Pattern of Clinical and Laboratory Presentation of Cerebral Malaria among Children in Nigeria.

Introduction: Cerebral malaria (CM) is the most lethal form of severe malaria with high case fatality rates. Overtime, there is an inherent risk in changing pattern of presentation of CM which, if the diagnosis is missed due to these changing factors, may portend a poor outcome. Variations in the pattern of clinic-laboratory presentations also make generalization difficult. This study was, therefore, set out to report the pattern of clinical and laboratory presentation of CM. Methods: This was a cross-sectional study among children aged 6 months to 14 years admitted with a diagnosis of CM as defined by the World Health Organization criteria. A pretested pro forma was filled, and detailed neurological examination and laboratory (biochemical, microbiology, and hematology) investigations were done. P <5% was considered statistically significant. Results: Sixty-four children were recruited with a mean age of 34.9 ± 24.9 months and a male-to-female ratio of 1.9:1. There were 87.5% of under-five children. Fever (96.9%) was the major presenting feature closely followed by convulsions (92.2%). Convulsions were mainly generalized (94.9%) and multiple (76.5%). Profound coma (Blantyre coma score of 0) was present in 12.5% of cases, and the leading features on examination were fever (84.4%) and pallor (75.0%). Retinal vessel whitening (48.4%) was the most common funduscopic abnormality. Metabolic acidosis (47.9%), severe anemia (14.1%), hyperglycemia (17.2%), and hypoglycemia (7.8%) were seen among the children. Few (1.6%) had hyperparasitemia and bacteremia (3.2%). Conclusion: Early recognition of the clinical presentation and prompt management may improve the outcome of cerebral malaria.

High blood lead levels of children in a gold mining community in Osun State, Nigeria: an urgent call for action.

BACKGROUND: Environmental exposure from artisanal gold mining activities is a major risk for high blood lead levels (BLLs) in children. Over the last decade, artisanal gold mining activities have been on a sharp increase in some parts of Nigeria. This study compared BLLs of children in the mining community of Itagunmodi and a 50-km distant non-mining community of Imesi-Ile, Osun State, Nigeria. METHODS: This community-based study investigated 234 apparently healthy children, with 117 each from Itagunmodi and Imesi-Ile. Relevant history, examination and laboratory findings including BLLs were recorded and analysed. RESULTS: All participants had BLLs above the cut-off value of 5 µg/dl. However, the mean BLL of subjects living in the gold-mining community (24.2±5.3 µg/dl) was significantly higher than for children in the non-mining area of Imesi-Ile (19.5±6.4 µg/dl; p<0.001). Children in the gold mining community were 3.07 times more likely to have a BLL ≥20 µg/dl than those in the non-mining environment (odds ratio [OR] 3.07 [95% confidence interval {CI} 1.79 to 5.2], p<0.001). Similarly, the odds of having a BLL ≥30 µg/dl was 7.84 times more likely among children living in gold mining Itagunmodi than in Imesi-Ile (OR 7.84 [95% CI 2.32 to 26.46], p<0.0001). BLL was not associated with socio-economic and nutritional status of the participants. CONCLUSIONS: In addition to introduction and enforcement of safe mining practices, regular screening for lead toxicity is advocated for children in these communities.

Clinical Utilities of Electrocardiography in the Diagnosis of Myocardial Ischemia in Children With Sickle Cell Anemia: Correlation With Serum Cardiac Troponin I.

BACKGROUND: Sickle cell anemia (SCA) is associated with recurrent vaso-occlusive crisis (VOC) and the risk of myocardial ischemia (MI). This study investigated the utility of electrocardiography (ECG) and cardiac troponin I (cTnI) in diagnosing MI during VOC. MATERIALS AND METHODS: Children with SCA 5 to 15 years of age in VOC (patients) and age-matched and sex-matched steady-state controls were studied. Their ECG and cTnI levels were measured at contact and after 4 to 6 weeks. RESULTS: One hundred eighty-six children (93 patients and 93 controls) were studied. The mean (SD) ages of the patients and controls were 8.8 (3.2) and 9.0 (3.1) years, respectively. The mean MI score was significantly higher for the patients, 1.7 (1.2), than the controls, 1.3 (1.0), P=0.002. A significantly higher proportion of the patients, 18 (19.4%), also had significant ischemia compared with the controls, 8 (8.6%), P=0.016. The median (interquartile range) serum cTnI level was significantly higher in the patients than the controls, P=0.006. All 7 of the patients with elevated cTnI had VOC. No significant correlation was found between MI score and cTnI in both groups. CONCLUSIONS: cTnI is elevated and ECG features of MI worsen during VOC. Longitudinal studies to investigate their evolvement over time are advocated.

Prevalence of ocular abnormalities in relation to sickle cell disease severity among children in South-western, Nigeria.

INTRODUCTION: Sickle cell disease (SCD) ranks high among genetic disorders worldwide. It is characterised by repeated vaso-occlusion with resultant end-organ damage. This process can occur in all vascular beds in the body, including ocular blood vessels and may cause irreversible blindness in advanced stages. Little is known of the relationship between the prevalence of ocular abnormalities among children with SCD and their disease severity. METHODS: A descriptive cross-sectional study was carried out at the Paediatric Haematology Clinics and the Eye Centre of the Obafemi Awolowo University Teaching Hospitals Complex (OAUTHC), Ile-Ife. Children with SCD in steady state were recruited from the Haematology Clinics and examined for ocular abnormalities at the Eye Centre of the hospital. The subjects SCD severity grade was determined using a previously validated scoring system. RESULTS: One hundred and twenty (120) children aged 5 to 15 years were examined. Of these, 72 had one or more ocular abnormalities giving the prevalence of ocular abnormalities among them to be 60.0%. Though a higher proportion of children with moderate disease, 23 (65.7%) of 35, compared to those with mild disease, 49 (57.6%) of 85 had ocular abnormalities, this difference was not statistically significant, p = 0.412. CONCLUSION: Ocular abnormalities among Nigerian children with SCD are common even in steady-state, but not significantly associated with disease severity. Periodic screening for ocular abnormalities should thus be done on them irrespective of disease severity.

Outcome of short-term emergency department observation care of children with sickle cell disease and vaso-occlusive crises: initial experience from south-western Nigeria.

BACKGROUND: Short-term emergency department (ED) observation care may prevent prolonged and unnecessary hospital admission in patients with sickle pain. This study highlights the outcomes of short-term ED care of acute pain in children with sickle cell disease (SCD). METHODS: Children aged 6 mo to 19 y with SCD and painful crises who were managed by short-term ED care from July 2017 to June 2019 were studied retrospectively. Biodata, pain score, type of care, length of hospital stay, inpatient transfer rate (the proportion that required transfer for full admission) and return rate (the proportion that returned to the hospital for retreatment of unresolved pain) were documented. RESULTS: From July 2017 to June 2019, 122 children with SCD were admitted to the ED for painful crises, of whom 118 (96.7%) with 167 hospital visits were managed by short-term ED observation care. The median length of stay was 10.5 h. In 50.3% of encounters, patients were successfully managed without requiring further care. However, in 17.4% of encounters, they had their ED observation care terminated and converted to full admission. The overall return rate for acute care within 1 wk for either persistence of symptoms or any other complaint was 31.7%. CONCLUSIONS: Dedicated short-term ED observation care has the potential to provide effective and timely management of acute pain in children with SCD.

Thrombospondin-1 and Vitamin D in Children With Sickle Cell Anemia.

BACKGROUND: Thrombospondin-1 (TSP-1) and 25-hydroxyvitamin D (25-OHD) play significant roles in the pathogenesis of sickle cell anemia (SCA). TSP-1 enhances cellular adhesion/inflammation, hence contributing to vaso-occlusive crisis (VOC); vitamin D, in contrast, retards inflammation and may lower rate of pain episodes. We determined serum levels of TSP-1 and 25-OHD in Nigerian children with SCA and their matched hemoglobin AA controls; and assess the relationship between the 2 biomarkers. METHODS: In total 90 children (32 SCA in steady state, 30 SCA in VOC, and 28 HbAA controls) were studied. Serum TSP-1 and 25-OHD levels were measured with ELISA and HPLC, respectively. RESULTS: The mean TSP-1 of children with VOC was significantly higher than those in steady state (P=0.022) and HbAA controls (P<0.001). Similarly, the mean TSP-1 of those in steady state was higher than the controls (P=0.007). However, mean serum 25-OHD of the children with VOC was significantly lower than those in steady state (28.9±8.2 ng/mL vs. 37.1±12.3 ng/mL, P =0.004). There was a significant inverse correlation between TSP-1 and 25-OHD among the VOC subgroup, r=-0.57, P=0.001. The mean TSP-1 of the 28 children with SCA who had suboptimal vitamin D (213.5±118.6 ng/mL) was higher than 144.2±58.7 ng/mL of the 34 SCA who had normal serum vitamin D, P=0.008. CONCLUSIONS: Children with SCA, especially those with VOC, had high serum TSP-1 and low 25-OHD. Also, an inverse relationship exist between serum 25-OHD and TSP-1 in children with VOC. These findings provide basis for further studies into the regulation of TSP-1 by vitamin D.

Prevalence of Vitamin A deficiency among under-five children in South-Western Nigeria.

BACKGROUND AND AIM: Vitamin A deficiency (VAD) constitutes a major nutritional concern in developing countries. It contributes significantly to the morbidity and mortality of under-five children and can result in impaired resistance to infection as well as increased risk of death. The aim of this study was to determine the prevalence of VAD among Southwestern Nigerian children. METHODS: Apparently healthy children aged between 6 months and 5 years were recruited for the study. Their serum retinol levels were determined by high-performance liquid chromatography. RESULTS: Of the 170 children studied, nine (5.3%) had VAD, although none had severe VAD. The prevalence of VAD did not show statistically significant variation with age (P = 0.159), sex (P = 1.000), social class (P = 0.740), immunisation status (P = 0.197) or nutritional status (P = 0.090). CONCLUSION: The prevalence of VAD among Nigerian children appears to have reduced, compared with previous reports; however, further studies are required to assess the current national prevalence, so as to design programmes that can achieve further reduction in the proportion of children affected.

Sickle cell disease in southwestern Nigeria: assessment of knowledge of primary health care workers and available facilities.

Background: Patients with sickle cell disease (SCD) benefit optimally from comprehensive care. In Nigeria, despite the huge burden, involvement of community health workers (CHWs) in the management of SCD is poor. Methods: This community-based study assessed SCD-related knowledge of 182 CHWs from the 46 primary health care (PHC) centres in Ilesa, southwestern Nigeria. Available facilities and management practices for SCD care at these centres were also evaluated using pretested self-administered questionnaires and observational checklists. Results: The majority of CHWs (167/182 [91.8%]) knew that SCD is an inheritable blood disorder. However, only 32.4% and 26.4% knew that SCD can be diagnosed in the prenatal and neonatal periods, respectively. Also 37.4%, 49.5% and 67.6% knew about the role of chemoprophylaxis (folic acid/penicillin), adequate fluids and malaria prevention, respectively, in SCD care. Overall, 37.9% had good knowledge on the nature and care of the disease. Just 2/46 (4.3%) PHC centres treat patients with SCD. SCD-targeted nutritional counselling and referral to secondary/tertiary hospitals were poor and unorganized. No centre offered SCD screening, home visits or recordkeeping. Conclusions: The level of SCD care and knowledge of CHWs at PHC centres in southwestern Nigeria of early SCD diagnosis and crisis prevention is poor. CHWs should be regularly trained and equipped for basic SCD management, including early detection, crisis prevention, prompt referral and provision of basic genetic counselling, to dispel associated myths and stigma.

Vitamin A deficiency among under-five Nigerian children with diarrhoea.

BACKGROUND: Vitamin A deficiency (VAD) and diarrhoea are still important contributors to childhood deaths in Africa, and vitamin A deficient children are at increased risk as well as severity of diarrhoea. OBJECTIVES: To determine the prevalence of VAD and identify the associated factors among children with diarrhoea. METHODS: The study was a hospital-based cross-sectional descriptive study. Consecutive children with diarrhoea were recruited, provided they met the inclusion criteria. Serum retinol levels were determined by high performance liquid chromatography (HPLC) in one hundred and seventy under-five children who presented with diarrhoea at the Wesley Guild Hospital, Ilesa, Nigeria. RESULTS: The serum retinol levels of the children ranged from 0.29 - 2.35 µmol/L with a mean ± SD of 1.07 ± 0.42 µmol/L. Twenty seven (15.9%) were vitamin A deficient with three (1.8%) of these having severe VAD. Wasting was significantly associated with a higher prevalence of VAD [p = 0.023, OR (95% CI) = 3.08 (1.21 - 7.79)]. A significantly greater proportion of the subjects who had VAD were hospitalized, compared with the non-deficient ones [p = 0.001, OR (95% CI) = 4.40 (1.82 - 10.66)]. The only subject who died was vitamin A deficient. CONCLUSION: Wasting and hospitalization are factors that may indicate the presence of VAD in a child with diarrhoea. Vitamin A supplements should therefore be given, as part of the treatment for diarrhoea, to children who have wasting, especially when they require hospitalization.

A Multi-centre Survey of Acceptability of Newborn Screening for Sickle Cell Disease in Nigeria.

Background Sickle cell disease (SCD) is a major genetic disease that manifests early in life and may lead to significant morbidities. One of the health care services that have been effective in reducing the burden of SCD in developed countries is newborn screening (NBS) followed by pneumococcal vaccines, penicillin prophylaxis, and hydroxyurea treatment. Yet, in sub-Saharan African countries, where about 75% of annual affected babies worldwide are born, NBS programmes are largely unavailable. It is not clear whether this is due to technical challenges associated with setting up such programmes, or significant cultural and social barriers to its acceptance in such settings. Objective Our aim was to ascertain the attitudes to and acceptability of NBS in Nigeria among various socio-demographic groups including health professionals, undergraduate students, parents of children with SCD and SCD patients. Methods Data on socio-demographic characteristics, knowledge of SCD and attitude towards NBS were collected using a semi-structured pre-tested questionnaire from April to July 2014 across 15 health institutions and university campuses in Nigeria. Data were collected from 1,301 respondents across Nigeria. Results There was good knowledge of SCD as an inherited blood disorder. Although 86% of respondents (n = 1,119) supported NBS, there was a statistically significant relationship between support for NBS and age (p = 003), educational status (p = 000) and religion (p = 000). Conclusion This study suggests that there is a good acceptability of NBS across Nigeria. The main barriers to its use are likely to be financial and practical, rather than social or cultural.

The Association of Serum 25-Hydroxyvitamin D With Biomarkers of Hemolysis in Pediatric Patients With Sickle Cell Disease.

Although vitamin D deficiency (VDD) has been linked to anemia among sickle cell disease (SCD), its relationship with hemolysis is unclear. Serum 25-hydroxyvitamin D and biomarkers of hemolysis (hemoglobin [Hb]/hematocrit, reticulocyte percentage, absolute reticulocyte, and lactate dehydrogenase [LDH] levels) in 36 hydroxyurea-naive SCD children were quantified. Correlations were significantly positive with Hb/hematocrit (r=0.40, P=0.017; r=0.45, P=0.006, respectively); inverse with reticulocyte percentage, absolute reticulocyte, and LDH (r=-0.44, P=0.008; r=-0.47, P=0.007; r=-0.45, P=0.007, respectively). In VDD groups, Hb was lower (P=0.014), reticulocyte counts and LDH were higher (P=0.047 and 0.003, respectively). Serum 25-hydroxyvitamin D correlated with biomarkers of hemolysis in SCD and VDD may play a role in SCD pathogenesis.

Impact of Hydroxyurea on Anthropometry and Serum 25-Hydroxyvitamin D Among Children With Sickle Cell Disease.

OBJECTIVE: To evaluate the impact of hydroxyurea (HU) on nutritional status and serum 25-hydroxyvitamin D (25-OHD) of children with sickle cell disease (SCD). DESIGN: Anthropometry and serum 25-OHD were determined in 98 children with SCD, comprising of 68 in HU-group and 30 in HU-naive group. RESULTS: Underweight was more common among HU-naive group (33.3% vs. 10.3%, P=0.009), while 79.4% of HU-group against 56.7% HU-naive had normal body mass index percentile for age and sex, P=0.028. None of the HU-group compared with 13.3% of the HU-naive had severe vitamin D deficiency, P=0.002. The mean 25-OHD of the HU-group was also higher (24.1±1.2 vs. 19.1±9.8 ng/mL, P=0.007). CONCLUSIONS: HU possibly ameliorate growth retardation and vitamin D deficiency in children with SCD.

Foetal Haemoglobin and Disease Severity in Nigerian Children with Sickle Cell Anaemia.

BACKGROUND: Foetal haemoglobin (HbF) is a major modifying factor influencing sickle cell disease (SCD) severity. Despite this, HbF estimation is not routinely done in Nigeria. The relationship between HbF and SCD severity among affected children is also poorly studied. METHODS: In this descriptive cross-sectional study, we determined the relationship between steady state HbF levels and disease severity of Nigerian children aged 1 - 15 years with homozygous SCD. For each child, the socio-demographic characteristics and SCD clinical severity were determined. The latter was assessed based on the frequency of significant painful episodes, blood transfusion, and hospitalisation in the preceding 12 months; lifetime cumulative incidence of SCD-related complications; the degree of splenic and hepatic enlargement; current haematocrit and leucocyte count. Foetal haemoglobin levels were quantified with high-performance liquid chromatography. RESULTS: The mean HbF level of the 105 children with SCA was 9.9 ± 6.0%. Male had significantly lower mean HbF levels than females, 8.0 ± 5.6% vs. 12.2 ± 5.8% (p < 0.001). None of the children had severe disease. However, the 32 children with moderate disease had significantly lower mean foetal haemoglobin levels than the 73 with mild disease (7.7 ± 5.6% vs 10.8 ± 6.0% respectively). The mean HbF level was also significantly lower in children who had a history of acute chest syndrome and stroke compared to those without these complications, p = 0.002 and 0.010 respectively. CONCLUSION: Children with SCA who had a moderate disease and those with a history of life-threatening complications such as stroke and acute chest syndrome had significantly low HbF levels. Therefore, it is recommended that facilities for early quantification of foetal haemoglobin and HbF inducement were made available to reduce the morbidity and mortality among these children.

Comparative study of the growth and nutritional status of Brazilian and Nigerian school-aged children with sickle cell disease.

Background: Comparative studies of patients in different sociogeographic/ecological zones may unravel potential environmental and nutritional factors influencing disease phenotype. In sickle cell disease (SCD), differential access to comprehensive care may influence their growth and nutritional status. Methods: From June 2015 to February 2016, steady-state nutritional parameters of 109 Brazilian and 95 Nigerian children with SCD attending routine clinic visits at Universidade Federal de São Paulo, Brazil and Obafemi Awolowo University Teaching Hospital, Ile-Ife (Ilesa unit), respectively, were compared. Results: A relatively high proportion of the children in both centres (23.5%) were wasted [body-mass index (BMI)-for-age z-score<-2). BMI-for-age z-score, height-for-age z-score, upper arm fat area and fat percentage were lower in the Nigerian cohorts. More Nigerians, 29.5% (28/95) against 18.3% (20/109) were wasted, and had short stature, [12.6% (12/95) vs. 3.7% (4/109)] than Brazilians. A higher proportion of Brazilian patients were overweight or obese (9.2 vs. 4.3%), and taller for age (15.6 vs. 8.4%). None of the Nigerian patients had severe vitamin D deficiency, only 12.6% (12/95) had suboptimal vitamin D and 1.1% (1/95) had low serum zinc levels, unlike 79.8% (87/109) of the Brazilian patients with suboptimal vitamin D and 10.1% (11/109) with low zinc. Conclusion: Undernutrition is still prevalent among the two cohorts. Nigerian patients were thinner and had reduced linear growth for age. This observation justifies the continued need for specialized nutritional care for children with SCD. In addition to hydroxyurea therapy, research is needed to determine appropriate nutritional intervention and exercise regimens for these children.

Blood transfusion services for patients with sickle cell disease in Nigeria.

BACKGROUND: Safe, timely red blood cell transfusion saves lives and chronic transfusion therapy (CTT) prevents or limits morbidities such as stroke, therefore improving quality of life of patients with sickle cell disease (SCD). METHODS: This questionnaire-based study assessed the ability of sickle cell centers in Nigeria to provide safe blood to patients with SCD between March and August 2014. RESULTS: Out of the 73 hospitals contacted, responses were obtained from 31. Twenty four (78%) hospitals were unable to transfuse patients regularly due to blood scarcity. Packed red blood cells were available in 14 (45%), while only one provided leukocyte-depletion. Most centers assessed donor risk and screened for HIV in 30 (97%), hepatitis B in 31(100%) and hepatitis C in 27 (87%) hospitals. Extended phenotyping and alloantibody screening were not available in any center. A quarter of the hospitals could monitor iron overload, but only using serum ferritin. Access to iron chelators was limited and expensive. Seventeen (55%) tertiary hospitals offered CTT by top-up or manual exchange transfusion; previous stroke was the most common indication. CONCLUSION: Current efforts of Nigerian public hospitals to provide safe blood and CTT fall short of best practice. Provision of apheresis machines, improvement of voluntary non-remunerated donor drive, screening for red cell antigens and antibodies, and availability of iron chelators would significantly improve SCD care in Nigeria.

Interleukin-1ß and interleukin-6 gene polymorphisms are associated with manifestations of sickle cell anemia.

Sickle cell anemia (SCA), a disorder characterized by both acute and chronic inflammation, exhibits substantial phenotypic variability. Interleukin-1 beta (IL-1ß) and IL-6 are important in acute and chronic diseases, and their single nucleotide polymorphisms (SNPs) have been considered as predictors of prognosis in several inflammatory conditions. This study aims at exploring possible association of IL-1ß and IL-6 SNPs as potential genetic modifiers and or predictors of SCA clinical and laboratory phenotypes. This cross-sectional study involved 107 SCA patients and 110 age, sex and ethnicity-matched healthy individuals. The SNPs were identified by PCR-RFLP for IL-1ß (-511C>T and +3954C>T) and IL-6 (-597G>A and -174G>C) genes. Associations between these SNPs and the clinical and laboratory profiles of patients with SCA were then determined. Allelic and genotypic frequencies of IL-1ß and IL-6 SNPs between patients with SCA and controls were similar and followed HWE. IL-1ß +3954C>T SNP was associated with increased risk of osteonecrosis, elevated pulmonary arterial pressure and lower absolute reticulocyte count, while IL-6 -597G>A was associated with higher likelihood of retinopathy and leg ulcer. These data indicate that IL-1ß and IL-6 gene SNPs are associated with SCA complications among Brazilian patients and may act as genetic predictors of SCA clinical heterogeneity.

The rate and cost of hospitalisation in children with sickle cell anaemia and its implications in a developing economy.

BACKGROUND: There is paucity of data on the cost and rate of hospitalization in children with sickle cell anaemia (SCA) in most developing nations. OBJECTIVE: To estimate the rate and cost of hospitalization in children with SCA in Nigeria and evaluate the economic burdens on their families. METHODS: The number and duration of hospitalizations; estimated aggregate family's monthly income, cost of care and percentage of the mean annual income spent on hospitalization for each respondent were obtained using a structured questionnaire. RESULTS: The mean age of the 73 children was 61.1(44.3) months; M:F was 1:1.6. They had 183 admissions (average of 2.5(1.9) admissions per child per year). The mean family monthly income was $250.37, while the average cost of care per hospitalization per subject was $132.67. The total cost of care during the year was $24,278.37. About one-third of the caregivers spent at least 10% of their estimated annual income as total cost of hospitalization. CONCLUSION: The rate and the cost of hospitalization for children with SCA and the percentage of income spent on hospitalization were too high in our environment. Government should strengthen the National Health Insurance Scheme and subsidise the cost of care to these children.