Cholelithiasis in children and adolescents with sickle cell disease: Experience in a resource-limited setting.

Background: Sickle cell disease (SCD) remains prevalent in Nigeria and can be complicated by cholelithiasis even in children. There is still a dearth of knowledge about the occurrence of cholelithiasis in these children. The present study is aimed to determine the prevalence of cholelithiasis in pediatric SCD in Lagos and documents relevant socio-demographic and clinical correlates. Subjects and Methods: This was a cross-sectional study of children and adolescents aged 1-19 years with SCD attending the Paediatric Haematology Clinic of the Lagos University Teaching Hospital. One hundred and forty-seven children were consecutively recruited into the study over 3 months and they all had sonographic examination of the gall bladder. The association between cholelithiasis, sociodemographic data, clinical symptoms, laboratory parameters, and the use of hydroxyurea was also documented. Results: The median age (range) of the study participants was 9.0 (1-19) years and majority were males (59.9%). The prevalence of cholelithiasis was 13.6% and the condition was most prevalent in adolescents (21.4%) compared to the younger children (6.5%). All the children with cholelithiasis were asymptomatic. Age and the frequency of crisis were significantly associated with cholelithiasis on multivariate analysis (P = 0.03, 0.045, respectively). The use of hydroxyurea was not significantly related to the occurrence of cholelithiasis. Conclusion: The prevalence of cholelithiasis observed in this study is high. Routine screening of older children and adolescents with SCD, especially with the frequent crisis is suggested. Longitudinal studies to establish the relationship between hydroxyurea and cholelithiasis is also advocated.

Résumé Contexte: La drépanocytose (SCD) reste répandue au Nigéria et peut être compliquée par une cholélithiase même chez les enfants. Il y a encore un manque de connaissances sur la survenue de la cholélithiase chez ces enfants. La présente étude vise à déterminer la prevalence de la cholélithiase dans la drépanocytose pédiatrique à Lagos et documente les corrélats sociodémographiques et cliniques pertinents. Sujets et méthodes: ce était une étude transversale menée auprès d'enfants et d'adolescents âgés de 1 à 19 ans atteints de drépanocytose et fréquentant la clinique d'hématologie pédiatrique de Lagos Hôpital universitaire. Cent quarante-sept enfants ont été recrutés consécutivement dans l'étude pendant 3 mois et ils ont tous eu un examen échographique de la vésicule biliaire. L'association entre cholélithiase, données sociodémographiques, symptômes cliniques, laboratoire paramètres, et l'utilisation de l'hydroxyurée a également été documentée. Résultats: l'âge médian (intervalle) des participants à l'étude était de 9,0 (1­19) ans et la majorité étaient des hommes (59,9%). La prévalence de la cholélithiase était de 13,6% et la maladie était la plus répandue chez les adolescents (21,4%) par rapport aux enfants plus jeunes (6,5%). Tous les enfants atteints de cholélithiase étaient asymptomatiques. L'âge et la fréquence des crises étaient significativement associée à la cholélithiase sur l'analyse multivariée (P = 0,03, 0,045, respectivement). L'utilisation de l'hydroxyurée n'était pas significativement liées à la survenue de cholélithiase. Conclusion: La prévalence de la cholélithiase observée dans cette étude est élevée. Dépistage de routine les enfants plus âgés et les adolescents atteints de SCD, en particulier avec la crise fréquente, sont suggérés. Études longitudinales pour établir la relation entre l'hydroxyurée et la cholélithiase est également préconisée. Mots-clés: Adolescents, enfants, cholélithiase, Nigéria, drépanocytose.

A 5-year multidisciplinary care outcomes in children with wilms' tumour managed at a tertiary centre: A retrospective observational study.

BACKGROUND: Over the last two decades, there has been significant improvement in the outcomes of children with Wilms' tumour (WT) in high income countries (HICs) with approximately 85% survival rate globally. This is partly attributable to a multi-disciplinary team approach to care and the evolution of more robust treatment measures. A previous review in our centre prior to multi-disciplinary team shows a survival rate of 31.48%, However, the survival rates from low- and middle-income countries are still low when compared to HICs due to delays in access to care at all levels, poor to non-existent health insurance coverage, limited workforce resources, weak health-care systems and infrastructure. The aim of this study is to determine the impact of a multi-disciplinary team approach on the treatment outcomes of children with WT. METHODOLOGY: This is a 5-year retrospective review of all patients managed with WT at the Lagos University Teaching Hospital, Lagos, Nigeria. Information was extracted from the patients' case notes, operation notes and ward admission records. The data were analysed with SPSS 25, and P < 0.05 was considered to be statistically significant. RESULTS: Forty patients were included in the study; male to female ratio was 1.6:1. The disease occurred in the right kidney in 23 patients (57.5%) and on the left in 17 patients (42.5%). The average duration of symptoms before presentation was 3.6 months (range 1-7 months), majority of patients presented with abdominal masses and were assessed as per unit protocol with abdominal Computerized tomography scan, chest X-ray and abdominal ultrasound scan to assign the patient International Society of Paediatric oncology regimen. The predominant stage at surgery was Stage III 26 (65%), while Stage IV was 9 (22.5%). Morbidity after chemotherapy was 10 (25%). Twenty-five patients (63%) completed chemotherapy while 15 patients (37%) started chemotherapy but defaulted midway. The 5-year survival rate was 75%. Increasing age and male sex were associated with reduced odds of mortality; however, this was not statistically significant. Increased duration of treatment, being treated with chemotherapy alone, as well as advanced tumour stage and histology were associated with increased odds of mortality, however, this was not statistically significant. CONCLUSION: The development of an institutional WT treatment pathway involving a multidisciplinary team has resulted in improved outcomes. There is need for increased community awareness to improve the time to presentation.

Pediatric Oncology in Nigeria: A Panoramic View.

PURPOSE: A large number of children still die as a result of cancer in low- to middle-income countries, and factors such has poor infrastructure, inadequate human resources, and poorly developed health insurance are responsible for most of these deaths. Nigeria is a country with a young population and a struggling health system. We aimed to survey pediatric oncologists in Nigeria using an online survey instrument. METHODS: We surveyed the national group of pediatric oncologists using an instrument designed to assess manpower availability, infrastructural support, support services, and presence of radiotherapy and medications. RESULTS: A total of 14 institutions responded, represented by 24 oncologists of the 42 oncologists on the platform, with a response rate of 57.1%. Most of the oncologists had practiced for more than 10 years, but only two institutions had a dedicated pediatric oncology ward. There was no population-based pediatric oncology tumor registry. Molecular diagnostic capability was not available, nor was a structurally efficient radiotherapy support service. The centers also struggled with inadequate blood and blood product provision. CONCLUSION: Pediatric oncology services in Nigeria are still grappling with weak human capital, poorly developed infrastructure, weak regional and national referral systems, and poor support services.

Human immunodeficiency virus status in malnourished children seen at Lagos.

INTRODUCTION: Human immunodeficiency virus and protein energy malnutrition are still prevalent in Nigeria and the occurrence of the two conditions together confers a poor prognosis. The aim of this study was to determine the current categories of malnutrition amongst under-5 children in Lagos, document their HIV status and determine any peculiarities in the clinical features, haematological and some biochemical profile in these children. METHODS: The study was a cross-sectional study conducted at the Paediatric departments of the Lagos University Teaching Hospital and the Massey Street Children's Hospital, both in Lagos, over a 6-month period. All the subjects had anthropometry, HIV testing, full blood count and serum proteins done. The factors associated with HIV status were determined with the logistic regression analysis. RESULTS: Two hundred and fourteen (214) malnourished children ≤5 years, including 25 (11.7%) with HIV were recruited in the study. Among the study participants, 150 (70.1%) and 54 (29.9%) had moderate and severe malnutrition, respectively. Fever, cough and diarrhea were the most common symptoms in the study participants. The haematological indices were comparable in the two groups, the serum globulin levels though higher in the HIV infected group was not statistically significantly different from the non-infected group.(p = 0.66). None of the factors explored on multivariate analysis was able to predict the occurrence of the infection in this cohort. CONCLUSION: Malnourished children remain a high risk group for HIV infection and the prevalence of the infection obtained in this group of children is still unacceptably high. Discriminatory features between malnutrition and HIV remains difficult. The presence of hyperglobulinaemia on laboratory analysis in a malnourished child may heighten the suspicion of possible underlying associated HIV infection. Screening of malnourished children for HIV infection and further longitudinal studies on malnourished children with HIV is advocated.

Enuresis in children and adolescents with sickle cell anaemia is more frequent and substantially different from the general population.

BACKGROUND: No large studies have examined the prevalence of enuresis, its various forms and risk factors in children with sickle cell anaemia (SCA) in Sub-Saharan Africa using standardised definitions. We determined age and gender-specific prevalence of enuresis and compared the nature of enuresis in children with and without SCA. We also identified predictors of enuresis in children with SCA. METHODS: Caregivers of children with SCA attending a tertiary centre haematology clinic in Nigeria were interviewed using a questionnaire. In addition, a separate questionnaire was completed for every sibling aged 5-17 years whose haemoglobin genotype was known. Enuresis and its various forms were defined using the definitions of the International Children's Continence Society. RESULTS: The study involved 243 children with SCA and 243 controls matched for age and sex. The mean age of the study cohort was 9.9 (3.4). Females made up 45.7% of the cohorts. The prevalence of enuresis was 49.4% and 29.6% in children with and without SCA, respectively (p = 0.009). In both groups, the prevalence of enuresis declined with age but remained five times higher at 25% in children with SCA aged 14-17 years compared with controls. Also, children with SCA and enuresis were older, more likely to have non-monosymptomatic enuresis and wet at least three nights per week than controls. Independent predictors of enuresis in children with SCA were a family history of enuresis and young age. CONCLUSION: Children with SCA had more frequent and more severe enuresis which persisted to late adolescence than age and sex-matched controls. These features indicate a subset of enuresis that is difficult to treat in the general population. Young age and enuresis in a family member define a subset of children with SCA more likely to have enuresis. Healthcare workers need to discuss enuresis with parents of children with SCA and offer referral to continence services.

A survey of genetic fetal-haemoglobin modifiers in Nigerian patients with sickle cell anaemia.

Genetic variants at three quantitative trait loci (QTL) for fetal haemoglobin (HbF), BCL11A, HBS1L-MYB and the ß-globin gene cluster, have attracted interest as potential targets of therapeutic strategies for HbF reactivation in sickle cell anaemia (SCA). We carried out the first systematic evaluation of critical single nucleotide polymorphisms at these disease modifier loci in Nigerian patients with SCA. Common variants for BCL11A and HBS1L-MYB were strongly associated with HbF levels. At both loci, secondary association signals were detected, illustrating the mapping resolution attainable in this population. For BCL11A, the two independent sites of association were represented by rs1427407 (primary site, p = 7.0 x 10(-10)) and rs6545816 (secondary site, conditioned on rs1427407: p = 0.02) and for HBS1L-MYB by rs9402686 (HMIP-2B, p = 1.23 x 10(-4)) and rs66650371 (HMIP-2A, p = 0.002). Haplotype analysis revealed similarities in the genetic architecture of BCL11A and HBS1L-MYB in Nigerian patients. Variants at both loci also alleviated anaemia. The variant allele for the γ globin gene promoter polymorphism XmnI-HBG2 was too infrequent in our patients to be evaluated in this relatively small study. Studying the large and diverse SCA patient populations in African countries such as Nigeria will be key for a clearer understanding of how these loci work and for the discovery of new disease modifier genes.

Wasting and stunting are still prevalent in children with sickle cell anaemia in Lagos, Nigeria.

BACKGROUND: Sickle cell anaemia (SCA) is associated with growth failure. However, recent reports indicate high rates of overweight or obesity among children with SCA in developed countries. It is unclear whether overweight or obesity is also common in children with SCA in developing countries. The objectives of the study were to determine the prevalence of overweight or obesity, wasting and stunting and identify predictors of wasting and stunting among children with SCA in Nigeria. METHOD: Children with SCA attending a public-funded tertiary hospital clinic were studied. Weight, height, haemoglobin, haemoglobin fractions and white cell count were measured. Anthropometric values were converted to z scores and referenced to the WHO Child Growth Standards and WHO Reference 2007. The proportions with wasting, stunting and overweight or obesity were determined. Regression analysis was used to identify the predictors of wasting and stunting. RESULTS: Two hundred and thirty-three children [mean (±SD) age of 9.0 (±4.0) years, 60.9 % males] participated in the study. Wasting, stunting and overweight or obesity rates were 22.7 %, 11.6 % and 1.7 %, respectively. Boys and children from low socioeconomic class were 3.25 (1.45-7.29) and 2.42 (1.14-5.18) times more likely to be wasted respectively, while both wasting and stunting were more common with increasing age [adjusted OR of 1.33 (1.18-1.51) and 1.15 (1.01-1.32) respectively]. Sickle cell-related complications and intake of oral penicillin and hydroxyurea were not associated with wasting and stunting. CONCLUSION: Overweight or obesity is uncommon while wasting and stunting are still prevalent in children with SCA in Lagos. The strongest predictors of wasting and stunting were older age, male gender and low socioeconomic status.

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.

Prevalence of Wasting, Stunting, and Underweight Among HIV Infected Underfives', in Lagos Using W.H.O z Score.

BACKGROUND: HIV affects more than 2.3 million children worldwide and 90% live in Africa. Malnutrition is also a major problem in Africa with 25% of children under the age of five being malnourished. OBJECTIVE: The study is to determine the nutritional status of HIV infected children using weight-for-age, height-for-age and weight-for-height. METHODS: This was a cross sectional descriptive study where the severity of malnutrition based on weight for age, height for age and weight for weight for height of HIV infected children were compared with controls. RESULTS: The study showed that both HIV infected children and controls were both wasted stunted and underweight, however the severity was more marked in the HIV infected children. The prevalence of wasting was 17.5% in the HIV group compared to 6.6% of the controls, while 17.1% and 7.5% in the HIV infected and controls respectively were stunted. The HIV infected children were more underweight 18.5% compared to the non-infected 8%. CONCLUSION: HIV infected children were three times more wasted, stunted and under-weight than the controls and was statistically significant.

Kidney function of HIV-infected children in Lagos, Nigeria: using Filler's serum cystatin C-based formula.

BACKGROUND: Limited data is available on kidney function in HIV-infected children in sub-Saharan Africa. In addition, malnutrition in these children further reduces the utility of diagnostic methods such as creatinine-based estimates of glomerular filtration rate. We determined the serum cystatin C level and estimated glomerular filtration rate of 60 antiretroviral-naïve, HIV-infected children and 60 apparently healthy age and sex matched children. METHODS: Serum cystatin C level was measured using enzyme-linked immunosorbent assay technique, while glomerular filtration rate was estimated using Filler's serum cystatin C formula. Student t test, Mann Whitney U test, Pearson chi square and Fisher's exact test were used, where appropriate, to test difference between groups. RESULTS: Compared to the controls, the HIV-infected group had significantly higher median (interquartile range) serum cystatin C levels {0.77 (0.29) mg/l versus 0.66 (0.20) mg/l; p = 0.025} and a higher proportion of children with serum cystatin C level >1 mg/l {10 (16.7%) versus one (1.7%); p = 0.004}. The HIV-infected children had a mean (+/- SD) eGFR of 96.8 (+/- 36.1) ml/min/1.73 m2 compared with 110.5 (+/- 27.8) ml/min/1.73 m2 in the controls (p = 0.021). After controlling for age, sex and body mass index, only the study group (HIV infected versus control) remained a significant predictor of serum cystatin C level (beta = -0.216, p = 0.021). The proportion of HIV-infected children with eGFR <60 ml/min/1.73 m2 was eight (13.3%) versus none (0%) in the control group (p = 0.006). However, the serum cystatin C level, eGFR and proportions of children with serum cystatin C level >1 mg/l and eGFR <60 ml/min/1.73 m2 were not significantly different between the HIV-infected children with advanced disease and those with milder disease. CONCLUSIONS: HIV-infected children in Nigeria have higher serum cystatin C level and lower eGFR compared to age and sex matched controls.

T-lymphocyte subsets in apparently healthy nigerian children.

Population studies showed that there are differences in T-lymphocytes subpopulation of normal children in different regions, and reference values in an area might be different from another. This study compared the values in our population with CDC and WHO reference values. Blood samples from 279 healthy, HIV-negative children <12 years of age were analysed for complete blood count, CD3+, CD4+, CD8+ counts and percentages. Except for CD8%, mean values for all parameters measured significantly decreased with age. CD4+ counts were higher in females than males, P < .05. Using the WHO criteria, 15.9% of subjects had low total lymphocyte count and 20.6% had low CD4 count. Children <3 years had median CD4% lower than WHO normal values. Our median CD4+ counts correlated with CDC values. Values used by WHO in infants are higher than ours. We suggest that our children be assessed using CDC reference values which correlate with ours.

Prevalence of proteinuria among HIV-infected children attending a tertiary hospital in Lagos, Nigeria.

Sub-Saharan Africa is the epicentre of the HIV pandemic but there are few reports of HIV-related kidney diseases in children in this region. This study aimed to determine the prevalence of proteinuria in HIV-infected children at the Lagos University Teaching Hospital. Proteinuria was determined using urine protein-creatinine ratio. CD4+ cell count was determined for all the HIV-infected children. The mean age of the HIV-infected children was 74.4 +/- 35.6 months with a male: female ratio of 3:2. Compared with 6% of the 50 controls 20.5% of the 88 HIV-infected children had proteinuria (p = 0.026). Of 20 children with advanced clinical stage 40% had proteinuria compared with 14.7% of 68 children with milder stage (p = 0.004). Similarly, proteinuria was commoner among those with severe immunosuppression (p = 0.014). HAART use was not associated with significant difference in proteinuria prevalence (p = 0.491). Proteinuria was frequent among HIV-infected children, especially among those with advanced disease.

Adherence to antiretroviral therapy among HIV-infected children attending a donor-funded clinic at a tertiary hospital in Nigeria.

The success of antiretroviral therapy (ART) depends on a high level of adherence to a life-long regimen of antiretroviral drugs (ARVs). Since the scale-up of access to ARVs in Nigeria, few studies have determined the level of adherence of ART among children. This study was undertaken to determine the level of ART adherence among paediatric patients at an outpatient clinic, the reasons for non-adherence, and the factors associated with adherence, according to caregivers' reports. Out of a total of 212 children, 183 (86%) were adherent in the three days preceding the interview, while 29 (14%) were not adherent. Drug exhaustion at home (16 children), followed by 'child slept through' (7 children) and 'caregiver away' were the most common reasons for a child having missed one or more ARV doses. Independent factors for adherence were male gender (odds ratio [OR] = 2.85; 95% confidence interval [CI]: 1.17-6.92) and attendance at last scheduled clinic appointment (OR = 4.76; 95% CI: 1.73-13.04). The caregiver's highest educational attainment, distance travelled to the clinic, use of medication reminders, formulation of ARVs, duration of HAART usage, age of the child and orphan status were not significantly associated with adherence to drug treatment. The overall level of adherence was high and similar to the rate reported prior to free access to ART services in Nigeria. Among child patients on HAART, there is a need to identify factors affecting clinic attendance and drug exhaustion at home.

Constraints and prospects in the management of pediatric HIV/AIDS.

BACKGROUND: Pediatric HIV/AIDS is increasing in Nigeria through mother-to-child transmission. Lack of diagnostic facility and affordability of therapy are major constraints. These factors were examined in Lagos University Teaching Hospital (LUTH) between 1996 and 2002. MATERIALS AND METHODS: Case records of pediatric HIV/AIDS patients were examined for age, sex, mode of diagnosis, associated illnesses, treatment outcome and socioeconomic and HIV status of the parents. RESULTS: Out of 124 cases confirmed to have HIV/AIDS, 56.5% were aged <18 months and 89.5% had > or =4 clinical features at presentation. There was an increasing trend in the number of cases from 1996 to 2002. Diagnosis was by WHO clinical criteria as no polymerase chain reaction (PCR), was done and only 12.1% had CD4+ count done. The commonest associated illness was tuberculosis (25.8%). Only 20.2% were placed on antiretroviral drugs during the period. Mothers were significantly younger than fathers (P<0.05) and were more likely to be HIV positive. High rate of discharges against medical advice and default from follow-up occurred. CONCLUSION: Pediatric HIV/AIDS is on the increase at LUTH, and mothers were more HIV infected than fathers. The prohibitive cost of drugs prevented most patients from receiving therapy.