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Background: Human parechovirus particularly genotype 3 (HPeV3) is an emerging infection affecting predominantly young infants. The potential for neurologic sequelae in a vulnerable subset is increasingly apparent. A review of 2 epidemics of human parechovirus (HpeV) infection in 2013 and in 2015 in Queensland, Australia, was undertaken, with an emphasis on identifying adverse neurodevelopmental outcome. Methods: All hospitalized cases with laboratory-confirmed HPeV infection between October 2013 June 2016 were identified. Clinical, demographic, laboratory and imaging data were collected and correlated with reported developmental outcome. Results: Laboratory-confirmed HPeV infections were identified in 202 patients across 25 hospitals; 86.6% (n = 175) were younger than 3 months 16.3% (n = 33) received intensive care admission. Of 142 cerebrospinal fluid samples which were HPeV polymerase chain reaction positive, all 89 isolates successfully genotyped were HPeV3. Clinical information was available for 145 children; 53.1% (n = 77) had follow-up from a pediatrician, of whom 14% (n = 11) had neurodevelopmental sequelae, ranging from hypotonia and gross motor delay to spastic quadriplegic cerebral palsy and cortical visual impairment. Of 15 children with initially abnormal brain magnetic resonance imaging, 47% (n = 7) had neurodevelopmental concerns, the remainder had normal development at follow-up between 6 and 15 months of age. Conclusions: This is the largest cohort of HPeV3 cases with clinical data and pediatrician-assessed neurodevelopmental follow-up to date. Developmental concerns were identified in 11 children at early follow-up. Abnormal magnetic resonance imaging during acute infection did not specifically predict poor neurodevelopmental in short-term follow-up. Continued follow-up of infants and further imaging correlation is needed to explore predictors of long-term morbidity.

Background Bedaquiline improves treatment outcomes in patients with rifampin-resistant TB (RR-TB) but prolongs the QT-interval and carries a black-box warning by the U.S. Food and Drug Administration. The World Health Organization recommends that all patients with RR-TB receive a regimen containing bedaquiline, yet a phase 3 clinical trial demonstrating its cardiac safety has not been published. Methods We conducted an observational cohort study of RR-TB patients from 3 provinces in South Africa who received regimens containing bedaquiline. We performed rigorous cardiac monitoring, including electrocardiograms (ECGs) performed in triplicate at four time points during bedaquiline therapy. Participants were followed until the end of therapy or 24 months. Outcomes included final tuberculosis treatment outcome and QT-prolongation, defined as any QTcF>500 ms or an absolute change from baseline (△ QTcF) >60 ms. Results We enrolled 195 eligible participants, of whom 40% had extensively drug-resistant (XDR) TB. Most participants (97%) received concurrent clofazimine. 74% of participants were cured or successfully completed treatment, and outcomes did not differ by HIV status. QTcF continued to increase throughout bedaquiline therapy, with a mean increase of 23.7 (SD 22.7) ms from baseline to month 6. Four participants experienced a QTcF>500 ms and 19 experienced a △QTcF>60 ms. Older age was independently associated with QT-prolongation. QT-prolongation was neither more common nor severe in participants receiving concurrent lopinavir-ritonavir. Conclusions Severe QT-prolongation was uncommon and did not require permanent discontinuation of either bedaquiline or clofazimine. Close QT-monitoring may be advisable in older patients.

Aim: The human parechovirus (HPeV) has emerged as a pathogen causing sepsis-like presentations in young infants, but there is a lack of data on HPeV presentations requiring intensive care support. We aimed to characterise the clinical presentation, disease severity, management and outcome of a population-based cohort of children with microbiologically confirmed HPeV infection requiring admission to paediatric intensive care units (PICUs) in Queensland, Australia during a recent outbreak. Methods: This was a multicentre retrospective study of children admitted to PICU between 1 January 2015 and 31 December 2016 with confirmed HPeV infection. Results: Thirty infants (median age 20 days) with HPeV genotype 3 were admitted to PICU, representing 16% of all children with HPeV admitted to hospital and 6.4% of non-elective PICU admissions in children <1 year of age. Children requiring PICU admission were younger than children admitted to hospital (P = 0.001). Apnoea, haemodynamic instability with tachycardia and seizures represented the main reasons for PICU admission. Eleven children (37%) required mechanical ventilation for a median duration of 62 h, 22 (73%) received fluid boluses and 7 (23%) were treated with vasoactive agents for a median duration of 53 h. Median length of stay was 2.62 days. A total of 24 children (80%) fulfilled sepsis criteria, 14 (47%) severe sepsis and 7 (23%) septic shock criteria. Eight (27%) had abnormal brain magnetic resonance imaging. No patient died. Conclusions: We confirm that HPeV infection is an important cause of sepsis-like syndrome in infants with substantial associated morbidity. Optimal management and long-term outcomes require further investigation.