Ugandan Children Research Articles

Azithromycin in severe malaria bacterial co-infection in African children (TABS-PKPD): a phase II randomised controlled trial.

African children with severe malaria are at increased risk of non-typhoidal salmonellae co-infection. Broad-spectrum antibiotics are recommended by guidelines but the optimal class and dose have not been established. We investigated the optimal dose of oral dispersible azithromycin and whether simple clinical criteria and point-of-care biomarkers could target antibiotics to those at greatest risk of bacterial co-infection. We conducted a phase I/II trial in Ugandan children with severe malaria comparing a 5-day course of azithromycin: 10, 15 and 20 mg/kg of azithromycin (prescribed by weight bands) spanning the dose-range effective for other salmonellae infection. We generated relevant pharmacokinetic (PK) data by sparse sampling during dosing intervals and investigated associations between azithromycin exposure and potential mechanisms (PK-pharmacodynamics) using change in C-reactive protein (CRP), a putative marker of sepsis, at 72 h (continuous) and microbiological cure (7-day) (binary), alone and as a composite with 7-day and 90-day survival. To assess whether clinical or biomarkers could identify those at risk of sepsis, a non-severe malaria control was concurrently enrolled. Between January 2020 and January 2022, 105 cases were randomised azithromycin doses: 35 to 10mg/kg, 35 to 15mg/kg and 35 to 20mg/kg. Fifty non-severe malaria controls were concurrently enrolled. CRP reduced in all arms by 72h with a mean reduction of 65.8mg/L (95% CI 57.1, 74.5) in the 10mg/kg arm, 64.8mg/L (95% CI 56.5, 73.1; p = 0.87) in the 20mg/kg arm and a smaller reduction 51.2mg/L (95% CI 42.9, 59.5; p = 0.02) in the 15mg/kg arm. Microbiological cure alone outcome was not analysed as only one pathogen was found among cases. Three events contributed to the composite outcome of 7-day survival and microbiological cure, with no events in the 15mg/kg arm. The odds ratio comparing 20 vs 10mg/kg was 0.50 (95% CI 0.04, 5.79); p = 0.58. Due to the low number of pathogens identified, it was not possible to identify better methods for targeting antibiotics including both the cases and controls. We found no evidence for an association between systemic azithromycin exposure and reduction in CRP. Further work is needed to better identify children at highest risk from bacterial co-infection. ISRCTN49726849 (registered on 27th October 2017).

Dynamics of osteopontin levels and correlation with parasitemia in acute malaria in Uganda and Sweden

BackgroundMalaria remains a significant public health concern, especially for the deadliest parasite, Plasmodium falciparum. During acute malaria, various cytokines, including osteopontin (OPN), regulate the immune response. OPN has been shown to be protective against malaria in mice. Nonetheless, its precise function and potential ability to control parasites during acute malaria in humans remain poorly understood.ResultsBlood samples were collected from Swedish adults with imported malaria, Ugandan children and adults with symptomatic malaria (including follow-up after 42 days), Ugandans with non-malarial fever and healthy individuals from both Uganda and Sweden. Parasitemia was determined by microscopy. Malaria-negative samples were verified by LAMP. OPN and interferon-γ (IFN- γ) levels were measured using ELISA. In children, OPN levels were significantly higher during acute infection compared to levels after 42 days, whereas Ugandan adults showed no difference. Swedish adults with imported malaria had elevated OPN levels compared to both Swedish controls and Ugandan adults with malaria. Parasitemia was significantly correlated with both OPN and IFN-γ levels across the entire cohort. While a significant correlation between OPN and IFN-γ was evident overall, it remained statistically significant only in Ugandan adults when analyzed by subgroups. This suggests that OPN is not just a general marker of inflammation but may be regulated differently during the development of malaria immunity.ConclusionsIn acute malaria, elevated OPN levels showed a stronger correlation with lack of immunity than age. These findings underscore the potential importance of OPN in malaria, particularly in non-immune individuals.

Sub- and supratherapeutic efavirenz plasma concentrations with risk for HIV therapy failure are mainly genetically explained in Ugandan children: The prospective GENEFA cohort study.

Interindividual variations in efavirenz (EFV) plasma concentrations are extensive, but paediatric data on its consequences for viral control are scarce. The aim of this study was to explore the role of genetic variation in achieving therapeutic efavirenz plasma concentrations in a cohort of Ugandan children and the linkage between genetic CYP2B6 variants, EFV plasma variability, viral resistance and viral outcome. Ninety-nine treatment-naïve children, aged 3-12 years and living with HIV, were followed for 24 weeks after ART initiation assessing mid-dose efavirenz plasma concentrations, HIV RNA, HIV drug resistance and adherence. Polymorphisms in genes coding for drug-metabolizing enzymes were genotyped. Efavirenz concentrations were determined by liquid chromatography coupled with high-resolution tandem mass spectrometry. Metabolizer phenotype was predicted from composite genotypes of CYP2B6 (c.516G>T and c.983 T>C). A mixed effects restricted maximum likelihood regression model was used to identify important factors for efavirenz exposure. Efavirenz plasma concentrations were below the therapeutic interval (1000-4000 mg/mL) in 12-17% and above in 21-24% of measurements. Eight children had persisting subtherapeutic concentrations, five of which failed virologically and three acquired at least one new resistant mutation. Multivariate modelling explained 70% of interindividual variation in plasma concentration, with treatment duration, adherence, CYP2B6c.136A>G, and metabolizer phenotype as independent predictors of EFV concentration. In univariate analysis, metabolizer phenotype explained 50% of interindividual variation. Metabolizer phenotype explained 50% of interindividual variation in efavirenz plasma concentration. Autoinduction was not confirmed and >33% of the concentrations were outside the therapeutic interval. Subtherapeutic concentrations worsened virological resistance and outcomes. Genotype-based dosing may help avert both sub- and supratherapeutic efavirenz plasma concentrations in Ugandan children.

Low prevalence of soil transmitted helminth infection in Ugandan children hospitalized with severe malaria.

Co-infection by intestinal helminths and Plasmodium spp. may be common in endemic communities. Several studies have identified a relationship between helminth infection, Plasmodium spp. infection and malaria severity. However, the relationship is not well defined, and results are inconclusive. We analyzed 202 stool samples from a cohort of children with severe malaria enrolled in two hospitals in Uganda from 2014-2017 and asymptomatic community children from the same household or neighborhood and enrolled at the same time, all 6 months to 48 months of age. We investigated if intestinal helminth infection modified risk of severe malaria. We extracted nucleic acids from stool and tested them for six helminth species ( Anyclostoma duodenale, Ascaris lumbricoides, Necator americanus, Strongyloides stercolaris, Trichuris trichiura, Shistosoma mansoni ) using highly sensitive quantitative PCR. We found a low prevalence of infection by ≥1 intestinal helminth species in children with severe malaria (5.1%, n=9/177) and community control children (4.0%, n=1/25). Infection by ≥1 of the helminths assessed was not associated with severe malaria (aRR = 1.0, 95% Confidence Interval = 0.82, 1.3, p = 0.78). In 2003 Uganda instituted a national deworming program, with anti-helminth medication provided twice annually to children 6 months to 5 years of age. In these areas of Uganda, the national deworming campaign has been highly successful, as stool-based helminth infection was rare even when using highly sensitive methods of detection and was not a major contributor to risk of severe malaria.

Oral health status and factors associated with oral health of primary school children in Gulu district, northern Uganda

BackgroundGlobally, oral diseases remain a major public health problem. However, there is limited information about the oral health status and factors associated with oral disease among children in Uganda. The aim of this study was to examine the oral health status and factors associated with oral health of primary school children in urban and rural areas of the Gulu district of northern Uganda.MethodsA comparative cross-sectional study was conducted among 356 school children aged 11–13 years attending six schools located in urban and rural areas. The children received a clinical oral examination and participated in a questionnaire survey that collected information on sociodemographic and oral health knowledge, attitude, and practices. All data were entered and analysed using IBM SPSS Statistics for Windows, Version 26.0. Armonk, NY: IBM Corp statistical software. Logistic regression analyses examined factors associated with dental caries and gingival bleeding.ResultsOf the 356 children (11–13 years) included, the mean age was 12.2 years, 140 (39.3%) were male and 176 (49.4%) were from urban areas. The proportion of school children with dental caries was 33.6% (n = 119), with the mean decayed, missing due to caries, and filled teeth (DMFT) index of 0.81 (25th percentile = 0; 75th percentile = 1.00). There was no significant difference in caries prevalence between rural and urban children (31.6% versus 35.6%, p = 0.33). Of the children involved in the study, 141(39.8%) had gum bleeding. The mean oral knowledge score was 2.85 ± 1.53 (range, 0–7), while the mean attitude, hygiene practice, frequency of sweets consumption, and oral health related impact scores were 4.25 ± 1.23 (range, 1–6), 5.40 ± 1.81 (range, 0–9), 25.66 ± 4.29 (range 9–54) and 2.1 ± 1.65 (range, 0–6), respectively. Using logistic regression analyses, as oral health knowledge score increased the odds of not having dental caries increased (aOR = 1.19, 95% CI 1.02–1.39).ConclusionThe prevalence of dental caries and gum bleeding of primary school children in Gulu district is high. Children lacked knowledge on causes of oral disease, and behaviour towards oral disease prevention. In addition, oral health knowledge scores were significantly associated with dental caries. Oral health education programs in schools should emphasise providing skills-based education.

Poverty Reduction and Family Functioning: Results from an Experimental Study in Sub-Saharan Africa

The study tests the effect of poverty-reduction intervention on family functioning reported by AIDS-orphaned children in extended families in Southern Uganda by asking two questions: (1) based on children’s reports, how does poverty reduction intervention affect family functioning? and (2) to what extent do these effects vary by a child’s gender and orphanhood status? Informed by the social causation theory, family stress model, and asset theory, the study aims to address the existing knowledge gap on effects of poverty reduction interventions on family functioning in low-income families caring for AIDS orphaned children in Uganda. We ran multilevel regression models using longitudinal data collected in a cluster-randomized controlled trial from N = 1410 children (n = 621 boys and n = 789 girls) recruited from 48 rural primary schools in Uganda. Survey data was collected every 12 months over the course of 5 years. The average age of children at enrollment was 13 years. We found significant positive effects of the intervention on family cohesion, family communication, and child-caregiver relationship. Effects vary by child’s gender and orphanhood category. Intervention improves family communication for boys, while improving family cohesion and quality of child-caregiver relationship for girls. Single maternal orphans reported improved family communication, while single paternal orphans reported improved child-caregiver relationship. Poverty reduction interventions are important to improve family functioning for low-income families. Variations by child’s gender and orphanhood status have not been reported in previous studies, and our findings underscore the importance of continued research in this area.

Improving oxygen services for children in Uganda

Improving oxygen services for children in Uganda

Clinical immunity to malaria involves epigenetic reprogramming of innate immune cells.

The regulation of inflammation is a critical aspect of disease tolerance and naturally acquired clinical immunity to malaria. Here, we demonstrate using RNA sequencing and epigenetic landscape profiling by cytometry by time-of-flight, that the regulation of inflammatory pathways during asymptomatic parasitemia occurs downstream of pathogen sensing-at the epigenetic level. The abundance of certain epigenetic markers (methylation of H3K27 and dimethylation of arginine residues) and decreased prevalence of histone variant H3.3 correlated with suppressed cytokine responses among monocytes of Ugandan children. Such an epigenetic signature was observed across diverse immune cell populations and not only characterized active asymptomatic parasitemia but also correlated with future long-term disease tolerance and clinical immunity when observed in uninfected children. Pseudotime analyses revealed a potential trajectory of epigenetic change that correlated with a child's age and recent parasite exposure and paralleled the acquisition of clinical immunity. Thus, our data support a model whereby exposure to Plasmodium falciparum induces epigenetic changes that regulate excessive inflammation and contribute to naturally acquire clinical immunity to malaria.

Correlates of body composition in children with stunting: A cross-sectional study in Uganda

Development of body composition (BC) may be disrupted in children with stunting. Such disruption may affect the later risk of excess adiposity and metabolic health, yet few studies have investigated correlates of BC in children with stunting. We aimed to investigate nutritional status, infection and inflammation, breastfeeding behaviors, and other factors as correlates of BC in children with stunting. Among Ugandan children with a height-for-age z-score <-2, BC was estimated using bioelectrical impedance analysis and compared with United Kingdom references. We used multiple linear regression analysis to identify correlates of fat mass (FM), fat-free mass (FFM), FM-index (FMI), and FFM index (FFMI) and height, adjusting for gender and age. In 750 children aged 1-5 y, FMI was 0.46 (95% confidence interval [CI]: 0.38, 0.54] and FFMI 0.18 [95% CI: 0.11, 0.26) z-scores lower than United Kingdom references. Elevated serum α1-acid glycoprotein was associated with 1.14 [0.76, 1.52] cm lower height, 0.50 [0.35, 0.65] kg/m2 less FFMI, and 0.48 [0.31, 0.66] kg/m2 greater FMI. Similar, weaker, associations for elevated serum C-reactive protein were detected. A positive malaria rapid test was associated with 0.64 [0.25, 1.02] cm shorter height, but 0.36 [0.18, 0.54] kg/m2 greater FMI. Anemia (according to hemoglobin) was associated with 0.20 [0.07, 0.33] kg less FFM in proportion to shorter height. Longer breastfeeding duration was associated with 0.03 [0.02, 0.04] kg greater FFM per month, in proportion to greater height. These children exhibited deficits in FM and FFM, proportionally to their stunted height, compared with United Kingdom references. Systemic inflammation correlated inversely with linear growth and FFM but positively with fatness, making it a possible target for intervention where fat-free tissue accretion is desirable. Longer breastfeeding may offer protection to lean linear growth, but findings for micronutrients were less clear. Longitudinal studies are warranted to support these findings. The study was registered at www.isrctn.com (Ref.ISRCTN13093195).

Sex-disaggregated analysis of acute kidney injury in hospitalized children with sickle cell anemia in Uganda.

A growing body of research is categorizing sex differences in both sickle cell anemia (SCA) and acute kidney injury (AKI); however, most of this work is being conducted in high-resource settings. Here, we evaluated risk factors and clinical parameters associated with AKI and AKI severity, stratified by sex, in a cohort of children hospitalized with SCA and vaso-occlusive pain crisis (VOC). The purpose of this study was to explore sex disparities in a high-risk, vulnerable population. This study was a secondary analysis of data collected from a cohort of Ugandan children between 2 and 18 yr of age prospectively enrolled. A total of 185 children were enrolled in the primary study; 41.6% were female and 58.4% were male, with a median age of 8.9 yr. Incident or worsening AKI (P = 0.026) occurred more frequently in female compared with male children, despite no differences in AKI on admission. Female children also had altered markers of renal function including higher creatinine levels at admission (P = 0.03), higher peak creatinine (P = 0.006), and higher urine neutrophil gelatinase-associated lipocalin (NGAL) at admission (P = 0.003) compared with male children. Female children had elevated total (P = 0.045) and conjugated bilirubin at admission (P = 0.02) compared with male children and higher rates of hematuria at admission (P = 0.004). Here, we report sex differences in AKI in children with SCA and VOC, including increased incidence and worsening of AKI in female pediatric patients, in association with an increase in biological indicators of poor renal function including creatinine, estimated glomerular filtration rate, and NGAL.NEW & NOTEWORTHY In this study, we report an increased risk of developing acute kidney injury (AKI) during hospitalization, worsening AKI, and death among females with sickle cell anemia (SCA) hospitalized with an acute pain crisis compared with males. The sex differences in AKI were not explained by socioeconomic differences, severity of pain, or disease severity among females compared with males. Together, these data suggest that female children with SCA may be at increased risk of AKI.

Academic achievement in Ugandan children with sickle cell anaemia: A cross-sectional study.

Academic achievement in school-age children is crucial for advancing learning goals. Children with sickle cell anaemia (SCA) in Sub-Saharan Africa may be at risk of disease-associated school difficulties. Limited data exist on the academic achievement of children with SCA in the region. This study aimed to assess academic achievement of children with SCA in Uganda compared to siblings without SCA. A cross-sectional study conducted at Mulago Hospital SCA Clinic in Uganda. School-going children (6-12 years) with SCA and age-matched sibling controls without SCA. Academic achievement was tested using the Wide Range Achievement Test, Fourth Edition (WRAT4). Outcome measures were spelling, mathematical computation, word reading, and sentence comprehension by age-normalized Z-scores on the WRAT4 test. Among 68 SCA and 69 control, the mean age (standard deviation) was 9.44 (2.04) and 9.42 (2.02) years and males were 55.9% and 46.4% respectively. Mean haemoglobin was 7.9 (SD 0.89)g/dL in the SCA group versus 12.8 (SD 0.89)g/dL in the controls, (p<0.001). Children with SCA scored lower in spelling, (mean difference [95% confidence interval] - 0.36 [-0.02 to -0.69], p=0.04) and mathematical computation, (mean difference [95% confidence interval] -0.51 [-0.17 to -0.85], p=0.003) than the controls. In the SCA group, lower scores in spelling correlated with age, while males performed better than females in mathematical computation. School-aged children with SCA are at risk of poor performance in spelling and mathematical computation. Our findings support the need for educational evaluation and possible support, especially in these two areas.

Associations Between Fatty Acid Levels and Perinatal HIV Status and In-Utero/Peripartum Antiretroviral Therapy (IPA) Exposure Among Ugandan Children and Adolescents

Associations Between Fatty Acid Levels and Perinatal HIV Status and In-Utero/Peripartum Antiretroviral Therapy (IPA) Exposure Among Ugandan Children and Adolescents

Heparin-Binding Protein Stratifies Mortality Risk Among Ugandan Children Hospitalized With Respiratory Distress.

Current prognostic tools do not reliably and objectively identify children with pneumonia at risk of a severe or life-threatening episode. Heparin-binding protein (HBP) is a host immune protein that is released in response to infection. We hypothesized that measuring HBP concentrations at hospital admission could help risk-stratify children with pneumonia and identify those at higher risk of an adverse prognosis. We evaluated the prognostic accuracy of HBP for predicting in-hospital mortality among children with respiratory distress, and whether HBP could improve the accuracy of validated composite clinical severity scores. Of 778 Ugandan children under 5 years of age and presenting with clinically defined pneumonia, 60 (7.7%) died during hospital admission. HBP concentrations at presentation were significantly higher in children with fatal outcomes (median, 76 ng/mL [interquartile range {IQR}, 41-150]) compared to children who survived (median, 31 ng/mL [IQR, 18-57]) (P < .001). Children with HBP >41 ng/mL on admission had an elevated risk of death (hazard ratio, 5.3 [95% confidence interval {CI}, 2.9-9.5]; P < .0001). In receiver operating characteristic (ROC) curve analysis, HBP concentrations distinguished between fatal and nonfatal outcomes (area under the ROC curve, 0.75 [95% CI, .66-.84]) and significantly improved the prediction provided by the Respiratory Index of Severity in Children, a composite clinical severity score (P = .0026). Measuring HBP at presentation could help identify children at risk of severe and fatal pneumonia. Adding HBP to clinical scores could improve the recognition and triage of children with pneumonia at risk of death.

Time to treatment-seeking by caretakers of children under-five with diarrhea and associated factors in Uganda: a multilevel proportional hazards analysis

BackgroundDiarrhea is considered to be one of the major public health concerns in developing countries. It has a detrimental impact, reflecting one of the highest child mortality rates globally, especially in Sub-Saharan Africa, where 2 out of every 10 children in Uganda under the age of five die. The objective of this study was to investigate the factors associated with time to treatment seeking by caretakers of children under-five with Diarrhea in Uganda.MethodDOVE dataset of 745 caretakers in a prospective and retrospective incidence-based study using multi-stage sampling design was used in the assessment. The analysis was done using a time-to-event approach using life tables, Kaplan Meier survival analysis and multilevel proportional hazards model.ResultsKaplan-Meier survival analysis indicated the median time to seeking treatment among 745 caretakers of children under-Five after onset of diarrhea was 2 days. The multi-level proportional hazards model of a Weibull distribution showed that the estimated frailty variance was 0.13, indicating heterogeneity of treatment seeking time by caretakers of under-five children with diarrhea across regions in Uganda. Significant factors found to influence time to treatment-seeking by caretakers of children under-five with diarrhea were, male children (HR = 0.82; 95% CI = 0.71–0.95, p = 0.010), belonging to richest wealth quintile (HR = 1.37; 95% CI = 1.05–1.78, p = 0.022), and residing more than 5 km away from a health facility (HR = 0.68; 95% CI = 0.56–0.84, p = 0.000).ConclusionsThere are delays in seeking diarrhea treatment in Uganda because two days are enough to claim a life after dehydration.The policymakers should pay attention to formulate effective intervention to sensitize caregivers on the importance of early treatment-seeking behavior to avoid severe malnutrition caused by diarrhea. Community awareness program should also be encouraged particularly in areas of more than 5 km from the health facility to make people aware of the necessity to take prompt action to seek care in the early stage.

Seroprevalence of SARS-CoV-2 and risk factors for infection among children in Uganda: a serial cross-sectional study.

Understanding COVID-19's impact on children is vital for public health policy, yet age-specific data is scarce, especially in Uganda. This study examines SARS-CoV-2 seroprevalence and risk factors among Ugandan children at two timepoints, along with COVID-19-related knowledge and practices in households, including adult vaccination status. Baseline surveys were conducted in 12 communities from April to May 2021 (post-Alpha wave) and follow-up surveys in 32 communities from November 2021 to March 2022 (Omicron wave). Household questionnaires and blood samples were collected to test for malaria by microscopy and for SARS-CoV-2 using a Luminex assay. Seroprevalence was estimated at both the survey and community level. Mixed-effects logistic regression models assessed the association between individual and household factors and SARS-CoV-2 seropositivity in children, adjusting for household clustering. More households reported disruptions in daily life at baseline compared to follow-up, though economic impacts lingered. By the follow-up survey, 52.7% of adults had received at least one COVID-19 vaccine dose. Overall seroprevalence in children was higher at follow-up compared to baseline (71.6% versus 19.2%, p < 0.001). Seroprevalence in children ranged across communities from 6-37% at baseline and 50-90% at follow-up. At baseline, children from the poorest households were more likely to be infected. Increasing age remained the only consistent risk factor for SARS-CoV-2 seroconversion at both timepoints. Results indicate that a larger number of children were infected by the Delta and Omicron waves of COVID-19 compared to the Alpha wave. This study is the largest seroprevalence survey in children in Uganda, providing evidence that most children were infected with SARS-CoV-2 before the vaccine was widely available to pediatric populations. Pediatric infections were vastly underreported by case counts, highlighting the importance of seroprevalence surveys in assessing disease burden when testing and reporting rates are limited and many cases are mild or asymptomatic.

The 2024 Pediatric Sepsis Challenge: Predicting In-Hospital Mortality in Children With Suspected Sepsis in Uganda.

The aim of this "Technical Note" is to inform the pediatric critical care data research community about the "2024 Pediatric Sepsis Data Challenge." This competition aims to facilitate the development of open-source algorithms to predict in-hospital mortality in Ugandan children with sepsis. The challenge is to first develop an algorithm using a synthetic training dataset, which will then be scored according to standard diagnostic testing criteria, and then be evaluated against a nonsynthetic test dataset. The datasets originate from admissions to six hospitals in Uganda (2017-2020) and include 3837 children, 6 to 60 months old, who were confirmed or suspected to have a diagnosis of sepsis. The synthetic dataset was created from a random subset of the original data. The test validation dataset closely resembles the synthetic dataset. The challenge should generate an optimal model for predicting in-hospital mortality. Following external validation, this model could be used to improve the outcomes for children with proven or suspected sepsis in low- and middle-income settings.

Pharmacokinetic-Guided Hydroxyurea to Reduce Transfusions in Ugandan Children with Sickle Cell Anemia: Study Design of the Alternative Dosing And Prevention of Transfusions Trial.

People with sickle cell anemia (SCA) may require frequent blood transfusions to treat acute and chronic complications. Hydroxyurea is a life-saving treatment for SCA that could also decrease the need for blood transfusions. Inadequate medication access and challenges in dose optimization limit the widespread use of hydroxyurea in Africa. If feasible, pharmacokinetic (PK) dosing might improve dose determination to minimize toxicities and maximize clinical benefits. The Alternative Dosing And Prevention of Transfusions (ADAPT, NCT05662098) trial will analyze the impact of hydroxyurea on transfusion rate and serve as a pilot study to evaluate the feasibility of PK-guided hydroxyurea dosing in Uganda. Herein we describe the rationale and design of ADAPT, a prospective cohort study of ∼100 children with SCA in Jinja, Uganda. The primary hypothesis is that hydroxyurea will decrease blood transfusion use by ≥ 50%, comparing the transfusion incidence rate ratio between a 3-month pretreatment and a 12-month treatment period. A key secondary hypothesis is that our PK-dosing approach will generate a suitable hydroxyurea dose for ≥80% of participants. Every ADAPT participant will undergo hydroxyurea PK testing, and if a dose is generated within 15-35 mg/kg/day, participants will start on their individualized dose. If not, they will start on a default dose of 20 mg/kg/day. Hydroxyurea dose optimization will occur with periodic dose adjustments. Overall, demonstrating the reduction in blood transfusion utilization with hydroxyurea treatment would provide leverage to increase hydroxyurea access, and PK-guided hydroxyurea dosing should optimize the safe and effective treatment of SCA across sub-Saharan Africa.

The longitudinal impact of an evidence-based multiple family group intervention (Amaka Amasanyufu) on family cohesion among children in Uganda: Analysis of the cluster randomized SMART Africa-Uganda scale-up study (2016-2022).

Family functioning plays a critical role in childhood disruptive behavior disorders (The Family Journal, 2003, 11(1), 33-41; Research in Nursing and Health, 2016, 39(4), 229-243). Yet, there is limited research on the impact of evidence-based family strengthening interventions on improving family cohesion as a protective factor among children experiencing behavioral challenges. To address this gap, we analyzed data (N = 636) from the SMART Africa-Uganda study (2016-2022), a cluster randomized clinical trial testing an evidence-based family-strengthening intervention called Amaka Amasanyufu (translated as "Happy Families" in the local language). Children aged 8-13 and their caregivers were recruited from 26 public primary schools that were randomized to: (1) control condition receiving generalized psychosocial literature (10 schools), (2) intervention delivered via parent peers (eight schools), and (3) intervention delivered via community healthcare workers (eight schools). Children completed the family cohesion questionnaire at baseline, 8 weeks, 16 weeks, and 6 months post-intervention completion. The intervention effectiveness was evaluated via a three-level logistic mixed effects model with pairwise comparisons across study conditions within each time point. Participants in the parent-peer intervention group had greater odds of being in the higher family cohesion group than participants in the control group at 8 weeks (OR = 3.24), 16 weeks (OR = 1.88) and 6 months (OR = 2.07). At 8 weeks, 16 weeks, and 6 months, participants in the community health worker group had 3.98, 2.08, and 1.79 times greater odds of being in the higher family cohesion group than participants in the control group, respectively. Our findings strengthen the evidence base for Amaka Amansayufu as an effective intervention that can be utilized in SSA to improve family cohesion in families with children experiencing behavioral challenges.

Improving alcohol and substance use screening in school-age children: translation, adaptation and psychometric evaluation of the CRAFFT tool for Lumasaaba, Uganda

BackgroundChildren at risk of substance use disorders (SUD) should be detected using brief structured tools for early intervention. This study sought to translate and adapt the Car, Relax, Alone, Forget, Family/Friends, Trouble (CRAFFT) tool to determine its diagnostic accuracy, and the optimum cut-point to identify substance use disorders (SUD) risk in Ugandan children aged 6 to 13 years.MethodsThis was a sequential mixed-methods study conducted in two phases. In the first qualitative phase, in Kampala and Mbale, the clinician-administered CRAFFT tool version 2.1 was translated into the local Lumasaaba dialect and culturally adapted through focus group discussions (FGDs) and in-depth interviews, in collaboration with the tool’s authors. Expert reviews and translations by bilingual experts provided insights on linguistic comprehensibility and cultural appropriateness, while pilot testing with the target population evaluated the tool’s preliminary effectiveness. In the second phase, the CRAFFT tool, adapted to Lumasaaba, was quantitatively validated against the Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID) for diagnosing SUD in Mbale district, through a survey. Participants, chosen randomly from schools stratified according to ownership, location, and school size, were assessed for the tool’s reliability and validity, including comparisons to the MINI KID as the Gold Standard for diagnosing SUD. Data were analyzed using STATA-15. Receiver-operating-characteristic analysis was performed to determine the sensitivity, specificity, and criterion validity of the CRAFFT with the MINI-KID.ResultsOf the 470 children enrolled, 2.1% (n = 10) had missing data on key variables, leaving 460 for analysis. The median age and interquartile range (IQR) was 11 (9–12) years and 56.6% were girls. A total of 116 (25.2%) children had consumed alcohol in the last twelve-month period and 7 (1.5%) had used other substances. The mean CRAFFT score for all the children (n = 460) was 0.32 (SD 0.95). The prevalence of any alcohol use disorder (2 or more positive answers on the MINI KID) in the last 12 months was 7.2% (n = 32). The Lumasaaba version of the CRAFFT tool demonstrated good internal consistency (Cronbach’s α = 0.86) and inter-item correlation (Spearman correlation coefficient of 0.84 (p < 0.001). At a cut-off score of 1.00, the CRAFFT had optimal sensitivity (91%) and specificity (92%) (Area Under the Curve (AUC) 0.91; 95% CI 0.86–0.97) to screen for SUD. A total of 62 (13.5%) had CRAFFT scores of > 1.ConclusionThe Lumasaaba version of the CRAFFT tool has sufficient sensitivity and specificity to identify school-age children at risk of SUD.

Long-Term Effects of Preschool Subsidies and Cash Transfers on Child Development: Evidence from Uganda

Shortly before the onset of the Covid-19 pandemic, three-to-five-year-old children in Uganda were randomly offered a subsidy to attend full-day preschool for one year. A second treatment group received cash transfers that were at least as large as the cost of the preschool subsidy provided, while a third group received both. Children who attended preschool prior to the pandemic have better anthropometric outcomes three years later. We do not find persistent effects on their learning outcomes. Effects of cash transfers on child development are similar to those of the preschool subsidy.