Safety, efficacy and effectiveness of cold-adapted, live, attenuated, trivalent, intranasal influenza vaccine in adults and children.

Studies in children and adults revealed cold-adapted, live, attenuated, trivalent, intranasal influenza vaccine (CAIV-T) to be well accepted, well tolerated and highly protective against culture-confirmed influenza, and to provide significant health benefits. A 2 year, multicentre, double-blind, placebo-controlled efficacy field trial of CAIV-T in children aged 15-71 months with annual re-immunization revealed the vaccine to be highly protective against culture-confirmed influenza. Vaccine induced serum and secretory antibodies in vaccinated children. Overall, during 2 years of study, vaccine was 92% protective against culture-confirmed influenza. During the second year of study the vaccine was 86% protective against influenza A/Sydney/5/97-like virus, a significantly drifted strain not well matched to the vaccine. Antibody studies on children given CAIV-T revealed that high titres of cross-reacting antibodies to influenza A/Sydney/5/97 were induced with vaccination by live attenuated influenza A/Wuhan/359/95-like vaccine. Effectiveness measures revealed significant reductions in febrile illness (21% reduction in year 1, 19% reduction in year 2), febrile otitis media (33% reduction in year 1, 16% reduction in year 2) and associated antibiotic use among vaccinated children compared with placebo recipients. In adults, vaccination with CAIV-T resulted in protection during experimental challenge with virulent wild-type viruses. An effectiveness trial in adults demonstrated significant benefits of CAIV-T vaccine (28% reduction in days of missed work for febrile upper respiratory illness days with associated 45% reduction in days taking antibiotics). General use of CAIV-T has the potential to significantly reduce the impact of influenza in children and adults.     

Selective infection of lower respiratory tract by respiratory viruses in children with recurrent respiratory tract infections.

Thirty preschool children presenting with recurrent respiratory infections and their unaffected siblings were observed prospectively for a year. The index children experienced more episodes of acute respiratory infection than their siblings. Respiratory viruses were the major cause of respiratory infections. The index children had lower respiratory tract disease, predominantly wheeze, during 34% of proved respiratory virus infections compared with 11% of such infections experienced by the control children (p less than 0.02). Atopic children had an increased tendency to wheeze that did not reach significance, but atopy was not associated with increased susceptibility to respiratory infections.     

Factors affecting the choice of cooking fuel, cooking place and respiratory health in the Accra metropolitan area, Ghana

Indoor air pollution resulting from the combustion of solid fuels has been identified as a major health threat in the developing world. This study examines how the choice of cooking fuel, place of cooking and behavioural risk factors affect respiratory health infections in Accra, Ghana. About 65.3% of respondents use charcoal and 4.2% use unprocessed wood. A total of 241 (25.4%) respondents who cook had had respiratory health symptoms in the two weeks preceding the study. Household socioeconomic status and educational attainment of respondents were found to have a significant impact on respiratory health through their particular influence on the choice of cooking fuel. Households that use wood and charcoal have a high incidence of respiratory health symptoms. The poor are more affected by respiratory health problems due to their heavy dependence on solid fuels as compared with their wealthy counterparts. Households that cook in multiple purpose rooms are more affected by respiratory health problems than those that cook outdoors. There is a positive correlation between the presence of children in the kitchen during cooking and the incidence of respiratory health symptoms among children (r=0.31, p<0.0001). Poverty and lack of education and awareness are the major factors affecting the choice of cooking fuel, place of cooking and respiratory health in Accra.     

Breast-feeding and respiratory syncytial virus infection.

The pattern of breast-feeding in 127 infants admitted to hospital with respiratory syncytial virus infection was compared with that in 503 age-matched controls. Thirty per cent of children with infection had been breast-fed compared with 49% of controls. The approximate relative risk of being admitted to hospital with respiratory syncytial virus infection if not breast-fed was 2.2. Several other factors were also considered, including an assessment of maternal care and home environment; the mother''s age, marital state, and smoking habits; the number of siblings; and gestation. Adverse factors were all associated with an increased risk of admission with infection, but breast-feeding still appeared to provide protection after controlling for these other factors in turn. These findings provide further support for encouraging mothers to breast-feed their infants and should prompt further studies into the immune status of mothers and into the nature of the protective factors in their breast milk.     

Immunostimulating activity of polycomponent vaccine "Immunovac-VP-4" and grippol after their combined administration

The experimental study of the immunostimulating activity of therapeutic bacterial polycomponent vaccine VP-4 and prophylactic vaccine grippol, introduced both separately and in combination, on mice infected with Salmonella typhimurium, used as a model. Both preparations were found to produce an immunomodulating effect. The combined subcutaneous injection of VP-4 and grippol did not decrease their immunostimulating activity, but their separate administration at an interval of 14 days resulted in essential decrease in the protective activity of each of these two preparations. As shown on the model of Klebsiella infection in mice, challenged 4 weeks after immunization, VP-4 ensured the survival of 78.6% of mice, while after the injection of grippol their survival rate was not different from that of the group of intact animals. The evaluation of the immunostimulating activity of these preparations under the conditions of the prophylaxis of influenza and acute respiratory infections in organized groups of children revealed that the use of VP-4 alone or grippol in combination with VP-4 considerably decreased the number of secondary bacterial complications in children.     

Acute Respiratory Infections in Children: Part II. A Trial of Polyvalent Virus Vaccine

A new polyvalent respiratory virus vaccine has been evaluated in a double-blind trial involving infants and children. Five hundred and sixteen healthy infants and children were given either nine-strain polyvalent respiratory virus vaccine or placebo. The vaccine contained four Influenza strains, three Adenovirus strains and two Parainfluenza strains. Serologic studies revealed that persistent protective antibody levels were achieved with only the Asian Influenza component.The children were followed up clinically for a one-year period and each respiratory illness was recorded. No protection appeared to have been conferred by the vaccine, and indeed a significantly greater number of respiratory illnesses occurred among the vaccinated group.     

The role of secretory antibodies in adenovirus infection

The protective role of secretory antibodies in the development of adenovirus infection has been established. More severe and prolonged course of adenovirus infection, accompanied by the involvement of the lower respiratory tract in the process, has been noted in patients with low titers of antibodies, or their absence, in secretions (O to 1:4). The presence of secretory antibodies in a titer of 1:8 considerably alleviated the course of the disease. The antibody titer 1:16 (according to the data of the passive hemagglutination test) has proved to be protective for children and adults in adenovirus infection. The results of the determination of antibodies in the secretions of the upper respiratory tract in the passive hemagglutination test may be used for the purposes of prognostication.     

The extent of protective footwear use among school-age rural children at high risk for podoconiosis and socio-economic correlates: A household cross-sectional survey in Southern Ethiopia

BackgroundPodoconiosis is preventable if genetically susceptible people wear shoes starting from an early age and do so consistently. However, lack of routine use of footwear is one of the major risk factors for podoconiosis and several other foot-related Neglected Tropical Diseases (NTDs). This study is aimed at describing the extent of footwear use among school-age rural children susceptible to the disease and investigating associated socioeconomic factors.MethodsCross sectional surveys were conducted in 330 randomly selected households in Wolaita zone, southern Ethiopia. A household head and a child aged between 9 and 15 years were recruited from each household. Household heads provided socioeconomic data while children were asked about their footwear ownership and footwear use.ResultsNearly half (49.5%) of the children reported either walking barefoot or wearing under-protective footwear in a range of situations. Girls, older children, those in higher school grades, who belonged to families with higher socio-economic status, and those who owned a larger number of pairs of footwear reported more protective use of footwear. The linear regression model constituting the adequacy of footwear ownership and interaction term (i.e. family socioeconomic status by adequacy of footwear ownership) variables explained 30% of variance in the protective use of footwear (AR² = 0.307). The interaction effect of adequate ownership of footwear and family socioeconomic status consistently predicted the protective use of footwear among children (β = -0.175, p<0.01) though the main effect of adequacy of footwear ownership was stronger (β = 0.507, p<0.001).ConclusionIncreased adoption of protective footwear is needed to effectively prevent school-age children living in endemic areas from developing podoconiosis and other neglected tropical diseases. Interventions aimed to improve the protective footwear use should consider approaches that also increase the socio-economic capacity of families in podoconiosis endemic communities.     

Is There Still Room for Novel Viral Pathogens in Pediatric Respiratory Tract Infections?

Viruses are the most frequent cause of respiratory disease in children. However, despite the advanced diagnostic methods currently in use, in 20 to 50% of respiratory samples a specific pathogen cannot be detected. In this work, we used a metagenomic approach and deep sequencing to examine respiratory samples from children with lower and upper respiratory tract infections that had been previously found negative for 6 bacteria and 15 respiratory viruses by PCR. Nasal washings from 25 children (out of 250) hospitalized with a diagnosis of pneumonia and nasopharyngeal swabs from 46 outpatient children (out of 526) were studied. DNA reads for at least one virus commonly associated to respiratory infections was found in 20 of 25 hospitalized patients, while reads for pathogenic respiratory bacteria were detected in the remaining 5 children. For outpatients, all the samples were pooled into 25 DNA libraries for sequencing. In this case, in 22 of the 25 sequenced libraries at least one respiratory virus was identified, while in all other, but one, pathogenic bacteria were detected. In both patient groups reads for respiratory syncytial virus, coronavirus-OC43, and rhinovirus were identified. In addition, viruses less frequently associated to respiratory infections were also found. Saffold virus was detected in outpatient but not in hospitalized children. Anellovirus, rotavirus, and astrovirus, as well as several animal and plant viruses were detected in both groups. No novel viruses were identified. Adding up the deep sequencing results to the PCR data, 79.2% of 250 hospitalized and 76.6% of 526 ambulatory patients were positive for viruses, and all other children, but one, had pathogenic respiratory bacteria identified. These results suggest that at least in the type of populations studied and with the sampling methods used the odds of finding novel, clinically relevant viruses, in pediatric respiratory infections are low.     

Mucopolysaccharides in bronchial secretion of children.

The diseases of respiratory system are nowadays one of the important medical, economical and social problems of modern civilization. A common symptom of these diseases regardless of their etiology, character, klinical manifestation and morphological findings is hypersecretion of bronchial sputum. Tracheobronchial mucus is produced by mucous bronchial glands and goblet cells. This mucus represents at physiological condition about 5 micrometer thick cover on mucous of nasopharynx, larynx, trachea, bronchi up to terminal bronchioles. Protective function of mucus cover resposes in mechanical and humoral barrier and also in removing the inhaled particles and their transport to the upper part of the respiratory system. In spite of the fact, that bronchial secretion has an important role in protective mechanism and in thermal and water exchange of respiratory tract, this secretion is not sufficiently scrutinized mainly of children yet.     

Respiratory illness and home environment of ethnic groups

Factors contributing to differences in the prevalences of respiratory symptoms and diseases among ethnic groups were studied in primary schoolchildren living in 20 inner city areas of England in 1983. The raised prevalences of respiratory symptoms in these groups were compared with results from a national representative sample of children studied in 1982. Data on age, sex, respiratory illness, and social and environmental variables were obtained by questionnaire for 4815 children living in inner cities. The children were classified as white, Afro-Caribbean, Urdu, Gujarati, Punjabi, other Asian, or “other.” Significant differences in the prevalence of respiratory conditions were found among the ethnic groups after allowance was made for the effects of interfering variables. Except for asthma all conditions were most prevalent in Afro-Caribbeans and whites. In these two ethnic groups respiratory illness was significantly associated with belonging to a one parent family and the combined use of gas cookers and paraffin heaters at home.Respiratory illness was found to vary in prevalence among ethnic groups but may be perceived differently by different groups. Further studies, measuring lung function, are necessary.     

Upper respiratory tract microbial communities, acute otitis media pathogens, and antibiotic use in healthy and sick children

The composition of the upper respiratory tract microbial community may influence the risk for colonization by the acute otitis media (AOM) pathogens Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. We used culture-independent methods to describe upper respiratory tract microbial communities in healthy children and children with upper respiratory tract infection with and without concurrent AOM. Nasal swabs and data were collected in a cross-sectional study of 240 children between 6 months and 3 years of age. Swabs were cultured for S. pneumoniae, and real-time PCR was used to identify S. pneumoniae, H. influenzae, and M. catarrhalis. The V1-V2 16S rRNA gene regions were sequenced using 454 pyrosequencing. Microbial communities were described using a taxon-based approach. Colonization by S. pneumoniae, H. influenzae, and M. catarrhalis was associated with lower levels of diversity in upper respiratory tract flora. We identified commensal taxa that were negatively associated with colonization by each AOM bacterial pathogen and with AOM. The balance of these relationships differed according to the colonizing AOM pathogen and history of antibiotic use. Children with antibiotic use in the past 6 months and a greater abundance of taxa, including Lactococcus and Propionibacterium, were less likely to have AOM than healthy children (odds ratio [OR], 0.46; 95% confidence interval [CI], 0.25 to 0.85). Children with no antibiotic use in the past 6 months, a low abundance of Streptococcus and Haemophilus, and a high abundance of Corynebacterium and Dolosigranulum were less likely to have AOM (OR, 0.51; 95% CI, 0.31 to 0.83). An increased understanding of polymicrobial interactions will facilitate the development of effective AOM prevention strategies.     

Mechanisms of illness during respiratory syncytial virus infection: the lungs, the virus and the immune response

Multiple factors, including cardiopulmonary anatomy, direct viral effects and the immune response can affect the severity of lower respiratory tract disease caused by respiratory syncytial virus (RSV). RSV is the most frequent viral respiratory cause of hospitalization in infants and young children in the world. In this review, we discuss the mechanisms of illness associated with severe RSV lower respiratory tract disease. A better understanding of the factors affecting the course of illness and their interplay should allow development of effective therapies in the future.     

Clinical and immunological effect of vaccination against Haemophilus influenzae, type B, in children with disorders of the nervous system

Observations on 277 children aged 3 months to 4 years with lesions of the nervous system, immunized with vaccine Act-HIB (Aventis Pasteur, France), were carried out in groups of children. The significant decrease of the level of Hib nasopharyngeal carrier state in 3.3 times and the decrease of total morbidity in acute infections of respiratory and ENT organs in 2.7 times occurred after immunization was revealed. The immunological effect of immunization on the level of protective titers against H. influenzae, type b, in children with organic CNS lesions in children was shown.     

Can folic acid protect against congenital heart defects in down syndrome?

BACKGROUND: Several studies have suggested a protective effect of folic acid (FA) on congenital heart anomalies. Down syndrome (DS) infants are known to have a high frequency of heart anomalies. Not all children with DS suffer from heart anomalies, which raises the question whether maternal factors might affect the risk of these anomalies. Our objectives were to investigate whether first-trimester FA use protects against heart anomalies among DS children. METHODS: Women with liveborn DS children participating in the Slone Epidemiology Center Birth Defects Study between 1976 and 1997 were included. We performed case-control analyses using DS, with heart anomalies as cases and DS, without heart anomalies as controls. Subanalyses were performed for defects that have been associated with FA in non-DS populations (conotruncal, ventricular septal [VSD]) and for those that are associated with DS (ostium secundum type atrial septal defects [ASD] and endocardial cushion defects [ECD]). Exposure was defined as the use of any FA-containing product for an average of at least 4 days per week during the first 12 weeks of pregnancy, whereas no exposure was defined as no use of FA in these 12 weeks. RESULTS: Of the 223 cases, 110 (49%) were exposed versus 84 (46%) of the 184 controls. After adjustment for possible confounders, no protective effect of FA was found on heart anomalies overall (OR 0.95, 95% CI: 0.61-1.47) nor separately for conotruncal defects, VSDs, ASDs, or ECDs. CONCLUSIONS: Our study does not show a protective effect of FA on heart anomalies among infants with DS.     

Candidate Human Genetic Polymorphisms and Severe Malaria in a Tanzanian Population

Human genetic background strongly influences susceptibility to malaria infection and progression to severe disease and death. Classical genetic studies identified haemoglobinopathies and erythrocyte-associated polymorphisms, as protective against severe disease. High throughput genotyping by mass spectrometry allows multiple single nucleotide polymorphisms (SNPs) to be examined simultaneously. We compared the prevalence of 65 human SNP''s, previously associated with altered risk of malaria, between Tanzanian children with and without severe malaria. Five hundred children, aged 1–10 years, with severe malaria were recruited from those admitted to hospital in Muheza, Tanzania and compared with matched controls. Genotyping was performed by Sequenom MassArray, and conventional PCR was used to detect deletions in the alpha-thalassaemia gene. SNPs in two X-linked genes were associated with altered risk of severe malaria in females but not in males: heterozygosity for one or other of two SNPs in the G6PD gene was associated with protection from all forms of severe disease whilst two SNPs in the gene encoding CD40L were associated with respiratory distress. A SNP in the adenyl cyclase 9 (ADCY9) gene was associated with protection from acidosis whilst a polymorphism in the IL-1α gene (IL1A) was associated with an increased risk of acidosis. SNPs in the genes encoding IL-13 and reticulon-3 (RTN3) were associated with increased risk of cerebral malaria. This study confirms previously known genetic associations with protection from severe malaria (HbS, G6PD). It identifies two X-linked genes associated with altered risk of severe malaria in females, identifies mutations in ADCY9, IL1A and CD40L as being associated with altered risk of severe respiratory distress and acidosis, both of which are characterised by high serum lactate levels, and also identifies novel genetic associations with severe malaria (TRIM5) and cerebral malaria(IL-13 and RTN3). Further studies are required to test the generality of these associations and to understand their functional consequences.     

The impact of heat waves on children’s health: a systematic review

Young children are thought to be particularly sensitive to heat waves, but relatively less research attention has been paid to this field to date. A systematic review was conducted to elucidate the relationship between heat waves and children’s health. Literature published up to August 2012 were identified using the following MeSH terms and keywords: “heatwave”, “heat wave”, “child health”, “morbidity”, “hospital admission”, “emergency department visit”, “family practice”, “primary health care”, “death” and “mortality”. Of the 628 publications identified, 12 met the selection criteria. The existing literature does not consistently suggest that mortality among children increases significantly during heat waves, even though infants were associated with more heat-related deaths. Exposure to heat waves in the perinatal period may pose a threat to children’s health. Pediatric diseases or conditions associated with heat waves include renal disease, respiratory disease, electrolyte imbalance and fever. Future research should focus on how to develop a consistent definition of a heat wave from a children’s health perspective, identifying the best measure of children’s exposure to heat waves, exploring sensitive outcome measures to quantify the impact of heat waves on children, evaluating the possible impacts of heat waves on children’s birth outcomes, and understanding the differences in vulnerability to heat waves among children of different ages and from different income countries. Projection of the children’s disease burden caused by heat waves under climate change scenarios, and development of effective heat wave mitigation and adaptation strategies that incorporate other child protective health measures, are also strongly recommended.     

Psychosocial adjustment and craniofacial malformations in childhood

Forty-three children between the ages of 6 and 13 years with congenital facial anomalies underwent psychosocial evaluation prior to surgery. Also evaluated were healthy children matched to the craniofacial subjects by sex, age, intelligence, and economic background. Relative to this comparison group, the craniofacial children were found to have poorer self-concept, greater anxiety at the time of evaluation, and more introversion. Parents of the craniofacial children noted more frequent negative social encounters for their children and more hyperactive behavior at home. Teachers reported more problematic classroom behavior. Examination of these results revealed craniofacial malformations to be associated with psychosocial limitations rather than marked deficits. These children tended to function less well than the comparison children, but with few exceptions, they were not functioning in a psychosocially deviant range. Explanations for the observed circumscribed impact of facial deformity include the use of denial as a coping mechanism, possible diminished significance of appearance for younger children, and the restricted environment experienced by most of the subjects. It can be predicted that time would render these protective influences ineffective, so that adolescent and young adult patients could be at far greater psychosocial risk.     

The role of health care workers and antiviral drugs in the control of pandemic influenza

Until a vaccine against the new strain becomes available, the response to newly emerged pandemic influenza will consist of the use of antiviral drugs and measures that limit exposure to infectious individuals. These first-line defence measures include isolating cases upon diagnosis, reducing close contacts, the use of personal protective equipment and hygiene, and using antiviral drugs for treatment and prophylaxis. There are significant 'costs' associated with control measures, so to justify such interventions it is important to assess their potential to reduce transmission. In this paper, we determine the effect that a number of different antiviral interventions have on the reproduction number of infectives and the probability that an imported infection fades out, and determine parameter scenarios for which these interventions are able to eliminate an emerging pandemic of influenza. We also assess the role that health care workers play in transmission and the extent to which providing them with antiviral prophylaxis and personal protective equipment modifies this role. Our results indicate that this class requires protection to avoid a greatly disproportionate contribution to early infective numbers, and for the maintenance of a stable health care system. Further, we show that the role children play in increasing transmission is moderate, in spite of closer mixing with other children.     

Affinity-Purified Respiratory Syncytial Virus Antibodies from Intravenous Immunoglobulin Exert Potent Antibody-Dependent Cellular Cytotoxicity

Mixed infections are one of the major therapeutic challenges, as the current strategies have had limited success. One of the most common and widespread conditions of mixed infection is respiratory syncytial virus-mediated pathology of the respiratory tract in children. There is a dire need for the development of novel therapeutic approaches during mixed infections. Therapeutic intravenous immunoglobulin preparations, obtained from plasma pools of healthy donors have been used in immune deficiencies. This study was thus designed to characterize the functional efficacy of RSV-specific antibodies in IVIg. To explore the functional ability of these affinity-purified RSV-specific antibodies, the antibody-dependent and complement dependent cytotoxicity was determined using peripheral cells of healthy donors. This study demonstrates the existence of highly potent RSV-specific antibodies in IVIg preparations and provides the basis for the use of IVIg as broad-spectrum protective shield to RSV-infected children during mixed infections.