Hydroxyurea dose optimisation for children with sickle cell anaemia in sub-Saharan Africa (REACH): extended follow-up of a multicentre, open-label, phase 1/2 trial.

Background: Realizing Effectiveness Across Continents with Hydroxyurea (REACH) is an open-label non-randomised trial of hydroxyurea (hydroxycarbamide) in children with sickle cell anaemia in sub-Saharan Africa. The short-term results of REACH on safety, feasibility, and effectiveness of hydroxyurea were published previously. In this paper we report results from extended hydroxyurea treatment in the REACH cohort up to 8 years.

Seizures, focal neurological signs, and pneumococcal aetiology associate with impaired consciousness in childhood bacterial meningitis.

Aim: A low Glasgow Coma Scale Score (GCS) on admission is a known predictor of poor outcome from childhood bacterial meningitis. In turn, the factors associated with the admission GCS are less known. Our aim was to identify them, both for clinical alerts of reserved prognosis and to find potential targets for intervention.

Clinical Picture and Risk Factors for Poor Outcome in Streptococcus pneumoniae Meningitis of Childhood on Three Continents.

Background: Streptococcus pneumoniae meningitis (SpM) remains a major health burden worldwide, particularly in low- and middle-income countries. Identifying the patients at highest risk for mortality and disabling sequelae may reveal potentially avoidable predisposing factors and identify patients most in need of intensive care. We searched for factors that do not require laboratory facilities.

Pneumonia in childhood bacterial meningitis-Experience from three continents.

Introduction: Although concomitant pneumonia is sometimes diagnosed in childhood bacterial meningitis, its role in the illness course and prognosis is not known. We examined these associations using prospectively collected data from Finland, Latin America and Angola.

Methods: This was a secondary descriptive analysis of prospectively collected data (clinical and laboratory findings at admission, during hospitalisation and outcome) from five clinical bacterial meningitis trials.

Reducing transfusion utilization for children with sickle cell anemia in sub-Saharan Africa with hydroxyurea: Analysis from the phase I/II REACH trial.

Children with sickle cell anemia (SCA) in Africa frequently require transfusions for SCA complications. Despite limited blood supplies, strategies to reduce their transfusion needs have not been widely evaluated or implemented. We analyzed transfusion utilization in children with SCA before and during hydroxyurea treatment.

Targeting circulating labile heme as a defense strategy against malaria.

Severe presentations of malaria emerge as parasites invade and lyse red blood cells (RBC), producing extracellular hemoglobin (HB), from which labile heme is released. Here, we tested whether scavenging of extracellular HB and/or labile heme, by haptoglobin (HP) and/or hemopexin (HPX), respectively, counter the pathogenesis of severe presentations of malaria. We found that circulating labile heme is an independent risk factor for cerebral and non-cerebral presentations of severe malaria in children.

Differential expression of adhesion molecules in sickle cell anemia and gut microbiome effect.

Sickle cell anemia (SCA) causes a long-standing vascular inflammation state, leading to endothelial dysfunction and chronic overexpression of several adhesion molecules, which contributes to acute and constant vaso-occlusive (VOC) episodes. It has been demonstrated that hydroxyurea (HU) can reduce VOC events, organ damage, blood transfusions, and even the adhesion properties to endothelial cells of SCA subjects. Due to VOC episodes, these patients are also more susceptible to recurrent bacterial translocation and dysbiosis.

Early diagnosis of sickle cell disease at birth hospitals and vaccination centers in Angola using point-of-care tests.

Sickle cell disease (SCD) is a life-threatening blood disorder affecting >500 000 infants annually, mostly in sub-Saharan Africa. Most infants do not have access to an early diagnosis and die early from treatable complications of SCD. Universal newborn screening (NBS) is not yet available in any African country for a variety of reasons, including lack of laboratory capacity, difficulty in tracking affected infants, and the relatively short stay of mothers and newborns at maternity hospitals.

Are Genetic Modifiers the Answer to Different Responses to Hydroxyurea Treatment?-A Pharmacogenetic Study in Sickle Cell Anemia Angolan Children.

Sickle cell anemia (SCA) is an inherited disease affecting the hemoglobin that is particularly common in sub-Saharan Africa. Although monogenic, phenotypes are markedly heterogeneous in terms of severity and life span. Hydroxyurea is still the most common treatment for these patients, and the response to treatment is highly variable and seems to be an inherited trait.

Auditory Steady-State Response and Hearing Impairment in Survivors of Childhood Bacterial Meningitis in Luanda, Angola.

Survivors of childhood bacterial meningitis (BM) often develop hearing impairment (HI). In low- and middle-income countries (LMICs), BM continues to be a significant cause of hearing disability. We assessed hearing among BM survivors using auditory steady-state responses (ASSR), providing frequency-specific estimated audiograms, and examined whether ASSR would provide a greater understanding of BM-induced HI.

PCR-confirmed malaria among children presenting with a decreased level of consciousness in Angola: a prospective, observational study.

Background: In malaria-endemic areas, children presenting to hospitals with a decreased level of consciousness remain a diagnostic dilemma. The definition of cerebral malaria in a comatose child demands exclusion of other possible reasons, which requires in-depth investigations that are not easily available. The aim of this study was to investigate the frequency and clinical characteristics of PCR-confirmed malaria in a cohort of children with a decreased level of consciousness, look for potential features that would aid in differentiating children with malaria from those without, and assess the performance of traditional thick film microscopy against the cytb-qPCR-method.

High Concentration of Protein Oxidation Biomarker O-Tyr/Phe Predicts Better Outcome in Childhood Bacterial Meningitis.

Neuronal damage in bacterial meningitis (BM) partly stems from the host´s inflammatory response and induced oxidative stress (OS). We studied the association of cerebrospinal fluid (CSF) biomarkers indicating oxidative damage to proteins with course of illness and outcome in childhood BM in Angola. Ortho-tyrosine/phenylalanine (o-Tyr/Phe), 3-chlorotyrosine/para-tyrosine (3Cl-Tyr/p-Tyr), and 3-nitrotyrosine/para-tyrosine (3NO-Tyr/p-Tyr) concentration ratios were measured in 79 BM admission CSF samples, employing liquid chromatography coupled to tandem mass spectrometry.

Efficacy and safety of pharmacological interventions for managing sickle cell disease complications in children and adolescents: Systematic review with network meta-analysis.

This study aimed to synthesize the evidence on the effects of disease-modifying agents for managing sickle cell disease (SCD) in children and adolescents by means of a systematic review with network meta-analyses, surface under the cumulative ranking curve (SUCRA) and stochastic multicriteria acceptability analyses (SMAA) (CRD42022328471). Eightteen randomized controlled trials (hydroxyurea [n = 7], l-arginine [n = 3], antiplatelets [n = 2], immunotherapy/monoclonal antibodies [n = 2], sulfates [n = 2], docosahexaenoic acid [n = 1], niprisan [n = 1]) were analyzed. SUCRA and SMAA demonstrated that hydroxyurea at higher doses (30 mg/kg/day) or at fixed doses (20 mg/kg/day) and immunotherapy/monoclonal antibodies are more effective for preventing vaso-occlusive crisis (i.

The Effect of Blood Transfusion on the Survival of Children with Both Severe Anemia and Bacterial Meningitis.

In areas with suboptimal resources, blood transfusion may not be feasible even when mandatory for severely anemic children with a life-threatening disease. We evaluated how much not having received a transfusion affected the survival in 171 children with an admission blood hemoglobin level of < 6 g/dL and bacterial meningitis in Luanda, Angola. Of these children, 75% (128 of 171) had received a blood transfusion during hospitalization, but 25% (43 of 171) had not.

Spatiotemporal variation in risk of Shigella infection in childhood: a global risk mapping and prediction model using individual participant data.

Background: Diarrhoeal disease is a leading cause of childhood illness and death globally, and Shigella is a major aetiological contributor for which a vaccine might soon be available. The primary objective of this study was to model the spatiotemporal variation in paediatric Shigella infection and map its predicted prevalence across low-income and middle-income countries (LMICs).

Methods: Individual participant data for Shigella positivity in stool samples were sourced from multiple LMIC-based studies of children aged 59 months or younger.

Microbial gut evaluation in an angolan paediatric population with sickle cell disease.

Sickle cell disease (SCD) is one of the most common genetic conditions worldwide. It can contribute up to 90% of under-5 mortality in sub-Saharan Africa. Clinical manifestations are very heterogeneous, and the intestinal microbiome appears to be crucial in the modulation of inflammation, cell adhesion and induction of aged neutrophils, the main interveners of recurrent vaso-occlusive crisis.

How Hydroxyurea Alters the Gut Microbiome: A Longitudinal Study Involving Angolan Children with Sickle Cell Anemia.

Sickle cell anemia (SCA) is an inherited hematological disorder and a serious global health problem, especially in Sub-Saharan Africa. Although hydroxyurea (HU) is the leading treatment for patients with SCA, its effects on the gut microbiome have not yet been explored. In this context, the aim of this study was to investigate this association by characterizing the gut microbiome of an Angolan SCA pediatric population before and after 6 months of HU treatment.

Bacterial Meningitis in Children With Sickle Cell Disease in Angola.

Sickle cell disease (SCD) was found in 10% of children with bacterial meningitis (BM) in Luanda, 5-fold more than in the general population. BM children with SCD versus BM children without SCD had higher inflammatory markers, more often had pneumococcal meningitis (71% vs. 39%), and either died (39% vs.