Grndma: Initial reports from an adult sickle cell registry in Malawi Free

Sickle Cell Disease (SCD) is the most common monogenic disorder in the world. It is caused by a mutation in the β-globin subunit of adult hemoglobin. An estimated 300,000 affected infants are born annually worldwide, 75% of whom reside in sub-Saharan Africa (SSA). Between 50%-90% of affected infants in SSA die before their fifth birthday. However, significant progress has been made to improve access to comprehensive SCD care in SSA in recent years. Hydroxyurea (HU), which is a disease-modifying drug, has brought about a significant decrease in both morbidity and mortality in screened children. Malawi's successful universal HU policy has resulted in increased survival into adulthood in those children who have been screened for SCD in early childhood. The majority of adult SCD research has been conducted in high-resource settings. The need for studies of the full spectrum of SCD-related complications experienced by adults in SSA is substantial, since this population will, with wider adoption of screening and treatment, continue to expand in low-resource settings over the coming decades.

The Globin Regional Data and Discovery (GRNDaD) registry is a multisite prospective registry developed in the US by providers caring for children and adults with SCD. Here, we modeled a local-site patient registry in Malawi, using similar data fields, in the Globin Regional Data, Malawi (GRNDMA), which aims to describe disease characteristics and quality of life among adults attending the SCD clinic at the tertiary level Kamuzu Central Hospital (KCH) in Lilongwe, Malawi. Interrogated fields include clinical history, physical examination, laboratory measures, and Patient Reported Outcomes Measurement Information System (PROMIS) survey data. Adult SCD patients were recruited during routine clinic visits in the Adult Hematology clinic at KCH, and this study is ongoing.

To date, we have recruited 138 participants with a median age of 21 [range 18.0, 25.0], 37% of whom have been hospitalized >ten times during their life, 35% of whom have been transfused >three times total, and all of whom have SS or SBeta0. The mean hemoglobin is 8.4 g/dL (standard deviation, SD, 1.7), and the mean white cell count is 10.4 x 109/L (SD 4.7). The mean systolic BP (SBP) was 117mm/Hg (12.1) with a range of 87-154. Mean creatinine was 0.6 mg/dL (SD 0.3). 13.8% (N=19) of our adult patients had proteinuria on dipstick; of these, ten had 1+ proteinuria and three had 3+ proteinuria. The median length of HU use was 5.2 years [range 20 days, 18.5 years]. Using bivariant analyses, proteinuria associated with age (p=0.043) and inversely with hemoglobin (p=0.026). PROMIS data indicated that 5.1% of participants reported feeling depressed “sometimes,” while 2.2% report feeling depressed “often.”

Conclusion: We describe a Malawian young Adult SCD population, all of whom have received universal access to hydroxyurea in the pediatric clinic at KCH. The supply of hydroxyurea is less stable in the adult clinic, and dosing can be erratic. Some of these young adults already have significant kidney disease with proteinuria detected in >10%. In comparison, Aloni et al (2014) found proteinuria in 6.2% in a cohort in Democratic Republic of Congo (DRC). Although this cohort was much younger, it suggests that longer survival and/or modifying genetic factors may play a role in the development of proteinuria. We will monitor renal function carefully going forward, compare our data with an age-matched control from an American cohort (GRNDaD), and will focus on improving blood pressure control. Unexpectedly, the qualitative PROMIS studies showed fewer mental health challenges in this adult population than our informal interviews with patients had suggested. Our own experience in an American population (Little unpublished) had suggested a possible under-reporting of mental health challenges in newly engaged clinics, until a clinical rapport has been established. We will continue longitudinal collection of patient-reported outcomes through the GRNDMa registry and assess changes as provider care stabilizes. The GRNDMa registry has helped us to identify areas of clinical concern for adults in SSA who are living with SCD. Further prospective data collection in SSA will help us to better understand evolving health needs while guiding quality improvement and evidence-based interventions for this enlarging at-risk population.