Duration Of Infectious Episodes Research Articles

Perinatal and Other Risk Factors for Common Infections in Infancy: A Prospective Cohort Study.

Limited data from prospective cohort studies in high-income countries are available on the perinatal risk factors for common infections in children. Our hypothesis was that perinatal factors may be risk factors for infectious episodes during the first year of life. In this prospective Health and Early Life Microbiota birth cohort study of full-term infants (n = 1052) born in 2016-2018, the number and duration of infection episodes were collected online at weekly to monthly intervals. In a multivariate regression model, the main exposures were perinatal factors such as mode of delivery and intrapartum antibiotics. Environmental factors were additional exposures. The outcomes were the number and duration of infectious episodes in the first year of life. The mean number of infection episodes was 4.2 (2.9 SD). The mean duration of infection symptoms was 44 days (40 SD). Upper respiratory infections accounted for 83% of the episodes (3674/4455). Perinatal factors were not associated with the number nor the duration of infection episodes, but cesarean section was associated with an increased occurrence of urinary tract infections in infancy [adjusted odds ratio (aOR): 3.6; 95% confidence interval (CI): 1.13-11.1]. Of the additional exposures male sex (aOR: 1.1; 95% CI: 1.0-1.2) and the presence of siblings (aOR: 1.3; 95% CI: 1.2-1.4) were associated with the number of infection episodes. This prospective cohort study showed that perinatal factors, mode of delivery and intrapartum antibiotics were not associated with the risk of common infections in infancy, but cesarean delivery was associated with a risk of urinary tract infections.

Open Comparative, Randomized Controlled Clinical Study of a New Immunostimulating Bacterial Lysate in the Prophylaxis of Upper Respiratory Tract Infections

One hundred and fourteen patients with a medical history of recurrent upper respiratory tract infections (at least four episodes in the year preceding this open comparative study) were randomly assigned to three groups of 38 patients each. The first group received, by sublingual route, Ismigen, a new immunostimulating lysate (Polivalent Mechanical Bacterial Lysate, PMBL) obtained by mechanical lysis of 48 billion bacteria commonly responsible for upper respiratory tract infections; the second group received an oral immunostimulating lysate (CLBL) obtained by chemical lysis of 36 billion bacteria. A third group served as control and did not receive any immunostimulating treatment (Control NT). One tablet a day of PMBL was given to the first group for the first ten days during three consecutive months; the patients of the second group received one capsule a day of CLBL with the same treatment schedule. At the end of the treatment period the patients of the 3 groups were followed up for 3 months. The primary end point was the number of acute upper respiratory tract infections (URTIs) that occurred during the three months of treatment and three months of follow-up. Secondary endpoints were: the number of patients free from disease, the duration of infectious episodes, the number of working days lost because of disease, the need for a concomitant antibiotic treatment, and the safety of the two treatments. During the treatment period the mean number (+/- SD) of URTIs per patient was 0.34 (0.48) in the PMBL group, 1.0 (0.83) and 1.23 (0.77) in the CLBL and Control NT groups, respectively. Results of PMBL treatment were significantly better (p < 0.05) than the results in the other two groups; CLBL was not significantly different from the control group. In the three months of follow-up, the mean number (+/- SD) of URTIs per patient was: 0.42 (0.55) in the PMBL group, 0.92 (0.67) in the CLBL group, and 1.55 (0.88) in the Control NT group. The PMBL group was significantly better than the other two (p < 0.05). During the 6-month study, significantly more patients of the PMBL group remained free from respiratory infections in comparison to the other two groups. As regards other secondary end points (duration of infectious episodes and number of working days lost), the mean values of the PMBL group were statistically significantly lower than those of the other two groups, in both the treatment and follow-up periods. No PMBL treated patient needed concomitant administration of an antibiotic, while 9 patients of the CLBL group received such treatment (p < 0.05). No patient reported adverse events.

Ribosome-component immune modulation of respiratory tract infections in children

More than 25% of infants in their first year of life and 18% of children aged between 1 and 4 years suffer from recurrent respiratory infections (RRIs) in Western countries. Although RRIs are self-limiting as a rule, complications may include otitis media, sinusitis, and bronchial and pulmonary infections. This study was designed to present the available data on immune modulators (defined as drugs that interact with the immune system and modulate immune function by stimulating a more rapid and effective immune response). A ribosome-component immune modulator (RCIM) designed to stimulate both specific and nonspecific immunity in children and thus prevent or alleviate RRI is also described. A narrative review of the literature was performed with a focus on clinical trials. Double-blind, placebo-controlled studies have shown that an RCIM effectively prevents recurrent bronchopulmonary and ear-nose-throat infections; in particular, the number, severity, and duration of infectious episodes and the numbers of antibiotic courses, concomitant medications, and days away from school (children) or the workplace (parents) were reduced. Use of a RCIM is clinically efficacious, incurs minimal risk of adverse events, and, thus, represents a consistent therapeutic approach for RRIs.

A preventive measure for otitis media in children with upper respiratory tract infections

Recurrent upper respiratory tract infections (URTI) are very common in patients of all ages. Rhinitis, bronchitis, chronic sinusitis and otitis appear to be the prevalent forms of recurrent respiratory infections in the paediatric population. The aim of treatment is so the solution of the respiratory pathology and the also the prevention of their complications. Antibacterial therapy is still the classical treatment approach in patients both with respiratory tract infections and with otitis media, despite the fact that antibacterials have several well known drawbacks, especially when used to treat recurrent infections. Eighty-four paediatric patients of both sexes (range: 4–14 years) with otitis were enrolled in the study. Patients were included if they had a >2 years' history of recurrent or chronic respiratory infections, and/or had experienced at least three episodes requiring medical consultations and/or treatment during the winter prior to the study. The young patients were randomised to receive Immucytal (group A) or placebo (group B) treatment according to the following protocol: (1) starting therapy (1 month): one tablet daily in the morning 4 days per week for 3 consecutive weeks; (2) maintenance period (5 months): one tablet daily in the morning 4 days per week for 1 week every month. Placebo and Immucytal tablets were identical in shape and size, in order to maintain double-blind conditions. Patients of group A with recurrent URTI had a significantly decreased incidence of ENT infections, fever and shorter duration of illness, decreased requirement for ancillary medications and fewer work-days lost. The reduction in the incidence of infectious episodes became significant vs. placebo. A significantly improved outcome vs. placebo was also observed on the incidence of fever, frequency and duration of infectious episodes, ancillary therapies. Immucytal treatment was associated with significant changes in both immunological and auditory function parameters. Serum concentrations of immunoglobulins were significantly increased in Immucytal. For both evaluations, a significant difference between treatment groups was found ( P>0.001). Preventive strategies, such as ribosomal immunotherapy, may represent a valid alternative approach.

Prophylaxis with the Novel Immunomodulator Pidotimod Reduces the Frequency and Severity of Upper Respiratory Tract Infections in Children with Down's Syndrome

Down's syndrome (DS) is associated with several defects of both specific and non-specific immunity which may explain the enhanced susceptibility of DS subjects to viral and bacterial infections. In this study we have evaluated the effects of the new synthetic immunomodulator pidotimod in recurrent infections of the upper respiratory tract in a group of children with DS. It was an open trial vs untreated control, the pidotimod-treated group consisted of 14 subjects and the control group of 12. Pidotimod was administered at the dose of one 400 mg oral bottle/day for 90 days. There was a significant reduction in the frequency, severity and duration of infectious episodes in the pidotimod-treated group vs the untreated control group. The beneficial effects of pidotimod were also confirmed by a series of recordings made over the 90-day treatment period which showed a significant reduction in the number of days of fever, severity of the signs and symptoms of the acute episodes and use of antibiotics and antipyretic drugs. Pidotimod was well tolerated and no clinical, hematological or biochemical side-effects were noted.

Prevention of Recurrent Infections

This study investigated the role of ribosomal immunotherapy ('Ribomunyl') in the rehabilitation of 153 children aged 7 to 14 years who had chronic diseases of the respiratory tract or ear, nose and throat (ENT) and were living in the Aral region (Kazakhstan). Diagnoses included chronic tonsillitis (n = 8), adenoid polyps (n = IS), chronic pharyngitis (n = 42), chronic otitis (n = 23), and other chronic respiratory infections (n = 65). These children received ribosomal immunotherapy. To enable comparison of the study parameters, there was a control group consisting of relatively healthy children. The effect of ribosomal immunotherapy was evaluated on the basis of clinical signs, duration of remissions and duration of antibacterial treatment courses, and by immune indices, which were determined by special immune methods: definition of CD3, CD4, CD8 and 3F3 cells, and serum JgM, IgG and IgA levels. The children from the Aral region with chronic respiratory tract and ENT diseases were found to have reduced CD3 cell counts (-20%), sharply increased numbers of CD4 cells, and higher concentrations (+30%) of IgG compared with the healthier control group. The average duration of infectious episodes in children with recurrent infections was 90 to 94 days over the previous winter, and the average duration of antibacterial therapy for each episode of acute respiratory disease was 8 days. After 6 winter months of ribosomal immunotherapy, the average duration of infectious episodes was 40 days, while the average duration of one-course antibacterial therapy for acute respiratory disease was 4 days. The number of CD3 cells had increased but remained 10% below the level of the control group; the number of CD4 cells had increased 2-fold.

Molecular regulation of hematopoietic cytokines: implications and indications for clinical use in pediatric oncology.

Proliferation and differentiation of hematopoietic progenitor cells are regulated by a network of stimulatory and inhibitory cytokines. An understanding of the molecular mechanisms of growth control may provide a physiologic basis for the innovative therapy of bone marrow disorders. Among various accessory cells, bone marrow T lymphocytes are capable of stimulating, as well as inhibiting, hematopoietic progenitor cells. We have now elucidated molecular mechanisms regulating the differential expression of T cell genes encoding for the stimulatory and inhibitory hematopoietic programs. Stimulation of hematopoiesis requires granulocyte-macrophage colony stimulating factor (GM-CSF), whereas inhibition requires interferon-gamma (IF gamma). Both cytokines can be induced by interleukin-2 (IL2). The T cell IL2 receptor consists of a 75 kD chain (p75) mainly expressed on a subset of resting T cells and a 55 kD chain (p55) which is strongly expressed upon T cell activation. P55 and p75 associate on activated T cells to form a dimeric receptor molecule exhibiting high affinity for IL2. The p75 monomer has an intermediate affinity for IL2. Expression of p55 in the context of the high affinity IL2 receptor constitutes a requirement for T cell IFg release. In contrast, p75 alone is capable of mediating the production of GM-CSF. Thus, T cells may be capable of selective production of cytokines with specific effects in hematopoietic growth control. Utilizing a human peripheral blood leukocyte genomic library, we identified various clones containing the entire GM-CSF gene, including coding and regulatory regions. Cloning of the GM-CSF gene allowed clinical studies utilizing recombinant DNA-derived GM-CSF. Chemotherapy-induced neutropenia contributes to both complications of cytotoxic therapy as well as increased relapse incidence of underlying disease. In a prospective randomized study, we have demonstrated that GM-CSF abrogates neutropenia following aplasiogenic chemotherapy in children and adolescents with solid tumors, and that GM-CSF may reduce the duration of infectious episodes after cytotoxic therapy. Next, we escalated the cumulative doses of cytotoxic therapy in an ablative regimen followed by hematopoietic stem cell transplantation to treat patients with poor prognosis pediatric tumors. Morbidity of this highly toxic ablative regimen depends on the duration of myeloid aplasia. Median duration of aplasia following hyper-VAMP was 13 days with CM-CSF and 29 days without GM-CSF. In addition, we have employed p55 blocking monoclonal antibody for prevention of graft vs. host disease in bone marrow transplantation. The understanding of specific molecular mechanisms of hematopoietic immuno-regulation can thus be utilized to provide novel approaches to the treatment of bone marrow failure and cancer.