Picornaviruses in cerebrospinal fluid of children with meningitis in Luanda, Angola

Human enteroviruses are the most common cause of viral meningitis. Viral-bacterial interaction may affect the clinical course and outcome of bacterial meningitis. In Africa, viruses might be responsible for 14-25% of all meningitis cases. However, only few studies from Africa have reported detection of viruses in the cerebrospinal fluid (CSF) or mixed viral-bacterial infections of the central nervous system (CNS). The aim of the present study was to investigate the presence of picornaviruses in the CSF of children suffering from meningitis in Luanda, Angola. The study included 142 consecutive children enrolled in a prospective study of bacterial meningitis in Luanda between 2005 and 2006, from whom a CSF sample was available. CSF samples were obtained at hospital admission, stored in a deep-freeze, and transported to Finland for testing by real-time PCR for picornaviruses. Enteroviruses were detected in 4 (3%) of 142 children with presumed bacterial meningitis. A 5-month-old girl with rhinovirus and Haemophilus influenzae meningitis recovered uneventfully. An 8-year-old girl with human enterovirus and pneumococcal meningitis developed no sequelae. A 2-month-old girl with human enterovirus and malaria recovered quickly. A 7-month-old girl with human enterovirus was treated for presumed tuberculous meningitis and survived with severe sequelae. Mixed infections of the CNS with picornaviruses and bacteria are rare. Detection of an enterovirus does not affect the clinical picture and outcome of bacterial meningitis.     

Screening for enteroviral meningitis in infants and children—Is it useful in clinical practice?

Enteroviral meningitis in infants and children commonly leads to hospital admission. Diagnosing viral meningitis can be difficult clinically. We examined the usefulness of enteroviral polymerase chain reaction (PCR) testing using cerebrospinal fluid (CSF) samples on clinical practice by comparing positive enteroviral CSF PCR cases (n = 39/136) to negative controls using both clinical outcomes and laboratory parameters. A positive result correlated with a reduced admission to high dependency unit, reduced the duration of antibiotics and a shorter length of stay (P < .05). Adjusted CSF white cell count > 5/μL correlated with positive PCR (P < .05) but would have missed 32% of cases of enteroviral meningitis. Following these findings, an algorithm for the management of suspected viral meningitis has been introduced.     

Incidence and outcome of pneumococcal meningitis in northern England

Since pneumococcal meningitis continues to have high mortality and morbidity, and may be under-reported to national surveillance systems, the present study was conducted to assess the incidence, features, and outcomes of microbiologically confirmed cases of pneumococcal meningitis in North Yorkshire, England, between 1997 and 2002. The review revealed 50 cases, which accounted for an incidence of 1.1. per 100,000 per year. The incidence was markedly seasonal, with 76% of cases occurring in the winter months. Mortality was 28%, and 28% of the survivors suffered long-term sequelae. A high Glasgow Coma Score on hospital admission was significantly associated with survival. There were 12 children in the study, aged 2 months to 2 years, and none of them would have been classified as candidates for conjugate pneumococcal vaccination according to UK recommendations.     

Role of the virology laboratory in diagnosis and management of patients with central nervous system disease.

A number of viruses cause acute central nervous system disease. The two major clinical presentations are aseptic meningitis and the less common meningoencephalitis. Clinical virology laboratories are now more widely available than a decade ago; they can be operated on a modest scale and can be tailored to the needs of the patients they serve. Most laboratories can provide diagnostic information on diseases caused by enteroviruses, herpesviruses, and human immunodeficiency virus. Antiviral therapy for herpes simplex virus is now available. By providing a rapid diagnostic test or isolation of the virus or both, the virology laboratory plays a direct role in guiding antiviral therapy for patients with herpes simplex encephalitis. Although there is no specific drug available for enteroviruses, attention needs to be paid to these viruses since they are the most common cause of nonbacterial meningitis and the most common pathogens causing hospitalization for suspected sepsis in young infants in the United States during the warm months of the year. When the virology laboratory maximizes the speed of viral detection or isolation, it can make a significant impact on management of these patients. Early viral diagnosis benefits patients with enteroviral meningitis, most of whom are hospitalized and treated for bacterial sepsis or meningitis or both; these patients have the advantage of early withdrawal of antibiotics and intravenous therapy, early hospital discharge, and avoidance of the risks and costs of unnecessary tests and treatment. Enteroviral infection in young infants also is a risk factor for possible long-term sequelae. For compromised patients, the diagnostic information helps in selecting specific immunoglobulin therapy. Good communication between the physician and the laboratory will result in the most benefit to patients with central nervous system viral infection.     

Impact of rapid enterovirus molecular diagnosis on the management of infants,children, and adults with aseptic meningitis

Enteroviruses (EV) are the main etiological agents of aseptic meningitis. Diagnosis is made by detecting the genome using RT‐PCR. The aim of the study was to evaluate the impact of a positive diagnosis on the management of infants, children, and adults. During 2005, 442 patients were admitted to hospital with suspected meningitis. Clinical and laboratory data and initial treatment were recorded for all patients with enteroviral meningitis. The turnaround time of tests and the length of hospital stay were analyzed. The results showed that EV‐PCR detected EV in 69 patients (16%), 23% (16/69) were adults. About 18% of CSF samples had no pleocytosis. After positive PCR results, 63% of children were discharged immediately (mean 2 hr 30 min) and 95% within 24 hr. Infants and adults were discharged later (after 1.8 and 2 days, respectively). The use of antibiotics was significantly lower in children than in infants and adults. The PCR results allowed discontinuation of antibiotics in 50–60% of all patients treated. Patients received acyclovir in 16% of cases (7% children vs. 50% adults) and 23% (11% vs. 69%) underwent a CT scan. Clinical data were compared between patients whose positive EV‐PCR results were available within 24 hr (n = 32) and those whose results were available > 24 hr after collection of CSF (n = 14). Duration of antibiotic treatment (difference: 2.3 days; P = 0.05) was reduced between the two groups. No statistical difference in the length of stay was observed. The EV‐PCR assay should be performed daily in hospital laboratory practice and considered as part of the initial management of meningitis. J. Med. Virol. 81:42–48, 2009. © 2008 Wiley‐Liss, Inc.     

Longitudinal observation of parechovirus in stool samples from Norwegian infants

Parechoviruses are assumed to be common infectious agents, but their epidemiologic and pathogenic properties are not well known. The aim of the present study was to assess the prevalence and molecular epidemiology of Parechovirus in Norwegian infants, as well as to investigate whether the presence of virus correlated with symptoms of infection. A group of 102 infants was longitudinally followed: 51 infants with a high genetic risk for type 1 diabetes (aged 3-35 months), and 51 children without this genotype (aged 3-12). Stool samples were obtained each month, and symptoms of infection were recorded regularly on questionnaires. Human parechovirus was detected in 11.3% of 1,941 samples examined by real-time RT-PCR. There was a distinct seasonality, peaking from September to December. By 12 months of age, 43% of the infants had had at least one infection, while 86% of the infants had encountered the virus by the end of the second year. Based on the VP1 sequence, human parechovirus 1 was the most prevalent type (76%), followed by human parechovirus 3 (13%), human parechovirus 6 (9%), an unclassified human parechovirus (1%), and human parechovirus 2 (1%). Ljungan virus, a murine parechovirus, was examined with a separate real-time RT-PCR, but no virus was detected. There was no significant association between infections and the following symptoms: coughing, sneezing, fever, diarrhea or vomiting. In conclusion, human parechovirus infects frequently infants at an early age without causing disease.     

Genetic characterization of enterovirus 71 isolated from patients with severe disease by comparative analysis of complete genomes

Enterovirus 71 (EV71) which causes mild illness in children is also associated with severe neurological complications. This study analyzed the complete genomes of EV71 strains derived from mild and severe diseases in order to determine whether the differences of EV71 genomes were responsible for different clinical presentations. Compared to complete genomes of EV71 strains derived from mild cases (less virulent strains), nucleotide differences in EV71 strains isolated from severe cases (more virulent strains) were observed primarily in the internal ribosomal entry site (IRES) of the 5'-untranslated region (UTR), which is vital for the cap-independent translation of viral proteins. In the protein-coding region, an E-Q substitution at amino acid position 145 of structural protein VP1 that occurred in more than one of more virulent strains was observed. This site is known to be related functionally to receptor binding and virulence in mice. Overall, strains (Group III) isolated from patients with fatal or severe sequelae outcomes had greater sequence substitutions in the 5'-UTR and/or protein-coding region and exhibited a relatively low-average homology to less virulent strains across the entire genome, indicating the possibility of significant genomic diversity in the most virulent EV71 strains. Further studies of EV71 pathogenesis should examine the significance of genomic diversity and the effects of multiple mutations in a viral population.     

Presentation and outcome of tuberculous meningitis among children: experiences from a tertiary children's hospital

Background

Diagnosis of tuberculous meningitis (TBM) is complicated and outcome is poor especially in resource limited settings. Early diagnosis and prompt treatment are vital in effective treatment. We set out to describe experiences in the management and immediate outcome of TBM a tertiary-level children''s hospital in a high HIV and tuberculosis co-infection setting.

Methods

This retrospective study included children who were diagnosed with TBM in the year 2009. A pre-coded questionnaire was used to extract data on presentation, diagnostics, treatment and outcome at the time of hospital discharge. Data was analyzed using STATA statistical package (StataCorp, Version 11).

Results

Of the 40 children diagnosed with TBM, 6 (15%) had definitive TBM, 17 (42.5%) had probable TBM and 17 (42.5%) had possible TBM. The cerebrospinal fluid (CSF) chemistry and cells were abnormal in 39/40 (98%). Mantoux test was reactive in 16/29 (55%) and 17/30 (57%) had Chest X-rays suggestive of tuberculosis. Only 3/21 (14%) had positive sputum tuberculosis culture and 89% (32/36) had neuro-imaging abnormalities. Outcome at discharge was; 8% died, 49% improved with neurological sequelae and 43% improved without sequelae. Having TBM stage 3 at admission was associated with mortality (p=0.001).

Conclusions

Most children had early diagnosis of TBM and mortality was lower than in previous studies. We recommend a larger prospective study to further understand the outcome of TBM.     

Longitudinal outcomes of Haemophilus influenzae meningitis in school-age children

The purpose of this study was to investigate long-term outcomes of Haemophilus influenzae Type b meningitis in a cohort of school-age survivors. Findings from an initial assessment at mean age 10 years revealed neuropsychological, achievement, and behavioral sequelae in the children with neurologic complications during the acute-phase illness (H. Taylor, C. Schatschneider, & D. Rich, 1992). Here, the cohort was reassessed 1 and 2 years after the initial evaluation to investigate age-related influences on disease sequelae. After excluding children with hearing loss, the sample was divided into 2 groups: an affected group of 39 children with acute-phase neurologic complications and an unaffected group of 73 children without these complications. Growth-curve modeling showed poorer outcomes at the final assessment and less rapid improvement at follow-up for the affected group. Later age at assessment and later age at illness were associated with larger group differences in some outcomes. Results suggest that children with diffuse early brain insults are at risk for later-emerging sequelae.     

Seizures and other neurologic sequelae of bacterial meningitis in children

BACKGROUND. Although the mortality rate among children with bacterial meningitis has decreased dramatically in recent decades, some patients are left with neurologic sequelae. It has not been clearly established which features of the acute illness predict the chronic neurologic sequelae, including late seizures or epilepsy. METHODS. We followed 185 infants and children prospectively during and after acute bacterial meningitis. The mean duration of follow-up was 8.9 years (range, 0.1 to 15.5). During the first six years standard neurologic examinations were performed; telephone interviews were conducted thereafter. RESULTS. One month after meningitis, 69 children (37 percent) had neurologic abnormalities. Many of these signs resolved within a year, leaving only 26 children (14 percent) with persistent deficits: 18 (10 percent) had only sensorineural hearing loss, and 8 (4 percent) had multiple neurologic deficits. Thirteen children (7 percent) had one or more late seizures not associated with fever. The presence of persistent neurologic deficits indicative of cerebral injury was the only independent predictor of late afebrile seizures (P less than 0.001). CONCLUSIONS. After bacterial meningitis only children with permanent neurologic deficits are at high risk for epilepsy. Those with normal examinations after the acute illness have an excellent change of escaping serious neurologic sequelae, including epilepsy.     

Lymphocytic meningitis: incidence, causes and outcomes over five years

Over a five-year period 114 cases of lymphocytic meningitis were admitted to a general hospital. Case notes were reviewed to determine incidence, causes and outcomes and to identify what clinical features, cerebrospinal fluid (CSF) parameters or other tests were useful in elucidating a cause. Of 114 patients with lymphocytic meningitis 44 had viral meningitis, six viral encephalitis, and seven had other infective meningo-encephalitis. Seven patients had carcinomatous meningitis, nine had an autoimmune/inflammatory process, thirteen had a demyelinating central nervous system (CNS) disorder, and two had an inflammatory neuropathy. In 26 patients no diagnosis was reached. Six of these showed clear steroid responsiveness. Overall lymphocytic meningitis had a good prognosis. Clinical and CSF characteristics were important in diagnosis and prognosis. Recommendations on management of these cases are presented.     

Role of viral-bacterial associations in meningitis in children]

A total of 50 section cases of meningitis in children were investigated. All patients revealed acute viral respiratory infections with generalization, including lesions of the central nervous system (CNS). In 14 children moreover meningococcal infection was diagnosed. In 30 children lesions of the CNS were due to mixed bacterial microflora. In 6 children along with acute viral respiratory infections (AVRI) mycoplasmosis was also revealed. Etiology of the process was determined on the basis of characteristic structural changes in the CNS and other organs, findings of virological and bacteriological investigations. In the majority of children the intravascular blood coagulation was observed. Waterhouse-Friderichsen's syndrome was revealed mainly in meningococcal infection. In order to ascertain the data obtained case records of 120 children, who had undergone treatment in connection with meningococcal infection, were analysed. It turned out that all 42 children, who had developed this disease independently, recovered. Combination of the disease with AVRI led to fatal outcomes in 12 cases out of 72.     

Sensitive, stimulating caregiving predicts cognitive and behavioral resilience in neurodevelopmentally at-risk infants

Although neurodevelopmental impairment is a risk factor for poor cognitive and behavioral outcomes, associations between early and later functioning are only moderate in magnitude, and it is likely that other factors intervene to modify this trajectory. The current study tested the hypothesis that sensitive, stimulating caregiving would promote positive behavioral and cognitive outcomes among children who were at risk based on the results of a neurodevelopmental screener and a temperament inventory. The sample comprised 1,720 infants and toddlers from the National Survey of Child and Adolescent Well-Being, a longitudinal study of children who were involved with child welfare services. Children were first assessed between 3 and 24 months of age and subsequently 18 months later. Children who experienced improvements in the amount of sensitive, stimulating caregiving they received had positive cognitive and behavioral outcomes 18 months later, despite early levels of neurodevelopmental risk. The association between changes in caregiving quality and changes in children's functioning was stronger for children who were removed from the care of their biological parents before the follow-up assessment than for children who remained in the care of biological parents, suggesting a causal role for caregiving quality on children's outcomes.     

Neurodevelopmental Outcomes in Infants and Children With Single-Suture Craniosynostosis: A Systematic Review

Children with single-suture craniosynostosis (SSC) are increasingly considered to be at high risk of adverse neurodevelopmental outcomes. This systematic review aimed to synthesise and critically appraise the existing literature on the neurodevelopmental features of SSC, with particular attention to methodological quality. A total of 33 articles based on 27 cohorts met inclusion criteria. In the context of variable methodological design and quality, most neurodevelopmental studies indicated that children with SSC are at increased risk for difficulties in cognitive, language, and motor domains during infancy (both pre- and post-surgery) and childhood. Limited information exists on factors influencing outcome.     

Serial Long-Term Growth and Neurodevelopment of Very-Low-Birth-Weight Infants: 2022 Update on the Korean Neonatal Network

BackgroundWe aimed to evaluate the long-term growth and neurodevelopmental outcomes of very-low-birth-weight infants (VLBWIs, birth weight < 1,500 g) born between 2013, the establishment of the Korean Neonatal Network (KNN), and 2018, both at 18–24 months of corrected age and three years of age, using a nationwide large cohort, and to evaluate whether these outcomes have improved over time since 2013.MethodsThis study used data from the annual reports of the KNN for 18–24 months of corrected age (follow-up 1) and three years of age (follow-up 2). Follow-up 1 data were collected from 10,065 eligible VLBWIs born between January 1, 2013, and December 31, 2018. Follow-up 2 data were collected from 8,156 eligible VLBWIs born between January 1, 2013, and December 31, 2017.ResultsThe overall follow-up rates of VLBWIs at follow-ups 1 and 2 were 74.6% (7,512/10,065) and 57.7% (4,702/8,156), respectively. The overall mortality rate between discharge from the neonatal intensive care unit and follow-up 1 was 1% (104/10,065). The overall mortality rate between follow-ups 1 and 2 was 0.049% (4/8,156). Growth restrictions decreased over time, especially weight growth restrictions, which significantly decreased according to era (17% in infants born in 2013–2014 and 13% in infants born in 2017–2018). Fewer infants were re-hospitalized and required rehabilitative support according to era at follow-up 1. More infants had language developmental delays and required language support according to era, both at follow-ups 1 and 2. The incidence of cerebral palsy has significantly decreased over time, from 6% in infants born in 2013–2014 to 4% in infants born in 2017–2018 at follow-up 1, and from 8% in infants born in 2013–2014 to 5% in infants born in 2017 at follow-up 2.ConclusionLong-term outcomes of VLBWIs regarding weight growth and cerebral palsy, the most common motor disability in childhood, have improved serially according to era since 2013. However, the rate of infants with language delays requiring language support has increased according to era. Further studies are required on the increased trends of language delay and language support while improving motor outcomes.     

Patterns of developmental and behavioral progress for young brain‐injured children during interdisciplinary intervention

Pediatric hospital rehabilitation teams and community‐based early intervention programs confront the increasing demand to treat infants and preschoolers suffering both acquired and congenital brain injuries. However, few outcome studies are available to provide clear and practical guidance to their efforts. Specialists require more complete knowledge of the problems and the possibilities for these young handicapped children. Needed research can establish norms for progress and recovery, which can be used to evaluate individual gains, to provide prognoses, and to monitor interdisciplinary treatment impact. Our preliminary research traced comparative patterns of developmental and behavioral progress during intervention for infants and preschoolers suffering acquired and congenital brain injuries. In addition, this study documented treatment impact for both brain injury groups. Results demonstrated the existence of very similar overall progress and recovery patterns within both groups. An intensive interdisiplinary treatment approach proved to be responsible for facilitating developmental and behavioral gains beyond levels expected due to maturation. Practical implications of these results for early intervention teams are detailed.     

New estimates of the prevalence of neurological and sensory sequelae and mortality associated with congenital cytomegalovirus infection

Congenital CMV is a major cause of neurological and sensory impairment in children. Reliable estimates of the prevalence of permanent sequelae and mortality associated with congenital CMV are needed to guide development of education and prevention programmes and to gauge the financial costs associated with this disease. To calculate such estimates, this review used data solely from studies in which children with congenital CMV were identified through universal screening. Based on 15 studies with a total of 117 986 infants screened, the overall CMV birth prevalence estimate was 0.7%. The percentage of infected children with CMV-specific symptoms at birth was 12.7%. The percentage of symptomatic children with permanent sequelae was 40-58%. The percentage of children without symptoms at birth who developed permanent sequelae was estimated to be 13.5%. The true burden of congenital CMV infection is unclear because data on important outcomes, such as visual impairment, are lacking and follow-up of infected children has been too short to fully identify late-onset sequelae. Therefore, the estimates of permanent sequelae associated with congenital CMV presented here are likely underestimates. Future studies should extend follow-up of CMV-infected children identified through universal screening and include the evaluation of visual impairment.     

Tuberculous meningo-encephalitis in pediatrics. Considerations on 71 cases (1968-1993)

The tuberculous meningitis is an uncommon but severe complication of the tuberculosis mainly in childhood. Neurological sequelae are frequent and high mortality rate, till now, occurs. We reviewed the medical records of 71 cases and we evaluated the most frequent symptoms before the admission and signs and symptoms on the admission according to prognosis. An early diagnosis and specific anti-tuberculous treatment are essential in order to prevent permanent neurological sequelae and fatal outcome     

Trends in viral meningitis hospitalisations and notifications in the North Eastern Health Board (1997 - 2001): a cause for concern?

This study aimed to compare trends in both hospital admissions and notifications of viral meningitis in the North Eastern Health Board (NEHB). Hospital admissions from 1997 to 2001, involving NEHB residents with an infectious disease diagnosis, were examined and viral meningitis cases were analyzed. During this period 265 NEHB residents were admitted to hospital with viral meningitis--an increase of 429% between 1997 and 2001 with the bulk of this increase during 2000 and 2001. A total of 1,234 bed days were taken up by this cohort and the mean length of stay was 4.5 days (95% CI 4.2 - 4.9). The number of viral meningitis notifications in the NEHB was 38 (ranging from 4 in 1997 to 11 in 2001). This number is much lower than expected given the corresponding number of hospital admissions for the same period. Thus, most cases were not notified which means that current surveillance systems under-estimate the disease burden of viral meningitis. Such under-reporting has implications for infectious disease policy in Ireland.