Objectives: The aim of this study was to evaluate the existing newborn sickle haemoglobinopathy screening programme in Jamaica. Methods: A retrospective analysis of infants screened during the period 8 November 1995 to 22 July 2006 was performed. Patient data for analyses was restricted to patients with homozygous (Hb SS) sickle cell disease. Published data from the Jamaican Sickle Cell Cohort Study was used to make comparisons with the study sample. Results: The study sample consisted of 435 patients with Hb SS disease. Acute chest syndrome was the most common clinical (non-death) event accounting for ∼50% of all events. Acute splenic sequestration, no longer a significant cause of mortality, was responsible for ∼32% of clinical events. Seven deaths (1.8%) occurred during the study period compared with 17.6% to the same age in the Jamaican Sickle Cell Cohort Study. There was a lower proportion of hospital admissions and episodes of serious illness in the study group compared with controls. Conclusions: Survival estimates for the study sample showed improvement compared with the Jamaican Sickle Cell Cohort Study. This study continues to demonstrate the benefits of, and as such shows support for, newborn screening and early interventions in sickle cell disease. In addition, it highlights some of the areas for continued focus and research development. Although the current system is providing an essential and beneficial service, the study emphasizes the need for newborn screening programmes to be comprehensive care systems to be fully effective.

Chronic transfusion therapy is the treatment of choice for preventing stroke recurrence in children with sickle cell disease (SCD). The majority of children affected by this devastating complication live in the developing world where access to regular blood transfusions may be impractical. Since 2000, in the absence of regular blood supplies, all children at the Sickle Cell Unit who had experienced a first clinical stroke were offered hydroxyurea (HU) as the only intervention to prevent stroke recurrence. Forty‐four children were identified as having experienced a first clinical stroke between January 1, 2000 and September 30, 2009; one died at that presentation. Forty‐three children were therefore followed for 111 person‐years, of whom 10 (23.3%) agreed to start HU. Only one child in the HU group, incidence rate 2/100 person‐years, had clinical stroke recurrence, compared to 20/33 in the non‐HU group, incidence rate 29/100 person‐years (Hazard ratio (HR) 9.4 [95% Confidence interval (CI): 1.3–70.6]; P = 0.03). When the groups were compared, in the non‐HU group, four died (vs. zero), 13 (53% vs. 10%) had moderate–severe physical disability (P = 0.017), and 12 (44% vs. 20%) required special education or were too disabled to attend school. Our data support the role of HU as a useful intervention for prevention of stroke recurrence in SCD when transfusion programs are not available or practical. Am. J. Hematol., 2011. © 2011 Wiley‐Liss, Inc.

Children with sickle cell anemia (SCA) and conditional transcranial Doppler (TCD) ultrasound velocities (170-199 cm/sec) may develop stroke. However, with limited available clinical data, the current standard of care for conditional TCD velocities is observation. The efficacy of hydroxyurea in preventing conversion from conditional to abnormal TCD (≥200 cm/sec), which confers a higher stroke risk, has not been studied prospectively in a randomized trial. Sparing Conversion to Abnormal TCD Elevation (SCATE #NCT01531387) was an NHLBI-funded Phase III multicenter international clinical trial comparing alternative therapy (hydroxyurea) to standard care (observation) to prevent conversion from conditional to abnormal TCD velocity in children with SCA. SCATE enrolled 38 children from the United States, Jamaica, and Brazil [HbSS (36), HbSβ0-thalassemia (1), and HbSD (1), median age 5.4 years (range, 2.7-9.8)]. Due to slow patient accrual and administrative delays, SCATE was terminated early. In an intention-to-treat analysis, the cumulative incidence of abnormal conversion was 9% (95% CI 0 to 35%) in the hydroxyurea arm and 47% (95% CI 6 to 81%) in observation arm at 15 months (p=0.16). In post-hoc analysis according to treatment received, significantly fewer children on hydroxyurea converted to abnormal TCD velocities, compared to observation (0% versus 50%, p=0.02). After a mean of 10.1 months, a significant change in mean TCD velocity was observed with hydroxyurea treatment (−15.5 versus +10.2 cm/sec, p=0.02). No stroke events occurred in either arm. Hydroxyurea reduces TCD velocities in children with SCA and conditional velocities.

Background: It is known that there is significant morbidity associated with urinary tract infection and with renal dysfunction in sickle cell disease (SCD). However, it is not known if there are potential adverse outcomes associated with asymptomatic bacteriuria (ASB) infections in sickle cell disease if left untreated. This study was undertaken to determine the prevalence of ASB, in a cohort of patients with SCD.Methods: This is a cross-sectional study of patients in the Jamaican Sickle Cell Cohort. Aseptically collected mid-stream urine (MSU) samples were obtained from 266 patients for urinalysis, culture and sensitivity analysis. Proteinuria was measured by urine dipsticks. Individuals with abnormal urine culture results had repeat urine culture. Serum creatinine was measured and steady state haematology and uric acid concentrations were obtained from clinical records. This was completed at a primary care health clinic dedicated to sickle cell diseases in Kingston, Jamaica. There were 133 males and 133 females in the sample studied. The mean age (mean ± sd) of participants was 26.6 ± 2.5 years. The main outcome measures were the culture of ≥ 10 5 colony forming units of a urinary tract pathogen per milliliter of urine from a MSU specimen on a single occasion (probable ASB) or on consecutive occasions (confirmed ASB). Results:Of the 266 urines collected, 234 were sterile and 29 had significant bacteriuria yielding a prevalence of probable ASB of 10.9% (29/266). Fourteen patients had confirmed ASB (prevalence 5.3%) of which 13 had pyuria. Controlling for genotype, females were 14.7 times more likely to have confirmed ASB compared to males (95%CI 1.8 to 121.0). The number of recorded visits for symptomatic UTI was increased by a factor of 2.5 (95% CI 1.4 to 4.5, p < 0.005) but serum creatinine, uric acid and haematology values were not different in patients with confirmed ASB compared with those with sterile urine. There was no association with history of gram negative sepsis. Conclusion:ASB is a significant problem in individuals with SCD and may be the source of pathogens in UTI. However, further research is needed to determine the clinical significance of ASB in SCD.

We undertook a cost effectiveness analysis (CEA) of hydroxyurea (HU) in preventing stroke recurrence and/or death. We followed 43 children with sickle cell disease from 2000 to 2009 after having a first clinical stroke, of whom 10 opted for HU therapy. HU use led to decreased stroke recurrence and death without significantly increasing the annual cost of care per patient (J$83,250 vs. J$76,901, P = 0.491). The incremental cost effectiveness ratio (ICER) for prevention of stroke recurrence amounted to J$169,238 (US$1,900), while that for death prevention equalled J$635,843 (US$7,140). HU may be recommended when safe and affordable transfusion therapy is not feasible.

Summary Although there is some evidence that epilepsy is more common in Sickle Cell Disease (SCD), we sought to establish the incidence rates, risk factors for and specific types of seizures in a SCD cohort followed from birth, and how seizure occurrence affects morbidity and mortality. We examined all records of persons in the Jamaica cohort Study of Sickle Cell Disease (JSSCD) clinically identified as having experienced a seizure during their lifetime. At first presentation, seizures were classified as Febrile Convulsion, Acute Symptomatic Seizure or Single Unprovoked Seizure. The seizure classification was revised to include Epilepsy if seizures recurred. Thirty‐eight persons in the JSSCD (N = 543) were identified with seizures. The 5‐year cumulative incidence of febrile convulsions was 2·2%. The incidence rate of epilepsy (all genotypes) was 100/100 000 person‐years, 139/100 000 for the SS genotype. Despite limited availability of diagnostic investigations, clinical seizures were associated with increased all‐cause mortality. Male gender (Odds Ratio [OR]: 4·0[95% confidence interval [CI]; 1·03–20·0]) and dactylitis in childhood (OR: 17·4 [95% CI; 4·82–62·85]) were associated with increased risk of developing epilepsy. Epilepsy in persons with SCD is 2–3 times more common than in non‐sickle populations and is associated with increased all‐cause mortality in all sickle cell genotypes.

This study investigated the association of nutritional and haematological variables with maximum time-averaged mean velocity (TAMV) measured by transcranial Doppler (TCD) velocity and the agreement of classification between two protocols. TCD categories included: normal (<170 cm/s), conditional (170-199 cm/s) and abnormal (≥200 cm/s) based on TAMV in distal internal carotid artery (dICA), middle cerebral artery (MCA), internal carotid bifurcation, anterior and posterior cerebral arteries. Of 358 children with sickle cell anaemia (SCA) examined, the mean age (±standard deviation) was 7·4 ± 2·7 years; 13·1% and 6·7% had conditional and abnormal velocities, respectively. Children with abnormal TCD velocities had higher prevalence of prior stroke (P = 0·006). Increased TAMV was associated with younger age (P = 0·001), lower weight (P = 0·001), height (P = 0·007) and oxygen saturation (P = 0·005). There was no association of TAMV with height-age or body mass index (BMI) z-scores. Adjusting for gender, BMI z-score, age, previous stroke and oxygen saturation, mean corpuscular volume (P = 0·005) and reticulocyte count (P = 0·013) were positively associated with TAMV, while haemoglobin concentration (P = 0·009) was negatively associated. There was good agreement [99%; weighted Kappa 0·98 (95% confidence interval 0·89-1), P = 0·0001] in TCD classification using data from five vessels versus two vessels (dICA and MCA). Haematological variables, rather than nutritional status, may be useful markers that identify high-risk children with SCA.

SUMMARYWe report a case with interesting imaging findings as well as an unfortunate but not unexpected clinical outcome. Our patient, an 8-year-old Jamaican boy of Afro-Caribbean descent with homozygous sickle cell disease, presented with left-sided upper limb weakness. He had a history of recurrent cerebrovascular accidents and transient ischaemic attacks beginning at 4 years of age. MRI revealed old bilateral infarctions and the ivy sign on fluid-attenuated inversion recovery sequences. MR angiography demonstrated numerous collaterals, most apparently arising from the left internal carotid, consistent with moyamoya syndrome. The patient had a full recovery and remained well for almost 2 years when he suffered another stroke. BACKGROUND