Characteristics and outcomes of human parechovirus infection in infants (2008-2012).

UNLABELLED: Human parechoviruses (HPeVs) cause a spectrum of disease ranging from self-limiting illness to severe disease and, sometimes, death. We describe the clinical characteristics and outcomes of HPeV infection in infants. The study describes the clinical and laboratory characteristics and outcomes of infants with HPeV infection during 2008-2012, from three paediatric hospitals in London each with a paediatric intensive care unit. The infants were retrospectively identified through laboratory and patient discharge databases and diagnosed through HPeV PCR. Fifty infants were identified. Half required admission to PICU. Infants less than 3 months were more likely to require PICU (16/25: p < 0.01). Clinical signs at presentation were often indistinguishable from those of bacterial sepsis and meningitis, but inflammatory markers were nearly always (95 % of cases) within normal ranges. Brain MRI showed white matter changes in 10/12 infants. Three of 19 infants with follow-up data (16 %) had significant neurological sequelae. CONCLUSION: HPeV may cause severe disease and long-term neurological sequelae in young infants. HPeV should be considered in infants with clinical features of sepsis/meningitis with normal CSF microscopy. Prospective observational studies are warranted to better define the epidemiology of infection and thus inform future treatment trials.

Underdosing of antiretrovirals in UK and Irish children with HIV as an example of problems in prescribing medicines to children, 1997-2005: cohort study.

OBJECTIVE: To measure the extent of underdosing of antiretroviral drugs in children. DESIGN: Multicentre cohort study. SETTING: Clinical centres in hospitals in the United Kingdom and Ireland in the collaborative HIV paediatric study (CHIPS). PARTICIPANTS: 615 HIV infected children aged 2-12 years receiving antiretrovirals. MAIN OUTCOME MEASURES: Doses relative to weight and height compared with current recommended doses in 2004 European guidelines. RESULTS: The CHIPS cohort of 934 children comprises 80% of diagnosed HIV infected children in the UK and Ireland between January 1997 and March 2005, of which 66% (615) aged 2-12 years were prescribed antiretrovirals. Actual doses standardised to weight or surface area varied widely across individual drugs, antiretroviral class, and calendar time, with children underdosed (prescribed less than 90% of current recommended doses) from 6-62% child time at risk. Three serious issues in prescribing antiretrovirals, which may also be relevant to paediatric prescribing in general, were identified. Firstly, dosing was inadequate before incorrect recommendations at licensing were later revised when important pharmacokinetic results emerged. Secondly, guidelines stating dosage alternatives (by weight/surface area) for the same drug led to different and inconsistent doses. And, thirdly, ongoing growth was not adjusted for. CONCLUSIONS: Largely inadvertently, HIV infected children in the United Kingdom and Ireland have been underdosed with antiretrovirals, highlighting problems applicable throughout paediatric prescribing.