Efficacy and safety of ribosome-component immune modulator for preventing recurrent respiratory infections in socialized children.

Attending day care is associated with recurrent respiratory infections (RRIs) and asthma. Ribosomal immunotherapy may confer protection against RRIs in children. This study was designed to assess the efficacy of a ribosome-component immune modulator (RCIM) as preventive treatment of respiratory infections in socialized children aged ≤5 years, with or without a history of frequent RRI. In a multicenter, Italian, randomized, double-blind, placebo-controlled, parallel-group study, 164 socialized day care center children (mean age, 3.8 ± 1.1 years) were treated with RCIM or placebo for 6 months and followed-up for additional 6 months. Outcomes are presented for the intent-to-treat population. In socialized children with five or less RRIs (n = 95; 49 RCIM and 46 placebo, group A) the duration of the infectious episodes was significantly shorter with RCIM than with placebo (6 months, 3.7 ± 2.1 versus 4.5 ± 1.9 days, p = 0.040; 12 months, 3.6 ± 2.0 versus 4.7 ± 2.5 days, p = 0.015). The proportion of patients reporting no respiratory infectious episodes with RCIM at 6 and 12 months was also significantly larger in group A (20.4% versus 4.4% placebo; p = 0.028). No such differences were found in children with more than five RRIs in the preceding year (n = 63; 32 RCIM and 31 placebo, group B). In all children, general well-being improved significantly more under RCIM than under placebo (11.6 ± 1.8% versus 10.2 ± 1.8%; p = 0.002). No statistically significant between-treatment differences were observed for other end points. Both treatments were similarly well tolerated. Six-month treatment with RCIM effectively prevented the 12-month risk of RRIs in children <5 years old and with five or less RRIs in the preceding year.

Rationale for the clinical use of a ribosome-component immune modulator.

Vaccines have long been used to boost the immune system and to confer protection against microbial infections. In contrast, immunotherapy based on ribosomal preparations has been proposed to enhance both specific and nonspecific immune responses (in particular, the mucosal immune defense system) against common respiratory tract pathogens. The aim of this review is to summarize current knowledge on the ability of a combination of four immunogenic ribosomal fractions from different bacteria species and of the extracted fraction from the membrane of Klebsiella pneumoniae to modulate several immune functions. The immunomodulatory activity of the ribosome component is attributed to the presence of highly purified epitopes from cellular fractions obtained by bacterial lysis. The ribosomal preparation is hypothesized to induce a T-dependent immune response consequent network with proliferation of B lymphocytes and production of secretory high-affinity antibodies (in particular, IgA), as well as the creation of a specific immune memory. Indeed, this agent stimulates the activity of macrophages, polymorphonuclear cells, and natural killer cells. The "ideal" vaccine is a highly purified protein bound to a carrier and an adjuvant that enhances the vaccination effect.

Cost effective analysis of ribosome-component immune modulation.

In childhood, recurrent airway infections are the most common cause for medical visits and hospitalizations. Their economic impact is considerable and their treatment accounts for a substantial quota of the health care budget. Despite documented efficacy and safety, ribosomal bacterial vaccine and membrane fraction use is still limited by being prevalently considered for prevention rather than treatment. The objective of this study was to analyze the economic benefit achieved with ribosomal immunotherapy. A review was performed of available literature data on economic parameters. Pharmacoeconomic studies published during the past few years showed how the use of ribosome component immune modulator is capable of reducing expenditure associated with treatment of recurrent respiratory infection and allows achievement of substantial savings in terms of cost, time, and loss of productivity. The initial cost of prevention in patients suffering from chronic respiratory infections is offset by a subsequent saving arising from less recurrence of disease. Direct management costs such as therapy courses, medical visits, medical exams, hospitalizations, etc., and indirect costs such as absence from school and work are not routinely considered by primary care physicians.

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.

Ribosome-component immune modulation of respiratory tract infections in adults.

The standard therapeutic strategy for bacterial episodes (and bacterial superinfections) is the repeated use of antibiotics. Although antibiotics are fast acting and curative, they do not prevent recurrence or complications. The incidence of recurrent respiratory infections and a substantial increase of costs justify preventive measures based on boosting the patients' immune system by immunomodulation using bacterial products, which, in the long term, stimulates immunity and reduces recurrence of infection. This study was designed to review the epidemiological features of respiratory infections and prevention strategies in adults. A narrative review was performed of the relevant literature. Several products of the immune modulator class are available: bacterial lysates, bacterial membrane component by-products, chemically synthesized compounds, and specific bacterial components (ribosome-component immune modulator [RCIM]). The clinical efficacy of the RCIM has specific and nonspecific immunostimulant properties. Efficacy is mainly documented by decreased recurrent episodes of infection and prescription and need for antibiotics. Benefits are generally observed after 3 months of treatment and are maintained for 6 months. Clinical trial evidence is accruing of the efficacy of RCIM in preventing recurrence of upper and lower airway infections or relapses in adults.