Cost-effectiveness of strategies for preventing paediatric lower respiratory infections associated with respiratory syncytial virus in eight Chinese cities

BackgroundNew monoclonal antibodies (mAbs) and vaccines against RSV with promising efficacy and protection duration are expected to be available in the near future. We evaluated the cost-effectiveness of the administration of maternal immunisation (MI), infant mAb (IA) and paediatric immunisation (PI) as well as their combinations in eight Chinese cities.MethodsWe used a static model to estimate the impact of these preventive interventions on reducing the burden of RSV-ALRI in twelve monthly birth cohorts from a societal perspective. In addition to year-round administration, we also considered seasonal administration of MI and IA (i.e., administered only to children born in selected months). The primary outcome was threshold strategy cost (TSC), defined as the maximum costs per child for a strategy to be cost-effective.ResultsWith a willingness-to-pay threshold of one national GDP per capita per QALY gained for all the cities, TSC of year-round strategies was: (i) US$2.4 (95% CI: 1.9-3.4) to US$14.7 (11.6-21.4) for MI; (ii) US$19.9 (16.9-25.9) to US$144.2 (124.6-184.7) for IA; (iii) US$28.7 (22.0-42.0) to US$201.0 (156.5-298.6) for PI; (iv) US$31.1 (24.0-45.5) to US$220.7 (172.0-327.3) for maternal plus paediatric immunisation (MPI); and (v) US$41.3 (32.6-58.9) to US$306.2 (244.1-441.3) for infant mAb plus paediatric immunisation (AP). In all cities, the top ten seasonal strategies (ranked by TSC) protected infants from 5 or fewer monthly birth cohorts.ConclusionsAdministration of these interventions could be cost-effective if they are suitably priced. Suitably-timed seasonal administration could be more cost-effective than their year-round counterpart. Our results can inform the optimal strategy once these preventive interventions are commercially available.     

RSV neutralization assays – Use in immune response assessment

Respiratory syncytial virus (RSV) is a leading cause of respiratory illness among children and infants worldwide, yet no licensed vaccine exists to reduce the risk of disease. At least 16 RSV vaccine candidates are currently in clinical development and many are designed to induce robust virus neutralizing immune responses. RSV neutralizing antibody (nAb)-mediated interventions such as intravenous immunoglobulin (IVIG) and palivizumab provide passive protection against serious lower respiratory tract disease due to RSV, validating nAbs as a correlate of protection. To identify correlates of protection for vaccine candidates that have demonstrated their protective efficacy, an investigator can use assays designed to measure nAb responses. However, there is no standard method of measurement; individual laboratories have developed their own methods to measure the ability of nAbs to reduce the infectivity of a defined virus dose in a variety of cell lines, leading to establishment of the broad variety of RSV neutralization assay formats currently in use.Standardizing the RSV neutralization assay is an essential step toward better assessment of nAb responses to vaccine candidates. Use of a common reference standard by all makes comparing the immunogenicity of different vaccine candidates feasible. In the context of vaccine development, the WHO 1^st International Standard for Antiserum to RSV (RSV IS) has been shown to be suitable for harmonizing results across laboratories and assay formats used to measure nAb titers to RSV/A and RSV/B in human sera.This review describes the broad variety of RSV virus neutralization assay formats currently in use and the importance of the RSV IS for harmonization of results across formats and across laboratories. It also outlines good practices for key assay components and data analysis to promote the quality and consistency of measuring RSV nAb titers in serum specimens.     

Characteristics of steroid hormone binding systems in hepatocyte plasma membranes

Parameters of binding of cortisone and estradiol to plasma membranes of rat hepatocytes were studied by the method of liquid scintillation radiometry. The presence of two systems for the binding of these hormones in the membranes was demonstrated. One system is specific (saturable) and binds hormones in physiological concentrations. The capacity and affinity of this system for cortisone are significantly higher than for estradiol. The binding parameters within the temperature range from 4 to 37°C for cortisone and estradiol respectively are: Dissociation constant 2.1–3 and 2.7–4.5 nM, number of binding sites 2–2.4 and 0.14–0.18 nmoles/mg protein. Experiments with p-chloromercuribenzoate demonstrate the role of proteins in the working of this system. The second (unsaturable) system is nonspecific and its function is determined by the lipid component of the membranes. The affinity of corticosteroids for hepatocytes is probably due to the activity of the (saturable) specific system of the plasma membranes of these cells.Department of Molecular Pharmacology and Radiobiology, Medico-Biological Faculty, N. I. Pirogov Second Moscow Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR N. A. Yudaev.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 89, No. 2, pp. 172–174, February, 1980.     

Electrophoretic investigation of nuclear membrane ribonucleases of rat liver and hepatoma-27 cells

Preparations of the nuclear membranes were obtained from purified nuclei of rat liver and hepatoma-27 cells, and from them enzyme-containing extracts of acid-soluble proteins were then prepared. The protein extracts were subjected to disk electrophoresis in 15% polyacrylamide gel. Ribonucleases (RNases) which are constituents of the acid-soluble proteins of the nuclear membranes of normal liver were found to be present as several different components which differed in their electrophoretic mobility and in several physicochemical properties from crystalline bovine RNase and the RNase of nuclear chromatin.Institute of Problems in Oncology, Academy of Sciences of the Ukrainian SSR, Kiev. N. K. Kol'tsov Institute of Developmental Biology, Academy of Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR R. E. Kavetskii.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 84, No. 12, pp. 670–672, December, 1977.     

Usefulness of basement membrane markers in tumoural pathology

The distribution of basement membrane (BM) markers, type IV collagen, laminin (LM), heparan sulphate proteoglycan (HSP) and fibronectin (FN) has been studied by indirect immunofluorescence using specific antibodies, in tumoural pathology. The disrupted pattern of BM by these markers in severe dysplastic lesions of the breasts, the bronchi and uterine cervix provides evidence for malignancy. In invasive carcinomas, there is generally a loss of these BM components, with FN persisting in the stroma. The loss of these markers in BM is concomitant and superimposable in double staining studies. In embryonic tumours, the presence of BM markers is related to a mesenchymal differentiation of malignant cells with pericellular FN and/or maturation towards organoid structures with BM. In sarcomas, there is a loss of the pericellular BM staining around most transformed muscular and Schwann cells and adipocytes. The persistence of this labelling in some well-differentiated areas can help to diagnose the nature of the sarcoma. The persistence of intercellular filaments of FN corresponds to the mesenchymal and/or sarcomatous nature of undifferentiated anaplastic proliferations.     

Connective tissue repair in circumferential periodontal defects in dogs following use of a biodegradable membrane

A biodegradable polylactic acid membrane was evaluated for its ability to enhance periodontal regeneration. In 8 Labrador dogs, circumferential defects were created around the maxillary 1st premolars. The defects were combination "1-wall vertical and horizontal". A membrane was adjusted to cover the defect on one side of the jaw, while the contralateral tooth served as control without membrane. After 3 months, healing was evaluated histologically. The results demonstrated that the amount of connective tissue repair with newly formed cementum approximated 50% of the defect height for both test and control groups. Thus, no advantage to the use of membrane was found, which is contradictory to the findings of our previous dog study using the same biodegradable membrane. The possible reasons for this difference in results are discussed relative to suggested mechanisms for membrane effects in periodontal regeneration.     

Azelastine and allergen transduction signal in MC9 mast cells

Summary MC9 mast cells, sensitized with monoclonal IgE antibody specific for 2,4-dinitrophenyl (DNP) group, were exposed to DNP-BSA and the pH and cytosolic calcium signals were recorded by using the fluorescent probes BCECF and Fura-2 respectively. DNP-BSA induced cell alkalinization was fully inhibited by azelastine with IC₅₀ (1.6±0.5 mol/l, mean±SEM, n = 5) similar to that required to inhibit histamine release (1.4 mol/l), Conversely, high azelastine concentrations (> 100 mol/l) were required to inhibit DNP-BSA-dependent cell calcium mobilization (IC₅₀200 mol/l, n = 3). Amiloride, but not the H₁ histamine antagonist pyrilamine, was able to inhibit the DNP-BSA induced pH signal. In acidified mast cells, azelastine potently inhibited Na⁺:H⁺ exchange activity (IC₅₀ = 7.7±3.6 × 10^–6 M, mean±SEM, n = 3). Conversely, in mouse spleen lymphocytes azelastine was unable to inhibit the amiloride-sensitive pH signal induced by concanavalin A. In conclusion, the inhibition of histamine release by azelastine is not due to an interference with the cytosolic calcium signal. Conversely, azelastine potently antagonized the allergen-dependent Na⁺: H⁺ exchange activation, suggesting an action on the protein kinase C signaling pathway. Correspondence to: R. P. Garay at the above address     

Determination of microviscosity and location of 1,3-Di(1-pyrenyl)propane in brain membranes

We determined the microviscosity of synaptosomal plasma membrane vesicles (SPMV) isolated from bovine cerebral cortex and liposomes of total lipids (SPMTL) and phospholipids (SPMPL) extracted from SPMV. Changes in the microviscosity induced by the range and rate of lateral diffusion were measured by the intramolecular excimerization of 1,3-di(1-pyrenyl)-propane (Py-3-Py). The microviscosity values of the direct probe environment in SPMV, SPMTL and SPMPL were 38.17, 31.11 and 27.64 cP, respectively, at 37°C and the activation energies (E_a) of the excimer formation of Py-3-Py in SPMV, SPMTL and SPMPL were 8.236, 7.448 amd 7.025 kcal/mol, respectively. Probe location was measured by polarity and polarizability parameters of the probe Py-3-Py and probe analogues, pyrene, 1-pyrenenonanol and 1-pyrenemethyl-3β-hydroxy-22,23-bisnor-5-cholenate (PMC), incorporated into membranes or solubilized in reference solvents. There existed a good linear relationship between the first absorption peak of the¹L_a band and the polarizability parameter (n ²−1)/(2n ²+1). The calculated refractive index values for SPMV, SPMTL and SPMPL were close to 1.50, which is higher than that of liquid paraffin (n=1.475). The probe location was also determined by using a polarity parameter (f−1/2f¹). Here f=(ε−1)/(2ε+1) is the dielectric constant function and f'=(n ²−1)/(2n ²+1) is the refractive index function. A correlation existed between the monomer fluorescence intensity ratio and the solvent polarity parameter. The probes incorporated in SPMV, SPMTL, and SPMPL report a polarity value close to that of 1-hexanol (ε=13.29). In conclusion, Py-3-Py is located completely inside the membrane, not in the very hydrophobic core, but displaced toward the polar head groups of phospholipid molecules, e.g., central methylene region of aliphatic chains of phospholipid molecules.