Management of nontuberculous mycobacterial lymphadenitis in a tertiary care children's hospital: A 20year experience.

PURPOSE: Nontuberculous mycobacteria are uncommon cause of chronic cervicofacial lymphadenitis in healthy children. We describe clinical features and management strategies of cervicofacial nontuberculous mycobacterium lymphadenitis in a tertiary pediatric hospital. METHODS: Retrospective analysis of medical records of children discharged from 1992 to 2014 with a diagnosis of cervicofacial nontuberculous mycobacterium was made. Diagnosis certainty was based on microhistological investigations. Clinical stage was evaluated according to lymph node size and presence of fistulas. Successful therapy was defined by the regression of the lymph node enlargement (>75%) or complete surgical excision without relapse. RESULTS: Cervicofacial nontuberculous mycobacterium was diagnosed in 33 patients. Complete excision was performed in 73% of cases primarily observed in our hospital, while 83% of those referred from other hospitals required further surgical treatment. No case of relapse was observed after one year of follow-up. CONCLUSIONS: We recommend surgical approach as the first therapeutic option in the management of cervicofacial nontuberculous mycobacterium lymphadenitis. LEVELS OF EVIDENCE: Prognosis and Retrospective Study - Level II.

A case of neonatal human parechovirus encephalitis with a favourable outcome.

Human parechoviruses (HPeVs) are a new family of neurotropic viruses that cause central nervous system (CNS) infections similar to enterovirus (EVs) meningoencephalitis in the neonatal period, resulting in white matter lesions that can be visualized with cranial ultrasonography and magnetic resonance imaging, and correlated to a large spectrum of neurological outcomes. HPeV should be suspected in neonates with signs and symptoms of sepsis-like illness or CNS disease. We report a case of neonatal HPeV encephalitis, diagnosed on the basis of clinical and radiological findings and HPeV RT-PCR, with a good neurological outcome.

Spontaneously regressing leukoencephalopathy with bilateral temporal cysts in congenital rubella infection.

Very little is known regarding neuroimaging findings in patients with congenital rubella syndrome. We report a 1.9-year-old boy with congenital rubella syndrome who presented in the neonatal period with severe multisystem involvement and diffuse leukoencephalopathy with subcortical anterior temporal cysts, which showed spontaneous improvement during a period of 3 years.

Multiple ganciclovir-resistant strains in a newborn with symptomatic congenital human cytomegalovirus infection.

A case of human cytomegalovirus (HCMV) drug-resistance in a congenitally infected newborn is described. Unusual aspects of this case include: (i) the detection of an extremely complex virus population, composed of a mixture of wild-type (wt) and multiple mutant ganciclovir (GCV) and valganciclovir (val-GCV) resistant strains carrying a variety of known mutations in UL97; (ii) the identification of novel UL97 mutations and (iii) the first time detection of combined UL97 drug resistance mutations in the same viral strain. In detail, four known UL97 single-nucleotide mutations (A594T/V, M460V/I, C592G), a new amino-acid substitution (C607S), and a new deletion (597-600) in one of the three UL97 hot spots for GCV/val-GCV resistance (codons 460, 520 and 590-607) were detected. In addition, the combination of M460V+A594V and M460V+C592G was observed for the first time. The emergence of HCMV drug-resistance in symptomatic congenital infections chronically treated with GCV or val-GCV should be taken into account. The immaturity of the neonatal immune system may contribute to selection of complex virus populations in these patients.

Detection of ganciclovir resistance mutations by pyrosequencing in HCMV-infected pediatric patients.

BACKGROUND: Human cytomegalovirus (HCMV) is an opportunistic pathogen especially for immuno-suppressed subjects that might develop pharmacological resistance in patients undergoing prolonged antiviral treatment. Ganciclovir (GCV) is the drug used as first choice therapy in affected children and a GCV-resistant phenotype is mainly linked to mutations of the viral protein kinase UL97. OBJECTIVES: Here a new quantitative pyrosequence (PSQ) method is presented that allows detection and quantification of the viral species carrying the more frequent UL97 mutations responsible for GCV resistance in clinical samples (>80% of known cases). STUDY DESIGN: The system has been validated using two independent approaches (cloning and sequencing of UL-97 gene fragments and real-time PCR) and clinical samples derived from 3 pediatric patients. RESULTS: The UL97 pyrosequencing analysis has indicated a significant increase of mutant viruses carrying the H520Q and C592G mutations. In particular, the H520Q viral mutation, known to increase GCV resistance (IC50=10) increased around 5 times during hospitalization. In addition, C592G (known to have IC50=2.9) also increased 3 times. CONCLUSIONS: PSQ is a quick, cheap, high throughput and sensitive analysis method to detect GCV-associated resistance mutation useful to follow antiviral therapy in perinatal CMV-infection as well as in immune-suppressed patients.

Fibrosis in chronic hepatitis C acquired in infancy: is it only a matter of time?

OBJECTIVE: The natural history of chronic hepatitis C acquired in infancy is not well understood. The progression of fibrosis was analyzed in untreated children with chronic hepatitis C virus infection and no other hepatotoxic cofactors. METHODS: A total of 112 pediatric patients (13 with paired liver biopsies) were considered. Fibrosis was assessed by METAVIR score (i.e., stage F1 to F4). The ratio between the stage of fibrosis (METAVIR units) and the presumed duration of infection represented the "estimated" rate of fibrosis progression per year. In patients with paired biopsies, the "observed" rate of fibrosis progression was defined as the difference between the stage of fibrosis in the two biopsies divided by the time interval between them. RESULTS: Both age of patients at biopsy and duration of infection correlated with stage of fibrosis (p < 0.002 and p < 0.0005, respectively). Stage of fibrosis differed significantly between patients with infection lasting less or more than 10 yr (p < 0.0006). Sex, hepatitis C virus genotype, and route of infection did not correlate with stage of fibrosis. Among the 13 patients with paired biopsies, stage of fibrosis increased in seven and did not change in six; the median rate of estimated fibrosis progression per year was 0.142. The difference between estimated and observed fibrosis progression rates was significant (coefficient of determination, r(2) = 0.031), which demonstrated that the prediction of the fibrosis progression was unreliable in 97% of patients. CONCLUSIONS: Chronic hepatitis C acquired in childhood is a progressive, slow-moving, fibrotic disease. Fibrosis progression inferred on the basis of linear mathematical models should be critically evaluated in the clinical practice.