Hematopoietic SCT for the Black African and non-Black African variants of sickle cell anemia.

Sickle cell anemia (SCA) remains associated with high risks of morbidity and early death. Allogeneic hematopoietic SCT (HSCT) is the only curative treatment for SCA. We report our experience with transplantation in a group of patients with the non-Black African variant and the Black African variant of SCA. This study included 40 consecutive SCA patients (13 patients with the non-Black African variant and 27 with the Black African variant) who underwent BM transplantation from HLA-identical sibling donors between June 2004 and May 2013, following a myeloablative-conditioning regimen. All patients obtained sustained engraftment. One patient (non-Black African variant) became a stable mixed chimera with 25% donor cells more than 6 years after transplantation. The probabilities of survival, SCA-free survival and TRM at 5 years after transplant were 91%, 91% and 9%, respectively. All surviving patients remained free of any SCA-related events after transplantation. Our results confirm that it is possible to offer a greater than 90% chance of cure to children with SCA. HSCT should be considered the standard of care for who have an HLA-identical donor, before complications result from the sickling of RBC.

Outcome of holistic care in Nigerian patients with sickle cell anaemia.

Holistic care of patients with sickle cell anaemia (HbSS) was carried out in a dedicated support group and clinic in Lagos. This paper examines the outcome of this initiative using mortality, hospital admission and blood transfusion rates from inception in April 1988 to December 1995. Patients with sickle cell disorder and their families were admitted to the Sickle Cell Club and its associated Sickle Cell Clinic. All patients and parents were counselled on recruitment and were regularly followed up within an interactive family friendly environment. Other measures included preventive health and nutritional education, prompt treatment of illness and free supplies of vitamin supplements, malarial prophylactic and other necessary medication. The records of consecutive patients with HbSS were reviewed for this study. Over the study period, the number of subjects increased from 290 in 1988 to 1223 in 1995. The mortality rate fell from 20.6% in 1988 to 0.6% in 1995 (P < 0.0001); the number of hospital admissions fell from 350 (119%) in 1988 to 30 (4%) in 1995 (P < 0.0001); the number of patients transfused with blood fell from 260 (90%) in 1988 to 25 (2%) in 1995 (P < 0.00001). We conclude that the provision of well-organized holistic care can significantly reduce illness and deaths and improve the quality of lives of people living with HbSS in developing countries.

Efficacy of natural honey in the healing of leg ulcers in sickle cell anaemia.

In order to assess the reported efficacy of natural honey in the healing of chronic ulcers, the efficacy of locally applied natural honey was compared to that of Eusol solution in an open trial involving 20 patients with sickle cell anaemia (SS) who were in steady clinical states and had chronic leg ulceration. All patients were admitted to hospital for the 4 week duration of the trial for bed rest, daily aseptic dressings, and weekly measurement of the size of the ulcer. Fifteen patients with a total of 19 leg ulcers were evaluable at the end of the trial. Eleven ulcers were dressed with honey while 8 were dressed with Eusol. No significant differences were found in rates of healing of the ulcers in either treatment groups. This trial does not support the suggestion that natural honey is superior to Eusol in the healing of chronic sickle cell leg ulceration.

Acute sickle cell syndromes in Nigerian adults.

The pattern of acute illness was determined in 102 adolescents and adults with sickle cell anaemia who presented to the emergency unit of a Lagos hospital. The patients had a mean age of 20.5 years (SD 13.1) and a male-female ratio of 1.5. The symptoms included fever (72%), fatigue and weakness (59%), anorexia (59%) and pain (57.5%) while major clinical signs were pallor (100%), jaundice (71%) and hepatomegaly (68%). Sixty-eight per cent of patients had sickle cell crises, including one with hemiplegic stroke, 10% with combined anaemia and pain crises, 33% with anaemia crises only and 23.5% with pain crises only. Sixty-three per cent had infection which was malaria in 24.5%, bacterial in 17% and viral in 6%. Of 16 patients with pyrexia of unknown origin, seven responded to treatment with chloroquine and eight to antibiotics. Infection was detected in 50% of the patients with sickle cell crises. The association between anaemia crises and malaria was significant (P < 0.05). Of the eight deaths, seven (88%) had anaemia crises. In contrast to studies conducted two decades ago in the same hospital, the prevalence of anaemia crises now exceeds that of pain crises and malaria now exceeds that of bacterial infection. Severe symptomatic anaemia (anaemia crisis) was more frequently associated with infection (mostly malaria) than was bone pain crisis. The Girdle pain crisis more frequently resulted in a fatal outcome than the uncomplicated bone pain crisis.

Application of polymerase chain reaction to the prenatal diagnosis of sickle cell anaemia in Nigeria.

Although sickle-cell disease is very common in Nigeria, control by prenatal testing is lacking. The polymerase chain reaction-based technology combined with chorionic villi sampling has enabled us to offer prenatal diagnosis of sickle cell disease to 50 pregnant women who were at risk of bearing children with sickle cell anaemia. DNA was extracted from the villus and subjected to either PCR and restriction enzyme (Dde I) analysis (36 samples) or to PCR-ARMS procedure (12 samples) or to both procedures when the results by the first procedure were equivocal (2 samples). The genotypic distribution was 13AA, 25AS and 11SS. In one case, it was not possible to determine the genotype of the villi by both methods. A post delivery genotype analysis confirms the correctness of prenatal diagnosis in all the 42 subjects that has so far reported. The results clearly demonstrate the usefulness of the PCR method in the prenatal diagnosis of sickle-cell anaemia in this environment.

Initiation of prenatal diagnosis of sickle-cell disorders in Africa.

We introduced prenatal diagnosis of SCD in Nigeria in order to meet a rising demand. Our approach and experience are documented as a guide to others in countries with similar problems. A cost-recovery fee charged only to sustain the service predictably limited access to it. Ultrasound-guided transcervical (TC) or transabdominal (TA) sampling of 124 chorionic villi was done from nine weeks' gestation. All couples carried the sickle trait (AS) and 52 (51 per cent) women had previously had children with sickle-cell anaemia. 72 samples were obtained by the TA and 52 by the TC route. 7.2 per cent miscarried after CVS but the miscarriage rate was significantly higher (p=0.023) after TC CVS (13.5 per cent) than after TA CVS (2.8 per cent) and also higher in the first 62 (11.3 per cent) than after the last 62 CVS (3.2 per cent). DNA analysis of CVS indicated Hb AA in 29 (23.4 per cent), AS in 67 (54 per cent) and SS in 23 (18.5 per cent). No result was obtainable in five subjects for technical reasons. 96 per cent of the women with SS fetuses terminated the pregnancies. The need for a standby source of electricity where supply is unreliable and for providing an equitable service to all couples at risk are highlighted.

The influence of socio-economic status on the severity of sickle cell disease.

The influence of socio-economic status on morbidity was studied in 122 unselected consecutive patients with homozygous sickle cell disease in steady state. They included 65 females and 57 males, divided into three social classes (I, II and III, from highest to lowest). The morbidity indices used were, frequency of bone pain crisis, leg ulceration, growth index and the degree of anaemia as denoted by the mean steady haemoglobin level. It was found that the frequency of bone pain crisis was significantly higher in social class III patients than in social class I and social class II (P < 0.01). Leg ulceration was significantly more common in patients of social class III than in patients of social class I (P < 0.05). There was no correlation between the growth index and social class (r = 0.067, P > 0.05). The mean haemoglobin level was found to fall slightly from the highest to the lowest social class although the differences were not statistically significant. Our findings suggest that socio-economic status has some modifying influence on morbidity in sickle cell disease.

Pernicious anaemia in Africans.

Ten cases of pernicious anaemia seen over a 15-year period (1973-1988) in a Lagos hospital are presented. Their ages ranged from 34 to 67 with a mean of 53.6 years. Females outnumbered males 6 to 4. Complications seen include gastric carcinoma, myelopathy, peripheral neuropathy, skin hyperpigmentation, hair depigmentation and diarrhoea. Reluctance to consider the diagnosis owing to firmly held notions of its rarity and a penchant for empirically treating chronic anaemias with all available haematinics and blood transfusion are probably contributory to its underdiagnosis. The fact that seven of the patients presented were seen in the last three years and three of them in the last one year raises the possibility of an increasing incidence of pernicious anaemia in Africans. The disease may be much less rare in Africans than once believed, and medical education should emphasize its existence and advocate greater care in the management of chronic anaemias.

An analysis of tetanus deaths in Lagos.

Between 1974 and 1984, 418 patients with tetanus, aged 10 years and older, represented 64.8% of all admissions to the intensive care unit of the Lagos University Teaching Hospital. Students accounted for the largest single group with tetanus, which mainly occurred during the dry season. There was a male preponderance (1.4 to 1), but no appreciable sex influence on mortality rates (46.1% for men; 44.6% for women). The mean mortality rate was 45.5%, with the highest mortality occurring in the elderly. Other high risk factors identified were neck and head injuries, post abortal or post partum states, hyperpyrexia, and tachycardia.

Submandibular chronic sialadenitis presenting with alcohol-induced pain.

A 32 year old man with alcohol-induced pain over a right submandibular swelling is described. Excision biopsy of this swelling revealed chronic sialadenitis and the symptoms promptly ceased following this excision. We speculate on the possible pathophysiological mechanism.

Training of counsellors on sickle-cell disorders in Africa.

Falling infant and childhood mortality rates, especially in urban centres, have allowed greater survival of individuals with sickle-cell disorders (SCD), and the need to provide appropriate services has become pressing. The training and employment of counsellors on SCD, shown here to be popular and feasible, seems an essential first step towards the development of a community-based and appropriate policy for coping with SCD in Africa.

A profile of sickle cell disease in Nigeria.

Nigeria has a population of 112 million with an annual growth rate of 3.2%. About 25% of adults throughout the country have the sickle cell trait, AS, while the Hb C trait is largely confined to the Yoruba people of southwestern Nigeria in whom it occurs in about 6%. Other variant hemoglobins including beta thalassemia are rare, but alpha thalassemia occurs in 39% (32% with 3 alpha-globin genes; 7% with 2 alpha-globin genes). Of a total of 5.4 million expected live births in 1988, about 90,000 will have SCD and 1.1 million the trait, AS. The clinical phenotype of sickle cell anemia is severe with manifestations occurring very early in childhood and mean Hb level 7.6 g/dl with HbF 5.9%. A very high infant mortality due to infections occurs especially in rural areas. Gallstones, leg ulcerations, and stroke appear less common than in American sicklers, and aplastic crises have not been described. Poor availability of resources to the public health and welfare sectors and economic inflation are severely curtailing access to appropriate medical and social services. This situation is frustrating to the families of a growing number of surviving patients in urban or middle to upper income groups. Efforts to create more awareness of SCD are paradoxically increasing frustration and stigmatization in the absence of a commensurate improvement of services. Any measures aimed at enhancing the sensitization of health professionals, policy makers, and resource allocators to the pertinent issues in the control of SCD would seem to be at this stage an important step in the right direction.

Chronic leukaemia: an African experience.

One hundred and eighteen patients with chronic leukaemias were seen at the Lagos University Teaching Hospital, Nigeria, between 1964 and 1982. There were 75 patients with chronic granulocytic leukaemia (CGL) and 43 patients with chronic lymphocytic leukaemia (CLL). Although most of them presented with the familiar features of chronic leukaemias, a few features were remarkably different from those reported in some of the Caucasian series. CLL is less common than CGL in contrast to their relative incidence in Caucasians. Our patients generally presented with more massive splenomegaly and more severe anaemia, which could be attributed to late presentation, endemic malaria and possibly increased hypersplenism. The peak-age incidence in our patients with CGL was found in a younger age group (20-40 yr) than in the Caucasian series. When compared with a Caucasian series, our CGL patients on presentation had a significantly higher proportion of immature cells (blasts and promyelocytes) (P less than 0.05), probably reflecting their more delayed presentation. Follow up was generally poor as a result of a high default rate. Survival duration of both leukaemias was generally lower than in Caucasian series and for CGL patients there was a significant negative correlation between survival and spleen size at presentation, while for CLL patients there was a significant association between poor survival duration and high white cell count at presentation.

The hemoglobinopathies and pregnancy in Lagos.

Thirty-four patients with abnormal hemoglobin were studied through 42 pregnancies under one obstetrician. There were 30 patients with sickle cell anemia (HbSS), two with sickle cell hemoglobin C disease (HbSC) and two with homozygous hemoglobin C disease (HbCC). There were 39 live births (including one pair of twins), and four perinatal deaths. The patients with HbSC and HbCC had five uncomplicated pregnancies and deliveries. Of the 36 pregnancies in patients with HbSS one aborted at 12 weeks. Intra-uterine growth retardation (14.3%) and pregnancy-induced hypertension (14.3%) were the most serious pregnancy complications. No patient had more than one crisis. Only one out of the 10 patients transfused needed more than two units of blood throughout pregnancy. The mean gestation at delivery was 37.5 +/- 3.2 (S.D.) weeks. The mean birth weight was 2.7 +/- 0.6 (S.D.) kg. The perinatal mortality was 114.3 per thousand live births and there was one maternal death.

The pattern of leucocyte response to surgical trauma in the African Negro.

The leucocyte response to surgical trauma in the Nigerian Negro is investigated. The surgical operations were graded, according to the degree of anticipated tissue trauma, into minor, intermediate and major, in 66 patients (27 males and 39 females) who had elective surgical operations with no sign of infection. The peripheral blood total and differential leucocyte counts were determined pre-operatively and at 2 h, 24 h, and 7 days postoperatively. A highly significant increase (P less than 0.001) in the total leucocyte, polymorphonuclear leucocyte (PMN) and stab cell counts occurred 2 h and 24 h after major surgery. These changes persisted for 7 days after major surgery except for the stab cell count which was by then no longer significantly raised. Similarly, highly significant increases occurred in the total and PMN counts 2 h and 24 h after intermediate surgery. The increases were not significant by the 7th postoperative day. There was a decrease in the lymphocyte counts after major surgery which was not significant at 2 h but was just significant (P less than 0.05) 24 h postoperatively. There was a return to the pre-operative level by the 7th postoperative day. There were no significant changes in the leucocyte counts after minor surgery or in the monocyte, eosinophil and basophil counts after intermediate or major surgery. Despite lower pre-operative total leucocyte (WBC) and PMN counts found in this study, the total leucocyte and PMN response to surgical trauma in the Nigerian Negro is similar to previous observations made in the Caucasian. The response of lymphocytes in the Nigerian Negro, however, differs from that reported in the Caucasian and demands further study.

Ultrastructure and cell cycle distribution of bone marrow cells in protein-energy malnutrition.

Bone marrow aspirates from four children with kwashiorkor and three with marasmus were studied using the techniques of electron microscopy and combined Feulgen microspectrophotometry and 3H-thymidine autoradiography. The majority of the erythroblasts were ultrastructurally normal, the distribution of the early polychromatic erythroblasts between the various stages of the cell cycle was normal or almost normal, and the macrophages did not contain ingested erythroblasts. Since erythropoietin production has been shown to be normal in protein-energy malnutrition, these findings suggest that at least in some cases of PEM the impairment of erythropoiesis results primarily from an abnormality in the erythroid progenitor cell pool rather than from dyserythropoiesis and ineffective erythropoiesis. In one afebrile and apparently uninfected patient with marasmus, a substantial proportion of the neutrophil granulocytes and their more mature precursors contained electron-dense, myelin-containing intracytoplasmic structures which were presumed to be abnormal primary granules. In four of the patients, the 3H-thymidine labelling index of the neutrophil promyelocyte-myelocyte pool was increased. In addition, in all of the cases, neutrophils at various stages of degradation were readily found within the cytoplasm of some of the macrophages. Thus, whereas the techniques employed did not reveal a major disturbance in the morphologically recognizable precursor cells of the erythroid series in PEM, they demonstrated some abnormalities in such cells of the neutrophil series.

Antenatal iron supplementation in sickle cell disease.

Fourteen pregnant women with sickle cell disease (11 SS and 3 SC) were randomized into two groups to receive routine antenatal supplementation either with ferrous gluconate or with placebo tablets. Their hemoglobin levels and bone marrow iron content were determined prenatally and 6 weeks post partum. The fetal weights and the incidence of pain crisis in both groups were recorded. Using an iron content grading from 0 to 5, no marrow of any subject showed iron depletion. The placebo group showed an aggregate postnatal loss of 4 grades of iron repletion while the iron supplemented group showed an aggregate gain of 2 grades. There were no significant differences between the birth weight or the incidence of pain crises in both groups. We conclude that routine iron supplementation is not justified in pregnant women with sickle cell disease, as it would tend to increase already adequate or excessive iron body stores. We recommend that a clear need for iron should be established before iron supplementation is prescribed to them.

Chronic tonsillitis, tonsillectomy and sickle cell crises.

A study of the effect of tonsillectomy on the frequency of sickle cell pain crises was carried out on 15 patients with sickle cell disease (Hb SS) who presented with complaints of frequent pain crises and were found to have chronic tonsillitis. They comprised 9 females and 6 males and ranged in age from 6 to 35 years, with a mean of 15 years. Tonsillectomy was performed under general anaesthesia. The mean number of pain crises in the one-year period after tonsillectomy was 1.5 and was significantly less than the mean number 4.7 in the one year preceding the operation (p less than 0.001). Four patients failed to show a reduced number of crises and these were those whose tonsils at operation showed no pus in their tonsillar crypts. It is thus observed that chronic tonsillitis, symptoms of which may not be volunteered at examination, is a potent inductor of sickle cell pain crisis and that tonsillectomy is an effective mode of treatment, especially when the tonsillar crypts contain pus.

Testicular dysfunction in men with sickle cell disease.

In order to assess the role of the gonads and anterior pituitary gland in the production of poor quality semen of males with homozygous sickle cell disease (SCD) serum gonadotrophins, namely follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin and serum testosterone, were assayed radioimmunologically in 33 men with sickle cell disease and in 29 age-matched normal control subjects. Our results show a significantly lower mean serum testosterone, a higher mean FSH and prolactin in SCD subjects than in normal controls. No single SCD subject had significantly low serum testosterone associated with low FSH, LH or prolactin. The tendency for higher gonadotrophins associated with lower testosterone in subjects with SCD suggests that the hypothalamic/pituitary function in these patients is intact and that the primary fault leading to poor sperm production lies in the testes.