Childhood Viral Infections Research Articles

Immune responses to viral infections: Relevance for asthma

Severe respiratory viral infections in childhood are associated with the development of asthma later in life. Rhinovirus, respiratory syncytial virus and metapneumovirus are of particular importance as triggers of asthma. Effects of virus infection on dendritic cell function in the airways may predispose children to allergic sensitization. Asthmatic subjects may have impaired interferon responses to viral infection that also predispose to allergic sensitization. Difference in Toll-like receptor expression on airway epithelial cells is a potential mechanism for the altered immune responses of asthmatic children.

Acute osteomyelitis as a complication of varicella

Varicella is a common viral infection in childhood, and acute osteomyelitis is one of the rare but serious complications. We report two cases of osteomyelitis as a complication of varicella. The possibilities and limitations of the different imaging modalities are discussed, as well as imaging findings during the course of this condition.

Worms, germs and IBD: Is it your mother’s fault?

Worms, germs and IBD: Is it your mother’s fault?

Bronchite récidivante de l'enfant : voyage au bout de l'allergène

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease especially in anatomic features and in disease severity. The only proven genetic factor so far identified in its pathogenesis is alpha1-antitrypsin deficiency, although this accounts for less than 1% of individuals with COPD. Exposure to deleterious environmental factors is equally significant but only 15% of smokers develop COPD. The prevalence of COPD is increased in industrialized countries and, as with asthma, this suggests a genetic influence with modification of phenotype expression secondary to interaction between genetic and environmental factors. The childhood origin of adult COPD is supported by a number of epidemiologic studies. This hypothesis is based on: (1) an increased prevalence of asthma, especially in children and young adults; (2) persistence of infantile asthma into adolescence and adulthood; (3) the risk of progression of childhood viral respiratory infections to COPD; and (4) familial transmission of a functional phenotype of certain forms of adult COPD.

Childhood Infections as Risk Factors for Multiple Sclerosis: Belgrade Case-Control Study

The aim of this case-control study was to analyze the role of childhood infections and vaccinations in patients with MS in the Belgrade population. The study group comprised 110 cases with definite MS according to Poser’s criteria, in whom onset symptoms occurred up to 2 years prior to the interview. An equal number of controls, individually matched by sex, age and area of residence, was recruited from patients with various nonautoimmune neurological disorders. Measles (OR = 2.6, 95%CI 1.4–5.0), chickenpox (OR = 3.0, 95%CI 1.5–6.0), rubella (OR = 2.4, 95%CI 1.2–4.7), whooping cough (OR = 1.9, 95%CI 0.8–4.4), and mumps (OR = 1.8, 95%CI 0.8–4.5), at age ≤7 years, were more frequently reported by MS cases. The total number of childhood viral infections (including measles, rubella, chickenpox, and mumps) at age ≤7 years was significantly higher in MS cases than in controls (OR = 1.8, 95%CI 1.4–2.5). Concerning vaccinations, no statistically significant differences were found between groups. According to multivariate analysis, rubella (OR = 2.5, 95%CI 1.4–4.4, p = 0.001) and measles (OR = 2.4, 95%CI 1.3–4.3, p = 0.003) at age ≤7 years were significantly related to MS.

Introducción

Asthma is the most frequent chronic disease in childhood. Its prevalence varies (in Spain between 12 % in coastal regions and 6 % in the Castilian plateau). Asthma represents chronic inflammation of the airways associated with an increase in bronchial reactivity to various stimuli, leading to reduced air flow and subsequent remodeling of the bronchial wall. Asthma usually begins in the first few years of life and 30 % of patients will continue to be asthmatic throughout their lives. The main characteristic associated with the persistence of asthma in adulthood seems to be allergy. Another risk factor is the presence of bronchial hyperreactivity. Wheezing associated with viral infections in childhood shows a favorable outcome when not associated with atopic features. The atopic disposition is caused by the interaction between genetic and distinct environmental factors (allergens), as well as by the various clinical manifestations that favor a mainly Th2 response, with interleukins that lead to the formation of specific IgE, pro-inflammatory cytokines, bronchial hyperreactivity, etc. In most cases, asthma is mainly an allergic process, mediated by an IgE mechanism. Inhalation of allergens is considered the most important cause of the onset of asthma in predisposed children. First the presence of an allergen gives rise to sensitization, with the formation of specific IgE. In a subsequent contact, mediators are released, with inflammatory response of the airways and an increase in bronchial hyperreactivity. If the presence of the allergen is prolonged, inflammation and subsequent healing may lead to irreversible damage to the bronchial wall and permanent deterioration of respiratory function. In children with asthma, the aim is to modify the natural history of the disease and prevent its persistence in adulthood. This involves identifying the allergen or allergens causing the symptoms, confirming the role of these allergens in clinical manifestations through specific challenge tests and, lastly, indicating the treatment be followed.

A laboratory-based introduction to seroepidemiology and its use in vaccination programme design

The development of vaccination programmes relies on an understanding of the epidemiology and transmission dynamics of the pathogen. Whilst these concepts could be delivered using the traditional lecture format, a practical workshop approach would encourage deeper understanding and appreciation. However, an authentic laboratory-based seroepidemiological study using human and pathogen material would be costly, logistically complicated and raise ethical issues. The workshop presented here uses a cheap and safe model of an infectious disease immuno assay alongside spreadsheet analysis as a tool for introducing aspects of infectious disease epidemiology, and some theoretical concepts used in mass immunisation programme design. It isdesigned to represent a typical directly-transmitted childhood viral infection (e.g. measles) within a community prior to mass immunisation. Results can be discussed through comparison with a hypothetical data set and interms of herd immunity, endemicity and the type of transmission as well as average age at infection, the basic reproduction number (Ro) and other parameters of importance to vaccination programme design.

Viral infections and childhood asthma.

Formulating hypotheses on the pathogenetic links between viral infection in childhood and asthma requires an undisputed definition of asthma. Unfortunately, many wheezing syndromes have been recognized in the pediatric age group, which are the subject of a vivid controversy on the exact terminology. Leaving a detailed definition of childhood asthma aside, at least four different wheezing syndrome have been associated with viral infections: ( 1 ) wheezing-associated respiratory infections in infancy and early childhood, ( 2 ) asthma attacks associated with or elicited by viral upper respiratory tract infections in older children, ( 3 ) recurrent wheezing episodes after viral bronchiolitis, and ( 4 ) atopic asthma. There is no doubt that some overlap exists between these various wheezing syndromes. Epidemiological observations have stimulated the study of possible pathogenetic mechanisms underlying the relation between viral respiratory tract infections and these wheezing syndromes.

Mechanisms and advances in allergic diseases

There have been many attempts to explain the increases in the incidence of allergic diseases, including hay fever and allergic asthma, that have been documented worldwide in recent decades. Epidemiologic studies offer rich opportunities to uncover sometimes unexpected correlations between lifestyle, environmental exposures, temporal development of the immune system, and genetics. Examples include the differing prevalence of atopy, bronchial hyperresponsiveness, and asthma in East and West Germany around the time of reunification, which suggests that a ″western” lifestyle presents a greater risk for the development of allergic responses than the more traditionally suspected factor of outdoor air pollutant levels. Other epidemiologic studies suggest how infections may interface with an atopic patterning: Evidence from natural measles exposure and nonwheeze-inducing lower respiratory tract infections in young children implicate early childhood viral infections as protective against the development of atopy and airway allergic sensitivity, although in later life viral airway infections exacerbate asthma symptoms. These studies and others involving the scrutiny of lymphocyte subtypes in atopic individuals, notably TH1 and TH2 cells, are helping to formulate a theory of interdependence between the early development of the immune system, allergen exposure, and the diverse community of airway cells whose secretory products generate the final physiologic response pattern. (J Allergy Clin Immunol 2000;105:S593-8.)

Mechanisms and advances in allergic diseases

<h2>Abstract</h2> There have been many attempts to explain the increases in the incidence of allergic diseases, including hay fever and allergic asthma, that have been documented worldwide in recent decades. Epidemiologic studies offer rich opportunities to uncover sometimes unexpected correlations between lifestyle, environmental exposures, temporal development of the immune system, and genetics. Examples include the differing prevalence of atopy, bronchial hyperresponsiveness, and asthma in East and West Germany around the time of reunification, which suggests that a ″western" lifestyle presents a greater risk for the development of allergic responses than the more traditionally suspected factor of outdoor air pollutant levels. Other epidemiologic studies suggest how infections may interface with an atopic patterning: Evidence from natural measles exposure and nonwheeze-inducing lower respiratory tract infections in young children implicate early childhood viral infections as protective against the development of atopy and airway allergic sensitivity, although in later life viral airway infections exacerbate asthma symptoms. These studies and others involving the scrutiny of lymphocyte subtypes in atopic individuals, notably T_H1 and T_H2 cells, are helping to formulate a theory of interdependence between the early development of the immune system, allergen exposure, and the diverse community of airway cells whose secretory products generate the final physiologic response pattern. (J Allergy Clin Immunol 2000;105:S593-8.)

Childhood viral infection and the pathogenesis of asthma and chronic obstructive lung disease.

Many epidemiologic studies have implicated childhood respiratory infections as an independent risk factor for the subsequent development of persistent asthma and chronic obstructive pulmonary disease (COPD). The majority of these childhood infections are viral in origin, and great strides are being made in understanding their pathogenesis at the molecular level. Some viruses, such as respiratory syncytial virus-a common cause of childhood bronchiolitis-stimulate the helper T cell type 2 (Th2) pattern of immune responses associated with allergic inflammation. Other viruses, such as adenovirus, appear to persist as latent infections in the airways of patients with COPD, and adenoviral E1A protein is capable of amplifying host genes, possibly including those involved in cigarette smoke-induced lung inflammation. Studies of the chronic, low-grade peripheral lung inflammation caused by adenoviral infection of guinea pigs will enable examination of the possibility that latent infection may induce resistance to the antiinflammatory actions of corticosteroids. Studies of the molecular mechanisms of viral infections of the airways could provide important insights into the nature of the inflammatory process involved in asthma and COPD. Hogg JC. Childhood viral infection and the pathogenesis of asthma and chronic obstructive lung disease.

Bronchiectasis: accuracy of high-resolution CT in the differentiation of specific diseases.

The aim of the study was to determine whether various causes of bronchiectasis can be differentiated by the pattern and distribution of abnormalities seen on high-resolution CT. The retrospective study included 82 consecutive patients who had a specific diagnosis of bronchiectasis proven by appropriate clinical and laboratory criteria. All patients underwent high-resolution CT scanning (1- to 1.5-mm collimation). The CT scans were assessed for the presence, extent, type, and anatomic distribution of bronchiectasis by two independent observers who were not aware of the clinical data. The observers recorded their most likely diagnosis and the degree of confidence in that diagnosis. The two independent observers made a correct diagnosis in 61% of cases (100/164 interpretations). On average, a correct diagnosis was made in 19 (68%) of 28 cases of cystic fibrosis, 16 (67%) of 24 cases of previous tuberculosis, six (43%) of 14 cases of previous childhood infection, five (56%) of nine cases of allergic bronchopulmonary aspergillosis, and four (57%) of seven cases of other causes of bronchiectasis. We found moderate agreement between the observers for the correct diagnosis (kappa = .53) and good agreement for the presence or absence of bronchiectasis in each lobe (kappa = .71). The pattern and distribution of abnormalities revealed by high-resolution CT in patients with bronchiectasis are influenced by the underlying cause. Bilateral, predominantly upper lobe, bronchiectasis is seen most commonly in patients with cystic fibrosis and allergic bronchopulmonary aspergillosis, unilateral upper lobe predominance in patients with tuberculosis, and lower lobe predominance in patients after childhood viral infection.

Directly transmitted infections modeling considering an age-structured contact rate

Mathematical models dealing with childhood viral infections consider the spread of disease according to the law of mass action. This law states that there are random encounters (or contacts) among susceptible and infectious individuals. Therefore, mathematical descriptions of the transmission of infections are heavily dependent on the assumptions concerning the contact rate. In order to develop an age-structured contact rate model, a pattern of contacts among individuals in a community is developed by stochastic processes.

Beclomethasone of little benefit in childhood viral infections

Beclomethasone of little benefit in childhood viral infections

Influence of the Pineal Gland on the Expression of Experimental Allergic Encephalomyelitis: Possible Relationship to the Aquisition of Multiple Sclerosis

Experimental allergic encephalomyelitis (EAE), a T-cell mediated autoimmune disease, is widely considered as an animal model of multiple sclerosis (MS). It is believed that breakdown of the blood brain barrier (BBB) reflects the initial mechanism in the induction of EAE. It has been reported that while neonatally pinealectomized Wistar rats develop extensive pathological changes and severe neurologic deficits upon induction of EAE with allogeneic spinal cord in adjuvant, adult rats pinealectomized at 6 weeks of age appeared resistant to the induction of EAE. These findings suggest that: (a) the pineal gland influences the expression of EAE and, by inference, the integrity of the BBB; and (b) there is an age-related window of susceptibility to the development of EAE possibly related to the level of maturation of the pineal gland and functional integrity of the BBB. This age-related susceptibility to the development of EAE in rats may be relevant to the timing of aquision of MS where a viral infection in childhood is thought to initiate the induction of autosensitization to myelin antigens. More specifically, it is suggested that the viral infection associated with the development of MS most likely is acquired in infancy prior to the establishment of the melatonin circadian rhythms between 3 and 9 months of age.

The transmission dynamics and control of hepatitis B virus in The Gambia.

A deterministic, compartmental, mathematical model is used to describe the transmission dynamics of hepatitis B virus (HBV) in a high endemicity country. All three major transmission routes are included in the model, that is, perinatal, horizontal and sexual transmission. The model also reflects the demography of a typical developing country, and incorporates age-dependence in the rates of transmission and the probability of becoming a chronic carrier. Numerical simulations of the model are shown to capture the observed age-specific patterns of serological markers. The sensitivity of the model to age-specific heterogeneities and routes of transmission is investigated. The model is used in a preliminary study of the possible implications of mass infant immunization on HBV epidemiology, and the results suggest that eradication of HBV may be achieved by immunizing less than 70 per cent infants, which is relatively low compared to most childhood viral infections. This is due in part to the interaction between changes to the average age at infection under immunization, and the nature of age-dependence in the force of infection and the probability of becoming a carrier. However, numerical results also suggest that eradication may take many decades to be achieved, largely due to the presence of a pool of chronic carriers. Furthermore, there may be a significant lag between the implementation of mass infant immunization and a decline in the incidence of liver cancer.

Allergic and Immunologic Aspects of Meniere's Disease

Meniere's disease, although idiopathic by definition, has been ascribed to a variety of causes, which more recently include autoimmune factors. Interest in the role of allergy in Meniere's disease has also increased. Studies from this institution and elsewhere provide evidence that allergy and immunologic factors play a role in Meniere's disease in at least some patients. The symptoms of Meniere's disease are thought to be produced by a sudden influx of fluid into the endolymphatic sac, producing a rupture of Reissner's membrane in the cochlea. The endolymphatic sac is capable of trapping antigen and generating its own immune response. It has a highly vascular subepithelial space containing numerous fenestrated blood vessels that are peripheral and "leaky." At least three mechanisms by which allergy may play a role in the production of fluid in the endolymphatic sac are described: the endolymphatic sac itself might be a "target organ" of mediator released from systemic inhalant or food reactions; deposition of circulating immune complex may produce inflammation and interfere with the sac's filtering capability; and a predisposing viral infection in childhood that produces a mild impairment of endolymphatic sac function may interact with allergies in adulthood and cause the endolymphatic sac to decompensate, resulting in endolymphatic hydrops. The endolymphatic sac is the seat of immune reactivity in the inner ear. Repeated inflammatory reactions can produce sac dysfunction and eventual production of Meniere's disease.

Allergic and immunologic aspects of Meniere's disease

Meniere's disease, although idiopathic by definition, has been ascribed to a variety of causes, which more recently include autoimmune factors. Interest in the role of allergy in Meniere's disease has also increased. Studies from this institution and elsewhere provide evidence that allergy and immunologic factors play a role in Meniere's disease in at least some patients. The symptoms of Meniere's disease are thought to be produced by a sudden influx of fluid into the endolymphatic sac, producing a rupture of Reissner's membrane in the cochlea. The endolymphatic sac is capable of trapping antigen and generating its own immune response. It has a highly vascular subepithelial space containing numerous fenestrated blood vessels that are peripheral and “leaky.” At least three mechanisms by which allergy may play a role in the production of fluid in the endolymphatic sac are described: the endolymphatic sac itself might be a “target organ” of mediator released from systemic inhalant or food reactions; deposition of circulating immune complex may produce inflammation and interfere with the sac's filtering capability; and a predisposing viral infection in childhood that produces a mild impairment of endolymphatic sac function may interact with allergies in adulthood and cause the endolymphatic sac to decompensate, resulting in endolymphatic hydrops. The endolymphatic sac is the seat of immune reactivity in the inner ear. Repeated inflammatory reactions can produce sac dysfunction and eventual production of Meniere's disease. (Otolaryngol Head Neck Surg 1996;114:360-5.)

Towards eradication of measles virus: global progress and strategy evaluation

Despite an increase in global measles vaccine coverage from under 20% in 1980 to around 80% in 1990, measles remains a major cause of morbidity and mortality world-wide. This paper addresses a number of issues relating to efforts to control measles, namely, (i) at the global level, how might we assess the impact of measles vaccination on the incidence of infection and associated disease, and, (ii), at the strategic level, how can we utilise an understanding of the transmission dynamics of childhood viral infections to aid the design of optimal immunisation programmes? Based on WHO vaccine coverage data, and organising countries according to similarities in demographic and epidemiological parameters, an age-structured model of measles transmission is used to capture the non-linear dynamics of infection and mass vaccination and to generate projections of the impact of measles immunization world-wide. The results provide a crude indication of the percentage reduction in measles cases by year 2000 (compared with no immunization) and suggest an approximately 70% reduction in cases over all ages, and 77% reduction in cases under 5 years (where there is the greatest risk of case fatality); these suggest that WHO targets for 1995 are unlikely to be achieved. In the second part of the paper, examples are given to illustrate the usefulness of a modelling approach in evaluating measles immunization policy. The introduction of MMR vaccine in the UK in 1988 has resulted in measles incidence falling to an all time low and attention has turned to the requirements of elimination. A realistic age structured model, validated using extensive serological data, is used to compare the merits of single or two dose strategies. Based upon recent estimates of vaccine efficacy (90%) and coverage (92% by end of second year of life) it is suggested that a two-dose policy with a pre-school second dose given irrespective of vaccine history is required to prevent the build up of susceptibles to epidemic proportions in the longer term. In a second example, prompted by the success of the campaign approach to polio and measles elimination in Central and South America, simple models are used to explore and quantify the process by which pulse vaccination programmes (i.e. repeated application across a wide age range) act to control transmission.

The control of childhood viral infections by pulse vaccination.

Pulse vaccination, the repeated application of vaccine over a defined age range, is gaining prominence as a strategy for the elimination of childhood viral infections such as measles and polio. However, unlike routine or continuous mass infant immunization, epidemiological understanding of this control method is in its infancy. This paper develops initial work by Agur et al. (1993) using simple steady-state and age-structured dynamic models to extend the theory of the mechanism of action of pulse vaccination, and to explore the relationship between the maximum permitted interval between pulses and key epidemiological, demographic and vaccination variables. Initially, a conceptual model is presented to illustrate the principles of pulse vaccination and to make comparison with routine immunization procedures. An ordinary differential equation model, which assumes homogeneous mixing, is then used to derive equilibrium expressions for the pulse interval in relation to (i) different demographic profiles, (ii) population growth characteristics (stationary or exponentially increasing), (iii) combined routine and pulse immunization, and (iv) the age range vaccinated. Finally, simulations using age-structured compartmental deterministic models illustrate complex epidemiological dynamics associated with pulse vaccination, particularly where there is age heterogeneity in contact rates in the population. The resultant uncertainty in defining an optimal pulse interval raises concerns of a practical nature.