Hydroxyurea is associated with later onset of acute splenic sequestration crisis in sickle cell disease: Lessons from the European Sickle Cell Disease Cohort-Hydroxyurea (ESCORT-HU) study.

Acute splenic sequestration crisis (ASSC) is a potentially life-threatening complication of sickle cell disease (SCD), typically occurring in young patients under 5 years of age, with a median age at first episode of less than 2 years. Because a beneficial effect of hydroxyurea (HU) on spleen perfusion and splenic function has been suspected, we hypothesized that HU treatment might be associated with later onset of ASSC in patients with SCD. To investigate this hypothesis, we analyzed data from the ESCORT-HU study on a large cohort of patients with SCD receiving HU, enrolled between January 2009 and June 2017 with a follow-up of 7309 patient-years of observation. The median age at ASSC of the 14 patients who experienced a first episode of ASSC during the study period was 8.0 [IQR: 5.0-24.1] years. The median age at HU initiation was significantly lower in these 14 patients (4.8 [IQR: 3.3-18.7] years) compared to the 1664 patients without ASSC (19.9 [8.8-33.4] years, p = .0008). These findings suggest that ASSC may occur at an unusually late age in patients receiving HU, possibly reflecting longer preservation of spleen perfusion and function secondary to early initiation of HU. Further studies are needed to better characterize the effects of HU on spleen perfusion/function and on the occurrence of ASSC in patients with SCD (ClinicalTrials.gov identifier: NCT02516579; European registry ENCEPP/SDPP/10565).

Using pentamidine to treat cutaneous leishmaniasis in children: a 10-year study in French Guiana.

There are little data on pentamidine as a treatment for paediatric cutaneous leishmaniasis (CL). The objective of this study was to describe the effectiveness and safety of pentamidine over a 10-year period. Every child seen in French Guiana between 2010 and 2020 with proven CL and treated with pentamidine was included. In total, 55 children met the inclusion criteria - 23 girls and 32 boys. There were 38 patients (38/55, 69%) with a > 50% improvement at 1 month after pentamidine treatment and a complete cure at 3 months; 16 children had a < 50% improvement at 1 month and were given a second dose. Of these 16, 8 showed a complete cure at 3 months, 5 were lost to follow-up and 3 showed therapeutic failure at 3 months. The overall cure rate was 84% (46/55) after one or two doses. In terms of the safety of pentamidine, no severe adverse events (grade ≥ 3) were reported.

Infant mortality in French Guiana between 2001 and 2017 : Trends and comparisons with mainland France.

BACKGROUND: French Guiana is a French overseas territory which combines a well-funded universal health system and a population where half are under the poverty line. In this context, we aimed to measure and describe the causes of infant mortality and, because French Guiana is a French territory, to compare them with mainland France. METHODS: National death certificate data between 2001 and 2017 was used. RESULTS: Overall, 6.9 % of deaths before 65 years concerned infants <1 year (in mainland France 2.6%). The infant mortality rate over the 2001-2017 period was 2.6 times that of mainland France (1159.5 vs 446.2 per 100,000 infants <1 year) with excess incidence in perinatal causes, malformations and chromosomal anomalies, accidents, infectious causes, and in poorly defined conditions. Over time, there seemed to be a reduction of infant mortality for all the main causes, except for congenital malformations and chromosomal anomalies, which, on the contrary, seemed to increase. The data sources did not allow to study the weight of social factors or place of residence. CONCLUSIONS: All causes of infant mortality seemed to decline over time except malformations and chromosomal anomalies, which increased. Although exposure to heavy metals, infectious diseases are potential explanations we cannot pinpoint the cause of this increase with the available data. The present results suggest infant mortality and malformations should benefit from more detailed data sources in order to better assess and alleviate the burden of infant mortality in French Guiana.

Saliva for molecular detection of SARS-CoV-2 in pre-school and school-age children.

SARS-CoV-2 diagnosis is a cornerstone for the management of coronavirus disease 2019 (COVID-19). Numerous studies have assessed saliva performance over nasopharyngeal sampling (NPS), but data in young children are still rare. We explored saliva performance for SARS-CoV-2 detection by RT-PCR according to the time interval from initial symptoms or patient serological status. We collected 509 NPS and saliva paired samples at initial diagnosis from 166 children under 12 years of age (including 57 children under 6), 106 between 12 and 17, and 237 adults. In children under 12, overall detection rate for SARS-CoV-2 was comparable in saliva and NPS, with an overall agreement of 89.8%. Saliva sensitivity was significantly lower than that of NPS (77.1% compared to 95.8%) in pre-school and school-age children but regained 96% when considering seronegative children only. This pattern was also observed to a lesser degree in adolescents but not in adults. Sensitivity of saliva was independent of symptoms, in contrary to NPS, whose sensitivity decreased significantly in asymptomatic subjects. Performance of saliva is excellent in children under 12 at early stages of infection. This reinforces saliva as a collection method for early and unbiased SARS-CoV-2 detection and a less invasive alternative for young children.

In utero Zika virus exposure and neurodevelopment at 24 months in toddlers normocephalic at birth: a cohort study.

BACKGROUND: In utero exposure to Zika virus (ZIKV) is known to be associated with birth defects. The impact of in utero ZIKV exposure on neurodevelopmental outcomes in early childhood remains unclear. The objective of this study was to determine the impact of in utero ZIKV exposure on neurodevelopment at 24 months of age among toddlers who were born normocephalic to women who were pregnant during the 2016 ZIKV outbreak in French territories in the Americas. METHODS: We conducted a population-based mother-child cohort study of women whose pregnancies overlapped with the 2016 ZIKV epidemic in Guadeloupe, Martinique, and French Guiana. Infants were included in this analysis if maternal ZIKV infection during pregnancy could be determined, the newborn had a gestational age ≥ 35 weeks, there were no abnormal transfontanelle cerebral ultrasound findings after delivery or no abnormal ultrasound findings on the last ultrasound performed during the third trimester of the mother's pregnancy, there was an absence of microcephaly at birth, and the parent completed the 24-month neurodevelopment assessment of the infant at 24 months (± 1 month) of age. ZIKV exposure of the toddler was determined by evidence of maternal ZIKV infection during pregnancy. Neurodevelopment assessments included the Ages and Stages Questionnaire (ASQ) for five dimensions of general development-communication, gross motor, fine motor, problem solving, and personal-social skills; the Modified Checklist for Autism on Toddlers (M-CHAT) for behavior; and the French MacArthur Inventory Scales (IFDC) for French language acquisition. RESULTS: Between June 2018 and August 2019, 156 toddlers with and 79 toddlers without in utero ZIKV exposure completed neurodevelopment assessments. Twenty-four (15.4%) ZIKV-exposed toddlers and 20 (25.3%) ZIKV-unexposed toddlers had an ASQ result below the reference - 2SD cut-off (P = 0.10) for at least one of the five ASQ dimensions. CONCLUSION: In one of the largest population-based cohorts of in utero ZIKV-exposed, normocephalic newborns to date, there were minimal differences apparent in neurodevelopment outcomes at 24 months of age compared to ZIKV-unexposed toddlers at 24 months of age. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02810210 . Registered 20 June 2016.

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.

How I Treat Acute Chest Syndrome in Asthmatic Children with Sickle Cell Disease. A Practical Review.

Asthma is associated with increased rate of acute chest syndrome (ACS), pain episodes and premature death. Differentiating between an acute asthma exacerbation and ACS is a challenge clinically as they can present with similar symptoms. Clinicians should be aware of symptoms of asthma or broncho spasm in any children with sickle cell disease, as adequate treatments are required. In this mini-review, we selected 16 clinical studies, published in English between 2004 and 2016, and reviewed all of the abstracts and references of the selected articles. We subsequently selected articles that were focused on asthma in children with sickle cell disease. Given the pathophysiological mechanisms of ACS and the association between asthma and sickle cell disease, the management approach of asthmatic children should be clarified. Bronchodilators should be used if there are clinical features suggestive of a history of asthma or evidence of acute broncho spasm. The indication for cortisone should be reassessed. This literature review failed to conclude on therapeutic modalities of ACS in asthmatic children with sickle cell disease. Only a well designed, multicenter adequately-powered randomized controlled study of each of them will allow assessing their real benefits and risks.

Angiostrongylus cantonensis Infection of Central Nervous System, Guiana Shield.

We report a case of eosinophilic meningitis complicated by transverse myelitis caused by Angiostrongylus cantonensis in a 10-year-old boy from Brazil who had traveled to Suriname. We confirmed diagnosis by serology and real-time PCR in the cerebrospinal fluid. The medical community should be aware of angiostrongyliasis in the Guiana Shield.

High mortality due to congenital malformations in children aged < 1 year in French Guiana.

BACKGROUND: In French Guiana, pregnant women may be exposed to infectious, environmental, and social risks leading to congenital malformation. The objective of the study was to study mortality rates from congenital malformations among infants < 1 year and to compare them with those in mainland France. METHODS: We used the CEPI DC (INSERM) database, which compiles annual data from death certificates in all French territories using the International Classification of Diseases. Annual deaths for French Guiana and mainland France between 2005 and 2015 were compiled. The age category studied was children less than 1 year and deaths from congenital malformations, deformations and chromosomal abnormalities were compiled. Crude risk ratios and 95% confidence intervals were calculated to quantify the excess risk of disease in French Guiana. RESULTS: In French Guiana between 2005 and 2015 there were 666 deaths of children aged < 1 year, among which, 132 (19.8%) were due to congenital malformations and chromosomal anomalies. Overall the risk ratio of death from congenital malformations and chromosomal anomalies between French Guiana and mainland France was 2.7 (1.5-4.7), P < 0.001 for neurological congenital malformations it was 4.8 (1.2-19.7), P = 0.01 and for congenital malformations of the circulatory system it was 3.3 (1.5-6.9), P = 0.001. CONCLUSIONS: The incidence of death from congenital malformations or chromosomal anomalies in French Guiana was significantly higher than in mainland France. Explanations for this may be infections, genetic causes, nutritional causes, and toxic causes that are prevalent. There is a need to identify factors that predispose children born in French Guiana to having a higher risk of congenital malformations and chromosomal anomalies.

Mother's obesity and high child's waist circumference are predictive factors of severe child's obesity: an observational study in French Guiana.

BACKGROUND: This study aims to describe the predictive factors of severe obesity in children followed in French Guiana. METHODS: In this observational study, the patients from the French Guianese Childhood Obesity Group database were prospectively included, after giving a statement of patient's non opposition. RESULTS: Our group classifications revealed that 36 of 150 (24%) participants were classified as being metabolically abnormal obesity" (MAO), while 114 of 150 (76%) were categorized as metabolically normal obesity" (MNO). MAO-patients were older. Their mothers had more severe obesity. We also observed that their systolic blood pressure was higher. The median Z-score BMI of children with MAO was 4, 9 [4, 05-5, 38], which shows a more obese condition than the MNO group. The median waist-to-height ratio (WTHR) of our study population was high, either 0.63 [0.54-0.59]. No significant differences in the term of pregnancy, father's obesity, gender, birth weight, feeding, diastolic blood pressure and WTHR were found between the two groups. The predictors of MAO status, after adjusting for age and sex, were mother's obesity and high child's waist circumference. Among the comorbidity, there were two Down syndrome, one Cornelia de Lange syndrome, one Nephrotic Syndrome and one Epilepsy. The leptin hormone and insulin levels were higher in MAO than in MNO, while 25-OH D-vitamin was higher in MNO. CONCLUSION: This study indicates the need to incorporate waist circumference into routine clinical practice, in addition to traditional measures of weight, height, body mass index and waist-to-height ratio.

Paediatric Bone and Joint Infections in French Guiana: A 6 Year Retrospective Review.

The epidemiology of paediatric bone and joint infections from South America is poorly known. We herein report a retrospective study conducted in whole French Guiana from January 2010 to December 2015. Medical charts of 55 previously healthy children were analysed, identifying 27 with osteomyelitis, 22 with septic arthritis and 6 with multifocal infections and/or osteoarthritis. The male:female ratio was 2.2:1, and the mean age was 7.5 years. Eighty percent children were ≥36 months old who had predominantly osteomyelitis related to methicillin-susceptible Staphylococcus aureus (p < 0.05) in the course of neglected skin infections. Five children presented with multi-systemic infections resulting in one fatality, mainly caused by S. aureus producing Panton-Valentine leucocidin (p < 0.01). In contrast, children aged 6-36 months had more likely culture-negative infections (p < 0.05), septic arthritis and mild clinical and biological features. Further prospective studies are required to better guide rational diagnostic and therapeutic strategies.

CAREST--Multilingual Regional Integration for Health Promotion and Research on Sickle Cell Disease and Thalassemia.

Sickle cell disease (SCD) is a significant problem in the Caribbean, where many individuals have African and Asian forebears. However, reliable prevalence data and specific health care programs for SCD are often missing in this region. Closer collaboration between Caribbean territories initiated in 2006 to set up strategies to promote better equity in the health care system for SCD patients led to the formation of CAREST: the Caribbean Network of Researchers on Sickle Cell Disease and Thalassemia. We present the effectiveness of collaborations established by CAREST to promote SCD newborn screening programs and early childhood care, to facilitate health worker training and approaches for prevention and treatment of SCD complications, and to carry out inter-Caribbean research studies.

Genetic Information to Share with Parents when Newborn Screening Reveals the Presence of Sickle Cell Trait.

The primary purpose of newborn screening for sickle cell disease is to diagnose the disease before the appearance of symptoms and to initiate early treatment. To answer the question "What genetic information needs to be communicated to parents when newborn screening reveals the presence of a sickle cell trait," we conducted a survey using a self-administered online questionnaire. We received responses from 122 healthcare workers and members of sickle cell disease associations, in France and French overseas departments. Our results showed similar positions on this issue. The information conveyed is not consistent and is the result of grassroots initiatives. The negative consequences generated by this information could be reduced when this information is delivered by a multidisciplinary team, within the framework of a dedicated consultation. This information on sickle cell trait status should be given in at least three key periods: the neonatal period, early adolescence, and later adolescence, when reproductive implications become important. Neonatal screening programs should develop systems that allow referring physicians to easily access the results of neonatal screening electronically. Harmonization of practices should allow a better analysis of the consequences of this counselling on family projects.

Clinical outcomes of COVID-19 in patients with sickle cell disease in French Guiana.

Objectives: French Guiana also suffered concrete epidemiological consequences of the SARS-CoV2 epidemic. These regions are home to a large number of sickle cell patients who are at risk of developing severe forms of COVID-19. This study aimed to describe the characteristics and prognosis of patients with sickle disease infected with SARS-CoV2 during the first and second epidemic waves of 2020 in French Guiana. Design: We conducted a multicenter, retrospective cohort study that included sickle cell patients followed up in French Guiana. Results: Among the 79 patients infected with SARS-CoV2, there were 26 children <18 years. Forty-two patients were hospitalized and 37 were outpatients. Respiratory illness (38 %), vaso-occlusive crises (18 %), and acute chest syndrome (8 %) were the main causes of hospitalization. There were two cases of pulmonary embolism and one case of deep limb thrombosis. Seven patients were transferred to the ICU. Of these, three received mechanical ventilation, and two died. The deceased patients had the SS phenotype (a 16-year-old boy and a 32-year-old man), both of whom exhibited severe pneumonitis complicated by COVID-19. Conclusion: Despite the two deaths, the overall outcome was favorable.

Incidence of Pediatric Cancers in French Guiana: How Does It Compare to Global Estimates?

French Guiana is a French territory in South America. The exposome of persons living there is quite different from that in mainland France and the ethnic make-up of the population is also quite different. Poverty is also widespread with difficulties in accessing care magnified by the low medical-professional density. In this singular context, we aimed to measure the incidence of pediatric cancers and to compare it with other continents. We used French Guiana's certified cancer registry to study this between 2003 and 2017. Incidences were standardized using the world population with three strata: 0-4 years, 5-9 years, and 10-14 years. There were 164 solid tumors or hematologic malignancies diagnosed in children under the age of 15 (92 in boys and 72 in girls). Over the study period, the standardized incidence rate was 14.1 per 100,000 among children aged under 15 years. There was no significant trend during the study period. The three most common causes of cancer were leukemias-mostly lymphoblastic-CNS tumors, and sarcoma. The standardized incidence of pediatric cancers in French Guiana was similar to those in Western Europe and North America. As others have discovered, we found that males tended to be more likely to develop cancer, notably leukemia, CNS tumors, sarcoma, and retinoblastoma. As elsewhere, the predominant cancer types changed with age. Our initial assumption was that given the singular context of French Guiana, there may have been differences in pediatric cancer incidences. Here we showed that overall, contrary to our assumption and to trends in tropical countries, the incidence of pediatric cancers was in a range between Western Europe and North America with some apparent but non-significant differences in the main types of cancers observed in global statistics. Quality cancer registry data in this tropical region confirm the suspicion that lower incidences in tropical low- and middle-income countries are likely to result from incomplete diagnosis and data collection.

[Sickle cell disease in French Guiana: assessing 30 years of neonatal screening (1992-2021)]. / La drépanocytose en Guyane : bilan de 30 années de dépistage néonatal (1992-2021).

Background: Sickle cell disease is one of the most common genetic diseases in France. In French Guiana, neonatal screening was introduced in 1992, at the same time as other screening programs for childhood diseases. The aim of this study is to describe the organization of newborn screening for sickle cell disease in French Guiana. Materials and methods: We used several data sources: data collected from hospital records since 2005, activity reports from the national neonatal screening program and data from screening campaigns organized by the Drepaguyane association between 2010 and 2021 on 1,300 subjects. Blood samples from newborns are collected by capillary or venous sampling and absorbed on blotting paper (Guthrie) at the same time as those for other neonatal screenings. The dried papers are sent to the inter-regional laboratory in Lille, for further processing. In Saint-Laurent-du-Maroni, in order to reduce the proportion of people lost to follow-up, a double screening is carried out and the results are returned before discharge from the maternity hospital. All data were entered into an anonymous Excel file. The data were analyzed using STATA software. Results: Among the 175,593 screened neonates between 1992 and 2021, screening detected 823 infants with sickle cell disease and 17,950 heterozygotes. Sickle cell genotypes include 493 SS (60%), 302 SC (37%) and 28 S-Beta-thalassemia (3%). The incidence of sickle cell disease was 1/213, 95% CI [1/236-1/204], and that of heterozygotes 1/10, IC 95% [1/12-1/8]. The majority of these children (52%) were from the Maroni region. The delay between screening and test results was 7 days. Only pathological results (homozygous, heterozygous) were communicated to parents and/or the attending physician by post. These data confirm the upward trend in the number of children screened for sickle cell disease in French Guiana. Data from screening campaigns organized by the Drepaguyane association have enabled to describe the distribution of the various abnormal hemoglobin fractions, and to confirm that HbS is more frequent in Western French Guiana. In Cayenne, in 2021, the active file comprised 699 patients, including 266 children under 18 years old. Discussion and conclusion: This study provides valuable data on 30 years of neonatal screening for sickle cell disease in French Guiana, and on the evolution of sickle cell disease patients. It confirms that French Guiana is the French territory with the highest incidence of sickle cell disease. This incidence continues to rise over time. The study reveals the improvement in the organization of sickle cell disease management in French Guiana between 1992, when screening was introduced, and the present day. It highlights the role of patient associations in the fight against this disease, by organizing awareness and screening campaigns. These data will be used to guide public health policies in the pursuit of improved care and primary prevention.