Association of early childhood diarrhea and cryptosporidiosis with impaired physical fitness and cognitive function four-seven years later in a poor urban community in northeast Brazil

To determine potential, long-term deficits associated with early childhood diarrhea and parasitic infections, we studied the physical fitness (by the Harvard Step Test) and cognitive function (by standardized tests noted below) of 26 children who had complete surveillance for diarrhea in their first 2 years of life and who had continued surveillance until 6-9 years of age in a poor urban community (favela) in Fortaleza in northeast Brazil. Early childhood diarrhea at 0-2 years of age correlated with reduced fitness by the Harvard Step Test at 6-9 years of age (P = 0.03) even after controlling for anthropometric and muscle area effects, anemia, intestinal helminths, Giardia infections, respiratory illnesses, and socioeconomic variables. Early childhood cryptosporidial infections (6 with diarrhea and 3 without diarrhea) were also associated with reduced fitness at 6-9 year of age, even when controlling for current nutritional status. Early diarrhea did not correlate with activity scores (P = 0.697), and early diarrhea remained significantly correlated with fitness scores (P = 0.035) after controlling for activity scores. Early diarrhea burdens also correlated in pilot studies with impaired cognitive function using a McCarthy Draw-A-Design (P = 0.01; P = 0.017 when controlling for early helminth infections), Wechsler Intelligence Scale for Children coding tasks (P = 0.031), and backward digit span tests (P = 0.045). These findings document for the first time a potentially substantial impact of early childhood diarrhea and cryptosporidial infections on subsequent functional status. If confirmed, these findings have major implications for calculations of global disability adjusted life years and for the importance and potential cost effectiveness of targeted interventions for early childhood diarrhea.     

Immunogenicity and efficacy of childhood vaccines in HIV-1-infected children

Children infected by HIV-1 are particularly vulnerable to severe, recurrent, or unusual infections by vaccine-preventable pathogens. Routine immunisations seem to be generally safe for HIV-1-infected children, but responses may be suboptimal. Early HIV-1-induced immune attrition associated with viral replication may particularly interfere with the development of memory responses. In high HIV-1 prevalence regions, the accumulation of susceptible hosts may compromise disease-control efforts. Although early control of viral replication through treatment with highly active therapy may preserve immune function and responses to routine childhood vaccines, availability is limited in the areas most affected. In this review, we provide an overview of the immunogenicity and efficacy of childhood vaccines in HIV-1-infected children. The possible immunological bases for defective responses are discussed; unanswered questions and the need for further research are delineated.     

Angeborene Immundefekte

Primary (inborn) immunodeficiency is caused by gene defects that impact both the innate and the adaptive immune system. Individuals with an immunedeficiency primarily come to medical attention with recurrent infections. Most diagnoses are first made in childhood and include cellular immunodeficiency, defects of phagocyte function and other primary immunodeficiencies. Antibody deficiencies, particularly common variable immunodeficiency (CVID) and complement defects may, however, not become manifested until adulthood. A pathological susceptibility to infection in adults is defined as more than three infections per year that require treatment with antibiotics and last longer than 4 weeks each. Clinical clues for immunodeficiency are pathological susceptibility to infections and immune dysregulation. The former is characterized by frequent and severe infections with often unusual pathogens, localization, course and/or intensity. Immune dysregulation comprises granulomas, autoimmune diseases, recurrent fever/chronic inflammation, tendency to eczema, lymphoproliferation and chronic enteritis. There are evidence-based guidelines and consensus documents for the diagnosis and treatment of primary immunodeficiencies. Therapeutic approaches depend on the nature of the immune defect and range from immunoglobulin substitution for antibody deficiencies to bone marrow transplantation for severe cellular immune defects.     

Early childhood diarrhea is associated with diminished cognitive function 4 to 7 years later in children in a northeast Brazilian shantytown

Diarrhea is well recognized as a leading cause of childhood mortality and morbidity in developing countries; however, possible long-term cognitive deficits from heavy diarrhea burdens in early childhood remain poorly defined. To assess the potential long-term impact of early childhood diarrhea (in the first 2 years of life) on cognitive function in later childhood, we studied the cognitive function of a cohort of children in an urban Brazilian shantytown with a high incidence of early childhood diarrhea. Forty-six children (age range, 6-10 years) with complete diarrhea surveillance during their first 2 years of life were given a battery of five cognitive tests. Test of Non-Verbal Intelligence-III (TONI) scores were inversely correlated with early childhood diarrhea (P = .01), even when controlling for maternal education, duration of breast-feeding, and early childhood helminthiasis (Ascaris or Trichuris). Furthermore, Wechsler Intelligence Scale for Children (WISC-III) Coding Tasks and WISC-III Digit Span (reverse and total) scores were also significantly lower in the 17 children with a history of early childhood persistent diarrhea (PD; P < .05), even when controlling for helminths and maternal education. No correlations were seen between diarrhea rates and Wide Range Assessment of Memory and Learning subtests or WISC-III Mazes. This report (with larger numbers of participants and new tests) confirms and substantially extends previous pilot studies, showing that long-term cognitive deficits are associated with early childhood diarrhea. These findings have important implications for the importance of interventions that may reduce early childhood diarrheal illnesses or their consequences.     

The Link between Cannabis Use,Immune System,and Viral Infections

Cannabis continues to be the most used drug in the world today. Research shows that cannabis use is associated with a wide range of adverse health consequences that may involve almost every physiological and biochemical system including respiratory/pulmonary complications such as chronic cough and emphysema, impairment of immune function, and increased risk of acquiring or transmitting viral infections such as HIV, HCV, and others. The review of published research shows that cannabis use may impair immune function in many instances and thereby exerts an impact on viral infections including human immune deficiency virus (HIV), hepatitis C infection (HCV), and human T-cell lymphotropic type I and II virus (HTLV-I/II). The need for more research is also highlighted in the areas of long-term effects of cannabis use on pulmonary/respiratory diseases, immune dysfunction and the risk of infection transmission, and the molecular/genetic basis of immune dysfunction in chronic cannabis users.     

The role of diet on intestinal microbiota metabolism: downstream impacts on host immune function and health,and therapeutic implications

Dietary impacts on health may be one of the oldest concepts in medicine; however, only in recent years have technical advances in mass spectroscopy, gnotobiology, and bacterial sequencing enabled our understanding of human physiology to progress to the point where we can begin to understand how individual dietary components can affect specific illnesses. This review explores the current understanding of the complex interplay between dietary factors and the host microbiome, concentrating on the downstream implications on host immune function and the pathogenesis of disease. We discuss the influence of the gut microbiome on body habitus and explore the primary and secondary effects of diet on enteric microbial community structure. We address the impact of consumption of non-digestible polysaccharides (prebiotics and fiber), choline, carnitine, iron, and fats on host health as mediated by the enteric microbiome. Disease processes emphasized include non-alcoholic fatty liver disease/non-alcoholic steatohepatitis, IBD, and cardiovascular disease/atherosclerosis. The concepts presented in this review have important clinical implications, although more work needs to be done to develop fully and validate potential therapeutic approaches. Specific dietary interventions offer exciting potential for nontoxic, physiologic ways to alter enteric microbial structure and metabolism to benefit the natural history of many intestinal and systemic disorders.     

Cancer in the elderly: basic science and clinical aspects

The incidence of cancer increases progressively with age. Rearrangements of genomes have been found to accompany cellular aging. These factors, in concert with age-dependent alterations in immune function and host defense, may help to explain the increased risk of malignant disease in aged persons. The clinical presentation and natural history of neoplasia are also affected by aging. This conference reviews recent developments in these areas, examines the effects of drug use in the elderly and implications for management, and discusses current information on how age may influence the response of cancer to therapy.     

Otitis Media in Infancy and the Development of Asthma and Atopic Disease

Otitis media is a frequent respiratory infection of early childhood and it is important to fully understand the long-term complications and sequelae. Literature examining otitis media in early childhood and subsequent development of atopic disease is sparse despite there being vast literature on the association between respiratory infections and atopic disease. Current data support the hypothesis that otitis media infections in early life, especially frequent or severe infections, influence the developing immune system, resulting in increased risk for asthma. Recent findings have also reported an association between otitis media and eczema. Atopic children and those with a family history of atopy appear to be at greater risk. Future work should investigate the specific mechanisms involved. It is possible that vaccines and preventive strategies aimed at reducing the burden of otitis media could also reduce the burden of childhood asthma and atopic disease.     

An updated review on Cryptosporidium and Giardia

Cryptosporidium and Giardia are two of the most commonly occurring enteric protozoans. They are responsible for diarrheal diseases that may lead to nutritional deficiencies and significant morbidity and mortality, especially among children in developing countries and patients who have immune defects. Both are difficult to diagnose with microscopic techniques. This article provides an updated review of the epidemiology, pathogenesis, clinical manifestations, and treatment of Cryptosporidium and Giardia.     

Hepatitis B virus and hepatitis C virus infections in children

PURPOSE OF REVIEW: To analyse the most relevant recent information on efficacy, duration and coverage of anti-hepatitis B virus vaccination; correlates of mother-to-child hepatitis C virus transmission; the natural history and outcomes of hepatitis B and C virus infections in children; the efficacy and safety of specific therapies. RECENT FINDINGS: Insufficient hepatitis B virus vaccine coverage and incomplete or delayed vaccine cycles need improvement in many countries. Hepatitis B virus mutants may explain some fulminant hepatitis in perinatally infected infants and vaccine failures. No interventions to prevent vertical hepatitis C virus transmission have been identified. Spontaneous clearance of hepatitis B is lower in children than in adults, while the rates appear to be similar for hepatitis C. The disease progression is slower for both infections in childhood. Several studies support the efficacy and safety of interferons and lamivudine in chronic hepatitis B or of interferons and ribavirin in chronic hepatitis C in children, but the optimal therapy remains unclear. SUMMARY: There are doubts as to the long-term persistence of anti-hepatitis B immunization in low-endemicity areas. Routine hepatitis C virus testing in pregnancy is not recommended as there are no available prophylactic measures. Although hepatitis B and C virus infections are usually asymptomatic or with mild manifestations in childhood, concerns around their long-term clinical impact suggest the need for early treatment. Children should preferably be treated in the context of targeted trials for a better understanding of the efficacy and tolerance of drugs currently used in adults.     

HIV1 and the gut in the era of highly active antiretroviral therapy

The gut and its gut-associated lymphoid tissue serve as a preferential site for HIV1 entry, active viral replication, reservoir, and HIV-mediated CD4 cell apoptosis. The widespread use of highly active antiretroviral therapy (HAART) has resulted in a significant decrease in the incidence of opportunistic enteric pathogens as a consequence of immune recovery. Nonetheless, patients with advanced HIV1 disease who were recently diagnosed or have poor response to HAART can still suffer from opportunistic infections with pathogens such as Cryptosporidium, microsporidia, Isospora belli, Cyclospora cayetanensis, Mycobacterium avium complex, and cytomegalovirus, among others. This review describes the impact of HIV1 infection on gut immune function, the salient features of the most common opportunistic enteric pathogens and HIV-associated enteropathy, and the effects of immune reconstitution after introduction of HAART.     

Malaria and anemia

Anemia due to infection is a major health problem in endemic areas for young children and pregnant women. The anemia is caused by excess removal of nonparasitized erythrocytes in addition to immune destruction of parasitized red cells, and impaired compensation for this loss by bone marrow dysfunction. The pathogenesis is complex, and a predominant mechanism has not been identified. Certain parasite and host characteristics may modify the anemia. Concomitant infections and nutritional deficiencies also contribute to anemia and may interact with the malarial infection. Few preventive strategies exist, and the management of severe malarial anemia with blood transfusion carries a risk of HIV transmission. The current increase in malaria-specific childhood mortality in sub-Saharan Africa attributed to drug-resistant infection is likely partly related to an increase in severe anemia. This review summarizes recent findings on the pathogenesis and epidemiology of malarial anemia.     

Mismatched pre- and postnatal nutrition leads to cardiovascular dysfunction and altered renal function in adulthood

The early life environment has long-term implications for the risk of developing cardiovascular (CV) disease in adulthood. Fetal responses to changes in maternal nutrition may be of immediate benefit to the fetus, but the long-term effects of these adaptations may prove detrimental if nutrition in postnatal life does not match that predicted by the fetus on the basis of its prenatal environment. We tested this predictive adaptive response hypothesis with respect to CV function in sheep. We observed that a mismatch between pre- and postnatal nutrient environments induced an altered CV function in adult male sheep that was not seen when environments were similar. Sheep that received postnatal undernutrition alone had altered growth, CV function, and basal hypothalamo-pituitary-adrenal axis activity in adulthood. Prenatal undernutrition induced greater weight gain by weaning compared with the prenatal control diet, which may provide a reserve in the face of a predicted poor diet in later life. In an adequate postnatal nutrient environment (i.e., relatively mismatched), these offspring exhibited cardiac hypertrophy and altered CV function in adulthood. These data support the concept that adult CV function can be determined by developmental responses to intrauterine nutrition made in expectation of the postnatal nutritional environment, and that if these predictions are not met, the adult may be maladapted and at greater risk of CV disease. Our findings have substantial implications for devising strategies to reduce the impact of a mismatch in nutrition levels in humans undergoing rapid socio-economic transitions in both developing and developed societies.     

The role of viruses in development or exacerbation of atopic asthma

Respiratory viral infections in early childhood have been linked to the development of persistent wheezing and asthma. Epidemiologic data indicate that, for the majority of children, virus-induced wheezing is a self-limited condition, with no long-term consequences. For a substantial minority, however, virus-induced wheezing is associated with persistent asthma and the potential for enhanced allergic sensitization. For the most part, this subset of patients is genetically predisposed; they are atopic children in whom respiratory viral infections trigger the early development of asthma by mechanisms that have not been fully elucidated. Both inflammatory and noninflammatory mechanisms may be involved. It does not appear that viral infection per se in early life is responsible for the induction of atopic asthma. Data from animal models provide support for the concept that enhanced allergic sensitization caused by increased uptake of allergen during infection may play a critical role, as well as T-cell-mediated immune responses to viral infection, which may favor eosinophilic inflammatory responses and the development of altered airway function to inhaled methacholine. Recent advances in our understanding of the interactions between respiratory viruses and the development of reactive airway disease offer new possibilities for preventive treatment in children at risk for developing persistent wheezing and asthma exacerbation as a result of viral infection.     

食管癌术后早期肠内营养支持的疗效分析

目的分析食管癌患者术后早期进行肠内营养对患者免疫功能影响和应用效果。方法选取我院2017年1月至2019年6月收治的102例食管癌患者作为本次研究对象,将患者按随机数字法分为两组,每组患者均为51例。对其中一组食管癌患者使用早期肠内营养支持,设为研究组;另外一组患者进行标准的肠外营养支持,设定为对照组。对两组患者在术前1天(T0)、进行营养支持的第1天(T1)和1周时间(T2)的营养指标、细胞免疫指标以及体液免疫指标等情况做检测,记录检测数据并对比分析。结果两组患者T2时检测出的营养指标、细胞免疫指标以及体液免疫指标等水平都要高于T1。研究组患者T2时各项指标比对照组患者改善得更好,两组间对比有统计学差异(P<0.05)。结论早期肠内营养支持能够使食管癌患者营养指标、细胞免疫指标以及体液免疫等指标得到改善效果,值得临床大力推广。     

Pediatric sleep apnea: implications of the epidemic of childhood overweight

Over the last 30 years, the prevalence of overweight across all pediatric age groups and ethnicities has increased substantially, with the current prevalence of overweight among adolescents estimated to be approximately 30%. Current evidence suggests that overweight is modestly associated with obstructive sleep apnea syndrome (OSAS) among young children, but strongly associated with OSAS in older children and adolescents. The rising incidence of pediatric overweight likely will impact the prevalence, presentation, and treatment of childhood OSAS. The subgroup of children who may be especially susceptible include ethnic minorities and those from households with caregivers from low socioeconomic groups. OSAS, by exposing children to recurrent intermittent hypoxemia or oxidative stress, may amplify the adverse effects of adiposity on systemic inflammation and metabolic perturbations associated with vascular disease and diabetes. When these conditions manifest early in life, they have the potential to alter physiology at critical developmental stages, or, if persistent, provide cumulative exposures that may powerfully alter long-term health profiles. An increased prevalence of overweight also may impact the response to adenotonsillectomy as a primary treatment for childhood OSAS. The high and anticipated increased prevalence of pediatric OSAS mandates assessment of optimal approaches for preventing and treating both OSAS and overweight across the pediatric age range. In this Pulmonary Perspective, the interrelationships between pediatric OSAS and overweight are reviewed, and the implications of the overweight epidemic on childhood OSAS are discussed.     

Endotoxin: friend or foe?

Endotoxin in our living environment has been of increasing interest to our global community of allergists. Initially and largely studied for its capacity to mediate septic shock (and earning its "-toxin" suffix), we have since come to understand that endotoxin in the dust of many occupational settings also is an occult respiratory culprit, inducing airflow obstruction and aggravating asthma and allergies. More recently, environmental endotoxin has been implicated as a microbial exposure in early childhood that may have an atopy-protective effect by augmenting early Th1-type immune development. Although seemingly paradoxical, endotoxin's dual nature ultimately may serve to enlighten our understanding of how such bioactive exposures can interact with and guide our immune systems in both health and disease.     

Persistent diarrhea signals a critical period of increased diarrhea burdens and nutritional shortfalls: a prospective cohort study among children in northeastern Brazil

Persistent diarrhea (PD; duration >/=14 days) is a growing part of the global burden of diarrheal diseases. A 45-month prospective cohort study (with illness, nutritional, and microbiologic surveillance) was conducted in a shantytown in northeastern Brazil, to elucidate the epidemiology, nutritional impact, and causes of PD in early childhood (0-3 years of age). A nested case-control design was used to examine children's diarrhea burden and nutritional status before and after a first PD illness. PD illnesses accounted for 8% of episodes and 34% of days of diarrhea. First PD illnesses were preceded by a doubling of acute diarrhea burdens, were followed by further 2.6-3.5-fold increased diarrhea burdens for 18 months, and were associated with acute weight shortfalls. Exclusively breast-fed children had 8-fold lower diarrhea rates than did weaned children. PD-associated etiologic agents included Cryptosporidium, Giardia, enteric adenoviruses, and enterotoxigenic Escherichia coli. PD signals growth shortfalls and increased diarrhea burdens; children with PD merit extended support, and the illness warrants further study to elucidate its prevention, treatment, and impact.     

Use of probiotics and prebiotics in infant feeding

Gut colonization by beneficial bacteria in early life is necessary for establishing the gut mucosal barrier, maturation of the immune system and preventing infections with enteric pathogens. Mode of delivery, prematurity, breastfeeding, and use of antibiotics are some of many factors that have been described to influence early life colonization. Dysbiosis, the absence of normal colonization, is associated with many disease conditions. Pre- and probiotics are commonly used as supplementation in infant formula, such as prebiotic oligosaccharides for stimulation of Bifidobacterium growth aiming to mimic the high levels of these commensal bacteria in the gut of breastfed infants. Studies suggest that probiotic supplementation may be beneficial in prevention and management of disease (e.g., reducing the risk of necrotizing enterocolitis in preterm infants and treatment of acute gastroenteritis in children). Although these studies show promising beneficial effects, the long-term risks or health benefits of pre- and probiotic supplementation are not clear.     

Enteral and parenteral nutrition in the care of patients with short-bowel syndrome

Short-bowel syndrome is a challenging entity for the gastroenterologist, requiring integration of medical, nutritional, surgical and psychological therapies. Treatment must be based on the patient's age, remaining gastrointestinal anatomy, baseline nutritional status and underlying general health as well as the numerous complications which may arise. This chapter reviews physiological alterations that occur with short-bowel syndrome and how therapies can be tailored to most adequately meet the needs of these patients. Emphasis on early stages of therapy to enhance intestinal adaptation is focused on as management during this time has a significant impact on the long-term outcome of these patients.