Elham Hossny

Monovalent Type 1 Oral Poliovirus Vaccine in Newborns

BACKGROUND In 1988, the World Health Assembly resolved to eradicate poliomyelitis. Although substantial progress toward this goal has been made, eradication remains elusive. In 2004, the World Health Organization called for the development of a potentially more immunogenic monovalent type 1 oral poliovirus vaccine. METHODS We conducted a trial in Egypt to compare the immunogenicity of a newly licensed monovalent type 1 oral poliovirus vaccine with that of a trivalent oral poliovirus vaccine. Subjects were randomly assigned to receive one dose of monovalent type 1 oral poliovirus vaccine or trivalent oral poliovirus vaccine at birth. Thirty days after birth, a single challenge dose of monovalent type 1 oral poliovirus vaccine was administered in all subjects. Shedding of serotype 1 poliovirus was assessed through day 60. RESULTS A total of 530 subjects were enrolled, and 421 fulfilled the study requirements. Thirty days after the study vaccines were administered, the rate of seroconversion to type 1 poliovirus was 55.4% in the monovalent-vaccine group, as compared with 32.1% in the trivalent-vaccine group (P<0.001). Among those with a high reciprocal titer of maternally derived antibodies against type 1 poliovirus (>64), 46.0% of the subjects in the monovalent-vaccine group underwent seroconversion, as compared with 21.3% in the trivalent-vaccine group (P<0.001). Seven days after administration of the challenge dose of monovalent type 1 vaccine, a significantly lower proportion of subjects in the monovalent-vaccine group than in the trivalent-vaccine group excreted type 1 poliovirus (25.9% vs. 41.5%, P=0.001). None of the serious adverse events reported were attributed to the trial interventions. CONCLUSIONS When given at birth, monovalent type 1 oral poliovirus vaccine is superior to trivalent oral poliovirus vaccine in inducing humoral antibodies against type 1 poliovirus, overcoming high preexisting levels of maternally derived antibodies, and increasing the resistance to excretion of type 1 poliovirus after administration of a challenge dose. (Current Controlled Trials number, ISRCTN76316509.)

Update on the use of immunoglobulin in human disease: A review of evidence.

&NA; Human immunoglobulin preparations for intravenous or subcutaneous administration are the cornerstone of treatment in patients with primary immunodeficiency diseases affecting the humoral immune system. Intravenous preparations have a number of important uses in the treatment of other diseases in humans as well, some for which acceptable treatment alternatives do not exist. We provide an update of the evidence‐based guideline on immunoglobulin therapy, last published in 2006. Given the potential risks and inherent scarcity of human immunoglobulin, careful consideration of its indications and administration is warranted.

Vascular endothelial growth factor overexpression in induced sputum of children with bronchial asthma

Vascular endothelial growth factor (VEGF) induces angiogenesis and increases vascular permeability participating in narrowing of the airway lumen that follows lung injury. We sought to investigate the expression of VEGF in induced sputum during and after recovery from acute episodes of bronchial asthma in children. Eighteen asthmatic children with acute attacks of varying severity were subjected to VEGF estimation by an enzymatic immunoassay in induced sputum. They were followed up till complete remission of symptoms and signs and were then retested. VEGF was also estimated in sputum induced from age 34 and sex‐matched healthy children enrolled as a control group. The sputum VEGF levels during acute asthma [median = 71 ng/ml; mean (s.d.) = 114.6 (121.8) ng/ml] were significantly higher than the levels estimated during remission [median = 50 ng/ml; mean (s.d.) = 45.7 (24.2) ng/ml] and both were higher than the corresponding levels of the control group [median = 36 ng/ml; mean (s.d.) = 31.3 (17.2) ng/ml]. VEGF levels during asthmatic episodes correlated positively to the recovery levels (r = 0.6, p = 0.009). The patients’ VEGF expression did not vary with asthma severity, serum total IgE concentration, peripheral blood eosinophil count, or erythrocyte sedimentation rate of patients. Children on corticosteroids inhalation therapy at enrollment had sputum VEGF levels that were comparable to those on other therapies. The increased expression of sputum VEGF in asthmatic children reinforces the concept that it might have a pathogenetic role in bronchial asthma and may represent a biomarker of airway inflammation.

Anti‐centromere antibodies as a marker of Raynaud's phenomenon in pediatric rheumatologic diseases

To examine the possible relationship between anti‐centromere antibodies (ACA) and pediatric rheumatologic diseases, we investigated the presence of ACA (using enzyme immunoassay) in the sera of 45 children and adolescents with such diseases and compared the results with a group of 42 age‐ and gender‐matched healthy subjects. ACA were present (≥ 10 U/ml) in three out of five patients (60%) with scleroderma (SCD), in seven out of 16 (43.8%) patients with systemic lupus erythematosus (SLE), in two out of five patients (40%) with mixed connective tissue disease (MCTD), in one out of four patients (25%) with dermatomyositis (DMS), and in two out of 14 patients (14.3%) with juvenile rheumatoid arthritis (JRA). ACA were also detected in a single patient with anti‐phospholipid syndrome (APL) who had digital gangrene and hemiparesis, as well as in two healthy subjects. ACA positivity was related to the presence of Raynauds phenomenon in the studied sample, as 86% of patients suffering from the phenomenon were ACA positive. ACA positivity was associated with older age, high blood pressure and high erythrocyte sedimentation rate (ESR) values, and lower hemoglobin and weight and height percentile values. It was also higher among anti‐nuclear antibody‐positive subjects. Raynauds phenomenon and ACA positivity shared almost the same clinical and laboratory associations in the studied patients. Thus, ACA are probably among the markers of Raynauds phenomenon in pediatric rheumatologic diseases. Their value as predictors of future development of the phenomenon needs further evaluation.

The use of inhaled corticosteroids in pediatric asthma: update

Despite the availability of several formulations of inhaled corticosteroids (ICS) and delivery devices for treatment of childhood asthma and despite the development of evidence-based guidelines, childhood asthma control remains suboptimal. Improving uptake of asthma management plans, both by families and practitioners, is needed. Adherence to daily ICS therapy is a key determinant of asthma control and this mandates that asthma education follow a repetitive pattern and involve literal explanation and physical demonstration of the optimal use of inhaler devices. The potential adverse effects of ICS need to be weighed against the benefit of these drugs to control persistent asthma especially that its safety profile is markedly better than oral glucocorticoids. This article reviews the key mechanisms of inhaled corticosteroid action; recommendations on dosage and therapeutic regimens; potential optimization of effectiveness by addressing inhaler technique and adherence to therapy; and updated knowledge on the real magnitude of adverse events.

Characterization of T and B cell repertoire diversity in patients with RAG deficiency

Differences in B and T cell repertoires in patients with RAG deficiency associate with clinical severity. Taking SCID genetics to the clinic Mutations that lead to deficiencies in the recombination-activating genes RAG1 and RAG2 result in a spectrum of immunodeficiencies ranging from loss of T and/or B cell repertoire diversity to a complete lack of T and B cells—severe combined immunodeficiency (SCID). Here, Lee et al. perform next-generation B and T cell repertoire sequencing on 12 patients with RAG mutations who have immunodeficiencies of varying severity. They found that the level of repertoire skewing was associated with the severity of disease and that specific repertoire deficiencies were associated with particular phenotypes. These data support a genotype-phenotype connection for primary immunodeficiencies. Recombination-activating genes 1 and 2 (RAG1 and RAG2) play a critical role in T and B cell development by initiating the recombination process that controls the expression of T cell receptor (TCR) and immunoglobulin genes. Mutations in the RAG1 and RAG2 genes in humans cause a broad spectrum of phenotypes, including severe combined immunodeficiency (SCID) with lack of T and B cells, Omenn syndrome, leaky SCID, and combined immunodeficiency with granulomas or autoimmunity (CID-G/AI). Using next-generation sequencing, we analyzed the TCR and B cell receptor (BCR) repertoire in 12 patients with RAG mutations presenting with Omenn syndrome (n = 5), leaky SCID (n = 3), or CID-G/AI (n = 4). Restriction of repertoire diversity skewed usage of variable (V), diversity (D), and joining (J) segment genes, and abnormalities of CDR3 length distribution were progressively more prominent in patients with a more severe phenotype. Skewed usage of V, D, and J segment genes was present also within unique sequences, indicating a primary restriction of repertoire. Patients with Omenn syndrome had a high proportion of class-switched immunoglobulin heavy chain transcripts and increased somatic hypermutation rate, suggesting in vivo activation of these B cells. These data provide a framework to better understand the phenotypic heterogeneity of RAG deficiency.

Response of Egyptian Infants with Protein Calorie Malnutrition to Hepatitis B Vaccination

The response to recombinant hepatitis B vaccine was assessed in 31 seronegative infants (2-26 months old) with protein calorie malnutrition (PCM), compared with 13 seronegative age- and sex-matched healthy infants. Both groups received three 10 micrograms vaccine doses at 0, 1, and 6 months. At month 8, all healthy infants and 87 per cent (27 out of 31) of PCM infants were seroprotected. Thus, hepatitis B vaccination (Engerix-B, SmithKline Beecham Biologicals) can be used effectively in PCM for mass vaccination in developing communities.

Antiperinuclear factor in the diagnosis of juvenile rheumatoid arthritis

The antiperinuclear factor (APF) was estimated by immunofluorescent microscopy in the sera of 32 children and adolescents with juvenile rheumatoid arthritis (JRA) in comparison to a group of 16 children and adolescents with other rheumatologic disorders and a group of 20 age‐matched healthy subjects. The APF was detected in 17 children with JRA (53%), in only one patient in the group of other rheumatologic disorders (6%), and in 2 healthy children (10%). Accordingly, APF had a sensitivity of 53%, a specificity of 92%, and a diagnostic efficiency of 74% in our series. APF was found to have a higher diagnostic gain in rheumatoid factor (RF) seronegative cases than did the RF in APF negative cases, meaning a higher sensitivity of APF as compared to the RF. The APF seropositivity was neither altered by the use of corticosteroids nor influenced by the age, gender, duration of illness, or number of joints affected. Three out of 5 patients with JRA had the APF detected in their synovial fluid; they were running rather a severe course of illness. The use of the APF could be an aid in the diagnosis of JRA.

Plasma endothelin-1 immunoreactivity in asthmatic children.

BACKGROUND Endothelin-1 (ET-1) has been formerly demonstrated to have potent vasocontractile as well as bronchoconstrictor effects in vitro. This followup study was aimed to evaluate the possible changes in ET-1 levels in the plasma of asthmatic children, according to disease activity and severity. METHODS Plasma ET-1 was estimated by enzyme-linked immunoadsorbent assay in 30 asthmatic patients (6 to 12 years old) during and after remission of an acute attack. Thirty age- and sex-matched healthy children were included as a control group. RESULTS Plasma ET-1 immunoreactivity was significantly increased in the asthmatic children during the attacks (17.2+/-6.9 pg/mL) in comparison to the levels during quiescence of symptoms (0.9+/-1.13 pg/mL). Further, both values were significantly higher than the control value (0.22+/-0.29 pg/mL). The severity of attacks as judged clinically and by peak expiratory flow rate measurement did not influence the plasma endothelin status; neither did the family history of atopy nor the absolute eosinophil count. However, serum total IgE levels could be positively correlated to the plasma endothelin concentrations measured after remission of the asthmatic attacks (P < 0.05). CONCLUSIONS Our findings reinforce the concept that ET-1 may be implicated in the pathogenesis of bronchoconstriction. This may encourage further studies on the value of ET-1 antagonism among alternative therapeutic modalities of childhood asthma.

Peanut sensitization in a group of allergic Egyptian children

BackgroundThere are no published data on peanut sensitization in Egypt and the problem of peanut allergy seems underestimated. We sought to screen for peanut sensitization in a group of atopic Egyptian children in relation to their phenotypic manifestations.MethodsWe consecutively enrolled 100 allergic children; 2-10 years old (mean 6.5 yr). The study measurements included clinical evaluation for site of allergy, possible precipitating factors, consumption of peanuts (starting age and last consumption), duration of breast feeding, current treatment, and family history of allergy as well as skin prick testing with a commercial peanut extract, and serum peanut specific and total IgE estimation. Children who were found sensitized to peanuts were subjected to an open oral peanut challenge test taking all necessary precautions.ResultsSeven subjects (7%) were sensitized and three out of six of them had positive oral challenge denoting allergy to peanuts. The sensitization rates did not vary significantly with gender, age, family history of allergy, breast feeding duration, clinical form of allergy, serum total IgE, or absolute eosinophil count. All peanut sensitive subjects had skin with or without respiratory allergy.ConclusionsPeanut allergy does not seem to be rare in atopic children in Egypt. Skin prick and specific IgE testing are effective screening tools to determine candidates for peanut oral challenging. Wider scale multicenter population-based studies are needed to assess the prevalence of peanut allergy and its clinical correlates in our country.