Laboratory diagnosis of CNS infections in children due to emerging and re-emerging neurotropic viruses.

Recent decades have witnessed the emergence and re-emergence of numerous medically important viruses that cause central nervous system (CNS) infections in children, e.g., Zika, West Nile, and enterovirus/parechovirus. Children with immature immune defenses and blood-brain barrier are more vulnerable to viral CNS infections and meningitis than adults. Viral invasion into the CNS causes meningitis, encephalitis, brain imaging abnormalities, and long-term neurodevelopmental sequelae. Rapid and accurate detection of neurotropic viral infections is essential for diagnosing CNS diseases and setting up an appropriate patient management plan. The addition of new molecular assays and next-generation sequencing has broadened diagnostic capabilities for identifying infectious meningitis/encephalitis. However, the expansion of test menu has led to new challenges in selecting appropriate tests and making accurate interpretation of test results. There are unmet gaps in development of rapid, sensitive and specific molecular assays for a growing list of emerging and re-emerging neurotropic viruses. Herein we will discuss the advances and challenges in the laboratory diagnosis of viral CNS infections in children. This review not only sheds light on selection and interpretation of a suitable diagnostic test for emerging/re-emerging neurotropic viruses, but also calls for more research on development and clinical utility study of novel molecular assays. IMPACT: Children with immature immune defenses and blood-brain barrier, especially neonates and infants, are more vulnerable to viral central nervous system infections and meningitis than adults. The addition of new molecular assays and next-generation sequencing has broadened diagnostic capabilities for identifying infectious meningitis and encephalitis. There are unmet gaps in the development of rapid, sensitive and specific molecular assays for a growing list of emerging and re-emerging neurotropic viruses.

Common seasonal respiratory viral infections in children before and during the coronavirus disease 2019 (COVID-19) pandemic.

OBJECTIVES: To describe the incidence of seasonal respiratory viral infections (s-RVIs) before and during the coronavirus disease 2019 (COVID-19) pandemic and to compare virus-specific patient outcomes in pediatric patients. DESIGN: A retrospective cross-sectional study including patient admissions to the Children's National Hospital between October 1, 2015, and December 31, 2020. RESULTS: Among 12,451 patient admissions between March 15 and December 31, 2020 (cohort 1), 8,162 (66%) were tested for severe acute respiratory coronavirus virus 2 (SARS-CoV-2), and 249 (2.0%) were positive. Among 10,986 patient admissions between April 1 and December 31, 2020 (cohort 2), 844 (8%) were tested for s-RV upon admission and 160 were positive. Thus, 1.5% of patient admissions were associated with laboratory-confirmed s-RVIs. Among the 49,901 patient admissions during a viral season between October 1, 2015, and March 31, 2020 (cohort 3), 7,539 (15%) were tested for s-RV upon admission and 4,531 were positive; thus, 9.0% of patient admissions were associated with laboratory-confirmed s-RVIs. hHRV/rENT was the most detected virus, but the detection rate decreased substantially (31% vs 18%; P < .001) during the COVID-19 pandemic. No patients had RSV, influenza, hMPV, hPIV, or hCoV detected upon admission after April 21, 2020. The 3 patient cohorts had no statistically significant difference in the percentage of ICU admissions (10.8% vs 15.0% vs 14.2%; P > .05) or death at discharge (0.8% vs 0.6% vs 0.5%; P > .05). CONCLUSIONS: Compared to COVID-19, s-RVI cases were associated with a higher proportion of inpatient admissions but were similar in ICU admission and death rates in hospitalized pediatric patients. Public health interventions for preventing COVID-19 were highly effective in preventing pediatrics s-RVIs.

Comparison of Clinical Features of COVID-19 vs Seasonal Influenza A and B in US Children.

Importance: Compared with seasonal influenza, the clinical features and epidemiologic characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus 2019 (COVID-19) in US children remain largely unknown. Objective: To describe the similarities and differences in clinical features between COVID-19 and seasonal influenza in US children. Design, Setting, and Participants: This retrospective cohort study included children who were diagnosed with laboratory-confirmed COVID-19 between March 25 and May 15, 2020, and children diagnosed with seasonal influenza between October 1, 2019, and June 6, 2020, at Children's National Hospital in the District of Columbia. Exposures: COVID-19 or influenza A or B. Main Outcomes and Measures: Rates of hospitalization, admission to the intensive care unit, and mechanical ventilator use and the association between underlying medical conditions, clinical symptoms, and COVID-19 vs seasonal influenza. Results: The study included 315 patients diagnosed with COVID-19 (164 [52%] male; median age, 8.3 years [range, 0.03-35.6 years]) and 1402 patients diagnosed with seasonal influenza (743 [53%] male; median age, 3.9 years [range, 0.04-40.4 years]). Patients with COVID-19 and those with seasonal influenza had a similar hospitalization rate (54 [17%] vs 291 [21%], P = .15), intensive care unit admission rate (18 [6%] vs 98 [7%], P = .42), and use of mechanical ventilators (10 [3%] vs 27 [2%], P = .17). More patients hospitalized with COVID-19 than with seasonal influenza reported fever (41 [76%] vs 159 [55%], P = .005), diarrhea or vomiting (14 [26%] vs 36 [12%], P = .01), headache (6 [11%] vs 9 [3%], P = .01), body ache or myalgia (12 [22%] vs 20 [7%], P = .001), and chest pain (6 [11%] vs 9 [3%], P = .01). Differences between patients hospitalized with COVID-19 vs influenza who reported cough (24 [48%] vs 90 [31%], P = .05) and shortness of breath (16 [30%] vs 59 [20%], P = .13) were not statistically significant. Conclusions and Relevance: In this cohort study of US children with COVID-19 or seasonal influenza, there was no difference in hospitalization rates, intensive care unit admission rates, and mechanical ventilator use between the 2 groups. More patients hospitalized with COVID-19 than with seasonal influenza reported clinical symptoms at the time of diagnosis.

Comparison of pandemic and seasonal influenza A infections in pediatric patients: were they different?

This retrospective cohort study revealed that the presence of pandemic H1N1 influenza resulted in a 77.7% increase of patient visits in the emergency department for influenza like illnesses and a 67.2% increase of hospital days in our hospital by comparing to a regular influenza season (2008-2009 season). However, median length of hospital stay was no different in either period (pandemic: 3 days versus seasonal: 4 days, P = 0.06). Except for the patients hospitalized for pandemic H1N1 influenza (n = 111) were older (median age: 4.7 years versus 1.6 years, P = 0.04) and tended to have pre-existing asthma (21.6% versus 9.0%, P = 0.07) than those hospitalized for seasonal influenza A infections (n = 44), this study found no significant difference between the two comparison groups with regards of other clinical and epidemiological features.

A local, regional, and national assessment of pediatric malaria in the United States.

BACKGROUND: Imported malaria remains a public health concern in the United States, but the health impact on children and the financial costs to society have not been well defined. METHODS: Inpatient and outpatient malaria cases diagnosed at Children's National Medical Center (CNMC) in Washington, DC over an 8-year period are retrospectively reviewed. Cases are mapped against Census Bureau population data. These observations are compared with the national burden of pediatric malaria, including both disease severity and cost, by reviewing inpatient malaria cases in the Pediatric Health Information System (PHIS), January 2003 to June 2008. RESULTS: At CNMC, malaria most commonly affects children who traveled to West Africa to visit friends and relatives. Poor adherence to prophylaxis and self-treatment with antimalarial medications were commonly identified. Mapping demonstrates case clustering in communities with large sub-Saharan African populations. The cumulative incidence (CI) of malaria at CNMC of 9.0 per 10,000 admissions is 7.6 times the national average. The CI of malaria at PHIS hospitals is 1.2 per 10,000 admissions with an average cost of $17,519. CONCLUSIONS: Malaria is a preventable disease for which the risk to life and costs of treatment are significant. Patterns of risk can be used by health planners to target prevention strategies at the community level. In regions with a high density of immigrants, particularly from sub-Saharan Africa, physicians must be aware of the risk, understand recommended prophylaxis and treatment regimens, and advocate for their appropriate use in the community.

Human parechovirus-3 infection: emerging pathogen in neonatal sepsis.

Human parechovirus-3 (HPeV-3) is an emerging pathogen that has been described as a cause of neonatal sepsis. Human parechoviruses are a family of viruses closely related to enteroviruses; however, enteroviral PCR will not detect HPeVs. We present clinical details of neonatal meningoencephalitis and hepatitis-coagulopathy syndrome caused by HPeV-3 infection.

Teaching pediatric laboratory medicine to pathology residents.

CONTEXT: Laboratory data are essential to the medical care of fetuses, infants, children, and adolescents. However, the performance and interpretation of laboratory tests on specimens from these patients, which may constitute a significant component of the workload in general hospitals and integrated health care systems as well as specialized perinatal or pediatric centers, present unique challenges to the clinical pathologist and the laboratory. Therefore, pathology residents should receive training in pediatric laboratory medicine. OBJECTIVE: Children's Health Improvement through Laboratory Diagnostics, a group of pathologists and laboratory scientists with interest and expertise in pediatric laboratory medicine, convened a task force to develop a list of curriculum topics, key resources, and training experiences in pediatric laboratory medicine for trainees in anatomic and clinical pathology or straight clinical pathology residency programs and in pediatric pathology fellowship programs. DATA SOURCES: Based on the experiences of 11 training programs, we have compiled a comprehensive list of pediatric topics in the areas of clinical chemistry, endocrinology, hematology, urinalysis, coagulation medicine, transfusion medicine, immunology, microbiology and virology, biochemical genetics, cytogenetics and molecular diagnostics, point of care testing, and laboratory management. This report also includes recommendations for training experiences and a list of key texts and other resources in pediatric laboratory medicine. CONCLUSIONS: Clinical pathologists should be trained to meet the laboratory medicine needs of pediatric patients and to assist the clinicians caring for these patients with the selection and interpretation of laboratory studies. This review helps program directors tailor their curricula to more effectively provide this training.

Characterizing vancomycin-resistant enterococci in neonatal intensive care.

Repetitive sequence-based polymerase chain reaction fingerprinting was used to characterize 23 vancomycin-nonsusceptible enterococcal isolates from 2003 to 2004. Five genetically related clusters spanned geographically distinct referring centers. DNA fingerprinting showed infant-to-infant transmission from referring institutions. Thus, community healthcare facilities are a source of vancomycin-nonsusceptible enterococci and should be targeted for increased infection control efforts.

Control of vancomycin-resistant enterococci in the neonatal intensive care unit.

BACKGROUND AND OBJECTIVE: Multidrug-resistant organisms (MDROs), such as vancomycin-resistant enterococci (VRE), cause serious infections, especially among high-risk patients in NICUs. When VRE was introduced and transmitted in our NICU despite recommended infection control practices, we instituted active surveillance cultures to determine their efficacy in detecting and controlling spread of VRE among high-risk infants. METHODS: Active surveillance cultures, other infection control measures, and a mandatory in-service education module on preventing MDRO transmission were implemented. Cultures were performed on NICU admission and then weekly during their stay. Molecular DNA fingerprinting of VRE isolates facilitated targeting efforts to eliminate clonal spread of VRE. Repetitive sequence PCR (rep-PCR)-based DNA fingerprinting was used to compare isolates recovered from patients with VRE infection or colonization. Environmental VRE cultures were performed around VRE-colonized or -infected patients. DNA fingerprints were prepared from the products of rep-PCR amplification and analyzed using software to determine strain genetic relatedness. RESULTS: Active surveillance cultures identified 65 patients with VRE colonization or infection among 1,820 admitted to the NICU. Rep-PCR performed on 60 VRE isolates identified 3 clusters. Cluster 1 included isolates from 21 patients and 4 isolates from the environment of the index patient. Clusters 2 and 3 included isolates from 23 and 3 patients, respectively. Similarity coefficients among the members of each cluster were 95% or greater. CONCLUSIONS: Control of transmission of multi-clonal VRE strains was achieved. Active surveillance cultures, together with implementation of other infection control measures, combined with rep-PCR DNA fingerprinting were instrumental in controlling VRE transmission in our NICU.

Cluster of Trichosporon mucoides in children associated with a faulty bronchoscope.

BACKGROUND: Several outbreaks of Pseudomonas aeruginosa infection associated with a specific model of fiberoptic bronchoscope have been reported. In a 3-week period in September 2000, we noticed an increased number of Trichosporon mucoides isolates recovered from bronchoalveolar lavage (BAL) specimens collected at our hospital. We investigated the circumstances surrounding these isolates. METHODS: Outbreak investigation was conducted, and the medical records of the affected patients were reviewed retrospectively for evidence of positive cultures for T. mucoides from BAL specimens. Specimens collected during the investigation were inoculated onto fungal culture medium and yeasts were identified with API-20C (BioMèrieux-Vitek). RESULTS: During the 3-week period BAL specimens from six patients yielded growth of T. mucoides. These six high risk patients had emergency bronchoscopy performed as a workup for pneumonia and/or respiratory distress. A Model BF XP-40 bronchoscope (Olympus) had been used in all six patients. Cultures of the bronchoscope (external body and the lumen), bronchoscope disinfector, 2% glutaraldehyde disinfecting solution and water filters/supply were performed. Only fluid from the bronchoscope lumen yielded growth of T. mucoides. Air sample cultures of the bronchoscopy suites were negative. Medical records review disclosed that affected patients were not readmitted with infection with T. mucoides and had no adverse outcomes. The bronchoscope was removed from service and returned to the manufacturer. CONCLUSION: Routine surveillance and aggressive investigation identified persistent T. mucoides contamination of one bronchoscope. The bronchoscope manufacturer later recalled the BF XP-40 model for corrective revision.

Risk of resistant infections with Enterobacteriaceae in hospitalized neonates.

OBJECTIVE: To determine the risk factors associated with progression from colonization to infection with health care-associated antimicrobial-nonsusceptible Enterobacteriaceae (ANE) in critically ill neonates. STUDY DESIGN: During a 3-year period (1998 to 2000), surveillance rectal cultures were performed on neonates admitted to our Level III neonatal intensive care unit after a cluster of four cases of ANE infection were identified in 1998. ANE were defined as members of the Enterobacteriaceae family that exhibited nonsusceptibility to ceftazidime or laboratory evidence of extended spectrum beta-lactamase (ESBL) production. RESULTS: A total of 1,710 patients were admitted to the neonatal intensive care unit during the study period. Of the 1,710 patients 300 (18%) were excluded from the risk factor analysis. Of the 1,410 remaining neonates the incidence of health care-associated ANE colonization was 17% (240 of 1,410 patients), and 14% of the colonized patients (34 of 240 patients) developed ANE infections. Of the 206 ANE-colonized patients who did not develop disease, 60 (29%) harbored ESBL-producing isolates. Of the 34 ANE-infected patients, 14 (41%) yielded growth of ESBL-producing isolates. Multiple logistic regression analysis revealed that colonized neonates with very low birth weights (<1,000 g) and those who had received prolonged exposures to antimicrobial agents were at increased risk of ANE infections. CONCLUSIONS: Colonization with ANE places hospitalized neonates at risk for development of systemic infections. Very low birth weight (<1,000 g) and prolonged exposure to antimicrobial agents were the only two independent risk factors associated with ANE infection.