Mycobacterial infection and atopy in childhood: A systematic review

The epidemiological relation between mycobacterial infection and the prevalence of atopic disease in humans is still unclear. This is in contrast to studies in murine models in which a clear suppression of atopic symptoms was observed after exposure to mycobacteria or mycobacterial products. We therefore wanted to provide a systematic overview of the published literature on the relationship between mycobacterial infection and atopic disease and to evaluate the causal relationship in a meta-analysis. The EMBASE and MEDLINE databases were searched systematically for papers published in the English literature (1966-2005) on the relation between mycobacterial infection and atopic disease. Original observational or interventional studies involving the paediatric population were included. Two authors independently reviewed articles for data on mycobacterial exposure and atopic disease outcome. Any differences were resolved by discussion. Of a total of 1201 hits, 23 studies (19 cross-sectionals, three case-controls and one prospective cohort) met the inclusion criteria. Only a minority of studies (40%) observed an association between mycobacterial infection and the prevalence of atopic disease outcome. In the meta-analysis, only studies containing data on mycobacterial exposure and atopic disease outcome variables were included. Only cross-sectional studies, in which the relation between a positive tuberculin skin test and allergic symptoms was studied, observed statistically significant negative correlation (odds ratio 0.63; 95% confidence interval: 0.51-0.79). The results of this review show that the evidence of the relationship of mycobacterial infection and atopic disease is based on observations of cross-sectional studies. In a meta-analysis, calculations showed a high level of heterogeneity (I(2)) within studies with similar design making it difficult to pool effects. This may partly be explained by differences in the type and definition of mycobacterial infection and lack of uniformity in the definition of atopy. The results show that only a minority of studies in the literature shows any evidence of inverse relationship between mycobacterial exposure and atopic disease outcome. The fact that the present epidemiological evidence on the relationship between mycobacterial infection and the development of atopic disease is based mainly on cross-sectional observational studies indicates the need for population-based prospective studies to address this issue. This issue needs to be addressed in view of recent suggestions to developing mycobacterial-based vaccines against atopic disease in the future.     

Clinical sepsis in neonates is responsible for the lower prevalence of developing allergy

BACKGROUND: The hygiene hypothesis proposes an association between the change in exposure to microbes and the increased incidence of atopic disease. The purpose of the present study was to perform a prospective epidemiological study of the effect of perinatal infection on the development of allergy. METHODS: Eight hundred and ten children were born at Umeda Gynecological Hospital in Yamaguchi prefecture in Japan between April 1997 and March 1998. A questionnaire survey on the development of allergic diseases was sent by mail in 2002. The presence or absence of neonatal infectious disease (clinical sepsis) and maternal complications during the gestational period and delivery, and the incidence of bacterial infection during the perinatal period, were investigated by examining hospital records. RESULTS: Data were obtained for 410 children (51%). One hundred and forty-eight children (36.1%) developed allergic diseases. Among children whose mothers had allergies, the percentage of children who developed allergic disease(s) was significantly lower in children who had had clinical sepsis in the neonatal period than in those without clinical sepsis (26.1% vs 49.7%, P < 0.03). CONCLUSIONS: Clinical sepsis in neonates might reduce the risk of developing allergic diseases in early childhood in children whose mothers have allergies.     

Early childhood infections and immunisation and the development of allergic disease in particular asthma in a high‐risk cohort: A prospective study of allergy‐prone children from birth to six years

Thomson JA, Widjaja C, Darmaputra AAP, Lowe A, Matheson MC, Bennett CM, Allen K, Abramson MJ, Hosking C, Hill D, Dharmage SC. Early childhood infections and immunisation and the development of allergic disease in particular asthma in a high‐risk cohort: a prospective study of allergy‐prone children from birth to six years.
Pediatr Allergy Immunol 2010: 21: 1076–1085.
© 2010 John Wiley & Sons A/S The role of early childhood infections and immunisation in the development of allergic diseases remains controversial. To examine these associations, six hundred and twenty infants with first‐degree relatives with allergic diseases were recruited into the Melbourne Atopy Cohort Study. Information on risk factors and outcomes was collected by interviewer administered questionnaire and was based on parental report and/or a physician’s diagnosis. Risk factors examined included early childhood infections (including gastroenteritis, otitis media and lower respiratory tract infections) and immunisations in the first 2 yr of life. Outcomes were current asthma, allergic rhinitis and eczema at 6 yr of age. Univariate and multivariate regression analysis were used to estimate relative risk (RR) and assess confounding. By 6 yr, 79% of the original cohort remained in the study. Those with at least three episodes of gastroenteritis showed an increased risk (crude RR 2.36, 95%CI 1.41 3.95; adjusted RR 2.03 95%CI 1.50 2.75) for the later development of asthma at age 6. Of the scheduled immunisations, Sabin immunisation in the second year had a reduced risk of asthma at 6 yr (crude RR 0.60, 95%CI 0.37 0.98; adjusted RR 0.63 95%CI 0.39 1.02). Combined diphtheria and tetanus (CDT) immunisation in the first year had an increased risk of asthma at 6 yr (RR 1.76, 95%CI 1.11 2.78; adjusted RR 1.88 95%CI 1.28 2.77). Recurrent gastroenteritis in early childhood is associated with a later risk of asthma. This may reflect a cause and effect relationship, or exposure to common risk factors. In contrast, Sabin immunisation in the second year is associated with a decreased risk of asthma in later childhood. CDT immunisation in the first year may be a risk factor for asthma, but the need for CDT immunisation may also be a marker of increased risk of asthma in later childhood.     

手卫生情况调查问卷及现场观察评估

目的 了解临床各科室医护人员手卫生相关知识掌握及执行情况.方法 通过不计名当场回收问卷形式评估手卫生相关知识,并现场观察了解手卫生实际执行情况.结果 此次调查共发放问卷203份,实际回收203份.在接触病人前、无菌操作前医护人员自评洗手率分别为33.5%和52.7%,其中医护人员吃饭前、上厕所前后、下班前洗手率大于90%,接触病人后洗手率为70.4%,其中接触体液及血液后的洗手率为100%,明显高于未接触体液者.而实际现场观察到的总洗手率为58.8%,调查问卷及现场观察两者结果基本一致.接触患者后的手卫生执行率以医师最高,为85.7%(P=0.002),接触患者直接范围之后的手卫生执行率以护士为最高,为44.2%(P=0.009).不同科室间,接触病人前、无菌操作前及接触病人直接范围后的手卫生执行率均以血液科最高,分别为68.4%、72.7%及94.2%(P=0.000);接触病人后以内科监护室及血液科的手卫生执行率最高,为86.5%及82.9%(P=0.000).大部分被访者对手卫生院内感染相关知识认识不足,无人答全问卷中相关院内感染英文缩写的全称,只有3.4%的被访者表示严格按照六步洗手法洗手;1人(0.5%)表示每次洗手时间>30 s.结论 医护人员对于手卫生相关知识了解不足,理论上了解手卫生的重要性,实际洗手依从性有待增强;应加强相关指导,提高洗手依从性,减少院内感染,有效保护医护人员自身及病人安全,降低医疗成本.     

Water,sanitation and hygiene interventions and the prevention and treatment of childhood acute malnutrition: A systematic review

Undernutrition is more prevalent among children living in unsanitary environments with inadequate water, sanitation and hygiene (WASH). Despite good evidence for the effect of WASH on multiple infectious diseases, evidence for the effect of WASH interventions on childhood undernutrition is less well established, particularly for acute malnutrition. To assess the effectiveness of WASH interventions in preventing and treating acute childhood malnutrition, we performed electronic searches to identify relevant studies published between 1 January 2000 and 13 May 2019. We included studies assessing the effect of WASH on prevention and treatment of acute malnutrition in children under 5 years of age. Data were extracted by two independent reviewers. We included 26 articles of 599 identified references with a total of 43,083 participants. Twenty-five studies reported on the effect of WASH on prevention, and two studies reported its effect on treatment of acute malnutrition. Current evidence does not show consistent associations of WASH conditions and interventions with prevention of acute malnutrition or with the improvement of its treatment outcomes. Only two high-quality randomized controlled trials (RCTs) demonstrated that improved water quality during severe acute malnutrition treatment improved recovery outcomes but did not prevent relapse. Many of the interventions consisted of a package of WASH services, making impossible to attribute the effect to one specific component. This highlights the need for high-quality, rigorous intervention studies assessing the effects of WASH interventions specifically designed to prevent acute malnutrition or improve its treatment.     

医护人员手卫生与医院感染的关系

手卫生工作是目前普遍公认的防止和控制医院感染的重要方法之一,但国内外医护人员手卫生执行情况却并不乐观,以致在实施医疗工作时其双手往往成了传播病原菌最常见的媒介,直接或者间接导致医院感染率的上升.总结分析医护人员洗手依从性差的原因,探讨一系列科学、可行的加强手卫生实施的方法,以期减少医院感染的发病率,减少医疗成本.     

Autism and the Immune System

As our knowledge of the interactions of the immune, nervous and endocrine systems progresses, complex links with the origin and course of psychopathology in childhood are revealed. In this article the neuroimmunological literature on autism is reviewed. Relevant aspects of immune functioning and the neuroendocrine-immune network are described. We present the immunological findings in autistic patients within two related conceptual frameworks: a viral and an autoimmune hypothesis. Interpretation of data is hampered by conceptual and methodological differences between studies. Both the clinical significance of the immune changes and the causal connection between immune changes and psycho-pathological phenomena in autism remain to he elucidated. Recommendations for further research are given.     

The interaction between early life upper respiratory tract infection and birth during the pollen season on rye-sensitized hay fever and ryegrass sensitization – a birth cohort study

Studies on early life viral respiratory infection and subsequent atopic disease in childhood have conflicting findings. Animal models show that viral respiratory infection in conjunction with allergen presentation can enhance sensitization. This prospective study assesses the influence of an upper respiratory tract infection (URI) in the first month of life and the season of birth on the development of hay fever and ryegrass allergen sensitization in childhood. From a Tasmanian cohort born during 1988 and 1989, a group of 498 children were followed up at 8 yr and another different group of 415 children were followed up at 16 yr. The ryegrass pollen season in Tasmania occurs in November and December. Forty‐four (9.6%) children in Follow‐up sample 1 and 47 (12.5%) children in Follow‐up sample 2 were born in the pollen season. The parental report of an early upper respiratory tract infection (EURI) was documented prospectively by a home interview at 1 month of age (median age 5.1 wk). Sensitization to ryegrass and house dust mite (HDM) was determined at 8 yr of age by skin prick testing and at 16 yr by ImmunoCap^®. Ryegrass sensitized hay fever was defined as a positive response to a question on hay fever plus the presence of ryegrass allergy. For children tested at age 8 and born in the pollen season, a EURI by postnatal interview was associated with an increased risk of ryegrass sensitization (OR 5.80 95% CI 1.07, 31.31) but not for children with a EURI born outside the pollen season (OR 0.62 95% CI 0.35, 1.08). Similarly, EURI was significantly associated with early onset (≤8 yr) ryegrass sensitized hay fever for children born in the pollen season (AOR 4.78 95% CI 1.17, 19.47) but was not associated with early onset ryegrass sensitized hay fever for children born outside the pollen season (AOR 0.76 95% CI 0.43, 1.33). These findings suggest that early life viral URI interacts with ryegrass allergen exposure in the development of ryegrass allergen sensitization and ryegrass sensitized hay fever symptoms.     

Neonatal hyperbilirubinemia and childhood allergic diseases: a systematic review

Studies have found a link between neonatal hyperbilirubinemia (NNH) and/or neonatal phototherapy (NPT) and childhood allergic diseases. The present systematic review was conducted to provide updated evidence and to provide direction regarding future research. A systematic search of the published literature was carried out. Observational studies including children up to 12 yr of age were included. Data extraction was carried out using a standardized data extraction form that was designed and pilot tested a priori. The analysis was carried out with the statistical software RevMan (version 5.2) [Protocol is registered at PROSPERO: CRD42014009943]. Of 79 citations retrieved, a total of 7 good quality studies (n = 101,499) were included in the final analysis. There was a significant increase in the odds of asthma and allergic rhinitis (AR) after NNH [asthma, OR 4.26 (95% CI 4.04–4.5); AR, OR 5.37 (95% CI 4.16–6.92)] and after NPT [asthma, OR 3.81 (95% CI 3.53–4.11); AR, OR 3.04(95% CI 2.13–4.32)]. A similar increase in the trend was noted for late onset of asthma after NNH [OR 4.1 (95% CI 2.82–5.94)], and hospitalization due to asthma after NPT [OR 3.56 (95% CI 2.93–4.33)]. The GRADE evidence generated was of ‘low quality’. The current evidence finds a significant increase in the odds of childhood allergic diseases after NNH and/or NPT. As observational studies were included, the evidence generated was of ‘low quality’. Future studies should try to elucidate the pathophysiologic link between NNH and/or NPT and childhood allergic diseases.     

Prevalence and Clinical Significance of Antithyroid Antibodies in Children with Immune Thrombocytopenic Purpura

Background and objective: To determine the prevalence and the clinical significance of thyroid autoantibodies and their influence on treatment response in children with idiopathic thrombocytopenic purpura (ITP). Patient and Method: We retrospectively analyzed the antithyroglobulin (anti-TG) and antithyroid peroxidase (anti-TPO) antibodies from the records of 151 ITP patients who were admitted to the Pediatric Hematology Department of Gaziantep University between 2009 and 2012. Results: Anti-TPO and/or anti-TG was found positive in 38 (36.8%) of 103 patients whose thyroid autoantibody levels were measured. The comparison of positivity ratios of autoantibodies between acute and chronic ITP patients showed no significant difference. However, the separate comparison of each group of ITP patients with control group showed significantly high positivity ratios of autoantibodies in ITP patients. The initial mean platelet count of anti-TPO positive patients at diagnosis was significantly less than that of the negative patients (P = .008). One month after treatment, platelet count of anti-TPO positive patients was significantly less than that of the negative patients (P = .01). Moreover, the mean platelet counts of anti-TPO positive patients were significantly less than those of the negative patients after intravenous immunoglobulin treatment (P < .001). Conclusion: We demonstrated that the thyroid-autoimmune-diseases-related autoantibodies are frequently found in childhood ITP. Although no recommendation is found in international guidelines regarding screening for thyroid autoantibodies in patients with ITP, in view of the high incidence of antithyroid antibodies and their potential negative effect on treatment response, screening these patients for such antibodies would be recommended.     

Pathology of Suspected Acquired Immune Deficiency Syndrome in Children: A Study of Eight Cases

Biopsy and/or autopsy material from lymphoreticular and other organs was studied in 8 children with suspected acquired immune deficiency syndrome (AIDS). One or both parents of each of these children had one or more of the recognized risk factors for AIDS, such as intravenous drug abuse, prostitution, Haitian origin. The following histologic patterns were noted in the lymph nodes: (1) follicular hyperplasia with normocellular paracortex, (2) follicular hyperplasia with depletion of paracortex, and (3) atrophy of follicles with depletion of paracortex. Lymphoid interstitial pneumonitis (LIP), a previously unreported lesion in AIDS, was present in 4 cases. It is suggested that the pulmonary lymphoid lesion may be part of a more generalized lymphoid hyperplasia involving B cells. The gross and microscopic features of the thymus, available in 2 of the 8 cases, indicated that the immunologic defect in these children was not of congenital type. Pathologic findings can be helpful in the diagnosis of the syndrome when correlated with clinical and immunologic features of suspected cases and of the pulmonary lesion. The latter is of importance in deciding the type of therapy to be given for the pulmonary disease process.     

Cow's milk protein intolerance in infants under 1 year of age: A prospective epidemiological study

Incidence and clinical manifestation of cow's milk protein intolerance (CMPI) were studied in 1158 unselected newborn infants followed prospectively from birth to 1 year of age. No food changes were required in 914 infants who were used as healthy controls. When CMPI was suspected (211 infants), diagnostic dietary interventions according to a standard protocol were performed. After exclusion of lactose intolerance, two positive cow's milk elimination/challenge tests were considered diagnostic of CMPI. Two hundred and eleven symptomatic infants were examined for possible CMPI. A large group of 80 infants improved on a lactose reduced formula. In 87/211 infants CMPI was excluded (sick controls). Finally CMPI was proven in 26 infants. The calculated incidence rate for CMPI was 2.8%. The principal symptoms in infants with CMPI were gastrointestinal, dermatological and respiratory in 50%, 31% and 19% respectively. A positive family history for atopy (first or second degree relatives) was more frequent in either CMPI infants (65%), or sick controls (63%) when compared to either healthy controls (35%) or infants improving on a low lactose formula (51%). Differences between patients with CMPI and sick controls were only found for the presence of atopy in at least 2 first degree relatives [(5/26 in CMPI infants and 4/87 in sick controls (P<0.05)] and for multiorgan involvement [10/26 infants with CMPI as opposed to 12/87 in the sick control group (P<0.02)]. These statistical differences are too weak to be of clinical value.     

Atopy, home environment and the risk of childhood-onset type 1 diabetes: a population-based case–control study

Background:  The marked increases in the incidence of type 1 diabetes in recent decades strongly suggest the role of environmental influences. These environmental influences remain largely unknown.
Objective:  To investigate atopy and home environment (such as children living at home, sharing a bedroom and house moves) as potential risk factors for type 1 diabetes.
Subjects and method:  In Northern Ireland, 175 children with type 1 diabetes and 4859 control children completed a questionnaire on atopy experience, family composition and home environment. Control children from two age groups (6–8 yr old and 13–14 yr old) were identified from randomly selected primary and secondary schools across Northern Ireland. Cases were identified from a population-based type 1 diabetes register.
Results:  There was little evidence of a difference in the proportion of participants with a history of atopy in the cases compared with controls. There was a significant reduction in the risk of diabetes in children who lived with more siblings {odds ratio (OR) = 0.58 [95% confidence interval (95% CI) 0.39–0.85] in children who lived with three or more siblings compared with one or none} and in children who moved house more often [OR = 0.59 (95% CI 0.40–0.88) in children who moved house twice or more compared with never].
Conclusion:  The reduced risk of type 1 diabetes in children living with siblings, sharing a bedroom and moving house more often could reflect the protection afforded by exposure to infections in early life and consequently may provide support for the hygiene hypothesis.     

Prolonged honeymoon phase in an adolescent with diabetes and thyrotoxicosis provides support for the accelerator hypothesis

Abstract:  A 14-yr-old female presented with diabetes and Graves' disease. Eighteen months later, she was euthyroid on carbimazole, and her haemoglobin A1c (HbA1c) was normal (5.2%) on a small insulin dose (0.3–0.4 units/kg/day). An assessment of her pancreatic beta-cell reserve, determined by comparing HbA1c and insulin dose, suggested that this was greater than other patients with type 1 diabetes in our service 18 months postdiagnosis (n = 185). We suspect that excess thyroid hormone led to an insulin-resistant state and accelerated her presentation with hyperglycaemia. Insulin resistance fell once normal thyroid function was restored and helped to attenuate further beta-cell destruction when beta-cell mass was relatively well preserved.     

Evaluation and Treatment of Children with Primary Immune Deficiency in the Emergency Department

The potential for morbidity and mortality in patients who have PID with febrile and nonfebrile illness is extremely high. Familiarity with the clinical manifestations of PID and collaboration with a pediatric immunologist are prerequisites for optimal short-term care of these complex patients. Conservative management with empiric broad-spectrum antimicrobials, early and aggressive surgical debridement of abscesses, and admission at a tertiary pediatric care center are often indicated.     

Dysfunctional schemas and cognitive distortions in psychopathology: a test of the specificity hypothesis

This study aimed at testing whether there were different types of dysfunctional schemas and cognitive distortions that could help to differentiate three emotional/behavioural problems, i.e., anxiety, depression, and aggression, from each other. Five hundred and eighty-one Chinese adolescents from five mainstream high schools in Hong Kong were recruited and completed several self-report questionnaires. Bivariate correlation showed an indiscriminate pattern of association between dysfunctional schemas, cognitive distortions, and the three emotional/behavioural problems. However, when the effects of the confounding correlated emotional/behavioural problems were controlled in regression analysis, different problems did show some specific association with different types of dysfunctional schemas and/or cognitive distortions. Despite some inconsistency, these findings generally supported a specificity hypothesis. Cognitive variables were thus not only relevant in understanding psychopathology, but their different patterns of association with anxiety, depression, and aggression also supported the separability of these three emotional/behavioural problems, despite their significant correlation.