Mutational spectral analysis at the HPRT locus in healthy children

There is growing evidence linking somatic mutational events during fetal development and childhood to an increasing number of multifactorial human diseases. Despite this, little is known about the relationship between endogenous and environmentally induced exogenous mutations during human development. Here we describe a comparative spectral analysis of somatic mutations at the hypoxanthine-guanine phosphoribosyltransferase (HPRT) reporter gene locus in healthy children. We observed an age-specific decrease in the proportion of large alterations and a corresponding increase in the proportion of small alterations with increasing age following birth (P<0.001). The age specific decrease in the proportion of large alterations (67-30%) was mainly due to a decrease in the proportion of aberrant variable (V), diversity (D) and joining (J) (V(D)J) recombinase mediated HPRT deletions (P<0.001). The increase in the proportion of small alterations with age (28-64%) was associated with an increase in transversions from 8% in children at the late stages of fetal development to 31% in children 12-16 years old (P=0.003). Transitions decreased with age, especially at CpG dinucleotides (P=0.010), as transversions increased (P=0.009). These patterns of mutations provide insight into important spontaneous, genotoxic, and site-specific recombinational somatic mutational events associated with the age-specific development of human disease in children as well as adults.     

Detection of enterohepatic and gastric helicobacter species in fecal specimens of children with Crohn's disease

Background: Although there is compelling evidence to support the role of bacteria in Crohn's disease (CD), there is currently no solid evidence to support the role of any one specific bacterial causative agent. Recent studies have suggested that members of the Helicobacteraceae may play a role in the development of CD. The aim of this study was to further investigate the presence of members of the Helicobacteraceae in children with and without CD.
Materials and methods: Fecal specimens from 29 children with CD, 11 healthy, normal controls, and 26 symptomatic controls with non-inflammatory bowel disease (IBD) pathology were obtained for DNA extraction and subjected to Helicobacteraceae -specific polymerase chain reaction (PCR). All PCR-positive samples were sequenced. The association between the presence of members of the Helicobacteraceae and each study group was statistically analysed using the Fisher's exact test.
Results: Based on Helicobacteraceae -specific PCR analysis, 59% (17 of 29) of the children with CD were positive, which was significantly higher than that in asymptomatic healthy children [9% (1 of 11); p  = .01] and that in symptomatic children with non-IBD pathology [0% (0/26); p  < .0001]. Sequencing of the 16S rRNA gene of positive samples revealed the presence of both enterohepatic Helicobacter species and Helicobacter pylori in fecal specimens.
Conclusions: For the first time, enterohepatic and gastric Helicobacter species have been identified in fecal specimens from children diagnosed with CD using PCR. Our data suggest that Helicobacter species may have a pathogenic role in the development of CD in a considerable proportion of children.     

An imbalance of T cell subgroups exists in children with sepsis

The purpose of this study is to explore the role of different T cell subgroups in the pathogenesis of sepsis in children. Flow cytometry was used to detect the changes in the activation status and the number of T cell subgroups in the peripheral blood of children with sepsis; healthy children were selected as the control group. Compared with healthy children, the number of CD4+ T cells in the peripheral blood of children with sepsis did not change significantly (Z = 1.945, P = 0.052); though the ratio decreased and the median level dropped from 34.6% to 30.7% (Z = 2.257, P = 0.024). However, the number of CD8+ T cells in the blood of children with sepsis increased, and the median level also increased from 0.2 × 10⁹/L to 0.4 × 10⁹/L (Z = ?2.404, P = 0.016). In addition, CD3+CD8+HLA-DR + cell level significantly increased, and the median level increased from 4.2% to 24.3% (Z = ?5.370, P = 0.000). There was a large heterogeneity in the hospitalization time of sepsis in clinical patients. Compared to patients with a mean hospital stay of 6 days, patients with a median hospital stay of 13 days had a lower CD3+CD4+CD25 + cells percentage, while the percentage of CD3+CD8+HLA-DR+ was higher, resulting in a more apparent increase of CD3+ CD8+HLA-DR+/CD3+CD4+CD25+. Therefore, the failure of CD4+ T cell activation and proliferation, and the excessive activation and proliferation of CD8+ T cells play an important role in the pathogenesis of sepsis. The increase of CD3+CD8+HLA-DR+/CD3+CD4+CD25 + ratio was associated with the extended course of sepsis.     

Meta-analysis of the immunogenicity and tolerability of pandemic influenza A 2009 (H1N1) vaccines

Background

Although the 2009 (H1N1) influenza pandemic officially ended in August 2010, the virus will probably circulate in future years. Several types of H1N1 vaccines have been tested including various dosages and adjuvants, and meta-analysis is needed to identify the best formulation.

Methods

We searched MEDLINE, EMBASE, and nine clinical trial registries to April 2011, in any language for randomized clinical trials (RCTs) on healthy children, adolescents, adults and the elderly. Primary outcome was the seroconversion rate according to hemagglutinination-inhibition (HI); secondary outcomes were adverse events. For the primary outcome, we used head-to-head meta-analysis and multiple-treatments meta-analysis.

Results

Eighteen RCTs could be included in all primary analyses, for a total of 76 arms (16,725 subjects). After 2 doses, all 2009 H1N1 split/subunit inactivated vaccines were highly immunogenic and overcome CPMP seroconversion criteria. After 1 dose only, all split/subunit vaccines induced a satisfactory immunogenicity (> = 70%) in adults and adolescents, while only some formulations showed acceptable results for children and elderly (non-adjuvanted at high-doses and oil-in-water adjuvanted vaccines). Vaccines with oil-in-water adjuvants were more immunogenic than both nonadjuvanted and aluminum-adjuvanted vaccines at equal doses and their immunogenicity at doses < = 6 µg (even with as little as 1.875 µg of hemagglutinin antigen) was not significantly lower than that achieved after higher doses. Finally, the rate of serious vaccine-related adverse events was low for all 2009 H1N1 vaccines (3 cases, resolved in 10 days, out of 22826 vaccinated subjects). However, mild to moderate adverse reactions were more (and very) frequent for oil-in-water adjuvanted vaccines.

Conclusions

Several one-dose formulations might be valid for future vaccines, but 2 doses may be needed for children, especially if a low-dose non-adjuvanted vaccine is used. Given that 15 RCTs were sponsored by vaccine manufacturers, future trials sponsored by non-industry agencies and comparing vaccines using different types of adjuvants are needed.     

Do aluminum vaccine adjuvants contribute to the rising prevalence of autism?

Autism spectrum disorders (ASD) are serious multisystem developmental disorders and an urgent global public health concern. Dysfunctional immunity and impaired brain function are core deficits in ASD. Aluminum (Al), the most commonly used vaccine adjuvant, is a demonstrated neurotoxin and a strong immune stimulator. Hence, adjuvant Al has the potential to induce neuroimmune disorders. When assessing adjuvant toxicity in children, two key points ought to be considered: (i) children should not be viewed as “small adults” as their unique physiology makes them much more vulnerable to toxic insults; and (ii) if exposure to Al from only few vaccines can lead to cognitive impairment and autoimmunity in adults, is it unreasonable to question whether the current pediatric schedules, often containing 18 Al adjuvanted vaccines, are safe for children? By applying Hill's criteria for establishing causality between exposure and outcome we investigated whether exposure to Al from vaccines could be contributing to the rise in ASD prevalence in the Western world. Our results show that: (i) children from countries with the highest ASD prevalence appear to have the highest exposure to Al from vaccines; (ii) the increase in exposure to Al adjuvants significantly correlates with the increase in ASD prevalence in the United States observed over the last two decades (Pearson r = 0.92, p < 0.0001); and (iii) a significant correlation exists between the amounts of Al administered to preschool children and the current prevalence of ASD in seven Western countries, particularly at 3-4 months of age (Pearson r = 0.89-0.94, p = 0.0018-0.0248). The application of the Hill's criteria to these data indicates that the correlation between Al in vaccines and ASD may be causal. Because children represent a fraction of the population most at risk for complications following exposure to Al, a more rigorous evaluation of Al adjuvant safety seems warranted.     

正常顺产儿与早产儿人巨细胞病毒和风疹病毒脐带血清抗体检测分析

通过间接酶联免疫法检测178份新生儿(正常顺产儿为114例,早产儿64例)脐带血血清中人巨细胞病毒(human cytomegalovirus,HCMV)和风疹病毒(rubella virus,RV)IgG和IgM抗体,并分析所测结果与临床表现的相关性。结果表明,178例新生儿脐带血血清中HCMV-IgG阳性标本为168例(94.38%),HCMV-IgM阳性标本为1例(0.56%);RV-IgG阳性标本为119例(66.85%);RV-IgM阳性标本为1例(0.56%)。其中,正常顺产儿脐带血中HCMV-IgM和RV-IgM阳性率均为0.87%(1/114),HCMV-IgG阳性率为94.73%(108/114),RV-IgG阳性率为61.40%(70/114),HCMV和RV IgG两者均阳性者为55.26%(63/114);早产儿HCMV-IgM和RV-IgM均为阴性(0/64),HCMV-IgG阳性率为93.75%(60/64),RV-IgG阳性率为76.56%(49/64),HCMV和RV IgG两者均阳性者为70.31%(45/64)。早产儿与正常顺产儿比较,早产儿的RV-IgG阳性率和HCMV和RV-IgG两者均阳性者均高于正常顺产儿,且差异有统计学意义(P<0.05)。可见,HCMV感染率较高,至今仍无有效的HCMV疫苗,应加大疫苗研发力度。所查新生儿RV-IgG阳性率为66.48%,提示中国33%以上的育龄期妇女有在孕早期暴露感染的机率,国家有必要加大该种疫苗的接种力度。     

Mechanisms leading to restoration of muscle size with exercise and transplantation after spinal cord injury

We have shown thatcycling exercise combined with fetal spinal cord transplantationrestored muscle mass reduced as a result of complete transection of thespinal cord. In this study, mechanisms whereby this combinedintervention increased the size of atrophied soleus and plantarismuscles were investigated. Rats were divided into five groups(n = 4, per group): control, nontransected; spinal cordtransected at T10 for 8 wk (Tx); spinal cord transected for 8 wk andexercised for the last 4 wk (TxEx); spinal cord transected for 8 wkwith transplantation of fetal spinal cord tissue into the lesion site 4 wk prior to death (TxTp); and spinal cord transected for 8 wk,exercised for the last 4 wk combined with transplantation 4 wk prior todeath (TxExTp). Tx soleus and plantaris muscles were decreased in sizecompared with control. Exercise and transplantation alone did notrestore muscle size in soleus, but exercise alone minimized atrophy inplantaris. However, the combination of exercise and transplantationresulted in a significant increase in muscle size in soleus andplantaris compared with transection alone. Furthermore, myofibernuclear number of soleus was decreased by 40% in Tx and was notaffected in TxEx or TxTp but was restored in TxExTp. A strongcorrelation (r = 0.85) between myofiber cross-sectional area and myofiber nuclear number was observed in soleus, but not inplantaris muscle, in which myonuclear number did not change with any ofthe experimental manipulations. 5'-Bromo-2'-deoxyuridine-positive nuclei inside the myofiber membrane were observed in TxExTp soleus muscles, indicating that satellite cells had divided and subsequently fused into myofibers, contributing to the increase in myonuclear number. The increase in satellite cell activity did not appear to becontrolled by the insulin-like growth factors (IGF), as IGF-I andIGF-II mRNA abundance was decreased in Tx soleus and plantaris, and wasnot restored with the interventions. These results indicate that,following a relatively long postinjury interval, exercise andtransplantation combined restore muscle size. Satellite cell fusion andrestoration of myofiber nuclear number contributed to increased musclesize in the soleus, but not in plantaris, suggesting that cellularmechanisms regulating muscle size differ between muscles with differentfiber type composition.

     

Adaptation of gait initiation in children with unilateral idiopathic clubfoot following conservative treatment

Children with unilateral clubfoot (CF) treated conservatively have residual foot deformities and triceps surae m. atrophy. Using surface electromyography of tibialis anterior (TA), gastrocnemius (GA), and peroneus longus muscles, simultaneously with ground reaction forces recordings, the present work assesses the influence of this pathology on the gait initiation process. Ten children with CF and 10 healthy children were investigated. In children with CF, the velocity of the centre of gravity (CG) at the end of gait initiation did not differ from that of healthy children, because of adaptations of anticipation and execution phases. CG velocity at the end of anticipation was lower in children with CF than in healthy children when the swing foot was the affected one, indicating that propulsion was less efficient in this condition. It is shown that this resulted from alterations in anticipation duration, initial centre of pressure position and TA and PL excitations. Execution was shortened when support was provided by the pathological foot: the motor program was adapted to shorten the phase during which equilibrium control might be deficient. Biomechanical characteristics of the execution phase of children with CF did not depend on the swing foot. This indicated that the sound foot cannot be used as a control for accessing residual deficiencies.     

Clinical immunological disorders in children from various observation cohorts exposed to radiation factor during various stages of oncogenesis

The immune status disorders and features depending on the radiation impact type in various cohorts of radiation observations long after the Chernobyl (CNPP) disaster and the possible role of these disorders in development of chronic somatic pathology in children are shown. Lymphocyte depletion, T-cell immunity component disorders in the form of cell contraction with CD3, CD4, CD8 markers and the B-cell immunity component disorders in the form of reducing the quantity of CD10, CD23 marker cells were observed in children subject to combined chronic irradiation by 131I, 137Cs, 90Sr radionuclides. The descendants of irradiated parents (the 1st generation; children of the Chernobyl accident consequences liquidators, children of the citizens of radiation contaminated territories with various 137Cs levels) had immunity disorders of different type. A change in the total amount of NK-cells (CD16(+)-lymphocytes) is the general sign for all radiation risk groups; however, people subject to direct radiation impact demonstrated reduction of the antitumor protection potency, whereas descendants of irradiated ones demonstrated its activation with typically increasing number of CD16(+)-lymphocytes. In all radiation risk groups, a tendency to reduction of a number of cells involved in the leukocytal activation with the "pluripotential activation" marker (CD38 marker cells), proliferating cells (CD71 marker cells) and the increase of relative amount of cells with apoptosis marker (CD95(+)-lymphocytes). Immune disorder markers under the radiation impact in various cohorts of children's observation are suggested: antigens: CD4, CD8, CD10, CD23, CD16, CD38, CB71, CD95.     

Psychological disturbance in children with haemophilia.

OBJECTIVE--To assess the need for formal psychotherapeutic intervention in children attending a children''s haemophilia clinic after some of them had been diagnosed as positive for HIV. DESIGN--Comparison of haemophiliac children with matched control groups of diabetic and healthy children. SETTING--The West of Scotland Children''s Haemophilia Centre, Glasgow. PATIENTS--43 Children aged 3 to 16 years with mild, moderate, and severe clotting disorders were matched with control groups of 46 diabetic children and 42 physically healthy children. INTERVENTIONS--Parents of children aged 3-5 years were interviewed with the behaviour screening questionnaire. Children aged 6 to 16 were assessed by parental and teacher report using standardised questionnaires and self report using a computerised depression inventory. All were scored numerically according to the presence of symptoms of emotional and behavioural problems. MAIN OUTCOME MEASURES--The groups were compared for mean scores on each rating device and for number of children achieving scores within the pathological range. RESULTS--In the 6-16 age group five haemophiliac children, five diabetic children, and three healthy children scored in the pathological range on the parent questionnaire, as did two, three, and five respectively on the teacher questionnaire and four, four, and eight on the depression inventory. There was no significant difference across the three groups. Analysis of mean scores similarly showed no significant difference across groups. In contrast, the single measure used for younger children showed an increase in behavioural difficulties among the diabetic children. CONCLUSION--Haemophiliac children attending the West of Scotland Centre were no more disturbed than their diabetic or healthy peers despite the identification of HIV infection within the clinic and the widespread adverse publicity associated with AIDS and HIV infection.     

Enhancement of American chestnut somatic seedling production

Somatic embryogenesis holds promise for mass propagation of American chestnut trees bred or genetically engineered for resistance to chestnut blight. However, low germination frequency of chestnut somatic embryos has limited somatic seedling production for this forest tree. We tested the effects of culture regime (semi-solid versus liquid), cold treatment, AC and somatic embryo morphology (i.e., cotyledon number) on germination and conversion of the somatic embryos. Cold treatment for 12 weeks was critical for conversion of chestnut somatic embryos to somatic seedlings, raising conversion frequencies for one line to 47%, compared to 7% with no cold treatment. AC improved germination and conversion frequency for one line to 77% and 59%, respectively, and kept roots from darkening. For two lines that produced embryos with one, two or three-plus cotyledons, cotyledon number did not affect germination or conversion frequency. We also established embryogenic American chestnut suspension cultures and adapted a fractionation/plating system that allowed us to produce populations of relatively synchronous somatic embryos for multiple lines. Embryos derived from suspension cultures of two lines tested had higher conversion frequencies (46% and 48%) than those from cultures maintained on semi-solid medium (7% and 30%). The improvements in manipulation of American chestnut embryogenic cultures described in this study have allowed over a 100-fold increase in somatic seedling production efficiency over what we reported previously and thus constitute a substantial advance toward the application of somatic embryogenesis for mass clonal propagation of the tree.     

Development of chronic obstructive pulmonary disease correlates with mini- and microsatellite locus instability

Allele distribution at a highly polymorphic minisatellite adjacent to the c-Hras1 gene as well as deletions of microsatellite markers, D3S966, D3S1298, D9S171, and a microsatellite within p53 gene, were examined in bronchial epithelium specimens obtained from 53 chronic obstructive pulmonary disease (COPD) patients and healthy donors. A higher frequency of rare Hras1 minisatellite alleles in COPD patients than in the individuals without pulmonary pathology (6.6% versus 2.2%; P < 0.05) was shown. This difference was most pronounced in the group of ten COPD patients with idiopathic pulmonary fibrosis. Three of these patients had rare Hras1 minisatellite allele (P < 0.02 in comparison with healthy controls). Alterations in at least one of the microsatellite markers (deletions or microsatellite instability) were detected in bronchial epithelium samples obtained from: 4 of 10 COPD patients with pneumofibrosis (40%); 15 of 43 COPD patients (34.9%) without pneumofibrosis; and 8 of 20 tobacco smokers (40%) without pulmonary pathology. These defects were not observed in the analogous samples obtained from healthy nonsmoking individuals. No statistically significant differences were revealed between COPD patients and healthy smokers upon comparison of both the total number of molecular defects and the number of defects in the individual chromosomal loci. The total number of molecular defects revealed in bronchial epithelium samples from the individuals of two groups examined correlated with the intensity of exposure to tobacco smoke carcinogens (r = 0.28; P < 0.05). These findings suggest that rare alleles at the Hras1 locus may be associated with hereditary predisposition to COPD and the development of pneumofibrosis, while mutations in microsatellite markers result from exposure to tobacco smoke carcinogens and are not associated with the appearance of these pathologies.     

Differential immunogenicity and protective efficacy of DNA vaccines expressing proteins of Mycobacterium tuberculosis in a mouse model

BALB/c mice were vaccinated three times (2-week intervals) with plasmid DNA separately encoding antigen Ag85B, ESAT-6 or Ag85A from Mycobacterium tuberculosis. The protective efficacy of these DNA vaccines against intravenous M. tuberculosis H37Rv challenge infection was measured by counting bacterial loads in spleen and lung and recording changes in lung pathology. The splenocyte proliferative response to the corresponding antigens and antigen-specific interferon (IFN)-γ secreted by splenocytes of the vaccinated mice were also detected. We found a clear hierarchy of protective efficacies among the three DNA vaccines tested in this study. Plasmid DNA encoding Ag85A provided the strongest protection and showed the least change in lung pathology, followed by plasmid DNAs encoding Ag85B and ESAT-6. However, DNA-85B reduced comparative bacterial load in lung tissue, as did DNA-85A. Compared to the control group, protective efficacies conferred by different DNA vaccines were consistent with the lymphoproliferative responses to the corresponding antigens as well as the secretions of antigen-specific IFN-γ. Our study demonstrates that both Ag85A and Ag85B are the most promising of the candidate antigens tested for future TB vaccine development.     

Age-dependent cognitive defects caused by local brain lesions of various geneses

The results of neuropsychological analysis of 808 children and adolescents 7–18 years of age were studied. Among the test subjects, 689 children were patients with local brain lesions (tumors, arachnoid cysts, vascular pathology, and congenital hydrocephaly) and 119 children were healthy. Both patients and healthy subjects were divided into four age groups: junior school age (7–9 years), prepubertal age (10–12 years), pubertal age (13–15 years), and senior school age (16–18 years). Cognitive defects were found and demonstrated to depend on the test subject’s age and the type of brain pathology.     

A study of the migration of larval Anisakis simplex (Nematoda: Ascaridida) in the Chilean hake, Merluccius gayi (Guichenot)

Hake were collected during four trips to investigate a possible migration from viscera to somatic musculature of larval Anisakis simplex. On each trip 150 hake were examined and separated in five groups of 30 hake. One group consisted of fish gutted immediately after capture; two other groups were gutted 15 h after capture, one of which had been left at environmental temperature, and the other put in ice; the remaining two groups (exposed to the same treatment) were gutted 30 h after capture. All fish flesh was digested (HCl-pepsin digest); all nematodes found in the digest and in the viscera were counted. There was no increase of larval nematodes in flesh at 15 and 30 h. Temperature did not affect the migration of larvae. A regression test did not show significant differences between groups. Finally, there was no correlation between number of larvae in viscera and in musculature.     

Haemophilus influenzae meningitis in Manitoba and the Keewatin District,NWT: potential for mass vaccination.

A community-based surveillance study of all central nervous system infections was carried out in Manitoba and the Keewatin District, NWT, between Apr. 1, 1981, and Mar. 31, 1984. There were 201 cases of bacterial meningitis in Manitoba over the study period, 81 (40%) caused by Haemophilus influenzae; all but one isolate tested were type b (Hib). There were nine cases of H. influenzae meningitis in the Keewatin District. The overall annual incidence rate of H. influenzae meningitis in Manitoba was 2.5/100,000; for children under 5 years the rate was 32.1/100,000. For the Keewatin District the corresponding rates were 69.6/100,000 and 530/100,000. A total of 85% and 100% of the cases of H. influenzae meningitis occurred by 24 months of age in Manitoba and the Keewatin District respectively. The age at onset was earlier in native Indian children (22 cases) and Inuit children (9 cases) than in non-native children (59 cases) (p less than 0.005); thus, vaccine prevention of Hib meningitis will likely be more difficult in native Indian and Métis children. Without evaluating the increased potential of H. influenzae vaccines to prevent nonmeningitic forms of disease, we concluded that mass childhood vaccination with polyribosylribitolphosphate (PRP) vaccine is not warranted in Manitoba or the Keewatin District. Immunogenicity studies suggest that administration of conjugated Hib vaccines such as PRP-D in infancy may prevent approximately one-third to two-thirds of cases of H. influenzae meningitis; these vaccines warrant consideration for use in mass childhood vaccination programs.     

Interaction between resistance training and flexibility training in healthy young adults

To test the hypothesis that increases in muscle strength and flexibility are developed by specific training programs, 43 healthy young adults were tested before and after 4 different interventions conducted twice a week for 12 weeks: (a) resistance training only (n = 13); (b) flexibility training only (n = 11); (c) resistance and flexibility training (n = 9); and (d) no intervention (n = 10). There was no change in either strength or flexibility in the control group (p > 0.05). Resistance training improved muscle strength either alone (+14%; effect size = 0.53; p < 0.001) or in combination with flexibility training (+16%; effect size = 0.66; p = 0.032), but did not change flexibility (p = 0.610). Flexibility increased with specific training alone (+33%; p < 0.001) or in combination with resistance training (+18%; p < 0.001). In conclusion, in young, healthy subjects, resistance training alone did not increase flexibility, but resistance training did not interfere with the increase in joint range of motion during flexibility training. These results support the concept that specific training should be employed in order to increase either muscle strength or flexibility.     

Biosomatic effects of the electromagnetic fields on view of the physiotherapy personnel health

The effects of electromagnetic fields (EMFs) in physiotherapy have been discussed mainly with regard to the patient's safety, while the operator's safety is neglected. This paper presents the medical assessment and specific tendencies in the health status of personnel in physical therapy wards – where the EMFs are everyday background factor. This paper summarizes the somatic part of results from the study among physiotherapy personnel from facilities with different equipment and work load by using survey card designed by us for health status screening in somatic and neurobehavioral aspects. The main specific somatic findings and complaints in investigated group include parodontosis – 42%; cardiovascular disorders – 41.6%; allergic conditions with skin or systemic manifestation – 40.8%; photosensibilization – 34.1%; skin diseases – 31.5%; musculoskeletal disorders – 30.0% and neoplasm disorders – 7.5%. Keeping in mind that better part of the personnel in the physical therapy units is female, a special attention was paid to the pathology of the reproductive system; menstrual disturbances are observed in 20.0%. These findings are collected in complex for the first time in physiotherapy personnel, and when data were available from other professional groups, we found a good correlation.     

The results of state trials of inactivated influenza vaccines for children

Controlled epidemiological surveillance covering the total number of 13,355 schoolchildren aged 11-14 years and adolescents was carried out with a view to compare the efficacies of inactivated influenza vaccines. The children were immunized intradermally in a single injection with inactivated influenza vaccines containing A (H3N2) and A (H1N1) hemagglutinins, 3.5 micrograms per 0.2 ml of the preparation each. The studies demonstrated the safety and low reactogenicity of these vaccines, as well as their high antigenic potency. In 1984 during mixed influenza B + A (H1N1) epidemic the preparations produced a pronounced prophylactic effect: the efficacy indices were 1.6-1.9 (p less than 0.001). The results obtained in these studies made it possible to recommend two inactivated influenza vaccines (chromatographic and centrifugal) for practical medicine with the aim of protecting children aged 11 years and over from influenza.     

The Cross-Neutralizing Activity of Enterovirus 71 Subgenotype C4 Vaccines in Healthy Chinese Infants and Children

Background

EV71 is one of major etiologic causes of hand-foot-mouth disease (HFMD) and leads to severe neurological complications in young children and infants. Recently inactivated EV71 vaccines have been developed by five manufactures and clinically show good safety and immunogenicity. However, the cross-neutralizing activity of these vaccines remains unclear, and is of particular interest because RNA recombination is seen more frequently in EV71 epidemics.

Methodology/Principal Findings

In this post-hoc study, sera from a subset of 119 infants and children in two clinical trials of EV71 subgenotype C4 vaccines (ClinicalTrials.gov Identifier: NCT01313715 and NCT01273246), were detected for neutralizing antibody (NTAb) titres with sera from infected patients as controls. Cytopathogenic effect method was employed to test NTAb against EV71 subgenotype B4, B5, C2, C4 and C5, which were prominent epidemic strains worldwide over the past decade. To validate the accuracy of the results, ELISpot assay was employed in parallel to detect NTAb in all the post-vaccine sera. After two-dose vaccination, 49 out of 53 participants in initially seronegative group and 52 out of 53 participants in initially seropositive group showed less than 4-fold differences in NTAb titers against five EV71 strains, whereas corresponding values among sera from pediatric patients recovering from EV71-induced HFMD and subclinically infected participants were 8/8 and 41/43, respectively. The geometric mean titers of participants against five subgenotypes EV71 all grew significantly after vaccinations, irrespective of the baseline NTAb titer. The relative fold increase in antibody titers (NTAb-FI) against B4, B5, C2, and C5 displayed a positive correlation to the NTAb-FI against C4.

Conclusions/Significance

The results demonstrated broad cross-neutralizing activity induced by two C4 EV71 vaccines in healthy Chinese infants and children. However, the degree of induced cross-protective immunity, and the potential escape evolution for EV71 still need to be monitored and researched in future for these new vaccines.