Influenza Virus Infection In Children Research Articles

Clinical Hematochemical Parameters in Differential Diagnosis between Pediatric SARS-CoV-2 and Influenza Virus Infection: An Automated Machine Learning Approach.

The influenza virus and the novel beta coronavirus (SARS-CoV-2) have similar transmission characteristics, and it is very difficult to distinguish them clinically. With the development of information technologies, novel opportunities have arisen for the application of intelligent software systems in disease diagnosis and patient triage. A cross-sectional study was conducted on 268 infants: 133 infants with a SARS-CoV-2 infection and 135 infants with an influenza virus infection. In total, 10 hematochemical variables were used to construct an automated machine learning model. An accuracy range from 53.8% to 60.7% was obtained by applying support vector machine, random forest, k-nearest neighbors, logistic regression, and neural network models. Alternatively, an automated model convincingly outperformed other models with an accuracy of 98.4%. The proposed automated algorithm recommended a random tree model, a randomization-based ensemble method, as the most appropriate for the given dataset. The application of automated machine learning in clinical practice can contribute to more objective, accurate, and rapid diagnosis of SARS-CoV-2 and influenza virus infections in children.

The protective effect of 999 XiaoErGanMao granules on the lungs and intestines of influenza A virus-infected mice

Context Gastrointestinal symptoms are a common complication of influenza virus infection in children, which the gut-lung axis become involved in its biological progress. The protective effect of 999 XiaoErGanMao granules (XEGMG) on multi-organ injury in viral pneumonia remains unclear. Objective To investigate the therapeutic effect of XEGMG on lungs and intestines injury in A/FM/1/47 (H1N1) influenza virus-infected mice. Materials and methods Male BALB/c mice were infected with the 2LD50 H1N1 influenza virus and then treated with XEGMG (6 or 12 g/kg) intragastrically once a day for 4 days. The lung and colon samples were then collected for pathological observation, and assays for inflammatory cytokines and intestinal barrier. Mouse feces were collected to evaluate the intestinal microbiota. Results Treating with XEGMG (12 g/kg) can mitigate body weight loss caused by 2LD50 H1N1 infection. It can also reduce lung index and pathological damage with the decreased inflammatory cytokines such as IL-6 and IL-1β. Furthermore, XEGMG (12 g/kg) can maintain the goblet cell number in the colons to protect the intestinal barrier and regulate the major flora such as Firmicutes, Bacteroidetes, and Muribaculaceae back to normal. Meanwhile, the expression of IL-17A in the colon tissues was significantly lower in the group of XEGMG (6, 12 g/kg) compared to H1N1 group. Discussion and conclusions XEGMG can protect against H1N1 invasion involved in gut-lung axis regulation. The results provide new evidence for the protective effect of XEGMG, which is beneficial to vulnerable children.

Serum 25-Hydroxyvitamin D Was Not Associated with Influenza Virus Infection in Children and Adults in Hong Kong, 2009–201

Background: Some studies have hypothesized that vitamin D may have a role to play in protection against influenza virus infections and illnesses, and that seasonal fluctuation in serum 25-hydroxyvitamin D [25(OH)D] may affect seasonal patterns of influenza virus infections.Objective: We aimed to investigate whether serum 25(OH)D concentrations were associated with the incidence of influenza virus infections and illnesses in children and adults in Hong Kong.Methods: In 2009–2010, 3030 children and adults of all ages from 796 households in Hong Kong were followed up to identify acute respiratory illnesses. Sera from 2694 participants were collected at baseline and after ∼1 mo, 6 mo, and 12 mo. Influenza virus infections were confirmed by reverse transcriptase–polymerase chain reaction performed on nasal and throat swab samples collected during illness episodes. Serologic evidence of influenza virus infection was measured by hemagglutination inhibition assays in unvaccinated participants. The serum 25(OH)D concentrations were measured after collection of all specimens. Each individual’s baseline serum 25(OH)D concentration on 1 January 2010 was predicted by a random-effects linear regression model.Results: We found that, in children and adults who had not received a seasonal influenza vaccine, baseline serum 25(OH)D concentrations (<50 nmol/L compared with ≥50 nmol/L) were not statistically significantly associated with serologic evidence of influenza A(H1N1)pdm09 (RR, 1.18; 95% CI: 0.85, 1.65) or seasonal influenza virus infections [including A(H3N2) and B virus] (RR, 1.13; 95% CI: 0.86, 1.49). In all participants, baseline serum 25(OH)D concentrations were not statistically significantly associated with polymerase chain reaction–confirmed influenza virus infection (RR, 1.15; 95% CI: 0.73, 1.83) and influenza-like illness (RR, 1.18; 95% CI: 0.98, 1.43).Conclusions: These findings indicate that lower serum vitamin D concentrations may not contribute to the seasonality of influenza and are not associated with an increased risk of influenza virus infections in persons of all ages in Hong Kong.

Successful Treatment of Complicated Influenza A(H3N2) Virus Infection and Rhabdomyolysis with Compassionate Use of IV Zanamivir

In 2019, EMA licensed intravenous (IV) zanamivir for severe influenza virus infection in children over 6 months as well as adults. Prior to that, it was possible via a compassionate use program. We present successful compassionate use of IV zanamivir in a 14-year-old female with severe influenza A(H3N2) and multi-organ failure, who had failed oral oseltamivir. Her illness was complicated by acute respiratory distress syndrome and rhabdomyolysis requiring extracorporeal membrane oxygenation and hemofiltration. Considering the broad safety margins with neuraminidase inhibitors, an adult dose of 600 mg IV BID was administered in this 60 kg patient. Influenza virus was cleared rapidly and undetectable on day 13. Creatine kinase (CK) values were dropping from 38,000 to 500 within nine days. Given the recent licensure of IV zanamivir, multi-center prospective observational studies in pediatric Intensive Care Unit patients would be beneficial to guide the most appropriate use of IV zanamivir in this vulnerable age group.

DDX58 Is Associated With Susceptibility to Severe Influenza Virus Infection in Children and Adolescents.

Seasonal influenza virus infection causes a range of disease severity, including lower respiratory tract infection with respiratory failure. We evaluated the association of common variants in interferon (IFN) regulatory genes with susceptibility to critical influenza infection in children. We performed targeted sequencing of 69 influenza-associated candidate genes in 348 children from 24 US centers admitted to the intensive care unit with influenza infection and lacking risk factors for severe influenza infection (PICFlu cohort, 59.4% male). As controls, whole genome sequencing from 675 children with asthma (CAMP cohort, 62.5% male) was compared. We assessed functional relevance using PICFlu whole blood gene expression levels for the gene and calculated IFN gene signature score. Common variants in DDX58, encoding the retinoic acid-inducible gene I (RIG-I) receptor, demonstrated association above or around the Bonferroni-corrected threshold (synonymous variant rs3205166; intronic variant rs4487862). The intronic single-nucleotide polymorphism rs4487862 minor allele was associated with decreased DDX58 expression and IFN signature (P < .05 and P = .0009, respectively) which provided evidence supporting the genetic variants' impact on RIG-I and IFN immunity. We provide evidence associating common gene variants in DDX58 with susceptibility to severe influenza infection in children. RIG-I may be essential for preventing life-threatening influenza-associated disease.

Characteristics and Results of Hospital Admission Caused by Influenza Virus Infections in Children under 5 Years Old.

The influenza virus is an infectious disease with acute respiratory tract infections, caused secondary bacterial infections and death. In this study, we aimed to determine which predictors were associated with the need for high-flow nasal cannula oxygen therapy (HFNC) and transition to intensive care for influenza virus and also to compare single viral pathogens with multiple ones. Inpatients under the age of 5 with influenza virus-related respiratory tract infections between November 2015 and March 2019 were included in the study. Demographic features, comorbidities, symptoms, secondary bacterial infection, need for HFNC and pediatric intensive care unit and respiratory support system, length of hospital stay, polymerase chain reaction tests were recorded. A total of 93 patients were included in the study. It was determined that 53.8% of the cases were male and 84.9% were under the age of 2. Comorbidities were present in 50.5% of the cases. Secondary bacterial pneumonia developed in 56.9% of the cases. Patients with secondary bacterial pneumonia had higher PICU need, HFNC need and hospital stay (p = 0.014, p ≤ 0.001 and p ≤ 0.001, respectively). Patients with comorbidity had longer hospital stays and a higher need for HFNC (p ≤ 0.001 and p = 0.001, respectively). In this study, it was determined that especially comorbidity and secondary bacterial infection aggravated the clinical treatment of hospitalized patients. Therefore, it was concluded that patients with comorbidity should be followed closely and secondary bacterial pneumonia should be recognized and treated early.

Surfactant protein D is a biomarker of influenza-related pediatric lung injury.

Biomarkers that can risk-stratify children with influenza virus lower respiratory infection may identify patients for targeted intervention. Early elevation of alveolar-related proteins in the bloodstream in these patients could indicate more severe lung damage portending worse outcomes. We used a mouse model of human influenza infection and evaluated relationships between lung pathophysiology and surfactant protein D (SP-D), SP-A, and Club cell protein 16 (CC16). We then measured SP-A, SP-D, and CC16 levels in plasma samples from 94 children with influenza-associated acute respiratory failure (PICFLU cohort), excluding children with underlying conditions explaining disease severity. We tested for associations between levels of circulating proteins and disease severity including the diagnosis of acute respiratory distress syndrome (ARDS), mechanical ventilator, intensive care unit and hospital days, and hospital mortality. Circulating SP-D showed a greater increase than SP-A and CC16 in mice with increased alveolar-vascular permeability following influenza infection. In the PICFLU cohort, SP-D was associated with moderate-severe ARDS diagnosis (p = 0.01) and with mechanical ventilator (r = 0.45, p = 0.002), ICU (r = 0.44, p = 0.002), and hospital days (r = 0.37, p = 0.001) in influenza-infected children without bacterial coinfection. Levels of SP-D were lower in children with secondary bacterial pneumonia (p = 0.01) and not associated with outcomes. CC16 and SP-A levels did not differ with bacterial coinfection and were not consistently associated with severe outcomes. SP-D has potential as an early circulating biomarker reflecting a degree of lung damage caused directly by influenza virus infection in children. Secondary bacterial pneumonia alters SP-D biomarker performance.

Routine blood parameters are helpful for early identification of influenza infection in children

BackgroundRoutine blood parameters, such as the lymphocyte (LYM) count, platelet (PLT) count, lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), lymphocytes multiplied by platelets (LYM*PLT) and mean platelet volume-to-platelet ratio (MPV/PLT), are widely used to predict the prognosis of infectious diseases. We aimed to explore the value of these parameters in the early identification of influenza virus infection in children.MethodsWe conducted a single-center, retrospective, observational study of fever with influenza-like symptoms in pediatric outpatients from different age groups and evaluated the predictive value of various routine blood parameters measured within 48 h of the onset of fever for influenza virus infection.ResultsThe LYM count, PLT count, LMR and LYM*PLT were lower, and the NLR and MPV/PLT were higher in children with an influenza infection (PCR-confirmed and symptomatic). The LYM count, LMR and LYM*PLT in the influenza infection group were lower in the 1- to 6-year-old subgroup, and the LMR and LYM*PLT in the influenza infection group were lower in the > 6-year-old subgroup. In the 1- to 6-year-old subgroup, the cutoff value of the LMR for predicting influenza A virus infection was 3.75, the sensitivity was 81.87%, the specificity was 84.31%, and the area under the curve (AUC) was 0.886; the cutoff value of the LMR for predicting influenza B virus infection was 3.71, the sensitivity was 73.58%, the specificity was 84.31%, and the AUC was 0.843. In the > 6-year-old subgroup, the cutoff value of the LMR for predicting influenza A virus infection was 3.05, the sensitivity was 89.27%, the specificity was 89.61%, and the AUC was 0.949; the cutoff value of the LMR for predicting influenza B virus infection was 2.88, the sensitivity was 83.19%, the specificity was 92.21%, and the AUC was 0.924.ConclusionsRoutine blood tests are simple, inexpensive and easy to perform, and they are useful for the early identification of influenza virus infection in children. The LMR had the strongest predictive value for influenza virus infection in children older than 1 year, particularly in children older than 6 years with influenza A virus infection.

Immune mechanisms of pulmonary intravascular coagulopathy in COVID-19 pneumonia.

SummaryThe lung pathology seen in patients with coronavirus disease 2019 (COVID-19) shows marked microvascular thrombosis and haemorrhage linked to extensive alveolar and interstitial inflammation that shares features with macrophage activation syndrome (MAS). We have termed the lung-restricted vascular immunopathology associated with COVID-19 as diffuse pulmonary intravascular coagulopathy, which in its early stages is distinct from disseminated intravascular coagulation. Increased circulating D-dimer concentrations (reflecting pulmonary vascular bed thrombosis with fibrinolysis) and elevated cardiac enzyme concentrations (reflecting emergent ventricular stress induced by pulmonary hypertension) in the face of normal fibrinogen and platelet levels are key early features of severe pulmonary intravascular coagulopathy related to COVID-19. Extensive immunothrombosis over a wide pulmonary vascular territory without confirmation of COVID-19 viraemia in early disease best explains the adverse impact of male sex, hypertension, obesity, and diabetes on the prognosis of patients with COVID-19. The immune mechanism underlying diffuse alveolar and pulmonary interstitial inflammation in COVID-19 involves a MAS-like state that triggers extensive immunothrombosis, which might unmask subclinical cardiovascular disease and is distinct from the MAS and disseminated intravascular coagulation that is more familiar to rheumatologists.

Study of Influenza Virus Infection in Children Hospitalized in Spain in Two Consecutive Influenza Seasons

Study of Influenza Virus Infection in Children Hospitalized in Spain in Two Consecutive Influenza Seasons

2346. Severe Head and Neck Infections Following Influenza Virus Infection in Children

BackgroundSeasonal influenza infection is associated with secondary bacterial complications involving the upper and lower respiratory tract. However, the association of influenza infection with secondary severe or complicated head and neck infections is not appreciated.MethodsWe performed a retrospective review of pediatric patients hospitalized at Texas Children’s Hospital with bacterial head or neck infections following influenza infection from October 2017 to March 2018. We queried the infectious diseases consult database using the search terms: orbital cellulitis, mastoiditis, retropharyngeal abscess, peritonsillar abscess, deep neck abscess, subdural empyema, Lemierre’s syndrome, and Pott’s puffy tumor. Based upon medical records review and ICD-10 codes, patients were included in this study if they had a head or neck infection and reported a positive rapid influenza diagnostic test within 30 days preceding hospital admission.ResultsWe identified 44 patients with head or neck infections, of which 6 patients met inclusion criteria (table). The male-to-female ratio was 5:1 and the median age was 11.6 years (range 1.7–13.9 years). Most patients were diagnosed with influenza during a period of high influenza activity and the median time from influenza diagnosis to hospital admission was 4.5 days (range 1–6 days). One patient had received seasonal influenza vaccination. Patients had a wide range of infections, including orbital cellulitis (3), retropharyngeal abscess (2), and 1 of each of the following: Lemierre’s syndrome, peritonsillar abscess, Pott’s puffy tumor, and subdural empyema; 4 also had sinusitis. A causative pathogen was established in four cases: methicillin-resistant Staphylococcus aureus, Streptococcus anginosus group, S. pyogenes, and S. intermedius. The median duration of hospitalization was 22 days (range 5–35 days) and treatment duration ranged from 3.5 to 6 weeks. All patients completed antibiotic treatment successfully and had favorable outcomes.ConclusionWe suggest that complicated bacterial head and neck infections may represent an under recognized co-infection or secondary complication of infection with influenza virus, further stressing the importance of prevention and treatment of influenza infection. Disclosures All authors: No reported disclosures.

Clinical and epidemiological characterization of influenza virus infections in children with severe acute respiratory infection in Maputo, Mozambique: Results from the implementation of sentinel surveillance, 2014 - 2016.

In Sub-Saharan Africa, where burden, impact, and incidence of acute respiratory infections (ARI) are the highest in the world, conversely, the epidemiology of influenza-associated severe acute respiratory infections (SARI) is incompletely known. The aim of this study was to describe the clinical and epidemiological features of influenza-associated SARI in hospitalized children in Maputo city, Mozambique. Nasopharyngeal and oropharyngeal swabs were collected from children aged 0–14 years old who met the case definition for SARI in two hospitals in Maputo city after their parents or legal representative consented to participate. A structured questionnaire was used to collect clinical and demographic data. Typing and subtyping of influenza were performed by real-time PCR. From January 2014 to December 2016, a total of 2,007 eligible children were recruited, of whom 1,997 (99.5%) were screened for influenza by real-time PCR. The median age of participants was 16.9 months (IQR: 7.0–38.9 months) and 53.9% (1076/1991) were male. A total of 77 were positive for influenza, yielding a frequency of 3.9% (77/1,991), with the highest frequency being reported in the age group 1–5 years old. Cases of influenza peaked twice each year, during which, its frequency reached up to 60%-80%. Among all influenza confirmed cases, 33.7% (26/77), 35.1% (27/77) and 28.6% (22/77) were typed as influenza A/H3N2, A/H1N1pdm09, and B, respectively. This represents the first report of influenza in urban/sub urban setting in Mozambique and the first evidence of distribution of strains of influenza in the country. Our data showed that frequency of influenza was lower than reported in a rural setting in Mozambique and the frequency of seasonal (A/H1N1pdm09) and (A/H3N2) subtypes were similar in children with SARI.

Immune response after a single intravenous peramivir administration in children with influenza.

Immune response after intravenous peramivir administration, which is approved for children with influenza infection in Japan, is unclear. Kinetics of viral load and serum cytokine levels before and after peramivir therapy were analysed in 17 and 8 hospitalized children infected with influenza A and B, respectively. Additionally, haemagglutination inhibition (HI) titre was measured. The first day of hospital admission was defined as day 0. Serum interleukin (IL)-6 levels in influenza-A-infected children significantly decreased after peramivir administration, unlike in those with influenza B where a decrease on day 1 was followed by an increase on day 2. Serum IL-6 kinetics were similar to viral load kinetics in both influenza-A- and B-infected children between days 0 and 2. Serum IL-8 levels gradually decreased after peramivir therapy in influenza-A-infected children but increased between days 1 and 2 in influenza-B-infected children. Conversely, serum IL-10 levels gradually decreased over time. Serum interferon-γ and granulocyte macrophage colony-stimulating factor levels remained low until day 5. Day 0-4 serum HI titres were <4-fold in all children infected with influenza A or B. Additionally, day 5 HI titres were positive in 4 of 6 influenza A cases and all 3 influenza B cases. Our results suggest that viral load and inflammatory cytokine kinetics were associated with the antiviral therapy used and that second peramivir administration should be considered in influenza B. The results also highlight antiviral agents as key determinants of the clinical course of influenza virus infection in children.

Serum 25-Hydroxyvitamin D Was Not Associated with Influenza Virus Infection in Children and Adults in Hong Kong, 2009-2010.

Some studies have hypothesized that vitamin D may have a role to play in protection against influenza virus infections and illnesses, and that seasonal fluctuation in serum 25-hydroxyvitamin D [25(OH)D] may affect seasonal patterns of influenza virus infections. We aimed to investigate whether serum 25(OH)D concentrations were associated with the incidence of influenza virus infections and illnesses in children and adults in Hong Kong. In 2009-2010, 3030 children and adults of all ages from 796 households in Hong Kong were followed up to identify acute respiratory illnesses. Sera from 2694 participants were collected at baseline and after ∼1 mo, 6 mo, and 12 mo. Influenza virus infections were confirmed by reverse transcriptase-polymerase chain reaction performed on nasal and throat swab samples collected during illness episodes. Serologic evidence of influenza virus infection was measured by hemagglutination inhibition assays in unvaccinated participants. The serum 25(OH)D concentrations were measured after collection of all specimens. Each individual's baseline serum 25(OH)D concentration on 1 January 2010 was predicted by a random-effects linear regression model. We found that, in children and adults who had not received a seasonal influenza vaccine, baseline serum 25(OH)D concentrations (<50 nmol/L compared with ≥50 nmol/L) were not statistically significantly associated with serologic evidence of influenza A(H1N1)pdm09 (RR, 1.18; 95% CI: 0.85, 1.65) or seasonal influenza virus infections [including A(H3N2) and B virus] (RR, 1.13; 95% CI: 0.86, 1.49). In all participants, baseline serum 25(OH)D concentrations were not statistically significantly associated with polymerase chain reaction-confirmed influenza virus infection (RR, 1.15; 95% CI: 0.73, 1.83) and influenza-like illness (RR, 1.18; 95% CI: 0.98, 1.43). These findings indicate that lower serum vitamin D concentrations may not contribute to the seasonality of influenza and are not associated with an increased risk of influenza virus infections in persons of all ages in Hong Kong.

Risk factors associated with severe influenza virus infections in hospitalized children during the 2013 to 2014 season.

An outbreak of influenza virus infection occurred in Taiwan from October 2013 to May 2014. We conducted a clinical study to identify risk factors associated with severe influenza virus infections in children. During the outbreak period, data from 110 hospitalized children with influenza virus infection were collected. We analyzed the data, the need for intensive care, and patient outcome to identify clinical features and risk factors of severe infections, defined as the need of intensive care. Of the 110 inpatients, there were 57 male and 53 female patients; the median age was 2.6 (interquartile range, 1.0-6.3) years. Nineteen patients required intensive care and two patients died. Children who were underweight (p=0.01) or those with neuromuscular disease (p=0.007) and digestive tract disease (p=0.03) were prone to severe infection. Occurrence of seizure (p=0.004), conscious disturbance (p=0.02), or low oxygen saturation at admission (p=0.04) predicted the need for intensive care. Higher initial absolute neutrophil count (p=0.02) and patch or pleural effusion on chest X-ray examination (p=0.02) were associated with severe infection. In the multivariable analysis, digestive tract disease [p=0.03; adjusted odds ratio (OR), 12.37; 95% confidence interval (CI), 1.28-119.43], seizure (p=0.001; adjusted OR, 49.54; 95% CI, 4.61-532.76) and conscious disturbance (p=0.006; adjusted OR, 131.61; 95% CI, 4.18-4141.64) were most significantly associated with severe influenza virus infection. Close monitoring of the important risk factors including underlying digestive tract diseases, seizure attack and conscious disturbance were recommended during the influenza season.

Plastic bronchitis associated with influenza virus infection in children: A report on 14 cases

BackgroundPlastic bronchitis (PB) is a rare disease characterized by formation of bronchial casts. It is usually associated with congenital heart disease, sickle cell disease, lymphoma, and lung diseases such as asthma and pneumonia. ObjectivesTo report 14 cases of PB with influenza A or influenza B infection. MethodsWe analyzed the clinical manifestations, bronchoscopic and histologic findings, clinical courses, and outcomes. ResultsThese cases indicate that PB is a life-threatening complication of severe influenza. Plastic bronchitis should be considered in the diagnosis of children with acute respiratory distress such as lung atelectasis accompanied by influenza. ConclusionsDiagnosis should be made by bronchial endoscopy and histopathology, and bronchial casts removed as early as possible.

Differences in Antibody Responses Between Trivalent Inactivated Influenza Vaccine and Live Attenuated Influenza Vaccine Correlate With the Kinetics and Magnitude of Interferon Signaling in Children

Live attenuated influenza vaccine (LAIV) and trivalent inactivated influenza vaccine (TIV) are effective for prevention of influenza virus infection in children, but the mechanisms associated with protection are not well defined. We analyzed the differences in B-cell responses and transcriptional profiles in children aged 6 months to 14 years immunized with these 2 vaccines. LAIV elicited a significant increase in naive, memory, and transitional B cells on day 30 after vaccination, whereas TIV elicited an increased number of plasmablasts on day 7. Antibody titers against the 3 vaccine strains (H1N1, H3N2, and B) were significantly higher in the TIV group and correlated with number of antibody-secreting cells. Both vaccines induced overexpression of interferon (IFN)-signaling genes but with different kinetics. TIV induced expression of IFN genes on day 1 after vaccination in all age groups, and LAIV induced expression of IFN genes on day 7 after vaccination but only in children <5 years old. IFN-related genes overexpressed in both vaccinated groups correlated with H3N2 antibody titers. These results suggest that LAIV and TIV induced significantly different B-cell responses in vaccinated children. Early induction of IFN appears to be important for development of antibody responses.

Chapter 30 - Neurologic aspects of influenza viruses

Although influenza A and B viruses are primarily known as respiratory viruses and mainly infected only the upper respiratory tract in humans, patients with influenza often develop signs and symptoms that are not due to the respiratory system. Frequently individuals with influenza develop headaches, meningismus, and even seizures in addition to their typical respiratory symptoms. In the past decades, influenza viruses have also been associated with serious non-respiratory signs. The famous 1918 strain of influenza was associated with von Economo's encephalitis lethargica and postencephalitic parkinsonism. In the 1960s influenza virus infections in children were associated with Reye's syndrome characterized often by fatty non-inflammatory hepatic disease and an encephalopathy with marked non-inflammatory cerebral edema. Intermittently children with influenza develop focal myalgia and myositis. Guillain–Barré syndrome was epidemiologically associated with the 1978 killed influenza vaccine but not subsequent vaccines. Although occasional children with influenza have developed encephalopathy, from 2000 through 2004 there was an increase in the number of serious cases of acute necrotizing encephalopathy accompanying infection with the influenza A 2009 strain. The current H5N1 strain of bird influenza occasionally infects humans with a high mortality rate and some appear to have central nervous signs. This chapter explores what is known about these influenza neurologic associations.

Biphasic Cuirass Ventilation for pandemic A (H1N1) influenza virus infection in children

Biphasic Cuirass Ventilation for pandemic A (H1N1) influenza virus infection in children

Neurological complications of pandemic influenza A H1N1 2009 infection: European case series and review

Neurological manifestations and outcomes of children with the 2009 H1N1 virus infection have been reported in three American series and from smaller cohorts and case reports worldwide. Of the 83 children admitted between April 2009 and March 2010 with H1N1 virus infection to a tertiary children’s hospital in a European setting, five children aged between 2 and 10 years had neurological symptoms. Four patients had seizures and encephalopathy at presentation. One patient presented with ataxia; one developed neuropsychiatric manifestations, and two developed movement disorders during the disease course. Early neuroimaging showed evidence of acute necrotising encephalopathy (ANE) in one case and non-specific white matter changes in another. Initial neuroimaging was normal for the other three, but interval MRI showed increased signal in bilateral periventricular distribution in one and significant cerebral volume loss in the other. Clinical outcomes varied: two recovered fully while three had residual seizures and/or significant cognitive deficits. Conclusion An analysis of our patients along with all reported cases reveal that seizures and encephalopathy were common neurological presentations associated with pandemic 2009 H1N1 influenza virus infection in children requiring hospital admission. Neuroimaging suggestive of ANE, basal ganglia involvement and volume loss appears to be associated with worse neurological outcome.