Detection of human herpesvirus 6 in pediatric CSF samples: causing disease or incidental distraction?

Interpretation of human herpesvirus type 6 (HHV6) detection in the cerebrospinal fluid (CSF) of children can be complex; the virus can cause acute infection, reactivation, or can be inherited chromosomally integrated (iciHHV6). Our objectives were to determine the prevalence of HHV6 including iciHHV6 in CSF and compare the clinical and laboratory characteristics with and without iciHHV6 in our patient population. Overall, the prevalence of HHV6 and iciHHV6 was 2.4% and 0.85%, respectively. Children with iciHHV6 were significantly younger and less likely to present with fever. Septic infants (≤60 days) accounted for 65.2% (15/23) of the iciHHV6 patients. Patients with iciHHV6 had higher viral loads in CSF and whole blood. Twenty-one (91.3%) patients with iciHHV6 and 12 (33.3%) without ici-HHV6 were determined to have an incidental detection of HHV6 not associated with presenting symptoms. Molecular detection of HHV6 in CSF is not always associated with HHV6 infection and may represent iciHHV6 particularly in infants evaluated for sepsis.

Update on nonpolio enterovirus and parechovirus infections in neonates and young infants.

PURPOSE OF REVIEW: To review the epidemiology, clinical manifestations, and treatment strategies of nonpolio enterovirus and parechovirus (PeV) infections, and identify research gaps. RECENT FINDINGS: There is currently no approved antiviral agent for enterovirus or PeV infections, although pocapavir may be provided on a compassionate basis. Elucidation of the structure and functional features of enterovirus and PeV may lead to novel therapeutic strategies, including vaccine development. SUMMARY: Nonpolio human enterovirus and PeV are common childhood infections that are most severe among neonates and young infants. Although most infections are asymptomatic, severe disease resulting in substantial morbidity and mortality occurs worldwide and has been associated with local outbreaks. Long-term sequelae are not well understood but have been reported following neonatal infection of the central nervous system. The lack of antiviral treatment and effective vaccines highlight important knowledge gaps. Active surveillance ultimately may inform preventive strategies.

Metapneumovirus Infections are Uncommon in Infants Younger than 60 Days of Age Admitted for Sepsis Evaluation.

The epidemiology and clinical manifestations of human metapneumovirus are not well studied in infants younger than 60 days of age. In this retrospective review of infants admitted for sepsis evaluation, we identified HMPV less frequently than other viral etiologies via nasopharyngeal multiplex polymerase chain reaction testing; in only 16 (1.9%) infants. Two infants had apneic episodes, but none had wheezing.

Myeloid-Derived Suppressor Cells and Clinical Outcomes in Children With COVID-19.

Background: Although children with COVID-19 account for fewer hospitalizations than adults, many develop severe disease requiring intensive care treatment. Critical illness due to COVID-19 has been associated with lymphopenia and functional immune suppression. Myeloid-derived suppressor cells (MDSCs) potently suppress T cells and are significantly increased in adults with severe COVID-19. The role of MDSCs in the immune response of children with COVID-19 is unknown. Aims: We hypothesized that children with severe COVID-19 will have expansion of MDSC populations compared to those with milder disease, and that higher proportions of MDSCs will correlate with clinical outcomes. Methods: We conducted a prospective, observational study on a convenience sample of children hospitalized with PCR-confirmed COVID-19 and pre-pandemic, uninfected healthy controls (HC). Blood samples were obtained within 48 h of admission and analyzed for MDSCs, T cells, and natural killer (NK) cells by flow cytometry. Demographic information and clinical outcomes were obtained from the electronic medical record and a dedicated survey built for this study. Results: Fifty children admitted to the hospital were enrolled; 28 diagnosed with symptomatic COVID-19 (10 requiring ICU admission) and 22 detected by universal screening (6 requiring ICU admission). We found that children with severe COVID-19 had a significantly higher percentage of MDSCs than those admitted to the ward and uninfected healthy controls. Increased percentages of MDSCs in peripheral blood mononuclear cells (PBMC) were associated with CD4+ T cell lymphopenia. MDSC expansion was associated with longer hospitalizations and need for respiratory support in children admitted with acute COVID-19. Conclusion: These findings suggest that MDSCs are part of the dysregulated immune responses observed in children with severe COVID-19 and may play a role in disease pathogenesis. Future mechanistic studies are required to further understand the function of MDSCs in the setting of SARS-CoV-2 infection in children.

Year-Round, Routine Testing of Multiple Body Site Specimens for Human Parechovirus in Young Febrile Infants.

OBJECTIVES: To test our hypothesis that routine year-round testing of specimens from multiple body sites and genotyping of detected virus would describe seasonal changes, increase diagnostic yield, and provide a better definition of clinical manifestations of human parechovirus (PeV-A) infections in young febrile infants. STUDY DESIGN: PeV-A reverse-transcriptase polymerase chain reaction (RT-PCR) analysis was incorporated in routine evaluation of infants aged ≤60 days hospitalized at Nationwide Children's Hospital for fever and/or suspected sepsis-like syndrome beginning in July 2013. We reviewed electronic medical records of infants who tested positive for PeV-A between July 2013 and September 2016. Genotyping was performed with specific type 3 RT-PCR and sequencing. RESULTS: Of 1475 infants evaluated, 130 (9%) tested positive for PeV-A in 1 or more sites: 100 (77%) in blood, 84 (65%) in a nonsterile site, and 53 (41%) in cerebrospinal fluid (CSF). Five infants (4%) were CSF-only positive, 31 (24%) were blood-only positive, and 20 (15%) were nonsterile site-only positive. PeV-A3 was the most common type (85%) and the only type detected in CSF. Although the majority (79%) of infections were diagnosed between July and December, PeV-A was detected year-round. The median age at detection was 29 days. Fever (96%), fussiness (75%), and lymphopenia (56%) were common. Among infants with PeV-A-positive CSF, 77% had no CSF pleocytosis. The median duration of hospitalization was 41 hours. Four infants had bacterial coinfections diagnosed within 24 hours of admission; 40 infants had viral coinfections. CONCLUSIONS: Although most frequent in summer and fall, PeV-A infections were encountered in every calendar month within the 3-year period of study. More than one-half of patients had PeV-A detected at more than 1 body site. Coinfections were common. PeV-A3 was the most common type identified and the only type detected in the CSF.

Accuracy of Two Point-of-Care Tests for Rapid Diagnosis of Bovine Tuberculosis at Animal Level using Non-Invasive Specimens.

Bovine tuberculosis (BTB) testing in cattle requires a significant investment of time, equipment, and labor. Novel, rapid, cheaper and accurate methods are needed. The Alere Determine TB lipoarabinomannan antigen (LAM-test) is a World Health Organization-endorsed point-of-care urine test designed to detect active TB disease in humans. The Lionex Animal TB Rapid Test (Lionex-test) is a novel animal specific TB diagnostic blood test. An animal level analysis was performed using urine (n = 141) and milk (n = 63) samples from depopulated BTB-suspected cattle to test the accuracy of the LAM-test when compared to results of positive TB detection by any routine BTB tests (BOVIGAM, necropsy, histology, culture, PCR) that are regularly performed by the United States Department of Agriculture (USDA). The agreement between the urine LAM-test and USDA standard tests were poor at varying testing time points. The same milk samples did not elicit statistically significant agreement with the Lionex-test, although positive trends were present. Hence, we cannot recommend the LAM-test as a valid BTB diagnostic test in cattle using either urine or milk. The Lionex-test's production of positive trends using milk samples suggests larger sample sizes may validate the Lionex-test in accurately diagnosing BTB in cattle using milk samples, potentially providing a quick and reliable field test for BTB.

Enfermedad diseminada por arañazo de gato: el amplio espectro de la presentación / Disseminated cat scratch disease: The wide variety of clinical presentations

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Strengthening the Chain of Survival: Cardiopulmonary Resuscitation Workshop for Caregivers of Children at Risk.

BACKGROUND: Parents and caregivers should receive training regarding pediatric cardiopulmonary resuscitation (CPR) because this knowledge improves survival. We conducted a study as part of a Patient Safety Project to improve caregivers' CPR knowledge and skills. We also aimed to improve the quality of patient care. METHODS: We performed a prospective, longitudinal study in 2013-2014 in a pediatric hospital. We enrolled the caregivers of all patients admitted with a diagnosis of an acute life-threatening event, apnea, or choking. We provided a 45-minute CPR workshop for parents at discharge and evaluated the results using a test before, immediately after, and at 1 and 3 months after the workshop. Participants also completed an evaluation survey about the CPR workshop. RESULTS: We admitted 62 patients [median age, 1 mo (0.5-2 mo)]. We provided 62 pediatric CPR workshops to 106 enrolled relatives. The median score was 5 (CI, 3-6) out of 10 at baseline, which increased to 8 (CI, 7-10) immediately after the workshop (P < 0.01). After 1 and 3 months, the median score was 8 (CI, 6-9; P < 0.01). The severity of the acute life-threatening event episode correlated with a better score (P = 0.02). The utility of the workshop scored 9.9 out of 10. CONCLUSIONS: This CPR workshop significantly increased CPR knowledge and confidence, and this was maintained up to 3 months post-training. Caregiver satisfaction was high.

Clinical and Radiologic Manifestations of Bone Infection in Children with Cat Scratch Disease.

We identified 13 patients with cat scratch (Bartonella henselae) bone infection among those admitted to a large tertiary care children's hospital over a 12-year period. The median age was 7 years and the median time from onset of illness to diagnosis was 10 days. Multifocal osteomyelitis involving spine and pelvis was common; no patient had a lytic bone lesion. Median treatment duration was 28 days (IQR, 24.5 days). Despite significant variations in treatment duration and antimicrobial therapy choices, all patients showed improvement.

Evaluation of proadrenomedullin as a diagnostic or prognostic biomarker of acute appendicitis in children.

INTRODUCTION: A delay in the diagnosis of acute appendicitis (AA), with the added complication of symptoms that mimic other self-limited causes of abdominal pain, can lead to an increase in ruptured appendices and morbimortality. None of the serum biomarkers evaluated to date have shown a predictive value for early diagnosis. OBJECTIVE: The objective of this study was to evaluate the usefulness of proadrenomedullin (MR-proADM) in the diagnosis of AA in children presenting with acute abdominal pain. METHODS: A single-center prospective observational study was conducted in 136 children who presented to the emergency department with suspected AA. RESULTS: Forty-four (32.5%) children had AA, and 9 (20.5%) had perforated appendicitis. The mean concentration of MR-proADM was significantly higher in children with AA than in children with nonspecific abdominal pain (NAP) (0.54 nmol/L; 95% confidence interval, 0.46-0.55 and 0.37 nmol/L; 95% confidence interval, 0.35-0.40, respectively). Performance characteristics of MR-proADM alone were not optimal. However, after combining best cutoff points, the combination of a C-reactive protein level of <0.3 mg/dL and a MR-proADM level of <0.34 nmol/L showed 100% sensitivity and negative predictive value, with 61% specificity. CONCLUSIONS: Although MR-proADM values are higher in children with AA than in children with nonspecific abdominal pain, these values do not help in the early diagnosis of AA. The combination of low C-reactive protein and low MR-proADM levels is useful for the identification of children with a low risk of AA.