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 Доказательная вакцинология. 
Автор Сообщение
Сообщение 
Замечательная статья с обширной библиографией про вакцинацию, оставляющая после прочтения противоречивое мнение.
М. б. кто-нибудь переведёт и пройдётся по ссылкам на первоисточники?

Duration of Humoral Immunity to Common Viral and Vaccine Antigens
Ian J. Amanna, Ph.D., Nichole E. Carlson, Ph.D., and Mark K. Slifka, Ph.D.
http://content.nejm.org/cgi/content/full/357/19/1903
ABSTRACT
Background Maintenance of long-term antibody responses is critical for protective immunity against many pathogens. However, the duration of humoral immunity and the role played by memory B cells remain poorly defined.
Methods We performed a longitudinal analysis of antibody titers specific for viral antigens (vaccinia, measles, mumps, rubella, varicella–zoster virus, and Epstein–Barr virus) and nonreplicating antigens (tetanus and diphtheria) in 45 subjects for a period of up to 26 years. In addition, we measured antigen-specific memory B cells by means of limiting-dilution analysis, and we compared memory B-cell frequencies to their corresponding serum antibody levels.
Results Antiviral antibody responses were remarkably stable, with half-lives ranging from an estimated 50 years for varicella–zoster virus to more than 200 years for other viruses such as measles and mumps. Antibody responses against tetanus and diphtheria antigens waned more quickly, with estimated half-lives of 11 years and 19 years, respectively. B-cell memory was long-lived, but there was no significant correlation between peripheral memory B-cell numbers and antibody levels for five of the eight antigens tested.
Conclusions These studies provide quantitative analysis of serologic memory for multiple antigens in subjects followed longitudinally over the course of more than one decade. In cases in which multiple exposures or repeated vaccinations were common, memory B-cell numbers did not correlate with antibody titers. This finding suggests that peripheral memory B cells and antibody-secreting plasma cells may represent independently regulated cell populations and may play different roles in the maintenance of protective immunity.
________________________________________
Recovery from acute viral or microbial infection often results in long-term or even lifelong immunity.1,2,3 Although the importance of sustaining protective humoral immunity is widely recognized, the mechanisms involved in this maintenance remain unclear.3,4,5,6,7,8,9,10 To address the issue of antibody maintenance after infection or vaccination, we conducted a longitudinal analysis of antibody titers against multiple antigens with the use of serum samples banked from a combination of scheduled (annual) and event-based collections. On the basis of these studies, we determined whether antigen-specific antibody responses were measurably boosted through environmental exposure, infection, or vaccination. Moreover, we determined the duration of serologic memory over long periods of time during which specific boosting of antibody titers was not observed.
Methods
Subjects
We recruited human subjects from the Oregon National Primate Research Center through campuswide e-mail, inviting them to provide serum samples for banking at enrollment and to provide additional serum samples from scheduled blood draws. Fifty-one people responded, providing written informed consent and completing an extensive medical-history questionnaire before providing samples for study. No inclusion criteria were used other than a requirement that the subject have at least three serum samples banked for 3 years or more before the study began. On the basis of this criterion, 6 subjects were excluded, and 45 subjects provided a total of 630 serum samples for analysis.
Samples were drawn annually as part of a centerwide, comprehensive program to permit serologic testing of people working in close proximity with nonhuman primates. In the event of an exposure to an animal (e.g., a scratch or bite), an additional serum sample was drawn. Blood samples were also drawn at weekly intervals after smallpox vaccination in a subgroup of eight subjects in order to monitor the acute phase of the immune response. The study was approved by the institutional review board of Oregon Health & Science University.
ELISA and Memory B-Cell Measurement
Measurement of antibodies by means of enzyme-linked immunosorbent assay (ELISA) was performed as previously described.11,12 Antigens included vaccinia (WR strain prepared in our laboratory), measles (Edmonston strain, Biodesign), mumps (Enders strain, Biodesign), rubella (HPV77 strain, Viral Antigens), varicella–zoster virus (Rod strain, Biodesign), Epstein–Barr virus gp125 (Viral Antigens), tetanus toxin (C-fragment), and diphtheria toxin (EMD Biosciences). International serum standards were obtained from the National Institute for Biological Standards and Controls in Hertfordshire, England. An optimized limiting-dilution assay was used to measure memory B cells.13
Statistical Analysis
Before the final analysis, antibody data were censored by excluding unvaccinated subjects, seronegative subjects, and subjects with test results that were equivocal (<200 ELISA units). A total of one to nine subjects were excluded, depending on the antigen. We removed data points obtained during or shortly after an acute immune response before determining antibody half-life estimates. For example, if more than a doubling of the titer was observed between contiguous time points (hereafter referred to as an antibody spike), then that time point and those from the next 3 years were removed from the analysis so that the rapid initial decrease in antibodies typically observed shortly after antigenic exposure14,15,16,17 would not influence the estimated long-term decay rate. A subject had to have at least three data points for a period of 3 years or more in order to be included in the final analysis. Tetanus and diphtheria vaccines are frequently administered in combination,18 so if an antibody spike was observed between contiguous data points for one antigen, a reexposure was assumed for the reciprocal antigen and removed from the analysis. Since tetanus–diphtheria toxoid revaccination is recommended every 5 to 10 years, contiguous data points separated by more than 5 years were not used for the analysis of these antigens.
To address possible changes before and after acute immune responses, the analysis was performed first for only the longest period of observation and then for all the data, with each period treated as an independent longitudinal series. The results of these two analyses did not differ. For each antigen described in this study, we present the results of the analysis in which all data were used.
Rates of antibody decay were estimated with the use of a longitudinal mixed-effects model (PROC MIXED; SAS version 9.1, SAS Institute). The model had a fixed effect for age and gaussian-distributed random intercepts and slopes (see the Supplementary Appendix, available with the full text of this article at www.nejm.org). Random components were assumed to be uncorrelated. Measures were logarithmically transformed (on a natural log scale) before analysis, resulting in a single-exponent decay model of the untransformed data. Visual inspection indicated that the linear model fitted the data for the subjects well. We assessed the influence of data for any one subject on the analysis with the use of cross-validation. The results were not influenced by any one person's series.
Half-life estimates were obtained by transforming the decay rate and the boundaries of the 95% confidence interval obtained from the fixed-effects slope component of the mixed-effects model. If a specific antibody level does not significantly decay or shows even a small insignificant increase over time (e.g., <1%), then the calculated half-life becomes infinity. To confirm the results from our mixed-effects model, we also fitted least-squares linear regression models to each series. The results from the two approaches were nearly identical (see the Supplementary Appendix). For each antigen, we determined whether the population slope was equal to zero in the mixed-effects model. The P values presented are two-sided, and a P value of less than 0.05 was considered to indicate statistical significance. The comparisons of memory B-cell frequencies and associated serum antibody titers were modeled through least-squares linear regression after log10 transformation.
Results
Serum Samples and Characteristics of the Subjects
A total of 630 serum samples from 45 subjects were obtained for this study or were obtained from the Oregon National Primate Research Center serum bank (Table 1). The majority of these serum samples were obtained from scheduled collections, with 50 samples (7.9%) obtained after an unscheduled event (e.g., exposure to an animal). Each subject provided, on average, 14.0 serum samples (median, 11) during an average period of 15.2 years (median, 15.6). The majority of subjects had received smallpox vaccination during childhood and had recovered from viral infections, including measles, mumps, rubella, Epstein–Barr virus, and varicella–zoster infections. The subjects in this cohort had common coexisting conditions but no specific immune deficiencies (Table 1 of the Supplementary Appendix). The duration of serum antibody production was determined with the use of a mixed-effects model of longitudinal analysis. Overall, antigen-specific antibody responses were long-lived, and we found no significant differences in antibody-maintenance patterns according to sex
Vaccinia
One potential mechanism for maintaining long-term immunity to a nonpersisting pathogen is through intermittent reexposure. To examine this possibility, we evaluated antibody responses after smallpox vaccination (Figure 1A). A total of 39 of 43 subjects born before 1972 (91%) were seropositive for vaccinia (Fig. 1A in the Supplementary Appendix), which is consistent with the findings of a previous study.11 Before 2003, when eight subjects received booster vaccination, there were only two instances of an antibody spike that was indicative of vaccination or exposure (0.3 event per 100 person-years). This finding is consistent with the discontinuation of routine vaccination in 1972 and the absence of endemic orthopoxviruses in North America that are known to infect humans. Excluding serum samples obtained after smallpox vaccination in 2003, a putative protective level of antiviral antibody11,21 was present in 28 of the 45 subjects (62%), and the level of vaccinia-specific antibodies decreased slowly, with an estimated half-life of 92 years (95% confidence interval [CI], 46 to infinity; P=0.049).
Figure 1. Antibody Responses after Viral Infection or Vaccination with Nonreplicating Protein Antigens.
Results of longitudinal analyses of serum titers of antibodies against eight antigens in 45 subjects are shown: vaccinia (Panel A), measles (Panel B), mumps (Panel C), rubella (Panel D), Epstein–Barr virus (EBV) (Panel E), varicella–zoster virus (VZV) (Panel F), tetanus (Panel G), and diphtheria (Panel H). To determine the antibody half-life during the maintenance phase of the immune response, data were censored by removing subjects with seronegative and equivocal samples. For seropositive subjects, time points at or up to 3 years after an antibody spike were removed before analysis. The estimated antibody half-lives, 95% confidence intervals (CI), interquartile ranges, and associated P values were obtained with the use of a mixed-effects model of longitudinal analysis. The shaded regions represent the cutoff between seropositive and seronegative serum titers as determined by enzyme-linked immunosorbent assay (ELISA), and the dotted lines indicate the putative protective levels of antibodies, if known. EU denotes ELISA units and IU international units. IU standards were not available for mumps, EBV, and VZV.

Measles
Measles is rare in the United States, but it remains a serious threat through importation.22 An analysis of measles-specific antibodies revealed that five subjects had spikes in serum antibody levels (Fig. 1B in the Supplementary Appendix). Two subjects received documented measles–mumps–rubella (MMR) vaccinations; one seroconverted, whereas the other seropositive subject had antibody titers that did not change after vaccination. Four subjects unknowingly contracted a cross-reactive but uncharacterized paramyxovirus infection from exposure to diseased nonhuman primates during a 1999 outbreak. On the basis of the antibody titers from the last available blood sample drawn before a recent MMR vaccination or serologic boosting during the 1999 outbreak of primate paramyxovirus, 43 of the 45 subjects (96%) were seropositive, with a putative protective level of at least 0.2 IU of antimeasles antibodies per milliliter23 in 41 subjects (91%) (Fig. 1B in the Supplementary Appendix). The decrease in measles-specific antibodies (Figure 1B) was not significant (P=0.94) and is likely to be maintained for life (estimated half-life, 3014 years; 95% CI, 104 to infinity).
Mumps
Although typically less severe than measles, mumps is another childhood disease with the potential for serious complications.18 In this cohort, 41 of 45 subjects (91%) were seropositive for mumps (Fig. 1C in the Supplementary Appendix). Two subjects received MMR vaccinations during the period of observation, and two other subjects had spikes in antibody levels, one in 1998 and the other in 2004. These spikes may have been the consequence of exposure to naturally occurring mumps rather than MMR vaccination. This incidence rate of 0.3 event per 100 person-years is consistent with a steady decrease in prevalence18 since routine vaccination began in 1977. Antibody responses to mumps (Figure 1C), like those to measles, were long-lived (estimated half-life, 542 years; 95% CI, 90 to infinity) and showed no significant decrease (P=0.69).
Rubella
Rubella was a leading cause of birth defects in the United States before immunization programs were implemented in the 1970s.18 A total of 40 of the 45 subjects in our cohort (89%) were seropositive for rubella (Fig. 1D in the Supplementary Appendix). We identified two subjects with documented MMR vaccinations and one subject with a spike in preexisting rubella-specific titers in 2003. Because of an 8-year gap between contiguous serum samples, it is unclear whether the change in this latter subject was due to a natural case of rubella or variability in serum titers. In any case, a spike in rubella-specific antibodies is uncommon, with a low overall incidence rate of 0.15 event per 100 person-years. A putative protective level of at least 10 IU of antirubella antibodies per milliliter24 was reached in 39 of the 45 subjects (87%). Rubella-specific immunity (Figure 1D) was maintained, with an estimated half-life of 114 years (95% CI, 48 to infinity) and no significant rate of decrease (P=0.15).
After reviewing the medical histories of the subjects, we identified six subjects in whom only vaccine-induced immunity against measles had developed, four subjects in whom vaccine-induced immunity against mumps had developed, and seven subjects in whom vaccine-induced immunity against rubella had developed. Exclusion of these subjects from the longitudinal analysis shown in Figure 1 had no substantial effect on the calculated duration of serum antibody responses (Table 2 of the Supplementary Appendix). Moreover, although reexposure to the same or a serologically cross-reactive virus may boost antibody titers, these data with regard to vaccinia, measles, mumps, and rubella indicate that repetitive environmental exposures and infections are not absolutely required for maintaining long-term antiviral antibody responses.
Epstein–Barr Virus and Varicella–Zoster Virus
In contrast to acute viral infections, chronic and latent viral infections may either persist or be reactivated from latency, thereby "boosting" immune responses in the infected person. Antibody titers were determined for two latent herpesviruses, Epstein–Barr virus and varicella–zoster virus. A total of 37 of the 45 subjects (82%) were seropositive for Epstein–Barr virus, with seroconversion in 1 subject occurring during the observation period (Fig. 1E in the Supplementary Appendix). Four seropositive subjects had antibody titers that spiked during observation, indicating that reactivation or reexposure events had occurred, but at a relatively low rate (0.6 event per 100 person-years). Humoral immunity against Epstein–Barr virus (Figure 1E) showed no significant decrease (P=0.99) and is likely to be maintained for life (estimated half-life, 11,552 years; 95% CI, 63 to infinity).
Unlike antibody responses to Epstein–Barr virus, antibody responses to varicella–zoster virus showed frequent fluctuations (Fig. 1F in the Supplementary Appendix). All 45 subjects were seropositive for varicella–zoster virus, and 10 of the 45 subjects (22%) had antibody spikes (1.6 events per 100 person-years). Two subjects described an episode of shingles at or near the time of the observed spike in antibody responses to varicella–zoster virus, one subject may have been exposed to recently vaccinated children, six subjects do not recall having shingles or any known exposure to patients with varicella–zoster virus, and information was not available for one subject. Immunity (Figure 1F) decreased slowly, with an estimated half-life of 50 years (95% CI, 30 to 153; P=0.005). Thus, although the infection is latent with evidence of the most frequent reexposure and reactivation events, varicella–zoster virus induced the most short-lived antibody response of the viruses we examined.
Tetanus and Diphtheria
Tetanus and diphtheria vaccination has been recommended since the 1940s, primarily with the combined tetanus–diphtheria toxoid vaccine for adults. This recommendation has resulted in a sharp decrease in the incidence of both diseases18 and prolonged maintenance of antibody titers (Figure 1G and 1H). A titer of more than 0.01 IU of antitetanus antibodies per milliliter is considered to be protective.25 ELISA titers of more than 0.16 IU per milliliter correlate well with neutralizing activity; a titer of 0.16 IU per milliliter is the lowest level reliably detected by means of ELISA26 and is similar to our detection limit of 0.15 IU per milliliter (200 ELISA units). Protective antitetanus responses (Fig. 1G in the Supplementary Appendix) were clearly identified in 42 of the 45 subjects (93%), but this response rate may not reflect the true number of protected persons, since 0.01 IU is below the limit of detection by ELISA. Frequent tetanus boosters resulted in 31 instances of an antibody spike in 27 subjects (4.9 events per 100 person-years) (Fig. 1G in the Supplementary Appendix). Tetanus-specific antibodies decreased rapidly, with an estimated half-life of 11 years (95% CI, 10 to 14; P<0.001), which is similar to the decrease shown in a model reported more than 40 years ago.27
To determine whether the rapid antibody decay observed with tetanus held true for other protein antigens, we measured immunity against diphtheria (Figure 1H). Antidiphtheria antibody titers of more than 0.01 IU per milliliter are considered to be protective,28 and in 40 of the 45 subjects (89%) diphtheria-specific antibodies remained above our detection limit (200 ELISA units, or 0.04 IU per milliliter) (Fig. 1H in the Supplementary Appendix). It is possible that the remaining five subjects also had sustained protective antidiphtheria immunity but that it could not be definitively measured in these studies. Diphtheria-specific antibody spikes were observed, typically in parallel to responses against tetanus, as expected because of the combined tetanus and diphtheria formulation recommended for adult vaccination. An analysis of diphtheria-specific antibodies indicated an estimated half-life of 19 years (95% CI, 14 to 33; P<0.001). These results suggest that antibody maintenance is greatly influenced by the nature of the antigen, with these proteins eliciting quantitatively shorter antibody responses than those observed after viral infection.
Antibody Maintenance in Individual Subjects
One model of antibody maintenance predicts that long-term responses are maintained by non–antigen-specific stimulation, also referred to as "bystander activation" of memory B cells during antigenically unrelated infections.3,8,29 To determine the potential effects of heterologous infection and vaccination, we measured humoral responses to eight antigens in four subjects followed longitudinally for more than 25 years and at weekly intervals after smallpox vaccination (Figure 2). Common immunologic events, including tetanus and diphtheria booster immunization (in Subjects 1 through 4), Epstein–Barr virus seroconversion (in Subject 2), and varicella–zoster virus reexposure or reactivation (in Subject 4), occurred during the period of observation but showed little effect on other antigen-specific antibody responses. After a defined infection with vaccinia (i.e., booster smallpox vaccination), there was little or no alteration in antibody responses to seven other antigens (<6% average change) (Figure 2), despite vaccinia-specific antibody responses that increased by approximately 4000% at the peak of the response. These results are consistent with those in six subjects who received booster smallpox vaccination and two subjects who received primary smallpox vaccination and later received either live yellow-fever vaccination or MMR vaccination (data not shown). Together, these findings suggest that nonspecific bystander activation is an unlikely mechanism in the maintenance of long-term antibody responses.
Tetanus and Diphtheria
Tetanus and diphtheria vaccination has been recommended since the 1940s, primarily with the combined tetanus–diphtheria toxoid vaccine for adults. This recommendation has resulted in a sharp decrease in the incidence of both diseases18 and prolonged maintenance of antibody titers (Figure 1G and 1H). A titer of more than 0.01 IU of antitetanus antibodies per milliliter is considered to be protective.25 ELISA titers of more than 0.16 IU per milliliter correlate well with neutralizing activity; a titer of 0.16 IU per milliliter is the lowest level reliably detected by means of ELISA26 and is similar to our detection limit of 0.15 IU per milliliter (200 ELISA units). Protective antitetanus responses (Fig. 1G in the Supplementary Appendix) were clearly identified in 42 of the 45 subjects (93%), but this response rate may not reflect the true number of protected persons, since 0.01 IU is below the limit of detection by ELISA. Frequent tetanus boosters resulted in 31 instances of an antibody spike in 27 subjects (4.9 events per 100 person-years) (Fig. 1G in the Supplementary Appendix). Tetanus-specific antibodies decreased rapidly, with an estimated half-life of 11 years (95% CI, 10 to 14; P<0.001), which is similar to the decrease shown in a model reported more than 40 years ago.27
To determine whether the rapid antibody decay observed with tetanus held true for other protein antigens, we measured immunity against diphtheria (Figure 1H). Antidiphtheria antibody titers of more than 0.01 IU per milliliter are considered to be protective,28 and in 40 of the 45 subjects (89%) diphtheria-specific antibodies remained above our detection limit (200 ELISA units, or 0.04 IU per milliliter) (Fig. 1H in the Supplementary Appendix). It is possible that the remaining five subjects also had sustained protective antidiphtheria immunity but that it could not be definitively measured in these studies. Diphtheria-specific antibody spikes were observed, typically in parallel to responses against tetanus, as expected because of the combined tetanus and diphtheria formulation recommended for adult vaccination. An analysis of diphtheria-specific antibodies indicated an estimated half-life of 19 years (95% CI, 14 to 33; P<0.001). These results suggest that antibody maintenance is greatly influenced by the nature of the antigen, with these proteins eliciting quantitatively shorter antibody responses than those observed after viral infection.
Antibody Maintenance in Individual Subjects
One model of antibody maintenance predicts that long-term responses are maintained by non–antigen-specific stimulation, also referred to as "bystander activation" of memory B cells during antigenically unrelated infections.3,8,29 To determine the potential effects of heterologous infection and vaccination, we measured humoral responses to eight antigens in four subjects followed longitudinally for more than 25 years and at weekly intervals after smallpox vaccination (Figure 2). Common immunologic events, including tetanus and diphtheria booster immunization (in Subjects 1 through 4), Epstein–Barr virus seroconversion (in Subject 2), and varicella–zoster virus reexposure or reactivation (in Subject 4), occurred during the period of observation but showed little effect on other antigen-specific antibody responses. After a defined infection with vaccinia (i.e., booster smallpox vaccination), there was little or no alteration in antibody responses to seven other antigens (<6% average change) (Figure 2), despite vaccinia-specific antibody responses that increased by approximately 4000% at the peak of the response. These results are consistent with those in six subjects who received booster smallpox vaccination and two subjects who received primary smallpox vaccination and later received either live yellow-fever vaccination or MMR vaccination (data not shown). Together, these findings suggest that nonspecific bystander activation is an unlikely mechanism in the maintenance of long-term antibody responses.
Figure 2. Longitudinal Analysis of Serum Antibody Titers in Representative Subjects.
Serum antibody responses against eight antigens were followed in four subjects with serum samples for a period of more than 25 years. Each subject received a booster smallpox vaccination in 2003, and serum antibody levels were monitored at close intervals after immunization (days 7, 14, 21, 30, and 60 after vaccination) to determine whether a defined viral infection would result in increased antibody production against other nonspecific antigens. Subject 1 (Panel A) was seronegative for Epstein–Barr virus (EBV), as indicated by a single data point of less than 200 ELISA units (EU). Subjects 2, 3, and 4 (Panels B, C, and D) were seropositive for EBV. VZV denotes varicella–zoster virus.
Individual variations in antibody maintenance (Figure 1) indicated that although the antigen itself plays an important role, it is not the sole factor determining the longevity of antibody responses. The findings in Subject 1 (Figure 2A) were largely representative of those in the overall cohort, with no measurable decrease in measles-specific antibodies and short-lived tetanus-specific and diphtheria-specific responses (estimated half-life, 14 and 12 years, respectively). Subject 2 (Figure 2B) had a similar pattern, with no decrease in measles-specific antibodies, whereas tetanus and diphtheria responses had half-lives estimated at 13 and 11 years, respectively. Subject 3 (Figure 2C) had a measles-specific antibody response that underwent a slow but measurable decrease (estimated half-life, 68 years), with tetanus antibodies showing the most rapid rate of decrease (estimated half-life, 8 years). Diphtheria-specific antibody titers did not decrease over the course of two decades, in sharp contrast to tetanus-specific antibody titers. The findings in Subject 4 (Figure 2D) are particularly intriguing because, with the exception of antibodies against Epstein–Barr virus (which showed no evidence of a decrease), all antibody responses decreased at relatively similar rates (estimated half-life, 14 to 31 years). Thus, the antigen, as well as one or more currently unknown host-specific factors, has a role in determining the duration of antibody-response patterns.
B-Cell Memory and Association with Antibody Levels
Plasma cells either maintain antibody levels independently30,31,32 or may require replenishment by the proliferation and differentiation of memory B cells. A requirement for all memory B-cell–dependent theories of antibody maintenance is that a correlation must exist between memory B-cell levels and antibody levels.3,8,29 With the use of a limiting-dilution analysis,13 we found that memory B cells in the circulation were remarkably long-lived (Figure 3A). Previous studies have shown that within 1 month after vaccination, memory B-cell numbers in the circulation are representative of the memory B-cell frequencies observed in other lymphoid compartments such as the spleen.33
Figure 3. Relationship between the Number of Memory B Cells, Age, and Serum Antibody Levels.
Panel A shows the results of an antigen-specific limiting-dilution assay performed for single time points for 40 subjects with available peripheral-blood mononuclear cells to determine memory B-cell frequencies for vaccinia, measles, mumps, rubella, varicella–zoster virus, Epstein–Barr virus, tetanus, and diphtheria. Solid circles represent samples with positive antibody titers (>200 ELISA units [EU]) or B-cell memory (>5 memory B cells per 106 B cells). Samples that scored below the level of detection for both antibody titer and B-cell memory are shown as open circles. Samples obtained during the acute phase (<1 year after exposure or a spike in the antibody titer) of an antigen-specific immune response are indicated as triangles. Dashed lines indicate the limit of detection. Panel B shows memory B-cell frequencies as compared with serum antibody titers from the corresponding blood sample. Seronegative and equivocal samples (<200 EU and <5 memory B cells per 106 B cells) and samples from subjects undergoing an acute immune response (<1 year after an antibody spike) were excluded before data analysis in order to focus on conditions involving long-term immunologic memory. The results of linear regression analysis are shown with the associated correlation coefficients for each comparison. EBV denotes Epstein–Barr virus, and VZV varicella–zoster virus.
We next compared memory B-cell frequencies with their corresponding serum antibody titers for eight antigens. A significant correlation between memory B-cell levels and antibody levels was observed after acute infection with measles, mumps, and rubella but not vaccinia (Table 3). There was also no significant correlation between memory B cells and antibodies against varicella–zoster virus or Epstein–Barr virus (viruses that maintain latent reservoirs) or for the tetanus–diphtheria vaccine antigens (Table 3). The strength of the correlation varied widely among antigens, suggesting that memory B-cell frequencies were a poor predictor of serum antibody levels (Figure 3B). For example, only 3% of the variability in antibody levels against tetanus could be explained by memory B-cell frequencies (R2=0.03). This finding suggests that memory B-cell–dependent replenishment of short-lived plasma cells is not likely to be a global mechanism for antibody maintenance.
Discussion
We investigated the longitudinal maintenance of antibody responses to eight antigens over a period of up to 26 years. Antibody responses after live viral infections had half-lives of 50 years or more, with many showing no measurable decrease. In contrast, responses to nonreplicating protein antigens (tetanus and diphtheria) decreased at a relatively rapid pace (estimated half-lives, 11 to 19 years), suggesting that within a particular person, antigen-specific mechanisms play a substantial role in determining the duration of humoral immunity.
On average, subjects were 52 years of age at the conclusion of the study, and most had contracted natural measles, mumps, or rubella infections during childhood. It is unknown whether vaccine-induced immunity is as long-lived as that induced by natural infection. Although the titers of vaccine-induced antibody responses appear to be lower than those reached after natural infection (data not shown), a longitudinal analysis of immunity against measles, mumps, and rubella suggests that serologic memory may be similar to natural infection (Supplementary Appendix). However, this result is based on a very small sample (two to five subjects), and further studies on antibody maintenance will be required before statistically meaningful comparisons can be made. This information is particularly important in contemporary populations in which asymptomatic reboosting of immunity by circulating natural or wild-type viruses appears to be relatively rare.
Two principal mechanisms for maintaining long-term humoral immunity have been proposed: memory B-cell–dependent antibody production by short-lived plasma cells and memory B-cell–independent antibody production by long-lived plasma cells.3,4,5,6,7,8,9,10 In memory B-cell–dependent models, memory B cells divide and differentiate into plasma cells after stimulation by persistent antigen, reinfection, cross-reactive antigens, or non–antigen-specific polyclonal activation. If polyclonal memory B-cell activation is the key to antibody maintenance,29 then the duration of antibody production should be the same, regardless of antigen specificity.
Moreover, hypotheses of memory B-cell dependence require that after each infection, a correlation between memory B cells — or at least peripheral memory B cells29 — and antibodies be maintained. This correlation has been noted in some instances35,36 but not in others.37,38 We found an association between memory B-cell levels and antibody levels for measles, mumps, and rubella but not for vaccinia, varicella–zoster virus, Epstein–Barr virus, tetanus, or diphtheria (Table 3). The associations with these first three viruses may reflect an epiphenomenon in which serum antibody levels and memory B cells are equally stable but independently maintained, without representing a direct cause-and-effect relationship.
If plasma-cell maintenance is memory B-cell–dependent, then booster vaccination or reinfection may reveal whether a cause-and-effect relationship is involved, because the association will continue to be maintained. However, if memory B cells and plasma cells are independently regulated, then multiple reexposures to antigens may cause divergence between memory B-cell levels and antibody levels. In support of this second hypothesis, antigens with the highest rates of boosting through vaccination or latent viral infection coincidentally showed the weakest association between memory B-cell titers and antibody titers (Table 3). Similarly, another study showed that multiple tetanus immunizations lead to a sustained increase in memory B cells without a concomitant increase in long-term antibody titers, indicating that memory B cells and antibody production are independently regulated.38
Long-lived plasma cells are another mechanism for maintaining serum antibodies. The existence of long-lived plasma cells was first shown in mice,30,31,32 and preliminary studies in human subjects depleted of CD20+ B cells provide further support for the long-lived plasma-cell hypothesis.39,40
Our cohort had seroprevalence rates of 82 to 100%, depending on the antigen being tested. All subjects had a response to at least five of the eight antigens tested; thus, no subjects had an overt inability to mount long-lasting antibody responses. Participants in this study were in good health overall, although certain persons had coexisting conditions such as high blood pressure or asthma (Table 1 in the Supplementary Appendix). Unrecognized confounders, including immune deficiencies and ablative treatments such as chemotherapy, may affect humoral immunity, resulting in more rapidly decaying antibody responses than those that we observed. Likewise, our findings are based on T-cell–dependent antibody responses, and the mechanisms involved in antibody persistence may differ for humoral immunity against T-cell–independent antigens, which is often short-lived. Greater insight into the factors that determine the duration of specific antibody responses will be important for future vaccine design, as well as for determining the timing of booster vaccinations required to sustain protective levels of immunity.
Supported by grants (PO1 AG023664, RR000163, RR000334, and RR024140) from the Public Health Service.
No potential conflict of interest relevant to this article was reported.
We thank the study subjects for their time and their participation in this study, J. Hall and D. Hess for obtaining serum samples, S. Carter for aid with organizing serum samples, and M. Lewis and E. Hammarlund for blood collection and processing.

Source Information
From the Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton (I.J.A., M.K.S.); and the Department of Public Health and Preventative Medicine, Division of Biostatistics, Oregon Health & Science University, Portland (N.E.C.).
Address reprint requests to Dr. Slifka at the Vaccine and Gene Therapy Institute, Oregon Health & Science University, 505 NW 185th Ave., Beaverton, OR 97006, or at slifkam@ohsu.edu.
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19. Hopkins RJ, Kramer WG, Blackwelder WC, et al. Safety and pharmacokinetic evaluation of intravenous vaccinia immune globulin in healthy volunteers. Clin Infect Dis 2004;39:759-766. [CrossRef][ISI][Medline]
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25. Wolters KL, Dehmel H. Abschliessende untersuchungen uber die Tetanus Prophylaxe durch active Immunisierung. Zeitschrift fur Hyeitschrift 1942;124:326-32.
26. Simonsen O, Bentzon MW, Heron I. ELISA for the routine determination of antitoxic immunity to tetanus. J Biol Stand 1986;14:231-239. [CrossRef][ISI][Medline]
27. Gottlieb S, McLaughlin FX, Levine L, Latham WC, Edsall G. Long-term immunity to tetanus -- a statistical evaluation and its clinical implications. Am J Public Health Nations Health 1964;54:961-971. [ISI][Medline]
28. Ipsen J. Circulating antitoxin at the onset of diphtheria in 425 patients. J Immunol 1946;54:325-347. [Free Full Text]
29. Bernasconi NL, Traggiai E, Lanzavecchia A. Maintenance of serological memory by polyclonal activation of human memory B cells. Science 2002;298:2199-2202. [Free Full Text]
30. Slifka MK. Mechanisms of antiviral immunity: studies on recombinant Listeria monocytogenes as a vaccine for inducing protective CTL memory and analysis of long-term antibody production after acute LCMV infection. Los Angeles: University of California, Los Angeles, 1996 (dissertation).
31. Manz RA, Thiel A, Radbruch A. Lifetime of plasma cells in the bone marrow. Nature 1997;388:133-134. [CrossRef][Medline]
32. Slifka MK, Antia R, Whitmire JK, Ahmed R. Humoral immunity due to long-lived plasma cells. Immunity 1998;8:363-372. [CrossRef][ISI][Medline]
33. Blink EJ, Light A, Kallies A, Nutt SL, Hodgkin PD, Tarlinton DM. Early appearance of germinal center-derived memory B cells and plasma cells in blood after primary immunization. J Exp Med 2005;201:545-554. [Free Full Text]
34. Bender R, Lange S. Adjusting for multiple testing -- when and how? J Clin Epidemiol 2001;54:343-349. [CrossRef][ISI][Medline]
35. Crotty S, Felgner P, Davies H, Glidewell J, Villarreal L, Ahmed R. Cutting edge: long-term B cell memory in humans after smallpox vaccination. J Immunol 2003;171:4969-4973. [Free Full Text]
36. Quinn CP, Dull PM, Semenova V, et al. Immune responses to Bacillus anthracis protective antigen in patients with bioterrorism-related cutaneous or inhalation anthrax. J Infect Dis 2004;190:1228-1236. [CrossRef][ISI][Medline]
37. Leyendeckers H, Odendahl M, Löhndorf A, et al. Correlation analysis between frequencies of circulating antigen-specific IgG-bearing memory B cells and serum titers of antigen-specific IgG. Eur J Immunol 1999;29:1406-1417. [CrossRef][ISI][Medline]
38. Nanan R, Heinrich D, Frosch M, Kreth HW. Acute and long-term effects of booster immunisation on frequencies of antigen-specific memory B-lymphocytes. Vaccine 2001;20:498-504. [CrossRef][ISI][Medline]
39. Cambridge G, Leandro MJ, Edwards JC, et al. Serologic changes following B lymphocyte depletion therapy for rheumatoid arthritis. Arthritis Rheum 2003;48:2146-2154. [CrossRef][ISI][Medline]
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Пт ноя 30, 2007 8:44 pm
Сообщение 
Вот замечательная статья про заболевания печени у китайцев, подтверждающая абсолютную неэффективность 20 летней вакцинации HVB.

Eur J Gastroenterol Hepatol. 2007 Aug;19(8):659-64.

Etiologies of chronic liver diseases in Hong Kong.

Fung KT, Fung J, Lai CL, Yuen MF.

Department of Medicine and Geriatrics, Kwong Wah Hospital, Hong Kong.

BACKGROUND: In Hong Kong, chronic hepatitis B (CHB) is endemic with a prevalence rate of 8.8%. Data, however, on chronic hepatitis C infection and other nonviral causes of chronic liver disease (CLD) are limited. AIM: To investigate the spectrum of CLDs in Hong Kong. METHODS: Records of all patients attending the Hepatology Clinic of Queen Mary Hospital, Hong Kong, in 2004 were reviewed to identify those with CLDs and their underlying causes. RESULTS: A total of 6106 patients were found to have CLD. CHB accounted for 89.4% of the cases, followed by chronic hepatitis C infection (5.1%). Nonviral causes accounted for the remaining 5.5% [alcoholic liver disease (ALD) (1.7%), nonalcoholic fatty liver disease (1.5%), primary biliary cirrhosis (PBC) (1.3%)]. Patients with CHB and Wilson's disease were significantly younger than patients with other causes (P<0.002). More than 90% of patients with autoimmune hepatitis and PBC were women. The prevalence of CHB infection was lower in patients with PBC than the general population. Among patients with ALD, the prevalence rate was higher for chronic hepatitis C but similar for CHB, as compared with the general population. CONCLUSIONS: Despite universal HBV vaccination since 1988, CHB remains the commonest cause of CLD in Hong Kong. PBC and nonalcoholic fatty liver disease were not rare in the Chinese population, being important causes of nonviral liver disease. The prevalence of chronic viral infection among patients with PBC or ALD confirmed the findings of other published literatures.

http://www.ncbi.nlm.nih.gov/sites/entre ... d_RVDocSum


Сб дек 15, 2007 3:52 pm
Сообщение 
Очень интересный огромный ресурс по вакцинологии на английском языке:
http://www.cdc.gov/vaccines/


Сб мар 29, 2008 4:27 pm
Сообщение 
Diagnostic Standards and Classification of Tuberculosis in Adults and Children.
«Interestingly, skin test reactivity resulting from vaccination does not correlate with protection against tuberculosis». American Thoracic Society.
http://www.thoracic.org/sections/public ... t1-20.html

Специфические вопросы политики относительно БЦЖ.
http://www.privivka.ru/info/library/foreign/?id=10
Время вакцинации для детей первого года жизни. БЦЖ в настоящее время рекомендуется прививать при рождении, или при первом контакте со службами здравоохранения. Вопрос предпочтительно ли прививать в первые дни жизни, либо в течение 1-2 месяцев жизни часто поднимался, но так и не был решен окончательно.
Повторные вакцинации (ревакцинации). Несмотря на то, что множество стран продолжает рекомендовать повторные вакцинации, это не одобрено ВОЗ.
Длительность эффекта. В настоящее время имеется слишком мало информации о длительности какой бы то ни было защиты, индуцируемой БЦЖ. Информация подобного рода необходима для оценки влияния программ вакцинации и для рациональных решений относительно полезности повторных вакцинаций.
Вакцинация работников здравоохранения. Работники служб здравоохранения в течение длительного времени рассматривались как группа риска по туберкулезу. Они в особенности подвержены риску инфицирования антиобиотикорезистентными штаммами M.tuberculosis. Недавний обзор исследований по изучению эффективности вакцинации БЦЖ среди врачей и медсестер показал, что в общем кумулятивные данные были достоверными в плане демонстрации приемлемого уровня защиты, несмотря на недостатки в методологии некоторых из исследований. Проведенная в медицинских учреждениях США оценка на основании модели "стоимость-выгода" показала, что применение вакцины даже с 13% эффективностью является выгодным.
Критерии для завершения программ вакцинации. Вероятно, в течение последующего десятилетия все большее число промышленно развитых стран будет переключаться с тактики сплошной вакцинации на селективную иммунизацию БЦЖ. Критерии IUATLD дают приблизительное руководство для принятия подобного рода решений.


Сб апр 05, 2008 5:02 pm
Сообщение 
Хотелось бы получить комментарии специалистов по статистике о достоверности исследований.
BMJ Clinical Evidens. Hepatitis B prevention.
http://clinicalevidence.bmj.com/ceweb/c ... rences.jsp

N Engl J Med. 1997 Jun 26.
Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children. Taiwan Childhood Hepatoma Study Group.
Chang MH, Chen CJ, Lai MS, Hsu HM, Wu TC, Kong MS, Liang DC, Shau WY, Chen DS.
Department of Pediatrics, National Taiwan University Hospital, Taipei.
BACKGROUND: A nationwide hepatitis B vaccination program was implemented in Taiwan in July 1984. To assess the effect of the program on the development of hepatocellular carcinoma, we studied the incidence of this cancer in children in Taiwan from 1981 to 1994. METHODS: We collected data on liver cancer in children from Taiwan's National Cancer Registry, which receives reports from each of the country's 142 hospitals with more than 50 beds. Data on childhood liver cancer were also obtained from Taiwan's 17 major medical centers. To prevent the inclusion of cases of hepatoblastoma, the primary analysis was confined to liver cancers in children six years of age or older. Data were also obtained on mortality from liver cancer among children. RESULTS: The average annual incidence of hepatocellular carcinoma in children 6 to 14 years of age declined from 0.70 per 100,000 children between 1981 and 1986 to 0.57 between 1986 and 1990, and to 0.36 between 1990 and 1994 (P<0.01). The corresponding rates of mortality from hepatocellular carcinoma also decreased. The incidence of hepatocellular carcinoma in children 6 to 9 years of age declined from 0.52 for those born between 1974 and 1984 to 0.13 for those born between 1984 and 1986 (P<0.001). CONCLUSIONS: Since the institution of Taiwan's program of universal hepatitis B vaccination, the incidence of hepatocellular carcinoma in children has declined.

Pediatrics. 1997 Mar;99(3).
Hepatitis B vaccination and hepatocellular carcinoma in Taiwan.
Lee CL, Ko YC.
Department of Pediatrics, Kaohsiung Municipal Min Sheng Hospital, Taiwan.
OBJECTIVE: In 1984, Taiwan started a large-scale hepatitis B vaccination program, enabling us to test the hypothesis that prevention of hepatitis B virus infection eventually decreases the incidence of hepatocellular carcinoma. METHODS: Groups aged 0 to 9 years and 10 to 100 years in each calendar year were defined as the study group and the reference group, respectively. The percentage of children vaccinated in the study group increased during recent years. The study group and the reference group were divided into 5-year age strata (0 to 4, 5 to 9, ..., 80 to 84, and 85 and over). Poisson regression was used to estimate age- and gender-adjusted liver carcinoma mortality rate ratios for 1974 through 1993, relative to 1974. RESULTS: The adjusted mortality rate ratios of liver carcinoma in the study group decreased significantly for 1992 and 1993, whereas in the reference group it did not show the same result. A significantly declining trend of liver carcinoma mortality rate ratios was observed in the study group after 1984, whereas the same trend was not found in the reference group. CONCLUSIONS: Our results support the hypothesis that hepatitis B vaccination can decrease the incidence of hepatocellular carcinoma.

Ann Intern Med. 2001 Nov 6.
Hepatitis B virus infection in children and adolescents in a hyperendemic area: 15 years after mass hepatitis B vaccination.
Ni YH, Chang MH, Huang LM, Chen HL, Hsu HY, Chiu TY, Tsai KS, Chen DS.
National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei 100, Taiwan.
BACKGROUND: Hepatitis B virus (HBV) infection is hyperendemic in Taiwan. Before universal HBV immunization was started in Taiwan in 1984, the carrier rate for hepatitis B surface antigen (HBsAg) was 15% to 20% in the general population. OBJECTIVE: To quantify the population impact of a mass vaccination program for HBV 15 years after its implementation. DESIGN: Descriptive analysis of serologic markers of HBV in healthy children and adolescents. SETTING: Chung-Cheng District, Taipei City, Taiwan, in 1999. PARTICIPANTS: 1357 persons younger than 15 years of age, who were born after the implementation of universal HBV vaccination, and 559 persons 15 to 20 years of age, who were born before the program began. MEASUREMENTS: Repeated serologic surveys similar to those done before and 5 and 10 years after the national vaccination program was implemented. All participants were tested for serum HBsAg, its antibody (anti-HBs), and hepatitis B core antibody (anti-HBc). RESULTS: During the 15 years since the vaccination program was implemented, the prevalence of HBsAg among persons younger than 15 years of age decreased from 9.8% in 1984 to 0.7% in 1999; among persons 15 to 20 years of age, the 1999 prevalence of HBsAg was 7% (P < 0.001). Hepatitis B core antibody seropositivity, which represents HBV infection, was found in 2.9% of persons younger than 15 years of age and in 20.6% of persons 15 to 20 years of age (P < 0.001); in the same age groups, the rate of anti-HBs seropositivity was 75.8% and 70.7%, respectively (P = 0.02). CONCLUSIONS: Universal vaccination significantly decreased the HBV carrier rate and infection rate among children and adolescents born since the program began. By decreasing the carrier pool, continuation of the national HBV immunization program should prevent HBV infection in the children of Taiwan, and, subsequently, adults as well.

J Pediatr. 2001 Sep;139(3).
Universal hepatitis B vaccination and the decreased mortality from fulminant hepatitis in infants in Taiwan.
Kao JH, Hsu HM, Shau WY, Chang MH, Chen DS.
Graduate Institute of Clinical Medicine, Department of Pediatrics, and Hepatitis Research Center, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan.
OBJECTIVES: To assess the annual mortality rate associated with fulminant hepatitis in infants before and after the mass immunization program that was launched in Taiwan in July 1984. STUDY DESIGN: From the National Mortality Registry System, the data on the mortality from fulminant hepatitis in infants from 1975 to 1998 were retrieved. Poisson regression analysis was used to assess the difference in average mortality from fulminant hepatitis in infants before (1975-1984) and after (1985-1998) the implementation of the mass hepatitis B vaccination program. RESULTS: The ratio of yearly mortality from 1975 to 1998 was 1.10 (P <.001), representing a progressive decrease in the number of the cases. The average mortality associated with fulminant hepatitis in infants from 1975 to 1984 and from 1985 to 1998 was 5.36 and 1.71 per 100,000 infants, respectively. The ratio of the average mortality in the period from 1985 to 1998 to that in the period from 1975 to 1984 was 0.32 (P <.001). CONCLUSIONS: These data indicate that since the institution of a program of mass hepatitis B vaccination in Taiwan, the mortality associated with fulminant hepatitis in infants has declined significantly.

На первый взгляд вроде эффективность доказана. Нет контрольной группы, отсутствие которой будет объяснено неэтичностью лишать ребёнка шанса на жизнь без рака печени или фульминантного гепатита. Как изменилась гетерогенность заболеваний печени за эти годы в связи с появлением новых методов диагностики?


Ср май 14, 2008 12:11 pm
Сообщение 
Вадим Асадулин писал(а):
Вот замечательная статья про заболевания печени у китайцев, подтверждающая абсолютную неэффективность 20 летней вакцинации HVB.

Eur J Gastroenterol Hepatol. 2007 Aug;19(8):659-64.

Etiologies of chronic liver diseases in Hong Kong.

Fung KT, Fung J, Lai CL, Yuen MF.

Department of Medicine and Geriatrics, Kwong Wah Hospital, Hong Kong.

BACKGROUND: In Hong Kong, chronic hepatitis B (CHB) is endemic with a prevalence rate of 8.8%. Data, however, on chronic hepatitis C infection and other nonviral causes of chronic liver disease (CLD) are limited. AIM: To investigate the spectrum of CLDs in Hong Kong. METHODS: Records of all patients attending the Hepatology Clinic of Queen Mary Hospital, Hong Kong, in 2004 were reviewed to identify those with CLDs and their underlying causes. RESULTS: A total of 6106 patients were found to have CLD. CHB accounted for 89.4% of the cases, followed by chronic hepatitis C infection (5.1%). Nonviral causes accounted for the remaining 5.5% [alcoholic liver disease (ALD) (1.7%), nonalcoholic fatty liver disease (1.5%), primary biliary cirrhosis (PBC) (1.3%)]. Patients with CHB and Wilson's disease were significantly younger than patients with other causes (P<0.002). More than 90% of patients with autoimmune hepatitis and PBC were women. The prevalence of CHB infection was lower in patients with PBC than the general population. Among patients with ALD, the prevalence rate was higher for chronic hepatitis C but similar for CHB, as compared with the general population. CONCLUSIONS: Despite universal HBV vaccination since 1988, CHB remains the commonest cause of CLD in Hong Kong. PBC and nonalcoholic fatty liver disease were not rare in the Chinese population, being important causes of nonviral liver disease. The prevalence of chronic viral infection among patients with PBC or ALD confirmed the findings of other published literatures.

http://www.ncbi.nlm.nih.gov/sites/entre ... d_RVDocSum


Такой комментарий я получил на сайте Солвей-Фарма от Маца Александра Наумовича из Москвы, торгующего биотехнологиями, иммунологией, препаратами крови №164, 14.5.2008, 21:40
Примечания:
Стиль и орфография источника сохранена.
Matz в переводе с немецкого - дурачок.

Для интересующихся перевёл абстракт по асадулинской ссылке.
Fung KT, Fung J, Lai CL, Yuen MF.
Этиология хронических заболеваний печени в Гон Конге
Eur J Gastroenterol Hepatol. 2007 Aug; 19 (8): 659-64.
ПРЕДПОСЫЛКИ: Гон Конг эндемичен по хроническому гепатиту В (ХГВ) с распространённость 8,8%. Данные по хроническому гепатиту С и другим невирусным хроническим печёночным заболеваниям (ХПЗ) недостаточны.
ЦЕЛЬ: исследовать структуру ХПЗ в Гон Конге. МЕТОДЫ: регистрация всех пациентов, поступающих в Клинику гепатологии Queen Mary Hospital в 2004 г. с идентификацией этиологии ХПЗ.
РЕЗУЛЬТАТЫ: всего обследовано 6106 больных, у которых диагносцировано ХПЗ. ХГВ был найден у 89,4%, хронический гепатит С (ХГС) – у 5,1%. Невирусная печёночная патология у оставшихся 5, 5%, [алкогольные поражения печени (АПП) – 1,7%], неалкогольная жировая дистрофия (1,5%), первичный милиарный цирроз (ПБЦ) 1,3%. Пациенты с ХГВ и болезнью Вильсона были существенно моложе страдающих другими заболевания печени (P > 0,002). Более 90% больных аутоиммунным гепатитом и ПБЦ – это женщины. Распространённость ХГВ была ниже среди страдающих ПБЦ, чем среди всего населения. Среди больных АПП чаще встречался ХГС, но с такой же частотой ХГВ, как и среди всего населения.
ЗАКЛЮЧЕНИЕ: Несмотря на всеобщую вакцинацию против гепатита В с 1988 г., ХПВ представляет собой самую частую причину ХПЗ в Гон Конге. ПБЦ и неалкогольная жировая дистрофия нередко встречаются среди китайцев в качестве главной причины невирусной патологии печени. Распространённость хронической вирусной инфекции среди больных ПБЦ или АПП подтверждается данными литературы.
Как видите, уважаемые читатели, нет там данных, «подтверждающих абсолютную неэффективность 20 летней вакцинации HVB», о которых взахлёб вопит Асадулин. Вакцинация предназначена для предохранения здоровых от инфекции гепатитом В, но существенно не снижает частоту хронического гепатита В, которая обусловлена до 10% иммуногенетически не отвечающих на вакцинацию (в статье, даже меньше, 8,8%). Для 91, 2% вакцина эффективна. Словом переводить с английского тибетский целитель не умеет и врёт напропалую. Но это не весенний дождь, а совсем иные, вульгарные звуки. Такие дела.
Антипрививочная пропаганда в интернете
http://www.solvay-pharma.ru/doctors/tab ... mid=6&p=16
Такие вот дела. Первичный милиарный цирроз печени! :x :fear:
Будем надеяться, что это опечатка!
Ребята, оторвитесь от огородных дел! Труба трубит!


Чт май 15, 2008 3:40 am
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Зарегистрирован: Вт фев 21, 2006 1:16 pm
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Откуда: Сердце Родины
Сообщение 
Вадим, по аббревиатуре в скобочках видно, что опечатка.

_________________
Где просто, там ангелов со сто, а где мудрено, там ни одного. (Преп. Амвросий Оптинский)


Чт май 15, 2008 9:46 pm
Профиль WWW
Сообщение 
Я бы согласился, что опечатка, но это - Мац, и к тому-же, фтизиатр! :D
Святому - святое снится.


Чт май 15, 2008 11:33 pm
Сообщение 
Результаты анализа причин развития реакций у детей при массовых прививках против гриппа.
д.м.н., профессор Лусс Людмила Васильевна
д.м.н., профессор Костинов Михаил Петрович
Интересный документ, похоже, что в комиссии кроме профессоров были и квалифицированные фельдшера, для убедительности нозология:
«Сопутствующие соматические заболевания, зарегистрированные у детей с ПВР:
- атопический дерматит – 1 ребенок;
- невротические и неврозоподобные состояния – 7 детей;
- повышенная нервно-рефлекторная возбудимость – 4 детей;
- вегето-сосудистая дистония – 4 детей;
- нарушения эндокринной системы – 3 детей;
- рецидивирующие заболевания ЖКТ – 6 детей;
- рецидивирующие заболевания дыхательной системы – 2 детей;
- множественные хронические очаги инфекции – 2 детей;
- инфекция мочевыделительной системы – 2 детей».
Как видно, не диагностировано ни одного случая сглаза или порчи.
А выводы говорят сами за себя: исследовали частоту осложнений, а получили эффективность вакцинации:
«Таким образом, установлено, что процент ПВР
у детей Пермского края был ниже теоретически возможных значений, а отечественная противогриппозная полимер-субъединичная тривалентная вакцина «Гриппол», в настоящее время, является самой безопасной и эффективной защитой человека от актуальных штаммов гриппа».
http://vnpoemp.ru/file/doc/rezultati_an ... grippa.doc


Вт июн 10, 2008 12:45 am
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Сообщение Re: Доказательная вакцинология.
Вакцинологи подкинули большой материал, якобы по Доказательной вакцинологии.
http://www.nfid.org/conferences/
http://clinicaltrials.gov/ct2/results?term=imovax+polio
Кто поможет разгрести эту кучу, м. б. есть уже готовые аналитические статьи?


Вт июн 29, 2010 2:25 pm
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Сообщение Re: Доказательная вакцинология.
Cochrane Database Syst Rev. 2011 Mar 16;(3):CD007879.
Hepatitis B vaccination during pregnancy for preventing infant infection.
Sangkomkamhang US, Lumbiganon P, Laopaiboon M.
Source.
Department of Obstetrics and Gynaecology, Khon Kaen Hospital, Srichan Road, Maung, Khon Kaen, Thailand, 40000.
Abstract.
BACKGROUND:
Infant hepatitis B infection increases risk of chronic infection, cirrhosis or liver cancer (hepatocellular carcinoma) in adult. Perinatal transmission is a common route of infection.
OBJECTIVES:
To assess the effectiveness and adverse effects of hepatitis B vaccine administered to pregnant women for preventing hepatitis B virus infection in infants.
SEARCH STRATEGY:
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 December 2010).
SELECTION CRITERIA:
Randomized controlled trials (RCTs) assessing hepatitis B vaccination compared with placebo or no treatment during pregnancy for preventing infant infection. We excluded quasi-RCTs and crossover studies.
DATA COLLECTION AND ANALYSIS:
Two review authors independently assessed trial eligibility.
MAIN RESULTS:
We were not able to include any studies.
AUTHORS' CONCLUSIONS:
We found no RCTs that assessed the effects of hepatitis B vaccine during pregnancy for preventing infant infection. Consequently, this review cannot provide guidance for clinical practice in this area. However, it does identify the need for well-designed randomized clinical trials for the effect of hepatitis B vaccine during pregnancy on the incidence of infant infection and adverse effects.
http://www.ncbi.nlm.nih.gov/pubmed/21412913
Отсутствие научных исследований в области профилактики заражения детей при вакцинации беременных.
Cochrane Database Syst Rev. 2008 Jul 16;(3):CD006481.
Hepatitis B immunisation in persons not previously exposed to hepatitis B or with unknown exposure status.
Mathew JL, El Dib R, Mathew PJ, Boxall EH, Brok J.
Source.
Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medial Education and Research (PGIMER), Chandigarh, India, 160012. jlmathew@rediffmail.com
Abstract.
BACKGROUND:
The benefits and harms of hepatitis B vaccination in persons not previously exposed to hepatitis B infection or with unknown exposure status have not been established.
OBJECTIVES:
To assess the benefits and harms of hepatitis B vaccination in people not previously exposed to hepatitis B infection or with unknown exposure status.
SEARCH STRATEGY:
Trials were identified from The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, LILACS,Science Citation Index Expanded (last search, March 2007). Additionally, we contacted experts and vaccine manufacturers, and read through reference lists for eligible trials.
SELECTION CRITERIA:
Randomised clinical trials comparing hepatitis B vaccine versus placebo, no intervention, or another vaccine in persons not previously exposed to hepatitis B (HBsAg negative) or with unknown exposure status.
DATA COLLECTION AND ANALYSIS:
The primary outcome was hepatitis B infection (detecting HBsAg, HBeAg, HBV DNA, or anti-HBc). Secondary outcomes were lack of sero-protection, antibody titre, clinical complications, adverse events, lack of compliance, and cost-effectiveness. Dichotomous outcomes were reported as relative risk (RR) with 95% confidence interval (CI), using intention-to-treat analysis assuming an unfavourable event for missing data. Sensitivity analyses based on methodological quality (risk of bias), available data analysis, intention-to-treat analysis assuming a favourable event for missing data, best-case scenario, and worst-case scenario were conducted.
MAIN RESULTS:
Twelve trials were eligible. All had high risk of bias and reporting was inconsistent. Hepatitis B vaccine did not show a clear effect on the risk of developing HBsAg (RR 0.96, 95% CI 0.89 to 1.03, 4 trials, 1230 participants) and anti-HBc (RR 0.81, 95% CI 0.61 to 1.07; 4 trials, 1230 participants, random-effects) when data were analysed using intention-to-treat analysis assuming an unfavourable event for missing data. Analysis based on data of available participants showed reduced risk of developing HBsAg (RR 0.12, 95% CI 0.03 to 0.44, 4 trials, 576 participants) and anti-HBc (RR 0.36, 95% CI 0.17 to 0.76, 4 trials, 576 participants, random-effects). Intention-to-treat analysis assuming favourable outcome for missing data showed similar reduction in risk. Hepatitis B vaccination had an unclear effect on the risk of lacking protective antibody levels (RR 0.57, 95% CI 0.26 to 1.27, 3 trials, 1210 participants, random-effects). Development of adverse events was sparsely reported.
AUTHORS' CONCLUSIONS:
In people not previously exposed to hepatitis B, vaccination has unclear effect on the risk of developing infection, as compared to no vaccination. The risk of lacking protective antibody levels as well as serious and non-serious adverse events appear comparable among recipients and non-recipients of hepatitis B vaccine.
http://www.ncbi.nlm.nih.gov/pubmed/18677780
Отсутствие эффекта от вакцинации против гепатита В.


Вс июл 31, 2011 8:47 am
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Сообщение Re: Доказательная вакцинология.
Цитата:
Отсутствие эффекта от вакцинации против гепатита В.

Кто бы сомневался!
Вот только Минздрав считает, что прививая младенцев в роддомах, наша медицина добилась резкого снижения заболеваемости гепатитом В. :shock:
Хотя те привитые детишки даже еще не успели вырасти до возраста, когда начинают вести беспорядочную половую жизнь и колоть наркотики одним шприцем...

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Вс июл 31, 2011 10:38 pm
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Сообщение Re: Доказательная вакцинология.
Похоже, Matz - (нем. – дурачок) от обсуждения фекалий перешёл к изучению предметов детского гардероба. Явный интеллектуальный рост! Решил разместить наш научный спор в открытом доступе, чтоб народ посмотрел какие новые аргументы появились в вакцинологии.
Цитата с закрытого врачебного форума.
«Чтобы со смыслом таскать сюда из PubMed копии, надо понимать, о чём написано и к чему. Асадулин, как я уже писал много лет тому назад, этого лишён. В первом абстракте кокрейновская база данных сделала попытку исследовать эффективность вакцинации беременных рекомбинантной HBs-вакциной для снижения риска последующего заболевания ребёнка гепатитом В. Однако рандомизированных клинических испытаний (РКИ), удовлетворяющих критериям базы, на эту тему среди публикаций не оказалось, поскольку ни один национальный календарь вакцинации беременных не предусматривает. Поставили задачу и ожидают.
Цитата моего сообщения: Отсутствие научных исследований в области профилактики заражения детей при вакцинации беременных.
Фраза безграмотна и нелепа, поскольку никто не утверждает обратное.
Во втором абстракте от 2008 Асадулин не справился с переводом вывода: In people not previously exposed to hepatitis B, vaccination has unclear effect on the risk of developing infection, as compared to no vaccination. The risk of lacking protective antibody levels as well as serious and non-serious adverse events appear comparable among recipients and non-recipients of hepatitis B vaccine. По-русски это означает: «У неэкспонированных индивидов, в сравнении с непривитыми, вакцинация против гепатита В не влияет на риск развитие инфекции. Риск отсутствия специфических антител и побочных реакций у привитых такой же, как и у непривитых». Другими словами, если нет риска заражения, то привитые и непривитые не различаются, а потенциальный риск отсутствия анти-HBs-антител (теоретически не более 10%) и реактогенности вакцинации у тех и других одинаков. В этом и не было сомнений.
Цитата моего сообщения: Отсутствие эффекта от вакцинации против гепатита В.
Это асадулинская фраза – чистое враньё. Стратегическая консультационная группа экспертов ВОЗ сделала диаметрально противоположный вывод о 95% эффективности первичного курса из трёх иммунизаций новорожденных, детей и молодых взрослых при HBs-вакцинации и взрослых любого возраста при HBs-ревакцинации [нерабочая ссылка] Честно скажу, что путающийся в соплях и подгузниках тибетский лечитель страсть как надоел бестолковостью и привиранием.
Мой комментарий. Что спорить с неэкспонированным индивидом? Надеюсь, что нерабочая ссылка на эффективность вакцинации будет исправлена и научные исследования проведены в соответствующем дизайне.


Чт авг 04, 2011 7:46 am
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Сообщение Re: Доказательная вакцинология.
А успокоиться-то вы бедному Мацу не даете! :D

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Пт авг 05, 2011 11:06 pm
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Сообщение Re: Доказательная вакцинология.
Моя борьба:
http://38mama.ru/forum/index.php?topic= ... 138547#new
:professor:


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