Mohammad S. Ehlayel

Protective effect of breastfeeding on diarrhea among children in a rapidly growing newly developed society.

OBJECTIVE. Our goal was to estimate the impact of a Shigella vaccine in an area where shigellosis is endemic by characterizing the disease burden and antibiotic-resistance profiles of isolates and by determining the prevalence of Shigella flexneri serotypes. PATIENTS AND METHODS. We conducted a 43-month-long prospective, community-based diarrheal disease surveillance in 442 children <72 months of age in the Peruvian Amazon between October 1, 2002, and April 15, 2006. RESULTS. The incidence of diarrheal disease was 4.38 episodes per child-year. The incidence rate for shigellosis was 0.34 episodes per child-year in children <72 months of age and peaked in children between 12 and 23 months at 0.43 episodes per child-year. Maternal education at or beyond the primary grade level, piped water supply, weight-for-age z score, and improved water-storage practices were the most significant determinants of disease in this community with living conditions comparable to many rural areas in the developing world. CONCLUSIONS. Children living in this region had a 20-fold higher rate of disease incidence detected by active surveillance as those recently estimated by passive detection. Most symptomatic disease was caused by S flexneri, although the diversity of serotypes will require a multivalent vaccine to have a significant impact on the burden of disease caused by shigellosis. Several other public health disease-control interventions targeted at water source and improved storage, nutritional interventions, and improved maternal education seem to have a greater impact than a univalent S flexneri 2a vaccine.

Low Penetrance, Broad Resistance, and Favorable Outcome of Interleukin 12 Receptor β1 Deficiency Medical and Immunological Implications

The clinical phenotype of interleukin 12 receptor β1 chain (IL-12Rβ1) deficiency and the function of human IL-12 in host defense remain largely unknown, due to the small number of patients reported. We now report 41 patients with complete IL-12Rβ1 deficiency from 17 countries. The only opportunistic infections observed, in 34 patients, were of childhood onset and caused by weakly virulent Salmonella or Mycobacteria (Bacille Calmette-Guérin -BCG- and environmental Mycobacteria). Three patients had clinical tuberculosis, one of whom also had salmonellosis. Unlike salmonellosis, mycobacterial infections did not recur. BCG inoculation and BCG disease were both effective against subsequent environmental mycobacteriosis, but not against salmonellosis. Excluding the probands, seven of the 12 affected siblings have remained free of case-definition opportunistic infection. Finally, only five deaths occurred in childhood, and the remaining 36 patients are alive and well. Thus, a diagnosis of IL-12Rβ1 deficiency should be considered in children with opportunistic mycobacteriosis or salmonellosis; healthy siblings of probands and selected cases of tuberculosis should also be investigated. The overall prognosis is good due to broad resistance to infection and the low penetrance and favorable outcome of infections. Unexpectedly, human IL-12 is redundant in protective immunity against most microorganisms other than Mycobacteria and Salmonella. Moreover, IL-12 is redundant for primary immunity to Mycobacteria and Salmonella in many individuals and for secondary immunity to Mycobacteria but not to Salmonella in most.

Vitamin D Deficiency as a Strong Predictor of Asthma in Children

Background: Epidemiological studies suggest a link between vitamin D deficiency in early life and development of asthma in later life. Aim: The aim of this study was to measure serum vitamin D levels in asthmatic children and to compare these to healthy non-asthmatic controls. Methods: Asthmatic (n = 483) and healthy control (n = 483) children were recruited from the Pediatric Allergy-Immunology Clinics of Hamad General Hospital and the Primary Health Care Clinics in Qatar from October 2009 to July 2010. All children were below 16 years of age and asthma was diagnosed by a physician. Parents of all children completed extensive questionnaires documenting demographics, child’s feeding practice and vitamin D intake. Serum vitamin D (25-hydroxyvitamin D), calcium, phosphorus, alkaline phosphatase, magnesium, creatinine and parathyroid hormone assays were performed. Subjects with serum containing less than 20 ng/ml vitamin D were deemed deficient. Results: Asthmatic children had significantly reduced serum vitamin D levels compared to non-asthmatic children (p < 0.001); 68.1% of all asthmatics were vitamin D deficient. Asthmatic children had significantly higher degrees of moderate (41.8 vs. 25.1%) and severe (26.3 vs. 11.0%) vitamin D deficiency compared to healthy controls (p < 0.001). Positive familial history of vitamin D deficiency (35.6%, p = 0.005) and asthma (36.4%, p = 0.009) were significantly higher in asthmatic children. Along with vitamin D deficiency, asthmatics also had reduced phosphorus (p < 0.001) and magnesium (p = 0.001) levels but elevated serum alkaline phosphatase (p < 0.001) and IgE (p < 0.001). The majority of asthmatic children had less exposure to sunlight (66.7%, p = 0.006) and less physical activity (71.3%, p < 0.001). Vitamin D deficiency was the strongest predictor of asthma in this population (OR 4.82; 95% CI 2.41–8.63, p < 0.001). Conclusion: The present study revealed that the majority of asthmatic children had vitamin D deficiency compared to control children. Vitamin D deficiency was the major predictor of asthma in Qatari children.

Primary immunodeficiency diseases: Genomic approaches delineate heterogeneous Mendelian disorders

Background: Primary immunodeficiency diseases (PIDDs) are clinically and genetically heterogeneous disorders thus far associated with mutations in more than 300 genes. The clinical phenotypes derived from distinct genotypes can overlap. Genetic etiology can be a prognostic indicator of disease severity and can influence treatment decisions. Objective: We sought to investigate the ability of whole‐exome screening methods to detect disease‐causing variants in patients with PIDDs. Methods: Patients with PIDDs from 278 families from 22 countries were investigated by using whole‐exome sequencing. Computational copy number variant (CNV) prediction pipelines and an exome‐tiling chromosomal microarray were also applied to identify intragenic CNVs. Analytic approaches initially focused on 475 known or candidate PIDD genes but were nonexclusive and further tailored based on clinical data, family history, and immunophenotyping. Results: A likely molecular diagnosis was achieved in 110 (40%) unrelated probands. Clinical diagnosis was revised in about half (60/110) and management was directly altered in nearly a quarter (26/110) of families based on molecular findings. Twelve PIDD‐causing CNVs were detected, including 7 smaller than 30 Kb that would not have been detected with conventional diagnostic CNV arrays. Conclusion: This high‐throughput genomic approach enabled detection of disease‐related variants in unexpected genes; permitted detection of low‐grade constitutional, somatic, and revertant mosaicism; and provided evidence of a mutational burden in mixed PIDD immunophenotypes.

Camel milk: an alternative for cow's milk allergy in children.

Treatment of cows milk allergy (CMA) in children includes avoidance of cows milk and providing a milk substitute. This study was designed to determine whether CMA children could safely consume camels milk as an alternative, and skin-prick test (SPT) to camels milk could be a reliable tool in selecting them. Between April 2007 and February 2010, children with confirmed CMA seen at the Allergy-Immunology Clinic, Hamad Medical Corp., were enrolled into this prospective cohort study. Subjects had a detailed history and medical examination, complete blood count with differential count, total serum IgE, and specific IgE test and SPT to cows milk. Patients with positive SPT and an elevated cows milk-specific IgE had negative SPT to camels milk. Of 35 children (23 male and 12 female children) aged 4-126 months (median, 21 months), 23 patients (65.7%) presented with acute urticaria, 17 (48.6%) with atopic dermatitis, 9 (25.7%) with anaphylaxis, 8 (22.9%) with failure to thrive, and 5 (14.3%) with chronic vomiting. Twenty-eight patients (80%) had family history of allergy. Twenty-six patients (74.3%) were breast-fed for ≤18 months. Mean white blood cell count was 9860.5 cells/μL, absolute eosinophil count was 1219 cells/μL, IgE was 682 IU/mL, and cows milk-specific IgE was 22.01 kU/L. Only 7 patients (20%) had positive SPT to camels milk and 28 (80%) were negative to camels milk. All patients with negative SPT took camels milk without any reactions. In children with CMA, SPT is a reliable clinical test in ruling out reactivity to camels milk so these children could safely take camels milk as an alternative nutrient.

Is high prevalence of vitamin D deficiency a correlate for attention deficit hyperactivity disorder

The aim of the study was to determine the association between vitamin D and attention deficit hyperactivity disorder (ADHD), and difference in the level of vitamin D in ADHD children and control. This a case–control study carried out in school health and primary health care clinics. A total of 1,331 children and adolescents who were diagnosed with ADHD based on clinical criteria and standardized questionnaires were enrolled in this study and were matched with 1,331 controls, aged 5–18xa0years old. Data on body mass index (BMI), clinical biochemistry variables including serum 25-hydroxyvitamin D were collected. The study found significant association between ADHD and vitamin D deficiency after adjusting for BMI and sex (adj. OR 1.54; 95xa0% CI 1.32–1.81; Pxa0<xa00.001). Majority of the ADHD children were in the age group 5–10xa0years (40.7xa0%), followed by 11–13xa0years (38.4xa0%). The proportion of BMI <85th percentile was significantly over represented in ADHD group as compared to healthy control (87.8 vs. 83xa0%; Pxa0<xa00.001, respectively), while on the other hand, BMI >95th percentile was over represented in the control than ADHD group (7.6 vs. 4.6xa0%; Pxa0<xa00.001, respectively). Mean values of vitamin D (ng/mL) were significantly lower in ADHD children (16.6xa0±xa07.8) than in healthy children (23.5xa0±xa09.0) (Pxa0<xa00.001). There was significant correlation between vitamin D deficiency and age (rxa0=xa0−0.191, Pxa0=xa00.001); calcium (rxa0=xa00.272, Pxa0=xa00.001); phosphorous (rxa0=xa00.284, Pxa0=xa00.001); magnesium (rxa0=xa00.292, Pxa0=xa00.001); and BMI (rxa0=xa00.498, Pxa0=xa00.001) in ADHD children. The vitamin D deficiency was higher in ADHD children compared to healthy children.

The impact of Vitamin D deficiency on asthma, allergic rhinitis and wheezing in children: An emerging public health problem.

Background: Vitamin D deficiency has been declared a public health problem for both adults and children worldwide. Asthma and related allergic diseases are the leading causes of morbidity in children. The objective of this study was to investigate the potential role of Vitamin D deficiency in childhood asthma and other allergic diseases such as allergic rhinitis and wheezing. Materials and Methods: This cross-sectional study was conducted in Primary Health Care Centers (PHCs), from March 2012 to October 2013. A total of 2350 Qatari children below the age of 16 were selected from PHCs, and 1833 agreed to participate in this study giving a response rate of (78%). Face-to-face interviews with parents of all the children were based on a questionnaire that included variables such as socio-demographic information, assessment of nondietary covariates, Vitamin D intake, type of feeding, and laboratory investigations. Their health status was assessed by serum Vitamin D (25-hydoxyvitamin D), family history and body mass index. Results: Most of the children who had asthma (38.5%), allergic rhinitis (34.8%) and wheezing (35.7%) were below 5 years. Consanguinity was significantly higher in parents of children with allergic rhinitis (48.6%), followed by those with asthma (46.4%) and wheezing (40.8%) than in healthy children (35.9%) (P < 0.001). The proportion of severe Vitamin D deficiency was significantly higher in children with wheezing (23.4%), allergic rhinitis (18.5%), and asthma (17%) than in healthy children (10.5%). Exposure to the sun was significantly less in Vitamin D deficient children with asthma (60.3%), allergic rhinitis (62.5%) and wheezing (64.4%) than in controls (47.1%) (P = 0.008). It was found that Vitamin D deficiency was a significant correlate for asthma (odds ratio [OR] =2.31; P < 0.001), allergic rhinitis (OR = 1.59; P < 0.001) and wheezing (relative risk = 1.29; P = 0.05). Conclusion: The study findings revealed a high prevalence of Vitamin D deficiency in children with asthma and allergic diseases. Vitamin D deficiency was a strong correlate for asthma, allergic rhinitis and wheezing.

Duration of breast-feeding and the risk of childhood allergic diseases in a developing country.

Exclusive breast-feeding (EBF) seems to reduce risk of allergies in the western countries, but there are few reports from developing countries. The purpose of this study was to assess the effect of EBF on the development of allergic diseases and eczema in a developing country. This is a cross-sectional survey done at the well-baby clinics of 11 primary health centers, Hamad Medical Corporation, Qatar. A multistage sampling design was used and a representative sample of 1500 children (0-5 years old) and mothers (18-47 years old) were surveyed between October 2006 and September 2007. Of them, 1278 mothers (85.2%) participated in the study. A confidential, anonymous questionnaire assessing breast-feeding and allergic diseases was completed by mothers bringing children for immunization. Questionnaire included allergic rhinitis, wheezing, eczema, type and duration of breast-feeding, parental smoking habits, number of siblings, family income, maternal education, and parental allergies. Univariate and multivariate statistical methods were performed for statistical analysis. More than one-half of the infants (59.3%) were on EBF. Length of breast-feeding was associated with maternal age. Prevalence of eczema (19.4%), allergic rhinitis (22.6%), and wheezing (12.7%) were significantly less frequent in those with prolonged (>6 months) compared with short-term fed infants. The association between EBF and eczema tended to be similar in children with a positive family history of atopy (p < 0.001) and eczema (p < 0.001) compared with those without. In children of developing countries, prolonged breast-feeding reduces the risk of developing allergic diseases and eczema even in the presence of maternal allergy, where it might be a practical, effective preventive measure.

Primary Immunodeficiency Diseases in Children: 15 Year Experience in a Tertiary Care Medical Center in Qatar

BackgroundPrimary immunodeficiency diseases (PID) are a group of heterogeneous, rare, genetic, mainly childhood disorders that affect specific components of immune system leading to serious complications.ObjectivesThis study is aimed at describing the prevalence and the categories of PID, the ages of onset and the diagnosis, the clinical presentations, the treatment modalities and the overall outcome of affected patients.Materials and MethodsA retrospective study was conducted on 131 pediatric patients (aged 0–14xa0years) diagnosed with PID at Hamad General Hospital during a 15-year period (1998–2012).ResultsData of 131 patients (75 males & 56 females) was analyzed with an estimated prevalence of 4.7 PID patients per 100,000 children younger than 14xa0years of age. The most common type of PID was predominantly antibody deficiency (23.7xa0%), followed by other well-defined immunodeficiency syndromes (22.9xa0%), 19.1xa0% combined T and B cell immunodeficiency, but rare CVID, and no cases of complement deficiency. The mean onset age was 24.01xa0months and diagnosis age was 42.2xa0months. Recurrent infections, particularly pneumonia (48.9xa0%), failure to thrive (34.4xa0%), otitis media (26xa0%), sepsis (23.7xa0%), and chronic diarrhoea (21.4xa0%) were commonest presenting conditions. P. aeruginosa (15.7xa0%), Salmonella species (13.2xa0%), and Non-TB mycobacteria (13.2xa0%) were the most common bacterial isolates. The overall mortality rate was 21.4xa0% with combined immunodeficiency’s accounting for 53.4xa0% of deaths.ConclusionsThis study reveals that PIDs are not rare in children in Qatar; and like other studies predominantly antibody deficiencies are the most common. Strategies that reinforce awareness and education of practicing physicians, bone marrow transplantation, and establishing PID national registry should be adopted to reduce mortality and morbidity of PID patients in Qatar.

Allergic diseases among children: nutritional prevention and intervention

Allergic diseases comprise a genetically heterogeneous group of chronic, immunomediated diseases. It has been clearly reported that the prevalence of these diseases has been on the rise for the last few decades, but at different rates, in various areas of the world. This paper discusses the epidemiology of allergic diseases among children and their negative impact on affected patients, their families, and societies. These effects include the adverse effects on quality of life and economic costs. Medical interest has shifted from tertiary or secondary prevention to primary prevention of these chronic diseases among high-risk infants in early life. Being simple, practical, and cost-effective are mandatory features for any candidate methods delivering these strategies. Dietary therapy fits this model well, as it is simple, practical, and cost-effective, and involves diverse methods. The highest priority strategy is feeding these infants breast milk. For those who are not breast-fed, there should be a strategy to maintain beneficial gut flora that positively influences intestinal immunity. We review the current use of probiotics, prebiotics, and synbiotics, and safety and adverse effects. Other dietary modalities of possible potential in achieving this primary prevention, such as a Mediterranean diet, use of milk formula with modified (hydrolyzed) proteins, and the role of micronutrients, are also explored. Breast-feeding is effective in reducing the risk of asthma, allergic rhinitis, and atopic eczema among children. In addition, breast milk constitutes a major source of support for gut microbe colonization, due to its bifidobacteria and galactooligosaccharide content. The literature lacks consensus in recommending the addition of probiotics to foods for prevention and treatment of allergic diseases, while prebiotics may prove to be effective in reducing atopy in healthy children. There is insufficient evidence to support soy formulas or amino acid formulas for prevention of allergic disease. A healthy diet, such as the Mediterranean diet, may have a protective effect on the development of asthma and atopy in children. In children with asthma and allergic diseases, vitamin D deficiency correlates strongly with asthma, allergic rhinitis, and wheezing.