Crusted scabies in children in France: a series of 20 cases.

To evaluate the risk factors for crusted scabies in children in France. The retrospective multicenter study, conducted in France, of children (aged < 18 years) with profuse and/or crusted scabies confirmed by dermoscopy and/or microscopy. Data were obtained using a standardized questionnaire. We included 20 children. The mean age was 4.5 years, and 70% of the patients were girls. Their medical history revealed a neurological pathology (agenesis of the corpus callosum; n = 1, 5.0%), prematurity (n = 1, 5.0%), Down syndrome (n = 1, 5.0%), atopic dermatitis (n = 2, 10%), and asthma (n = 2, 10.0%). Fifteen (75.0%) children were treated with steroids before being diagnosed with scabies: 12 (60.0%) with topical steroids, one (5.0%) with a systemic steroid, and two (10.0%) with inhaled steroids. One child (5.0%) lived in a precarious environment. The mean duration of pruritus was 3.4 months, and that of the skin lesions was 3.1 months. The most commonly affected areas for crusted scabies were the palms/hands (66.7%) and the armpits (33.3%). Thirteen children (65.0%) were hospitalized, 14 (70.0%) were treated with ivermectin and all received topical treatments; 85.7% were cured within an average of 38 days, but one child had a relapse 3 months later in the form of common scabies.Conclusion: The main risk factor for developing crusted scabies in France was the misdiagnosis and the use of corticosteroids, especially topical forms typically used in "healthy" children. Management of the children was effective and similar to that used in adults. What is Known: • Crusted scabies is an extremely contagious disease which is rarely reported in infancy, especially in healthy children. • The main risk factors include immunosuppression, physical debilitation, and intellectual disability. What is New: • The main risk factor of severe scabies in this study was delayed diagnosis associated with the use of topical or systemic corticosteroids. • The treatment was successful in 85.7% of cases, and 65% of children needed to be hospitalized.

Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 mimicking Kawasaki disease (Kawa-COVID-19): a multicentre cohort.

BACKGROUND: Current data suggest that COVID-19 is less frequent in children, with a milder course. However, over the past weeks, an increase in the number of children presenting to hospitals in the greater Paris region with a phenotype resembling Kawasaki disease (KD) has led to an alert by the French national health authorities. METHODS: Multicentre compilation of patients with KD in Paris region since April 2020, associated with the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ('Kawa-COVID-19'). A historical cohort of 'classical' KD served as a comparator. RESULTS: Sixteen patients were included (sex ratio=1, median age 10 years IQR (4·7 to 12.5)). SARS-CoV-2 was detected in 12 cases (69%), while a further three cases had documented recent contact with a quantitative PCR-positive individual (19%). Cardiac involvement included myocarditis in 44% (n=7). Factors prognostic for the development of severe disease (ie, requiring intensive care, n=7) were age over 5 years and ferritinaemia >1400 µg/L. Only five patients (31%) were successfully treated with a single intravenous immunoglobulin (IVIg) infusion, while 10 patients (62%) required a second line of treatment. The Kawa-COVID-19 cohort differed from a comparator group of 'classical' KD by older age at onset 10 vs 2 years (p<0.0001), lower platelet count (188 vs 383 G/L (p<0.0001)), a higher rate of myocarditis 7/16 vs 3/220 (p=0.0001) and resistance to first IVIg treatment 10/16 vs 45/220 (p=0.004). CONCLUSION: Kawa-COVID-19 likely represents a new systemic inflammatory syndrome temporally associated with SARS-CoV-2 infection in children. Further prospective international studies are necessary to confirm these findings and better understand the pathophysiology of Kawa-COVID-19. Trial registration number NCT02377245.

Mutations in the SRP54 gene cause severe congenital neutropenia as well as Shwachman-Diamond-like syndrome.

Congenital neutropenias (CNs) are rare heterogeneous genetic disorders, with about 25% of patients without known genetic defects. Using whole-exome sequencing, we identified a heterozygous mutation in the SRP54 gene, encoding the signal recognition particle (SRP) 54 GTPase protein, in 3 sporadic cases and 1 autosomal dominant family. We subsequently sequenced the SRP54 gene in 66 probands from the French CN registry. In total, we identified 23 mutated cases (16 sporadic, 7 familial) with 7 distinct germ line SRP54 mutations including a recurrent in-frame deletion (Thr117del) in 14 cases. In nearly all patients, neutropenia was chronic and profound with promyelocytic maturation arrest, occurring within the first months of life, and required long-term granulocyte colony-stimulating factor therapy with a poor response. Neutropenia was sometimes associated with a severe neurodevelopmental delay (n = 5) and/or an exocrine pancreatic insufficiency requiring enzyme supplementation (n = 3). The SRP54 protein is a key component of the ribonucleoprotein complex that mediates the co-translational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER). We showed that SRP54 was specifically upregulated during the in vitro granulocytic differentiation, and that SRP54 mutations or knockdown led to a drastically reduced proliferation of granulocytic cells associated with an enhanced P53-dependent apoptosis. Bone marrow examination of SRP54-mutated patients revealed a major dysgranulopoiesis and features of cellular ER stress and autophagy that were confirmed using SRP54-mutated primary cells and SRP54 knockdown cells. In conclusion, we characterized a pathological pathway, which represents the second most common cause of CN with maturation arrest in the French CN registry.

Appropriate thresholds for accurate screening for ß-thalassemias in the newborn period: results from a French center for newborn screening.

Objectives: Newborn screening (NBS) for ß-thalassemia is based on measuring the expression of the hemoglobin A (HbA) fraction. An absence or very low level of HbA at birth may indicate ß-thalassemia. The difficulty is that the HbA fraction at birth is correlated with gestational age (GA) and highly variable between individuals. We used HbA expressed in multiples of the normal (MoM) to evaluate relevant thresholds for NBS of ß-thalassemia. Methods: The chosen threshold (HbA≤0.25 MoM) was prospectively applied for 32 months in our regional NBS program for sickle cell disease, for all tests performed, to identify patients at risk of ß-thalassemia. Reliability of this threshold was evaluated at the end of the study. Results: In all, 343,036 newborns were tested, and 84 suspected cases of ß-thalassemia were detected by applying the threshold of HbA≤0.25 MoM. Among the n=64 cases with confirmatory tests, 14 were confirmed using molecular analysis as ß-thalassemia diseases, 37 were confirmed as ß-thalassemia trait and 13 were false-positive. Determination of the optimum threshold for ß-thalassemia screening showed that HbA≤0.16 MoM had a sensitivity of 100% and a specificity of 95.3%, whatever the GA. Conclusions: NBS for ß-thalassemia diseases is effective, regardless of the birth term, using the single robust threshold of HbA≤0.16 MoM. A higher threshold would also allow screening for carriers, which could be interesting when ß-thalassemia constitutes a public health problem.

Improvement of medical care in a cohort of newborns with sickle-cell disease in North Paris: impact of national guidelines.

We conducted a retrospective study on newborns with sickle-cell disease (SCD), born 1995-2009, followed in a multicentre hospital-based network. We assessed patient outcomes, medical care and compliance with the national guidelines published in December 2005. Data from 1033 patients (742 SS/Sß°-thalassaemia) with 6776 patient-years of follow-up were analysed (mean age 7·1 ± 3·9 years). SCD-related deaths (n = 13) occurred only in SS-genotype patients at a median age of 23·1 months, mainly due to acute anaemia (n = 5, including 2 acute splenic sequestrations) and infection (n = 3). Treatment non-compliance was associated with a 10-fold higher risk of SCD-related death (P = 0·01). Therapeutic intensification was provided for all stroke patients (n = 12), almost all patients with abnormal transcranial Doppler (TCD) (n = 76) or with >1 acute chest syndrome/lifetime (n = 64) and/or ≥3 severe vaso-occlusive crises/year (n = 100). Only 2/3 of patients with baseline haemoglobin <70 g/l received intensification, mainly for other severity criteria. Overall, hydroxycarbamide was under-prescribed, given to 2/3 of severe vaso-occlusive patients and 1/3 of severely anaemic patients. Nevertheless, introduction of the on-line guidelines was concomitant with an improvement in medical care in the 2006-2009 cohort with a trend towards increased survival at 5 years, from 98·3% to 99·2%, significantly increased TCD coverage (P = 0·004) and earlier initiation of intensification of therapy (P ≤ 0·01).

Dominant mutations in MIEF1 affect mitochondrial dynamics and cause a singular late onset optic neuropathy.

Inherited optic neuropathies are the most common mitochondrial diseases, leading to neurodegeneration involving the irreversible loss of retinal ganglion cells, optic nerve degeneration and central visual loss. Importantly, properly regulated mitochondrial dynamics are critical for maintaining cellular homeostasis, and are further regulated by MIEF1 (mitochondrial elongation factor 1) which encodes for MID51 (mitochondrial dynamics protein 51), an outer mitochondrial membrane protein that acts as an adaptor protein to regulate mitochondrial fission. However, dominant mutations in MIEF1 have not been previously linked to any human disease. Using targeted sequencing of genes involved in mitochondrial dynamics, we report the first heterozygous variants in MIEF1 linked to disease, which cause an unusual form of late-onset progressive optic neuropathy characterized by the initial loss of peripheral visual fields. Pathogenic MIEF1 variants linked to optic neuropathy do not disrupt MID51's localization to the outer mitochondrial membrane or its oligomerization, but rather, significantly disrupt mitochondrial network dynamics compared to wild-type MID51 in high spatial and temporal resolution confocal microscopy live imaging studies. Together, our study identifies dominant MIEF1 mutations as a cause for optic neuropathy and further highlights the important role of properly regulated mitochondrial dynamics in neurodegeneration.

Effectiveness and safety of azithromycin 1.5% eye drops for mass treatment of active trachoma in a highly endemic district in Cameroon.

OBJECTIVE: To evaluate the effectiveness and safety of azithromycin 1.5% eye drops under field conditions to reduce active trachoma in a highly endemic district in Cameroon. This is a follow-up of an initial report published in 2010. METHODS AND ANALYSIS: Three annual campaigns were performed in 2008, 2009 and 2010 to treat the population (~1 20 000 individuals) of the Kolofata Health District with topical azithromycin 1.5% (one drop in each eye, morning and evening for three consecutive days). The effectiveness of this intervention against active trachoma was assessed in children aged 1-9 years in cross-sectional studies prior to each mass treatment using a systematic sampling procedure (in 2008, 2009 and 2010) and then 1 year (2011) and 3 years (2013) after the last intervention among the villages with previously high active trachoma prevalence or never tested. RESULTS: The prevalence of trachomatous inflammation-follicular (TF) dropped from 24.0% (95% CI 20.7 to 27.5) before treatment to 2.8% (95% CI 2.2 to 3.7) 1 year after completion of the 3 year campaign. Trachomatous inflammation-intense was present in only 4 (0.2%) children 1 year after the third round of treatment. Three years after the last campaign, the surveillance survey among the most prevalent villages and villages never tested before showed a prevalence of 5.2% (95% CI 3.6 to 7.2) of active trachoma. Tolerance was excellent, with no report of treatment interruption, serious ocular or systemic adverse events. CONCLUSION: Annual mass treatment with azithromycin eye drops was shown to be effective in reducing TF to a level ≤5% one year after a 3-round annual mass treatment in an endemic region at the district level.

Changes in Reverse Transcription Polymerase Chain Reaction-positive Severe Acute Respiratory Syndrome Coronavirus 2 Rates in Adults and Children According to the Epidemic Stages.

From March 2, 2020, to April 26, 2020, 52,588 reverse transcription polymerase chain reaction (RT-PCR) tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were performed in France, 6490 in children and 46,098 in adults. The rate of RT-PCR-positive SARS-CoV-2 tests for children (5.9%) was always less than that for adults (20.3%) but vary according to the epidemic stage. The risk ratio of RT-PCR-positive SARS-CoV-2 tests for adults compared with children was 3.5 (95% confidence interval: 3.2-3.9) for the whole study period.

Epidemiology and Clinical Presentation of Children Hospitalized with SARS-CoV-2 Infection in Suburbs of Paris.

Understanding the clinical presentation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and prognosis in children is a major issue. Children often present mild symptoms, and some severe forms require paediatric intensive care, with in some cases a fatal prognosis. Our aim was to identify the epidemiological characteristics, clinical presentation, and prognosis of children with coronavirus disease 2019 (Covid-19) hospitalized in Paris suburb hospitals. In this prospective, observational, multicentre study, we included children hospitalized in paediatric departments of Paris suburb hospitals from 23 March 2020 to 10 May 2020, during the national lockdown in France with confirmed SARS-CoV-2 infection (positive RNA test on a nasopharyngeal swab) or highly suspected infection (clinical, biological, and/or radiological data features suggestive for SARS-CoV-2 infection). A total of 192 children were included for confirmed (n = 157) or highly suspected (n = 35) SARS-CoV-2 infection. The median age was one year old (interquartile range 0.125-11) with a sex ratio 1.3:1. Fever was recorded in 147 (76.6%) children and considered poorly tolerated in 29 (15.1%). The symptoms ranged from rhinorrhoea (34.4%) and gastrointestinal (35.5%) to respiratory distress (25%). Only 10 (5.2%) children had anosmia and five (2.6%) had chest pain. An underlying condition was identified in almost 30% of the children in our study. Overall, 24 (12.5%) children were admitted to paediatric intensive care units, 12 required mechanical ventilation, and three died. For children in Paris suburbs, most cases of Covid-19 showed mild or moderate clinical expression. However, one-eighth of children were admitted to paediatric intensive care units and three died.

Outcomes of cataract surgery performed by non-physician cataract surgeons in remote North Cameroon.

OBJECTIVE: To report the outcomes of cataract surgery performed by non-physician cataract surgeons due to lack of ophthalmologists in remote areas of North Cameroon. DESIGN: Prospective cohort study. SETTING: The main centre of the non-governmental organisation Ophtalmo Sans Frontières in Lagdo. PARTICIPANTS AND INTERVENTIONS: Age-related cataract surgery performed between 28 November 2016 and 17 May 2017. MAIN OUTCOMES MEASURES: The main outcome measure was presenting visual acuity (PVA) 1-4 weeks after surgery, classified according to the WHO as good (PVA ≥6/18), borderline (PVA 6/60-6/18) and poor (PVA <6/60). The WHO definition of blindness (visual acuity <3/60) and severe visual acuity (visual acuity 3/60-6/60) was used to assess the proportion of patients with a change in WHO category. RESULTS: We included 474 eyes of 474 patients; the mean (SD) age was 63.9 (15) years (42.2% female). At 1-4 weeks after surgery, the surgical outcome was good for 170 patients (41.1%), borderline for 213 (51.5%) and poor for 31 (7.5%). In all, 224 patients (47.2%) had blindness or severe visual impairment before cataract surgery and 22 (5.3%) at 1-4 weeks after surgery. Poor visual outcome was associated with older age (p=0.018), preoperative blindness or severe impairment (p=0.012) and surgical complications (p=0.019). CONCLUSION: Blindness and severe visual impairment were significantly decreased in the early postoperative period. Poor outcomes were associated with older age, low preoperative binocular visual acuity and intraoperative complications. Non-physician cataract surgeons may compensate for the lack of ophthalmologists in remote areas of low-income and middle-income countries.

Analysis of risk factors for myelodysplasias, leukemias and death from infection among patients with congenital neutropenia. Experience of the French Severe Chronic Neutropenia Study Group.

BACKGROUND AND OBJECTIVES: The two main complications of severe chronic neutropenia are fatal sepsis and myelodysplasia/acute leukemia (MDS/AL). Granulocyte colony-stimulating factor (G-CSF) therapy has significantly reduced the frequency and severity of infections, but its possible influence on the risk of malignancy is not known. DESIGN AND METHODS: The French Severe Chronic Neutropenia (SCN) Registry has prospectively collected data since 1994 on 231 patients with various forms of SCN, namely severe congenital neutropenia (n=101), cyclic neutropenia (n=60), glycogen storage disease type Ib (GSDIb) (n=15) and Shwachman-Diamond syndrome (SDS)(n=55). The median overall follow-up is 11.1 years. Parameters of exposure to G-CSF therapy, such as the time averaged dose, follow up after first use of G-CSF, and the cumulative dose, have been recorded. RESULTS: Eight septic deaths occurred, of which 6 among patients with severe congenital neutropenia and 2 in patients with cyclic neutropenia; none of these 8 patients was receiving G-CSF therapy. No septic deaths occurred during G-CSF therapy. Thirteen cases of MDS/AL were recorded. The cumulative incidence of MDS/AL was 2.7% (SD 1.3%) at 10 years and 8.1% (SD 2.7%) at 20 years. INTERPRETATION AND CONCLUSIONS: Risk factors for MDS/AL were the diagnostic category, the severity of neutropenia, younger age at diagnosis, and strong exposure to G-CSF. MDS/AL only occurred in patients with severe congenital neutropenia and SDS. Owing to their particular susceptibility to infections, patients with severe congenital neutropenia had the strongest exposure to G-CSF; the risk of leukemia increased with the degree of G-CSF exposure in this subgroup.

Contributions to the Improvement of Living Conditions among Neglected Populations with Trachoma.

OBJECTIVE: Trachoma (Chlamydia-triggered blinding infection) provoked irreversible visual impairment in about 8 million people in 2011, and the prevalence among children with dirty faces is more than three fold that among children with clean faces. In 250 villages with a high prevalence of trachoma (Kolofata district, Far North Region, Cameroon), the lack of water for facial cleanliness was reported during trachoma awareness campaigns. The objective of this study was to determine if the lack of water was linked with the absence of means to dig wells. METHODS: Wells, waterholes, motorcycles, irrigation pumps, electricity, goats and oxen, cell phones and distance from waterholes were recorded in January 2011 in 50 randomized villages of Kolofata's district. RESULTS: The number of villages with <25 goats and <5 oxen was 0 and the number of adults owning <1 goat was 0. The cost of a pail of water was 0.01 USD. Motorcycles, cell phones and televisions have been reported in more than 66% of villages. The cost for the construction of lined shaft wells ranged between 15-35 goats and 0.5-3 oxen; the cost for drinking water wells ranged between 50-200 goats and 3-30 oxen. DISCUSSION: No link between the means for digging wells at the village level and access to water was found. Social solidarity, which refers to a social debt owed by each person to his/her group, should be added to training guides to gauge its ability to release people from the dead end of having to wait for external assistance to gain access to water.

Clinical and microbiological assessment of trachoma in the kolofata health district, far north region, cameroon.

BACKGROUND AND AIMS: Trachoma is a sight-threatening process triggered by the infection of the conjunctiva with Chlamydiae. Blindness associated with trachoma was reported in Sahelian areas of Cameroon. However, data on the prevalence of this neglected infection in the Far North Region are not available. The aim of this study was a) to assess clinical trachoma and b) to detect Chlamydia in the conjunctiva of trachomatous populations living in the Far North Regions of Cameroon. METHODS: A total of 2,423 randomly selected children (1-10 years) and 1,590 women over 14 from randomly selected villages from the Kolofata Health District (115,000 inhabitants) were included in a cross-sectional study in February 2009. Trained staff examined and obtained conjunctival swabs from trachomatous subjects. DNA was extracted and amplified to detect Chlamydia DNA by real-time PCR. The quality of sampling was assessed by quantifying the number of epithelial cells. RESULTS: Children (2,397 or 98.9% of the predicted number) and women (1,543; 97.0%) were examined. The prevalence of follicular trachoma (TF) in children was 21% (95% CI 17.8-24.5) and of intense inflammatory trachoma (TI) 5.2% (95% CI 3.6-7.3). Among the women, trichiasis (TT) was observed in 3.4% (95% CI 2.4-4.7), corneal opacities (CO) in 1.4% (95% CI 0.8-2.3) and trachoma-related blindness in 0.9% (95% CI 0.4-1.8). Conditions related to income, illiteracy, latrines, water supply and animals wandering close to dwellings were similar in all the villages. PCR was positive in 35% of children with active trachoma and in 6% of adult females presenting TT and/or related corneal opacities. CONCLUSION: The prevalence of trachoma and the severe trachoma sequelae found during this survey underline the urgent need to implement efficient blindness prevention interventions to improve the visual future of the people in the Sahelian region.

Description and outcome of a cohort of 8 patients with WHIM syndrome from the French Severe Chronic Neutropenia Registry.

BACKGROUND: WHIM syndrome (WS), a rare congenital neutropenia due to mutations of the CXCR4 chemokine receptor, is associated with Human Papillomavirus (HPV)-induced Warts, Hypogammaglobulinemia, bacterial Infections and Myelokathexis. The long term follow up of eight patients highlights the clinical heterogeneity of this disease as well as the main therapeutic approaches and remaining challenges in the light of the recent development of new CXCR4 inhibitors. OBJECTIVE: This study aims to describe the natural history of WS based on a French cohort of 8 patients. METHODS: We have reviewed the clinical, biological and immunological features of patients with WS enrolled into the French Severe Chronic Neutropenia Registry. RESULTS: We identified four pedigrees with WS comprised of eight patients and one foetus. Estimated incidence for WS was of 0.23 per million births. Median age at the last visit was 29 years. Three pedigrees encompassing seven patients and the fetus displayed autosomal dominant heterozygous mutations of the CXCR4 gene, while one patient presented a wild-type CXCR4 gene. Two subjects exhibited congenital conotruncal heart malformations. In addition to neutropenia and myelokathexis, all patients presented deep monocytopenia and lymphopenia. Seven patients presented repeated bacterial Ears Nose Throat as well as severe bacterial infections that were curable with antibiotics. Four patients with late onset prophylaxis developed chronic obstructive pulmonary disease (COPD). Two patients reported atypical mycobacteria infections which in one case may have been responsible for one patient's death due to liver failure at the age of 40.6 years. HPV-related disease manifested in five subjects and progressed as invasive vulvar carcinoma with a fatal course in one patient at the age of 39.5 years. In addition, two patients developed T cell lymphoma skin cancer and basal cell carcinoma at the age of 38 and 65 years. CONCLUSIONS: Continuous prophylactic anti-infective measures, when started in early childhood, seem to effectively prevent further bacterial infections and the consequent development of COPD. Long-term follow up is needed to evaluate the effect of early anti-HPV targeted prophylaxis on the development of skin and genital warts.

Elimination of active trachoma after two topical mass treatments with azithromycin 1.5% eye drops.

BACKGROUND: Following an epidemiological study carried out in 2006 showing a high prevalence of blinding trachoma in the Far North Region of Cameroon, a trachoma elimination programme using the SAFE strategy was initiated: three yearly trachoma mass treatments were to be performed. METHODOLOGY/PRINCIPAL FINDINGS: The entire district population (120,000 persons) was treated with azithromycin 1.5% eye drops in February 2008 and January 2009. To assess the effect of treatment on the prevalence of active trachoma, three epidemiological studies were conducted on a representative sample of children aged between 1 and 10 years. The first study was performed just prior to the first treatment, the second just prior to the 2nd treatment and the third one, one year later. The prevalence of active forms of trachoma (TF + TI) dropped from 31.5% (95%CI 26.4-37.5) before treatment to 6.3% (95%CI 4.1-9.6) one year after first treatment; a reduction of nearly 80%. One year after the second treatment, the prevalence decreased to 3.1% (95%CI 2.0-4.9), a total reduction of 90%. Furthermore, there were no more TI cases (only TF). There was no report of serious or systemic side effects. Tolerance was excellent. CONCLUSIONS/SIGNIFICANCE: Active trachoma mass treatment with azithromycin 1.5% eye drops is feasible, well tolerated, and effective.