Unique Changes in the Incidence of Acute Chest Syndrome in Children With Sickle Cell Disease Unravel the Role of Respiratory Pathogens: A Time Series Analysis.

BACKGROUND: Acute chest syndrome (ACS) is a life-threatening complication of sickle cell disease (SCD). Although respiratory pathogens are frequently detected in children with ACS, their respective role in triggering the disease is still unclear. We hypothesized that the incidence of ACS followed the unprecedented population-level changes in respiratory pathogen dynamics after COVID-19-related nonpharmaceutical interventions (NPIs). RESEARCH QUESTION: What is the respective role of respiratory pathogens in ACS epidemiology? STUDY DESIGN AND METHODS: This study was an interrupted time series analysis of patient records from a national hospital-based surveillance system. All children aged < 18 years with SCD hospitalized for ACS in France between January 2015 and May 2022 were included. The monthly incidence of ACS per 1,000 children with SCD over time was analyzed by using a quasi-Poisson regression model. The circulation of 12 respiratory pathogens in the general pediatric population over the same period was included in the model to assess the fraction of ACS potentially attributable to each respiratory pathogen. RESULTS: Among the 55,941 hospitalizations of children with SCD, 2,306 episodes of ACS were included (median [interquartile range] age, 9 [5-13] years). A significant decrease was observed in ACS incidence after NPI implementation in March 2020 (-29.5%; 95% CI, -46.8 to -12.2; P = .001) and a significant increase after lifting of the NPIs in April 2021 (24.4%; 95% CI, 7.2 to 41.6; P = .007). Using population-level incidence of several respiratory pathogens, Streptococcus pneumoniae accounted for 30.9% (95% CI, 4.9 to 56.9; P = .02) of ACS incidence over the study period and influenza 6.8% (95% CI, 2.3 to 11.3; P = .004); other respiratory pathogens had only a minor role. INTERPRETATION: NPIs were associated with significant changes in ACS incidence concomitantly with major changes in the circulation of several respiratory pathogens in the general population. This unique epidemiologic situation allowed determination of the contribution of these respiratory pathogens, in particular S pneumoniae and influenza, to the burden of childhood ACS, highlighting the potential benefit of vaccine prevention in this vulnerable population.

Incidence of Acute Chest Syndrome in Children With Sickle Cell Disease Following Implementation of the 13-Valent Pneumococcal Conjugate Vaccine in France.

Importance: Acute chest syndrome (ACS) is one of the leading acute severe complications of sickle-cell disease (SCD). Although Streptococcus pneumoniae (S pneumoniae) is highly prevalent in children with SCD, its precise role in ACS is unclear. The efficacy of 13-valent pneumococcal conjugate vaccine (PCV13) implementation on ACS is still unknown. Objective: To assess the association of PCV13 implementation in the general pediatric population with the incidence of ACS in children with SCD. Design, Setting, and Participants: This cohort study used an interrupted time-series analysis of patient records from a national hospital-based French surveillance system. All children younger than 18 years with SCD (based on the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision definition) hospitalized in France between January 2007 and December 2019 were included. Exposures: PCV13 implementation. Main Outcomes and Measures: Monthly incidence of ACS per 1000 children with SCD over time as analyzed by segmented linear regression with autoregressive error; monthly incidence of hospitalization for vaso-occlusive crisis, asthma crisis, and acute pyelonephritis per 1000 children with SCD over the same period as the control outcomes. Results: Among the 107 694 hospitalizations of children with SCD, 4007 episodes of ACS were included (median [IQR] age, 8 [4-12] years; 2228 [55.6%] boys). PCV13 implementation in 2010 was followed by a significant decrease in the incidence of ACS (-0.9% per month; 95% CI, -1.4% to -0.4%; P < .001), with an estimated cumulative change of -41.8% (95% CI, -70.8% to -12.7%) by 2019. Sensitivity analyses yielded the same results, including the incidence of ACS adjusted for that of vaso-occlusive crisis over time. The results were similar among different age groups. By contrast, no change was found for the 3 control outcomes over the study period. Conclusions and Relevance: PCV13 implementation was associated with an important reduction in the incidence of ACS in children with SCD. This vaccine benefit provides new evidence of the key role of S pneumoniae in ACS and should be considered when estimating outcomes associated with current PCVs and the potential benefit of next-generation PCVs in children.

Imported schistosomiasis in Paris region of France: A multicenter study of prevalence and diagnostic methods.

BACKGROUND: There are few data on imported schistosomiasis - especially in children. The objectives of the present study were to estimate the prevalence of imported schistosomiasis in at-risk children in the greater Paris region of France and to compare diagnostic methods. METHOD: Children at risk of schistosomiasis who consulted or were hospitalized in four hospitals in the greater Paris region were prospectively included. Clinical and laboratory data were collected. Urine and feces samples were screened for Schistosoma spp. using microscopy, a point-of-care circulating cathodic antigen and a real-time polymerase chain reaction assay. Serum samples were screened using Western blot, ELISA, indirect hemagglutination, and immunochromatographic assays. The diagnosis was characterized as confirmed (positive microscopy analysis) and as suspected (positive ELISA and Western blot assays). The prevalence of schistosomiasis and the tests' performances were estimated using the latent class method. RESULTS: A total of 114 children were included. Most of the children were newly arrived migrants from sub-Saharan Africa. The mean age was 13.2 years-old. There were 12 (10.5%) confirmed cases and 13 (11.4%) suspected cases. Half of the confirmed and suspected cases were asymptomatic. The prevalence was 24.3%. The ELISA and the Western blot assays presented the same sensitivity (83%) and specificity (99%). The serum immunochromatographic assay also showed good performance. CONCLUSIONS: The high prevalence of imported schistosomiasis among at-risk children in the greater Paris region confirms the need for systematic screening. A serum immunochromatographic assay appears to be one of the most effective screening methods for a low cost.

Multiplex PCR reveals a high prevalence of multiple pathogens in traveller's diarrhoea in children.

OBJECTIVE: Traveller's diarrhoea (TD) is one of the most frequent illnesses affecting children returning from tropical countries. The purpose of this study was to assess the distribution of pathogens associated with TD in children using a multiplex PCR assay on stool samples. DESIGN: All the children admitted for TD in two university hospitals from 1 August to 15October during 2014 and 2015 were included in a prospective study. Stool samples were tested by a multiplex PCR FilmArray GI panel detecting 22 pathogens. Performances for the detection of major enteropathogenic bacteria (Salmonella, Shigella and Campylobacter spp) by multiplex PCR and conventional culture methods were compared. The prevalence of extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae was also determined. RESULTS: Fifty-nine children were included. In 58 cases (98%), at least one pathogen was identified, including 9 different enteropathogenic bacteria, 5 viruses and 2 parasites. Multiplex PCR enhanced the enteropathogenic bacteria detection by 25%. The most frequent pathogens were enteroaggregative Escherichia coli (n=32), enteropathogenic E. coli (n=26), enterotoxigenic E. coli (n=19), Salmonella enterica, enteroinvasive E. coli/Shigella (n=16 each), Cryptosporidium, sapovirus (n=11 each), Campylobacter jejuni, norovirus (n=10 each), rotavirus (n=9), Giardia (n=8) and Shiga-toxin-producing E. coli (n=4). Fifty-two coinfections were observed, notably including bacteria and viruses (n=21), multiple bacteria (n=14), or bacteria and parasites (n=10). ESBL were detected in 28 cases. Multiplex PCR could optimise the number of treated patients by 27% compared with stool cultures. CONCLUSION: Multiplex PCR on stools revealed a high prevalence of diverse enteric pathogens and coinfections in children with TD. Major enteropathogenic bacteria were more frequently detected by multiplex PCR compared with conventional culture. Finally, this technique allows the start of appropriate and early antibiotic treatment and seems to optimise the number of correctly treated patients.

Imported Schistosomiasis in Children: Clinical, Diagnostic Aspects And Outcome in 5 Tertiary Hospitals in France.

The objective of this retrospective study is to describe imported schistosomiasis in children in the Paris region between 2010 and 2015. Forty children with a diagnosis of schistosomiasis were included. Thirty-seven (93%) had a chronic urinary form with hematuria. The lost-to-follow up rate for the second consultation was 25%. The diagnosis and management of imported schistosomiasis must be improved-notably by raising awareness among clinicians and providing families with more information.

Retrospective study of imported falciparum malaria in French paediatric intensive care units.

OBJECTIVE: The World Health Organization (WHO) severity criteria for paediatric Plasmodium falciparum (Pf) malaria are based on studies in countries of endemic malaria. The relevance of these criteria for other countries remains unclear. We assessed the relevance of these criteria in an industrialised country. DESIGN: Retrospective case-control study. SETTING: Eight French university hospitals, from 2006 to 2012. PATIENTS: Children with Pf malaria admitted to paediatric intensive care units (cases: n=55) or paediatric emergency departments (controls: n=110). MAIN OUTCOME MEASURES: Descriptive analysis of WHO severity criteria and major interventions (mechanical ventilation, blood transfusion, fluid challenge, treatment of cerebral oedema, renal replacement therapy). Thresholds were set by receiver operating characteristics curve analysis. RESULTS: Altered consciousness (71% vs 5%), shock (24% vs 1%), renal failure (20% vs 1%), anaemia <50 g/L (7% vs 2%), acidosis (38% vs 0%), bilirubin level >50 µmol/L (25% vs 8%) and parasitaemia >10% (30% vs 8%) were more frequent in cases (p<0.01). All these criteria were associated with major interventions (p<0.001). Respiratory distress (six cases), and hypoglycaemia (two cases) were infrequent. Thrombocytopenia <50 000/mm3 (46% vs 7%) and anaemia (haemoglobin concentration <70 g/L (41% vs 13%)) were more frequent in cases (p<0.0001). CONCLUSIONS: The WHO severity criteria for paediatric Pf malaria are relevant for countries without endemic malaria. The infrequent but severe complications also provide a timely reminder of the morbidity and mortality associated with this condition worldwide. In non-endemic countries haemoglobin <70 g/L and platelet count <50 000/mm3 could be used as additional criteria to identify children needing high level of care.

Impact of unlabeled French antibiotic guidelines on antibiotic prescriptions for acute respiratory tract infections in 7 Pediatric Emergency Departments, 2009-2012.

From November 2009 to October 2012, implementation of guidelines, unlabeled by the French Agency of Health Products, changed the categories of antibiotics prescribed for acute respiratory tract infections in 7 pediatric emergency departments. During the study, 36,413 acute respiratory tract infections-related antibiotic prescriptions were prescribed. Amoxicillin prescriptions rose from 30.0% to 84.7%, while amoxicillin-clavulanate and cefpodoxime prescriptions decreased to 10.2% and 2.5%, respectively.

Pituitary stalk interruption syndrome in 53 postpubertal patients: factors influencing the heterogeneity of its presentation.

BACKGROUND: Pituitary stalk interruption syndrome (PSIS) may induce an isolated growth hormone (GH) deficiency or multiple hypothalamic-pituitary (HP) deficiencies. Patients with multiple HP deficiencies, primarily those with adrenocorticotropin (ACTH) deficiency, are at increased risk of morbidity and mortality. Our objective was to identify the factors influencing each symptom and the MRI features of the syndrome to enhance its diagnosis and genetic analysis. METHODS: This study was a retrospective, single-center, case-cohort study of 53 patients with PSIS who had reached pubertal age. RESULTS: Patients were classified as having an isolated GH deficiency (n = 24, Group 1) or HP deficiencies (n = 29, Group 2); of these, 19 had complete HP deficiency, and 10 had GH deficiency associated with TSH (n = 4), TSH and ACTH (n = 3), TSH and gonadotropin (n = 1) deficiencies or amenorrhea (n = 2). The following features were less frequent in Group 1 than in Group 2: breech presentation (4% vs 35%, P = 0.008), hypoglycemia (0% vs 59%, P<0.00001), micropenis (13% vs 69%, P<0.003), hypothalamic origin (0% vs 52%, P<0.000001), ophthalmic malformation (8% vs 38%, P<0.02) and psychomotor delay (0% vs 31%, P<0.004). The frequencies of all other malformations were similar in both groups (37% vs 59%). A visible pituitary stalk was characteristic of patients belonging to Group 1 (P<0.0002). The GH peak was greater in Group 1 than in Group 2 (P<0.0003), as was the anterior pituitary height (P = 0.01). CONCLUSION: The factors that best discriminate patients with multiple HP deficiencies from those with an isolated GH deficiency are breech presentation, hypoglycemia, and micropenis. No patient with an isolated GH deficiency had psychomotor delay, but associated malformations and/or syndromes, with the exception of ophthalmic disorders, occurred with similar frequencies in both groups. We have also shown that each of the above characteristics is associated with a given HP deficiency and/or malformation/syndrome in the majority of cases.

Clinical, biological and genetic analysis of 8 cases of congenital isolated adrenocorticotrophic hormone (ACTH) deficiency.

BACKGROUND: Congenital isolated adrenocorticotrophic hormone (ACTH) deficiency may be rare, but it could be an underestimated cause of neonatal death. Our objective was to shorten the time between first symptoms and diagnosis. METHODS: This single-centre retrospective case-cohort study was carried out on eight consecutive patients. RESULTS: Two had the neonatal form and 6 the late onset form. Six were admitted to an intensive care unit at least once for seizures with hypoglycemia, major hypothermia, fever, and/or collapsus. The 2 neonatal cases presented with hypoglycemia and in a state of "apparent death" at birth or hypothermia (29°C) at 6 days. All 6 late onset cases had also been admitted to an emergency department 1-3 times, but had left hospital incorrectly diagnosed. Their first symptoms were noted at 3-12.3 years, and they were diagnosed at 3.3-14.4 years. All had hypoglycemia, and 4 had had seizures. The presenting symptoms were vomiting and/or abdominal pain, asthenia, irritability, difficulty with physical activities, and anorexia. The school performance of 4 deteriorated. Two underwent psychotherapy and treatment for depression, which was stopped when Hydrocortisone® replacement therapy began. The plasma concentrations in spontaneous hypoglycemia were: ACTH<5 to 17.1 pg/mL, with concomitant cortisol <3.5 to 37 ng/mL. The plasma dehydroepiandrosterone sulfate (DHAS) concentrations were low in the 7 evaluated. The coding sequence of TPIT was normal in all. CONCLUSION: Several unexplained symptoms in a child, mainly gastro-intestinal symptoms and seizures due to hypoglycemia, may indicate ACTH deficiency. A low or normal basal plasma ACTH despite concomitant low cortisol at 8 a.m. and/or in spontaneous hypoglycemia, associated with low DHAS, in a patient not given corticosteroids is highly suggestive of ACTH deficiency. The isolated character of ACTH deficiency must be confirmed by determining the other hypothalamic-pituitary functions, and Hydrocortisone® replacement therapy initiated in emergency.