Severely ill children in low- and middle-income countries (LMICs) experience high rates of mortal... more Severely ill children in low- and middle-income countries (LMICs) experience high rates of mortality from a broad range of infectious diseases, with the risk of infection-related death compounded by co-existing undernutrition. How undernutrition and acute illness impact immune responses in young children in LMICs remains understudied, and it is unclear what aspects of immunity are compromised in this highly vulnerable population. To address this knowledge gap, we profiled longitudinal whole blood cytokine responses to Toll-like receptor (TLR) ligands among severely ill children (n=63; 2-23 months old) with varied nutritional backgrounds, enrolled in the CHAIN Network cohort from Kampala, Uganda, and Kilifi, Kenya, and compared these responses to similar-aged well children in local communities (n=41). Cytokine responses to ligands for TLR-4 and TLR-7/8, as well as Staphylococcus enterotoxin B (SEB), demonstrated transient impairment in T cell function among acutely ill children, wher...
Journal of Stroke and Cerebrovascular Diseases, 2022
OBJECTIVE Children with sickle cell anaemia (SCA) are highly susceptible to cerebrovascular injur... more OBJECTIVE Children with sickle cell anaemia (SCA) are highly susceptible to cerebrovascular injury. We performed brain magnetic resonance imaging and angiography (MRI-MRA) in Ugandan children with SCA to identify structural cerebrovascular abnormalities and examine their relationship to standardized clinical assessments. METHODS A sub-sample (n=81) was selected from a cross-sectional study of children attending SCA clinic, including 52 (64.2%) with and 29 (35.8%) without clinically detected abnormalities. Clinical evaluation included assessment for prior stroke, cognitive testing and cerebral arterial transcranial doppler (TCD) flow velocity. MRI-MRA scans were interpreted by at least two neuroradiologists. RESULTS Mean age was 6.5±2.7 years, with 39 (48.1%) female. Mean haemoglobin was 7.3±0.9 g/dl. Overall, 13 (16.0%) were malnourished. Infarcts and/or stenoses were detected in 55 (67.9%) participants, with stenoses primarily in the anterior circulation. Infarcts were seen in those with normal 17/29 (58.6%) or abnormal 34/52 (65.4%) clinical testing (p=0.181). Neither abnormal MRI nor MRA was associated with age, sex, haemoglobin, or malnutrition. Abnormal MRA was highly associated with infarcts (p<0.0001). Participants with abnormal imaging had two-fold higher proportion of stroke on exam and/or impaired cognition. Stroke on exam was strongly associated with an imaging abnormality after adjusting for age, sex, malnutrition, and haemoglobin (OR 11.8, 95%CI 1.87-74.2). CONCLUSION Over half of these SCA children had cerebrovascular infarcts and/or arterial stenoses. Cerebrovascular disease was frequently undetectable by clinical assessments. While rarely available in under-resourced settings, MRI-MRA brain imaging is an important tool for defining SCA cerebrovascular disease and for assessing impact of clinical intervention trials.
Childhood tuberculosis (TB) is consistently under-detected in most high-burden countries, includi... more Childhood tuberculosis (TB) is consistently under-detected in most high-burden countries, including Uganda, especially in young children at high risk for severe disease and mortality. TB preventive treatment (TPT) for high-risk child contacts is also poorly implemented. The centralised concentration of services for child TB at the referral level is a major challenge in the prevention, detection and treatment of TB in children. In 2015, the DETECT Child TB Project was implemented in two districts of Uganda and involved decentralisation of healthcare services for child TB from tertiary to primary healthcare facilities, along with establishing linkages to support community-based household contact screening and management. The intervention resulted in improved case finding of child and adult TB cases, improved treatment outcomes for child TB and high uptake and completion of TPT for eligible child contacts. A detailed description of the development and implementation of this project is ...
Additional file 4: Supplemental Figure 3. Weight gain velocity presented as mean (standard error)... more Additional file 4: Supplemental Figure 3. Weight gain velocity presented as mean (standard error) g/kg/d for children with severe acute malnutrition who stayed longer than 8 weeks in outpatient therapeutic care by edema at admission.
Additional file 2: Supplemental Figure 1. Spaghetti plot showing variability in weight gain veloc... more Additional file 2: Supplemental Figure 1. Spaghetti plot showing variability in weight gain velocity among four selected children with severe acute malnutrition by treatment phase. Data are presented as absolute values (g/kg/d). Child 1, 16 months old non-breastfed, HIV positive with oedema and diarrhoea at admission; child 2, 51 months old, non-breastfed, HIV negative and, with oedema and diarrhoea at admission; child 3, 11 months old, breastfed, HIV exposed and, with no diarrhoea or oedema at admission; child 4, 23 months old, non-breastfed, HIV exposed, with diarrhoea at admission and no oedema at admission.
To determine the prevalence of anaemia in children aged 6-24 months living in a high malaria tran... more To determine the prevalence of anaemia in children aged 6-24 months living in a high malaria transmission setting in Burundi, we used laboratory protocols to test anaemia using a portable hemocue analyser and screend for malaria using a Malaria Ag Pf/Pan rapid test; a rapid, qualitative test for the detection of HRP-II (Histidine rich protein II- HRP-2). We also detected Soil-Transmitted Helminthiasis and other faecal parasites microscopically by wet preparation and Kato-Katz technique. Laboratory protocols were used in cross-sectional that determined the prevalence and factors associated with anaemia in children aged 6-24 months living in a high malaria transmission setting in northern Burundi.
months whereas women, had a rate of 3.30 kg/m2 (95 % CI:-0.11, 6.72). There were minimal changes ... more months whereas women, had a rate of 3.30 kg/m2 (95 % CI:-0.11, 6.72). There were minimal changes in body Mupere et al. BMC Infectious Diseases 2014, 14:24
American Journal of Tropical Medicine and Hygiene, 2017
This analysis describes adherence to antibiotic guidelines during the first 48 hours of admission... more This analysis describes adherence to antibiotic guidelines during the first 48 hours of admission. Adherence was defined as a regimen consistent with institutional, national, or international recommendations.
A thesis submitted in fulfillment of the requirements of the degree of Doctor of Philosophy Depar... more A thesis submitted in fulfillment of the requirements of the degree of Doctor of Philosophy Department of Epidemiology and Biostatistics, Case Western Reserve University.
BACKGROUND A unique feature of previous Ebola outbreaks has been the relative sparing of children... more BACKGROUND A unique feature of previous Ebola outbreaks has been the relative sparing of children. For the first time, an out break of an unusual illness-Ebola haemorrhagic fever occurred in Northern Uganda Gulu district. OBJECTIVES To describe the epidemiologic and clinical aspects of hospitalised children and adolescents on the isolation wards. METHODS A retrospective descriptive survey of hospital records for hospitalised children and adolescents under 18 years on the isolation wards in Gulu, Northern Uganda was conducted. All patient test notes were consecutively reviewed and non was excluded because being deficient. RESULTS Analysis revealed that 90 out of the 218 national laboratory confirmed Ebola cases were children and adolescents with a case fatality of 40%. The mean age was 8.2 years +/- SD 5.6 with a range of 16.99 years. The youngest child on the isolation wards was 3 days old. The under fives contributed the highest admission (35%) among children and adolescents; and c...
Objectives Ninety-seven % of children living in the Katanga area of Kampala, Uganda, have elevate... more Objectives Ninety-seven % of children living in the Katanga area of Kampala, Uganda, have elevated blood lead (Pb), and 30% have elevated manganese (Mn). Children with iron deficiency (ID) may have higher blood concentrations of both metals as each share the same intestinal transported as iron (DMT1). We characterized the iron status of children living in Katanga and determined whether children with poorer iron status had elevated blood Pb and Mn. We hypothesized that higher concentrations of Pb and Mn will be associated with iron deficiency. Methods We measured plasma concentrations of iron biomarkers [hemoglobin (Hb), ferritin, soluble transferrin receptor (sTfR), hepcidin] in 100 children 6–59 months living in the Katanga urban settlement who had participated in a survey environmental metals exposure. We compared whole blood concentrations of Pb and Mn by different definitions of ID and by median hepcidin (Hb < 11.0 g/dL; sTfR > 8.3 mg/L; ferritin < 12.0 μg/L; hepcidin &...
Background Weight gain is routinely monitored to assess hydration and growth during treatment of ... more Background Weight gain is routinely monitored to assess hydration and growth during treatment of children with complicated severe acute malnutrition (SAM). However, changes in weight and mid-upper arm circumference (MUAC) gain velocities over time are scarcely described. We assessed weight and MUAC gain velocities in 6–59 mo-old children with complicated SAM by treatment phase and edema status. Methods This was a prospective study, nested in a randomized/probiotic trial (ISRCTN16454889). Weight and MUAC gain velocities were assessed by treatment phase and edema at admission using linear mixed-effects models. Results Among 400 children enrolled, the median (IQR) age was 15.0 (11.2;19.2) months, 58% were males, and 65% presented with edema. During inpatient therapeutic care (ITC), children with edema vs no edema at admission had negative weight gain velocity in the stabilization phase [differences at day 3 and 4 were − 11.26 (95% CI: − 20.73; − 1.79) g/kg/d and − 13.09 (95% CI: − 23.1...
PURPOSE Specialized multidisciplinary care is central to childhood cancer control. Expertise and ... more PURPOSE Specialized multidisciplinary care is central to childhood cancer control. Expertise and infrastructure in the pediatric disciplines of hematology, surgery, critical care, nursing, and pathology are as critical as pediatric oncology. Survival of the majority of children with cancer globally remains dismal because of the scarcity of multidisciplinary pediatric subspecialty services. We present the innovative approach and impact of Texas Children’s Global HOPE initiatives to cost-effectively develop capacity for specialized multidisciplinary cancer care for children in sub-Sahara Africa (SSA). METHODS Global HOPE designed and supports subspecialty training and contingent infrastructure building in SSA in the following disciplines that are critical to pediatric cancer care: pediatric hematology and oncology (PHO), pediatric surgery, pediatric critical care, anatomic and molecular pathology, and pediatric oncology nursing. Key principles underlying the design of each disciplinar...
Severely ill children in low- and middle-income countries (LMICs) experience high rates of mortal... more Severely ill children in low- and middle-income countries (LMICs) experience high rates of mortality from a broad range of infectious diseases, with the risk of infection-related death compounded by co-existing undernutrition. How undernutrition and acute illness impact immune responses in young children in LMICs remains understudied, and it is unclear what aspects of immunity are compromised in this highly vulnerable population. To address this knowledge gap, we profiled longitudinal whole blood cytokine responses to Toll-like receptor (TLR) ligands among severely ill children (n=63; 2-23 months old) with varied nutritional backgrounds, enrolled in the CHAIN Network cohort from Kampala, Uganda, and Kilifi, Kenya, and compared these responses to similar-aged well children in local communities (n=41). Cytokine responses to ligands for TLR-4 and TLR-7/8, as well as Staphylococcus enterotoxin B (SEB), demonstrated transient impairment in T cell function among acutely ill children, wher...
Journal of Stroke and Cerebrovascular Diseases, 2022
OBJECTIVE Children with sickle cell anaemia (SCA) are highly susceptible to cerebrovascular injur... more OBJECTIVE Children with sickle cell anaemia (SCA) are highly susceptible to cerebrovascular injury. We performed brain magnetic resonance imaging and angiography (MRI-MRA) in Ugandan children with SCA to identify structural cerebrovascular abnormalities and examine their relationship to standardized clinical assessments. METHODS A sub-sample (n=81) was selected from a cross-sectional study of children attending SCA clinic, including 52 (64.2%) with and 29 (35.8%) without clinically detected abnormalities. Clinical evaluation included assessment for prior stroke, cognitive testing and cerebral arterial transcranial doppler (TCD) flow velocity. MRI-MRA scans were interpreted by at least two neuroradiologists. RESULTS Mean age was 6.5±2.7 years, with 39 (48.1%) female. Mean haemoglobin was 7.3±0.9 g/dl. Overall, 13 (16.0%) were malnourished. Infarcts and/or stenoses were detected in 55 (67.9%) participants, with stenoses primarily in the anterior circulation. Infarcts were seen in those with normal 17/29 (58.6%) or abnormal 34/52 (65.4%) clinical testing (p=0.181). Neither abnormal MRI nor MRA was associated with age, sex, haemoglobin, or malnutrition. Abnormal MRA was highly associated with infarcts (p<0.0001). Participants with abnormal imaging had two-fold higher proportion of stroke on exam and/or impaired cognition. Stroke on exam was strongly associated with an imaging abnormality after adjusting for age, sex, malnutrition, and haemoglobin (OR 11.8, 95%CI 1.87-74.2). CONCLUSION Over half of these SCA children had cerebrovascular infarcts and/or arterial stenoses. Cerebrovascular disease was frequently undetectable by clinical assessments. While rarely available in under-resourced settings, MRI-MRA brain imaging is an important tool for defining SCA cerebrovascular disease and for assessing impact of clinical intervention trials.
Childhood tuberculosis (TB) is consistently under-detected in most high-burden countries, includi... more Childhood tuberculosis (TB) is consistently under-detected in most high-burden countries, including Uganda, especially in young children at high risk for severe disease and mortality. TB preventive treatment (TPT) for high-risk child contacts is also poorly implemented. The centralised concentration of services for child TB at the referral level is a major challenge in the prevention, detection and treatment of TB in children. In 2015, the DETECT Child TB Project was implemented in two districts of Uganda and involved decentralisation of healthcare services for child TB from tertiary to primary healthcare facilities, along with establishing linkages to support community-based household contact screening and management. The intervention resulted in improved case finding of child and adult TB cases, improved treatment outcomes for child TB and high uptake and completion of TPT for eligible child contacts. A detailed description of the development and implementation of this project is ...
Additional file 4: Supplemental Figure 3. Weight gain velocity presented as mean (standard error)... more Additional file 4: Supplemental Figure 3. Weight gain velocity presented as mean (standard error) g/kg/d for children with severe acute malnutrition who stayed longer than 8 weeks in outpatient therapeutic care by edema at admission.
Additional file 2: Supplemental Figure 1. Spaghetti plot showing variability in weight gain veloc... more Additional file 2: Supplemental Figure 1. Spaghetti plot showing variability in weight gain velocity among four selected children with severe acute malnutrition by treatment phase. Data are presented as absolute values (g/kg/d). Child 1, 16 months old non-breastfed, HIV positive with oedema and diarrhoea at admission; child 2, 51 months old, non-breastfed, HIV negative and, with oedema and diarrhoea at admission; child 3, 11 months old, breastfed, HIV exposed and, with no diarrhoea or oedema at admission; child 4, 23 months old, non-breastfed, HIV exposed, with diarrhoea at admission and no oedema at admission.
To determine the prevalence of anaemia in children aged 6-24 months living in a high malaria tran... more To determine the prevalence of anaemia in children aged 6-24 months living in a high malaria transmission setting in Burundi, we used laboratory protocols to test anaemia using a portable hemocue analyser and screend for malaria using a Malaria Ag Pf/Pan rapid test; a rapid, qualitative test for the detection of HRP-II (Histidine rich protein II- HRP-2). We also detected Soil-Transmitted Helminthiasis and other faecal parasites microscopically by wet preparation and Kato-Katz technique. Laboratory protocols were used in cross-sectional that determined the prevalence and factors associated with anaemia in children aged 6-24 months living in a high malaria transmission setting in northern Burundi.
months whereas women, had a rate of 3.30 kg/m2 (95 % CI:-0.11, 6.72). There were minimal changes ... more months whereas women, had a rate of 3.30 kg/m2 (95 % CI:-0.11, 6.72). There were minimal changes in body Mupere et al. BMC Infectious Diseases 2014, 14:24
American Journal of Tropical Medicine and Hygiene, 2017
This analysis describes adherence to antibiotic guidelines during the first 48 hours of admission... more This analysis describes adherence to antibiotic guidelines during the first 48 hours of admission. Adherence was defined as a regimen consistent with institutional, national, or international recommendations.
A thesis submitted in fulfillment of the requirements of the degree of Doctor of Philosophy Depar... more A thesis submitted in fulfillment of the requirements of the degree of Doctor of Philosophy Department of Epidemiology and Biostatistics, Case Western Reserve University.
BACKGROUND A unique feature of previous Ebola outbreaks has been the relative sparing of children... more BACKGROUND A unique feature of previous Ebola outbreaks has been the relative sparing of children. For the first time, an out break of an unusual illness-Ebola haemorrhagic fever occurred in Northern Uganda Gulu district. OBJECTIVES To describe the epidemiologic and clinical aspects of hospitalised children and adolescents on the isolation wards. METHODS A retrospective descriptive survey of hospital records for hospitalised children and adolescents under 18 years on the isolation wards in Gulu, Northern Uganda was conducted. All patient test notes were consecutively reviewed and non was excluded because being deficient. RESULTS Analysis revealed that 90 out of the 218 national laboratory confirmed Ebola cases were children and adolescents with a case fatality of 40%. The mean age was 8.2 years +/- SD 5.6 with a range of 16.99 years. The youngest child on the isolation wards was 3 days old. The under fives contributed the highest admission (35%) among children and adolescents; and c...
Objectives Ninety-seven % of children living in the Katanga area of Kampala, Uganda, have elevate... more Objectives Ninety-seven % of children living in the Katanga area of Kampala, Uganda, have elevated blood lead (Pb), and 30% have elevated manganese (Mn). Children with iron deficiency (ID) may have higher blood concentrations of both metals as each share the same intestinal transported as iron (DMT1). We characterized the iron status of children living in Katanga and determined whether children with poorer iron status had elevated blood Pb and Mn. We hypothesized that higher concentrations of Pb and Mn will be associated with iron deficiency. Methods We measured plasma concentrations of iron biomarkers [hemoglobin (Hb), ferritin, soluble transferrin receptor (sTfR), hepcidin] in 100 children 6–59 months living in the Katanga urban settlement who had participated in a survey environmental metals exposure. We compared whole blood concentrations of Pb and Mn by different definitions of ID and by median hepcidin (Hb < 11.0 g/dL; sTfR > 8.3 mg/L; ferritin < 12.0 μg/L; hepcidin &...
Background Weight gain is routinely monitored to assess hydration and growth during treatment of ... more Background Weight gain is routinely monitored to assess hydration and growth during treatment of children with complicated severe acute malnutrition (SAM). However, changes in weight and mid-upper arm circumference (MUAC) gain velocities over time are scarcely described. We assessed weight and MUAC gain velocities in 6–59 mo-old children with complicated SAM by treatment phase and edema status. Methods This was a prospective study, nested in a randomized/probiotic trial (ISRCTN16454889). Weight and MUAC gain velocities were assessed by treatment phase and edema at admission using linear mixed-effects models. Results Among 400 children enrolled, the median (IQR) age was 15.0 (11.2;19.2) months, 58% were males, and 65% presented with edema. During inpatient therapeutic care (ITC), children with edema vs no edema at admission had negative weight gain velocity in the stabilization phase [differences at day 3 and 4 were − 11.26 (95% CI: − 20.73; − 1.79) g/kg/d and − 13.09 (95% CI: − 23.1...
PURPOSE Specialized multidisciplinary care is central to childhood cancer control. Expertise and ... more PURPOSE Specialized multidisciplinary care is central to childhood cancer control. Expertise and infrastructure in the pediatric disciplines of hematology, surgery, critical care, nursing, and pathology are as critical as pediatric oncology. Survival of the majority of children with cancer globally remains dismal because of the scarcity of multidisciplinary pediatric subspecialty services. We present the innovative approach and impact of Texas Children’s Global HOPE initiatives to cost-effectively develop capacity for specialized multidisciplinary cancer care for children in sub-Sahara Africa (SSA). METHODS Global HOPE designed and supports subspecialty training and contingent infrastructure building in SSA in the following disciplines that are critical to pediatric cancer care: pediatric hematology and oncology (PHO), pediatric surgery, pediatric critical care, anatomic and molecular pathology, and pediatric oncology nursing. Key principles underlying the design of each disciplinar...
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