Severe Disease In Children Research Articles

Type III interferon signaling restricts enterovirus 71 infection of goblet cells.

Recent worldwide outbreaks of enterovirus 71 (EV71) have caused major epidemics of hand, foot, and mouth disease with severe neurological complications, including acute flaccid paralysis. EV71 is transmitted by the enteral route, but little is known about the mechanisms it uses to cross the human gastrointestinal tract. Using primary human intestinal epithelial monolayers, we show that EV71 infects the epithelium from the apical surface, where it preferentially infects goblet cells. We found that EV71 infection did not alter epithelial barrier function but did reduce the expression of goblet cell-derived mucins, suggesting that it alters goblet cell function. We also show that the intestinal epithelium responds to EV71 infection through the selective induction of type III interferons (IFNs), which restrict EV71 replication. Collectively, these findings define the early events associated with EV71 infections of the human intestinal epithelium and show that host IFN signaling controls replication in an IFN-specific manner.

Paediatric Active Enhanced Disease Surveillance (PAEDS) annual report 2016: Prospective hospital-based surveillance for serious paediatric conditions

The Paediatric Active Enhanced Disease Surveillance (PAEDS) network is a hospital-based active surveillance system employing prospective case ascertainment for selected serious childhood conditions, particularly vaccine preventable diseases and potential adverse events following immunisation (AEFI). PAEDS data is used to better understand these conditions, inform policy and practice under the National Immunisation Program, and enable rapid public health responses for certain conditions of public health importance. PAEDS enhances data available from other Australian surveillance systems by providing prospective, detailed clinical and laboratory information on children with selected conditions. This is the third annual PAEDS report, and presents surveillance data for 2016. Specialist nurses screened hospital admissions, emergency department records, laboratory and other data, on a daily basis in 5 paediatric tertiary referral hospitals in New South Wales, Victoria, South Australia, Western Australia and Queensland to identify children with the conditions under surveillance. Retrospective data on some conditions was also captured by an additional hospital in the Northern Territory. Standardised protocols and case definitions were used across all sites. Conditions under surveillance in 2016 included acute flaccid paralysis (AFP) (a syndrome associated with poliovirus infection), acute childhood encephalitis (ACE), influenza, intussusception (IS; a potential AEFI with rotavirus vaccines), pertussis, varicella-zoster virus infection (varicella and herpes zoster), invasive meningococcal and invasive Group A streptococcus diseases. Most protocols restrict eligibility to hospitalisations; Emergency Department (ED) only presentations are also included for some conditions. In 2016, there were 673 cases identified across all conditions under surveillance. Key outcomes of PAEDS included: contribution to national AFP surveillance to reach World Health Organization (WHO) reporting targets; identification of the leading infectious causes of acute encephalitis which included human parechovirus, influenza, enteroviruses, Mycoplasma pneumoniae, and bacterial meningo-encephalitis; demonstration of high influenza activity with vaccine effectiveness (VE) analysis demonstrating some protection offered through vaccination. All IS cases associated with vaccine receipt were reported to the relevant state health department. Varicella and herpes zoster case numbers increased from previous years associated with suboptimal vaccination in up to 40% of cases identified. Pertussis surveillance continued in 2016 with the addition of test negative controls captured for estimating vaccine effectiveness. Surveillance for invasive meningococcal disease showed predominance for serotype B in absence of immunisation, and new invasive group A streptococcus surveillance captured severe disease in children. PAEDS continues to provide unique policy-relevant data on serious paediatric conditions using hospital-based sentinel surveillance.

Salmonella enterica Serotype Panama: An exceptionally virulent cause of illness in children?

Salmonella enterica serotype Panama accounts for <1% of all reported cases of Salmonellosis. Previous reports suggest that it may be unusually virulent in children. We report the case of a family, five of six of whom developed a diarrheal illness due to this organism following exposure during a trip to Costa Rica. Included among these patients were three children, all of whom developed clinical shock requiring aggressive fluid resuscitation, and all of whom ultimately recovered. DNA fingerprinting, using pulsed-field gel electrophoresis, demonstrated that all three children were infected with an identical strain of Salmonella. Moreover, this strain was unique among strains recovered in Nebraska. Clinicians should be aware of the propensity of Salmonella enterica serotype Panama to cause especially severe disease in children; laboratory personnel should be aware of the unique need for thiourea buffering when attempting to perform pulsed-field gel electrophoresis analysis on such strains.

Vestibular and hearing disorders in obstructive sleep apnea patients

Introduction Obstructive sleep apnea (OSA) is a severe disease in children and adults presenting with complex interrelations between the respiratory system, on the one hand, and numerous systems and organs in the organism, on the other hand. This results in a variety of comorbidities which are difficult to treat. Aim The objective of the present communication is to analyze the basic diagnostic and therapeutic peculiarities of the vestibular and hearing disturbances in OSA patients. Materials and Methods During the period between 2015 and 2018, a total of 20 patients, 12 males and 8 females with OSA in whom hearing reduction because of acoustic nerve neuritis as well as tinnitus have been diagnosed. The following specialized examination methods were used: audiometry, optoacoustic emissions, video Head Impulse Test, polysomnography, etc. Results In nine patients, there was hearing impairment of mixed, i.e. conductance and reception type. Thanks to the treatment of OSA carried out, a substantial improvement of the subjective and objective status of the patients with hearing reduction and tinnitus has been observed.

Full genome characterization of two novel Alpha-coronavirus species from Italian bats

Coronaviruses (CoVs) have been detected worldwide in several bat species, which are considered the main reservoir. The attention to the high diversity of CoVs hosted by bats has increased during the last decade due to the high number of human infections caused by two zoonotic Beta-CoVs, SARS-CoV and MERS-CoV, that cause several respiratory diseases. Among coronaviruses, two Alpha-CoV strains (HuCoV-229E and HuCoV-NL63) cause mild respiratory disease that can change to severe disease in children, elderly and individuals affected by illnesses. Phylogenetic analysis conducted on bat Alpha-CoV strains revealed their evolutive correlation to human strains, suggesting their origin in bats. The genome of CoVs is characterized by a high frequency of mutations and recombination events, increasing their ability to switch hosts and their zoonotic potential. In this study, three strains of Alpha-CoV genera detected in Italian bats (Pipistrellus kuhlii) were fully sequenced by Next Generation Sequencing (NGS) and characterized. The complete genome analysis showed the correlation of the Italians strains with a Chinese strain detected in 2013 and, based on CoV molecular species demarcation, two new Alpha-CoV species were established. The analysis of a fragment of the RNA-dependent RNA polymerase (RdRp) showed the correlation of the Italian strains with CoVs that was only detected in the bat Pipistrellus genera (Pipistrellus kuhlii and Pipistrellus Pipistrellus) in European countries.

Rapid Progressive Glomerulonephritis in Children

Rapid Progressive Glomerulonephritis (RPGN) is a rare but very severe disease in children that often leads to acute and/or chronic renal failure requiring dialysis therapy. In this review, diagnostic criteria of RPGN including renal biopsy are discussed. An overview on general therapeutic strategies is discussed. Entities/diseases that cause RPGN are then described and special diagnostic and therapeutic features are given.

Paediatric Fabry disease: prognostic significance of ocular changes for disease severity.

BackgroundOcular signs of Fabry disease can be seen in the first decade of life.MethodsWe examined the occurrence of ocular signs in 232 paediatric patients in the Fabry Outcome Survey (FOS) international registry and looked for relationships between the presence of eye findings and disease severity as measured by the FOS Mainz severity score index (FOS-MSSI).ResultsAt least one ocular sign was found in 55/101 (54.5%) girls and 62/131 (47.3%) boys: cornea verticillata in 53/101 (52.5%) girls and 55/131 (42.0%) boys, vessel tortuosity in 17/98 (17.3%) girls and 32/131 (24.4%) boys, and posterior spoke-like lens opacities in 3/97 (3.1%) girls and 2/130 (1.5%) boys. Summary statistics showed higher median (range) age-adjusted FOS-MSSI total score indicating more severe disease in children with eye findings versus those without eye findings (0.5 [−11.0, 20.7] versus −2.3 [−11.1, 18.8]). At least one eye finding was observed in 59.1% of treated and 37.9% of untreated children.ConclusionsWe conclude that the presence of ocular signs, particularly cornea verticillata, correlates with more severe disease as indicated by FOS-MSSI scores in paediatric patients with Fabry disease. Ocular signs appear in roughly half of school-aged children with Fabry disease and are well-recognised as a valuable tool for diagnosis of Fabry disease in children; they also may help identify patients who are at risk for developing early severe manifestations of Fabry disease and who should be further evaluated and closely followed up.Electronic supplementary materialThe online version of this article (doi:10.1186/s12886-016-0374-2) contains supplementary material, which is available to authorized users.

Pediatric index of mortality 2 scores in pediatric intensive care unit patients

Background Comprehensive care for critically ill children in the pediatric intensive care unit (PICU) is done with the aim of achieving good outcomes. Severe disease in children is characterized by disruption of homeostatic processes, and can be evaluated by mortality scoring methods. There are several mortality scoring methods which can be used to predict mortality in children, the pediatric risk of mortality (PRISM) and pediatric index of mortality (PIM) are the most preferably used among all. The pediatric index of mortality 2(PIM2) is a key mortality prediction model for children receiving treatment in intensive care units, but its use has not been well validated in Indonesia.Objective To evaluate the performance of PIM2 model in PICU patients.Methods This cross-sectional study was conducted on PICU patients at Sanglah Hospital from November 2012 to April 2013. Patients underwent PIM2 scoring during their admission. The predictive ability of PIM2 scoring for patient mortality was analyzed using ROC curve.Results A total of 54 patients were included in this study, of whom 8 (14.8%) died. Discrimination between survival and death was assessed by the area under the receiver operating characteristic curve and found to be 0.81 (95% CI 0.59 to 1.03). Sensitivity was 75 (95%CI 36 to 96)% and specificity was 98 (95%CI 87 to 99)%. The PIM2 cut off value was ≥ -0.99.Conclusion The PIM 2 model has a good discriminatory power and calibration for predicting the mortality of children admitted to PICU and therefore is recommended for routine use in clinical practice. [

A Phenotypic High-Throughput Screen with RSV-Infected Primary Human Small Airway Epithelial Cells (SAECs)

Respiratory syncytial virus (RSV) is a commonly occurring pathogen that can cause severe disease in children, the elderly, and immunocompromised individuals with a large, unmet clinical need. We developed a high-throughput, primary cell-based antiviral RSV assay to enable identification of small molecules using cytopathic effect (CPE) as a phenotypic end point. To provide increased biological relevance, we developed our assay with primary human small airway epithelial cells (SAECs), which originate from known sites of RSV infection and replication instead of a more traditional immortalized cell line. Using purchased low-passage cells, cost-effective large-scale culture methods were developed to provide assay-ready frozen SAECs. A high-throughput screening campaign using the GSK Screening Collection was performed. The screen was executed in 384-well plates over a 12-week period with an average Z′ of 0.5. The screen yielded 17 post-entry hits with activity in the primary cells, which were not active in immortalized cells. Potencies for this class of compounds were equal between the primary and immortalize cell lines. For entry inhibitors, the number was much lower, with increased potency observed in immortalized cells. This is the first known use of frozen primary human cells for an RSV high-throughput screening phenotypic campaign.

Group A streptococcal bacteremia without a source is associated with less severe disease in children.

We analyzed characteristics of 86 Group A streptococcal bacteremia cases at Boston Children's Hospital from 1992 to 2012. Twenty-three percent of children had severe disease, using intensive care unit admission (18), disability (7) or death (2) as indicators. Children with bacteremia without a source (30% of cases) were less likely to have severe disease than children with focal infections in adjusted models.

Increased detection of G3P[9] and G6P[9] rotavirus strains in hospitalized children with acute diarrhea in Bulgaria

Rotavirus severe disease in children is now vaccine-preventable and the roll-out of vaccination programs globally is expected to make a significant impact in the reduction of morbidity and mortality in children <5years of age. Rotavirus is also a pathogen of other mammals and birds, and its segmented RNA genome can lead to the emergence of new or unusual strains in human population via interspecies transmission and reassortment events. Despite the efficacy and impact of rotavirus vaccine in preventing severe diarrhea, the correlates of protection remain largely unknown. Therefore, rotavirus strain surveillance before, during and after the introduction of immunization programs remains a crucial for monitoring rotavirus vaccine efficacy and impact. In this context, molecular characterization of 1323 Bulgarian rotavirus strains collected between June 2010 and May 2013 was performed. A total of 17 strains of interest were analyzed by partial sequence analysis. Twelve strains were characterized as G3P[9] and G6P[9] of potential animal origin. Phylogenetic analysis and comparisons with the same specificity strains detected sporadically between 2006 and 2010 revealed the constant circulation of these unusual human strains in Bulgaria, although in low prevalence, and their increased potential for person-to-person spread.

Classification and evolution of human rhinoviruses.

The historical classification of human rhinoviruses (RV) by serotyping has been replaced by a logical system of comparative sequencing. Given that strains must diverge within their capsid sequenced by a reasonable degree (>12-13 % pairwise base identities) before becoming immunologically distinct, the new nomenclature system makes allowances for the addition of new, future types, without compromising historical designations. Currently, three species, the RV-A, RV-B, and RV-C, are recognized. Of these, the RV-C, discovered in 2006, are the most unusual in terms of capsid structure, receptor use, and association with severe disease in children.

Follow-up on pediatric patients with bronchiolitis obliterans treated with corticosteroid pulse therapy.

BackgroundBronchiolitis obliterans (BO) is a rare but severe disease in children. Currently, there is no consensus on the treatment for BO with respect to the systemic use of corticosteroids. Here we report on the follow-up of children with a diagnosis of BO who were treated with corticosteroid pulse therapy.MethodsForty patients fulfilling the BO diagnosis criteria were treated with methylprednisolone pulse therapy in monthly cycles until clinical improvement. After the pulse therapy began, we analyzed the clinical and laboratory data at intervals. Statistical analyses were performed using non-parametric tests to compare repeated measures (Friedman, Wilcoxon) or paired nominal data (McNemar) (α = 5%).ResultsThe frequency of wheezing exacerbations and hospitalizations was reduced (p = 0.0042 and p < 0.0001, respectively) and oxygen saturation improved (p = 0.0002) in the pulse therapy-treated patients. Prolonged oral corticosteroid therapy was discontinued in 83% of these patients. The mean Z-score length for age improved from -1.08 to -0.63, and the mean Z-score weight for age improved from -0.91 to -0.59. The adverse effects during the infusion were temporary and none were serious.ConclusionsOur data suggest that pulse corticotherapy could be a safe alternative to prolonged systemic oral corticotherapy in children with BO, thus minimizing the adverse effects of the oral therapy. New prospective controlled studies are required to confirm this proposition.

Rotavirus Group A Surveillance and Genotype Distribution in Russian Federation in Seasons 2012-2013

Rotavirus infection is one of the primary causes of acute gastroenteritis in industrialized countries and may be a cause of severe disease in children. Here we present the results of analysis of specific indicators which characterize the burden of rotavirus infection in Russia such as passive surveillance data for rotavirus gastroenteritis cases (RG), the proportion of outbreaks of rotavirus per calendar month and laboratory-based data of rotavirus infection occurrence in lethal cases involving children. Specific features of rotavirus [P]G genotypes distribution in different geographic regions of Russia from 2012 through 2013 are also provided.

Resting Heart Rate in Children with Crimean–Congo Hemorrhagic Fever: A Tool to Identify Patients at Risk?

We aimed to assess the association between resting heart rate (RHR) and severe infection in children with Crimean-Congo hemorrhagic fever (CCHF). In all, 121 patients under 18 years of age with a laboratory-confirmed diagnosis of CCHF were enrolled in the study. Patients were classified into two groups based on disease severity (severe group and nonsevere group). RHR was measured by electrocardiography (ECG) on admission. Maximum P-wave duration (Pmax), P-wave dispersion (Pd), QRS duration, corrected QT interval, and QT dispersion were also measured. Mean age was 11.4±3.9 years and 84 patients were male. Twenty-six patients were classified as severe. Patients in this group had a higher RHR (103.6±10.4 vs. 80.5±8.1, p=0.001) than those with nonsevere disease. There was no difference in Pmax, Pd, QRS duration, QTcmax, or QTc dispersion. The optimal cutoff value of RHR to predict disease severity was>96 beats per minute (bpm), with 70.6% sensitivity and 50.1% specificity. Bleeding, thrombocytopenia (≤80×10(9)/L), elevated aspartate transaminase (AST) (>208 IU/L), elevated alanine transaminase (ALT) (>87 IU/L), elevated lactate dehydrogenase (LDH) (>566 IU/L), long activated partial thromboplastin time (aPTT) (>42 s), and increased hospitalization days were more frequent in patients with RHR >96 bpm. Multivariate logistic regression analysis revealed low platelet count (<80×10(9)/L), long aPTT (>42 s), high LDH (>566 IU/L), and elevated RHR (>96 bpm) as independent risk factors for severe disease. We conclude that elevated RHR was significantly associated with severe disease in children with CCHF, thus offering the potential to identify patients with increased risk.

Prediction of Severe Disease in Children with Diarrhea in a Resource-Limited Setting

ObjectiveTo investigate the accuracy of three clinical scales for predicting severe disease (severe dehydration or death) in children with diarrhea in a resource-limited setting.MethodsParticipants included 178 children admitted to three Rwandan hospitals with diarrhea. A local physician or nurse assessed each child on arrival using the World Health Organization (WHO) severe dehydration scale and the Centers for Disease Control (CDC) scale. Children were weighed on arrival and daily until they achieved a stable weight, with a 10% increase between admission weight and stable weight considered severe dehydration. The Clinical Dehydration Scale was then constructed post-hoc using the data collected for the other two scales. Receiver Operator Characteristic (ROC) curves were constructed for each scale compared to the composite outcome of severe dehydration or death. ResultsThe WHO severe dehydration scale, CDC scale, and Clinical Dehydration Scale had areas under the ROC curves (AUCs) of 0.72 (95% CI 0.60, 0.85), 0.73 (95% CI 0.62, 0.84), and 0.80 (95% CI 0.71, 0.89), respectively, in the full cohort. Only the Clinical Dehydration Scale was a significant predictor of severe disease when used in infants, with an AUC of 0.77 (95% CI 0.61, 0.93), and when used by nurses, with an AUC of 0.78 (95% CI 0.63, 0.93).ConclusionsWhile all three scales were moderate predictors of severe disease in children with diarrhea, scale accuracy varied based on provider training and age of the child. Future research should focus on developing or validating clinical tools that can be used accurately by nurses and other less-skilled providers to assess all children with diarrhea in resource-limited settings.

Patient characteristics and severity of human rhinovirus infections in children

BackgroundIt is increasingly recognized that human rhinoviruses (HRV) can be associated with severe infections. However, conflicting results have been reported on the relative prevalence and severity of the three HRV species. ObjectivesThe relative prevalence and clinical characteristics of HRV-A, B and C, in children attending a South London teaching hospital were investigated retrospectively. Study designChildren aged <16 years with episodes of respiratory tract infections and detectable entero/rhinovirus RNA in respiratory samples between November 2009 and December 2010 were investigated. Retrospective case review was performed and patients’ characteristics recorded. ResultsEntero/rhinoviruses were the commonest viral pathogens (498/2316; 21.5%). Amongst 204 infection episodes associated with entero/rhinovirus, 167 were typed HRV, HRV-C was the most prevalent (99/167, 59.3%) followed by HRV-A (60/167; 35.9%) and HRV-B (8/167, 4.8%). The severity spectrum of HRV-A and HRV-C infections were similar and affected all parts of the respiratory tract. Co-pathogens were observed in 54 (26.5%) episodes. Severity was increased in patients with non-viral co-pathogens and those with an underlying respiratory condition. Univariate and multiple regression analyses of potential prognostic variables including age, co-pathogens and underlying respiratory illnesses showed that mono-infection with HRV-C, as compared with other HRV species, was associated with more severe disease in young children <3 years. ConclusionsHRV-C was the most prevalent species and on its own was associated with severe disease in children <3 years. The association between infection with HRV species and clinical presentation is complex and affected by many confounding factors.

Prevalence, seasonality and severity of disease caused by pathogenic Escherichia coli in children with diarrhoea in Bolivia

The prevalence of infection caused by different categories of diarrhoeagenic E. coli (DEC) strains, including enteroaggregative (EAEC), enteropathogenic (EPEC), enterotoxigenic (ETEC), enteroinvasive (EIEC) and enterohaemorrhagic (EHEC) E. coli, in children who suffered from diarrhoea (n = 3943) or did not have diarrhoea (n = 1026) were analysed in two areas in Bolivia over a period of 4 years. We also analysed the seasonality of DEC infections and severity of diarrhoea in children with DEC infection and compared antibiotic resistance in DEC strains isolated from children with and without diarrhoea. Stool samples were analysed for the presence of DEC by culturing followed by PCR. The most prevalent DEC categories in samples from the children were: EAEC (11.2 %); ETEC (6.6 %); EPEC (5.8 %); and EIEC and EHEC (<1 %). DEC strains were isolated significantly more often from diarrhoea cases (21.6 %) than from controls (17.6 %; P = 0.002). The number of children with diarrhoea associated with EAEC, EPEC and ETEC infections peaked in the Bolivian winter (April-September), although the proportion of DEC-positive stool samples was higher during the warm rainy season (October-March). High levels of antibiotic resistance were detected among the DEC strains. In particular, resistance to tetracycline and sulfamethoxazole-trimethoprim was significantly higher in strains isolated from individuals with diarrhoea than in samples from controls. The severity of disease in children infected with EAEC, EPEC and ETEC varied from mild to severe diarrhoea, although disease severity did not differ significantly between the different DEC categories. ETEC, EPEC and EAEC are commonly found in Bolivia and may cause severe disease in children.

Comparison Of Moderate And Severe Hospitalized Pediatric 2009 H1N1 Influenza Cases

Since its discovery in 2009, H1N1 influenza (H1N1) has spread globally. Predictive factors for severe disease in children are not well defined. Our retrospective data collection and logistic regression analysis on 137 patients hospitalized between April 2009 and February 2010 at Children's Hospital and Research Center Oakland describe clinical and epidemiologic features of H1N1 in children and determines predictors of severe disease.

A High Burden of Respiratory Syncytial Virus Associated Pneumonia in Children Less than Two Years of Age in a South East Asian Refugee Population

BackgroundPneumonia is a major cause of childhood mortality and morbidity approximately 1.6 million deaths and 150 million episodes occur annually in children <5 years. Respiratory syncytial virus (RSV) may be responsible for up to 25% of cases and 12% of deaths making it an important potential vaccine target, although data from South East Asia is scarce.MethodsWe followed a birth cohort of Burmese refugee children, born over a one year period, for two years. Pneumonia episodes were diagnosed using WHO criteria. A chest radiograph, nasopharyngeal aspirate and non-specific markers of infection were taken during each episode.ResultsThe incidence of RSV-associated pneumonia was 0.24 (95% CI 0.22–0.26) episodes per child year. All children with pneumonia received antibiotic treatment, following WHO guidelines. The highest incidence was in the 2–12 month age group. The commonest diagnosis in a child with RSV-associated pneumonia was non-severe pneumonia (239/362∶66.0%), however the incidence of RSV-associated severe or very severe pneumonia was 0.08 (95% CI 0.01–0.10) episodes per child year. Birth in the wet season increased the risk of severe disease in children who had their first episode of RSV-associated pneumonia aged 2–11 months (OR 28.7, 95% CI 6.6–125.0, p<0.001). RSV episodes were highly seasonal being responsible for 80.0% of all the pneumonia episodes occurring each October and November over the study period.ConclusionsThere was a high incidence of RSV associated pneumonia in this refugee population. Interventions to prevent RSV infection have the potential to reduce the incidence of clinically diagnosed pneumonia and hence unnecessary antibiotic usage in this population.