Olayemi O. Omotade

Heritability of blood pressure in Nigerian families.

Objectives There are few studies of familial aggregation of blood pressure in African populations. This study was undertaken to provide estimates of heritability for four blood pressure phenotypes: systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and pulse pressure. Methods A population-based sample of 528 pedigrees or extended families, comprising 1825 measured individuals, was studied in a poor urban community in Ibadan, Nigeria. Results The mean SBP was 121.7 (SD 22.6) mmHg for men and 120.7 (SD 26.8) mmHg for women, while the mean DBP was 74.6 (SD 14.1) mmHg for men and 75.5 (SD 15.2) mmHg for women. The study sample was lean [mean body mass index (BMI) approximately 21 kg/m2]. Maximum-likelihood heritability estimates were obtained under a polygenic model with simultaneous estimation of household effects using a variance components method, as implemented in the SOLAR software package. Heritability estimates of the traits were 34% for SBP, 29% for DBP, 36% for MAP and 13% for pulse pressure. Household effects were statistically significant for DBP (7.1%) and MAP (4.5%). Measured covariates (age, sex and BMI) accounted for 25, 24, 26 and 16% of the total variance, respectively, for SBP, DBP, MAP and pulse pressure. Conclusions These figures suggest that, similar to that reported in other populations, blood pressure is a heritable trait. Studies similar to this are needed to describe the familial aggregation of other complex traits in sub-Saharan African populations and to serve as a prelude to the identification of susceptibility genes involved in the pathophysiology of common complex diseases, including blood pressure and hypertension.

Energy Expenditure and Adiposity in Nigerian and African American Women

Objective: Obesity is a prevalent condition in industrialized societies and is increasing around the world. We sought to assess the relative importance of resting energy expenditure (REE) and activity EE (AEE) in two populations with different rates of obesity.

Genetic effects on blood pressure localized to chromosomes 6 and 7.

Objective To identify quantitative trait loci (QTL) contributing to the variation in blood pressure in a west African population. Methods We conducted a multi-stage genome scan in a population sample from rural Nigeria. A 10 centimorgan genome-wide screen for log-transformed systolic blood pressure (SBP) and diastolic blood pressure (DBP) was first performed based on 1054 individuals from 188 families. In the second phase we performed a similar analysis in an independent sample of 621 individuals from 101 families. In a third follow-up fine mapping phase we genotyped 25 additional markers in the three regions identified in the first two phases. Results Genome-wide significant linkage evidence was found for SBP on chromosome 7p (lod = 4.73, genome wide P ≤ 0.01, point-wise P = 1.53 × 10−6) in the combined sample. Suggestive linkage evidence was also detected on 6q (lod = 2.9, point-wise P = 0.00013) and 7q (lod = 2.6, point-wise P = 0.00027) for SBP, and 7q (lod = 1.6, point-wise P = 0.003) for DBP. Conclusions This study has identified several regions that may harbor genetic variants affecting the variation in blood pressure. Further association mapping under the linkage peaks will be required to refine the linkage evidence that has emerged from our analysis.

Early home treatment of childhood fevers with ineffective antimalarials is deleterious in the outcome of severe malaria

BackgroundEarly diagnosis and prompt treatment including appropriate home-based treatment of malaria is a major strategy for malaria control. A major determinant of clinical outcome in case management is compliance and adherence to effective antimalarial regimen. Home-based malaria treatment with inappropriate medicines is ineffective and there is insufficient evidence on how this contributes to the outcome of severe malaria. This study evaluated the effects of pre-hospital antimalarial drugs use on the presentation and outcome of severe malaria in children in Ibadan, Nigeria.MethodsTwo hundred and sixty-eight children with a median age of 30 months comprising 114 children with cerebral malaria and 154 with severe malarial anaemia (as defined by WHO) were prospectively enrolled. Data on socio-demographic data, treatments given at home, clinical course and outcome of admission were collected and analysed.ResultsA total of 168 children had treatment with an antimalarial treatment at home before presenting at the hospital when there was no improvement. There were no significant differences in the haematocrit levels, parasite counts and nutritional status of the pre-hospital treated and untreated groups. The most commonly used antimalarial medicine was chloroquine. Treatment policy was revised to Artemesinin-based Combination Therapy (ACT) in 2005 as a response to unacceptable levels of therapeutic failures with chloroquine, however chloroquine use remains high. The risk of presenting as cerebral malaria was 1.63 times higher with pre-hospital use of chloroquine for treatment of malaria, with a four-fold increase in the risk of mortality. Controlling for other confounding factors including age and clinical severity, pre-hospital treatment with chloroquine was an independent predictor of mortality.ConclusionThis study showed that, home treatment with chloroquine significantly impacts on the outcome of severe malaria. This finding underscores the need for wide-scale monitoring to withdraw chloroquine from circulation in Nigeria and efforts intensified at promoting prompt treatment with effective medicines in the community.

Relative Height and Weight among Children and Adolescents of Rural Southwestern Nigeria

Background: There are few data describing the relative height and weight patterns of children and adolescents in rural Nigeria, despite a prevalence of stunting of over 38% among children younger than 5 years. Aim: The present study documented the height and weight patterns relative to international standards among children and adolescents aged 5–20 years in rural Nigeria. Subjects and methods: Children 5–20 years of age were enrolled from two rural villages. Height and weight were measured; body composition was estimated using bioelectrical impedance analysis. z-scores and centiles for height and body mass index were calculated; prevalences of low relative height (i.e.>2 standard deviations below mean for age and sex) and weight by sex and age were estimated. Results: A total of 623 participants (326 male and 297 female) were enrolled. The mean height-for-age z-score for males younger than 19 years was –2.1 and prevalence of low relative height was 50%. Among females, the mean height-for-age z-score was –1.2 during adolescence; only 15% of adolescent females were of low relative height. Based on BMI-for-age, 37% of the adolescent males and 23% of females were underweight. No children or adolescents were overweight based on BMI-for-age. Conclusions: Low relative height and underweight occur in a large proportion of children and adolescents in rural Nigeria, with the lowest relative heights and weights occurring in mid-adolescence and among males.

The Impact of Malaria in Pregnancy on Changes in Blood Pressure in Children During Their First Year of Life

We established a maternal birth cohort in Ibadan, Nigeria, where malaria is hyperendemic, to assess how intrauterine exposure to malaria affected infant blood pressure (BP) development. In a local maternity hospital, healthy pregnant women had regular blood films for malaria parasites from booking to delivery. Growth and BP were measured on 318 babies, all followed from birth to 3 and 12 months. Main outcomes were standardized measures of anthropometry and change in BP to 1 year. Babies exposed to maternal malaria were globally smaller at birth, and boys remained smaller at 3 months and 1 year. Change in systolic BP (SBP) during the year was greater in boys than in girls (20.9 versus 15.7 mm Hg; P=0.002) but greater in girls exposed to maternal malaria (18.7 versus 12.7 mm Hg; 95% confidence interval, 1–11 mm Hg; P=0.02). Eleven percent of boys (greater than twice than expected) had a SBP ≥95th percentile (hypertensive, US criteria), of whom 68% had maternal malaria exposure. On regression analysis (&bgr; coefficients, mm Hg), sex (boys>girls; &bgr;=4.4; 95% confidence interval, 1.1–7.7; P=0.01), maternal malaria exposure (3.64; 0.3–6.9; P=0.03), and weight change (2.4; 0.98–3.8/1 standard deviation score; P=0.001) all independently increased SBP change to 1 year, whereas increase in length decreased SBP (−1.98; −3.6 to −0.40). In conclusion, malaria-exposed boys had excess hypertension, whereas malaria-exposed girls a greater increase in SBP. Intrauterine exposure to malaria had sex-dependent effects on BP, independent of infant growth. Because infant–child–adult BP tracking is powerful, a malarial effect may contribute to the African burden of hypertension.

Maternal Malaria, Birth Size and Blood Pressure in Nigerian Newborns: Insights into the Developmental Origins of Hypertension from the Ibadan Growth Cohort

Background Hypertension is an increasing health issue in sub-Saharan Africa where malaria remains common in pregnancy. We established a birth cohort in Nigeria to evaluate the early impact of maternal malaria on newborn blood pressure (BP). Methods Anthropometric measurements, BP, blood films for malaria parasites and haematocrit were obtained in 436 mother-baby pairs. Women were grouped to distinguish between the timing of malaria parasitaemia as ‘No Malaria’, ‘Malaria during pregnancy only’ or ‘Malaria at delivery’, and parasite density as low (<1000 parasites/µl of blood) and high (≥1000/µl). Results Prevalence of maternal malaria parasitaemia was 48%, associated with younger maternal age (p<0.001), being primigravid (p = 0.022), lower haematocrit (p = 0.028). High parasite density through pregnancy had the largest effect on mean birth indices so that weight, length, head and mid-upper arm circumferences were smaller by 300 g, 1.1 cm, 0.7 cm and 0.4 cm respectively compared with ‘No malaria’ (all p≤0.005). In babies of mothers who had ‘malaria at delivery’, their SBPs adjusted for other confounders were lower respectively by 4.3 and 5.7 mmHg/kg compared with ‘malaria during pregnancy only’ or ‘none’. In contrast the mean newborn systolic (SBP) and diastolic BPs (DBP) adjusted for birth weight were higher by 1.7 and 1.4 mmHg/kg respectively in babies whose mothers had high compared with low parasitaemia. Conclusions As expected, prenatal malarial exposure had a significant impact on fetal growth rates. Malaria at delivery was associated with the lowest newborn BPs while malaria through pregnancy, which may attenuate growth of the vascular network, generated higher newborn BPs adjusted for size. These neonatal findings have potential implications for cardiovascular health in sub-Saharan Africa.

Tumour necrosis factor alpha promoter polymorphism, TNF-238 is associated with severe clinical outcome of falciparum malaria in Ibadan southwest Nigeria

Tumour necrosis factor (TNF) - α has been shown to play an important role in the pathogenesis of falciparum malaria. Two TNF promoter polymorphisms, TNF-308 and TNF-238 have been associated with differential activity and production of TNF. In order to investigate the association between TNF-308 and TNF-238 and the clinical outcome of malaria in a Nigerian population, the two TNF polymorphisms were analysed using Sequenom iPLEX Platform. A total of 782 children; 283 children with uncomplicated malaria, 255 children with severe malaria and 244 children with asymptomatic infection (controls) were studied. The distribution of TNF-308 and TNF-238 genotypes were consistent with the Hardy-Weinberg equilibrium. Distribution of both TNF polymorphisms differed significantly across all clinical groups (TNF-308: p=0.007; TNF-238: p=0.001). Further tests for association with severe malaria using genotype models controlling for age, parasitaemia and HbAS showed a significant association of the TNF-238 polymorphism with susceptibility to severe malaria (95% CI=1.43-6.02, OR=2.94, p=0.003237) The GG genotype of TNF-238 significantly increased the risk of developing cerebral malaria from asymptomatic malaria and uncomplicated malaria (95% CI=1.99-18.17, OR=6.02, p<0.001 and 95% CI=1.78-8.23, OR=3.84, p<0.001 respectively). No significant association was found between TNF-308 and malaria outcome. These results show thegenetic association of TNF-238 in the clinical outcome of malaria in Ibadan, southwest Nigeria. These findings add support to the role of TNF in the outcome of malaria infection. Further large scale studies across multiple malaria endemic populations will be required to determine the specific roles of TNF-308 and TNF-238 in the outcome of falciparum malaria infection.

Association of the sickle cell trait and the ABO blood group with clinical severity of malaria in southwest Nigeria

In regions of high Plasmodium falciparum malaria endemicity, certain erythrocyte polymorphisms confer resistance to severe disease. In this study, we evaluate the role of the sickle cell trait (HbS) and ABO blood groups in the clinical manifestations of childhood malaria in Southwest Nigeria. The subjects comprised 3100 children (53% males, median age 39 months), including 1400 children with uncomplicated malaria, 1000 children with asymptomatic malaria and 700 with severe malaria. Haemoglobin (Hb) types were determined using electrophoresis and serum agglutination techniques were used to determine ABO blood groups. Blood group O was the commonest ABO blood group (47.7%) in the study population, the others were A (22.5%), B (25.2%) and AB (4.6%). The frequencies of the HbAS and HbAC were 14.4% and 5.8%, respectively. In regression models adjusting for age, gender, parasite density and blood group, HbAS was associated with a reduced risk of severe malaria OR=0.46 (CI(95%): 0.273-0.773). Among severe malaria subjects, HbAS was associated with significantly lower parasite densities. The protective effect of blood group O was demonstrated with a decreased risk of severe malaria OR=0.743 (CI(95%): 0.566-0.976) after adjusting for age, gender and parasite density and Hb genotype. Blood group B was associated with increased risk of severe malaria OR=1.638 (CI(95%): 1.128-2.380) after adjusting for age, gender, packed cell volume, parasite density and Hb genotype. We have confirmed from this large study of Nigerian children the major protective effective of the sickle cell heterozygous state against both cerebral malaria and severe malarial anaemia. We also show that the B blood group is associated with an increased risk of severe malaria. In conclusion, the sickle cell haemoglobin type and ABO groups modulate the risk of severe malaria in Nigerian children.

Killer-cell immunoglobulin-like receptors and falciparum malaria in southwest Nigeria.

Killer-cell immunoglobulin-like receptors (KIRs) are a group of natural killer cell receptors (NKRs) that regulate NK-cell-mediated production of interferon gamma (IFN-γ) in response to infection. These receptors have recently been suggested to influence the severity of clinical Plasmodium falciparum malaria infection. We examined the KIR locus in relation to malaria in children from southwest Nigeria. Sequence specific priming (SSP)-PCR was used to detect the KIR genes. The presence or absence of fifteen different KIR genes was determined in each individual and the proportions compared across 3 clinical groups; asymptomatic malaria, uncomplicated clinical malaria and severe clinical malaria. The genes KIR2DL5, KIR2DS3 and KIR2DS5 were present in a significantly higher proportion of individuals in the asymptomatic control group than in the malaria cases. Furthermore, KIR2DS3 and KIR2DS5 were present in a higher proportion of uncomplicated malaria cases than severe malaria cases. Carriage c-AB2 genotype (which comprises all centromeric KIR genes including KIR2DL5, KIR2DS3 and KIR2DS5) decreases with severity of the disease suggesting that the KIR AB profile might be associated with protection from severe malaria infection in this population in Nigeria.