A Summer of Fevers and Fussiness: Eighteen Infants Admitted With Parechovirus Meningitis.

OBJECTIVE: To define the presentation, spectrum of illness, and outcomes in infants with parechovirus (PeV) meningitis admitted to our inpatient general pediatrics service during a spike in incidence of admissions in summer 2022. PATIENTS AND METHODS: This study is a retrospective case series of all patients aged 3 months and younger discharged from our institution with a CSF BioFire (BioFire Diagnostics, Salt Lake City, UT) FilmArray Polymerase Chain Reaction Meningitis/Encephalitis Panel result positive for PeV between January 1 and September 19, 2022. We collected and analyzed clinical and demographic data. RESULTS: Eighteen infants with PeV meningitis were admitted within our time frame, with 8 (44%) of the admissions occurring in July. Patients' mean age was 28.7 days and mean length of stay was 50.5 hours. Although all had a history of fever, only 72% were febrile on presentation. Laboratory findings showed a procalcitonin of less than 0.5 ng/mL in 86% of the 14 patients who had it drawn and no cerebrospinal fluid (CSF) pleocytosis in 83% of the patients who had CSF cell counts sent. Neutropenia was present in 17%. Although 89% of infants were given initial antibiotics, antibiotics were discontinued in 63% once their CSF panel returned positive for PeV, and in all by 48 hours. CONCLUSIONS: Infants hospitalized with PeV meningitis were febrile and fussy, but experienced uncomplicated hospital stays without neurological deficits. Parechovirus meningitis must be considered as a common cause of acute viral meningitis in young infants even without CSF pleocytosis. This study, although limited in scope and follow-up, can potentially assist in the diagnosis and treatment of PeV meningitis at other institutions.

Relevance of enteroviruses in neonatal meningitis.

INTRODUCTION: Enterovirus (EV) infections are the most frequent infections in the neonatal period and in many cases lead to hospital admission of the newborn (NB). The aim of this study was to determine the incidence of EV in the etiology of neonatal meningitis and to define the clinical characteristics of newborns with EV meningitis. MATERIAL AND METHOD: Retrospective observational cohort study. Including 91 NBs with meningitis and gestational age greater than 34 weeks gestational age (GA) attended in our center over a period of 16 years. RESULTS: The percentage of NBs with EV meningitis was higher than that of NBs with bacterial meningitis (BM) and accounted for 78% (n=71). Half of the NBs with EV infection had a history of epidemic environment among their caregivers. Fever was present in 96% of cases as a clinical sign and, in general, sensory disturbances represented the main neurological alterations. Antibiotics (ATB) were given to 71.4% of patients with EV infection. Detection of EV in CSF samples showed a high sensitivity for the diagnosis of EV meningitis. The most frequently implicated EV types were echovirus 11, coxsackievirus B5, echovirus 18, 25 and 7. CONCLUSIONS: The results of this series show that enterovirus infection is a common cause of neonatal meningitis. These data underline the importance of rapid EV testing of infants with suspected meningitis. This allows early diagnosis and reduces antibiotic treatment, hospitalization time and related costs.

Benign recurrent lymphocytic meningitis (Mollaret's meningitis) in Denmark: a nationwide cohort study.

BACKGROUND AND PURPOSE: Data on clinical features and outcomes of benign recurrent lymphocytic meningitis (BRLM) are limited. METHODS: This was a nationwide population-based cohort study of all adults hospitalized for BRLM associated with herpes simplex virus type 2 (HSV-2) at the departments of infectious diseases in Denmark from 2015 to 2020. Patients with single-episode HSV-2 meningitis were included for comparison. RESULTS: Forty-seven patients with BRLM (mean annual incidence 1.2/1,000,000 adults) and 118 with single-episode HSV-2 meningitis were included. The progression risk from HSV-2 meningitis to BRLM was 22% (95% confidence interval [CI] 15%-30%). The proportion of patients with the triad of headache, neck stiffness and photophobia/hyperacusis was similar between BRLM and single-episode HSV-2 meningitis (16/43 [37%] vs. 46/103 [45%]; p = 0.41), whilst the median cerebrospinal fluid leukocyte count was lower in BRLM (221 cells vs. 398 cells; p = 0.02). Unfavourable functional outcomes (Glasgow Outcome Scale score of 1-4) were less frequent in BRLM at all post-discharge follow-up visits. During the study period, 10 (21%) patients with BRLM were hospitalized for an additional recurrence (annual rate 6%, 95% CI 3%-12%). The hazard ratio for an additional recurrence was 3.93 (95% CI 1.02-15.3) for patients with three or more previous episodes of meningitis. CONCLUSIONS: Clinical features of BRLM were similar to those of single-episode HSV-2 meningitis, whilst post-discharge outcomes were more favourable. Patients with three or more previous episodes of meningitis had higher risk of an additional recurrence.

Enterovirus Meningitis without Pleocytosis: a Retrospective Observational Study in Adults.

Reverse-transcription polymerase chain reaction (RT-PCR)-confirmed enterovirus (EV) meningitis without pleocytosis has only been previously reported in children. In this study, we examined the frequency of EV meningitis without pleocytosis in adults and compared its clinical features. We retrospectively analyzed the data of adult patients with EV meningitis confirmed using cerebrospinal fluid (CSF) RT-PCR. Among the 17 patients included in this study, 58.8% showed no pleocytosis. The median age and clinical symptoms did not differ between the pleocytosis and non-pleocytosis groups. There were no statistically significant differences in seasonal variation or time from the onset of meningitis symptoms to lumbar puncture. The peripheral white blood cell (WBC) count in patients with pleocytosis was significantly higher than that in patients without pleocytosis. The median CSF pressure showed a higher trend in the non-pleocytosis group. Patients with CSF pressures higher than normal were more common in the non-pleocytosis group. The median CSF protein values were higher than the normal values in both groups. We confirmed the high frequency of EV meningitis without pleocytosis in adults. Accurate diagnosis using RT-PCR is necessary when meningitis symptoms are prominent during an EV epidemic, and CSF protein levels and pressure are high, even if the CSF WBC count is normal.

Separating the wheat from the chaff - Optimizing the diagnosis of enterovirus-associated meningitis.

BACKGROUND: Enteroviruses (EV) comprise the single most common cause of aseptic meningitis with variable geographical and temporal epidemiology. While EV-PCR in CSF is considered a gold standard for diagnosis, it is not-uncommon to use stool EV as a surrogate. Our aim was to assess the clinical significance of EV-PCR-positive CSF and stool in the investigation of patients with neurological symptoms. METHODS: In this retrospective study from Sheba Medical centre, the largest tertiary hospital in Israel, we collected demographic, clinical and laboratory data of patients with EV-PCR-positive between 2016 and 2020. A comparison between various combinations of EV-PCR-positive CSF and stool was conducted. Data regarding EV strain-type and cycle threshold (Ct) were crossed with clinical symptoms and temporal kinetics. RESULTS: Between 2016-2020, 448 CSF samples with positive EV-PCR were recorded from unique patients, the vast majority of which were diagnosed with meningitis (98%, 443/448). Unlike the diverse strain types of EV background activity, meningitis-related EV showed a clear epidemic pattern. In comparison with the EV CSF+/Stool+ group, the EV CSF-/Stool+ group had frequently more alternative pathogens detected and a higher stool Ct-value. Clinically, EV CSF-/Stool+ patients were less febrile and more lethargic and convulsive. DISCUSSION: The comparison of the EV CSF+/Stool+ and CSF-/Stool+ groups suggests that putative diagnosis of EV meningitis is prudent in the febrile, non-lethargic non-convulsive patients with an EV-PCR-positive stool. Otherwise, the detection of stool EV only, in a non-epidemic setup, especially with a high Ct-value, may be incidental and mandate a continuous diagnostic effort for an alternative culprit.

Increased detection of Echovirus 6-associated meningitis in patients hospitalized during the COVID-19 pandemic, Israel 2021-2022.

BACKGROUND: Outbreaks of enteroviral meningitis occur periodically and may lead to hospitalization and severe disease. OBJECTIVE: To analyze and describe the meningitis outbreak in patients hospitalized in Israel in 2021-2022, during the COVID-19 pandemic. RESULTS: In December 2021, before the emergence of the SARS-CoV-2 omicron variant, an off-season increase in enterovirus (EV) infections was observed among patients hospitalized with meningitis. In January 2022, enterovirus cases decreased by 66% in parallel with the peak of the Omicron wave, and then increased rapidly by 78% in March (compared with February) after a decline in Omicron cases. Sequencing of the enterovirus-positive samples showed a dominance of echovirus 6 (E-6) (29%) before and after the Omicron wave. Phylogenetic analysis found that all 29 samples were very similar and all clustered in the E-6 C1 subtype. The main E-6 symptoms observed were fever and headache, along with vomiting and neck stiffness. The median patient age was 25 years, with a broad range (0-60 years). CONCLUSION: An upsurge in enterovirus cases was observed after the decline of the SARS-CoV-2 omicron wave. The dominant subtype was E-6, which was present prior to the emergence of the omicron variant, but increased rapidly only after the omicron wave decline. We hypothesize that the omicron wave delayed the rise in E-6-associated meningitis.

Clinical features and prognostic factors in adults with viral meningitis.

Clinical features applicable to the entire spectrum of viral meningitis are limited, and prognostic factors for adverse outcomes are undetermined. This nationwide population-based prospective cohort study included all adults with presumed and microbiologically confirmed viral meningitis in Denmark from 2015 until 2020. Prognostic factors for an unfavourable outcome (Glasgow Outcome Scale score of 1-4) 30 days after discharge were examined by modified Poisson regression. In total, 1066 episodes of viral meningitis were included, yielding a mean annual incidence of 4.7 episodes per 100 000 persons. Pathogens were enteroviruses in 419/1066 (39%), herpes simplex virus type 2 in 171/1066 (16%), varicella-zoster virus in 162/1066 (15%), miscellaneous viruses in 31/1066 (3%) and remained unidentified in 283/1066 (27%). The median age was 33 years (IQR 27-44), and 576/1066 (54%) were females. In herpes simplex virus type 2 meningitis, 131/171 (77%) were females. Immunosuppression [32/162 (20%)] and shingles [90/149 (60%)] were frequent in varicella-zoster virus meningitis. The triad of headache, neck stiffness and hyperacusis or photophobia was present in 264/960 (28%). The median time until lumbar puncture was 3.0 h (IQR 1.3-7.1), and the median CSF leucocyte count was 160 cells/µl (IQR 60-358). The outcome was unfavourable in 216/1055 (20%) 30 days after discharge. Using unidentified pathogen as the reference, the adjusted relative risk of an unfavourable outcome was 1.34 (95% CI 0.95-1.88) for enteroviruses, 1.55 (95% CI 1.00-2.41) for herpes simplex virus type 2, 1.51 (95% CI 0.98-2.33) for varicella-zoster virus and 1.37 (95% CI 0.61-3.05) for miscellaneous viruses. The adjusted relative risk of an unfavourable outcome was 1.34 (95% CI 1.03-1.75) for females. Timing of acyclovir or valacyclovir was not associated with the outcome in meningitis caused by herpes simplex virus type 2 or varicella-zoster virus. In summary, the outcome of viral meningitis was similar among patients with different aetiologies, including those with presumed viral meningitis but without an identified pathogen. Females had an increased risk of an unfavourable outcome. Early antiviral treatment was not associated with an improved outcome in meningitis caused by herpes simplex virus type 2 or varicella-zoster virus.

[Influence of the COVID-19 pandemic on the occurrence of neurological infectious diseases]. / Einfluss der COVID-19-Pandemie auf das Auftreten neuroinfektiologischer Erkrankungen.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic a wide range of hygiene measures were implemented to contain the spread of infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Besides a mitigation of SARS-CoV­2, a decline in the number of other respiratory tract infections could be observed. Interestingly, the numbers for some infections of the central nervous system (CNS) decreased as well. OBJECTIVE: This review article shows the development of important CNS infections in Germany during the COVID-19 pandemic. MATERIAL AND METHOD: This article is based on relevant literature on the epidemiology of CNS infections during the COVID-19 pandemic up to autumn 2022. RESULTS: During the COVID-19 pandemic the frequency of bacterial meningitis caused by Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae significantly declined. The frequency of viral meningitis, particularly those caused by Enterovirus, decreased as well. In contrast, the number of patients suffering from tick-borne encephalitis significantly increased within the first year of the pandemic. DISCUSSION: During the pandemic there was a decrease in cases of bacterial and viral meningitis, most likely due to the general containment strategies and social contact restrictions. The increase of infections transmitted by ticks could be a consequence of changed leisure activities during the pandemic.

Epidemiology and Disease Burden of Hospitalized Children With Viral Central Nervous System Infections in China, 2016 to 2020.

BACKGROUND: Viral central nervous system (CNS) infections seriously threaten the life and health of children, with a high mortality and severe sequelae in China and globally. Surveillance of viral CNS infections in children is important, especially in hospitalized children, to facilitate disease evaluation. METHODS: In this study, we collected the data on the discharged Face Sheet of Medical Records from database from 2016 to 2020 and analyzed the epidemiologic characteristics and disease burden of hospitalized children (≤18 years old) with viral CNS infections in China. We classified the discharge diagnosis of viral CNS infection as viral encephalitis (VE), viral meningitis (VM), viral meningoencephalitis (VME), viral encephalomyelitis (VEM), and viral meningomyelitis (VMM). RESULTS: A total of 42,641 cases of viral CNS infections were included in the database, consisting of 39,279 cases with VE (92.47%), 2011 cases with VM (4.73%), 1189 cases with VME (2.80%), 118 cases with VEM (0.28%), and 44 cases with VMM (0.10%). The number of hospitalized patients with viral CNS infections accounted for 0.74% (42,641 of 5,790,910) of all hospitalized cases. The onset of viral CNS infections presented seasonal characteristic, with peaks in June to July and December to January. Seizures are the most frequent complication of this disorder. Median length of stay and inpatient expenditures for patients with viral CNS infections were 9 days and 1144.36 USD. Causative viruses were identified in 4.33% (1848 of 42,641) of patients. CONCLUSIONS: This study will help understand the clinical epidemiology and disease burden of hospitalized children with viral CNS infections in China.

Viral meningitis in Sudanese children: Differentiation, etiology and review of literature.

Diagnosis of viral meningitis (VM) is uncommon practice in Sudan and there is no local viral etiological map. We therefore intended to differentiate VM using standardized clinical codes and determine the involvement of herpes simplex virus types-1 and 2 (HSV-1/2), varicella zoster virus, non-polio human enteroviruses (HEVs), and human parechoviruses in meningeal infections in children in Sudan. This is a cross-sectional hospital-based study. Viral meningitis was differentiated in 503 suspected febrile attendee of Omdurman Hospital for Children following the criteria listed in the Clinical Case Definition for Aseptic/Viral Meningitis. Patients were children age 0 to 15 years. Viral nucleic acids (DNA/RNA) were extracted from cerebrospinal fluid (CSF) specimens using QIAamp® UltraSens Virus Technology. Complementary DNA was prepared from viral RNA using GoScriptTM Reverse Transcription System. Viral nucleic acids were amplified and detected using quantitative TaqMan® Real-Time and conventional polymerase chain reactions (PCRs). Hospital diagnosis of VM was assigned to 0%, when clinical codes were applied; we considered 3.2% as having VM among the total study population and as 40% among those with proven infectious meningitis. Two (0.4%) out of total 503 CSF specimens were positive for HSV-1; Ct values were 37.05 and 39.10 and virus copies were 652/PCR run (261 × 103/mL CSF) and 123/PCR run (49.3 × 103/mL CSF), respectively. Other 2 (0.4%) CSF specimens were positive for non-polio HEVs; Ct values were 37.70 and 38.30, and the approximate virus copies were 5E2/PCR run (~2E5/mL CSF) and 2E2/PCR run (~8E4/mL CSF), respectively. No genetic materials were detected for HSV-2, varicella zoster virus, and human parechoviruses. The diagnosis of VM was never assigned by the hospital despite fulfilling the clinical case definition. Virus detection rate was 10% among cases with proven infectious meningitis. Detected viruses were HSV-1 and non-polio HEVs. Positive virus PCRs in CSFs with normal cellular counts were seen.

Serotype analysis of pediatric enteroviral meningitis in Gwangju, Republic of Korea: Number of annual cases, distribution by age group, and characteristics of each serotype.

BACKGROUND: Enteroviral meningitis is a common disease in children; however, serotype data are still lacking, especially for late childhood. OBJECTIVES: This study analyzed the number of annual cases, distribution by age group, and characteristics of each serotype among children with enteroviral meningitis. STUDY DESIGN: After the initial screening of 1,009 children (<18 years) with viral meningitis between 2008 and 2021, the data of enteroviral meningitis were retrospectively reviewed. The number of annual cases and serotypes were investigated. The distribution of serotypes across different ages was reviewed. Clinical characteristics of the major serotypes (detected in at least 15 patients) were further examined. RESULTS: Among the 700 patients with enteroviral meningitis, serotypes were tested in 517 patients (73.9%), which could be typed in 370 patients (71.6%). EV-A71 was the most common serotype detected in 2010, 2012, and 2019. After 2020, enterovirus was rarely detected. The group B coxsackieviruses (CVBs) were commonly detected in neonates (CVB1, 33.3%) and infants (CVB5, 17.4%). The echoviruses were commonly detected beyond infancy; E30 was the most frequently detected in late childhood (14.4%) and adolescents (15.4%). EV-A71 was the most frequently detected in early childhood (17.2%). Between the 11 major serotypes, vomiting, headache, and irritability were more commonly associated with echoviruses (P <0.01). In EV-A71, neurologic symptoms and skin lesions were more common (P <0.01). CONCLUSION: The CVBs were commonly detected in neonates and infants, whereas the echoviruses were commonly detected beyond infancy and caused vomiting, headache, and irritability. EV-A71 was the most frequently detected in early childhood, frequently causing neurologic and dermatologic problems.

Enterovirus meningitis in Mayotte French Comoros Island, March-June 2019.

BACKGROUND: Enteroviruses (EV) are the most frequent cause of acute meningitis worldwide, and regularly responsible for outbreaks. Human parechoviruses (PeV) are associated with sepsis and meningitis in young infants. In Mayotte, a French department located in the Comoros archipelago, EVs and PeVs are not part of the routine screening of cerebrospinal fluids (CSFs) of patients with meningitis. Consequently, no data is available on EV or PeV epidemiology. AIM: Assess the need for EV and PeV diagnosis in Mayotte. METHODS: CSFs collected between March and June 2019 from patients addressed to Mayotte Hospital were retrospectively screened for EV and PeV by PCR. If positive for EV, genotyping was attempted. RESULTS: EV and PeV RT-PCR were performed on 122/263 (46%) CSFs (45 adults, 77 children). EV meningitis was diagnosed in 16/77 children (21%) with a median age of 32 days (8-62). One 30-days-aged infant presented with a PeV infection. Fever was reported in 94% cases (16/17), followed by gastrointestinal disorders in 29% cases (5/17). EV genotyping achieved identification for 10/16 (63%) EV-positive samples. Four different EV types were identified: Echovirus 16 (E-16, n = 6), EV-B100 (n = 2), and E-14 and E-18 (n = 1, each). CONCLUSION: EV/PeV prevalence of 14% highlights the importance of implementing this diagnosis which can impact duration of hospitalization and administration of antibiotics thus reducing risk of antimicrobial resistance. Surveillance of circulating EV types is needed to understand the range of enteroviruses detected in meningitis cases in places that have been underrepresented in enterovirus surveillance studies.

Decline in the number of patients with meningitis in German hospitals during the COVID-19 pandemic.

BACKGROUND AND OBJECTIVES: In 2020, a wide range of hygiene measures was implemented to mitigate infections caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In consequence, pulmonary infections due to other respiratory pathogens also decreased. Here, we evaluated the number of bacterial and viral meningitis and encephalitis cases during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: In a multicentre retrospective analysis of data from January 2016 until December 2020, numbers of patients diagnosed with bacterial meningitis and other types of CNS infections (such as viral meningitis and encephalitis) at 26 German hospitals were studied. Furthermore, the number of common meningitis-preceding ear-nose-throat infections (sinusitis, mastoiditis and otitis media) was evaluated. RESULTS: Compared to the previous years, the total number of patients diagnosed with pneumococcal meningitis was reduced (n = 64 patients/year in 2020 vs. n = 87 to 120 patients/year between 2016 and 2019, all p < 0.05). Additionally, the total number of patients diagnosed with otolaryngological infections was significantly lower (n = 1181 patients/year in 2020 vs. n = 1525 to 1754 patients/year between 2016 and 2019, all p < 0.001). We also observed a decline in viral meningitis and especially enterovirus meningitis (n = 25 patients/year in 2020 vs. n = 97 to 181 patients/year between 2016 and 2019, all p < 0.001). DISCUSSION: This multicentre retrospective analysis demonstrates a decline in the number of patients treated for viral and pneumococcal meningitis as well as otolaryngological infections in 2020 compared to previous years. Since the latter often precedes pneumococcal meningitis, this may point to the significance of the direct spread of pneumococci from an otolaryngological focus such as mastoiditis to the brain as one important pathophysiological route in the development of pneumococcal meningitis.

Epidemiological characteristics and climatic variability of viral meningitis in Kazakhstan, 2014-2019.

Background: The comprehensive epidemiology and impact of climate on viral meningitis (VM) in Kazakhstan are unknown. We aimed to study the incidence, in-hospital mortality and influence of climatic indicators on VM from 2014 to 2019. Methods: Nationwide electronic healthcare records were used to explore this study. ICD-10 codes of VM, demographics, and hospital outcomes were evaluated using descriptive statistics and survival analysis. Results: During the 2014-2019 period, 10,251 patients with VM were admitted to the hospital. 51.35% of them were children, 57.85% were males, and 85.9% were from the urban population. Enteroviral meningitis was the main cause of VM in children. The incidence rate was 13 and 18 cases per 100,000 population in 2014 and 2019, respectively. Case fatality rate was higher in 2015 (2.3%) and 2017 (2.0%). The regression model showed 1°C increment in the daily average temperature might be associated with a 1.05-fold (95% CI 1.047-1.051) increase in the daily rate of VM cases, 1hPa increment in the average air pressure and 1% increment in the daily average humidity might contribute to a decrease in the daily rate of VM cases with IRRs of 0.997 (95% CI 0.995-0.998) and 0.982 (95% CI 0.981-0.983), respectively. In-hospital mortality was 35% higher in males compared to females. Patients residing in rural locations had a 2-fold higher risk of in-hospital death, compared to city residents. Elderly patients had a 14-fold higher risk of in-hospital mortality, compared to younger patients. Conclusion: This is the first study in Kazakhstan investigating the epidemiology and impact of climate on VM using nationwide healthcare data. There was a tendency to decrease the incidence with outbreaks every 5 years, and mortality rates were higher for Russians and other ethnicities compared to Kazakhs, for males compared to females, for elder patients compared to younger patients, and for patients living in rural areas compared to city residents. The climatic parameters and the days of delay indicated a moderate interaction with the VM cases.

Clinical profile of children with parechovirus meningitis in Singapore.

Human parechovirus (HPeV) is one of the most common causes of aseptic meningitis in children worldwide. This study aims to review the epidemiology, clinical presentation, and cerebrospinal fluid (CSF) findings in HPeV meningitis and compare these with Enterovirus (EV) meningitis. This is a retrospective study of children aged ≤ 1 year admitted for HPeV meningitis between November 2015 and July 2017, with positive CSF HPeV PCR and negative blood and CSF bacterial cultures. The clinical findings were compared with a historical cohort of children with EV meningitis admitted between July 2008 and July 2011. There were 71 children with HPeV meningitis, aged between 2 and 127 days, with the majority (96%) being ≤ 90 days old. The most common symptoms reported were poor feeding (42%), tachycardia out of proportion to fever (27%), and lethargy (20%). Only 2 patients (3%) had CSF pleocytosis. Cerebral spinal fluid white blood cell counts ranged from 0 to 28 cells/mm3, with a median of 3 cells/mm3 [interquartile range (IQR) 1-6 cells/mm3]. When compared to our historical cohort of EV meningitis ≤ 90 days old, children with HPeV meningitis ≤ 90 days old were less likely to have CSF pleocytosis (OR 0.008, 95% CI 0.001-0.057). HPeV and EV meningitis are known to cause sepsis-like illness in infants < 90 days old. This study further supports this, with the requirement for fluid bolus therapy for tachycardia or poor perfusion noted to be higher in children with HPeV meningitis ≤ 90 days old (OR 6.3, 95% CI 2.7-14.2).

High rate of human enteroviruses among clinically suspected meningitis cases at selected Hospitals in Addis Ababa, Ethiopia.

BACKGROUND: Because of limited infrastructure and skilled human capital, the etiology of meningitis is rarely identified in developing countries like Ethiopia. This results in unnecessary antibiotics use, economic crisis, hospitalization, and related nosocomial infections. Thus, we aimed to assess the epidemiology of human enteroviruses (HEVs) among clinically suspected meningitis cases in Addis Ababa, Ethiopia. METHOD: A cross-sectional study was conducted from January to August 2020 at selected Hospitals in Addis Ababa, Ethiopia. Reverse transcriptase-polymerase chain reaction (RT-PCR) was conducted on cerebrospinal fluid (CSF) collected from 146 clinically suspected meningitis and bacterial culture-negative patients. SPSS v 21.0 was used for data analysis and bivariate correlation was done for the association between variables of interest. RESULTS: HEVs were detected in 39 (26.7%) of the 146 clinically suspected meningitis cases. Most of the HEVs cases 28 (71.9%) were detected in younger-aged infants less than 1 year. The most commonly observed clinical manifestations were vomiting (75.5%) followed by fever (56.8%) and impaired consciousness or irritability (50.7%). The mean length of hospital stay for patients with enteroviral meningitis was 9 days. Many patients with HEVs were recovered with sequelae (46.2%), and HEVs has contributed for one out of the nine meningeal deaths (11.1%). CONCLUSIONS: HEVs were found to be the commonest cause of morbidity and mortality in all age groups. Many of the patients were mistreated with antibiotics and hospitalized. The detection of HEVs in 26.7% of clinically suspected meningitis cases indicated the need for molecular tests in investigating the etiology of meningitis. Therefore, we suggest the introduction of molecular tests as a routine practice in referral hospitals and the need to further characterize circulating HEVs strains.

La Crosse Virus Disease in the United States, 2003-2019.

La Crosse virus (LACV) is an arthropod-borne virus that can cause a nonspecific febrile illness, meningitis, or encephalitis. We reviewed U.S. LACV surveillance data for 2003-2019, including human disease cases and nonhuman infections. Overall, 318 counties in 27 states, principally in the Great Lakes, mid-Atlantic, and southeastern regions, reported LACV activity. A total of 1,281 human LACV disease cases were reported, including 1,183 (92%) neuroinvasive disease cases. The median age of cases was 8 years (range: 1 month-95 years); 1,130 (88%) were aged < 18 years, and 754 (59%) were male. The most common clinical syndromes were encephalitis (N = 960; 75%) and meningitis (N = 219, 17%). The case fatality rate was 1% (N = 15). A median of 74 cases (range: 35-130) was reported per year. The average annual national incidence of neuroinvasive disease cases was 0.02 per 100,000 persons. West Virginia, North Carolina, Tennessee, and Ohio had the highest average annual state incidences (0.16-0.61 per 100,000), accounting for 80% (N = 1,030) of cases. No animal LACV infections were reported. Nine states reported LACV-positive mosquito pools, including three states with no reported human disease cases. La Crosse virus is the most common cause of pediatric neuroinvasive arboviral disease in the United States. However, surveillance data likely underestimate LACV disease incidence. Healthcare providers should consider LACV disease in patients, especially children, with febrile illness, meningitis, or encephalitis in areas where the virus circulates and advise their patients on ways to prevent mosquito bites.

Enterovirus Meningitis in Adults: A Prospective Nationwide Population-Based Cohort Study.

OBJECTIVE: To test the hypothesis that enterovirus meningitis (EM) is a frequent and self-limiting condition, the epidemiology of EM in adults was examined. METHODS: Using a prospective, nationwide, population-based database, all adults with EM confirmed by PCR of the CSF from 2015 to 2019 were included. Unfavorable outcome was defined as Glasgow Outcome Scale scores of 1-4 at discharge. Modified Poisson regression was used to compute adjusted relative risks (RRs). RESULTS: A total of 419 cases of EM in 418 adults (46% female, median age 31 years [interquartile range (IQR) 27-35]) yielded an incidence of 1.80/100,000/year. Admission diagnoses included CNS infection 247/397 (62%), other neurologic conditions 89/397 (22%), and cerebrovascular diseases 33/397 (8%). Genotype was available for 271 cases, of which echovirus 30 accounted for 155 (57%). Patients presented with headache 412/415 (99%), history of fever 303/372 (81%), photophobia 292/379 (77%), and neck stiffness 159/407 (39%). Fever (≥38.0°C) was observed in 192/399 (48%) at admission. The median CSF leukocyte count was 130 106/L (range 0-2,100) with polymorphonuclear predominance (>50%) in 110/396 (28%). Cranial imaging preceded lumbar puncture in 127/417 (30%) and was associated with non-CNS infection admission diagnoses and delayed lumbar puncture (median 4.8 hours [IQR 3.4-7.9] vs 1.5 [IQR 0.8-2.8], p < 0.001). Unfavorable outcome occurred in 99/419 (24%) at discharge; more often in female patients (RR 2.30 [1.58-3.33]) and less frequent in echovirus 30 (RR 0.67 [0.46-1.00]) in adjusted analyses. Outcome remained unfavorable in 22/379 (6%) after 6 months. CONCLUSIONS: EM is common among young, healthy adults. Although the long-term prognosis remains reassuring, a substantial proportion have moderate disability at discharge, especially female patients.

The impact of viral infections on childhood central nervous system infections.

BACKGROUND: Viruses are a common cause of central nervous system (CNS) infections. However, studies of CNS viral pathogens in pediatric patients are poorly explored because viral infections are often erroneously diagnosed as bacterial infections. METHODS: 299 CNS samples were collected from pediatric patients aged from one month to 14 years old. A total of 140 viral meningitis cases that met the inclusion criteria were included in this study. In 38 of the 140 cerebral spinal fluid (CSF) samples (27.1%), conventional and real-time PCR were used to identify viruses commonly associated with CNS infections. RESULTS: Among them, 23 patients (16.5%) tested positive for flaviviruses such as dengue, Zika, and yellow fever virus, eight patients (5.7%) were positive for enterovirus (ENTV), and six patients (4.3%) were positive for human herpesvirus 1/2. We also identified one case of dengue virus and ENTV co-infection. CONCLUSIONS: A correlation between clinical symptoms and laboratory findings for the viruses was identified. Our study also reinforces the importance of including viruses in the laboratory diagnosis of CNS infections especially flaviviruses, which assists public health authorities in implementing early interventions.

Analysis of enterovirus genotypes in the cerebrospinal fluid of children associated with aseptic meningitis in Liaocheng, China, from 2018 to 2019.

BACKGROUND: Aseptic meningitis is most often caused by enteroviruses (EVs), but EVs associated with aseptic meningitis have not yet been reported in Liaocheng. The aim of this study was to determine the prevalence and genetic characteristics of EVs causing aseptic meningitis in children in Liaocheng. METHODS: We reviewed the epidemiological and clinical characteristics of 504 paediatric cases of aseptic meningitis in Liaocheng from 2018 to 2019 and analysed the phylogeny of the predominant EV types causing this disease. RESULTS: A total of 107 children were positive for EV in cerebrospinal fluid samples by nested PCR. Most of the positive patients were children 13 years old or younger and had symptoms such as fever, headache and vomiting (P < 0.05). The seasons with the highest prevalence of EV-positive cases were summer and autumn. The 107 EV sequences belonged to 8 serotypes, and echovirus types 18, 6 and 11 were the three dominant serotypes in Liaocheng during the 2-year study period. Phylogenetic analyses demonstrated that the E18 and E6 isolates belonged to subgenotype C2, while the E11 isolates belonged to subgenotype D5. VP1 analysis suggested that only one lineage of these three types was cocirculating in the Liaocheng region. CONCLUSIONS: This study demonstrated the diverse EV genotypes contributing to a large outbreak of aseptic meningitis in Liaocheng. Therefore, large-scale surveillance is required to assess the epidemiology of EVs associated with aseptic meningitis and is important for the diagnosis and treatment of aseptic meningitis in Liaocheng.