HLA-A-B-C-DRB1-DQB1 phased haplotypes in 124 Nigerian families indicate extreme HLA diversity and low linkage disequilibrium in Central-West Africa.

The simultaneous typing of five-HLA loci at high resolution and the availability of pedigree data allowed us to characterize extended five-locus phased haplotypes in 124 Nigerian families and to compare the observed frequencies with those expected by an expectation-maximization algorithm for unphased data. Despite the occurrence of some frequent alleles at each locus (e.g. B*53:01, which is assumed to protect against Plasmodium falciparum), as many as 82% of the sampled individuals carry two unique five-locus haplotypes and only three extended haplotypes with frequency above 1% exhibit significant linkage disequilibrium. Although preliminary, these results reveal an extreme level of HLA diversity in the Nigerian population, which reflects both its multi-ethnic composition and the very ancient demographic history of African populations.

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.

The anaerobic and aerobic bacterial flora of leg ulcers in patients with sickle-cell disease.

Leg ulcers in 26 patients with sickle-cell disease (SCD) were studied bacteriologically over a period of 6 months. The average age of the patients was 20.92 years and the mean duration of the ulcers was 3.43 years. In order of frequency, Staphylococcus aureus, Pseudomonas aeruginosa, and Bacteroides melaninogenicus were the predominant organisms. Anaerobes were isolated from 14 (54%) of 26 patients and represent 21% of the total 77 isolates. The presence of anaerobes correlated well with odorous ulcers. Isolation of anaerobes from leg ulcers of patients with SCD has added to knowledge of bacterial infection in SCD.

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.

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.

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.

Ocular findings in homozygous sickle cell disease in Nigeria.

We report the ocular findings in 124 Nigerians with homozygous sickle cell disease. None had ocular symptoms. In order of frequency conjunctival vessel anomalies, tortuosity of the major retinal vessels and chorioretinal scars were found. The resemblance of sickle cell chorioretinal scars to toxoplasmic choroiditis is remarkable and should lead to the exclusion of sickle cell disease whenever such lesions are encountered. Angioid streaks, retinitis proliferans, retinal detachment and arteriovenous fans were not observed.

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.

The pattern of sickle cell disease in pregnancy in Lagos, Nigeria.

The outcome of pregnancy and labour in patients with sickle cell disease delivered at the Lagos University Teaching Hospital (LUTH) under one obstetrician between 1st January 1985 and 31st December, 1989 is analysed. There were 31 pregnancies in 28 patients with sickle cell anaemia (HbSS) and 10 pregnancies in seven patients with sickle cell haemoglobin C disease (HbSc). Six pregnancies in HbSS patients and two in HbSC were in patients who had not had specialized preconceptual care. There was one abortion in a patient with HbSC and one pair of twins in a patient with HbSS. The complication rate was high in HbSC patients as compared to a previous series but not as high as in patients with HbSS. The perinatal mortality rates were 233 and 111 per 1000 deliveries in HbSS and HbSC patients respectively. The maternal mortality rates were 129 and 111 per 1000 deliveries in HbSS and HbSC patients respectively. Two of the maternal deaths and four of the perinatal deaths occurred in HbSS patients who had had no preconceptual specialist care as opposed to those receiving specialist treatment. In the case of perinatal mortality, this was found to be statistically significant (p < 0.001).

PIP: Improvement in the medical care of patients with sickle cell disease has increased the numbers surviving into adulthood, increasing the numbers seen in pregnancy. Pregnancy aggravates the medical complications of the disease, and the disease complicates pregnancy, leading to high levels of maternal and perinatal mortality. There is evidence that the presence of the "S" gene affects the fetus adversely and rarely may contribute to maternal death. This paper reviews the pregnancies of patients with sickle cell disease who delivered between January 1, 1985, and December 31, 1989, at the Lagos University Teaching Hospital. All subjects were referred to one obstetrician. There were 31 pregnancies in 28 patients with sickle cell anemia (HbSS) and 10 pregnancies in 7 patients with sickle cell hemoglobin C disease (HbSc). 6 pregnancies in HbSS patients and 2 in HbSc were in patients who had not had specialized preconceptual care. There was one abortion in a patient with HbSC and one pair of twins in a patient with HbSS. The complication rate was high in HbSC patients compared to a previous series, but not as high as in patients with HbSS. Perinatal mortality rates were 233 and 111 per 1000 deliveries in HbSS and HbSC patients, respectively, while maternal mortality rates were 129 and 111 per 1000 deliveries in HbSS and HbSC patients, respectively. Two of the maternal deaths and four of the perinatal deaths occurred in HbSS patients who had had no preconceptual specialist care as opposed to those receiving specialist treatment.

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.

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.

Sickle cell anaemia in Nigeria: a comparison between Benin and Lagos.

The clinical and haematological features of 77 patients of Bini and 107 patients of Yoruba origin with homozygous sickle cell (SS) disease have been compared. The Bini population were generally younger and had a slightly lower incidence of alpha thalassaemia but even after correction for age and alpha thalassaemia status, this group had significantly lower HbA2 and higher HbF and MCV values. Clinically the Bini group had significantly less dactylitis and more acute chest syndrome. The decreased frequency of dactylitis is consistent with the higher HbF level in the Bini population and the mechanism of the other effects are discussed.

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.

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.

In-vivo neutrophil migration and nitroblue tetrazolium reduction in sickle cell disease.

In order to determine the contribution of neutrophil malfunction to the phenomenon of enhanced susceptibility of sickle cell disease patients to bacterial infection, the in-vivo neutrophil migration capacity in 23 sickle cell patients and in 14 normal controls; and the neutrophil reduction of nitroblue tetrazolium dye in 74 sickle cell patients and in 78 normal controls were studied. Secondarily the usefulness of the NBT test in distinguishing between osteomyelitis and uncomplicated bone pain was examined. No impairment of neutrophil migratory capacity was evident as no significant difference was observed between the mean migrated neutrophil count in the sickle cell subjects (1.99 X 10(9)/1) and that in normal controls (2.08 X 10(9)/1). The mean NBT scores were 19.9 +/- 8.9% in non-infected controls and 41.3 +/- 14.6% in infected controls (P less than 0.001). In sickle cell disease they were 23.6 +/- 6% in steady state subjects, 29.2 +/- 16.4% in sterile painful crises, 42.9 +/- 15% in non-osteomyelitic bacterial infection (P less than 0.001) and 18.9 +/- 4.2% during osteomyelitis. Thus all sickle cell subjects apart from those with osteomyelitis showed significant increases in the NBT scores during bacterial infection. The low score in sickle cell osteomyelitis is possibly associated with a relative neutrophil phagocytic defect which requires further elucidation. The NBT test was not useful in distinguishing uncomplicated painful crisis from early osteomyelitis in sickle cell disease.

Cholelithiasis and biliary tract disease in sickle-cell disease in Nigerians.

The incidence of biliary tract disease was investigated by oral cholecystography and/or intravenous cholangiography in 77 unselected Nigerians with homozygous sickle-cell disease (SCD). They included 32 males and 45 females with ages ranging from 8 to 31 years. The prevalence of cholelithiasis was 9% with equal sex incidence. The stones were always multiple and 71.4% of them were radio opaque. Visualization and contractility of all gall bladders examined were normal. The only patient with symptoms and signs which suggested biliary tract disease had no radiographic evidence of cholelithiasis and it was impossible to predict the presence of cholelithiasis from the incidence of abdominal crises in the patients. The prevalence of cholelithiasis is significantly less than that reported in American patients with SCD (35%) and different dietary habits are probably responsible for this.

Leg ulceration in sickle cell disease in Nigeria.

Leg ulceration was found in only 14 of 834 (1.7%) sickle cell patients seen in a Lagos Hospital. Ulcers were seen only in patients above the age of 12 years in whom the prevalence was 5.4%. Affected males outnumbered females 6 to 1. The aetiology was traumatic in 12 patients, spontaneous in three and due to furuncle in one. The commonest sites were around the ankles. Ulceration was not commoner in patients with low socioeconomic status. The simplest forms of aseptic treatment resulted in as variable a healing time as more complex forms of treatment, but a high recurrence rate of ulceration (71.4%) was the major problem. There remains no acceptable reason for the lower prevalence of leg ulceration in Africans with sickle cell disease, but the role of zinc in susceptibility to the ulcers deserves further investigation.

Acute illness in Nigerian children with sickle cell anaemia.

The pattern of illness in 60 consecutive children with homozygous sickle cell disease who attended the Paediatric Emergency Room of a busy Lagos hospital with acute illness was studied prospectively. Their ages ranged from 3 months to 13 years with a peak in the 2nd year. There were twice as many boys as girls. The commonest symptoms were fever, limb or abdominal pain and cough, and the commonest signs were pallor and hepatomegaly. Painful crises occurred in 27, anaemic crises in 11, and a combination of these in 12 children. Infection was detected in 76% of subjects in crises. Infection was found in 82% of all the children and was mainly bacterial. The commonest infections were pneumonia (35%), bacteraemia (32%), tonsillitis/pharyngitis (17%) and osteomyelitis (8%). The predominant bacteria isolated were Klebsiella spp (38%), E. coli (23%), Staph. aureus (23%), Staph. albus (23%) and Pseudomonas spp (23%). Some children had multiple isolates. Bacterial infection was a major cause of morbidity in very young children and merits appropriate control and preventive measures in this age group. The spectrum of bacteria isolated makes it unlikely that the specific anti-pneumococcal measures widely advocated in Europe and America for young children with SCA would be appropriate in Nigeria.