Department of Child Health
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Item Asymptomatic malaria parasitaemia and virological non-suppression among children living with HIV in a low transmission area in Accra, Ghana: a cross-sectional study(BMC Infectious Diseases, 2024) Afrane, A.K.A.; Alhassan, Y.; Amoah, L.E.; Nyarko, M. Y.; Addo-Lartey, A.Background Human Immunodeficiency Virus (HIV) and malaria are two major diseases in sub-Saharan Africa. Co-infection can significantly impact the clinical outcomes of both conditions. We assessed the proportion of HIV infected children at Korle Bu Teaching Hospital (KBTH) and Princess Marie Louise Hospital (PML) with malaria parasites. The association between asymptomatic malaria parasitaemia and virological non-suppression was also determined in these children. Methods This cross-sectional study of 277 asymptomatic malaria in children receiving care at paediatric HIV clinics at KBTH and PML was conducted from September to November 2022. Patients who had been on antiretroviral therapy (ART) for at least six months were eligible to participate. Structured questionnaires were used to collect socio-demographic information, malaria prevention behaviors, and ART-related data using in-person interviews. Microscopy and PCR were used to screen for malaria, and GeneXpert was used to determine viral load. To examine the determinants of malaria PCR positivity and virological non-suppression, chi-square tests and logistic regression were performed. Results The median age of the participants was 9 years (range: 6–12 years). Males comprised 158 (57%) of the study population. We detected 10 (3.6%) and 21 (7.6%) malaria cases by microscopy and PCR, respectively. Virological non-suppression (VL>1000 copies/ml) was observed in 82 (29.6%) of the 277 participants. Among the suppressed individuals, 62 (22.4%) exhibited low-level viraemia (VL level 40-1000 copies/ml) and 133 (48%) had undetectable viral load levels. No factors were associated with the presence of malaria PCR positivity carriage. Poor adherence to ART was associated with a five-fold increase in the risk of viral load non-suppression (AOR=4.89 [CI=2.00-11.98], p=0.001). Conclusion The proportion of children living with HIV with asymptomatic malaria parasitaemia was low. Approximately one-third of the study population had virological non-suppression. The interaction between malaria parasitemia and viral replication may not be the main cause for virological non-suppression in this low transmission areaItem Barriers to Decolonizing Global Health: Identification of Research Challenges Facing Investigators Residing in Low- and Middle-Income Countries(Global Health: Science and Practice, 2024) Anane-Binfoh, N.A.; Afaa, T.J.; Flaherty, K.E.; et al.local limitations on protected time for research, ethical review, technology, and training threaten the productivity and development of investigators in low- and middle-income countries. The National governments of many low- and middle-income countries underprioritize research or thwart its progress through political repression or instability. At the international level, investigators in low- and middle-income countries must compete with advantaged investigators from high-income nations for funding and publicationsItem Diagnostic accuracy of Xpert MTB/RIF Ultra for childhood tuberculosis in West Africa – a multicenter pragmatic study(International Journal of Infectious Diseases, 2024) Diallo, A.B.; Osman, K.A.; Tolofoudie, M.; et al.Objective: To evaluate the performance of Xpert Mycobacterium Tuberculosis/rifampicin (MTB/RIF) Ultra (Ultra) for diagnosis of childhood tuberculosis (TB) within public health systems. Methods: In this cross-sectional study, children aged <15 years with presumptive pulmonary TB were consecutively recruited and evaluated for TB at tertiary-level hospitals in Benin, Mali, and Ghana. Bivariate random-effects models were used to determine the pooled sensitivity and specificity of Ultra against culture. We also estimated its diagnostic yield against a composite microbiological reference standard (cMRS) of positive culture or Ultra. Results: Overall, 193 children were included in the analyses with a median (interquartile range) age of 4.0 (1.1-9.2) years, 88 (45.6%) were female, and 36 (18.7%) were HIV-positive. Thirty-one (16.1%) children had confirmed TB, 39 (20.2%) had unconfirmed TB, and 123 (63.7%) had unlikely TB. The pooled sensitivity and specificity of Ultra verified by culture were 55.0% (95% confidence interval [CI]: 28.0–79.0%) and 95.0% (95% CI: 88.0–98.0%), respectively. Against the cMRS, the diagnostic yield of Ultra and culture were 67.7% (95% CI: 48.6–83.3%) and 70.9% (95% CI: 51.9–85.8%), respectively. Conclusion: Ultra has suboptimal sensitivity in children with TB that were investigated under routine conditions in tertiary-level hospitals in three West African countriesItem Clinical and laboratory characteristics of children with sickle cell disease on hydroxyurea treated with artemether-lumefantrine for acute uncomplicated malaria(Frontiers in Public Health, 2023) Segbefia, C.; Amponsah, S.K.; Afrane, A.K.A.; et al.Introduction: Limited information exists on any interactions between hydroxyurea (HU) and antimalarials in sickle cell disease (SCD). We evaluated changes in clinical and laboratory parameters among children with SCD on HU therapy treated with artemether-lumefantrine (AL) for acute uncomplicated malaria (UM). Methods: A prospective, non-randomized, pilot study of 127 children with SCD (23, UM; 104, steady state) were recruited from three hospitals in Accra. UM participants were treated with standard doses of AL and followed up, on days 1, 2, 3, 7, 14, and 28. Venous blood was collected at baseline and follow-up days in participants with UM for determination of malaria parasitaemia, full blood count, reticulocytes, and clinical chemistry. Further, Plasmodium falciparum identification of rapid diagnostic test (RDT) positive samples was done using nested polymerase chain reaction (PCR). Results: Among SCD participants with UM, admission temperature, neutrophils, alanine-aminotransferase, gamma-glutamyl-transferase, and haemoglobin significantly differed between HU recipients (HU+) and steady state, while white blood cell, neutrophils, reticulocytes, bilirubin, urea, and temperature differed significantly between non-HU recipients (no-HU), and steady state. Mean parasitaemia (HU+, 2930.3 vs. no-HU, 1,060, p = 0.74) and adverse events (HU+, 13.9% vs. no-HU, 14.3%), were comparable (p = 0.94). Day 28 reticulocyte count was higher in the HU+ (0.24) (0.17 to 0.37) vs. no-HU, [0.15 (0.09 to 0.27), p = 0.022]. Significant differences in lymphocyte [HU+ 2.74 95% CI (−5.38 to 58.57) vs. no-HU −0.34 (−3.19 to 4.44), p = 0.024]; bilirubin [HU+, −4.44 (−16.36 to 20.74) vs. no-HU −18.37 (−108.79 to −7.16)]; and alanine aminotransferase, [HU+, −4.00 (−48.55 to 6.00) vs. no-HU, 7.00 (−22.00 to 22.00)] were observed during follow up Conclusion: Parasite clearance and adverse event occurrence were comparable between SCD children treated with AL irrespective of HU status. However, distinct patterns of changes in laboratory indices suggest the need for larger, more focused studies.Item Pain Frequency and Health Care Utilization Patterns in Women with Sickle Cell Disease Experiencing Menstruation-Associated Pain Crises(Journal of Women's Health, 2023) Segbefia, C.; Campbell, J.; Tartaglione, I.; et al.Background: Pain crises in sickle cell disease (SCD) lead to high rates of health care utilization. Historically, women have reported higher pain burdens than men, with recent studies showing a temporal association between pain crisis and menstruation. However, health care utilization patterns of SCD women with menstruation associated pain crises have not been reported. We studied the frequency, severity, and health care utilization of menstruation-associated pain crises in SCD women. Materials and Methods: A multinational, cross-sectional cohort study of the SCD phenotype was executed using a validated questionnaire and medical chart review from the Consortium for the Advancement of Sickle Cell Research (CASiRe) cohort. Total number of pain crises, emergency room/day hospital visits, and hospitalizations were collected from a subcohort of 178 SCD women within the past 6 months and previous year. Results: Thirty-nine percent of women reported menstruation-associated pain crises in their lifetime. These women were significantly more likely to be hospitalized compared with those who did not (mean 1.70 vs. 0.67, p = 0.0005). Women reporting menstruation-associated pain crises in the past 6 months also experienced increased hospitalizations compared with those who did not (mean 1.71 vs. 0.75, p = 0.0016). Forty percent of women reported at least four menstruation-associated pain crises in the past 6 months. Conclusions: Nearly 40% of SCD women have menstruation-associated pain crises. Menstruation-associated pain crises are associated with high pain burden and increased rates of hospitalization. Strategies are needed to address health care disparities within gynecologic care in SCD.Item Prospective identifcation of variables as outcomes for treatment (PIVOT): study protocol for a randomised, placebo-controlled trial of hydroxyurea for Ghanaian children and adults with haemoglobin SC disease(Trials, 2023) Smart, L.R.; Segbefa, C.I.; Amissah‑Arthur, K.N.; et al.Background Haemoglobin SC (HbSC) is a common form of sickle cell disease (SCD), especially among individuals of West African ancestry. Persons with HbSC disease sufer from the same clinical complications and reduced quality of life that afect those with sickle cell anaemia (HbSS/Sβ0 ). Retrospective anecdotal data suggest short-term safety and benefts of hydroxyurea for treating HbSC, yet rigorous prospective data are lacking regarding optimal dosing, clinical and laboratory efects, long-term safety and benefts, and appropriate endpoints to monitor. Prospective Investigation of Variables as Outcomes for Treatment (PIVOT) was designed with three aims: (1) to measure the toxici‑ ties of hydroxyurea treatment on laboratory parameters, (2) to assess the efects of hydroxyurea treatment on sickle-related clinical and laboratory parameters, and (3) to identify study endpoints suitable for a future defnitive phase III trial of hydroxyurea treatment of HbSC disease. Methods PIVOT is a randomised, placebo-controlled, double blind clinical trial of hydroxyurea. Approximately 120 children and 120 adults ages 5–50 years with HbSC disease will be enrolled, screened for 2 months, and then ran‑ domised 1:1 to once-daily oral hydroxyurea or placebo. Study treatment will be prescribed initially at 20±5 mg/kg/ day with an opportunity to escalate the dose twice over the frst 6 months. After 12 months of blinded study treat‑ ment, all participants will be ofered open-label hydroxyurea for up to 4 years. Safety outcomes include treatment-related cytopenias, whole blood viscosity, and adverse events. Efcacy outcomes include a variety of laboratory and clinical parameters over the frst 12 months of randomised treatment, including changes in haemoglobin and fetal haemoglobin, intracranial arterial velocities measured by transcranial Doppler ultrasound, cerebral oxygena‑ tion using near infrared spectrometry, spleen volume and kidney size by ultrasound, proteinuria, and retinal imaging. Exploratory outcomes include functional erythrocyte analyses with ektacytometry for red blood cell deformability and point-of-sickling, patient-reported outcomes using the PROMIS questionnaire, and 6-min walk test.Item Prospective identifcation of variables as outcomes for treatment (PIVOT): study protocol for a randomised, placebo-controlled trial of hydroxyurea for Ghanaian children and adults with haemoglobin SC disease(Trials, 2023) Smart, L.R.; Segbefa, C.I.; Latham, T.S.; et al.Background Haemoglobin SC (HbSC) is a common form of sickle cell disease (SCD), especially among individuals of West African ancestry. Persons with HbSC disease sufer from the same clinical complications and reduced quality of life that afect those with sickle cell anaemia (HbSS/Sβ0 ). Retrospective anecdotal data suggest short-term safety and benefts of hydroxyurea for treating HbSC, yet rigorous prospective data are lacking regarding optimal dosing, clinical and laboratory efects, long-term safety and benefts, and appropriate endpoints to monitor. Prospective Investigation of Variables as Outcomes for Treatment (PIVOT) was designed with three aims: (1) to measure the toxici‑ ties of hydroxyurea treatment on laboratory parameters, (2) to assess the efects of hydroxyurea treatment on sickle related clinical and laboratory parameters, and (3) to identify study endpoints suitable for a future defnitive phase III trial of hydroxyurea treatment of HbSC disease. Methods PIVOT is a randomised, placebo-controlled, double blind clinical trial of hydroxyurea. Approximately 120 children and 120 adults ages 5–50 years with HbSC disease will be enrolled, screened for 2 months, and then ran‑ domised 1:1 to once-daily oral hydroxyurea or placebo. Study treatment will be prescribed initially at 20±5 mg/kg/ day with an opportunity to escalate the dose twice over the frst 6 months. After 12 months of blinded study treat‑ ment, all participants will be ofered open-label hydroxyurea for up to 4 years. Safety outcomes include treatment related cytopenias, whole blood viscosity, and adverse events. Efcacy outcomes include a variety of laboratory and clinical parameters over the frst 12 months of randomised treatment, including changes in haemoglobin and fetal haemoglobin, intracranial arterial velocities measured by transcranial Doppler ultrasound, cerebral oxygena‑ tion using near infrared spectrometry, spleen volume and kidney size by ultrasound, proteinuria, and retinal imaging. Exploratory outcomes include functional erythrocyte analyses with ektacytometry for red blood cell deformability and point-of-sickling, patient-reported outcomes using the PROMIS questionnaire, and 6-min walk test. Discussion For children and adults with HbSC disease, PIVOT will determine the safety of hydroxyurea and identify measurable changes in laboratory and clinical parameters, suitable for future prospective testing in a defnitive multi centre phase III clinical trial.Item Multidimensional energy poverty and acute respiratory infection in children under 5 years of age: evidence from 22 low-income and middle income countrie(J Epidemiol Community Health, 2023) Stevens, M.; Zhou, S.; Osman, K.A.Background: In low-income and middle-income countries (LMICs), energy poverty has predominantly been studied from the unidimensional perspective of indoor air pollution. Acute respiratory infection (ARI) in children under 5 years of age is the most important disease associated with indoor air pollution attributable to solid fuel use in LMICs. This study aimed to extend the existing knowledge on the association between energy poverty and ARI among children under 5 years of age in LMICs, by adopting a multidimensional perspective. Methods: Using Demographic and Health Surveys from 22 LMICs, data from 483 088 children were analysed (mean age 2.00 years (SD 1.41); 51.3% male). Energy poverty was measured using the Multidimensional Energy Poverty Index (MEPI) (range 0–1), which comprises five dimensions of essential energy services. Binary logistic regression models were conducted to study the association between MEPI and ARI, adjusting for child, maternal, household and environmental characteristics. Results: A 0.1 increase in MEPI score was associated with greater odds of ARI (aOR 1.05; 95%CI 1.04 to 1.07). Likewise, MEPI indicators using biomass for cooking (aOR 1.15; 95%CI 1.07 to 1.23) and lack of access to electricity (aOR 1.17; 95%CI 1.10 to 1.26), entertainment/education appliances (aOR 1.07; 95%CI 1.02 to 1.13) and household appliances (aOR 1.12; 95%CI 1.04 to 1.21) were associated with greater odds of ARI. Conclusion: Multidimensional energy poverty was associated with greater odds of ARI in children under 5 years of age living in 22 LMICs. Hence, our findings justify the design and implementation of interventions that address energy poverty from a multidimensional perspective, integrating energy affordability and accessibility.Item Adherence to hydroxyurea therapy and health-related quality of life in children with sickle cell anaemia at Korle Bu Teaching Hospital in Ghana(Health Science Investigations Journal, 2023) Dwuma-Badu, D.; Segbefia, C.I.; Druye, A.A.; Dei-Adomakoh, Y.A.Background: Sickle cell anaemia (SCA) causes numerous acute and chronic complications, which can result in significant morbidity and mortality. Hydroxyurea (HU) therapy in individuals with SCA is associated with a reduction in disease severity. Objective: The study aimed to determine the relationship between adherence to HU therapy and health-related quality of life (HRQOL) scores in children with SCA (HbSS) at Korle Bu Teaching Hospital (KBTH) and identify any barriers to HU adherence. Methods: A cross-sectional descriptive study was conducted at the paediatric sickle cell clinic of the KBTH. One hundred and fifteen children aged 2 – 12 years with HbSS receiving HU therapy and their primary caregivers were enrolled on this study. Demographic and HU-related data were obtained from medical records and interviews with caregivers. The 8-item Morisky Medication Adherence Scale (MMAS-8 © ) and haematologic response based on mean corpuscular volume (MCV) were used to assess HU adherence. Caregivers and children aged 8 - 12 years also completed the Paediatric Quality of Life Inventory (PedsQLTM) SCD-module version 3.0. For children aged 5 – 7 years, the PedsQLTM SCD-module version 3.0 was administered by interview. Results: Seventy-nine (68.7%) of children had high adherence to HU therapy using the MMAS-8 © . The mean PedsQLTM scores were 96.9 ± 6.0 and 96.3 ± 7.2 for the child (n = 91) and caregiver (n = 114), respectively. Children with high HU adherence had significantly higher PedsQLTM scores than those with low or moderate adherence. Neither child's current MCV nor mean change in MCV correlated with child or caregiver PedsQLTM scores. The main barrier to HU adherence identified by children aged 8 years was forgetfulness, while the cost of HU was the main barrier to adherence reported by caregivers. Conclusion: Children with SCA with high adherence to HU had the highest HRQOL scores using the PedsQLTM SCD-module version 3.0. Routine assessment of barriers to HU adherence can provide important information to help guide relevant interventionsItem Cardiovascular physical examination as a screening tool for congenital heart disease in newborns at a teaching hospital in Ghana(Ghana Medical Journal, 2023) Owusu-Sekyere, F.; Goka, B.; Adzosii, D.; et al.Objectives: To determine the usefulness of cardiovascular physical examination (CPE) as a screening tool in a low-resource setting for detecting congenital heart disease (CHD) in newborns delivered at the Maternity Unit of Korle Bu Teaching Hospital (KBTH), Accra, Ghana. Design: A hospital-based cross-sectional study with a comparison group component. Setting: Maternity Unit of the KBTH, Accra, Ghana. Participants: Over eight months, newborns aged 1-14 days delivered at ≥ 34 weeks’ gestation at the Maternity Unit, KBTH, were recruited into the study. Intervention: Each newborn was examined using a set of CPE parameters for the presence of congenital heart disease. Those with suggestive features of CHD had a confirmatory echocardiogram test. Main Outcome Measure: Abnormal CPE features and their corresponding echocardiogram findings. Results: A total of 1607 were screened, with 52 newborns showing signs of CHD on CPE, of which 20 newborns were proven on echocardiogram to have congenital heart disease. Abnormal CPE parameter that was associated with CHD was murmur (P=0.001), dysmorphism (p=0.01), newborns with chest recessions (p=0.01) and lethargy (p=0.02). CPE’s sensitivity, specificity, and positive and negative predictive values were 95%, 60.7%, 36.5% and 98,1%, respectively. The most common acyanotic CHD found was isolated atrial septal defect (ASD), followed by patent ductus arteriosus (PDA). The only cyanotic CHD found was a case of tricuspid atresia. Conclusion: Cardiovascular physical examination at birth is an effective and inexpensive screening tool for detecting CHD in newborns, which can easily be utilised in low-resource settings.