Heather J. Zar (South Africa)
Red Cross Children's Hospital Department of Paediatrics and Child HealthAuthor Of 2 Presentations
POOLED EFFICACY OF NIRSEVIMAB AGAINST RSV LOWER RESPIRATORY TRACT INFECTION IN PRETERM AND TERM INFANTS
Abstract
Backgrounds:
Nirsevimab reduced medically attended (MA) respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) incidence in two double-blind, placebo-controlled studies (Phase IIb [NCT02878330]: healthy very and moderately preterm infants ≥29 to <35 weeks gestational age [wkGA], efficacy 70.1%; Phase III: MELODY [NCT03979313], healthy term and late preterm infants ≥35 wkGA, efficacy 74.5%). We report a pooled efficacy analysis of nirsevimab in term and preterm infants ≥29 wkGA through Day 151.
Methods
Infants were randomised 2:1 to receive either an intramuscular injection of nirsevimab (<5 kg, 50 mg; ≥5 kg, 100 mg) or placebo, before their first RSV season. Data were pooled from the Phase IIb and MELODY studies for those infants under the optimised dosing regimen (i.e., infants <5 kg at dosing and receiving the 50 mg dose from Phase IIb and all infants in MELODY) to evaluate efficacy (relative risk reduction versus placebo) against varying severities of MA RSV LRTI.
Results:
Overall, 860 infants from Phase IIb (median age at randomisation: 1.60 [range 0.1–6.4] months; female: 47.6%) and 1490 infants from MELODY (median age at randomisation: 2.60 [0.03–11.10] months; female: 48.4%) were included. Demographics were comparable across studies, except for GA and age at randomisation. Nirsevimab had an efficacy of 79.5% against MA RSV LRTI, 77.3% against RSV LRTI hospitalisation and 86.0% against very severe RSV LRTI through Day 151 (Figure). Consistent efficacy was observed across subgroups defined by age at randomisation, sex, ancestry, weight or geographical region and across endpoints of differing disease severity.
Conclusions/Learning Points:
In a pooled analysis of two randomised, placebo-controlled studies, prophylaxis with nirsevimab demonstrated consistent efficacy across severities of RSV LRTI through Day 151.
THE T-CELL ACTIVATION MARKER FOR TB (TAM-TB) IN “RAPAED-TB”- A NEW DIAGNOSTIC TOOL FOR PAEDIATRIC TB
Abstract
Backgrounds:
The diagnosis of tuberculosis (TB) in children remains the biggest hurdle in overcoming the epidemic. The blood-based T cell marker for TB assay (TAM TB) characterizes TB-specific CD4+ T cells based on the expression of surface markers. This approach allows a differentiation between latently and actively infected TB patients.
Methods
RaPaed-TB is a diagnostic validation study conducted in five countries enrolling children suspected of having TB. Alongside a thorough clinical and microbiological workup, a number of new tests are being evaluated including the TAM TB. The latter is a flow-cytometry based assay using a standardized kit which gives a result within 16-24h. Data cleaning is underway; presented data are preliminary and totals differ.
Results:
In total, 974 participants were enrolled with an overall microbiological confirmation rate (PCR/culture) of 24.2% (236/974), sufficient information for clinical case definition was available for 732 children. Overall, more than 890 TAM TBs were performed at enrolment. Using culture as reference standard, early analyses show a modest sensitivity of 60.8% (95%CI 48.8-72.0) and specificity of 83.5% (95%CI 77.0-88.9) in the overall cohort, with superior performance in children <1 year with a sensitivity of 80.0% (95%CI 51.9-95.7) and specificity of 85.0% (95%CI 62.1-96.8). Logistic regression was performed to explore determinants of TAM TB accuracy, generating strong evidence of TST-positivity increasing the odds for true-positivity in reference standard positive children by 5.06 (95%CI 1.83-13.99, p=0.0018). Further analyses are ongoing, and results are to be presented.
Conclusions/Learning Points:
RaPaed-TB is one of the largest TB diagnostic validation studies comparing several new tests ever performed in children. Presented data indicate a promising performance of TAM-TB, especially in the very young children.