Ten years of severe respiratory syncytial virus infections in a tertiary paediatric intensive care unit

Abstract

immediate resuscitation. Clinical examination showed pallor and microcephaly without organomegaly. A neonatal cranial ultrasound performed on day 2 demonstrated bilaterally enlarged ventricles with thalamic calcification (Fig. 1). He had pancytopenia and raised liver enzymes. Congenital infection was considered: TORCH serology, metabolic screening, full septic screening, lumbar puncture and fundoscopy were all normal. The patient had a prolonged NICU stay for management of developed congestive cardiac failure in the first week of life requiring neonatal intensive care; echocardiography showed concentric left ventricular hypertrophy with low ejection fraction. No cause for this infantile hypertrophic cardiomyopathy was identified, including by an extensive familial cardiomyopathy genetic panel. On follow-up, the child had global developmental delay and intermittent hospital admissions for lower respiratory tract infections and seizures. Brain magnetic resonance imaging performed at 3 months of age showed marked dilation of the lateral and third ventricles, cerebral atrophy, reduced myelination and abnormal cerebral white matter with subcortical cysts. Genetic testing identified a homozygous c.172G>A (p.Gly58Arg) mutation in the RNASEH2C Aicardi-Goutieres syndrome (AGS) gene in the child, and the parents were heterozygous for the variant. Currently, the child is bedridden, tracheostomy dependent on home oxygen and has intractable epilepsy.AGS is an autosomal recessive progressive encephalopathy with features mimicking congenital infections like TORCH with microcephaly, haematological abnormalities and organomegaly. 1,2 It is a result of mutations in TREX1 and the RNASEH2 complex, the dysfunctional proteins in AGS that act as nuclease enzymes breaking down DNA and RNA. Failure of nuclease activity probably results in an inappropriate innate immune response to retained selfnucleic acids involved in cellular repair and immune system regulation. 3 Brain imaging, CSF chemistry and genetic testing are the key investigations. AGS is considered an interferonopathyin other words, it is a pathological condition caused by the overproduction of IFNα. 4 The main laboratory findings are increased CSF and serum interferon alpha levels. The primary treatment is supportive. It is especially important to recognise genetic disorders that mimic congenital infection because of the risk of recurrence in subsequent pregnancies.

Burden of respiratory syncytial virus bronchiolitis on the Dutch pediatric intensive care units

“…The increase in PICU admissions reported in this study is higher than the twofold increase previously reported for specialized PICUs in Australia [4] and adds to the presumptive evidence that PICU burden of RSV bronchiolitis in developed countries has increased over the last decade [3][4][5][6]. The observed increase in PICU admissions was unlikely driven by increased comorbidity, as the comorbidity rate remained stable over time and is comparable with the rate reported in previous literature [4,6,14].…”

“…Although hospitalization numbers for RSV bronchiolitis seem to be decreasing, bronchiolitis-associated healthcare costs have increased in several countries since 2000 [3][4][5]. A possible reason for these rising costs may be increased usage of pediatric intensive care unit (PICU) facilities [3,4,6]. Although only 2% of children with RSV bronchiolitis require PICU admission for mechanical ventilation, it is estimated that PICU care accounts for 18% of the total RSV-related hospital costs [3].…”

Severity of bronchiolitis in infants is associated with their parents' tobacco habit

“…The sample we analyzed consisted of only 102 patients. However, it represents the complex PICU population with SAB, a situation that physicians face on a daily basis, and this sample has similar characteristics to others reported 23,24 .…”

The Association between Weather Conditions and Admissions to the Paediatric Intensive Care Unit for Respiratory Syncytial Virus Bronchiolitis

“…Up to 5% of RSV-infected children experience acute deterioration of bronchiolitis, necessitating admission to a paediatric intensive care unit (PICU) for mechanical ventilation [ 3 ]. Over the last two decades, studies from various countries around the world have reported an increase in the number of PICU admissions for RSV bronchiolitis, associated with rising health care costs and increased pressure on health care systems [ 3 , 4 , 5 ]. Likewise, the number of PICU admissions for RSV bronchiolitis has increased approximately fourfold in the Netherlands between 2003 and 2016 ( Figure 1 A) [ 6 ], but the reasons for this increase remain to be elucidated.…”