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Abstract Background Few studies have described post-discharge morbidity of children with specific manifestations of severe malaria (SM) beyond severe malarial anaemia or cerebral malaria. Methods Children 6 months to 4 years of age admitted at Jinja and Mulago hospitals in Uganda, with one or more of the five most common forms of SM, cerebral malaria (n = 53), respiratory distress syndrome (n = 108), malaria with complicated seizures (n = 160), severe malarial anaemia (n = 155) or prostration (n = 75), were followed for 12 months after discharge, alongside asymptomatic community children (CC) (n = 120) of similar ages recruited from the households or neighbourhoods of the children with SM. Incidence and risk of hospitalizations, death or outpatient clinic visits were compared between children with SM and CC. Results 312/551 (56.6%) of children with SM had one or more post-discharge hospitalization over 12 months, compared to 37/120 (30.8%) of CC. Frequency of hospitalization was similar across all forms of SM. Compared to CC, children with SM had a significantly higher risk of all-cause hospitalization (adjusted hazard ratio (aHR) 1.91, 95% confidence interval (CI) 1.39–2.63, p 80% of hospitalizations were due to severe malaria. Studies of post-discharge malaria chemoprevention are urgently needed for children with SM, to determine if this treatment can reduce post-discharge morbidity.

Abstract Background Cardiopulmonary resuscitation (CPR) is an emergency procedure performed to restore heart function to minimize anoxic injury to the brain following cardiac arrest. Despite the establishment of emergency department and training on Pediatric Advanced Life Support (PALS) at Muhimbili National Hospital (MNH) the outcomes of pediatric in-hospital cardiac arrest have not been documented. We ought to determine the outcomes and factors associated with 24-h survival after pediatric in-hospital cardiac arrests at MNH in Tanzania. Methods We conducted a retrospective study of all patients aged 1 month to 18 years who had in-hospital cardiac arrests (IHCA) prompting CPR in the Emergency Medicine Department (EMD) at MNH, Tanzania from January 2016 to December 2019. Data was collected from electronic medical record (Wellsoft) system using a standardized and pretested data collection form that recorded clinical baseline, pre-arrest, arrest, and post-arrest parameters. Bivariate and multivariable logistic regression analyses were performed to assess the influence of each factor on 24-h survival. Results A total of 11,951 critically ill patients were screened, and 257 (2.1%) had cardiac arrest at EMD. Among 136 patients enrolled, the median age was 1.5 years (interquartile range: 0.5–3 years) years, and the majority 108 (79.4%) aged ≤ 5 years, and 101 (74.3%) had been referred from peripheral hospitals. Overall stained return of spontaneous circulation was achieved in 70 (51.5%) patients, 24-h survival was attained in 43 (31.3%) of patients, and only 7 patients (5.2%) survived to hospital discharge. Factors independently associated with 24-h survival were CPR event during the day/evening (p = 0.033), duration of CPR ≤ 20 min (p = 0.000), reversible causes of cardiac arrest being identified (p = 0.001), and having assisted/mechanical ventilation after CPR (p = 0.002). Conclusion In our cohort of children with cardiac arrest, survival to hospital discharge was only 5%. Factors associated with 24-h survival were CPR events during the daytime, short duration of CPR, recognition of reversible causes of cardiac arrest, and receiving mechanical ventilation. Future studies should explore the detection of decompensation, the quality of CPR, and post-cardiac arrest care on the outcomes of IHCA.

Abstract Background Sub-Saharan Africa bears the highest burden of sickle cell disease (SCD) globally with Nigeria, Democratic Republic of Congo, Tanzania, Uganda being the most affected countries. Uganda reports approximately 20,000 SCD births annually, constituting 6.67% of reported global SCD births. Despite this, there is a paucity of comprehensive data on SCD from the African continent. SCD registries offer a promising avenue for conducting prospective studies, elucidating disease severity patterns, and evaluating the intricate interplay of social, environmental, and genetic factors. This paper describes the establishment of the Sickle Pan Africa Research Consortium (SPARCo) Uganda registry, encompassing its design, development, data collection, and key insights learned, aligning with collaborative efforts in Nigeria, Tanzania, and Ghana SPARCo registries. Methods The registry was created using pre-existing case report forms harmonized from the SPARCo data dictionary and ontology to fit Uganda clinical needs. The case report forms were developed with SCD data elements of interest including demographics, consent, baseline, clinical, laboratory and others. That data was then parsed into a customized REDCap database, configured to suit the optimized ontologies and support retrieval aggregations and analyses. Patients were enrolled from one national referral and three regional referral hospitals in Uganda. Results A nationwide electronic patient-consented registry for SCD was established from four regional hospitals. A total of 5,655 patients were enrolled from Mulago National Referral Hospital (58%), Jinja Regional Referral (14.4%), Mbale Regional Referral (16.9%), and Lira Regional Referral (10.7%) hospitals between June 2022 and October 2023. Conclusion Uganda has been able to develop a SCD registry consistent with data from Tanzania, Nigeria and Ghana. Our findings demonstrate that it’s feasible to develop longitudinal SCD registries in sub-Saharan Africa. These registries will be crucial for facilitating a range of studies, including the analysis of SCD clinical phenotypes and patient outcomes, newborn screening, and evaluation of hydroxyurea use, among others. This initiative underscores the potential for developing comprehensive disease registries in resource-limited settings, fostering collaborative, data-driven research efforts aimed at addressing the multifaceted challenges of SCD in Africa.

Background Sickle cell disease (SCD) is a prevalent inherited blood disorder. Globally, approximately 515 000 babies are born with SCD annually, with 75% of these births occurring in Africa. Integrating newborn screening (NBS) for SCD into primary healthcare structures, such as immunisation programmes, holds significant promise, with dried blood spots (DBS)-point-of-care technologies (POCT) like HaemoTypeSC offering cost-effective screening solutions. However, scaling up DBS-POCT for NBS of SCD in Africa remains challenging.Objective This study aims to explore individual, organisational and external factors that may influence the reliability, feasibility, acceptability, adoption and sustainability of using DBS-POCT with HaemoTypeSC for NBS of SCD at primary healthcare centres in African countries.Method This qualitative study will be conducted in seven African countries that are part of the SickleInAfrica consortium sites. The study design is informed by the Consolidated Framework for Implementation Research (CFIR) and the Implementation Outcome Model. Participants will be mothers whose babies have been diagnosed with SCD, healthcare professionals and policy-makers. In-depth interviews and focus group discussions will be used for data collection. Data analysis will be through thematic analysis.Ethics and dissemination Research ethics approvals have been obtained from the seven countries. Written informed consent will be obtained from all participants. The study results will be disseminated in peer-reviewed scientific journals, scientific conferences, reports to national ministries of public health and webinars.

Risk stratification and molecular targeting have been key to increasing cure rates for pediatric cancers in high-income countries. In contrast, precise diagnosis in low-resource settings is hindered by insufficient pathology infrastructure. The Global HOPE program aims to improve outcomes for pediatric cancer in Sub-Saharan Africa (SSA) by building local clinical care and diagnostic capacity. This study aimed to assess the feasibility of implementing molecular assays to improve leukemia diagnoses in SSA. Custom NanoString nCounter gene fusion assays, previously validated in the US, were used to test samples from suspected leukemia patients. The NanoString platform was chosen due to relatively low cost, minimal technical and bioinformatics expertise required, ability to test sub-optimal RNA, and rapid turnaround time. Fusion results were analyzed blindly, then compared to morphology and flow cytometry results. Of 117 leukemia samples, 74 were fusion-positive, 30 were negative, 7 were not interpretable, and 6 failed RNA quality. Nine additional samples were negative for leukemia by flow cytometry and negative for gene fusions. All 74 gene fusions aligned with the immunophenotype determined by flow cytometry. Fourteen samples had additional information available to further confirm the accuracy of the gene fusion results. The testing provided a more precise diagnosis in >60% of cases, and 9 cases were identified that could be treated with an available tyrosine kinase inhibitor, if detected at diagnosis. As risk-stratified and targeted therapies become more available in SSA, implementing this testing in real-time will enable the treatment of pediatric cancer to move toward incorporating risk stratification for optimized therapy.

Abstract Severe anemia is an important contributor to mortality in children with severe malaria. Anemia in malaria is a multi-factorial complication, since dyserythropoiesis, hemolysis and phagocytic clearance of uninfected red blood cells (RBCs) can contribute to this syndrome. High levels of oxidative stress and immune dysregulation have been proposed to contribute to severe malarial anemia, facilitating the clearance of uninfected RBCs. In a cohort of 552 Ugandan children with severe malaria, we measured the levels of xanthine oxidase (XO), an oxidative enzyme that is elevated in the plasma of malaria patients. The levels of XO in children with severe anemia were significantly higher compared to children with severe malaria not suffering from severe anemia. Levels of XO were inversely associated with RBC hemoglobin (ρ = − 0.25, p

Abstract Background Acute kidney injury (AKI) disproportionately affects individuals in low-and middle-income countries (LMIC). However, LMIC—particularly countries in sub-Saharan Africa— are under-represented in global AKI research. A critical barrier in diagnosing AKI is access to reliable serum creatinine results. We evaluated the utility of a point-of-care test to measure creatinine and diagnose AKI in Ugandan children with malaria. Methods Paired admission creatinine was assessed in 539 Ugandan children 6 months to 4 years of age hospitalized with severe malaria based on blood smear or rapid diagnostic test. Creatinine levels were measured using isotope dilution mass spectrometry (IDMS)-traceable methods. The reference creatinine was measured using the modified Jaffe method by a certified laboratory and the point-of-care testing was conducted using an i-STAT blood analyzer (i-STAT1, with and without adjustment for the partial pressure of carbon dioxide). AKI was defined and staged using the Kidney Disease: Improving Global Outcomes criteria. Results The mean age of children was 2.1 years, and 21.6% of children were stunted. Mortality was 7.6% in-hospital. Over the entire range of measured creatinine values (

ABSTRACT Severe malaria (SM) increases the risk of invasive bacterial infection, and there is evidence to suggest increased gastrointestinal permeability. Studies have shown sequestration of infected erythrocytes in intestinal microvasculature, and in vivo studies of rectal mucosa have demonstrated disruption of microvascular blood flow. However, the extent of intestinal injury in pediatric malaria is not well characterized. In this study, two serum biomarkers of intestinal injury, trefoil factor 3 (TFF3) and intestinal fatty acid binding protein (I-FABP), were analyzed in 598 children with SM and 120 healthy community children (CC), 6 months to 4 years of age. Serum was collected at enrollment and 1 month for laboratory studies, and participants were monitored for 12 months. Intestinal injury biomarkers were significantly elevated in children with SM, with 18.1% having levels of TFF3 and/or I-FABP greater than the 99th percentile of CC levels. TFF3 levels continued to be elevated at 1 month, while I-FABP levels were comparable to CC levels. Both markers predicted in-hospital mortality {odds ratio (OR) (95% confidence interval [CI]), 4.4 (2.7, 7.3) and 2.3 (1.7, 3.1)} for a natural log increase in TFF3 and I-FABP, respectively. TFF3 was also associated with postdischarge mortality (OR, 2.43 [95% CI, 1.1, 4.8]). Intestinal injury was associated with acute kidney injury (AKI), acidosis (P

Abstract Background In 2011, the World Health Organization recommended injectable artesunate as the first-line therapy for severe malaria (SM) due to its superiority in reducing mortality compared to quinine. There are limited data on long-term clinical and neurobehavioral outcomes after artemisinin use for treatment of SM. Methods From 2008 to 2013, 502 Ugandan children with two common forms of SM, cerebral malaria and severe malarial anemia, were enrolled in a prospective observational study assessing long-term neurobehavioral and cognitive outcomes following SM. Children were evaluated a week after hospital discharge, and 6, 12, and 24 months of follow-up, and returned to hospital for any illness. In this study, we evaluated the impact of artemisinin derivatives on survival, post-discharge hospital readmission or death, and neurocognitive and behavioral outcomes over 2 years of follow-up. Results 346 children received quinine and 156 received parenteral artemisinin therapy (artemether or artesunate). After adjustment for disease severity, artemisinin derivatives were associated with a 78% reduction in in-hospital mortality (adjusted odds ratio, 0.22; 95% CI, 0.07–0.67). Among cerebral malaria survivors, children treated with artemisinin derivatives also had reduced neurologic deficits at discharge (quinine, 41.7%; artemisinin derivatives, 23.7%, p=0.007). Over a 2-year follow-up, artemisinin derivatives as compared to quinine were associated with better adjusted scores (negative scores better) in internalizing behavior and executive function in children irrespective of the age at severe malaria episode. After adjusting for multiple comparisons, artemisinin derivatives were associated with better adjusted scores in behavior and executive function in children

Abstract Background Acute kidney injury (AKI) is increasingly recognized as a consequential clinical complication in children with severe malaria. However, approaches to estimate baseline creatinine (bSCr) are not standardized in this unique patient population. Prior to wide-spread utilization, bSCr estimation methods need to be evaluated in many populations, particularly in children from low-income countries. Methods We evaluated six methods to estimate bSCr in Ugandan children aged 6 months to 12 years of age in two cohorts of children with severe malaria (n = 1078) and healthy community children (n = 289). Using isotope dilution mass spectrometry (IDMS)-traceable creatinine measures from community children, we evaluated the bias, accuracy and precision of estimating bSCr using height-dependent and height-independent estimated glomerular filtration (eGFR) equations to back-calculate bSCr or estimating bSCr directly using published or population-specific norms. Results We compared methods to estimate bSCr in healthy community children against the IDMS-traceable SCr measure. The Pottel-age based equation, assuming a normal GFR of 120 mL/min per 1.73m2, was the more accurate method with minimal bias when compared to the Schwartz height-based equation. Using the different bSCr estimates, we demonstrated the prevalence of KDIGO-defined AKI in children with severe malaria ranged from 15.6–43.4%. The lowest estimate was derived using population upper levels of normal and the highest estimate was derived using the mean GFR of the community children (137 mL/min per 1.73m2) to back-calculate the bSCr. Irrespective of approach, AKI was strongly associated with mortality with a step-wise increase in mortality across AKI stages (p

Summary: Background: Globally, 85% of acute kidney injury (AKI) cases occur in low-and-middle-income countries. There is limited information on persistent kidney disease (acute kidney disease [AKD]) following severe malaria-associated AKI. Methods: Between March 28, 2014, and April 18, 2017, 598 children with severe malaria and 118 community children were enrolled in a two-site prospective cohort study in Uganda and followed up for 12 months. The Kidney Disease: Improving Global Outcomes (KDIGO) criteria were used to define AKI (primary exposure) and AKD at 1-month follow-up (primary outcome). Plasma neutrophil gelatinase-associated lipocalin (NGAL) was assessed as a structural biomarker of AKI. Findings: The prevalence of AKI was 45·3% with 21·5% of children having unresolved AKI at 24 h. AKI was more common in Eastern Uganda. In-hospital mortality increased across AKI stages from 1·8% in children without AKI to 26·5% with Stage 3 AKI (p

Abstract Background Sickle cell anemia (SCA) is the most common inherited hemoglobinopathy worldwide. Infection is a major cause of illness and death in children with SCA, especially in sub-Saharan Africa where an estimated 50–90% of affected children die before their fifth birthday. Interventions to reduce the incidence and severity of infections are needed urgently. A high proportion of adults and children with SCA are zinc-deficient, and zinc deficiency leads to impaired immunity and an increased risk of infection. Zinc supplementation has been shown to decrease the risk of infection in adolescents and adults, but there are no data on the effectiveness of zinc for prevention of infection in children

Abstract Orbital compression syndrome is a rare acute complication of sickle cell disease that may impair vision. Assessment by a multidisciplinary team incorporates detailed history and physical examination, fundoscopy, and appropriate imaging to exclude infections or neoplasms. Supportive treatment is adequate unless there is evidence of life‐threatening space‐occupying lesion warranting surgery.