Universal Newborn Screening For Sickle Cell Disease In Mozambique

This prospective mixed-methods hybrid effectiveness-implementation feasibility study will evaluate the feasibility and effectiveness of an implementation strategy package designed to improve early diagnosis and care entry for children born with sickle cell disease (SCD) in rural, low-resource settings. The implementation strategy package includes three components: 1) integration of essential products into national supply chain systems, 2) integration of systematic newborn screening using point-of-care-testing into clinical site workflows and 3) linkage of children who screen positive to a PEN-Plus Non-Communicable Disease (NCD) clinic for longitudinal care. Participants will be tracked longitudinally to evaluate protocol adoption over time and clinical outcomes among participating children at 2 years of age.

Primary Objective

• To test if combining three multi-level implementation strategies can facilitate systematic birth diagnosis and timely linkage to evidence-based care interventions for infants with SCD in under-resourced settings.

Secondary Objectives (Micro level):

• To test the clinical effectiveness of implementing the BB-SCD through the three combined implementation strategies to prevent excess mortality of children with SCD under the age of 2 years.
• To evaluate the effectiveness of combining the three implementation strategies to promote care retention among infants with SCD by 2 years of age.

Secondary Objectives (Meso level)

• To evaluate the institutional coverage and health facility staff adoption of the treatment for infants through the combined implementation strategies.
• To evaluate the need for a confirmatory test among positive and negative screening results using POCT.
• To conduct a cost-effectiveness analysis of the combined implementation strategies.

Secondary Objective (Macro level)

• To evaluate the operational effectiveness of integrating the procurement of SCD consumables into national supply chain systems to achieve sustainable availability, effective last mile delivery to relevant clinics and stockout avoidance.

All infants between birth and 6.0 months of age who were screened through the UNIQUE study and tested positive for SCD (HbSS, HbSC, or other form of SCD) or had indeterminate results.

Other: Point-of-care testing (POCT) -Patient participants

Infants between birth and 6.0 months of age who screen negative for SCD (HbAA) through the UNIQUE study or tested positive for sickle cell trait (HbAS).

Other: Point-of-care testing (POCT) - Healthy control participants

Healthcare staff ages ≥18 years working at secondary-level facilities involved in the UNIQUE study.

Other: Context Assessment for Community Health (COACH) survey · Other: Semi-structured interview

Administrative professionals with experience working in or around the national supply chain systems in Mozambique to support procurement, importation, customs clearance, storage, and in-country distribution of medical products.

Other: Semi-structured interview

Administrative professionals with experience working in the national public health system (e.g., Ministry of Health, MISAU) who oversee the delivery of health services to infants in-country, such as neonatal testing and vaccination programs.

Other: Semi-structured interview

Infants will be screened for Sickle Cell Disease using with point-of-care testing (POCT).

Infants will be screened for Sickle Cell Disease using with point-of-care testing (POCT) and prospectively monitored for survival.

The COACH survey will collect quantitative data on eight contextual factors that impact a site's ability to implement evidence-based interventions.

Interview questions will revolve primarily around the current process for SCD screening and care referrals, factors impacting newborn care delivery and screening, and challenges to integrating SCD newborn screening and care referral into standard care delivery.

Time frame: 3 years

Not reported in this registry record.

Time frame: 3 years

Not reported in this registry record.

Time frame: 2 years post-screening and therapy

The primary outcome measure will be 'Alive and in care: Yes or No'.

Time frame: 2 years post-screening and therapy

Not reported in this registry record.

Time frame: 3 years

Not reported in this registry record.

Time frame: 3 years

Not reported in this registry record.

Time frame: 3 years

Investigators will estimate the sensitivity (proportion of diseased subjects that yield a positive test result) and specificity (the proportion of non-diseased subjects that yield a negative test result) of the POCT for detecting SCD compared to the gold standard with basic proportions.

Time frame: 2 to 5 years

The standard formula known as incremental cost-effectiveness ratios (ICERs) will be used. ICER is a summary statistic used in economic evaluations to compare the relative value of different healthcare interventions. It is scored by comparing the resulting cost-per-QALY against a predefined threshold, where lower ICERs indicate better value.

Time frame: 2 to 5 years

The standard formula known as incremental cost-effectiveness ratios (ICERs) will be used. ICER is a summary statistic used in economic evaluations to compare the relative value of different healthcare interventions. It is scored by comparing the resulting cost-per-QALY against a predefined threshold, where lower ICERs indicate better value.

Time frame: 2 to 5 years

The standard formula known as incremental cost-effectiveness ratios (ICERs) will be used. ICER is a summary statistic used in economic evaluations to compare the relative value of different healthcare interventions. It is scored by comparing the resulting cost-per-QALY against a predefined threshold, where lower ICERs indicate better value.

Time frame: 5 years

Not reported in this registry record.

Universal Newborn Screening For Sickle Cell Disease In Mozambique