Pubertal development of transfusion-dependent thalassemia patients in the era of oral chelation with deferasirox: results from the French registry.

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Epidemiological profile of COVID-19 in the French overseas department Mayotte, 2020 to 2021.

BackgroundDuring the COVID-19 pandemic, national and local measures were implemented on the island of Mayotte, a French overseas department in the Indian Ocean with critical socioeconomic and health indicators.AimWe aimed to describe the COVID-19 outbreak in Mayotte from March 2020 to March 2021, with two waves from 9 March to 31 December 2020 and from 1 January to 14 March 2021, linked to Beta (20H/501Y.V2) variant.MethodsTo understand and assess the dynamic and the severity of the COVID-19 outbreak in Mayotte, surveillance and investigation/contact tracing systems were set up including virological, epidemiological, hospitalisation and mortality indicators.ResultsIn total, 18,131 cases were laboratory confirmed, with PCR or RAT. During the first wave, incidence rate (IR) peaked in week 19 2020 (133/100,000). New hospitalisations peaked in week 20 (54 patients, including seven to ICU). Testing rate increased tenfold during the second wave. Between mid-December 2020 and mid-January 2021, IR doubled (851/100,000 in week 5 2021) and positivity rate tripled (28% in week 6 2021). SARS-CoV-2 Beta variant (Pangolin B.1.351) was detected in more than 80% of positive samples. Hospital admissions peaked in week 6 2021 with 225 patients, including 30 to ICU.ConclusionThis massive second wave could be linked to the high transmissibility of the Beta variant. The increase in the number of cases has naturally led to a higher number of severe cases and an overburdening of the hospital. This study shows the value of a real-time epidemiological surveillance for better understanding crisis situations.

Acute Hemolytic Anemia Caused by G6PD Deficiency in Children in Mayotte: A Frequent and Severe Complication.

Severe hemolytic anemia is a rare complication of glucose-6-phosphate dehydrogenase (G6PD) deficiency. It occurs with the Mediterranean (Med) variant corresponding to a class 2 deficiency according to the World Health Organization (WHO) classification, and it correlates with a severe deficiency in G6PD activity. In Mayotte, the majority of patients have the African (A-) variant as a WHO class 3 deficiency. Yet we have observed numerous cases of severe hemolytic anemia defined by a hemoglobin level of <6 g/dL. In this study, we aimed to describe the epidemiological, clinical, and biological features as well as the treatment modalities of children presenting with a severe hemolytic crisis secondary to G6PD deficiency in Mayotte. The secondary objective was to study the disease genotype when this information was available. Between April 2013 and September 2020, 73 children presented with severe anemia because of G6PD deficiency in Mayotte. The median hemoglobin level during the hemolytic crises was 3.9 g/dL. All of the patients underwent a transfusion and hospitalization. Twenty patients had a disease genotype: 11 had the African mutation and 9 had the Med mutation. Although they are among the most common triggers of G6PD acute hemolytic anemia, drugs were found to not be present and fava bean ingestion was found in only 1 child. One of the specific triggers was traditional medicine, including Acalypha indica . Severe hemolytic crisis in children because of G6PD deficiency is a frequent occurrence in Mayotte. The patients had severe disease symptoms, but the severity did not correlate with the genotype: the African (A-) variant and the Med variant resulted in the same level of disease severity.

Multisystem Inflammatory Syndrome Associated With Severe Acute Respiratory Syndrome Coronavirus 2 in Children: A Case Series From Mayotte Island.

During the COVID-19 outbreak in the French overseas department Mayotte, 11 children developed multisystem inflammatory syndrome (MIS-C). They all had a fever and gastrointestinal symptoms. Six patients were admitted to intensive care unit; management included intravenous immunoglobulin and corticosteroid. Severe acute respiratory syndrome coronavirus 2 was documented in all patients. The risk of developing MIS-C was much higher than in all of France.

Tetraventricular Hydrocephalus Following Eosinophilic Meningitis due to Angiostrongylus cantonensis in a 14-Month-Old Boy From Mayotte: A Case Report.

Angiostrongylus cantonensis is endemic in Mayotte, and cases of meningitis due to angiostrongyliasis are regularly diagnosed in young children. In a 14-month-old boy with slow-onset psychomotor regression, brain magnetic resonance imaging revealed communicating hydrocephalus. Reverse transcription polymerase chain reaction for A. cantonensis on cerebrospinal fluid was positive. The evolution was favorable with repeated lumbar punctures and a 2-week treatment with albendazole and high-dose corticosteroids.

HbF-promoting polymorphisms may specifically reduce the residual risk of cerebral vasculopathy in SCA children with alpha-thalassemia.

Sickle cell anemia (SCA) is a disease characterized by abnormal red blood cell rheology. Because of their effects on HbS polymerization and red blood cell deformability, alpha-thalassemia and the residual HbF level are known genetic modifiers of the disease. The aim of our study was to determine if the number of HbF quantitative trait loci (QTL) would also favor a specific sub-phenotype of SCA as it is the case for alpha-thalassemia. Our results confirmed that alpha-thalassemia protected from cerebral vasculopathy but increased the risk for frequent painful vaso-occlusive crises. We also showed that more HbF-QTL may provide an additional and specific protection against cerebral vasculopathy but only for children with alpha-thalassemia (-α/αα or -α/-α genotypes).

High fetal hemoglobin level is associated with increased risk of cerebral vasculopathy in children with sickle cell disease in Mayotte.

BACKGROUND: Understanding the genetics underlying the heritable subphenotypes of sickle cell anemia, specific to each population, would be prognostically useful and could inform personalized therapeutics.The objective of this study was to describe the genetic modulators of sickle cell disease in a cohort of pediatric patients followed up in Mayotte. METHODS: This retrospective cohort study analyzed clinical and biological data, collected between January1st2007 and December 31st2017, in children younger than 18 years. RESULTS: We included 185 children with 72% SS, 16% Sß0-thalassemia and 12% Sß + thalassemia. The average age was 9.5 years; 10% of patients were lost to follow up. The Bantu haplotype was associated with an increase in hospitalizations and transfusions. The alpha-thalassemic mutation was associated with a decrease of hemolysis biological parameters (anemia, reticulocytes), and a decrease of cerebral vasculopathy. The Single Nucleotide Polymorphisms BCL11A rs4671393, BCL11A rs11886868, BCL11A rs1427407 and HMIP rs9399137 were associated with the group of children with HbF > 10%. Patients with HbF > 10% presented a significant risk of early onset of cerebral vasculopathy. CONCLUSIONS: The most remarkable result of our study was the association of SNPs with clinically relevant phenotypic groups. BCL11A rs4671393, BCL11A rs11886868, BCL11A rs1427407 and HMIP rs9399137 were correlated with HbF > 10%, a group that has a higher risk of cerebral vasculopathy and should be oriented towards the hemolytic sub-phenotype.

Evaluation of Outcomes and Quality of Care in Children with Sickle Cell Disease Diagnosed by Newborn Screening: A Real-World Nation-Wide Study in France.

This study's objective was to assess, on a national scale, residual risks of death, major disease-related events, and quality of care during the first five years in children diagnosed at birth with sickle cell disease (SCD). Data were retrospectively collected from medical files of all children with SCD born between 2006-2010 in France. Out of 1792 eligible subjects, 1620 patients (71.8% SS or S/beta°-thalassemia -SB°-) had available follow-up data, across 69 centers. Overall probability of survival by five years was 98.9%, with 12/18 deaths related to SCD. Probability of overt stroke by five years in SS/SB° patients was 1.1%, while transcranial Doppler (TCD) was performed in 81% before three years of age. A total of 26 patients had meningitis/septicemia (pneumococcal in eight cases). Prophylactic penicillin was started at a median age of 2.2 months and 87% of children had received appropriate conjugate pneumococcal vaccination at one year. By five years, the probability of survival without SCD-related events was 10.7% for SS/SB° patients. In contrast, hydroxyurea was prescribed in 13.7% and bone marrow transplant performed in nine patients only. In this study, residual risks of severe complications were low, probably resulting from a good national TCD, vaccination, and healthcare system coverage. Nonetheless, burden of disease remained high, stressing the need for disease-modifying or curative therapy.

Angiostrongylus cantonensis Infection on Mayotte Island, Indian Ocean, 2007-2012.

INTRODUCTION: Human angiostrongyliasis (HA) is a neurological helminthic disease caused by the lung worm Angiostrongylus cantonensis. It is suspected in the combination of travel or a residence in an endemic area and eosinophilic meningitis. In Mayotte, an island in the Indian Ocean, cases are rare but regular. The main objective of our study was to describe the epidemiological and diagnosis clues of HA in Mayotte. The secondary objectives were to evaluate the contribution of Real-Time Polymerase Chain Reaction (RT- PCR) for the diagnosis of HA, delineate the characteristics of the local transmission and ascertain the presence of A. cantonensis in Achatina fulica, the potential vector of the disease. MATERIALS AND METHODS: Between 2007 and 2012, all cases of eosinophilic meningitis were retrospectively included and investigated by RT- PCR in the CSF. Descriptive analysis was conducted for clinical, biological and radiological features, and were analyzed for all patients together with the search for prognostic factors for mortality. Concurrently, geolocalization and temporal parameters were studied to correlate the occurrence of the cases with rainfall seasons and snails were collected to enhance a parasitic carriage with real time PCR. RESULTS: During the 6-year period of the study, 14 cases were identified (2.3 cases/year) and 9 among 10 remaining CSF were positive in PCR. Among 14 cases of EM, 13 were less than 2 year-old children. The 1 year mortality rate was 5/14 (35.7%). Among survivors, 3/7 (42.8%) presented neurological sequelae. Factors associated with mortality were dysfunction of cranial nerves, abnormal brain imaging, and CSF glucose level inferior to 2 mmol/l. Occurrence of cases was temporarily and spatially correlated to the rainy season. Among the 64 collected giant snails, 6 (9.4%) were positive with A. cantonensis PCR. The likely main route of transmission was the children licking snails, carriers of the parasite. CONCLUSION: In Mayotte, HA was mainly found in paediatric cases under 2 years old, and evidenced a life-threatening disease. PCR seems to be a promising tool in the definitive diagnosis of HA. Population should be aware of the role of A. fulica, and not let the children have direct contact with the snails.

Genetic Modifiers of Sickle Cell Disease: A Genotype-Phenotype Relationship Study in a Cohort of 82 Children on Mayotte Island.

Sickle cell disease presents a great clinical variability that remains largely misunderstood. New disease protective genetic modifiers acting mainly through an increased Hb F level have recently been described. We studied relations between clinical and hematological phenotypes and known sickle cell disease genetic modifiers in patients from Mayotte Island, a remote French territory located in the Indian Ocean. Eighty-two children with sickle cell disease were enrolled; their median age was 5.9 years (range 1-18). Clinical and hematological features of sickle cell disease were retrospectively collected. Genetic studies included determination of ß-globin genotypes [Hb SS, Hb S-ß(0)-thalassemia (Hb S-ß(0)-thal), Hb S-ß(+)-thal], ß(S)-globin locus haplotype, α-thalassemia (α-thal), and single nucleotide polymorphisms (SNPs) located in quantitative trait loci for Hb F expression (XmnI polymorphism, BCL11A rs4671393 and rs11886868, intergenic region of HBS1L-MYB rs28384513, rs4895441 and rs9399137). Univariate and multivariate analyses were conducted. Twenty-eight percent of the patients had Hb S-ß-thal (eight different mutations in 21 patients), 55.0% had the -α(3.7) (rightward) deletion and 88.0% of the homozygous Hb SS patients were carrying a homozygous Bantu haplotype. In the multivariate model, the prognosis role of the SNP BCL11A rs4671393 was confirmed in the studied population showing a significant association with an elevated Hb F level and with a low hospitalization rate. The -α(3.7) deletion, XmnI polymorphism and intergenic region HBS1L-MYB SNPs were not significantly linked to any clinical criteria of severity. This report, the first to describe the main features of children with sickle cell disease on Mayotte Island, highlights the protective effect of the BCL11A polymorphism in this population.