Susceptible Infants Research Articles

Bacteroides dorei dominates gut microbiome prior to autoimmunity in Finnish children at high risk for type 1 diabetes.

The incidence of the autoimmune disease, type 1 diabetes (T1D), has increased dramatically over the last half century in many developed countries and is particularly high in Finland and other Nordic countries. Along with genetic predisposition, environmental factors are thought to play a critical role in this increase. As with other autoimmune diseases, the gut microbiome is thought to play a potential role in controlling progression to T1D in children with high genetic risk, but we know little about how the gut microbiome develops in children with high genetic risk for T1D. In this study, the early development of the gut microbiomes of 76 children at high genetic risk for T1D was determined using high-throughput 16S rRNA gene sequencing. Stool samples from children born in the same hospital in Turku, Finland were collected at monthly intervals beginning at 4–6 months after birth until 2.2 years of age. Of those 76 children, 29 seroconverted to T1D-related autoimmunity (cases) including 22 who later developed T1D, the remaining 47 subjects remained healthy (controls). While several significant compositional differences in low abundant species prior to seroconversion were found, one highly abundant group composed of two closely related species, Bacteroides dorei and Bacteroides vulgatus, was significantly higher in cases compared to controls prior to seroconversion. Metagenomic sequencing of samples high in the abundance of the B. dorei/vulgatus group before seroconversion, as well as longer 16S rRNA sequencing identified this group as Bacteroides dorei. The abundance of B. dorei peaked at 7.6 months in cases, over 8 months prior to the appearance of the first islet autoantibody, suggesting that early changes in the microbiome may be useful for predicting T1D autoimmunity in genetically susceptible infants. The cause of increased B. dorei abundance in cases is not known but its timing appears to coincide with the introduction of solid food.

What predicts postpartum pertussis booster vaccination? A controlled intervention trial

Background‘Cocooning’ aims to protect susceptible infants from pertussis via caregiver vaccination. Control trials evaluating educational interventions to promote cocooning are lacking. We evaluated the role of message-framing vs. standard health information in promoting pertussis vaccination. MethodsWe recruited postpartum women from a maternity hospital in Sydney, Australia (November 2010–July 2012). Participants self-completed a pertussis knowledge and attitudes questionnaire. We then assigned pertussis-susceptible (no pertussis vaccine ≤10 years) participants to receive a gain-framed, loss-framed pamphlet or control (Government Pertussis factsheet) using weekly sequential block allocation. Next, participants were offered a pertussis vaccine (dTpa) and completed a post-questionnaire on discharge. ResultsA baseline questionnaire was completed for 96.4% (1433/1486) of postpartum women approached. Missing data was excluded (n=29). Next, participants (1404) were screened for vaccine status: 324 (23%) reported prior pertussis booster vaccine receipt, leaving 1080 participants requiring vaccination. Among susceptible mothers, 70% (754/1080) were vaccinated post-intervention. Rates were similar between ‘gain’, ‘loss’ or ‘control’ pamphlets (69.1% vs. 71.8% vs. 68.8%; p=0.62). Intention to be vaccinated (OR 2.46, p<0.001; 95% CI: 1.69–3.58), perceived vaccine benefits (OR: 1.61, p<0.001; 95% CI: 1.25–2.15) and having received a vaccine recommendation (OR 1.68; p=0.025; 95% CI: 1.07–2.65) were independent predictors of vaccine uptake. At discharge, overall pertussis vaccine coverage had increased from 23% to 77% among women screened (1078/1404). ConclusionA cocooning strategy for pertussis vaccination can be highly effective when partially implemented within maternity hospitals, with information accompanied by a funded vaccine. Mothers were highly receptive to vaccination in the postnatal ward: facts about pertussis were as effective as message-framing in promoting a high uptake of 70%. Perceived vaccine benefits, intentions and vaccine recommendation were important predictors of uptake. Our intervention trial increased the existing pertussis vaccine coverage of 23–77%.

The burden of single virus and viral coinfections on severe lower respiratory tract infections among preterm infants: a prospective birth cohort study in Brazil.

Respiratory syncytial virus (RSV) is associated with severe lower respiratory tract infection (LRTI), especially in preterm infants. Other viruses, co-detected with RSV, may play a role in the severity of respiratory outcomes. This prospective epidemiologic study of severe LRTI incidence among children born ≤35 weeks gestational age at 3 sites in Brazil (2008-2010) followed a birth cohort for 1 year post-enrollment. Nasal washes from subjects with LRTI were tested for respiratory viruses using polymerase chain reaction. The primary outcome was the incidence of severe LRTI requiring hospitalization associated with RSV infection. Secondary outcomes included identification of viruses associated with LRTI, alone or coinfections, and risk factors associated with severe LRTI. Among 303 subjects, 176 (58.1%) experienced LRTI. Among these subjects, 162 had samples tested using polymerase chain reaction; 27.8% (45/162) experienced severe LRTI. More subjects with severe LRTI were infected with RSV (30/45, 66.7%) than with other viruses. RSV was present in 33.1% (143/432) of LRTI events tested, 57.3% (82/143) were coinfections. RSV was the virus most frequently associated with severe LRTIs (34/56 events, 60.7%); 50% (17/34 events) single and 50% coinfections. Significantly longer hospital stays were associated with LRTI events involving RSV coinfections compared with RSV single infections (P = 0.012). Infants with severe LRTIs had significantly lower mean RSV-IgG levels at study entry compared with those with nonsevere or no LRTIs (P < 0.05). This study confirms the association of RSV alone or as a coinfection with severe LRTI and reinforces the importance of providing adequate prophylaxis for susceptible infants.

Using the Health Belief Model to develop educational strategies to improve pertussis vaccination rates among preschool staff.

The number of pertussis or "whooping cough" cases has steadily increased in the United States in the last 20 years. Many of the cases are adults who have not kept up with current vaccination recommendations. Adults are unknowingly exposing susceptible infants and unvaccinated children to this potentially deadly disease. Pertussis can spread rapidly, especially in household, daycare, and school settings. This pilot study examines how school nurses can be instrumental in improving staff immunization rates for pertussis by using the Health Belief Model as a framework for educational strategies.

Cerebral tissue oxygenation index and SIDS.

* Abbreviations: SIDS — : sudden infant death syndrome SUID — : sudden unexpected infant death TOI — : tissue oxygenation index In this issue of Pediatrics , Fyfe et al present convincing evidence that cerebral tissue oxygenation index (TOI) is lower in habitually supine-sleeping preterm infants placed prone rather than supine, and that the cerebral TOI for preterm infants placed prone is lower than the TOI for term infants placed prone. Increased rates of sudden infant death syndrome (SIDS) among all infants sleeping prone, and even higher rates among preterm infants placed prone, provide the epidemiologic rationale for their physiologic studies.1,2 An established approach in attempting to understand sudden unexpected infant deaths (SUID), including SIDS, is the Triple Risk Model: a susceptible infant at a susceptible developmental stage is exposed to a stressor that cannot be overcome.3 The susceptible infants investigated by Fyfe et al were born before term and were studied at 2 to 4 weeks, 2 to 3 months, and 5 to 6 months post-term age, and compared with a group of infants born at term. Much recent study of SUID has focused on the interaction between sleep position and sleep microenvironment. This group from Australia has carried the torch in trying … Address correspondence to James S. Kemp, MD, St Louis Children’s Hospital, 1 Children’s Place, St Louis, MO 63130. E-mail: kemp_j{at}kids.wustl.edu

Pertussis resurgence in a highly vaccinated population, Mazandaran, North of Iran 2008-2011: an epidemiological analysis.

To describe the epidemiological characteristics of pertussis cases reported to Mazandaran Center for Diseases Control and Prevention (P-CDC) during the years 2008-2011 in Mazandaran, North of Iran. The patients included were those who fulfilled the WHO definition for pertussis or those clinically diagnosed by physicians. The demographic features of cases, their vaccination status, the incidence rate per 100,000 population, the relative proportion of cases for each age group, and their relation to vaccination status of the patients were all determined. During the study period, a total of 518 cases of pertussis were reported; of which 43 were confirmed. The highest incidence rate and the largest proportion were 135.5 cases/100,000 and 37.7%, respectively, observed in infants <12mo of age. Almost 35.7% of the cases were under vaccinated, however 54.4% of them were fully vaccinated. Pertussis infection has re-emerged in Mazandaran. It has caused a significant health problem in the susceptible young infants, and also among completely vaccinated children. Implementing strategies to protect these vulnerable infants and studies to evaluate the immunogenicity and efficacy of pertussis vaccine in Iran is recommended. It was difficult to confirm pertussis in the majority of cases, therefore, providing and improving laboratory diagnostic methods seems to be an urgent requirement.

Tissue factor inflammatory response regulated by promoter genotype and p38 MAPK in neonatal vs. adult microvascular endothelial cells

Variable tissue factor (TF) expression by human microvascular endothelial cells (HMVEC) may be regulated by two promoter haplotypes, distinguished by an 18-basepair deletion (D) or insertion (I) at -1,208. We sought to determine the relationship between these haplotypes and interleukin-1α (IL-1α)-induced TF expression in neonatal versus adult HMVEC. IL-1-stimulated TF mRNA, protein, and activity were significantly higher in neonatal compared to adult D/D donors. IL-1-stimulated HMVEC from neonatal D/D donors expressed threefold higher levels of TF mRNA, twofold higher TF protein, and fourfold increased TF activity compared to HMVEC from adult D/D donors. These results indicate that homozygosity for the D haplotype is characterized by increased response to IL-1 in neonates, but not adults. IL-1 induced increased phosphorylation of p38 mitogen-activated protein kinase (MAPK), which was significantly greater in neonatal compared to adult HMVEC. Moreover, inhibition of the p38 MAPK pathway reduced IL-1-stimulated TF mRNA expression in D/D neonatal but not adult HMVEC. Upregulation of D/D neonatal HMVEC TF expression by IL-1 is mediated through the p38 MAPK pathway. This heightened response of D/D neonatal HMVEC to inflammatory stimuli may contribute to increased microvascular coagulopathies in susceptible newborn infants.

The Consistent 50% Excess Male Infant Mortality from Sudden Infant Death Syndrome (SIDS) and Other Respiratory Diseases is Evidence of an X-Linkage

The male excess of infant mortality is well known but without causal explanation. We have inadvertently discovered while investigating sudden infant death syndrome (SIDS) that many causes of infant respiratory death have virtually the same male fraction as SIDS of about 0.61 male, subject to slight sampling variation. The only possible explanation for this consistency is that a recessive X-linkage is involved. We review the literature on infant mortality and propose that there exists a presently unidentified responsible X-linked gene that has a dominant allele with frequency p ≈ 1/3 and a corresponding recessive allele with frequency q ≈ 2/3, such that p+q=1. Either the dominant allele codes for an enzyme allowing anaerobic oxidation in respiratory control neurons or the recessive allele codes for a protein blocking anaerobic oxidation process in them. The gene and its alleles would only penetrate if, and only if, a susceptible infant attains an acute anoxic encephalopathy leading to critical respiratory control neuron death in the brainstem where the blood oxygen tension is the minimum in the entire body. Should the genetically susceptible infant dodge the potentially fatal anoxic condition, the gene may still penetrate later in childhood or adult life. Given an approximate 5% male birth excess, ~2/3 of the XY males will be at risk of having the recessive allele and q 2 ≈ 4/9 of XX females will be at similar risk. Therefore for ~1050 males born per 1000 females, ~700 males and ~444 females will be at risk with male fraction x ≈ 700/(700+444) ≈ 0.612. We show for 11 respiratory causes of death with over one half million cases, that the male fraction is ~0.604. It has not escaped our notice that a possible mode of prevention of SIDS may be possible.

Head injury and unclear mechanism of injury: Initial hematocrit less than 30 is predictive of abusive head trauma in young children

PurposeHead injury secondary to abusive head trauma (AHT) is a major cause of morbidity and mortality in susceptible young infants and children. Diagnosing AHT remains challenging and is often complicated by a questionable mechanism of injury. Concern of ionizing radiation risk to children undergoing head CT imaging warrants a selective approach. We aimed to evaluate initial findings that could direct further investigation of AHT. MethodsA retrospective review of the trauma databases at a two level one pediatric trauma centers was performed. We reviewed all patients age five years and under with a diagnosis of traumatic brain injury (TBI) from 2002–2011. ResultsA total of 1129 patients (mean age 1.7±1.7years; 64% male) with TBI were identified, 429 (38%) of which were the result of AHT. Complete data was available for 921 patients (82%) and were included in statistical evaluation. Forty-eight percent of patients in the AHT group had a hematocrit ≤30% on presentation compared to 19% of patients in the non-AHT group. On univariate analysis, a hematocrit of ≤30% was predictive of AHT as the cause of injury (P<.0001), as was a platelet count of greater than 400,000 (P<.0001). After controlling for age, sex, ISS, GCS on presentation, need for CPR, and survival to hospital discharge, hematocrit of ≤30% and platelets of greater than 400,000 were predictive of AHT as the cause of TBI (P<.05). ConclusionsIn the setting of head injury and unclear history of trauma, a hematocrit of ≤30% on presentation increases the likelihood of abusive head trauma in children up to the age of 5years.

A neurobiological model for cry-fuss problems in the first three to four months of life

Although problem crying in the first three to four months of life is usually self-limiting, it is not a trivial condition. Early intervention is important, yet families receive conflicting advice from health professionals. The past decade has seen significant advances in neuroscience, lactation science, and developmental psychology, including new insights into the significance of developmentally sensitive windows. We propose a neurobiological model to explain the mechanisms of cry-fuss problems in the first months of life, and the mechanisms which underlie effective intervention, with a view to facilitating research collaboration and consistency of advice across health disciplines. We hypothesise that crying in the first three to four neurodevelopmentally sensitive months signals activation of the hypothalamic–pituitary–adrenal axis and adrenergic neuronal circuitry in response to perceptions of discomfort or threat. Susceptible infants may be conditioned by early stress, for example, by unidentified feeding difficulties, into a sensitised stress response, which usually settles at three to four months of age with neurodevelopmental maturity. Bouts of prolonged and unsoothable crying result from positive feedback loops in the hypothalamic–pituitary–adrenal and adrenergic systems. Importantly, epigenetic modulation of the infant’s limbic neuronal circuitry may explain correlations between regulatory problems in the first months of life, and behavioural problems including feeding problems in later childhood.

Low-Dose Mercury Exposure in Early Life: Relevance of Thimerosal to Fetuses, Newborns and Infants

This review explores the different aspects of constitutional factors in early life that modulate toxicokinetics and toxicodynamics of low-dose mercury resulting from acute ethylmercury (etHg) exposure in Thimerosal-containing vaccines (TCV). Major databases were searched for human and experimental studies that addressed issues related to early life exposure to TCV. It can be concluded that: a) mercury load in fetuses, neonates, and infants resulting from TCVs remains in blood of neonates and infants at sufficient concentration and for enough time to penetrate the brain and to exert a neurologic impact and a probable influence on neurodevelopment of susceptible infants; b) etHg metabolism related to neurodevelopmental delays has been demonstrated experimentally and observed in population studies; c) unlike chronic Hg exposure during pregnancy, neurodevelopmental effects caused by acute (repeated/cumulative) early life exposure to TCV-etHg remain unrecognized; and d) the uncertainty surrounding low-dose toxicity of etHg is challenging but recent evidence indicates that avoiding cumulative insults by alkyl-mercury forms (which include Thimerosal) is warranted. It is important to a) maintain trust in vaccines while reinforcing current public health policies to abate mercury exposure in infancy; b) generally support WHO policies that recommend vaccination to prevent and control existing and impending infectious diseases; and c) not confuse the 'need' to use a specific 'product' (TCV) by accepting as 'innocuous' (or without consequences) the presence of a proven 'toxic alkyl-mercury' (etHg) at levels that have not been proven to be toxicologically safe.

The Environment Within: Exploring the Role of the Gut Microbiome in Health and Disease

The human genome codes for approximately 23,000 genes,1 yet some experts have suggested that the total information coded by the human genome alone is not enough to carry out all of the body’s biological functions.2 A growing number of studies suggest that part of what determines how the human body functions may be not only our own genes, but also the genes of the trillions of microorganisms that reside on and in our bodies. The genomes of the bacteria and viruses of the human gut alone are thought to encode 3.3 million genes.3 “The genetic richness and complexity of the bugs we carry is much richer than our own,” says Jayne Danska, an immunologist at the Hospital for Sick Children Research Institute in Ontario, Canada. “They serve as a buffer and interpreter of our environment. We are chimeric organisms.” Figure 1 False-color scanning electron micrograph shows the surface of the colon mucosa with pink clusters of rod-shaped bacteria, possibly Escherichia coli, attached. The genomes of the bacteria and viruses of the human gut alone are thought to encode 3.3 million ... A role for gut microbes in gastrointestinal function has been well documented since researchers first described differences in the fecal bacteria of people with inflammatory bowel disease.4 The molecular mechanisms responsible for the gut microbiome’s impact on metabolism and diseases throughout the body remain largely unknown. However, researchers are beginning to decipher how the microorganisms of the human intestinal tract influence biological functions beyond the gut and play a role in immunological, metabolic, and neurological diseases.

Commentary on “The Protest of a 6-Month-Old Girl: Is This a Prodrome of Autism?”

This commentary discusses the dilemmas and questions raised by Dr. Voran's interesting case study of a very young infant, relating to two issues: a) Jane, the infant (the difficulties involved in the interpretation of an infant's mind processes on the basis of her behavior), and b) the elusive concept of autism (consideration of recent scientific epigenetic studies support the hypothesis that the intrauterine environment may increase the risk for future development of autism spectrum disorder). Though we now understand more about the role of biogenetics in behavior, the etiology of autism remains unclear. However, the plasticity of the brain in the first year of an infant's life provides potential for successful treatment of susceptible infants who may develop autism, when they are identified, and treated as early as possible. The author of this commentary welcomes Dr. Voran's case study since it contributes to raising awareness to this important statement.

Loss of Passively Acquired Maternal Antibodies in Highly Vaccinated Populations: An Emerging Need to Define the Ontogeny of Infant Immune Responses

Protection against infectious diseases is provided to young infants by passive immunity through the transplacental transfer of immunoglobulin G during pregnancy and through immunoglobulin A in breast milk [1–7]. Despite the obvious benefits of these antibodies to the youngest infants, their levels wane over time, necessitating the development of active immunity through vaccination. The timing of primary vaccination is complex, driven by the need to provide protection prior to a time when the infant is likely to be exposed to disease, by the possibility of interference with vaccine-induced immunity by passively acquired maternal antibodies, and, finally, by considerations of the developing infant immune system [7–9]. The titers of transplacentally transferred passive antibodies (PA) provided to infants are, in part, determined by antibody titers present in the mother during pregnancy. These maternal titers are affected by her nutritional and immune status, and evidence demonstrates that antibody titers induced by vaccination are typically lower than titers induced by natural disease [3, 5, 6, 10]. After decades of vaccination against childhood diseases, it is clear that successful vaccine programs have resulted in dramatic decreases in morbidity and mortality. However, the increasing prevalence of vaccine-derived maternal antibodies has also led to unexpected outcomes. This is most evident in the emergence of measles susceptibility in young infants living in highly vaccinated populations where the measles vaccine has been in use for decades [11–14]. Historically, in developed nations protection against measles among infants <12 months of age was provided by a combination of PA and herd immunity, supported by high population immunization rates. However, this barrier has been disrupted, to a certain extent, by global importation of measles and, paradoxically, by the success of the measles vaccine programs, as vaccine-induced PA wanes earlier in infants as compared to PA derived from maternal natural infection [4, 8, 15, 16]. Measles outbreaks in countries with high measles vaccine coverage have demonstrated a shift in measles incidence to children <12 months of age [17–19], before primary measles vaccination commences in most developed countries. Further, the number of susceptible infants aged <12 months is expected to increase among highly vaccinated populations as the majority of women in child bearing years have vaccine-induced immunity to measles, with recent studies showing 99% of infants born to vaccinated mothers lacking detectable antibodies to measles by 6 months [3, 4]. Waaijenborg and colleagues eloquently highlight this phenomenon in this issue of the Journal by comparing titers of antibodies against measles, mumps, and rubella in 2 distinct populations in the Netherlands, one with high vaccination rates and one with opposition to vaccination and, thus, low vaccination rates and presumably higher rates of immunity induced by natural disease. As with previous studies, the authors note significantly lower measles antibody titers in infants born to women from the highly vaccinated populations in comparison to those born to mothers with presumed naturally induced immunity. In addition, the authors also compared mumps and rubella titers in the 2 populations, showing higher rubella titers in mothers from the population with low vaccination rates and low levels of mumps titers in both groups. Varicella was used in this study as a “control” disease because it is caused by a naturally circulating virus in Received and accepted 7 March 2013; electronically published 8 May 2013. Correspondence: Hayley A. Gans, MD, 300 Pasteur Dr, Rm G 312, Stanford University School of Medicine, Stanford, CA 94305-5208 (hagans@stanford.edu). The Journal of Infectious Diseases 2013;208:1–3 © The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. permissions@oup.com. DOI: 10.1093/infdis/jit144

Giant Cell Myocarditis and Endomyocardial Calcification in a 2.5-Month-Old Infant Triggered by Excessive Maternal Alcohol Abuse: Case Study of an Unusual Association

This report describes an unusual case of a 2.5-month-old infant's sudden death secondary to giant cell myocarditis and endomyocardial calcification, both unusual entities in pediatric patients. The mother had a history of excessive alcohol consumption during pregnancy and the postnatal period. No infectious etiologies, hypersensivity, or autoimmune disorders were identified. Therefore, the authors assume that alcohol exposure might be responsible for the inflammatory giant cell process complicated with endomyocardial calcification in susceptible infants. This report is the first to describe the rare form of noninfectious myocarditis complicated with endomyocardial calcification possibly triggered by a toxic agent. The authors discuss the possible interaction between these processes that led to the infant's sudden death.

Stability of parental care across siblings from undisturbed and challenged pregnancies: Intrinsic maternal dispositions of female rhesus monkeys.

The concept of fetal programming is based on the idea that the developmental trajectory of infants is adjusted in response to in utero conditions. In species with extended parental care, these prenatally derived tendencies are further substantiated by behavioral attributes of the mother during the postnatal period. We investigated the stability of maternal behavioral interactions with infant monkeys and carefully varied prenatal conditions across siblings reared by the same mother. We hypothesized that effects of prenatal disturbance and the infant's susceptibility would be differentially affected by maternal attributes. Using hierarchical linear modeling, we analyzed observational data on 121 rhesus macaques reared by a total of 35 multiparous mothers. A portion of the variance in 5 dyadic behaviors was statistically driven by the infant (or was unique to a particular mother-infant pair), but stable maternal propensities and a consistent style of care across siblings also substantially influenced behavioral interactions. Moreover, the magnitude and direction of the prenatal effects were contingent on a female's intrinsic dispositions. When mothers typically exhibited high levels of a corresponding behavior, responsiveness to infants was enhanced as a consequence of prenatal disturbance. The opposite was true for less expressive females. Challenges to the well-being of pregnancy thus served to accentuate maternal predispositions and served to magnify the range of variation in mother-infant behavior across the whole population.

Genetic and epigenetic variation of the glucocorticoid receptor (NR3C1) in placenta and infant neurobehavior.

The intrauterine environment can impact the developing infant by altering the function of the placenta through changes to the epigenetic regulatory features of this tissue. Genetic variation, too, may impact infant development or may modify the relationship between epigenetic alterations and infant outcomes. To examine the associations of these variations with early life infant neurodevelopment, we examined the extent of DNA methylation of the glucocorticoid receptor gene (NR3C1) promoter and a common single nucleotide polymorphism in the promoter region in a series of 186 placentas from healthy newborn infants. We associated these molecular features with specific summary measures from the NICU Network Neurobehavioral Scales. After controlling for genotype and confounders, we identified significant associations of NR3C1 methylation with infant quality of movement (p = .05) and with infant attention (p = .05), and a potential interaction between methylation and genotype on infant attention score. These results suggest that epigenetic alteration of the NR3C1 gene in the placentas of genetically susceptible infants can have impacts on neurodevelopment which may have lifelong impact on neurobehavioral and mental health outcomes. Further research is needed to more precisely define these relationships and the interaction between epigenetic alterations and genetic variations on infant health.

Intestinal Microbiota Shifts towards Elevated Commensal Escherichia coli Loads Abrogate Colonization Resistance against Campylobacter jejuni in Mice

BackgroundThe zoonotic pathogen Campylobacter jejuni is a leading cause of bacterial foodborne enterocolitis in humans worldwide. The understanding of immunopathology underlying human campylobacteriosis is hampered by the fact that mice display strong colonization resistance against the pathogen due to their host specific gut microbiota composition.Methodology/Principal FindingsSince the microbiota composition changes significantly during intestinal inflammation we dissected factors contributing to colonization resistance against C. jejuni in murine ileitis, colitis and in infant mice. In contrast to healthy animals C. jejuni could stably colonize mice suffering from intestinal inflammation. Strikingly, in mice with Toxoplasma gondii-induced acute ileitis, C. jejuni disseminated to mesenteric lymphnodes, spleen, liver, kidney, and blood. In infant mice C. jejuni infection induced enterocolitis. Mice suffering from intestinal inflammation and C. jejuni susceptible infant mice displayed characteristical microbiota shifts dominated by increased numbers of commensal Escherichia coli. To further dissect the pivotal role of those distinct microbiota shifts in abrogating colonization resistance, we investigated C. jejuni infection in healthy adult mice in which the microbiota was artificially modified by feeding live commensal E. coli. Strikingly, in animals harboring supra-physiological intestinal E. coli loads, colonization resistance was significantly diminished and C. jejuni infection induced enterocolitis mimicking key features of human campylobacteriosis.Conclusion/SignificanceMurine colonization resistance against C. jejuni is abrogated by changes in the microbiota composition towards elevated E. coli loads during intestinal inflammation as well as in infant mice. Intestinal inflammation and microbiota shifts thus represent potential risk factors for C. jejuni infection. Corresponding interplays between C. jejuni and microbiota might occur in human campylobacteriosis. Murine models introduced here mimick key features of human campylobacteriosis and allow for further analysis of immunological and molecular mechanisms of C. jejuni – host interactions.

Breastfeeding: More Than Just Good Nutrition

Breastfeeding: More Than Just Good Nutrition

Commentary on Providing Services to Students with Autism Spectrum Disorders

BACKGROUND The reported prevalence of ASDs in the United States as well as in other developed countries has increased dramatically in the last few years. This increase is likely the outcome of several factors: greater awareness of ASDs on the part of both parents and professionals, leading to earlier identification; changes in definitions related to ASDs (the wider use of the diagnostic category of Asperger's syndrome, for example); and perhaps an increase in environmental triggers of ASDs in genetically susceptible infants. At present, the best data on the prevalence of ASDs point to a rate of in 1 per 110 children, and a substantially higher rate in males. ASDs are defined behaviorally. There is no biological marker that points to a diagnosis of autism, and, as is well known in the medical field, the same symptoms can indicate various underlying conditions. About 10 percent of children diagnosed with ASDs have known medical conditions or disabilities such as Fragile X syndrome, but no such association has been identified in the other 90 percent of cases. The best current thinking is that there may be multiple genetic mutations contributing to susceptibility for ASDs. Although the pace of research into the causes of ASDs was very limited for many years, increased research funding to the National Institutes of Health, along with private funds, have substantially accelerated research opportunities. EARLY IDENTIFICATION AND EARLY INTERVENTION SERVICES A decrease in the age of identification of children at high risk for developing ASDs has occurred during the last few years as information about early warning signs or red flags for autism has been disseminated widely, and screening tools designed to identify ASDs in toddlers aged between 18 and 24 months have achieved wider use. Recent research appears to indicate that many children who are later diagnosed with autism can be identified by 12 months of age (Ozonoff, Losif, Baguio, Cook, Hill, Hutman et al., 2010). Researchers are also working on tools to identify infants aged between 12 and 15 months who are at high risk for developing ASDs. At present the mean age for diagnosis of ASDs is about 4 years, but that mean age is likely to decrease as a highly regarded evaluation tool, the Autism Diagnostic Observation Schedule (ASDOS), becomes available in a version designed for use with toddlers (publication is expected in 2012), and as other new diagnostic tools for use with toddlers at risk for ASDs gain broad acceptance. Because there is impressive evidence that early intervention is associated with better outcomes for infants and toddlers with ASDs (Bruder, 2010; Dawson, 2008), the importance of the development of such tools is clear. The Individuals with Disabilities Education Act (IDEA) Part C serves infants and toddlers with developmental delays from birth to age 3. Earlier identification of infants at high risk of developing ASDs and increased diagnostic evaluations of 2-year-olds at high risk should be accompanied by an expansion in the number of children receiving early intervention services. Such services are provided through each U.S. state, and there is great variation in the intensity of services delivered--some states provide such limited amounts of service time as to raise serious doubts about the effectiveness of those services. Moreover, with the budgetary strain that most states are currently experiencing, expansion of service intensity is very unlikely to occur in the foreseeable future, even though parents are already increasingly accessing private insurance and Medicaid waivers to help obtain adequate appropriate early intervention services for their children. When the topic of effectiveness of intervention arises, so too does a question about the availability of research-supported models for serving infants and young toddlers with ASDs. Until recently few such models existed. One of those models is the Early Start Denver Model for Young Children with Autism (Rogers & Dawson, 2010), a comprehensive model that incorporates behavioral principles within a developmental framework focused on social interaction, communication, and relationships. …