Objectives Given the fundamental role of newborn bloodspot screening (NBS) to enable prompt diagnosis and optimal clinical management of individuals with sickle cell disease (SCD), we sought to systematically assess enablers and barriers to implementation of NBS programmes for SCD in Africa using established qualitative research methods. Setting Childbirth centres and NBS laboratories from six countries in East, West and Southern Africa. Participants Eight programme leaders involved with establishing and operating NBS programmes for SCD in Angola, Democratic Republic of Congo, Ghana, Liberia, Nigeria and Tanzania. Primary and secondary outcome measures Data obtained through a structured, phased interview approach were analysed using a combination of inductive and deductive codes and used to determine primary themes related to the implementation and sustainability of SCD NBS programmes. Results Four primary themes emerged from the analysis relating to governance (eg, pragmatic considerations when deploying overcommitted clinical staff to perform NBS), technical (eg, design and execution of operational processes), cultural (eg, variability of knowledge and perceptions of community-based staff) and financial (eg, issues that can arise when external funding may effectively preclude government inputs) aspects. Key learnings included perceived factors that contribute to long-term NBS programme sustainability. Conclusions The establishment of enduring NBS programmes is a proven approach to improving the health of populations with SCD. Organising such programmes in Africa is feasible, but initial implementation does not assure sustainability. Our analysis suggests that future programmes should prioritise government partner participation and funding from the earliest stages of programme development.

We previously reported initial clinical results of post-transcriptional gene silencing of BCL11A expression (NCT 03282656) reversing the fetal to adult hemoglobin switch. A goal of this approach is to increase fetal hemoglobin (HbF) expression while coordinately reducing sickle hemoglobin (HbS) expression. The resulting combinatorial effect should prove effective in inhibiting HbS polymerization at lower physiologic oxygen values thereby mitigating disease complications. Here we report results of exploratory single-cell analysis of patients in which BCL11A is targeted molecularly and compare results with cells of patients treated with hydroxyurea (HU), the current standard of care. We use single-cell assays to assess HbF, HbS, oxygen saturation, and hemoglobin polymer content in RBCs for nine gene therapy trial subjects (BCL^shmiR, median HbF% = 27.9) and compare them to 10 HU-treated subjects demonstrating high and comparable levels of HbF (HU High Responders, median HbF% = 27.0). All BCL11A patients achieved the primary endpoint for NCT 03282656, which was defined by an absolute neutrophil count greater than or equal to 0.5 × 10⁹ cells/L for three consecutive days, achieved within 7 weeks following infusion. Flow cytometric assessment of single-RBC HbF and HbS shows fewer RBCs with high HbS% that would be most susceptible to sickling in BCL^shmiR vs. HU High Responders: median 42% of RBCs with HbS%>70% in BCL^shmiR vs. 61% in HU High Responders (p = 0.004). BCL^shmiR subjects also demonstrate more RBCs resistant to HbS polymerization at lower physiologic oxygen tension: median 32% vs. 25% in HU High Responders (p = 0.006). Gene therapy-induced BCL11A down-regulation reverses the fetal-to-adult hemoglobin switch and induces RBCs with higher HbF%, lower HbS%, and greater resistance to deoxygenation-induced polymerization in clinical trial subjects compared with a cohort of highly responsive hydroxyurea-treated subjects.

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In the United States, tonsillectomy is one of the most common surgical procedures in childhood.¹ A review of the Nationwide Inpatient Sample between 2001 and 2010 found a 6.4% overall complication rate in US children and adolescents after tonsillectomy, with hemorrhage being a common complication (1.2%).² Several potential risk factors have been identified, including increasing age,³ hot knife techniques,⁴ and tonsillitis as indication for tonsillectomy with or without adenoidectomy.^3,5

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