Efficacy of primary treatment with immunoglobulin plus ciclosporin for prevention of coronary artery abnormalities in patients with Kawasaki disease predicted to be at increased risk of non-response to intravenous immunoglobulin (KAICA): a randomised controlled, open-label, blinded-endpoints, phase 3 trial

From December 1989 through 1998, a total of 68 children with deep neck infection were enrolled into this study. The mean age was 5.9 years (range, 1 month-15.8 years). Infections in the retropharyngeal space (36.7%) were most common, followed by parapharyngeal space (30.8%), peritonsillar space (20.6%), and submandibular space (11.9%). Fever, neck pain, and swelling were the most frequent symptoms. The most common pathogens were viridans streptococci (41%, 16/39) and Staphylococcus aureus (26%, 10/39). Other isolates included Prevotella spp., Veillonella spp., Klebsiella pneumoniae, Escherichia coli, Morganella spp., and Enterobacter spp. Mixed infection was found in 46% (18/39) of patients. The mean duration of hospitalization was 12.4 days (range, 2-45 days). Complete resolution was achieved in 61 (89.7%) children. Complications occurred in 7 patients, including recurrence, mediastinal spread, bacteremia, and suppurative thyroiditis; the patient with mediastinal spread plus bacteremia died. Five patients had congenital cyst and 4 of them had complications or recurrence/relapse. In conclusion, infections in the retropharyngeal space and polymicrobial infections were most common in deep neck infection of Taiwan children.

Deep neck infections in children.

Human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) are leading causes of upper and lower respiratory tract infections in young children and among elderly and immunocompromised patients. The pathogenesis of hMPV-induced lung disease is poorly understood. The lung macrophage population consists of alveolar macrophages (AMs) residing at the luminal surface of alveoli and interstitial macrophages present within the parenchymal lung interstitium. The involvement of AMs in innate immune responses to virus infections remains elusive. In this study, BALB/c mice depleted of AMs by intranasal instillation of dichloromethylene bisphosphonate (L-CL2MBP) liposomes were examined for disease, lung inflammation, and viral replication after infection with hMPV or RSV. hMPV-infected mice lacking AMs exhibited improved disease in terms of body weight loss, lung inflammation, airway obstruction, and hyperresponsiveness compared with AM-competent mice. AM depletion was associated with significantly reduced hMPV titers in the lungs, suggesting that hMPV required AMs for early entry and replication in the lung. In contrast, AM depletion in the context of RSV infection was characterized by an increase in viral replication, worsened disease, and inflammation, with increased airway neutrophils and inflammatory dendritic cells. Overall, lack of AMs resulted in a broad-spectrum disruption in type I IFN and certain inflammatory cytokine production, including TNF and IL-6, while causing a virus-specific alteration in the profile of several immunomodulatory cytokines, chemokines, and growth factors. Our study demonstrates that AMs have distinct roles in the context of human infections caused by members of the Paramyxoviridae family.

/pdf/alveolar-macrophages-contribute-to-the-pathogenesis-of-human-397kdoseg8.pdf

Alveolar macrophages contribute to the pathogenesis of human metapneumovirus infection while protecting against respiratory syncytial virus infection.

©2017 Moe et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproductionin any medium, provided the original author and source are credited

/pdf/comparing-human-metapneumovirus-and-respiratory-syncytial-1uxquyh5kp.pdf

Comparing Human Metapneumovirus and Respiratory Syncytial Virus: Viral Co-Detections, Genotypes and Risk Factors for Severe Disease.

Paediatric human metapneumovirus infection: epidemiology, prevention and therapy.

The impact of human metapneumovirus (HMPV) in children aged >5 years and the risk factors associated with disease severity for all ages have not been well characterized. A retrospective cohort study of 238 children aged 0–15 years hospitalized over a 3-year period was performed. Medical records were reviewed for demographic information, clinical parameters and outcomes. Multivariable analyses were performed to identify independent factors associated with worse disease severity assessed by length of hospital stay (LOS), need for ICU care, respiratory support, and a disease severity score. Pulmonary diseases were associated with all outcomes of care, while congenital heart disease (CHD) and neuromuscular disorders were associated with longer LOS, and CHD and trisomy 21 were associated with worse severity scores independent of other covariables. Fever, retractions, use of steroids and albuterol were also associated with enhanced disease severity. Understanding the determinants of HMPV disease in children may help design targeted preventive strategies.

/pdf/human-metapneumovirus-infections-are-associated-with-severe-106wpj6v2v.pdf

Human metapneumovirus infections are associated with severe morbidity in hospitalized children of all ages

Author(s): Jaggi, Preeti; Wang, Wei; Dvorchik, Igor; Printz, Beth; Berry, Erika; Kovalchin, John P; Texter, Karen; Ramilo, Octavio; Burns, Jane C; Tremoulet, Adriana H | Abstract: BackgroundWe sought to determine if fever in the early postintravenous immunoglobulin (IVIG) time period (first 36 hours after IVIG completion) for Kawasaki disease, with or without additional infliximab, can predict IVIG resistance and coronary artery abnormalities (CAA).MethodsAcute Kawasaki disease subjects enrolled in a clinical trial of infliximab plus IVIG (n = 96) versus placebo/IVIG (n = 94) had temperatures recorded every 6 hours after completion of IVIG infusion. Fever was defined as temperature g38.0°C; patients with persistent or recrudescent fever g36 hours after completion of IVIG were classified as IVIG resistant. Multivariable logistic regression by fever pattern was performed to predict outcomes (IVIG resistance and CAA).ResultsThere was no difference in the time to defervescence between the infliximab/IVIG group (n = 96) versus placebo/IVIG group (n = 94). There was no fever after completion of IVIG in the majority of subjects [66% of those with no CAA (n = 139) and 76.5% of those with CAA, (n = 51)]. Although subjects with at least 1 fever 24-36 hours post-IVIG had a higher probability of IVIG resistance [odds ratio = 30.6 (95% confidence interval: 6.7-139.8); P l 0.0001], fever at 24-36 hours was not associated with higher likelihood of CAA. There were also 11% (n = 19) of IVIG responders who had fever at 24-36 hours post-IVIG. The majority of subjects with CAA (43 of 51, 84.3%) were identified by the initial echocardiogram, so the effect of fever on development of CAA could not be assessed.ConclusionsFever in the first 36 hours after IVIG completion is not predictive of CAA. Our data support refraining from retreatment until 36 hours after completion of IVIG.

/pdf/patterns-of-fever-in-children-after-primary-treatment-for-1ky8fyw9rb.pdf

Patterns of Fever in Children After Primary Treatment for Kawasaki Disease.

Objective: To determine if fever patterns in the first 36 hours after completion of intravenous immunoglobulin (IVIG) for Kawasaki disease (KD), with or without additional infliximab, can predict eventual resistance to treatment and coronary artery abnormalities (CAA). Study design: Subjects with acute KD enrolled in a clinical trial of infliximab plus IVIG (n=96) versus placebo plus IVIG (n=94) had temperatures taken axillary and either oral or rectal every 6 hours after completion of IVIG infusion. Fever was defined as any temperature >38.0oC and resistance to treatment was defined as persistent or recrudescent fever ≥36 hours after completion of IVIG. CAA was defined as a Z-score >2.5 based on the maximum internal diameters of the proximal right coronary or left anterior descending artery. Multivariable logistic regression was performed to predict two outcomes (resistance to treatment and development of CAA) by the variables of presence of fever at 0-12, 12-24, and 24-36 hours post IVIG. All analyses w...

Abstract O.38: Fever Patterns in KD Patients after Treatment with IVIG

Among hospitalized children with parapharyngeal or retropharyngeal infection, multivariate analysis was performed for the outcomes: successful treatment with antibiotics alone, absence of complications and length of stay less than 3 days. Those with apparent abscess on computed tomography scan had a lower probability of treatment with antimicrobials alone while older age was associated with increased probability of treatment with antibiotics alone.

Predictors for successful treatment of pediatric deep neck infections using antimicrobials alone.

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Human metapneumovirus infections are associated with severe morbidity in hospitalized children of all ages

Patterns of Fever in Children After Primary Treatment for Kawasaki Disease.

Abstract O.38: Fever Patterns in KD Patients after Treatment with IVIG

Predictors for successful treatment of pediatric deep neck infections using antimicrobials alone.