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To review and assess the efficiency of pre-emptive plerixafor administration for poor mobilization (PM) and to review and assess mobilization efficiency (≥2×10This retrospective study evaluated all patients with MM and lymphoma undergoing peripheral blood stem cell mobilization and collection at our institution between February 2014 and August 2021. Plerixafor was administered pre-emptively by a plateau of10 peripheral blood CD34+/µl after chemotherapy-based mobilization or CD34+ of8/µL on day 4 after mobilization with G-CSF alone. Between peak CD34+ levels of 10-15/µl, plerixafor will be used at the discretion of the treating physician.In total, 215 patients were enrolled. Among them, 80% had peak CD34+ level ≥20/µL, 11% had clear poor mobilization (peak CD34+ levels10/µL), and 9% had borderline PM (CD34+ between 10-19/µL). Plerixafor was administered pre-emptively in 13% of the patients and 75% of patients with borderline PM were collected without plerixafor, suggesting that plerixafor is not needed if CD34+15/µL on the anticipated collection day. Mobilization failed in only one patient (1%).Our data showed that with plerixafor pre-emptive administration, the primary endpoint was achieved for most patients identified with PM, preventing the need for a second mobilization attempt.

Alpha-1 antitrypsin deficiency is an autosomal, codominant disorder caused by mutations of the SERPINA1 gene. This genetic disorder is mainly associated with development of pulmonary emphysema and/or chronic liver disease and cirrhosis.Here we report a very rare alpha-1 antitrypsin Null Q0cairo homozygous mutation characterized by a complete absence of alpha-1 antitrypsin in the plasma, in a non-consanguineous Moroccan family. This mutation has been previously described in heterozygosis in only three cases worldwide: an Italian/Egyptian family and two Italian families (Zorzetto et al., 2005). The main clinical features in two members of this Moroccan family were the severity and precocity of bronchiectasis, quickly spreading and seriously limiting respiratory function and physical activity by the second decade of age. Moreover, the index case presented with many episodes of pulmonary infections concomitant with severe neutropenia. The third member of the family presented with ankylosing spondyloarthritis and developed panniculitis later but had no respiratory symptoms.The presence of this alpha-1-antitrypsin Q0cairo homozygous mutation could explain the severity of clinical manifestations. Moreover, our observations highlight a great variability of clinical expression for the same mutation: early severe bronchiectasis, panniculitis, rheumatologic manifestations. This study further underlines the importance of genotyping by whole SERPINA1 gene sequencing in addition to serum alpha-1 antitrypsin determination, to enable detection of alpha-1 antitrypsin deficiency due to rare genotypes. Keywords: Alpha-1 antitrypsin deficiency, Bronchiectasis, Panniculitis, Null mutation, SERPINA1 genotyping

Setting Tuberculosis spondylodiscitis (TS), or Pott's disease, an extra-pulmonary form of tuberculosis (TB), is rare and difficult to diagnose in children. Some cases of severe TB in children were recently explained by inborn errors of immunity affecting the interleukin-12/interferon-gamma (IL-12/IFN-γ) axis. Objective To analyse clinical data on Moroccan children with TS, and to perform immunological and genetic explorations of the IL-12/IFN-γ axis. Design We studied nine children with TS diagnosed between 2012 and 2014. We investigated the IL-12/IFN-γ circuit by both whole-blood assays and sequencing of the coding regions of 14 core genes of this pathway. Results A diagnosis of TS was based on a combination of clinical, biological, histological and radiological data. QuantiFERON(®)-TB Gold In-Tube results were positive in 75% of patients. Whole-blood assays showed normal IL-12 and IFN-γ production in all but one patient, who displayed impaired decreased response to IL-12. No candidate disease-causing mutations were detected in the exonic regions of the 14 genes. Conclusions TS diagnosis in children remains challenging, and is based largely on imaging. Further investigations of TS in children are required to determine the role of genetic defects in pathways that may or may not be related to the IL-12/IFN-γ axis.

WOS: 000350167200008, PubMed ID: 25703555, Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb) and a few related mycobacteria, is a devastating disease, killing more than a million individuals per year worldwide. However, its pathogenesis remains largely elusive, as only a small proportion of infected individuals develop clinical disease either during primary infection or during reactivation from latency or secondary infection. Subacute, hematogenous, and extrapulmonary disease tends to be more frequent in infants, children, and teenagers than in adults. Life-threatening primary TB of childhood can result from known acquired or inherited immunodeficiencies, although the vast majority of cases remain unexplained. We review here the conditions conferring a predisposition to childhood clinical diseases caused by mycobacteria, including not only M.tb but also weakly virulent mycobacteria, such as BCG vaccines and environmental mycobacteria. Infections with weakly virulent mycobacteria are much rarer than TB, but the inherited and acquired immunodeficiencies underlying these infections are much better known. Their study has also provided genetic and immunological insights into childhood TB, as illustrated by the discovery of single-gene inborn errors of IFN- immunity underlying severe cases of TB. Novel findings are expected from ongoing and future human genetic studies of childhood TB in countries that combine a high proportion of consanguineous marriages, a high incidence of TB, and an excellent clinical care, such as Iran, Morocco, and Turkey., European Research CouncilEuropean Research Council (ERC) [ERC-2010-AdG-268777]; French National Research Agency (ANR)French National Research Agency (ANR) [ANR-10-IAHU-01, ANR-08-MIEN-014-02]; Institut National de la Sante et de la Recherche Medicale, Universite Paris DescartesInstitut National de la Sante et de la Recherche Medicale (Inserm); St. Giles Foundation; Rockefeller University from the National Center for Research Resources [8ULTR000043]; National Center for Advancing Sciences (NCATS) of the National Institute of Health; Rockefeller University; National Institute of Allergy and Infectious DiseasesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Allergy & Infectious Diseases (NIAID) [U01AI088685, R01AI089970, R37AI095983], We thank all clinicians from many countries around the world for their help and contribution in the investigation of TB patients. Special thanks to A. Strickler and J. F. Emile for providing the pictures. We also thank all members of the Necker and Rockefeller branches of the Laboratory of Human Genetics of Infectious Diseases. This work was supported by grants from the European Research Council (ERC-2010-AdG-268777), the French National Research Agency (ANR) under "the Investments for the Future" grant number ANR-10-IAHU-01, ANR-08-MIEN-014-02, Institut National de la Sante et de la Recherche Medicale, Universite Paris Descartes, the St. Giles Foundation, the Rockefeller University grant number 8ULTR000043 from the National Center for Research Resources and the National Center for Advancing Sciences (NCATS) of the National Institute of Health, the Rockefeller University, the National Institute of Allergy and Infectious Diseases grant number U01AI088685, R01AI089970, and R37AI095983. The authors have no financial or commercial conflict of interest to declare.

IL-12 receptor β1 deficiency (IL-12Rβ1) predisposes patients to mycobacteria and Salmonella infections. We report a case of IL-12Rβ1 deficiency with a fatal multi-resistant Salmonella enteritidis infection. This boy was born after from a consanguineous marriage, and diagnosed as having a IL-12Rβ1 deficiency since the age of 3 months. He presented with recurrent Salmonella enteritidis essentially digestive localization, complicated by purulent pericarditis at the same germ at the age of two and a half years. At the age of 3, a colonic infiltration due to a Salmonella enteritidis resistant to antibiotics, was complicated by acute intussusception, and the child died. The IL-12Rβ1 deficiency is considered as having a good prognosis, in contrast to what happened in our patient. We review therapeutic issues in these patients.

Le Syndrome hyper IgM est un déficit immunitaire héréditaire bien connu, décrit pour la première fois en 1961. Il est causé par un défaut au niveau des lymphocytes B, caractérisé par un taux sérique normal ou élevé des IgM et un taux bas ou nul des IgG, IgA, IgE résultant d'une déficience de la commutation isotypique. Ses manifestations cliniques sont dominées par les infections à répétition, surtout du tube digestif, de la sphère ORL et des poumons. Le syndrome est causé par un défaut de commutation de classe d'immunoglobuline dans les cellules B, et une diminution de la capacité des monocytes à induire la prolifération des lymphocytes T. Le résultat net de tous ces défauts est la susceptibilité accrue aux infections opportunistes à Pneumocystis jiroveci, Cryptosporidium spp et d'autres organismes intracellulaires, ainsi qu'une fréquence élevée d'infections bactériennes et virales. L'intérêt de ce projet est d'illustrer l'importance de la compréhension des mécanismes physiopathologiques associés à cette susceptibilité accrue aux infections, ce qui permettra une meilleure prise en charge diagnostique et thérapeutique des patients atteint du Syndrome hyper IgM (SHIM).

Resume Les craniostenoses correspondent a la soudure prematuree d’une ou plusieurs sutures crâniennes responsable ainsi de deformations craniofaciales ou parfois de complications neurologiques. Le scanner spirale avec reconstructions 3D est l’examen cle pour le diagnostic des craniostenoses qu’elles soient simples ou syndromiques et contribue au bilan pretherapeutique. Les auteurs font une mise au point sur les craniostenoses et leur exploration ainsi qu’une revue iconographique de ses differents types.

Resume Les tumeurs intraventriculaires sont des tumeurs rares, d’etiologies variables et le plus souvent benignes. L’approche etiologique se fait en fonction de l’âge du patient, de la localisation et des caracteristiques semiologiques de la tumeur. L’imagerie, notamment l’IRM, est l’examen de choix pour le diagnostic positif et le bilan d’extension. L’objectif de ce travail est de preciser l’apport de l’imagerie dans la caracterisation semiologique des tumeurs intraventriculaires et la gamme diagnostique a evoquer en fonction du siege et de l’aspect tumoral.

Streptococcus intermedius is a member of the Streptococcus anginosus group, also known as the Streptococcus milleri group. Although this is a commensal agent of the mouth and upper airways, it has been recognized as an important pathogen in the formation of abscesses. However, it has rarely been involved in the formation of brain abscess in children. We report 4 pediatric cases of brain abscess caused by S. intermedius. Three boys and 1 girl, all aged over 2 years, were admitted for a febrile meningeal syndrome and seizures, caused by a S. intermedius brain abscess. Diagnosis was obtained by brain imaging combined with culture of cerebrospinal fluid. The outcome was favorable after antibiotic therapy and abscess puncture. S. intermedius should be considered a potential pathogen involved in the development of brain abscess in children.

An increased incidence and severity of invasive group A streptococcus (GAS) infections over the past decade have been reported by several authors, but GAS remains an uncommon cause of bacterial meningitis. The aim of this study was to describe and analyze the clinical and biological data of GAS meningitis by reporting 10 new cases of pediatric GAS meningitis and making a literature review. The mean age of patients, seven girls and three boys, was 3 years. There was a history of preexisting or concomitant community-acquired infection in five patients over 10. The outcome was fatal in two cases. All patients received an initial empirical antimicrobial therapy with a third generation cephalosporin switched in six cases to amoxicillin. The prognosis for this type of streptococcal meningitis is usually good, but death may occur even in children without any identified risk factor for severe infection.

Lead colic is a rare cause of abdominal pain. The diagnosis of lead poisoning is most often mentioned in at risk populations (children, psychotic). We report the case of a 2 year old child that was presented for acute abdomen. Abdominal plain radiograph showed multiple intra-colonic metallic particles and suggested lead poisoning diagnosis. Anamnesis found a notion of pica and consumption of peeling paint. Elevated blood lead levels (BLL) confirmed the diagnosis. The lead poisoning is a public health problem especially in children, but its manifestation by a lead colic is rare and could simulate an acute abdomen table.The Pan African Medical Journal 2016;24

International audience; X-linked agammagobulinemia (XLA) is a primary immunodeficiency caused by Bruton's tyrosine kinase (BTK) gene defect. XLA patients have absent or reduced number of peripheral B cells and a profound deficiency in all immunoglobulin isotypes. This multicenter study reports the clinical, immunological and molecular features of Bruton's disease in 40 North African male patients. Fifty male out of 63 (male and female) patients diagnosed with serum agammaglobulinemia and non detectable to less than 2 % peripheral B cells were enrolled. The search for BTK gene mutations was performed for all of them by genomic DNA amplification and Sanger sequencing. We identified 33 different mutations in the BTK gene in 40 patients including 12 missense mutations, 6 nonsense mutations, 6 splice-site mutations, 5 frameshift, 2 large deletions, one complex mutation and one in-frame deletion. Seventeen of these mutations are novel. This large series shows a lower frequency of XLA among male patients from North Africa with agammaglobulinemia and absent to low B cells compared with other international studies (63.5 % vs 85 %). No strong evidence for genotype-phenotype correlation was observed. This study adds to other reports from highly consanguineous North African populations, showing lower frequency of X-linked forms as compared to AR forms of the same primary immunodeficiency. Furthermore, a large number of novel BTK mutations were identified and could further help identify carriers for genetic counseling.

Botulism is a rare but serious disease; it affects both the peripheral nervous system, causing diffuse paralysis, and the autonomous nervous system, inducing vegetative disturbances which worsen the vital prognosis. In Morocco, botulism is exceptional, except some sporadic cases. The authors present a series of food-born botulism in 5 infants, out of 45 cases of strong suspicion of botulism during an epidemic in Morocco in August 1999. They analyze epidemiological, clinical, neurophysiological, toxicological and evolutionary aspects. Within the 15 cases included in the protocol, 5 were infants, aged 3 to 12 years. The clinical presentation was complete and severe in 1 case (peripheral motor deficit in 4 limbs, vegetative disturbances), complete and of mild severity in 3, and benign in the last case. Electrophysiological investigation found a constant incrementation at high frequency. Botulinum neurotoxin was found in 3 cases. Evolution was favourable in 3 cases, with total recovery; but severe in the others, with motor sequelae in 1 case and 1 death in the other. This work underlines the severity of botulism, the limits of serology, which constitutes currently the only available tool for confirmation, but it is negative in half of all cases. They also point out the diagnostic value of neurophysiology, especially high frequency incrementation, which may be a diagnostic alternative, especially in cases of negative serology.

Chylothorax is a rare disease (1-2 % of pleural effusions), with a prevalence between 1/8600 and 1/15,000 births. It is characterized by the presence of chyle in the pleural cavity. Three categories of chylothorax are known: congenital chylothorax, which can be either idiopathic or the result of a malformation, and traumatic chylothorax (mostly postoperative). We report the observation of a 9-month-old infant with idiopathic chylothorax revealed by respiratory symptoms, with pleural effusion and collapse of the ipsilateral lung on chest X-ray and ultrasound examination. Cytology and chemical analysis of the pleural fluid showed an exudative liquid with a chylous aspect, a high concentration of albumin (52 g/dL), triglycerides (11.42 g/L), and a high number of cells (6600 cells/mL), with lymphocyte predominance (96 %). The culture was sterile. Chylothorax is usually revealed by dyspnea, but also by nausea, vomiting, anorexia and/or malnutrition. The diagnosis is suspected when milky white fluid is obtained from thoracocentesis and is confirmed by the presence of a triglyceride level greater than 1.2 mmol/L and more than 1000 cells/mL, with lymphocyte predominance. The treatment of chylothorax can be either conservative or surgical. Conservative treatment (medical) has four goals: ensure pleural emptiness, decrease production of chyle, restore and/or maintain proper nutritional status, and treatment of the cause when identified. Surgical intervention is indicated when conservative management fails and aims to stop a radical and permanent leakage of chyle.

Primary immunodeficiencies (PIDs) are a large group of diseases characterized by susceptibility to infections. We provide the first comprehensive report on PIDs in Morocco, the epidemiological, clinical, etiological and outcome features which have never before been described. A national registry was established in 2008, grouping together data for PID patients diagnosed since 1998. In total, 421 patients were diagnosed between 1998 and 2012. Parental consanguinity was common (recorded for 43.2 % of patients) and the median time to diagnosis was 2.0 years. Overall, 27.4 % of patients were considered to have well defined syndromes with immunodeficiency (48 cases of hyper-IgE syndrome and 40 of ataxia-telangiectasia); 22.7 % had predominantly antibody deficiencies (29 cases of agammaglobulinemia and 24 of CVID); 20.6 % had combined immunodeficiencies (37 cases of SCID and 26 of MHC II deficiencies) and 17.5 % had phagocyte disorders (14 cases of SCN and 10 of CGD). The principal clinical signs were lower respiratory tract infections (60.8 %), skin infections (33.5 %) and candidiasis (26.1 %). Mortality reached 28.8 %, and only ten patients underwent bone marrow transplantation. We analyzed the impact on mortality of residence, family history, parental consanguinity, date of diagnosis and time to diagnosis, but only date of diagnosis had a significant effect. The observed prevalence of PID was 0.81/100,000 inhabitants, suggesting considerable underdiagnosis and a need to increase awareness of these conditions in Morocco. The distribution of PIDs was different from that reported in Western countries, with a particularly high proportion of SCID, MHC II deficiencies, hyper-IgE syndrome and autosomal recessive agammaglobulinemia. However, we have now organized a national network, which should improve diagnosis rates in remote regions.

A 12-year-old daughter of consanguineous Moroccan parents was diagnosed with cyclic neutropenia, based on a combination of recurrent gingivostomatitis, a fluctuating neutrophil count, and several episodes of severe neutropenia. No ELA2 gene mutations were found. At age 19 years she presented with edema of the limbs, proteinuria and renal failure. Renal amyloidosis AA was diagnosed by biopsy. Gene mutations associated with family Mediterranean fever (FMF) were sought, and a homozygous mutation (M694V) was found in the MFEV gene. This is the novel finding of FMF that masqueraded as cyclic neutropenia.

Chronic granulomatous disease (CGD) is characterized by an inability of phagocytes to produce reactive oxygen species (ROS), which are required to kill some microorganisms. CGD patients are known to suffer from recurrent bacterial and/or fungal infections from the first year of life onwards. From 2009 to 2013, 12 cases of CGD were diagnosed in Morocco. We describe here these Moroccan cases of CGD.We investigated the genetic, immunological and clinical features of 12 Moroccan patients with CGD from 10 unrelated kindreds.All patients were children suffering from recurrent bacterial and/or fungal infections. All cases displayed impaired NADPH oxidase activity in nitroblue tetrazolium (NBT), dihydrorhodamine (DHR) or 2',7' dichlorofluorescein diacetate (DCFH-DA) assays. Mutation analysis revealed the presence of four different mutations of CYBB in four kindreds, a recurrent mutation of NCF1 in three kindreds, and a new mutation of NCF2 in three patients from a single kindred. A large deletion of CYBB gene has detected in a patient. The causal mutation in the remaining one kindred was not identified.The clinical features and infectious agents found in these patients were similar to those in CGD patients from elsewhere. The results of mutation analysis differed between kindreds, revealing a high level of genetic and allelic heterogeneity among Moroccan CGD patients. The small number of patients in our cohort probably reflects a lack of awareness of physicians. Further studies on a large cohort are required to determine the incidence and prevalence of the disease, and to improve the description of the genetic and clinical features of CGD patients in Morocco.

IL-12 receptor β1 deficiency (IL-12Rβ1) predisposes patients to mycobacteria and Salmonella infections. We report a case of IL-12Rβ1 deficiency with a fatal multi-resistant Salmonella enteritidis infection. This boy was born after from a consanguineous marriage, and diagnosed as having a IL-12Rβ1 deficiency since the age of 3 months. He presented with recurrent Salmonella enteritidis essentially digestive localization, complicated by purulent pericarditis at the same germ at the age of two and a half years. At the age of 3, a colonic infiltration due to a Salmonella enteritidis resistant to antibiotics, was complicated by acute intussusception, and the child died. The IL-12Rβ1 deficiency is considered as having a good prognosis, in contrast to what happened in our patient. We review therapeutic issues in these patients.

Streptococcus intermedius is a member of the Streptococcus anginosus group, also known as the Streptococcus milleri group. Although this is a commensal agent of the mouth and upper airways, it has been recognized as an important pathogen in the formation of abscesses. However, it has rarely been involved in the formation of brain abscess in children. We report 4 pediatric cases of brain abscess caused by S. intermedius. Three boys and 1 girl, all aged over 2 years, were admitted for a febrile meningeal syndrome and seizures, caused by a S. intermedius brain abscess. Diagnosis was obtained by brain imaging combined with culture of cerebrospinal fluid. The outcome was favorable after antibiotic therapy and abscess puncture. S. intermedius should be considered a potential pathogen involved in the development of brain abscess in children.

An increased incidence and severity of invasive group A streptococcus (GAS) infections over the past decade have been reported by several authors, but GAS remains an uncommon cause of bacterial meningitis. The aim of this study was to describe and analyze the clinical and biological data of GAS meningitis by reporting 10 new cases of pediatric GAS meningitis and making a literature review. The mean age of patients, seven girls and three boys, was 3 years. There was a history of preexisting or concomitant community-acquired infection in five patients over 10. The outcome was fatal in two cases. All patients received an initial empirical antimicrobial therapy with a third generation cephalosporin switched in six cases to amoxicillin. The prognosis for this type of streptococcal meningitis is usually good, but death may occur even in children without any identified risk factor for severe infection.

Chylothorax is a rare disease (1-2 % of pleural effusions), with a prevalence between 1/8600 and 1/15,000 births. It is characterized by the presence of chyle in the pleural cavity. Three categories of chylothorax are known: congenital chylothorax, which can be either idiopathic or the result of a malformation, and traumatic chylothorax (mostly postoperative). We report the observation of a 9-month-old infant with idiopathic chylothorax revealed by respiratory symptoms, with pleural effusion and collapse of the ipsilateral lung on chest X-ray and ultrasound examination. Cytology and chemical analysis of the pleural fluid showed an exudative liquid with a chylous aspect, a high concentration of albumin (52 g/dL), triglycerides (11.42 g/L), and a high number of cells (6600 cells/mL), with lymphocyte predominance (96 %). The culture was sterile. Chylothorax is usually revealed by dyspnea, but also by nausea, vomiting, anorexia and/or malnutrition. The diagnosis is suspected when milky white fluid is obtained from thoracocentesis and is confirmed by the presence of a triglyceride level greater than 1.2 mmol/L and more than 1000 cells/mL, with lymphocyte predominance. The treatment of chylothorax can be either conservative or surgical. Conservative treatment (medical) has four goals: ensure pleural emptiness, decrease production of chyle, restore and/or maintain proper nutritional status, and treatment of the cause when identified. Surgical intervention is indicated when conservative management fails and aims to stop a radical and permanent leakage of chyle.

WOS: 000289458800016, PubMed ID: 21533230, Background and Objectives: In the last decade, autosomal recessive IL-12R beta 11 deficiency has been diagnosed in four children with severe tuberculosis from three unrelated families from Morocco, Spain, and Turkey, providing proof-of-principle that tuberculosis in otherwise healthy children may result from single-gene inborn errors of immunity. We aimed to estimate the fraction of children developing severe tuberculosis due to IL-12R beta 1 deficiency in areas endemic for tuberculosis and where parental consanguinity is common. Methods and Principal Findings: We searched for IL12RB1 mutations in a series of 50 children from Iran, Morocco, and Turkey. All children had established severe pulmonary and/or disseminated tuberculosis requiring hospitalization and were otherwise normally resistant to weakly virulent BCG vaccines and environmental mycobacteria. In one child from Iran and another from Morocco, homozygosity for loss-of-function IL12RB1 alleles was documented, resulting in complete IL-12R beta 1 deficiency. Despite the small sample studied, our findings suggest that IL-12R beta 1 deficiency is not a very rare cause of pediatric tuberculosis in these countries, where it should be considered in selected children with severe disease. Significance: This finding may have important medical implications, as recombinant IFN-gamma is an effective treatment for mycobacterial infections in IL-12R beta 1-deficient patients. It also provides additional support for the view that severe tuberculosis in childhood may result from a collection of single-gene inborn errors of immunity., Schlumberger Foundation; BNP-Paribas Foundation; Foundation for Medical Research (FRM)Fondation pour la Recherche Medicale; Institut Universitaire de France; French National Agency for Research (ANR)French National Research Agency (ANR); EUEuropean Union (EU) [HEALTH-F3-2008-200732]; Bill and Melinda Gates FoundationGates Foundation; St. Giles Foundation; Jeffrey Modell Foundation; Talecris Biotherapeutics; Rockefeller University Center for Clinical and Translational Science [5UL1RR024143]; Rockefeller University; National Institute of Allergy and Infectious DiseasesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Allergy & Infectious Diseases (NIAID) [1U01AI088685], The Laboratory of Human Genetics of Infectious Diseases is supported in part by grants from the Schlumberger Foundation, the BNP-Paribas Foundation, The Foundation for Medical Research (FRM), the "Institut Universitaire de France," the French National Agency for Research (ANR), the EU-grant HOMITB (HEALTH-F3-2008-200732), the Bill and Melinda Gates Foundation, the St. Giles Foundation, the Jeffrey Modell Foundation and Talecris Biotherapeutics, the Rockefeller University Center for Clinical and Translational Science grant number 5UL1RR024143, the Rockefeller University, and the National Institute of Allergy and Infectious Diseases grant number 1U01AI088685. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding received for this study.

Major histocompatibility complex class II plays a key role in the immune response, by presenting processed antigens to CD4+ lymphocytes. Major histocompatibility complex class II expression is controlled at the transcriptional level by at least four trans-acting genes: CIITA, RFXANK, RFX5 and RFXAP. Defects in these regulatory genes cause MHC class II immunodeficiency, which is frequent in North Africa. The aim of this study was to describe the immunological and molecular characteristics of ten unrelated Moroccan patients with MHC class II deficiency. Immunological examinations revealed a lack of expression of MHC class II molecules at the surface of peripheral blood mononuclear cells, low CD4+ T lymphocyte counts and variable serum immunoglobulin (IgG, IgM and IgA) levels. In addition, no MHC class II (HLA DR) expression was observed on lymphoblasts. The molecular analysis identified the same homozygous 752delG26 mutation in the RFXANK genes of all patients. This finding confirms the association between the high frequency of the combined immunodeficiency and the defect in MHC class II expression and provides strong evidence for a founder effect of the 752delG26 mutation in the North African population. These findings should facilitate the establishment of molecular diagnosis and improve genetic counselling for affected Moroccan families.

La survenue d'un cas de meningite purulente dans une collectivite seme une panique de plus en plus importante, car la meningite purulente reste une pathologie grave mettant en jeu le pronostic vital et pouvant engendrer des sequelles neurosensorielles redoutables. Cela justifie une strategie de prevention qui associe la vaccination et l'antibioprophylaxie. Cette derniere tente de prescrire un traitement antibiotique avant qu'une infection se declare chez un sujet qui se trouve dans une situation pathologique l'exposant a un risque infectieux grave. Le sujet « contactest une personne ayant eu chaque jour plus de 4 heures de contact avec le cas index, et cela durant la semaine ayant precede la maladie du cas index.

Botulism is a rare but serious disease; it affects both the peripheral nervous system, causing diffuse paralysis, and the autonomous nervous system, inducing vegetative disturbances which worsen the vital prognosis. In Morocco, botulism is exceptional, except some sporadic cases. The authors present a series of food-born botulism in 5 infants, out of 45 cases of strong suspicion of botulism during an epidemic in Morocco in August 1999. They analyze epidemiological, clinical, neurophysiological, toxicological and evolutionary aspects. Within the 15 cases included in the protocol, 5 were infants, aged 3 to 12 years. The clinical presentation was complete and severe in 1 case (peripheral motor deficit in 4 limbs, vegetative disturbances), complete and of mild severity in 3, and benign in the last case. Electrophysiological investigation found a constant incrementation at high frequency. Botulinum neurotoxin was found in 3 cases. Evolution was favourable in 3 cases, with total recovery; but severe in the others, with motor sequelae in 1 case and 1 death in the other. This work underlines the severity of botulism, the limits of serology, which constitutes currently the only available tool for confirmation, but it is negative in half of all cases. They also point out the diagnostic value of neurophysiology, especially high frequency incrementation, which may be a diagnostic alternative, especially in cases of negative serology.