Arnon Broides

The contribution of smoking and exposure to tobacco smoke to Streptococcus pneumoniae and Haemophilus influenzae carriage in children and their mothers.

BACKGROUND Exposure to tobacco smoke is associated with higher risk of Streptococcus pneumoniae and Haemophilus influenzae infection. The aim of this study was to determine the influence of smoking and exposure to tobacco smoke on S. pneumoniae and H. influenzae carriage rates in children and their mothers. PATIENTS AND METHODS We performed a cross-sectional surveillance study of nasopharyngeal and oropharyngeal carriage of S. pneumoniae and H. influenzae in 208 children aged <60 months and their mothers. Smoking exposure and medical history were recorded. Carriage rates for children and their mothers in nasopharyngeal and oropharyngeal specimens were analyzed on the basis of smoking exposure. RESULTS The S. pneumoniae carriage rate was higher among children exposed to smoking than among nonexposed children (76% vs. 60%; P=.016). Exposed children more frequently carried S. pneumoniae serotypes included in the conjugate 7-valent vaccine, compared with nonexposed children (49% vs. 30% of all S. pneumoniae-positive nasopharyngeal cultures; P=.02). Carriage rates of S. pneumoniae were higher among mothers who smoked than among mothers exposed to smoking and among nonexposed mothers (32%, 15%, and 12%, respectively; P=.03). There were no differences in H. influenzae carriage rates between children and mothers from smoking and nonsmoking families. CONCLUSIONS Exposure to tobacco smoke increased S. pneumoniae carriage rates in general and for carriage of serotypes included in the conjugate 7-valent vaccine in particular in children. Smoking mothers had a higher S. pneumoniae carriage rate than did nonsmoking mothers. Smoking or exposure to smoking did not increase H. influenzae carriage rates in children and mothers.

Relative Importance of Nasopharyngeal versus Oropharyngeal Sampling for Isolation of Streptococcus pneumoniae and Haemophilus influenzae from Healthy and Sick Individuals Varies with Age

ABSTRACT Streptococcus pneumoniae and Haemophilus influenzae carriage is a useful index for measuring the emergence of resistance and outcome in vaccination trials. We performed a study to determine which sampling site, nasopharynx (NP) or oropharynx (OP), yields the highest rate of S. pneumoniae and H. influenzae isolation at different ages. Both NP and OP cultures were obtained from 216 children aged <60 months and their mothers. The total S. pneumoniae carriage rate was 68% among children and 15% among mothers (P < 0.001). Using NP alone for the isolation of S. pneumoniae would have missed 2, 2, and 42% and using OP alone would have missed 77, 66, and 45% of S. pneumoniae in children aged 0 to 23 months, 24 to 59 months, and mothers, respectively. Using NP cultures alone for H. influenzae would have missed 23, 24, and 81% of the isolates, respectively. The respective figures for H. influenzae isolation from OP alone are 38, 29, and 9%. In children, S. pneumoniae was carried mainly in the NP while H. influenzae was equally carried in the NP and OP. In mothers, S. pneumoniae was carried equally in the NP and OP while H. influenzae was carried significantly more often in the OP. In children, H. influenzae colonization increased during illness, mainly in the NP. Culturing only one site significantly reduced the recovery of H. influenzae at all ages. NP cultures for S. pneumoniae detected close to 100% of isolates in children but only 58% of isolates in mothers.

Clinical Features of Candidiasis in Patients With Inherited Interleukin 12 Receptor β1 Deficiency

BACKGROUND Interleukin 12Rβ1 (IL-12Rβ1)-deficient patients are prone to clinical disease caused by mycobacteria, Salmonella, and other intramacrophagic pathogens, probably because of impaired interleukin 12-dependent interferon γ production. About 25% of patients also display mucocutaneous candidiasis, probably owing to impaired interleukin 23-dependent interleukin 17 immunity. The clinical features and outcome of candidiasis in these patients have not been described before, to our knowledge. We report here the clinical signs of candidiasis in 35 patients with IL-12Rβ1 deficiency. RESULTS Most (n = 71) of the 76 episodes of candidiasis were mucocutaneous. Isolated oropharyngeal candidiasis (OPC) was the most common presentation (59 episodes, 34 patients) and was recurrent or persistent in 26 patients. Esophageal candidiasis (n = 7) was associated with proven OPC in 2 episodes, and cutaneous candidiasis (n = 2) with OPC in 1 patient, whereas isolated vulvovaginal candidiasis (VVC; n = 3) was not. Five episodes of proven invasive candidiasis were documented in 4 patients; 1 of these episodes was community acquired in the absence of any other comorbid condition. The first episode of candidiasis occurred earlier in life (median age±standard deviation, 1.5 ± 7.87 years) than infections with environmental mycobacteria (4.29 ± 11.9 years), Mycobacterium tuberculosis (4 ± 3.12 years), or Salmonella species (4.58 ± 4.17 years) or other rare infections (3 ± 11.67 years). Candidiasis was the first documented infection in 19 of the 35 patients, despite the vaccination of 10 of these 19 patients with live bacille Calmette-Guérin. CONCLUSIONS Patients who are deficient in IL-12Rβ1 may have candidiasis, usually mucocutaneous, which is frequently recurrent or persistent. Candidiasis may be the first clinical manifestation in these patients.

Acute Otitis Media Caused by Moraxella catarrhalis: Epidemiologic and Clinical Characteristics

BACKGROUND This study describes the epidemiologic, microbiologic, and otologic features and selected signs and symptoms of acute otitis media (AOM) caused by Moraxella catarrhalis and compares them with AOM caused by other bacterial pathogens. METHODS Patients aged <5 years with culture-positive AOM from whom a middle ear fluid specimen was obtained and cultured during 1999-2006 were enrolled in the study. RESULTS Of a total of 12,799 AOM episodes, 8198 (64%) were culture positive, with isolation of 10,382 pathogens: Haemophilus influenzae, 4982 (48.0%); Streptococcus pneumoniae, 4450 (42.9%); M. catarrhalis, 501 (4.8%); and group A streptococci, 449 (4.3%). The distribution of single versus mixed M. catarrhalis infection was significantly different compared with the 3 other pathogens (165 cases [32.9%] as a single pathogen of all M. catarrhalis AOM episodes vs 3108 [62.4%] in AOM caused by H. influenzae, 2592 [58.2%] in AOM caused by S. pneumoniae, and 304 [67.7%] in AOM caused by group A streptococci; P < .001 for all comparisons). In multivariate analysis, M. catarrhalis AOM was more frequent in patients experiencing their first AOM episode versus recurrent AOM and mixed infections. M. catarrhalis AOM was associated with lower proportions of spontaneous perforation of tympanic membrane compared with all other pathogens. None of the AOM episodes caused by M. catarrhalis was associated with mastoiditis. CONCLUSIONS Compared with AOM caused by other pathogens, AOM caused by M. catarrhalis is characterized by a higher proportion of mixed infections, younger age at diagnosis, a lower proportion of spontaneous perforation of the tympanic membrane, and no mastoiditis.

Epidemiologic and microbiologic characteristics of culture-positive spontaneous otorrhea in children with acute otitis media.

Objectives: We aimed to describe the epidemiologic and microbiologic characteristics of acute otitis media (AOM) with spontaneous otorrhea in children and compare it with AOM with intact tympanic membrane in children who underwent tympanocentesis. Patients and Methods: All infants and young children aged <3 years with culture-positive AOM of ≤7 days duration diagnosed during 1999 to 2006 and in whom epidemiologic and microbiologic data were available, were analyzed. Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pyogenes were considered true AOM pathogens. Multivariable regression analysis models adjusting for age, gender, ethnicity, seasonality, previous antibiotics, AOM history, tympanocentesis history, and pathogens isolated, were used. Results: Of 12,617 AOM patients from whom a middle ear fluid was obtained, 5247 (42%) culture-positive patients were enrolled; spontaneous otorrhea was observed in 822 (15%) patients. Patients with spontaneous otorrhea were older than patients with AOM who underwent tympanocentesis (15.8 ± 8.2 vs. 9.7 ± 6.7 months, respectively, P < 0.01; 36.9% vs. 69.1%, respectively, were <12 months, P < 0.01). S. pyogenes was found in a higher proportion (47/822, 5.7% vs. 44/4425, 1%, P < 0.01) and H. influenzae in a lower proportion (264/822, 32.1% vs. 1805/4425, 40.8%, P < 0.01) among patients with spontaneous otorrhea than in patients with AOM and tympanocentesis. In the multivariate model, Bedouin ethnicity (OR: 1.5, 95% CI: 1.2–1.7, P < 0.001), age (OR: 1.1, 95% CI: 1.0–1.11, P < 0.001) for each consecutive month, lack of antibiotic treatment for the 48 hours preceding diagnosis (OR: 2.1, 95% CI: 1.7–2.6, P < 0.001), ≥1 previous AOM episode (OR: 3.2, 95% CI: 2.6–4.0, P < 0.001), >1 previous tympanocentesis (OR: 1.4, 95% CI: 1.4–1.7, P = 0.001), and infection with S. pyogenes (OR: 8.2, 95% CI: 5.4–12.3, P < 0.001) were independent risk factors for AOM presenting as spontaneous otorrhea. Conclusions: AOM presenting as spontaneous otorrhea in patients less than 3 years of age is characterized by older age, previous repeated tympanocenteses, ≥1 previous AOM episodes, lack of recent antibiotic treatment, and infection with S. pyogene.

IL-12Rβ1 deficiency: mutation update and description of the IL12RB1 variation database

IL‐12Rβ1 deficiency is an autosomal recessive disorder characterized by predisposition to recurrent and/or severe infections caused by otherwise poorly pathogenic mycobacteria and salmonella. IL‐12Rβ1 is a receptor chain of both the IL‐12 and the IL‐23 receptor and deficiency of IL‐12Rβ1 thus abolishes both IL‐12 and IL‐23 signaling. IL‐12Rβ1 deficiency is caused by bi‐allelic mutations in the IL12RB1 gene. Mutations resulting in premature stop codons, such as nonsense, frame shift, and splice site mutations, represent the majority of IL‐12Rβ1 deficiency causing mutations (66%; 46/70). Also every other morbid mutation completely inactivates the IL‐12Rβ1 protein. In addition to disease‐causing mutations, rare and common variations with unknown functional effect have been reported in IL12RB1. All these variants have been deposited in the online IL12RB1 variation database (www.LOVD.nl/IL12RB1). In this article, we review the function of IL‐12Rβ1 and molecular genetics of human IL12RB1.

Cytology of middle ear fluid during acute otitis media.

Background. Limited information is available on the cellular characteristics of the middle ear fluid (MEF) during acute otitis media (AOM). Objectives. To determine the white blood cell (WBC) composition of the MEF in AOM before and during antibiotic therapy. Materials and methods. Total WBC and differential counts were determined in the MEF of 96 infants and children (ages 2 weeks to 3 years) with AOM who were receiving antibiotics. WBC counts were reported as number of WBC/mg MEF (mean ± sd). Results. One hundred forty-five MEF samples were obtained by tympanocentesis at enrollment (Day 1), and 36 samples were collected on Days 4 to 5 after initiation of antibiotic therapy. Sixty-one percent of the patients were <1 year of age, and 38% were receiving antibiotic therapy at enrollment. Twenty-eight MEF samples were paired (same ear, Day 1 and Days 4 to 5). One hundred twelve pathogens were isolated from 95 of 145 (66%) culture-positive samples obtained on Day 1: 67 Haemophilus influenzae, 40 Streptococcus pneumoniae and 5 others. MEF WBC counts were lower on Day 1 in patients who had received previous antibiotic therapy than in those who had not (432.4± 412.8 vs. 590.5 ± 436.8, P = 0.03). WBC counts were higher on Day 1 in culture-positive than in culture-negative samples (603.9 ± 504.9 vs. 421.4 ± 373.4, P = 0.02). WBC counts were higher on Day 1 in MEF samples positive for S. pneumoniae than in those positive for H. influenzae (799.2 ± 641.5 vs. 506.4 ± 401.9, P = 0.04). There were no differences in the number of neutrophil WBC present in the samples obtained on Day 1 vs. Days 4 to 5 or between samples positive vs. samples negative for bacterial pathogens. Conclusions. WBC counts were higher in the MEF of patients with culture-positive AOM than in those with culture-negative AOM and in those with AOM caused by S. pneumoniae.

Current management of pediatric acute otitis media

Acute otitis media (AOM) is the most common childhood bacterial infection for which antibiotics are prescribed worldwide. The most common pathogens causing AOM in children are Streptococcus pneumoniae, nontypeable Haemophilus influenzae, Moraxella catarrhalis and Group A streptococcus. Antibiotic resistance is increasing among the bacterial pathogens causing AOM, with percentages of penicillin- and macrolide-resistant S. pneumoniae strains estimated to be between 30 and 70%, and of β-lactamase-producing H. influenzae ranging between 20 and 40%. The introduction of the seven-valent pneumococcal conjugated vaccine had a major role in decreasing the number of vaccine-related S. pneumoniae AOM episodes, recurrent AOM cases and cases requiring the insertion of ventilation tubes. In parallel, it caused a rapid shift in the microbiology of AOM, characterized by an increase in the number of nonvaccine S. pneumoniae serotypes and H. influenzae isolates. The management of AOM in childhood has evolved considerably during recent years as a result of the new insights provided by the publication of the American Academy of Pediatrics and American Academy of Family Physicians guidelines for the treatment of AOM. The new treatment guidelines establish a clear hierarchy among various antibacterials used in the treatment of AOM and also the use of an age-stratified approach to AOM by recommending an observation strategy (‘watchful waiting’) without the use of antibacterials for some groups of AOM patients. Adherence to such a policy in patients with uncertain/questionable AOM diagnosis and/or mild-to-moderate symptoms, in addition to its implementation in patients over 2 years of age, could substantially reduce the use of antibacterials for the treatment of AOM and play a major role in the strategy of decreasing antibacterial resistance.

Molecular assessment of thymus capabilities in the evaluation of T-cell immunodeficiency.

T-cell immunodeficiency may pose a diagnostic challenge to clinicians, especially when the basic T-cell immune workup is not sufficiently informative. An intensive assessment of thymus capabilities that involves either measuring the recent thymic emigrant cells or analyzing the T-cell receptor (TCR) repertoire is often required to estimate the severity and nature of the immune disorder. A comprehensive T-cell immune workup, including TCR excision circles (TRECs) and TCR repertoire analyses, was performed in three patients with various degrees of severity of T-cell immunodeficiency. All three patients had normal peripheral CD3+ T lymphocytes. TCR repertoire analysis revealed oligoclonal (patient 1), restricted (patient 2), and near-normal (patient 3) patterns. TREC quantification was significantly reduced in patients 1 and 2 but normal in patient 3. Based on clinical features at presentation and at follow-up, and supported by the results of immunologic studies, patients 1 and 2 were diagnosed as having significant T-cell immunodeficiency and patient 3 as having T-cell immunocompetence. Assessment of thymus capabilities by TRECs and TCR repertoire analyses is helpful in diagnosing patients with T-cell immunodeficiency and should be part of the evaluation of every patient suspected of having that condition.

Home accidents in Arab Bedouin children in southern Israel.

Home accidents are a major health problem; no data about the specific types of home accidents in the pediatric Bedouin population of southern Israel is available. We sought to delineate the specific types of home accidents in Arab Bedouin children in southern Israel. The study was conducted in a primary care clinic in an Arab Bedouin town in southern Israel. An interview of every patient or parent who presented to the clinic for a home accident in a child from December 2000 until mid November 2001was conducted. A total of 235 accidents were recorded from 219 patients (153 males and 66 females). The most prevalent injury was burns (85 cases- 36.1%) followed by falls (67 cases - 28.5%), contusions (31cases -13.2%), lacerations (29 cases - 12.3%), and nail penetrations (19 cases -8%). Thirteen patients were hospitalized, 6 with burns and 7 due to falls. A total of 209 days of hospitalization were recorded, 195 days due to burn and 14 days due to falls, (p < 0.05). Burn rates were highest in children younger than 2 years of age, 39/57 (68.4%), and an increased risk for burns was significantly correlated to younger age (p < 0.0001). We conclude that in our study population, burns represent the most prevalent home accident and that burns cause a much longer hospital stay than any other type of accident. The risk for burns is correlated to younger age. A burn prevention plan is needed.