Antibody Levels In Individuals Research Articles

O13 Mumps virus detection by PCR and culture during an outbreak in a highly unvaccinated population

Objective: Rabies virus has the highest case to fatality ratio of any infectious disease; however, vaccines and immunoglobulins are available for preand post-exposure prophylaxis. Due to the risk of possible hypersensitivity reactions, repeated booster doses of rabies vaccine should be administered only when necessary to people at risk of exposure. It is recommend that antibody testing be performed 2 years following primary immunization, followed by the administration of a booster dose if the neutralizing antibody titre falls below 0.5 International Units per ml (IU/ml). The objective of this work was to determine if the recommended testing interval following primary immunization is sufficient to maintain adequate antibody titres in healthy adults. Methods: During the establishment of the rabies laboratory at the NML in 2007, all employees determined to be at risk of exposure were vaccinated against rabies virus. Rabies vaccine was administered in 3 doses on days 0, 7, and 21. Antibody levels were monitored one month post-vaccination and subsequently every 6 months. Data from this testing were analyzed to determine if the vaccinated employees maintained adequate antibody titres for a minimum of 2 years following primary immunization. Results: The antibody titres of 12 employees were assessed 1 month after vaccination and subsequently every 6 months. All 12 employees demonstrated an acceptable antibody titre 1 month after vaccination, although the titres of 2 of the 12 employees were very low (0.5 IU/ml and 0.65 IU/ml). These 2 employees received a booster dose of vaccine immediately. Two other employees demonstrated a substantial drop in titre when subsequently tested 6 months later, resulting in a decision to administer a booster dose of vaccine to these employees who work directly with rabies virus. The antibody titre of these 4 employees has remained high throughout the follow-up testing intervals. Conclusions: Had the recommended testing interval of 2 years been followed, the antibody levels of 4 of the 12 employees may have potentially fallen below the acceptable level of 0.5 IU/ml. This indicates that some healthy individuals may not maintain an antibody titre of 0.5 IU/ml for at least 2 years following primary immunization. All persons at risk of exposure, especially those persons working directly with the live virus, should be monitored carefully. It may be advisable to administer a booster dose of vaccine 1 year following the primary vaccine series to reinforce antibody levels in individuals receiving pre-exposure vaccination for rabies virus.

O12 Antibody response to rabies vaccine in healthy adults following primary immunization and the importance of occupational health surveillance programs

Objective: Rabies virus has the highest case to fatality ratio of any infectious disease; however, vaccines and immunoglobulins are available for preand post-exposure prophylaxis. Due to the risk of possible hypersensitivity reactions, repeated booster doses of rabies vaccine should be administered only when necessary to people at risk of exposure. It is recommend that antibody testing be performed 2 years following primary immunization, followed by the administration of a booster dose if the neutralizing antibody titre falls below 0.5 International Units per ml (IU/ml). The objective of this work was to determine if the recommended testing interval following primary immunization is sufficient to maintain adequate antibody titres in healthy adults. Methods: During the establishment of the rabies laboratory at the NML in 2007, all employees determined to be at risk of exposure were vaccinated against rabies virus. Rabies vaccine was administered in 3 doses on days 0, 7, and 21. Antibody levels were monitored one month post-vaccination and subsequently every 6 months. Data from this testing were analyzed to determine if the vaccinated employees maintained adequate antibody titres for a minimum of 2 years following primary immunization. Results: The antibody titres of 12 employees were assessed 1 month after vaccination and subsequently every 6 months. All 12 employees demonstrated an acceptable antibody titre 1 month after vaccination, although the titres of 2 of the 12 employees were very low (0.5 IU/ml and 0.65 IU/ml). These 2 employees received a booster dose of vaccine immediately. Two other employees demonstrated a substantial drop in titre when subsequently tested 6 months later, resulting in a decision to administer a booster dose of vaccine to these employees who work directly with rabies virus. The antibody titre of these 4 employees has remained high throughout the follow-up testing intervals. Conclusions: Had the recommended testing interval of 2 years been followed, the antibody levels of 4 of the 12 employees may have potentially fallen below the acceptable level of 0.5 IU/ml. This indicates that some healthy individuals may not maintain an antibody titre of 0.5 IU/ml for at least 2 years following primary immunization. All persons at risk of exposure, especially those persons working directly with the live virus, should be monitored carefully. It may be advisable to administer a booster dose of vaccine 1 year following the primary vaccine series to reinforce antibody levels in individuals receiving pre-exposure vaccination for rabies virus.

Long-term persistence of anti-HPV-16 and -18 antibodies induced by vaccination with the AS04-adjuvanted cervical cancer vaccine: Modeling of sustained antibody responses

Objectives Strong and sustained HPV-16 and -18 antibody responses have been observed in previously unexposed women aged 15–25 years vaccinated with the AS04-adjuvanted HPV-16/18 L1 virus-like particle vaccine. While awaiting the extended results of ongoing trials, our objective was to predict the long-term persistence of anti-HPV-16/18 antibodies in vaccinees by applying three statistical models using immunogenicity data from vaccinated women with serum samples collected up to 6.4 years after first vaccination. Two different data lock-points (up to 5.5 years and up to 6.4 years) were used to assess the robustness of the models. Methods Three statistical models were applied to estimate the long-term persistence of anti-HPV-16/18 antibodies in 393 women vaccinated with the AS04-adjuvanted HPV-16/18 vaccine. Individual antibody levels for each study participant at each timepoint up to 6.4 years were input to previously published power-law and modified power-law models. The power-law model estimates antibody decay over time. The modified power-law model takes into account both antibody persistence over time and immune memory. A third model, the piece-wise model, fits the data based on three different non-overlapping intervals (between Months 7 and 12, Months 12 and 21, and over 21 months), corresponding to the observed decay of vaccine-induced antibodies. Results HPV-16 and -18 antibodies peaked at Month 7 and gradually plateaued at Months 18–24 and remained stable through 6.4 years. Mean antibody levels at the last timepoint were several fold higher than those associated with natural infection. All three models predict that HPV-16 and -18 mean antibody levels will remain well above those associated with natural infection for at least 20 years, when using data from 5.5 as well as 6.4 years' follow-up. Predictions are similar for the modified power-law model and improve with longer follow-up for both the power-law and the piece-wise models. Conclusions Vaccination with the AS04-adjuvanted HPV-16/18 vaccine is predicted to provide long-term persistence for both HPV-16 and -18 antibodies, independent of the statistical model applied. Model predictions are based on conservative mathematical assumptions. Since the input of longer term data of up to 6.4 years showed an improved profile compared with that for data up to 5.5 years, the predictions of antibody persistence based on population means are conservative when predicting that antibody levels will remain well above levels induced by natural infection for 20 years.

Evaluation of IgG-ELISA for the diagnosis of Schistosoma japonicum in a high prevalence, low intensity endemic area of China

Antibody-based diagnostic methods for detecting infection with Schistosoma japonicum have been developed and integrated into the national control program in China; however, the utility of these methods compared with conventional coprological methods remains unclear. In two consecutive years, we compared the performance characteristics of Kato–Katz with a commercially available enzyme-linked immunosorbent assay (ELISA) that detects anti-egg antigen IgG antibodies in a high prevalence, low intensity village in China (1025 subjects in 2005 and 652 subjects in 2006). In comparison with Kato–Katz based on duplicate stool specimens, each read in triplicate, the sensitivity of IgG-ELISA was high, ranging from 79.3% to 87.4% but with a relatively low specificity of 38.9% to 53.5%. The positive predictive value ranged from 20.8% to 24.6% while the negative predictive value ranged from 93.1% to 94.4%. When analyzed as continuous variables, there was a poor correlation between EPG (eggs per gram feces) and antibody level in both years ( r 2005 = 0.23 and r 2006 = 0.41). We detected a trend toward reduced sensitivity at lower infection intensity as measured by Kato–Katz in 2005 ( P = 0.262) and 2006 ( P = 0.287). We evaluated changes in antibody levels and the prevalence of positive antibody in the cohort of subjects examined in both 2005 and 2006 ( n = 565). The prevalence of positive antibody but not the continuous antibody level, decreased in individuals who were uninfected at both time points or who transitioned from infected to uninfected as assessed by Kato–Katz. In this cohort, the distribution of antibody levels measured in 2006 among individuals who were positive by Kato–Katz in 2006 broadly overlapped with the distribution of antibody levels in individuals who were negative by Kato–Katz in both 2005 and 2006. Our results indicate fairly poor performance characteristics of the anti-egg antigen IgG-ELISA for the detection of active infection with S. japonicum in our community based sample and are in contrast with other reports based on more selected populations. The high prevalence but low intensity of S. japonicum in our study community reflects the evolving epidemiology of schistosomiasis in communities receiving intermittent treatment with praziquantel in China. We suggest marked caution in implementing anti-egg antigen IgG-ELISA based diagnosis for either individual level diagnosis or population-based targeting for national control programs.

Clinical bacteriology and immunology in acute otitis media in children

Acute otitis media (AOM) is the most common disease seen in childhood. Streptococcus pneumoniae, non-typeable Haemophilus influenzae (NTHi), and Moraxella catarrhalis are the most frequent pathogens of all AOM episodes. The high prevalence of drug-resistant pathogens such as penicillin-resistant S. pneumoniae (PRSP) and betalactamase producing or nonproducing ampicillin-resistant H. influenzae (BLPAR or BLNAR) is causing serious clinical problems worldwide. PRSP and BLNAR have become important risk factors for intractable clinical outcome of AOM. PRSP causes a three times higher incidence of intractable AOM than susceptible strains. BLNAR strains show penicillin-binding protein gene mutation and are not only resistant to ampicillin, but also have reduced susceptibility to cephalosporin. The resistant H. influenzae pathogen has shown clonal dissemination in Japan in ways different from those of penicillin-resistant S. pneumoniae. Protection against AOM due to these pathogens may depend on pathogen-specific antibodies. Pneumococcal capsular polysaccharides (PCPs) are type specific and poorly immunogenic in children younger than 2 years old. Approximately 50% of otitis-prone children showed subnormal levels of anti-PCP IgG2 antibody. In our immunological study in children with otitis media, however, otitis-prone children were not unusually vulnerable to infections except those resulting in otitis media. This fact seems to refute the presence of a broad immunological deficit in these children. Some pathogen-specific antibodies may be directed against protein immunogens such as pneumococcal surface protein A (PspA) of S. pneumoniae, P6 of NTHi, and UspA of M. catarrhalis. The levels of antibody to P6 of NTHi in healthy children were significantly higher than those in the otitis-prone children after the age of 18 months. In general, individual antibody levels in otitis-prone individuals did not have an age-dependent rise. The failure to develop a good antibody response to common antigens such as PspA and P6 may enable the pathogen to cause persistent or recurrent disease.

Wuchereria bancrofti in a community with seasonal transmission: stability of microfilaraemia, antigenaemia and filarial-specific antibody concentrations.

The effect of seasonal transmission on microfilaraemia, antigenaemia and filarial-specific antibody levels in individuals infected with Wuchereria bancrofti was investigated in a follow-up study in an endemic community in north-eastern Tanzania. The subjects were 37 adult male residents who were found to be positive for circulating filarial antigen (CFA) at the beginning of the study (26 of whom were also found microfilaraemic with W. bancrofti at this time). Blood samples were collected from each subject in July 1998, January 1999 and July 1999, during the seasons when transmission intensity was high, low and high, respectively. The mean intensities of microfilaraemia and the mean concentrations of CFA were each slightly higher during the low-transmission season than during the two high-transmission seasons but the differences were not statistically significant (P > 0.05). Similarly, the mean levels of filarial-specific IgG1, IgG2, IgG3, IgG4 or IgE did not differ to a statistically significant degree between the three examination times. Microfilaraemias and the levels of CFA and filarial-specific antibodies all therefore appeared to be remarkably stable and largely unaffected by the seasonal variation in transmission. That no variation in the mean IgG4/IgE ratio was observed over the study period may indicate that the level of resistance to W. bancrofti infection in the study subjects was also unaffected by the transmission season.

Wuchereria bancroftiin a community with seasonal transmission: stability of microfilaraemia, antigenaemia and filarial-specific antibody concentrations

The effect of seasonal transmission on microfilaraemia, antigenaemia and filarial-specific antibody levels in individuals infected with Wuchereria bancrofti was investigated in a follow-up study in an endemic community in north-eastern Tanzania. The subjects were 37 adult male residents who were found to be positive for circulating filarial antigen (CFA) at the beginning of the study (26 of whom were also found microfilaraemic with W. bancrofti at this time). Blood samples were collected from each subject in July 1998, January 1999 and July 1999, during the seasons when transmission intensity was high, low and high, respectively. The mean intensities of microfilaraemia and the mean concentrations of CFA were each slightly higher during the low-transmission season than during the two high-transmission seasons but the differences were not statistically significant (P > 0.05). Similarly, the mean levels of filarial-specific IgG1, IgG2, IgG3, IgG4 or IgE did not differ to a statistically significant degree between the three examination times. Microfilaraemias and the levels of CFA and filarial-specific antibodies all therefore appeared to be remarkably stable and largely unaffected by the seasonal variation in transmission. That no variation in the mean IgG4/IgE ratio was observed over the study period may indicate that the level of resistance to W. bancrofti infection in the study subjects was also unaffected by the transmission season.

A prospective study of cytomegalovirus, herpes simplex virus 1, and coronary heart disease: the atherosclerosis risk in communities (ARIC) study.

Conflicting evidence exists implicating infectious disease in the pathological processes leading to coronary heart disease (CHD). The objective of this article is to describe the relationship of previous infection with cytomegalovirus (CMV) and herpes simplex virus 1 to incident CHD in a population-based cohort study. Using a nested case-cohort design from the Atherosclerosis Risk in Communities Study, antibody levels to CMV and herpes simplex virus 1 were determined in serum samples that had been frozen at the baseline examination in participants free of CHD. Determinations were made in those who developed incident CHD (n=221) during follow-up of up to 5 years from baseline and in a stratified random sample of all participants (n=515). The population with the highest antibody levels of CMV (approximately the upper 20%) showed an increased relative risk (RR) of CHD of 1.76 (95% confidence interval, 1.00-3.11), adjusting for age, sex, and race. After adjustment for additional covariates of hypertension, diabetes, years of education, cigarette smoking, low-density lipoprotein and high-density lipoprotein cholesterol levels, and fibrinogen level, the RR increased slightly. Based on a priori hypotheses, the RR of CHD at the highest antibody levels in individuals with diabetes was particularly large but with wide confidence intervals (RR, 9.2; 95% confidence interval, 1.8-47.0), and the interaction between high levels of antibody to CMV and diabetes was statistically significant (P=.05). There was no association of CHD with the highest herpes simplex virus 1 antibody levels (adjusted RR, 0.77; 95% confidence interval, 0.36-1.62). High levels of CMV antibodies are significantly associated with incident CHD. Infection with CMV, particularly in more susceptible disease states such as diabetes, may be an important risk factor for CHD.

Inactivated hepatitis A vaccine-induced antibodies: Follow-up and estimates of long-term persistence

To estimate the long-term persistence of anti-HAV antibodies, 120 (schedule 0-6) and 194 (schedule 0-12) adults were vaccinated and followed-up annually for 6 years. Shortly after the last dose, anti-HAV levels fell sharply (annual decline rate delta > 65%). Thereafter, delta diminished to 10-15%. GMTs 5.5 years after the last dose were 522 mIU/ml (0-6 group) and 749 mIU/ml (0-12 group); all subjects except one maintained detectable antibodies. The average delta over the whole follow-up period was 15-20%, resulting in an estimated persistence of anti-HAV levels > or =20 mIU/ml for 20-25 years. These estimates were similar for both applied calculation methods (GMT or individual based) and both vaccination schedules. Because the individual antibody levels tended to stabilise between the last two measurements, the hypothesis of a slow, log-linear decrease and its matching calculation methods might be subject to reconsideration. With the current methodology, however, detectable antibodies are estimated to persist for 20-25 years.

Relationships between exposure to spores from Rhizopus microsporus and Paecilomyces variotii and serum IgG antibodies in wood trimmers.

A longitudinal study of wood trimmers exposed to mould spores was carried out from 1985 to 1988. Exposure to airborne spores from Rhizopus microsporus ssp. rhizopodiformis and Paecilomyces variotii was measured by scanning electron microscopy of filter samples. Specific IgG antibodies to these moulds were measured by ELISA in serum samples collected at half-year intervals. Antibody levels to R. microsporus and P. variotii were higher in wood trimmers than in other sawmill workers whose jobs had an assumed lower exposure to mould spores. Antibody levels were significantly elevated after periods with high exposure compared to antibody levels in the same wood trimmers after periods with low exposure. Antibodies were also found in newly employed wood trimmers. These wood trimmers were exposed to 1,300 x 10(3) R. microsporus spores/m3 and 130 x 10(3) P. variotii spores/m3 (arithmetic mean exposure). Antibody levels in the newly employed wood trimmers were similar to antibody levels in wood trimmers who had already worked in the trimming department before the start of the study. Antibody levels to R. microsporus and P. variotii in wood trimmers can be regarded as indicators of fairly recent exposure. There were, however, large differences between the individual antibody levels of similarly exposed wood trimmers.

Age-related change in anti-carbohydrate antibody levels.

It has been proposed that immunity declines with age. Most evidence for this hypothesis has been obtained from cross-sectional samples of unrelated populations that differ in age, antigen exposure, and morbidity. In the present study, the authors used serum samples collected repeatedly from the same persons in longitudinal studies. Two representative samples of the population in Göteborg, Sweden were obtained; the first was studied at ages 38, 50, and 62 years, and the second at ages 70, 75, 79, and 81 years, respectively. The phosphorylcholine determinant of pneumococcal teichoic acid and the B blood group determinant were selected as model polysaccharide antigens. The results demonstrate a consistent decline in individual antibody levels in the decades before age 70 years but not later. Antibodies to phosphorylcholine and blood group B were highly parallel, suggesting that the decline was a general phenomenon for antibodies to polysaccharide antigens.

ELISA of paragonimiasis in cat by crude and purified antigens of Paragonimus westermani

Enzyme-linked immunosorbent assay (ELISA) using crude and affinity-purified antigens of adult worms of Paragonimus westermani was performed for infected cat sera with different worm burden, from preinfection to 18th week after infection. Crude antigen was used with supernatant of homogenated worms by freezing-thawing method, and the supernate was centrifuged for l hour at 10,000 rpm at 4C. Affinity-purified antigen (antibody-bound antigen) was prepared from fractions (bound and unbound) of crude antigen by affinity chromatography on CNBr-activated sepharose 4B, and IgG as a ligand was prepared from paragonimiasis cat serum (6 months infected) obtained by ammonium sulfate (40-45 per cent saturated) precipitation method. By SDS-PAGE, crude antigen showed 22 polypeptide fractions while purified antigen showed 4 fractions: 36, 400, 34,700,27,600 and 11,500 in molecular weights. All cats were divided into five groups(G1-G5) by different worm burdens. The mean of recovered worms (+/-SD) and the number of cats in each group are as follows:G1, 2 worms(0) and 4 cats; G2, 4.75(+/-0.66) and eight; G3, 10.75(+/-1.92) and four; G4, 25.20(+/-3.43) and five; G5, 48(+/-12.63) and five cats. The results were summarized as follows: The antibody levels(OD value) increased by worm burden in G1 to G4 generally. However, individual antibody levels were not exactly related with worm burden in all groups, especially there was a wide difference in G4 and G5. These results suggested that the worm burden in G4 (about 20 - 30 worms) is enough to produce antibody maximum in cats of 2~3 kg weight. The antibody levels increased significantly (p<0.05) compared to control sera at the 3rd week in G1 and G2, at the 2nd week in G3, and at the 1st week in G4 and G5. Especially in the 4th week, OD value increased more in G1(p<0.001) and in G2 to G5(p<0.01). In the pattern of antibody levels by ELISA in each group, OD in G1 increased to the 18th week continuously, in G2 OD was maintained same after the 16th week, but in G3 it decresed after the 16th week, and it was maintained same in G4 and G5 after the 14th week. The antibody levels by ELISA with the affinity-purified antigen were higher than those with crude antigen in all groups generally. Especially, the difference of OD values between two antigens was larger from the 4th to the 10th week. In G1 and G2 OD with purified antigen was higher than that with crude one to the 18th week. It was also higher in G3 than that with crude antigen to the 16th week and OD of G4 and G5 were higher before the 14th week than that with crude antigen, however became lower at the 16th week. Consequently, the antibody level in ELISA with affinity-purified antigen was more sensitive at the early weeks after infection and in light infection groups than that with crude antigen.

Autoantibodies in thyrotoxicosis: a quantitative study of their behavior in relation to the course and outcome of treatment.

Many previous investigations have looked into the association between thyroid autoantibodies and the course of thyrotoxicosis. However, the interpretation of these studies is often difficult, owing to their largely retrospective nature, and comparability is limited because of differences in criteria and sampling schedules. The purpose of this study was to investigate prospectively the serial changes in autoantibodies under carefully controlled conditions during treatment of thyrotoxicosis, and to relate these changes to clinical outcome and surgical histology. Sixty-seven patients with Graves’ disease were studied for 24 months; 34 were treated medically and 33 surgically. Anti-thyroglobulin (anti-Tg) and anti-microsomal (anti-M) antibodies were measured on 16 occasions. The frequency of patients showing anti-Tg fell progressively irrespective of the type of treatment, while that showing anti-M fell initially but rose again. Weak associations were found between anti-Tg and suppressibility after 5 months of drug treatment, between the cumulative amount of anti-M and the final TSH levels in those who remained euthyroid after drugs, and between the circulating levels of anti-M just before surgery and the frequency of clinical hypothyroidism 18 months later. However, no significant correlation emerged between the cumulative amount of antibody during the two-year period and the final TSH level or clinical result after surgery, nor between the prevailing antibody level and surgical histology. Wide, rapid and apparently random fluctuations of antibody levels in individuals cast considerable doubt upon the value of single estimations in the distinction of antibody-positive from antibody-negative members of a thyrotoxic population. We conclude that the measurement of thyroid autoantibodies in Graves’ disease has little practical value for the clinician.

STUDIES OF THE NATURAL HISTORY OF HERPES SIMPLEX INFECTIONS

In a detailed study of 12 individuals with primary herpetic stomatitis the virus was recovered from the mouth and stools during the acute stage, convalescence, and for varying periods of time thereafter. The average time period during which virus could be recovered from these sources was 23 days after the onset of the disease. Virus could not be recovered from the blood or spinal fluid, but patients were not available for study before the third day of the disease. Neutralizing antibodies to herpes simplex were first demonstrated in the serum from the fourth to seventh day of the disease. The antibodies attained a maximum level during the second or third week. Considerable differences in individual antibody levels were noted. The maximum antibody concentration was not maintained and dropped to relatively low levels over varying periods of time in each patient studied. Herpes simplex virus was recovered from the mouths of many individuals presenting no clinical evidence of herpetic infection. The virus was recovered from 7% of 571 normal individuals of various ages. It was recovered from 1 infant out of 97 under 6 months of age, from 20% of 72 children of 7 months to 2 years, from 9% of 199 children 3 to 14 years of age and from 2.5% of the 185 adults. The incidence of normal carriers was found to be highest (26%) in Negro children in the 7 months to 2 year age group. Neutralizing antibodies were demonstrated in the serum of 43% of white and 71.4% of Negro children in the 7 month to 2 year age group. The serum of 84.7% of white and 86% of Negro children in the 3 to 14 year age group contained antibodies to herpes. In adults 90% of white and 96% of Negro individuals had antibodies to herpes in the serum. Natural active immunity appears to be established at an earlier age in the segments of the population in which the highest carrier rate was demonstrated. Neutralizing antibodies were demonstrated in the serum of 76% of white infants and in 90% of Negro infants 6 months of age and under. The placental transmission of neutralizing antibodies was demonstrated. Approximately the same level of antibody was found to be present in the maternal serum and in the serum obtained from the placenta.