Immune biomarkers in relation to exposure to particulate matter: a cross-sectional survey in 17 cities of Central Europe.

Human population data on air pollution and its effects on the immune system are scarce. A survey was conducted within the framework of the Central European Study of Air Quality and Respiratory Health (CESAR) to measure a panel of immune biomarkers in children of Bulgaria, Czech Republic, Hungary, Poland, Romania, and Slovakia. Seventeen cities were chosen to represent a wide range of exposure to outdoor air pollution. In each, ambient particulate matter of less than 10 microns diameter and less than 2.5 microns diameter (PM10 and PM2.5) were measured with a Harvard impactor. Blood was collected from 366 school children aged 9 to 11 yr between 11 April and 10 May 1996. The percentage of B, total T, CD4+, CD8+, and natural killer (NK) lymphocytes was determined by flow cytometry (Becton Dickinson); total immunoglobulins of class G, M, A and E (IgG, IgM, IgA, and IgE) were measured in serum using nephelometry (Behring). Associations between PM and each log-transformed biomarker concentration were studied by linear regression, in a two-stage model. The yearly average concentrations varied from 41 to 96 micrograms/m3 for PM10 across the 17 study areas, from 29 to 67 micrograms/m3 for PM2.5, and from 12 to 38 micrograms/m3 for PM10-2.5 (coarse). Number of B, CD4+, CD8+, and NK lymphocytes increased with increasing concentration of PM, having adjusted for age, gender, parental smoking, laboratory of analysis, and recent respiratory illness. Differences in lymphocyte number were larger and statistically significant for exposure to PM2.5. Similar results were found when we examined the association between PM and lymphocyte number separately for each laboratory. Total IgG was increased with increasing concentration of PM, significantly in the case of PM2.5. When we repeated the analyses with two other statistical approaches the results did not differ from those reported here. The effect of coarse PM on lymphocyte numbers appears small in comparison to PM2.5. One possible interpretation of our findings is that long-term exposure to airborne particulates leads to inflammation of the airways and activation of the cellular and humoral immune system.

Investigation of the results obtained following repeated boosters with Di-Te vaccine in HIV positive children.

The paper is an attempt to study the effect of repeated boosters with Di-Te vaccine in positive children. The efficacy of their administration (vaccinal coverage degree, level of secreted antitoxins, the persistency of the immune response) and their influence upon the subsequent evolution of HIV infection are investigated.

Antitetanus and antidiphtheria immunity in newborns.

The level of antitetanus and antidiphtheria immunity was evaluated in 280 pairs (mother-newborn) and in 56 pairs where mothers (aged 19-26 yrs.) were vaccinated in the 7th month of pregnancy with an adsorbed tetanus vaccine dose. The results revealed a high antitetanus immunity level both in mothers and newborns (93.57% and 92.85% respectively) and a low antidiphtheria protection level (79.64% and 77.14%). Immunization of pregnant women ensures a 100% passive protection of newborns against tetanus before administration of the first vaccine doses. The data obtained also proved that placental transfer of the specific circulating antibodies was high (98.58% and 95% for diphtheria). The high percentage of newborns susceptible to diphtheria toxinfection points to the need to immunize mothers-to-be with low combined diphthero-tetanus (d-T) vaccine doses and to closely observe vaccination programme (Ministry of Health) of children with combined diphthero-tetanus-pertussis vaccine (CDTPV) at an early age (two months).

Antidiphtheria and antitetanus immunity in various age groups (0-70 yrs) in Romania.

The evaluation of the antidiphtheria and antitetanus immunity level is still a topical question. The paper approaches the study of antidiphtheria and antitetanus immunity on age groups in 3,768 and, respectively, 4,001 subjects. In the studied population, the results of estimating immunity revealed an antidiphtheria percentage of 87.16% and a protection level against tetanus of 94.47%. The immunity level against both diphtheria and tetanus varied depending upon the studied age. The highest susceptibility values against diphtheria (29.42%) were recorded in the 6th decade and against tetanus (18.89-28.27%) in the 6th and, respectively, 7th decade. A high antidiphtheria and antitetanus immunity level (over 90%) was reported in children and young people after the IIIrd and IVth boosters).

Negatively charged liposomes as immunological adjuvant for tetanus and diphtheria toxoids.

The aim of this study is to develop the previous research on tetanus toxoid and improve the level of antibodies against tetanus and diphtheria toxoids using liposomes as adjuvant. The results show that negatively charged liposomes enhance the immune effects of the combination of the two vaccines.

Liposomes as immunological adjuvants for tetanus vaccine.

Finding a new immunological adjuvant has been a challenge all along. The aim of our study is to improve the level of antibodies against tetanus using liposomes as adjuvant. As can be seen from the results of our study, the liposomes are a competitive candidate in this respect.

Antidiphtheria and antitetanus immunity of recruits in Romania.

The concern for maintaining a high antidiphtheria and antitetanus immunity level is permanent. The paper approaches the study of antidiphtheria and antitetanus immunity levels in a group of young recruits (who had been administered a DT booster 5-7 yrs before). The titres of antibodies were determined concomitantly by the neutralization test (NT) in vivo and by the passive hemagglutination assay (PHA) in vitro. The results obtained by the neutralization tests revealed (by the estimations shown by the geometrical means) a high antidiphtheria and antitetanus immunity level proved by an exceeding of the protection limits (0.03 IU/ml and 0.01 IU/ml) of 89 x and 953 x, respectively. The analysis of individual titres obtained by NT showed that of 540 subjects in whom diphtheria antitoxin was determined, 93.52% had protective titres, while of 619 subjects in whom the tetanus antitoxin was evaluated, 97.26% were immune. The results obtained by PHA were comparable with those obtained using the reference methods.

Experimental study on estimating the immunogenic potency of diphtheria and/or tetanus toxoids in monovaccines and associated vaccines.

The results obtained using the "classical" active immunoprotection tests on guinea pigs, biometrically interpreted by the regression analysis in "PROBIT" systems revealed that the biopreparations of the Cantacuzino Institute meet the validity conditions related to the parallelism of the "slopes" enabling the calculation of ED50 and of the relative potencies against the reference preparations. The results also showed that the relative potencies of the biopreparations tested by the two methodologies were very close. The geometrical means and the geometrical standard deviations of the titrers obtained in mice pointed to the similarity of the values following inoculation of the Cantacuzino Institute preparations on the one hand and of the international reference preparation on the other.

Experimental study upon the efficacy of some accelerated vaccination schedules in tetanus prophylaxis.

In an attempt to accelerate the antitetanic vaccine-induced immune response necessary particularly in subjects with tetanigenic wounds, groups of guinea pigs or rabbits were i.d. or s.c. immunized with a nonadsorbed purified and concentrated toxoid. Concomitantly, lots of control animals were i.m. immunized with tetanic vaccine adsorbed on aluminium phosphate. The immune response was estimated by testing the serum antitetanus antitoxic titre and the resistance of guinea pigs to tetanic intoxication. The results obtained revealed a variety of responses to vaccination in which differed terms of the species of animals and the applied immunization schedule. When single vaccine doses were used the protective antitetanus limit was reached in seven days in rabbits and after ten days in guinea pigs; the adsorbed vaccine induced a stronger immune response than the non-adsorbed vaccine. When multiple immunization doses were used the non-adsorbed tetanus vaccine induced, especially in rabbits, a more rapid response that the adsorbed vaccine. The vaccination schedules used in laboratory animals and which have yielded the best results in this experiment will be analysed and checked on human subjects in a further study.

Investigations concerning the possibility to replace the Schick test by the passive hemagglutination reaction for evaluating the diphtheria immunity level in population.

The evaluation of Schick test results as compared to the results obtained by determination of diphtheria antitoxin concentration in blood using the neutralizing test on rabbit--Jensen on the one hand and to those obtained by the passive hemagglutination reaction on the other has revealed some discrepancies against the two tests: 7.09% (4.08% pseudo-protected, 3.01 pseudo-susceptible) as against TN-Jensen and 8.6% (5.59% pseudo-protected and 3.01% pseudo-susceptible) as against the passive hemagglutination reaction results. The reported discrepancies were due to the fact that the results of Schick test did not correlate perfectly with the amount of circulating antitoxin, the diphtheria immunity level was wrongly indicated by the Schick test. The passive hemagglutination reaction has proved to be adequate to mass-screening investigations being capable to replace Schick test.

Experimental study on intradermal antitetanus antityphoid immunization.

A new type of concentrated unadsorbed Tetanus vaccine was administered in animals by intradermal route, associated or not with Typhoid vaccine. The results of the laboratory tests demonstrated that this vaccine is innocuous and produces minimal reactions. A single doses of Tetanus vaccine inoculated in guinea pig or rabbit resulted in a relevant titer which increased when the Typhoid vaccine was associated. Also, in such immunized guinea pigs, a remarkable resistance to tetanic toxin was achieved. The levels of the active or passive typhoid-protective power as well as that of the agglutinating antibodies were not influenced by the association of the Tetanus vaccine to the Typhoid vaccine. Therefore, when the Typhoid vaccine suspended in Tetanus vaccine was administered intradermally to the animals by Jet injector, it had not a negative effect for none of the two components, had a beneficial effect upon the levels of determined antibody production and allowed an easier and more rapid administration of these vaccines.

Intradermal antitetanic-antityphoid booster by jet injection.

The immunogenicity and the reactogenicity of an unadsorbed Tetanus vaccine, intradermally administered in man as a booster immunization associated or not with lyophilized Typhoid vaccine, were comparatively studied. There were no differences in postvaccinal reactions between the Tetanus vaccine administered alone or associated with Typhoid vaccine as well as between the unadsorbed and adsorbed Tetanus vaccine. The booster inoculation carried out with Tetanus vaccine by i.d. route with doses of 10 Lf/0.1 ml proved to be effective, inducing to all the subjects a definite protective titre, maintaining for at least one year.

Intradermal antityphoid-antitetanus vaccination by jet injection.

A lyophilized, heat-killed, phenol preserved typhoid vaccine (5 x 10(8) cells) suspended in 0.1 ml unadsorbed concentrated tetanus vaccine (10 Lf) was administered in man by intradermal route. This association of the two vaccines resulted in milder postvaccinal reactions: moreover, the immunological properties of typhoid vaccine, as certified by the passive protection test of the mouse with sera of the vaccines and the H and O agglutinin titres found in these immune sera, were perfectly conserved. Consequently, the mixed typhoid-tetanus vaccination in man by intradermal route is possible and advantageous for practical and economical reasons.

Antityphoid and antitetanic intradermal vaccination of chronic neuropsychic patients in a typhoid fever outbreak.

Intradermal immunization of 229 chronic neuropsychic patients in Gura Ocnitzei Sanatorium, Dîmbovitza County, where a typhoid fever outbreak burst, was performed with a freeze-dried typhoid vaccine, suspended in purified and concentrated tetanic anatoxin. Adverse reactions were minimal and immunologic response, evaluated by laboratory tests, was good, reaching the level of that obtained as a result of classic vaccination methods (subcutaneous antityphoid and intramuscular anti-tetanic). Both after vaccination and also booster O and H agglutinating titers increased 4-7 times and anti-S. typhi. seroprotecting effect reached and maintained a high level. Moreover, antityphoid vaccination permitted epidemic focus limiting and its complete extinguishing after booster. Antitetanic vaccination resulted in protecting titers settlement (greater than or equal to 0.01 IU/ml) in all previously non-protected persons (1/3 of all subjects) and in the increase of protecting titers, existing before vaccination in the other persons.

Study of specific immune response to unadsorbed concentrated tetanus vaccine administered by intradermal route to non-immunized persons in the last ten years.

Investigations of anti-tetanus response, in 404 subjects, most of them aged 60, being non-immunized for at least 10 years, stressed out the fact that 28.7% were not protected and 6.18% presented a protecting titer of 0.01 IU/ml, evaluated by "in vivo" protection test in mice. Some subjects were immunized with unadsorbed Tetanus vaccine (10 Lf/0.1 ml/dose) by i.d. route, using Jet-injector, and the others with adsorbed Tetanus vaccine (0.5 ml/dose), by i.m. route, using the needle and syringe. The vaccines were well tolerated and adverse reactions were not recorded. After 30 days, a single vaccine dose produced a protecting effect in 97.45% of non-protected subjects, belonging to i.d. immunized group, and also in 93.33% belonging to i.m. immunized group. 30 days after the administration of a second dose, protection set up in all subjects, no matter of vaccine type and administration route used. For a continuous reduction of tetanus morbidity, the authors suggest a specific periodical immunization of non-protected persons, selected by serological screening, using unadsorbed Tetanus vaccine, administered by i.d. route by means of the Jet-injector.

[The relationships between antitoxic titers determined in a group of young people before and after booster ADT by the in vivo neutralization test. Comparative NT-PHAR evaluations]. / Relations entre les titres antitoxiques déterminés sur un lot de jeunes gens, avant et après le rappel à l'ATPA, par le test de neutralisation "in vivo". Evaluations comparatives TN-RHAP.

The geometrical mean of antitoxic titers determined in a lot of immunized young men who received, 5-7 years before, a booster with diphtheria-tetanus bivaccine, was of 1.54 (x/divided by 10.54) I.U./ml. At one month after another booster, performed with Tetanus toxoid (adsorbed), an increase of 34 times was recorded, the geometrical mean reaching the value of 52.67 (x/divided by 10.42 I.U./ml). The covering coefficients of the minimal protective antitoxin level have increased from 154 to 5267, in the estimation performed at the level of geometrical mean (calculating the ratio between the value of this indicator and that of the protection limit) and from 1623 to 54935, or from 15 to 505, respectively, in the estimations performed at the levels of the limits of the statistical range of one geometric standard deviation (Mg x/divided by D Sg). The study of the relations between pre- and post-antitoxic titers, performed by the linear regression analysis, leads to an equation whose slope evidenced the lower amplitude of the booster titers, along the increase of previous titers. The study of the inter-methods (neutralization-passive haemagglutination) regression allowed to obtain a correlation coefficient, between methods, of r = 0.83 and to perform the transposition of the minimal protective N.T. level (0.01 I.U.) in the terms of passive haemagglutination reaction, at the titer of 160 (0.3 PHAU/ml), for the p less than or equal to 0.05 probability level.

[The immunogenic capacity of soluble "vaccinia" antigen (fractionated smallpox vaccine) administered simultaneously with inactivated typhoid vaccine and with purified and concentrated tetanus anatoxin]. / La capacité immunogène de l'antigène soluble "vaccinia" (vaccin fractionné antivariolique) administré simultanément avec le vaccin typhoïdique inactivé et avec l'anatoxine tétanique purifiée et concentrée.

In this study we have investigated the immune humoral response in the associated vaccination with smallpox, tetanus and typhoid fractionated vaccine (trivaccine) administered in two series at 1 month interval, by dermojet, in a group of young people of 18-20 years old. The results were comparatively estimated with those obtained in two groups of young people of the same age (control group), separately immunized with two components of the tri-vaccine: fractionated smallpox vaccine and tetanus toxoid, following-up the humoral response to the two vaccine components. It was find that, at the end of the surveillance period, similar results were obtained for the testing group and control group, the antibody titers (in geometric mean) presenting very close values: 1/1,140,463 for the testing group, and 1/1,053,583 for the control group against vaccinia component, and 1/1,86,880,586 for the testing group and 1/79,900,431 for the control group, against the tetanus component. The results obtained entitle us to propose this vaccination scheme for the vaccination practice.