Multiplex label-free biosensor for detection of autoantibodies in human serum: Tool for new kinetics-based diagnostics of autoimmune diseases.

A multiplex label-free biosensor is developed for diagnostics of autoimmune diseases by highly sensitive measuring in human serum both critical characteristics of autoantibody: concentration and native kinetic parameters that reflect autoantibody aggressiveness to the organism's tissues. The biosensor is based on the spectral-correlation interferometry and image processing of a microarray glass biochip, affordable to be single-used in medical applications. Simultaneous 25-min detection and activity characterization of several autoantibodies in the same serum sample have been demonstrated for anti-thyroglobulin (anti-TG) and anti-thyroid peroxidase (anti-TPO) as models. The biosensor offers extremely high sensitivity: limits of detection in serum are 1.7 IU/mL and 6 IU/mL for anti-TPO and anti-TG, respectively. The dynamic range covers the whole range of clinically relevant concentrations of the autoantibodies up to 1000 IU/mL. The developed method of characterization of autoantibody activity by recording the kinetics of their binding with free native antigens is based on autoantibody polyvalency. The measurements in clinical serum samples have shown that the native kinetic parameters are independent of concentration. The proposed biosensor and method of native kinetic registration can be used to develop new criteria for comprehensive diagnostics of autoimmune diseases, based not only on traditional measurements of concentration but also on quantitative evaluation of autoantibody aggressiveness. The developed method can be adapted to other label-free sensors such as those based on the surface plasmon resonance, optical waveguides, etc.

Data on characterization of glass biochips and validation of the label-free biosensor for detection of autoantibodies in human serum.

The data represent in-depth characterization of a novel method for highly sensitive simultaneous measuring in human serum of both critical parameters of autoantibodies: concentration and native kinetics. The latter refers to autoantibody interaction with free, not immobilized, antigen. The method and related biosensors are based on the spectral-correlation and spectral-phase interferometry. The data cover: multi-factor optimization and quantitative characterization of the developed affordable single-used biochips, including X-ray photoelectron spectroscopy (XPS) control of chemical modifications of the surface during fabrication; antibody screening; optimization and verification of protocols for label-free biosensing in human serum; mathematical model for fitting experimental data and calculation of kinetic constants of interaction of autoantibodies with free antigen; comprehensive verification of the method specificity; correlation between the data obtained with the developed biosensor and with enzyme linked immunosorbent assay (ELISA); comparison of analytical characteristics of the developed biosensor with the most advanced label-based methods. The data importance is confirmed by a companion paper (DOI 10.1016/j.bios.2020.112187), which shows that the combination of mentioned autoantibody parameters is promising for more accurate criteria for early diagnostics and efficient therapy of autoimmune disorders. The obtained data can be used in development of a wide range of biosensors, both label-free and based on various labels.

Effect of HMG-CoA-reductase inhibitor on DNA synthesis and free radical oxidation in the gastric mucosa under normal conditions and during indometacin-induced ulcerative process in the stomach of albino mice.

We studied the effect of simvastatin (24 mg/kg per os for 30 days) on DNA synthesis ((3)H-thymidine autoradiography) and free radical oxidation (chemiluminescent method) in the gastric mucosa of albino mice under normal conditions and in ulcerative process induced by single indometacin administration. Simvastatin treatment activated free radical oxidation, which was seen from enhanced chemiluminescence in the mucosa homogenate (by 1.7-4.6 times). Administration of indometacin against the background of simvastatin treatment potentiated local oxidative stress and inhibited DNA synthesis. Under these conditions, the area of ulcerative lesion in the gastric mucosa increased by 3.0 times.

How many doses of diphtheria toxoid are required for protection in adults? Results of a case-control study among 40- to 49-year-old adults in the Russian Federation.

During the Russian diphtheria epidemic of the 1990s, adults had an unexpectedly high rate of disease. A retrospective, matched case-control study was done to measure the effectiveness of one, two, or three or more doses of diphtheria toxoid against diphtheria among 40- to 49-year-old Russians. Thirty-nine diphtheria case-patients and 117 controls were studied. Previous vaccinations were included if one dose was received within the previous 10 years. Five cases (13%) and 33 controls (28%) had received three or more doses of vaccine. The matched odds ratio was 0.3 (95% confidence interval, 0.1-0.9) for three or more doses compared with no doses, which was a vaccine effectiveness of 70% (95% confidence interval, 10-90). A trend existed toward milder disease with increasing doses (chi2 test for trend, P=.02). The results suggest that Russian adults, who were unlikely to have acquired immunity to diphtheria through immunization or natural infection, required at least three doses of diphtheria toxoid for reliable protection against disease.

Role of health communications in Russia's diphtheria immunization program.

As part of a broader program in health communication assistance, project staff from Basic Support for Institutionalizing Child Survival worked with staff from Russia's oblast (regional) public health agencies to design and implement communication activities supporting local diphtheria immunization efforts. Because aggressive community outreach efforts and strong administrative sanctions had already achieved impressive adult coverage rates for first doses of diphtheria toxoid vaccine, communication interventions emphasized the need for second and third doses. Outcomes were assessed through vaccination coverage data and more qualitative measures. In one project site, the increase in adult coverage (two or more doses) was very modest. In a second site, with a stronger communications component, coverage increased significantly (from 20% to 80%). Although it is not possible to disentangle completely the effects of communications from other aspects of oblast immunization programs, these and other outcome data suggest that health communications can play an important role in Russia's ongoing mass immunization efforts.

Epidemiology of epidemic diphtheria in three regions, Russia, 1994-1996.

BACKGROUND: A massive diphtheria epidemic which began in the former Soviet Union in 1990 is the first large-scale diphtheria epidemic in developed countries in more than 30 years and has primarily affected adults. In response, health authorities attempted to maximize vaccination for children and conducted an unprecedented campaign to vaccinate adults. METHODS: We analyzed diphtheria surveillance data (case report forms and diphtheria vaccine coverage data) from three Russian regions from January 1994 to December 1996 and estimated vaccine effectiveness by the screening method. RESULTS: We reviewed records from 2243 (97.2%) of 2307 reported cases. The highest cumulative incidence in the period was among children aged 5 to 9 years (106 cases per 100,000 population); adults aged 40-49 years had the highest adult incidence for disease (88 cases per 100,000) and the highest incidence of any age group of clinically severe disease (29 cases per 100,000) and death (5.1 deaths per 100,000). The incidence among women aged 2049 years (82 per 100,000 women) was higher than among men (47 per 100,000, p<0.01). The annual incidence decreased from 25.2 cases per 100,000 population in 1994 to 9.4 cases per 100,000 in 1996. The decrease occurred as adult coverage increased from an estimated 25-30% in December 1992 to 88% in December 1995. Vaccine effectiveness was high among both children and adults. CONCLUSIONS: The Russian diphtheria epidemic primarily affected adults, especially women; this pattern is likely representative of diphtheria epidemics in immunized populations. Raising childhood immunization coverage and mass adult vaccination was effective in controlling the Russian epidemic. An improved understanding of the current epidemiology of diphtheria will be useful to design public health responses to prevent or control modern epidemics.

Risk of diphtheria among schoolchildren in the Russian Federation in relation to time since last vaccination.

BACKGROUND: Between 1990 and 1996, more than 110,000 cases and 2900 deaths from diphtheria were reported in the Russian Federation. In 1994, because disease rates were high among children aged 7-10 years, the age of administration of the second booster dose of diphtheria vaccine was lowered from 9 years to 6 years, the age of school entry. To assess the impact of this policy change, we did a matched case-control study in three Russian cities. METHODS: Children aged 6-8 years who had diphtheria between September, 1994, and December, 1996, were each matched with five to seven children acting as controls who were within 3 months of age of the case and were from the same class at school. We did a matched analysis using conditional logistic regression. FINDINGS: We analysed the immunisation records of 58 cases and 306 controls. All but one case and all controls had received at least three doses of diphtheria-toxoid vaccine. 19 (33%) cases and 144 (47%) controls had received a booster dose of diphtheria toxoid within the previous 2 years. Cases were more likely than were controls to have received only four doses rather than five (odds ratio 2.8 [95% CI 1.2-6.5]) and to have a time since the last dose of diphtheria toxoid of 3-4 years (3.1 [1.1-9.1]) or 5-7 years (15.0 [2.5-89.0]), compared with children for whom it was 2 years or less. On multivariate analysis only a time since the last dose of 5-7 years remained significantly associated with disease (matched odds ratio adjusted for total number of doses 10.9 [1.6-75.1]). CONCLUSION: A booster dose of diphtheria-toxoid vaccine given to children in the Russian Federation at 6-8 years of age reduced the interval since the last dose of diphtheria toxoid and improved protection against diphtheria.

PIP: More than 110,000 cases and 2900 deaths from diphtheria were reported in the Russian Federation in 1990-96. In response to the high disease rates in children 7-10 years of age, the timing of the second booster dose of diphtheria vaccine was lowered in 1994 from 9 to 6 years of age--the age of school entry. The impact of this change was assessed in a matched, retrospective, case-control study conducted in three Russian cities. 58 children 6-8 years old who had diphtheria between September 1994 and December 1996 were matched with 306 controls within 3 months of age and from the same school class. All but one case and all controls had received at least three doses of diphtheria toxoid vaccine and 19 cases (33%) and 144 controls (47%) had received a booster dose of the vaccine within the previous 2 years. Cases were more likely than controls to have received 4 rather than 5 doses (odds ratio (OR), 2.8; 95% confidence interval (CI), 1.2-6.5) and to have an interval since the last vaccine dose of 3-4 years (OR, 3.1; 95% CI, 1.1-9.1) or 5-7 years (OR, 15.0; 95% CI, 2.5-89.0) compared with children for whom it was 2 years or less since the last dose. In the multivariate analysis, only time since the last vaccine dose of 5-7 years was significantly associated with disease (matched OR adjusted for total number of doses, 10.9; 95% CI, 1.6-75.1). These findings indicate that a booster dose of diphtheria toxoid at the age of school entry is effective in preventing diphtheria among school-aged children. This evidence should be considered in the development of routine childhood immunization schedules in countries where diphtheria remains endemic.

[A comparative study of live and inactivated influenza vaccines: the organization of the observation and the results of a study of their reactogenicity and immunogenicity]. / Sravnitel'noe izuchenie zhivoi i inaktivirovannykh grippoznykh vaktsin: organizatsiia nabliudeniia i rezul'taty izucheniia reaktogennosti i immunogennosti.

Schoolchildren of 30 to 34 schools of Novgorod were vaccinated over a three-year period with Russian live cold-adapted attenuated vaccine for children and whole-virus inactivated vaccines and placebo for comparative field study of the vaccines properties and efficacy. In control trials both bi- and trivalent live attenuated vaccines were well tolerated and areactogenic. A whole-virus inactivated trivalent vaccine induced mild and moderate fever and local reactions in 2-4% of the vaccinees. Special observations are necessary to establish the possibility of use and to determine a dose of this inactivated vaccine for immunization of children, especially those of 7-10 years of age. All the vaccines induced HI antibody production in 50-80% and antineuraminidase in 50-70% of seronegative children. The pattern of the results was similar to that in revaccinated children with preexisting antibody at a level of 1:20, but much lower in children with the initial titre above 1:20. After the 3rd year of vaccination the immune response of the vaccinees was similar, most of the results depending on the initial antibody titre and also on the change of vaccine strains. This raises a question of the expediency of annual influenza revaccination of the same person after 2 years of successful immunization and of the necessity of vaccine strains replacement after 2-3 years of use.

Efficacy of live attenuated and inactivated influenza vaccines in schoolchildren and their unvaccinated contacts in Novgorod, Russia.

Children aged 7-14 years in Novgorod, Russia, were given Russian live cold-adapted or inactivated influenza vaccines or placebo over a 2-year period. Schools were randomly assigned as a whole to one of the preparations. In the first year, the vaccines were bivalent, containing types A (H3N2) and A (H1N1) components. In the second year, the vaccines also contained a type B component. In the first year, all viruses isolated were type A (H3N2); in the second, about three-quarters of the isolates were type B and the rest type A (H1N1). During both years, the vaccines protected the vaccinated children. Where significant differences existed, the live attenuated vaccine was more protective than the inactivated. Vaccination rates in schools in which live attenuated vaccines had been used were inversely related to illness rates of staff and unvaccinated children, suggesting that viral transmission had been reduced by the vaccine.

[Medico-social characteristics of migrant pulmonary tuberculosis patients]. / Mekiko-sotsial'naia kharakteristika bol'nykh tuberkulezom legkikh migraantov.

The dispensary records of 5296 pulmonary tuberculosis patients who moved to the Krasnodar Territory during 5 years were analyzed. The excretors were 50.6%; 17.3% (ex-convicts) were registered in a dispensary. This group of patients refused to be on dispensary record more often than other migrants, had difficulties in contacting with medical personnel, more frequently suffered from concurrent alcoholism. Children's infection in these asocial families was 3 times higher than that in socially favourable tuberculosis foci.