results: Meningitis was perceived as the most severe disease and COVID-19 as having the highest likelihood of infection. Concern regarding vaccine side effects was most evident for the COVID-19 vaccine. Student year level and profession resulted in statistically significant differences for all three assessed perceptions. Substantial differences were also identified regarding views on immunization belief statements. Conclusion: This study identified considerable heterogeneity in Saudi healthcare students' perceptions and beliefs regarding immunization-preventable diseases and vaccination. Further education is required to produce well-informed and confident healthcare professionals around these issues.

Cerebrospinal fluid viral etiology of patients with suspected central nervous system infections during the COVID-19 outbreak (preprint)

Purpose: Although viral etiology of central nervous system (CNS) infections such as meningitis and encephalitis are investigated widely worldwide, it remains to be declared under the COVID-19 pandemic. In this study, we aimed to investigate the etiology of viral CNS infections in patients hospitalized in a single referral hospital during the outbreak in Iran. Methods: We retrospectively collected the CSF samples and reviewed the medical records of patients hospitalized with suspected viral CNS infection in Shiraz, a large city in southern Iran, from April 2021 to May 2022. One hundred sixty-six cerebrospinal fluid (CSF) samples were tested primarily for detection of HSV 1 and 2 and were retrospectively analyzed by primers PCR targeted to coronavirus 2 (SARS-COV-2), human herpesviruses 1 to 6 (HHV-1 to -6), polyomaviruses JC, and enteroviruses (EV). Results: Of the total CSF samples analyzed by PCR, 22 (13.3%) were positive for only one viral pathogen, and just one (0.6%) sample was detected with multiple viruses (HSV-1 and CMV). The SARS-COV-2 (n=6) was the second most common viral etiology just after Herpes simplex virus (HSV-1) 6.6% (11 cases). Other detected viruses were CMV for 1.8% (3), VZV for 1.2 % (2), and JC for 0.6% (1) of the cases. Conclusion: According to the above, the spread of SARS-COV-2 during the COVID-19 pandemic, alongside HSV-1, CMV, and VZV in Iran, was significant. As a result, it can play an essential role in development of CNS-related diseases, which required urgent diagnosis and treatment.

Meningitis and encephalitis in Poland in 2020.

INTRODUCTION: Meningitis and/or encephalitis are one of the main infectious diseases of the nervous system. These diseases are most commonly caused by bacterial and viral etiological factors. In this publication, meningitis and/or encephalitis caused by Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae and those with a viral origin - in Poland, most often caused by tick-borne encephalitis virus - are presented in detail. In addition to epidemiological surveillance, immunoprophylaxis in the form of mandatory and recommended vaccinations is used in Poland to prevent these infections. AIM OF THE STUDY: The aim of this study was to to assess the epidemiological situation of meningitis and encephalitis in Poland, in 2020. MATERIAL AND METHODS: To analyse the epidemiological situation of neuroinfections in Poland were used data sent to NIPH NIH - NRI by Voivodeship Sanitary and Epidemiological Stations and published in the annual bulletins: "Infectious diseases and poisonings in Poland in 2020" and "Protective vaccination in Poland in 2020" and individual epidemiological interviews registered in the EpiBaza system. RESULTS: In 2020, a total of 831 cases of meningitis and/or encephalitis were registered in Poland. This is a decrease in incidence of up to 62.9% compared to 2019. For infections of bacterial etiology, including cases of neuroborreliosis (incidence of 2.40 per 100,000), the number of cases decreased by 60.4% (from 931 to 369). In the viral infection group, there was a 64.9% decrease (from 1,318 to 462 cases). Of all registered cases, 56% were infections with a viral etiology. Compared to 2019, the number of cases with an S. pneumoniae etiology decreased by 61.3% and for N. meningitidis by 41.1%. It is interesting to note that, in the case of H. influenzae, we can speak of a 20% increase in cases compared to the previous year. In addition, we can see a decrease in the incidence of tick-borne encephalitis - from 265 in 2019 to 158 in 2020 (a decrease of 40.4%). SUMMARY AND CONCLUSIONS: Overall, a downward trend in incidence was shown for both bacterial and viral meningitis and/or encephalitis. The SARS-CoV-2 pandemic and the introduction of restrictions on personto-person contact and various forms of activity, resulting in a reduction in pathogen transmission, were key to the significant reduction in the number of meningitis and/or encephalitis cases in 2020, but a reduction in the availability of medical facilities or the completeness of case reports due to the burden of anti-epidemic measures on the Sanitary Inspectorate cannot be excluded either. Only in the case of cases caused by H. influenzae was a slight increase observed compared to the previous year (12 versus 10 cases). Meningoencephalitis and/or encephalitis, due to its wide etiological range, poses a major challenge to the health care system, particularly in terms of correct clinical diagnosis.

The first case of meningitis associated with SARS-CoV-2 BA.2 variant infection with persistent viremia.

Severe neurological disorders and vascular events during COVID-19 have been described. Here, we describe the first case of a female patient infected with the SARS-CoV-2 BA.2 Omicron variant of concern with meningitis with newly diagnosed central demyelinating disease.

COVID-19 and Serious Bacterial Infection in Febrile Infants Less Than 60 Days Old.

INTRODUCTION: The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to the coronavirus disease 2019 (COVID-19) pandemic that drastically impacted the United States. The evidence was not clear on how SARS-CoV-2 infection impacted children, given the high prevalence of SAR-CoV-2 infection. Febrile infants less than 60 days old are an ongoing challenge to risk-stratify for serious bacterial infection (SBI), including urinary tract infection (UTI), bacteremia, and meningitis. We hypothesized there would be a lower rate of SBI in SARS-CoV-2 positive febrile infants compared to those SARS-CoV-2 negative. METHODS: This was a retrospective chart review with a nested, age-matched, case-control study performed from March 2020-June 2021. Infants less than 60 days old presenting with fever were assigned groups based on SARS-CoV-2 infection. Blood, urine, and cerebrospinal fluid cultures were used as the gold standard to diagnose SBI. We compared overall rate of SBI as well as individual rates of SBI between each group. We performed a subgroup analysis evaluating the age group 29-60 days old. RESULTS: A total of 164 subjects met criteria for analysis: 30 COVID-19 positive and 134 COVID-19 negative subjects. Rate of SBI was 17.9% (95% confidence interval [CI]: 11.8-25.5%) in the COVID-19 negative group compared to 0% (95% CI: 0.0%-11.1%) in the COVID-19 group, which demonstrated statistical significance (p = 0.008). In the age-matched data, we found statistical significance for any SBI (p = <0.001). For individual rates of SBI, we found statistical significance for UTI (p = <0.001) and bacteremia (p = <0.001). The 29-60 days-old subgroup analysis did not achieve statistical significance (p = 0.11). CONCLUSION: This study demonstrated the utility of including SARS-CoV-2 infection as part of the risk stratification of febrile infants less than 60 days old. While overall there is a low incidence of bacteremia and meningitis in this age group, these results can contribute to existing literature and potentially help decrease invasive testing and exposure to broad-spectrum antibiotics.

Rotavirus meningitis in an adult with transient aphasia.

We identified an additional case of documented Rotavirus meningitis in an adult with full medical history. A previously healthy 37-year-old patient presented herself for transient aphasia associated with fever and headaches at the end of a one-week history of gastroenteritis. Cerebrospinal fluid (CSF) analysis revealed lymphocytic meningitis, and treatment with aciclovir was initiated. Rotavirus A reverse transcription-polymerase chain reaction (RT-PCR) was positive in CSF and the patient's stools in favor of Rotavirus meningitis. Testing for other viruses was negative. Magnetic resonance imaging (MRI) showed no signs of encephalitis. Aphasia was resolutive in less than 12 hours, and no neurological symptoms relapsed. All symptoms evolved favorably despite aciclovir discontinuation. Viral sequencing methods have recently identified unexpected viruses as potential causative agents in meningitis, including Rotavirus. We confirm the detectability of Rotavirus in the analysis of CSF in the context of Rotavirus gastroenteritis in an adult. This case suggests postviral headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL) syndrome may be linked to previously undetected direct viral infection of the central nervous system. Therefore, clinicians should consider Rotavirus meningitis in diagnosing meningitis associated with gastroenteritis in adults.

Meningitis caused by Capnocytophaga canimorsus in a COVID-19 patient: a rare complication of dog bites.

Capnocytophaga canimorsus is a gram-negative rod that is part of the commensal microbiota of dogs' and cats' mouths. In this case, we report an 85-year-old man with COVID-19 who had his right arm bitten by a dog. His symptoms were impaired consciousness, agitation and aggressive behavior. Physical examination revealed neck stiffness and Brudzinski's sign. The cerebrospinal fluid culture was compatible with Capnocytophaga canimorsus. He required intensive care and received a 14-day prescription of meropenem. After 40 days of hospitalization, the patient was fully recovered and was discharged. This case highlights the importance of physician and microbiologist be awareness of this disease, mainly in patients with neurological symptoms after a dog or cat bite.

Zoster Meningitis in an Immunocompetent Child after COVID-19 Vaccination, California, USA.

Varicella zoster virus reactivation after COVID-19 vaccination has been reported in older or immunocompromised adults. We report zoster meningitis from live-attenuated varicella vaccine reactivation in an immunocompetent child after COVID-19 vaccination. This type of case is rare; COVID-19 and varicella vaccines remain safe and effective for appropriate recipients in the pediatric population.

Varicella-Zoster Virus (VZV) Meningitis in an Immunocompetent Adult after BNT162b2 mRNA COVID-19 Vaccination: A Case Report.

We present, to our knowledge, the second case report of a 46-year old female who developed varicella-zoster virus (VZV) meningitis after BNT162b2 mRNA COVID-19 vaccination. The patient is immunocompetent and has no known predisposing risk factors for developing VZV meningitis. The patient received acyclovir therapy and subsequently had a complete recovery. We describe possible mechanisms of VZV meningitis after mRNA COVID-19 vaccination.

Varicella zoster meningitis following COVID-19 vaccination: a report of two cases.

Most of the adverse effects reported in patients who have received COVID-19 vaccines have been mild. However, possible serious adverse effects are being monitored cautiously. There have also been a number of case reports of reactivation of varicella zoster infection within 28 days after immunization with mRNA COVID-19 vaccines. A few cases have also been reported after viral vector and inactivated COVID-19 vaccination. The incidence of meningitis following varicella zoster virus infection is rare. In the current study, we report two cases of male patients who received two different types of COVID-19 vaccine (inactivated and viral vector) and developed varicella zoster meningitis within 10 days after vaccination.

A Case Report of Herpes Zoster Ophthalmicus and Meningitis After COVID-19 Vaccination.

There are several reports that herpes zoster characterized by reactivation of varicella zoster virus (VZV) following coronavirus disease 2019 (COVID-19) vaccines can occur. Herein, we report VZV meningitis, herpes zoster ophthalmicus (HZO), and late neurotrophic keratitis after receiving a second dose of messenger RNA (mRNA) COVID-19 vaccine. A 74-year-old man developed a vesicular skin rash on the forehead, scalp, nose, and left upper eyelid with a severe headache. Five days earlier, he received a second dose of the BNT162b2 mRNA vaccine on his left arm. Ocular examination revealed conjunctival hyperemia and pseudodendrite in the peripheral cornea. VZV was detected in the cerebrospinal fluid using polymerase chain reaction. The patient was diagnosed with HZO and meningitis. The patient was treated with intravenous acyclovir and topical acyclovir ointment and levofloxacin 1.5% eye drops. One month later, he developed a central epithelial defect with a rolled margin, typical of a neurotrophic ulcer. Treatment with a therapeutic contact lens and a combination of topical recombinant human epithelial growth factor and ofloxacin ointment was initiated. At six months after vaccination, the slit-lamp examination findings were stable with a mild corneal superficial stromal haze.

Autoimmune meningoencephalitis associated with anti-glutamic acid decarboxylase antibody following covid-19 infection: A case report Written informed consent was obtained from the patient to publish this report in accordance with the journal’s patient consent policy (preprint)

Anti-glutamic acid decarboxylase(Anti-GAD) are associated with various neurologic condition; but, no meningitis has been reported with it, so far. Evidence demonstrates the associated of autoimmune meningoencephalitis with Covid-19 infection. Here we report a 44-year-old female with progressive loss of consciousness with anti-GAD65 meningoencephalitis after Covid-19 infection.