Kawarabi: Administrative Structuring of a Multicenter Research Collaborative to Study Kawasaki Disease in the Arab Countries.

Kawasaki disease (KD), the leading cause of acquired heart disease in children in developed countries, merits conducting detailed studies in Arab countries. We introduce Kawarabi, as a multicenter research collaborative effort dedicated to improving diagnosis, care, and outcome of children and adults with KD in the Arab world. During the COVID-19 pandemic, there emerged a new multisystem inflammatory syndrome in children; a disease similar to KD. This highlighted the challenges that Arab physicians face in diagnosing and managing children with KD and KD-like illnesses. Kawarabi brings together experts in North America and Arab nations to study this family of diseases in a not-for-profit, voluntary scientific collaborative setting. Bylaws addressing the vision, objectives, structure, and governance of Kawarabi were established, and vetted by the 45 organizing members in 2021. An initial scientific publication showed evidence of a decreased level of awareness of the disease in the general population, as well as the lack of access to resources available for physicians caring for children with KD in Arab countries. Kawarabi has since held several educational webinars and an inaugural yearly meeting. The groundwork for future initiatives targeted at increasing awareness and understanding of the management and the long-term outcomes of children with KD in the region was established. Data on KD in the Arab world are lacking. Kawarabi is a multicenter research collaborative organization that has the unique resources, diversified ethnic makeup, and energy, to accomplish significant advances in our understanding and management of KD and its variants.

Access to Care and Therapy for Kawasaki Disease in the Arab Countries: A Kawasaki Disease Arab Initiative (Kawarabi) Multicenter Survey.

Kawasaki Disease (KD) is still the most common acquired heart disease in children below the age of five years; it has been well described in the developed world; however, data from the Arab world are limited to case reports or single-center case series. In an effort of optimizing KD research in the Arab world, a group of physicians and researchers established the KD Arab Initiative (Kawarabi) in 2021, and published the first survey, which showed disparities in the availability of intravenous immunoglobulin (IVIG); this had prompted Kawarabi to assess the access to care and therapy of KD patients in Arab countries. A 32 structured questions survey was conducted in thirteen Arab countries and addressed KD patients' access to healthcare in urban and rural settings. The survey results showed that access to care was uniform across large, mid-size cities and rural areas in 7/13 (54%) countries, while in 6/13 (46%) countries, it was in favor of large and mid-size cities over rural areas. The quality of medical services received by children with KD in large cities was rated as excellent in 6/13 or good in 7/13 countries compared to fair in 4/13 or poor in 4/13 countries in rural areas. Availability of IVIG was limited (23%) in mid-size cities and almost impossible (23%) in rural areas. The KD patients in mid-size cities and rural areas have limited access to standard healthcare in the Arab world. This survey laid the foundation for future Kawarabi endeavors to improve the care of children with KD.

Kawasaki Disease Arab Initiative [Kawarabi]: Establishment and Results of a Multicenter Survey.

Studies on Kawasaki disease (KD) in Arab countries are scarce, often providing incomplete data. This along with the benefits of multicenter research collaboratives led to the creation of the KD Arab Initiative [Kawarabi] consortium. An anonymous survey was completed among potential collaborative Arab medical institutions to assess burden of KD in those countries and resources available to physicians. An online 32-item survey was distributed to participating institutions after conducting face validity. One survey per institution was collected. Nineteen physicians from 12 countries completed the survey representing 19 out of 20 institutions (response rate of 95%). Fifteen (79%) institutions referred to the 2017 American Heart Association guidelines when managing a patient with KD. Intravenous immunoglobulin (IVIG) is not readily available at 2 institutions (11%) yet available in the country. In one center (5%), IVIG is imported on-demand. The knowledge and awareness among countries' general population was graded (0 to 10) at median/interquartiles (IQR) 3 (2-5) and at median/IQR 7 (6-8) in the medical community outside their institution. Practice variations in KD management and treatment across Arab countries require solid proactive collaboration. The low awareness and knowledge estimates about KD among the general population contrasted with a high level among the medical community. The Kawarabi collaborative will offer a platform to assess disease burden of KD, among Arab population, decrease practice variation and foster population-based knowledge.

Characteristics and etiologies of short stature in children: Experience of an endocrine clinic in a Tunisian tertiary care hospital.

BACKGROUND: Short stature is a common reason for referral to pediatric endocrinology clinics. It may be a manifestation of a pathological condition requiring early treatment. The aim of this study was to describe the characteristics and etiologies of short stature among children referred to the pediatric endocrinology clinic of the main pediatric tertiary care center in Tunisia. METHODS: Retrospective and descriptive study in the endocrinology unit of children referred for short stature between January 2012 and December 2016. Data on the patients' medical history, physical findings, laboratory tests, bone age and chromosomal analysis were collected. RESULTS: 470 children (266 males and 204 females) were referred during that period. 214 (45.5%) had normal height, and 80.8% of them were referred by general practitioners. The other 256 children (54.5%) had a confirmed short stature (mean age :7.2 years, mean height: -2.77 SDS). Endocrinological causes were the most common(43% GHD, 4% hypothyroidism) followed by intrauterine growth retardation IUGR (24%), genetic syndromes (8.4%), chronic pediatric diseases (7.8%), skeletal dysplasia (6.2%), normal variant of short stature (5%), and psychosocial deprivation (1.2%). Among non-endocrine causes, Turner syndrome was the most common genetic syndrome (4.4%), achondroplasia the main skeletal dysplasia (4%) and celiac disease the main chronic disease (3.4%). CONCLUSIONS: ST is largely overestimated in our country. Therefore, it is important to insist on adequate measurement and analysis of growth parameters to avoid unnecessary investigations. GHD and IUGR were the most common causes. Celiac disease, though frequent in Tunisia, is not a common cause of short stature.

Congenital hypothyroidism presenting with reversible renal impairment: an under-recognised problem?

BACKGROUND: Hypothyroidism with impairment of renal function and raised creatinine phosphokinase (CPK) is described in adults and children with acquired hypothyroidism, but not in congenital hypothyroidism. CASE PRESENTATION: A male infant born at term weighing 3390 g was seen aged 2 months with prolonged jaundice. Examination showed somnolence, umbilical hernia, enlarged fontanelles and lower limb edema; length 55 cm (-1.5 SD), weight 5.4 kg (-0.13 SD). Biochemistry showed fT4 < 1 pmol/L, TSH = 1044.36 µUI/mL, creatinine 77 µmol/L(normal <35 µmol/L), estimated glomerular filtration rate (GFR) 26 ml/min/1.73 m2, CPK 3952.5 IU/L (normal<400 IU/L). Ultrasound showed no thyroid tissue in the neck. In view of the renal impairment, peritoneal dialysis was initially contemplated but postponed and the child received levothyroxine 10 µg/kg/day. Two months later thyroid function tests, CPK and renal function had all normalized with creatinine 19 µmol/L and GFR 116 ml/min/1.73m2. DISCUSSION: Reversible renal impairment is attributable to severe congenital hypothyroidism causing decreased myocardial contractility and cardiac output and to a direct effect on the kidneys. Thyroid function should be checked in infants with renal impairment of unknown cause. Cautious fluid management is indicated in hypothyroid infants. Hypothyroidism may also be associated with elevated serum CPK levels but resolves with thyroxin therapy.

Influenza A/H1N1 pdm 09 in children's Hospital Bechir Hamza of Tunis.

BACKGROUND: Influenza A (H1N1) is a contagious acute respiratory infection caused a pandemic in 2009. The outcome was variable among populations. AIM: To describe a clinical spectrum and the outcome of Tunisian children with pandemic H1N1/09 influenza virus. METHODS: This is a retrospective, descriptive study of children with pandemic H1N1/09 influenza virus hospitalized in the children's hospital of tunis, between November 2009 and February 2010. The diagnosis was made on positive rapid test or PCR. RESULTS: thirty two children were included. The median age was 12 months. The most frequently symptoms were: fever (87,5%), digestive disorders ( 59,4%) and dyspnea (15,6%). The mean length of stay was 3,8 days. The outcome was complicated by a bacterial infection (56,3%), and one death. CONCLUSION: Mild form of H1N1/influenza virus is the most common presentation; however severe forms can be observed especially in infants.

A Founder Effect of c.257 + 2T > C Mutation in NCF2 Gene Underlies Severe Chronic Granulomatous Disease in Eleven Patients.

Chronic granulomatous disease (CGD) is the prototypic functional neutrophil disorder caused by genetic defects in one of the five genes encoding the superoxide-generating nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase subunits of phagocytes. Mutations causing the most prevalent form of CGD in western populations are located in the X-linked-CYBB gene. The four remaining autosomal recessive (AR) forms collectively account for one-third of CGD cases. We investigated the clinical and molecular features of eleven patients with CGD from 6 consanguineous families, originating from contiguous regions in the west of Tunisia. The patients' clinical phenotype is characterized by a high incidence of mycobacterial infections. Five out of the eleven patients died despite treatment arguing in favor of a severe clinical form of CGD. These findings correlated with the absence of functional p67phox protein as well as the absence of residual reactive oxygen intermediates (ROI) production. Genetic analysis showed the presence, in all patients, of a unique mutation (c.257 + 2T > C) in NCF2 gene predicted to affect RNA splicing. Segregating analysis using nine polymorphic markers overlapping the NCF2 gene revealed a common haplotype spanning 4.1 Mb. The founder event responsible for this mutation was estimated to have arisen approximately 175 years ago. These findings will facilitate the implementation of preventive approaches through genetic counseling in affected consanguineous families.

δ0-Thalassemia in cis of ßKnossos globin gene: first homozygous description in thalassemia intermedia Libyans and first combination with codon 39 (C→T) in thalassemia intermedia Tunisian patients.

BACKGROUND: ß-Thalassemia is the most common disease among hemoglobinopathies in North African and Arab populations. In the present study we report the first description of the ß-Knossos codon27 (G→T) (ßKnossos) allele in cis with the δ059 (-A) mutation in thalassemia intermedia patients in Tunisia and Libya. METHODS: This identification was carried out by sequencing analysis of the whole coding regions of the δ- and ß-globin genes. RESULTS: We noted that heterozygous inheritance of the ßKnossos mutation results in a mild ß-thalassemia phenotype with a low level of HbA2 while homozygous leads to intermediate ß-thalassemia with an atypical high performance liquid chromatogram showing a complete absence of HbA2 and HbF. Compound heterozygosity of the ßKnossos with ß0 codon39 (C→T) is identified in a Tunisian proband for the first time and gives rise to a mild phenotype. In both families, the δ0 codon59 (-A) and the ßKnossos alleles were found to be associated with a single Mediterranean ß-haplotype I similar to that observed in previous reports from Algeria, Egypt, Cyprus, and Turkey. CONCLUSIONS: The chromosome supporting the ßKnossos and the δ0 codon59 (-A) alleles seems to be of a single Mediterranean origin. Premarital screening studies in families in which only one of the parents has typical aspects of ß-thalassemia trait and the other has a normal HbA2 level associated with abnormal red cell indices becomes a necessity to avoid missing thalassemia carriers.

Datura stramonium L. poisoning in a geophagous child: a case report.

Datura stramonium L. (DS) is a wild-growing plant widely distributed and easily accessible. It contains a variety of toxic anticholinergic alkaloids such as atropine, hyoscamine, and scopolamine. Voluntary or accidental ingestion can produce severe anticholinergic poisoning. We report an unusual case of DS intoxication occurring in a geophagous young child after accidental ingestion of the plant. Our case is original because of the young age of the victim and the underlying geophagia facilitating the occurrence of poisoning.

Abdominal tuberculosis in children.

BACKGROUND: Abdominal tuberculosis (TB) includes infection of the gastrointestinal tract, peritoneum, mesentery, abdominal lymph nodes, liver, spleen, and pancreas. The most common forms of abdominal TB in children are adhesive peritonitis and nodal disease. PATIENTS AND METHODS: We report our experience with abdominal TB treated in our hospital from 1995 to 2008. RESULTS: Thirteen patients (3 boys and 10 girls) of mean age 9.8 years were diagnosed as having abdominal TB. Eight patients presented with abdominal distension and abdominal pain. Fever was seen in 4 patients. One patient had surgical abdominal pain and 2 had abdominal mass. Two patients had coexisting pleural effusion and 1 of them had multifocal TB. Abdominal TB involved peritoneum in 9, abdominal lymph nodes in 7, gastrointestinal tract in 3, spleen in 2 patients, and liver in 1. Ascitic fluid analysis of 9 patients showed exudative fluid with predominately lymphocytes. Laparotomy was performed in 3 patients. The diagnosis of abdominal TB was confirmed histopathologically in 5 patients and microbiologically in 3. The remaining patients had been diagnosed by ascitic fluid diagnostic features, abdominal imaging, tuberculin skin test, history of exposure, and a positive response to antituberculous treatment. Twelve patients completed the antituberculous therapy without any complications. One patient with multifocal TB had neurological sequelae. CONCLUSIONS: In the areas with a high prevalence of tuberculosis and confirmatory investigations are inadequately available, treatment may be initiated, based on strong clinical diagnosis and supportive investigations. In such situations, it is the response to therapy that indirectly proves the diagnosis.

Central system nervous tuberculosis in infants.

The lack of specific symptoms and signs in patients with tuberculous meningitis makes early diagnosis difficult. In this report, we reviewed the clinical features and laboratory findings of 6 infants with central system nervous tuberculosis during a 10-year period. One of the patients had multifocal tuberculosis. The mean time to the diagnosis was 32 +/- 13.4 days. A contact source was identified in only 2 patients. All 6 patients had abnormal cerebrospinal fluid findings, less than 500 cells/microL with lymphocytic predominance. Computerized tomography (CT) and/or magnetic resonance imaging (MRI) revealed hydrocephalus with basal enhancement in 2 patients. One patient developed pontocerebellar and pituitary tuberculomas, which were responsible for compression and diabetes insipidus, 1 year after antituberculous treatment. These localizations are very rare. On the follow-up, 3 patients had hypoacousia and only 1 had severe sequelae, despite a diagnostic delay.

Extra-pulmonary tuberculosis in children: a study of 41 cases.

BACKGROUND: Extrapulmonary tuberculosis accounts for up to one third of all cases of tuberculosis and children show a higher predisposition to the development of extra-pulmonary tuberculosis. AIM: To review the clinical features of the extrapulmonary tuberculosis in children. METHODS: forty one children with extrapulmonary tuberculosis followed in the Children Hospital of Tunis between January 1995 and December 2007 were reviewed. RESULTS: Extrapulmonary tuberculosis constitutes 57.9% of all cases of tuberculosis. Male to female ratio was 0.7 and the mean age was 7.5 years. The most commonly involved sites were the peripheral lymphadenitis (14 cases) followed by abdominal (11 cases), central nervous system (7 cases), osteoarticular (5 cases) and multifocal (4 cases). A positive family history of active tuberculosis was detected in 22.5% of the cases. Diagnosis delay was 4.7 months. Sequelae observed during the follow up were: neurosensory in 5 cases, and vertebral deformation in 1 case. CONCLUSION: extrapulmonary tuberculosis represents an important fraction of tuberculosis in our study. The most common form is lymph nodes localization followed by abdominal and central system nervous forms. Neurosensory sequelae were frequent in central system nervous tuberculosis.

[Chronic granulomatous disease in childhood]. / La maladie granulomateuse chronique de l'enfant.

Chronic granulomatous disease (GCD) of childhood is a rare inherited immunodeficiency. It is characterized clinically by the occurrence of severe and recurrent uncontrollable infections, which often lead to death in early childhood. The underlying biologic anomaly is a defective microbicidal capacity of phagocytosis with abnormal oxidative response during phagocytosis. Histologically, the GCD is characterized by a spectrum of histopathological features in a wide range of tissue specimens, often demonstrating features of active chronic inflammation, with or without non-caseating granuloma formation. The presence of numerous pigmented macrophages in association with such an inflammation should raise suspicion of the diagnosis. We report a case of a GCD in an 11-year-old boy and study the anatomoclinic features of this rare entity.

Etiology and outcome of bronchiectasis in children: a study of 41 patients.

BACKGROUND: Bronchiectasis remains an important cause of chronic suppurative lung disease in the developing world. The aim of this study is to describe the epidemiological characteristics, clinical features, underlying aetiologies and outcome of bronchiectasis in the paediatric hospital of Tunis. METHODS: A retrospective study of 41 children with bronchiectasis was conducted between January 1994 and December 2006. Diagnosis was made in patients with clinical suspicion of bronchiectasis associated with abnormalities on chest X ray (n=37) and/or on high resolution computed tomography (HRCT) (n=36). RESULTS: Mean age at diagnosis was 5 years 9 months; (range: 6 months-14 years). Persistent cough and bronchorrhea were the most common symptoms. Fourteen patients (34%) had dyspnoea on first presentation, 11 of them (26.8%) had chest deformation and/or finger clubbing. Haemoptysis was noted in only two cases. Mean time to diagnosis from symptom onset was 2.7 years (range: 2 months-4 years). The underlying aetiologies were identified in 52% of patients. Cystic fibrosis (17%), previous pneumonic illness (9.7%), primary ciliary dyskinesia (9.7%) and immunodeficiency (9.7%) were the most common causes. After a mean follow-up of 6.6 years, the annual lower respiratory infection rate decreased from 7.2 +/- 3 to 3.1 +/- 2.6 (p<0.05), Twenty one point nine per cent of patients had chronic respiratory failure and five patients required surgery. CONCLUSIONS: Delays diagnosis of bronchiectasis remains important in our country. Congenital and indeterminate aetiologies are the most common forms. Prognosis is poor with a high prevalence of chronic respiratory failure.

[Epidemiologic profile and management pediatric medical emergencie's consultants of Tunisian child's hospital]. / Profil epidemiologique et prise en charge des consultants des urgences medicales pediatriques de l'hopital d'enfants de Tunis.

BACKGROUND: the pediatric medical emergencie's of Tunisian child's hospital service manages all children fifteen years old. It receives 45,000 children in year in average. THE AIMS: Establish an epidemiologic profile of consultants and study the encountred morbidity. METHODS: We made a transversal describing study of the pediatric emergencie's activity during three successive months in 2004 (February, March, April). We described the characteristics of the population consulting this service, study the severity and immediate behaviours in emergencies. RESULTS: The number of all consultants is 10,560 children during these three months. 54.9% of cases are between one month old and two years old, 54.7% of them are boys. The recruitment mode is direct in 92.9% of cases. The maximum of consultants is in the week-ends with an average of 129 patients per day. In the other days of the week, the average number is 115 +/- 27 patients per day ant the extrems are 75 and 225 patients per day. In the morning, a third of the daily activity is made. the morbidity is dominated by the pulmonary pathologies in 39.9% of cases otorhinolarygologic affections in 31.8% of cases gastroenterologic pathologies in 6.72% of cases and brain system's pathology in 3.43% of cases. The neonatal affection represents 2.74% of total consultants. At the end of the consultations, 38.7% of patients go back home with medical prescriptions. 45.6% of them receive nebulisations and 21.3% are hospitalized. The bulk is the first dysfunction of the emergencies service. The second dysfunction is the inappropriate use of this service which works like a first structure. Some affections such as febrile seizures, pyelonephritis are excessively hospitalized in 97.5% and 100% respectively. CONCLUSION: The dysfunction of pediatric medical emergencies's service can be improved by sanitary education of the parents about the role of emergencie's service and the formation of the doctors in the management of patients suffering from usual emergencies.

[Hyperlipidaemia associated to inaugurated diabetic ketoacidosis]. / Hyperlipemie associee a une acidocetose diabetique inaugurale.

Severe hyperlipidaemia in presenting diabetic ketoacidosis was rarely reported in child. We report the case of a three-year-old girl with presenting diabetic ketoacidosis. Family history was negative for hyperlipidaemia. Serum was creamy pink in gross appearance. The child has a hyperlipidaemia with serum triglycerides 18.5 mmol/l and serum cholesterol 13.8 mmol/l. The hyperlipidaemia disappeared with insulin therapy within seven days. We study the clinical, laboratory, pathogenic and evolution features of this uncommon trouble in diabetic children.

Childhood leishmaniasis: report of 106 cases.

In Tunisia there are three epidemic clinical forms of cutaneous leishmaniasis. They are associated with three different species of Leishmania and are observed in different geographical areas. We undertook a single-center retrospective analysis of childhood leishmaniasis in order to describe epidemio-clinical profile, therapeutic characteristics and clinical outcomes of affected patients. The study comprises 166 children with 132 lesions of cutaneous leishmaniasis. The subjects ages range from 5 months to 15 years (average 8.75 years). The F:M sex ratio is 1.3. Leishmaniasis affects grown-up children in 74.5 percent of the cases. All of our patients live in an endemic area. The face is affected in 76.5 percent of cases. Mucosal leishmaniasis is present in 9 children (6.8 %). Clinical diagnosis confirmed by the parasitologic smear or histopathological examination in 89.6 percent of the cases. Treatment with intralesional meglumine antimoniate is done for 67 patients; the treatment regimen is one local injection (1 ml/cm(2)) per week until recovery. Systemic meglumine antimoniate is the initial therapy for 25 patients. Meglumine antimoniate treatment is well tolerated with no side-effects. All leishmaniasis lesions heal within an average period of 2.18 months. Childhood cutaneous leishmaniais is common in Tunisia. It has the characteristics of sporadic leishmaniasis. Mucosal leishmaniasis has a favorable outcome with no destruction, nor scaring deformity. The standard treatment remains intralesional meglumine antimoniate.

The rapid effects of 1,25-dihydroxyvitamin D3 require the vitamin D receptor and influence 24-hydroxylase activity: studies in human skin fibroblasts bearing vitamin D receptor mutations.

If both rapid and genomic pathways may co-exist in the same cell, the involvement of the nuclear vitamin D receptor (VDR) in the rapid effects of 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) remains unclear. We therefore studied rapid and long term effects of 1,25-(OH)(2)D(3) in cultured skin fibroblasts from three patients with severe vitamin D-resistant rickets and one age-matched control. Patients bear homozygous missense VDR mutations that abolished either VDR binding to DNA (patient 1, mutation K45E) or its stable ligand binding (patients 2 and 3, mutation W286R). In patient 1 cells, 1,25-(OH)(2)D(3) (1 pm-10 nm) had no effect on either intracellular calcium or 24-hydroxylase (enzyme activity and mRNA expression). In contrast, cells bearing the W286R mutation had calcium responses to 1,25-(OH)(2)D(3) (profile and magnitude) and 24-hydroxylase responses to low (1 pm-100 pm) 1,25-(OH)(2)D(3) concentrations (activity, CYP24, and ferredoxin mRNAs) similar to those of controls. The blocker of Ca(2+) channels, verapamil, impeded both rapid (calcium) and long term (24-hydroxylase activity, CYP24, and ferredoxin mRNAs) responses in patient and control fibroblasts. The MEK 1/2 kinase inhibitor PD98059 also blocked the CYP24 mRNA response. Taken together, these results suggest that 1,25-(OH)(2)D(3) rapid effects require the presence of VDR and control, in part, the first step of 1,25-(OH)(2)D(3) catabolism via increased mRNA expression of the CYP24 and ferredoxin genes in the 24-hydroxylase complex.