The beta thalassaemia trait in Jamaica.

The objective of this study was to review the prevalence and features of the beta thalassaemia trait in Jamaican populations. Screening of 221,306 newborns over the last 46 years has given an indication of the distribution and prevalence of beta thalassaemia genes, and screening of 16,612 senior school students in Manchester parish, central Jamaica, has provided their haematological features. The prevalence of the beta thalassaemia trait predicted from double heterozygotes was 0.8% of 100,000 babies in Kingston, 0.9% of 121,306 newborns in southwest Jamaica, and 0.9% of school students in Manchester. Mild beta+ thalassaemia variants (-88 C>T, -29 A>G, -90 C>T, polyA T>C) accounted for 75% of Kingston newborns, 76% of newborns in southwest Jamaica, and 89% of Manchester students. Severe beta+ thalassaemia variants were uncommon. Betao thalassaemia variants occurred in 43 patients and resulted from 11 different variants of which the IVSII-849 A>G accounted for 25 (58%) subjects. Red cell indices in IVSII-781 C>G did not differ significantly from HbAA, and this is probably a harmless polymorphism rather than a form of beta+ thalassaemia; the removal of 6 cases in school screening had a minimal effect on the frequency of the beta thalassaemia trait. Red cell indices in the beta+ and betao thalassaemia traits followed established patterns, although both were associated with increased HbF levels. The benign nature of beta+ thalassaemia genes in Jamaica means that cases of sickle cell-beta+ thalassaemia are likely to be overlooked, and important clinical questions such as the role of pneumococcal prophylaxis remain to be answered.

Early splenomegaly and septicaemia in homozygous sickle cell disease: A birth cohort study.

BACKGROUND: Patients with homozygous sickle cell disease (HbSS) and clinical splenomegaly by 6 months of age appeared at greater risk of invasive infections after 5 years of the Jamaican Cohort Study. We determined whether this risk remained significant over a longer study period, using a more rigorous definition of infection and examining the contribution of potential confounders. METHODS: Newborn screening of 100,000 consecutive deliveries during 1973-1981 detected 311 births with HbSS. Age at first clinical splenomegaly was used to categorize 285 of these patients in whom this could be determined: at or before 7 months (early), after 7 months (later), or 'never' palpated despite repeated examinations. Infective episodes were confined to 'first infections confirmed by positive culture'. Using a generalized linear model, the risk of septicaemia was assessed in each group, after adjusting for potential confounders. RESULTS: Of 93 'first infections', 42 occurred in 105 subjects in the 'early' group, 49 in 157 subjects in the 'later' group, and two in 23 subjects in the 'never' group; the observed to expected ratio of 1.42, 0.90 and 0.22 was highly significant (p = .003). Assessed as risk ratios, 'early' splenomegaly had a significantly higher risk ratio (RR) for septicaemia (RR = 7.4, confidence interval [CI]: 1.1-50.7, p < .05) when compared to the 'never' group adjusting for vaccine exposure and foetal haemoglobin concentration. The most common organisms were Streptococcus pneumoniae, Salmonella species, Haemophilus influenzae and Staphylococcus aureus. CONCLUSION: Early clinical splenomegaly in HbSS remains a predictor of septicaemia, defining a group that may require closer monitoring.

The haematology of Jamaicans: red cell indices in HbAA, HbAS, HbAC, and HbA-HPFH genotypes.

Based in the parish of Manchester in central Jamaica, the Manchester Project offered free detection of haemoglobin genotype to senior classes in 15 secondary schools between 2008 and 2013. Restricting the database to 15,103 students aged 15.0-19.9 years provided an opportunity to examine the red cell characteristics of the different haemoglobin genotypes, including normal (HbAA) in 85.0%, the sickle cell trait (HbAS) in 9.7%, HbC trait (HbAC) in 3.5% and hereditary persistence of foetal haemoglobin (HbA-HPFH) in 0.4%. Compared to the normal HbAA phenotype, HbAS had significantly increased mean cell haemoglobin concentration (MCHC), red cell count (RBC), and red cell distribution width (RDW) and decreased mean cell volume (MCV) and mean cell haemoglobin (MCH), these differences being even more marked in HbAC. Compared to HbAA, the HbA-HPFH had significantly increased RDW, but there were no consistent differences in other red cell indices, and there were no significant differences in haematological indices between the two common deletion HPFH variants, HPFH-1 and HPFH-2. Although these changes are unlikely to be clinically significant, they contribute to an understanding of the haematological spectrum of the common haemoglobin genotypes in peoples of African origin.

Pregnancy outcome in homozygous sickle cell disease: observations from the Jamaican Birth Cohort.

OBJECTIVE: To document pregnancy outcome in homozygous sickle cell (SS) disease and in age-matched controls with a normal haemoglobin genotype followed from birth for up to 45 years. METHODS: A total of 100 000 consecutive non-operative deliveries screened for sickle cell disease at the main Government maternity hospital in Kingston, Jamaica between 1973 and 1981 detected 311 (149 female) babies with SS disease who were matched by age and gender with 250 (129 female) controls with an AA haemoglobin phenotype. These individuals have been followed from birth with prospective assessment of menarche and detailed documentation of all pregnancies. RESULTS: There were 177 pregnancies in 71 SS patients and 226 pregnancies in 74 AA controls. Mothers with SS disease had more spontaneous abortions (adjusted relative risk [aRR] 3.2, 95% CI 1.6-6.1), fewer live births (aRR 0.7, 95% CI 0.6-0.9) and their offspring were more likely to have a gestational age <37 weeks (aRR 2.1, 95% CI 1.1-3.7) and low birthweight <2.5 kg (aRR 3.0, 95% CI 1.6-5.3). They were more prone to acute chest syndrome (aRR 13.7, 95% CI 4.1-45.5), urinary tract infection (aRR 12.8, 95% CI 1.3-125.9), pre-eclampsia/eclampsia (aRR 3.1, 95% CI 1.1-8.8), retained placenta (aRR 10.1, 95% CI 1.1-90.3), sepsis (Fisher's Exact test 0.04) and pregnancy-related deaths (Fisher's Exact test 0.02). Four of five deaths were attributable to acute chest syndrome. There was no genotypic difference in pregnancy-induced hypertension or postpartum haemorrhage. CONCLUSION: Pregnancy in SS disease carries risks for both mother and child. The variable characteristics of pregnancy-related deaths complicate their prevention. TWEETABLE ABSTRACT: Pregnancy in SS disease compared with controls showed increased abortions and stillbirths, fewer live births and maternal deaths in 7% patients.

Voluntary premarital screening to prevent sickle cell disease in Jamaica: does it work?

To determine whether identifying haemoglobin genotype, and providing education and counselling to senior school students will influence their choice of partner and reduce the frequency of births with sickle cell disease. The Manchester Project provided free voluntary blood tests to determine haemoglobin genotype to the fifth and sixth forms (grades 11-13), median age of 16.7 years, of all 15 secondary schools in the parish of Manchester in south central Jamaica. A total of 16,636 students complied, and counselling was offered to carriers of abnormal genes over 6 years (2008-2013). The genotypes of their offspring were determined by newborn screening of 66,892 deliveries in 12 regional hospitals over 8 years (2008-2015). The study focused on the genotypes of live deliveries to female students with the four most common haemoglobin genotypes: 7905 with an AA genotype, 898 with the sickle cell trait, 326 with the HbC trait and 78 with the beta thalassaemia trait. A total of 2442 live deliveries were identified by the end of 2015 in mothers screened at school. Eleven babies had clinically significant genotypes, and the prevalence of SS and SC disease did not differ from that predicted by random mating. First pregnancy was not delayed in AS or AC mothers. There was no evidence that knowledge of maternal haemoglobin genotype influenced choice of partner. On an interview, mothers of affected babies correctly recalled their genotype, but either did not discuss this with their partners or the latter refused to be tested. Subjects delaying child bearing for tertiary education would be largely excluded from the present study of first pregnancies and may make greater use of this information. Future options are a greater role for prenatal diagnosis.

Newborn screening for sickle cell disease in Jamaica: logistics and experience with umbilical cord samples.

The study aims to describe the logistics and results of a programme for newborn screening for sickle cell disease based on samples from the umbilical cord. Samples were dried on Guthrie cards and analysed by high pressure liquid chromatography. All suspected clinically significant abnormal genotypes were confirmed by age 4-6 weeks with family studies and then recruited to local sickle cell clinics. The programme has screened 66,833 samples with the sickle cell trait in 9.8 % and the HbC trait in 3.8 %. Sickle cell syndromes occurred in 407 babies (204 SS, 148 SC, 35 Sbeta+ thalassaemia, 6 Sbetao thalassaemia, 6 sickle cell-variants, 8 sickle cell-hereditary persistence of fetal haemoglobin) and HbC syndromes in 42 (22 CC, 14 Cbeta+ thalassaemia, 1 Cbetao thalassaemia, 5 HbC- hereditary persistence of fetal haemoglobin). Focusing on the year 2015, screening was performed in 15,408, compliance with sample collection was 98.1 %, and maternal contamination occurred in 335 (2.6 %) but in only 0.05 % did diagnostic confusion require patient recall and further tests. This model of newborn screening for sickle cell disease is accurate, robust and economic. It is hoped that it may be helpful for other societies with high prevalence of abnormal haemoglobins and limited resources, who are planning to embark on newborn screening for sickle cell disease.

The Chhattisgarh state screening programme for the sickle cell gene: a cost-effective approach to a public health problem.

In India, the Chhattisgarh State screening programme for sickle haemoglobin focuses on children aged 3-15 years and has screened over 1,050,440 subjects over the last 6 years. Commencing in the District around the capital Raipur, this programme has now completed screening in 7 of the 27 Districts of Chhattisgarh State. Screening is initially performed by solubility tests on fingerprick samples in the field and those with positive tests have venipunctures for haemoglobin electrophoresis. The frequency of the sickle cell trait was 9.64 % and of the SS phenotype 0.29 % with only two Districts in Hardy-Weinberg equilibrium, most Districts showing an excess of the SS 'phenotype' most readily explained by symptomatic selection. The estimated costs were US$0.28 (solubility tests alone) and US$0.60 (haemoglobin electrophoresis). Of the social groupings commonly used in India, the OBC's (other backward classes) had the highest frequencies of the sickle cell gene mutations, followed by the Scheduled Tribes and the Scheduled Castes. The objectives of the programme were the detection of sickle cell disease for prospective clinical management and of the sickle cell trait for purposes of genetic counselling. The former objective is being met for diagnosis although the success of referral to clinic services requires audit. The objective of genetic counselling is compromised by the failure of the screening test to detect other genes of potential clinical significance such as HbD Punjab and the beta thalassaemia trait. Despite these exceptions, the detection of HbS appears relatively robust and could be another condition factored into the traditions of partner selection amongst the underprivileged communities of this state. Overall, the Chhattisgarh programme seeks to address the daunting challenges of large populations carrying the sickle cell gene and maybe a useful model for elsewhere.

Newborn Screening for Sickle Cell Disease: Jamaican Experience.

OBJECTIVES: To review the history of newborn screening for sickle cell disease with especial reference to Jamaica. METHODS: A summary was done of the history, the development of associated laboratory technology and the implementation of newborn screening for sickle cell disease in Jamaica. RESULTS: Screening was initiated at Victoria Jubilee Hospital, Kingston from 1973-1981, reactivated in 1995 and extended to the University Hospital of the West Indies in 1997 and to Spanish Town Hospital in 1998. From August 2008, there was a progressive recruitment of 12 hospitals in the south and west of Jamaica which has raised the frequency of islandwide newborn coverage from 25% in 1973 to 81%. The results of this extended programme in southwest Jamaica are presented. Dried blood spots collected from the umbilical cord proved stable, cheap and efficient; mean sample collection rates were 98%, maternal contamination occurred in < 1% and caused diagnostic confusion in < 0.1%. By March 31, 2015, a total of 54 566 births have been screened, detecting 161 with homozygous sickle cell (SS) disease, 125 with sickle cell-haemoglobin C (SC) disease and 36 with sickle cell-beta thalassaemia. Of the 327 babies with clinically significant sickle cell syndromes, all except five who died within seven days of birth were confirmed by four to six weeks and recruited to local sickle cell clinics. CONCLUSION: Early detection of sickle cell disease and recruitment to clinics is known to reduce its morbidity and mortality. The methods currently detailed provide an effective and economic model of newborn screening which may be of value elsewhere.

Jamaica, the Caribbean and sickle cell disease.

The development of research interests in sickle cell disease has been traced from the first recorded case, the founding of the University Hospital of the West Indies and the Jamaican Sickle Cell Unit with its influence on clinical practice in this disease worldwide.

Homozygous sickle cell disease in Uganda and Jamaica a comparison of Bantu and Benin haplotypes.

OBJECTIVE: To compare the haematological and clinical features of homozygous sickle cell (SS) disease in Bantu and Benin haplotypes in a cross-sectional study of 115 Ugandan patients attending the Sickle Cell Clinic at Mulago Hospital, Kampala, Uganda, with 311 patients in the Jamaican Cohort Study METHODS: This involved comparison of clinical features and haematology with special reference to genetic determinants of severity including fetal haemoglobin levels, beta-globin haplotype and alpha thalassaemia status. RESULTS: The Bantu haplotype accounted for 94% of HbS chromosomes in Ugandan patients and the Benin haplotype for 76% of HbS chromosomes in Jamaica. Ugandan patients were marginally more likely to have alpha thalassaemia, had similar total haemoglobin and fetal haemoglobin levels but had higher reticulocyte counts and total bilirubin levels consistent with greater haemolysis. Ugandan patients had less leg ulceration and priapism, but the mode of clinical presentation, prevalence of dactylitis, features of bone pain and degree of delay in sexual development, assessed by menarche, were similar in the groups. In Ugandan patients, a history of anaemic episodes was common but these were poorly documented. CONCLUSION: The haematological and clinical features of the Bantu haplotype in Uganda were broadly similar to the Benin haplotype in Jamaica except for less leg ulceration and priapism and possibly greater haemolysis among Ugandan subjects. Anaemic episodes in Uganda were treated empirically by transfusion often without a clear diagnosis; better documentation including reticulocyte counts and observations on spleen size is necessary to evolve appropriate models of care.

Perinatal factors in students admitted to the University of the West Indies data from the Jamaican Perinatal Study.

OBJECTIVE: To compare perinatal and social factors in students admitted to The University of the West Indies (UWI), Kingston, Jamaica, at age 18 years with those in the rest of the Jamaican Perinatal Cohort. METHOD: The Jamaican Perinatal Survey recorded demographic and perinatal details in 10 527 or 97% of births in Jamaica in September and October 1986. Eighteen years later 140 of these were admitted to the UWI in Kingston, Jamaica. The perinatal features of these UWI students have been compared with the rest of the Perinatal Survey Cohort. RESULTS: Mothers of UWI students were older (p < 0.001), more likely to be married at the time of birth (p < 0.001), had earlier and more complete antenatal care (p < 0.05) and greater educational achievement at time of pregnancy (p < 0.001). These mothers of UWI students were also more likely to have diabetes (p < 0.01), operative deliveries (p < 0.01) and to attend private hospitals (p < 0.01). The UWI students had fewer siblings by their mothers (p < 0.05), were less likely to be low birthweight babies (p = 0.035) and more likely to be full-term (37-42 weeks) than lower gestational age (p = 0.005). Differences in Apgar scores did not reach statistical significance. CONCLUSIONS: The students of the University of the West Indies were more likely to come from smaller families with features indicative of a better quality of life. They were also of higher birthweight and tended to be full-term. The lack of association of Apgar scores with educational attainment is noteworthy.

The changing face of homozygous sickle cell disease: 102 patients over 60 years.

Earlier reports on homozygous sickle cell (SS) disease have been biased by severely affected cases. The Jamaican clinic which seeks to avoid such bias has 102 patients surviving beyond 60 years. The objective of this study was to examine the features of elderly cases and assess factors determining survival and the behaviour of this disease with advancing age. A retrospective review of all cases and prospective assessment in survivors was conducted at The Sickle Cell Clinic at the University of the West Indies, Kingston, Jamaica previously operated by the MRC Laboratories. All patients with SS disease born prior to December 31, 1943 who would, by January 2004, have passed their 60th birthday were traced and their current status ascertained. The molecular and clinical features were assessed and observations on the clinical behaviour of the disease and of haematology and biochemistry are presented. Of the 102 patients, 58 had died, four had emigrated and 40 were alive, resident in Jamaica and aged 60-87 years. Survival was associated with female gender and higher foetal haemoglobin but not with alpha-thalassaemia or beta-globin haplotype. A tendency to familial clustering among elderly survivors did not reach statistical significance. Painful crises ameliorated with age and there was a benign course in pregnancy. Mean haemoglobin levels fell with age and were generally associated with rising creatinine levels indicating the importance of renal failure. Elderly survivors present some features of intrinsic mildness but also manifest age-related amelioration of painful crises and falling haemoglobin levels from progressive renal damage.

Inhaled nitric oxide for acute chest syndrome in people with sickle cell disease.

BACKGROUND: Acute chest syndrome has been defined as a new infiltrate visible on chest radiograph associated with one or more symptoms, such as fever, cough, sputum production, tachypnea, dyspnea, or new-onset hypoxia. Symptoms and complications of this syndrome, whether of infectious or non-infectious origin, vary quite widely in people with sickle cell disease. Lung infection tends to predominate in children, whilst infarction appears more common in adults. However, these are often interrelated and may occur concurrently. The differences in clinical course and severity are suggestive of multiple causes for acute chest syndrome. Successful treatment depends principally on high-quality supportive care. The syndrome and its treatment have been extensively studied, but the response to antibiotics, anticoagulants, and other conventional therapies remains disappointing. The potential of inhaled nitric oxide as a treatment option has more recently provoked considerable interest. Nitric oxide appears to play a major role in both the regulation of vascular muscle tone at the cellular level and in platelet aggregation (clumping). Much of the pathophysiology of sickle cell disease is consistent with a mechanism of nitric oxide depletion and although there has been extensive research on the pathophysiology of acute chest syndrome, the possible therapeutic role of inhaled nitric oxide for acute chest syndrome in sickle cell disease is still to be determined. OBJECTIVES: To assess the effectiveness of inhaled nitric oxide for treating acute chest syndrome by comparing improvement in symptoms and clinical outcomes against standard care. SEARCH STRATEGY: We searched The Group's Haemoglobinopathies Trials Register, which comprises references identified from comprehensive electronic database searches and handsearching of relevant journals and abstract books of conference proceedings. In July 2007 the following clinical trials registers were searched: ClinicalTrials.gov (www.clinicaltrials.gov/); the WHO International Clinical Trials Registry Platform (www.who.int/trialsearch/); Current Controlled Trials (www.controlled-trials.com/) and CLINICALTRIALS.COM (www.clinicaltrials.com/). Most recent search of the Trials Register: November 2007. SELECTION CRITERIA: All randomised or quasi-randomised controlled trials of people with sickle cell disease suffering from acute chest syndrome, comparing the use of inhaled nitric oxide to placebo or standard care for any single or multiple treatment and over any time period. DATA COLLECTION AND ANALYSIS: No studies identified were eligible for inclusion. MAIN RESULTS: No studies identified were eligible for inclusion. AUTHORS' CONCLUSIONS: There is a need for well-designed, adequately-powered randomised controlled trial to assess the benefits and risks of this form of treatment as an adjunct to established therapies.

Bacteraemia in homozygous sickle cell disease in Africa: is pneumococcal prophylaxis justified?

BACKGROUND: The high frequency of Streptococcus pneumoniae as a cause of bacteraemia in homozygous sickle cell (SS) disease and its effective prevention has led to the routine use of pneumococcal prophylaxis in developed countries. The reported infrequency of this organism as a cause of bacteraemia in SS disease in Africa raises questions on the epidemiology of bacterial infection and on the need for pneumococcal prophylaxis in that continent. METHODS: A study of blood cultures in 155 Ugandan children (165 episodes) with SS disease and axillary temperatures of > or =38 degrees C, attending the University Teaching Hospital in Kampala (Uganda, East Africa). RESULTS: Positive blood cultures, obtained in 47/165 episodes, showed Staphylococcus aureus in 28 (60%) samples, Haemophilus influenzae in 9 (19%), Staphylococcus epidermidis in 4 (9%), and single cases of Streptococcus viridans, Escherichia coli and an unidentified Gram negative rod. Streptococcus pneumoniae was identified in only 3 (6%) episode. CONCLUSION: The infrequent isolation of Streptococcus pneumoniae from febrile children with SS disease in this study and in four other studies from Nigeria raises questions on a different spectrum of bacterial causes for bacteraemia in malarial areas. There are several possible explanations for this finding, but the data cast sufficient doubt on the case for pneumococcal prophylaxis for a controlled trial on its effectiveness in that environment to seem justified. These data are necessary to determine its role in African children and to provide the evidence base for healthcare authorities in equatorial Africa.

Growth curves for normal Jamaican neonates / Curvas de crecimiento en los neonatos jamaicanos normales

The aim of this study was to provide standards for the assessment of birthweight, head circumference and crown-heel length for normal, singleton newborns of predominantly West African descent. Data were collected for 10 482 or 94of all recorded births in Jamaica during the two-month period September 1 to October 31, 1986. After editing procedures, data were available for 6178 (birthweight), 5975 (head circumference), and 5990 (crown-heel length). The data presented in tables and growth curves include birthweight, head circumference and crown-heel length for males and females separately, for gestational ages 30-43 weeks. Data sets from the University Hospital of the West Indies in 1990 and 1999 were used to explore the possibility of secular change over the period 1986-1999. In conclusion, these ethnic and gender-specific growth curves are based on the most extensive dataset currently available in Jamaica for babies of West African descent.

Growth curves for normal Jamaican neonates.

The aim of this study was to provide standards for the assessment of birthweight, head circumference and crown-heel length for normal, singleton newborns of predominantly West African descent. Data were collected for 10 482 or 94% of all recorded births in Jamaica during the two-month period September 1 to October 31, 1986. After editing procedures, data were available for 6178 (birthweight), 5975 (head circumference), and 5990 (crown-heel length). The data presented in tables and growth curves include birthweight, head circumference and crown-heel length for males and females separately, for gestational ages 30-43 weeks. Data sets from the University Hospital of the West Indies in 1990 and 1999 were used to explore the possibility of secular change over the period 1986-1999. In conclusion, these ethnic and gender-specific growth curves are based on the most extensive dataset currently available in Jamaica for babies of West African descent.

Phenotype/genotype relationships in sickle cell disease: a pilot twin study.

The roles of genetic and non-genetic factors in the haematology, growth and clinical features of sickle cell disease have been studied in nine identical twin pairs (six homozygous sickle cell disease, three sickle cell-haemoglobin C disease). A comparison group of 350 age-gender matched sibling pairs, selected to have an age difference of <5 years, was used for assessing the concordance of numerical data. Attained height, weight at attained height, fetal haemoglobin, total haemoglobin, mean cell volume, mean cell haemoglobin and total bilirubin levels showed significantly greater correlation in identical twins than in siblings. Twins showed similarities in the prevalence and degree of splenomegaly, susceptibility to priapism, and in onset of menarche, but other clinical complications were discordant in prevalence and severity. These findings suggest that physical growth and many haematological characteristics are subject to genetic influences, but that non-genetic factors contribute to the variance in disease manifestations.

Sickle haemoglobin and haemoglobin Stanleyville II: possible confusion with sickle cell-haemoglobin C disease.

OBJECTIVES: To bring to the attention of East African practitioners, the characteristics of Hb Stanleyville II, its interaction with HbS, and the resemblance of the double heterozygote to sickle cell-haemoglobin C (SC) disease. DATA SOURCES: A prospective study of 100 patients with Sickle Cell (SS) disease in the steady state attending the sickle cell Clinic at Mulago Hospital, Kampala, Uganda. STUDY SELECTION: Out of 100 patients with SS disease, two were also heterozygous for an alpha chain variant identified as Hb Stanleyville II. CONCLUSIONS: In association with HbS, Hb Stanleyville II produces a hybrid haemoglobin band which on alkaline haemoglobin electrophoresis, travels in the position of HbC. Such cases may cause confusion with sickle cell-haemoglobin C (SC) disease. The index cases in both families had associated alpha thalassaemia but from this small group, no conclusions may be drawn on the haematological or clinical significance of the interaction of Hb Stanleyville II with SS disease.

Sickle cell disease in Uganda: a time for action.

OBJECTIVES: To draw attention to the extent of homozygous sickle cell (SS) disease as a public health problem in Uganda where a mean 20% frequency of the sickle cell trait implies that 25,000 babies with SS disease are born each year. To highlight the dangers of applying interventions developed in non-malarial areas to regions where malaria may change the natural history and outcome of sickle cell disease. DATA SOURCES: The published literature from Africa and from the US and Caribbean in populations of African ancestry. STUDY SELECTION: The world literature especially, that derived from the US, Caribbean, and equatorial Africa. DATA EXTRACTION AND SYNTHESIS: In non-malarial areas, simple interventions applied early in life have significantly improved survival and the quality of life. Two well documented interventions are pneumococcal prophylaxis and the early parental diagnosis of acute splenic sequestration. The available literature from Africa suggests that neither of these may be appropriate in malarial areas. CONCLUSIONS: Manifestations of SS disease differ in malarial areas and it is questionable whether interventions developed in non-malarial areas apply. There is an urgent need to document the causes of death so that locally appropriate interventions may be developed to improve survival. Equally urgent is the need to define the pattern of clinical problems so that models of care may be evolved for use in malarial areas. Without this knowledge, health care planners will not have the information necessary to develop strategies and limited resources may be inappropriately deployed.