Seroepidemiology of invasive pneumococcal disease in Queensland, 1990 to 1997

Serotypes responsible for 842 cases of invasive pneumococcal disease in Queensland between February 1990 and October 1997 were identified. Type 14 caused 37.5% of episodes in children aged 0-4 years and 19.2% of adult cases. Types 6A, 6B, 14, 18C, and 19F were significantly more frequent in young children while types 3, 4, 7F, 9V and 23F predominated in adults. The regional incidence of type 14 and 7F disease differed significantly in Southeast and Far North Queensland. Coverage for 87% of children aged less than 5 years in this study would be provided by a recently advocated polysaccharide-protein conjugate vaccine containing capsular antigens of types 4, 6B, 9V, 14, 18C, 19F and 23F. Similarly, more than 90% of adults would be covered by the currently available 23- valent polysaccaride vaccine.     

High immunogenicity and good tolerability of a new hepatitis A vaccine candidate

Immunogenicity and tolerability of a new formalin-inactivated, alum-adjuvanted whole virus vaccine against hepatitis A (VAQTA, MSD, West Point, USA) were evaluated by immunizing 52 healthy, anti-HAV negative volunteers with a 1 ml dose. A booster dose was given 6 months later. In these young adult vaccinees [27 males and 25 females, 19-34 (mean 26) years of age] VAQTA proved to be well tolerated and highly immunogenic. Two weeks after administration of one vaccine dose, all but one of the recipients (98%) had anti-HAV concentrations above the presumed minimum protective level of 10 IU l-1 with a geometric mean concentration (GMC) of 165 IU l-1. After 4 weeks, a 100% seroconversion rate could be demonstrated with a fourfold increase of the GMC to 728 IU l-1. Six months after vaccination, all but one of the 50 volunteers coming back for booster (98%) showed anti-HAV levels within the protective range. The antibody concentrations had decreased in the majority of vaccinees to a GMC of 362 IU l-1. The booster dose given at that time was shown to be very effective, leading to a pronounced rise of anti-HAV levels in all recipients with a 17-fold increase of the GMC to 6040 IU l-1. Six months after the booster, all vaccinees were still seropositive with a GMC of 3444 IU l-1. Higher antibody levels were found in females, the difference being significant 4 weeks and 6 months after vaccination and 4 weeks after booster. No serious local or systemic adverse reactions were observed.     

The immunogenicity of three Haemophilus influenzae type B conjugate vaccines after a primary vaccination series in Philippine infants

Serum antibody responses to three Haemophilus influenzae type b (Hib) capsular polysaccharide-protein conjugate vaccine (PRP-OMP, PRP-T, and HbOC) were evaluated in 174 Philippine infants after a primary vaccination series. Children were randomized to receive one of the Hib vaccines (Hib groups) or into a control group. Vaccination was carried out at six, 10 and 14 weeks of age based on the local Expanded Program of Immunization schedule. Sera were collected at six weeks of age for the Hib groups and one month after the third dose for all subjects. Anti-Hib concentrations were determined by the Farr-type radioimmunoassay. There were no significant differences (P = 0.3626) in the prevaccination anti-Hib geometric mean concentration (GMC) among the three Hib groups. Differences in the GMC after the primary series of three doses were significant (P < 0.0001); GMC was highest for PRP-T (6.62 micrograms/ml), followed by HbOC (1.9 micrograms/ml), then PRP-OMP (1.06 micrograms/ml), and lowest for the control group (0.11 microgram/ml). We conclude that all three Hib conjugate vaccines (PRP-T, HbOC, and PRP-OMP) were immunogenic after three primary doses among Philippine infants.     

Oligoclonality of serum immunoglobulin G antibody responses to Streptococcus pneumoniae capsular polysaccharide serotypes 6B, 14, and 23F

Serum antibodies (Abs) specific for the capsular polysaccharides of Streptococcus pneumoniae provide protection against invasive pneumococcal disease. Previous studies indicate that Abs to pneumococcal polysaccharide (PPS) serotypes 1 and 6B have limited clonal diversity. To determine if restricted diversity was a feature common to other PPS specificities, we examined the light (L)-chain expression and isoelectric heterogeneity of type 6B, 14, and 23F Abs elicited in 15 adults following PPS vaccination. At the population level, both PPS-6B and PPS-14 Abs expressed kappa and lambda chains, although 6B Abs more frequently expressed lambda chains lambda and 14 Abs more frequently expressed kappa chains. In individual sera, Abs were generally skewed towards either kappa or lambda expression. 23F-specific Abs had predominantly kappa chains. Isoelectric focusing analyses showed that sera contained one or at most a few immunoglobulin G Ab spectrotypes to all three respective capsular serotypes, a result indicative of oligoclonality. A sequence analysis of a purified PPS-14-specific Ab having a single spectrotype gave uniform amino-terminal sequences for both the heavy chain (V(H)III subgroup) and the L chain (kappaIII-A27 V region). From these results we conclude that within individual adults, serum Ab responses to PPS serotypes 6B, 14, and 23F derive from a small number of dominant B-cell clones, and consequently variable-region expression is probably individually limited as well. Oligoclonality appears to be a general characteristic of human PPS-specific Ab repertoires, and we suggest that this property could lead to individual differences in Ab fine specificity and/or functional activity against encapsulated pneumococci.     

Overwhelming postsplenectomy infection with vaccine-type Streptococcus pneumoniae in a 12-year-old girl despite vaccination and antibiotic prophylaxis

This report describes a 12-year-old girl who developed vaccine-type pneumococcal septicemia (type 4, Danish nomenclature) 2 years after splenectomy for recurrent idiopathic thrombocytopenia despite vaccination with the 23-valent vaccine 4 weeks before surgery and antibiotic prophylaxis with penicillin V. The disease presented as high fever with shivering and vomiting followed by disseminated petechiae and a deteriorated general condition. Initial laboratory studies showed severe sepsis with leucocytopenia and thrombocytopenia, a markedly elevated CRP, and disseminated intravascular coagulation. Despite antibiotic treatment, which was initiated with clindamycin, cefotaxime and trimethoprim/sulfamethoxazole and was switched to cefotaxime and penicillin after the result of the blood culture had been obtained, the patient had to be ventilated, and hemofiltration became necessary because of acute renal insufficiency. Furthermore, she required amputation of all her toes because of severe necrosis. No type-specific pneumococcal antibody titers were detected during and after infection. It remains unclear whether the susceptibility to Streptococcus pneumoniae was due to primary failure of antibody production or a decline in antibody levels after vaccination. Patients and/or their relatives should be informed that neither vaccination nor continuous antibiotic prophylaxis can guarantee full protection against infection with S. pneumoniae in patients after splenectomy.     

Serologic responses of young colostrum fed dairy calves to antigens of Pasteurella haemolytica A1

The potential and limitations of early calfhood vaccination to induce active immunity to Pasteurella haemolytica A1 in conventional colostrum fed calves were investigated. Holstein dairy calves (n = 29) were vaccinated at 2 and 4 weeks of age, or at 6 and 8 weeks of age with a commercial culture supernatant vaccine (Presponse, Langford Inc., Guelph, Ont., Canada), or remained unvaccinated as controls. Serum antibody titres were measured using an indirect bacterial agglutination assay, a leukotoxin neutralization assay, and enzyme immunoassays for antibodies of the IgM, IgG1, and IgG2 isotypes binding purified capsular polysaccharide of P. haemolytica A1. Seroconversion (fourfold or greater increase in serum antibody titre) rates were compared using Fisher's exact test. The effects of passive antibody titres and age on response to vaccination were assessed by linear modelling. Vaccination at 2 and 4 weeks of age was associated with 40%, and 0% of calves seroconverting on the basis of agglutinating antibody titres, and leukotoxin neutralizing titres respectively, and 50%, 0%, and 0% seroconverting on the basis of IgM, IgG1 and IgG2 antibodies to capsular polysaccharide, respectively. Agglutinating antibody responses were not related to prevaccination antibody titres, or to age at vaccination. Higher responses (p = 0.08) to leukotoxin were observed in older calves (after taking differences in prevaccination titres into account). Statistical analyses of responses to capsular polysaccharide among calves with comparable prevaccination IgG1 antibody titres revealed significantly higher IgM, IgG1 and IgG2 responses in older calves. Rising titres of IgM antibodies in nonvaccinated calves after 5 weeks of age suggest natural exposure to P. haemolytica A1 or antigens which result in serologic cross-reactions as a means of priming immune responses.     

C1q, a subunit of the first component of complement, enhances antibody-mediated apoptosis of cultured rat glomerular mesangial cells

We have shown previously that IgG2a anti-Thy-1 MoAb (ER4G) induces apoptosis of rat mesangial cells (GMC) in vitro. Since the classical complement pathway plays an essential role in Thy-1 nephritis, we analysed whether C1q, a subunit of the first component of complement, enhances the ER4G-mediated apoptosis of rat GMC. Two different subclasses of anti-Thy-1 MoAb, ER4G (IgG2a) and ER14 (IgG1), were used. It was established that ER4G binds C1q efficiently, while ER14 reacts poorly with C1q. For the experiments of apoptosis, quiescent rat GMC were exposed for 1 h at 37 degrees C to a fixed concentration of anti-Thy-1 MoAb and incubated further for 16 h at 37 degrees C in the presence or absence of C1q. GMC exposed to medium (M-GMC) followed by incubation of the cells with medium alone was used as controls. Apoptosis was assessed by morphological studies and quantitative analysis on FACS using FITC-annexin V (the annexin V methods) or bicolour FACS analysis using FITC-annexin V and propidium iodide (the annexin V/PI method). With the annexin V method, M-GMC revealed 9.4 +/- 1.4% apoptosis. C1q had only marginal effects on apoptosis of M-GMC. GMC exposed to ER4G (ER4G-GMC) and further incubated with medium in the absence of C1q resulted in 25.7 +/- 5.7% apoptosis (P < 0.01 relative to control). Incubation of ER4G-GMC together with 100 microg/ml of C1q significantly increased GMC-apoptosis up to 39.4 +/- 4.9% (P < 0.01 relative to ER4G-GMC incubated in the absence of C1q). This enhancing effect of C1q on apoptosis of ER4G-GMC was time- and dose-dependent. In contrast, C1q did not significantly alter the apoptosis of either GMC exposed to ER14 (ER14-GMC) or to F(ab')2-ER4G (F(ab')2-ER4G-GMC), while ER14-GMC or F(ab')2-ER4G-GMC incubated with medium resulted in significant apoptosis compared with control. These results were supported by morphological studies and bicolour FACS analyses in time course experiments using the annexin V/PI method. The effect of C1q is dependent on the presence of intact C1q-containing globular heads and does not occur with collagen-like fragments of C1q. Furthermore, incubation of ER4G-GMC with anti-mouse K-chain antibodies also increased ER4G-mediated GMC-apoptosis. These results indicate for the first time that C1q enhances antibody-mediated apoptosis of rat GMC in vitro, presumably by its binding to ER4G and probably by additional cross-linking of Thy-1 on the surface of GMC.     

Nonsteroidal anti-inflammatory drug use and Alzheimer-type pathology in aging

Infant rats were passively immunized to determine the protective capacity of pneumococcal anticapsular antibodies. Animal-passaged strains of Streptococcus pneumoniae serotypes 1, 4, 5, 6b, 7f, 9v, 14, 18c, 19f, and 23f were used as challenge inocula (1-1500 cfu) in a model of pulmonary infection that resulted in bacteremia, meningitis, and death. From untreated control animals, histologic sections of lung demonstrated infiltrative pneumonia and lung homogenate cultures grew S. pneumoniae at concentrations of 10(3)-10(8) cfu per gram of lung tissue. A type-specific anti-capsular antibody serum concentration of 0.1-1.15 microg/mL resulted in a statistically significant reduction in mortality compared with the reduction in untreated controls, except for serotype 14, which required 2.32 microg/mL for a significant reduction in mortality. The serum antibody level that provided 50% reduction in mortality ranged from 0.1-3.5 microg/mL for all serotypes.     

Antibody response to pneumococcal polysaccharide vaccine in young, adult and old mice

The anti-pneumococcal antibody response was studied in young (5-week-old) and adult (10-week-old) BALB/c and CBA/J mice and in adult (9-10-week-old) and old (12-, 18- and 24-month-old) AB6F1 and B6D2F1 mice after s.c. immunization with a 23-valent pneumococcal polysaccharide vaccine. Both young and adult mice showed a significant IgM antibody response to the vaccine 6 days after immunization with 1-11 micrograms antigen. There were significant immune responses to serotypes 1, 2, 4 and 7F in contrast to small responses to serotypes 14, 19F and 23F after immunization with the vaccine. One month after immunization, there were only marginal differences in IgM anti-pneumococcal antibody levels to the vaccine (anti-PPS) between immunized and unimmunized BALB/c mice, whereas in CBA/J mice the anti-PPS remained higher in immunized than in unimmunized mice. Immunization of old mice induced a significant IgM antibody response 6 days after immunization, but the anti-PPS thereafter decreased rapidly towards preimmunization values in AB6F1 mice. A significant IgG anti-PPS was not detected in any of the mice studied. The IgA anti-PPS tended to vary over time with no consistent pattern. It is important to carefully consider age and strain of the mice used when studying the immune response to pneumococcal polysaccharide antigens.     

Pneumococcal polysaccharide vaccine in children with chronic renal disease: a prospective study of antibody response and duration

We studied the antibody response to pneumococcal serotypes 3 and 14 after pneumococcal polysaccharide vaccine was administered to 41 children with renal disease. One month after vaccination, 76% and 61% of patients achieved at least a twofold titer rise to serotypes 3 and 14, respectively; this finding was comparable to historic control values. One year after vaccination, the majority of patients retained protective antibody levels. Achieving a titer > or = 1.0 microgram/ml IgG at 1 month was highly predictive of retaining a protective antibody level > or = 0.15 microgram/ml at 1 year.     

Emergence of further serotypes of multiple drug-resistant Streptococcus pneumoniae in Queensland

We describe 27 cases of multiple drug-resistant pneumococcal infection in Queensland children (7 cases) and adults (20 cases), between February 1995 and October 1996. Seven patients had invasive disease. Serotypes were those commonly associated with paediatric infections and included types 19F (15 strains), 14 (6), 23F (4), 6A (1) and 19A (1). No rifampicin or vancomycin resistance was encountered. However, pneumococci fully resistant to cotrimoxazole, erythromycin and tetracycline were isolated from 25 of 27 cases (93%). Strains with high level resistance to penicillin and chloramphenicol were also recovered from 16 (59%) and 19 (70%) patients respectively. Twelve of 16 penicillin-resistant isolates showed intermediate resistance to ceftriaxone and two strains were fully resistant to this antibiotic. Clones of types 19F and 14 pneumococci, each with two distinctive resistance patterns, appear to be established in south-east Queensland.     

Decline in meningococcal antibody levels in African children 5 years after vaccination and the lack of an effect of booster immunization

Antibodies to group A meningococcal polysaccharide were measured by hemagglutination (HA) and by ELISA in sera obtained from Gambian children before vaccination and 3 weeks, 2 years, and 5 years after vaccination with a group A + group C meningococcal capsular polysaccharide vaccine. Children were 1-4 years old at the time of vaccination. Most showed a good initial response to vaccination, including those aged 1-2 years. However, antibody titers declined progressively during follow-up, and 5 years after vaccination, antibody titers measured by both HA and ELISA had returned to prevaccination levels. This decline was not influenced significantly by a booster dose of vaccine given 2 years after initial immunization. Administration of malaria chemoprophylaxis reduced the rate at which antibody levels fell after initial immunization. Sustained protection of children against group A meningococcal disease will require the development of vaccines that are immunogenic in infants and that can induce T cell memory.     

Immunogenicity of pneumococcal vaccine in persons with spinal cord injury

OBJECTIVE: To determine immunogenicity and optimum timing for administering the 23-valent pneumococcal vaccine after spinal cord injury (SCI). DESIGN: Double-blind, randomized, placebo control study. SETTING: SCI unit in a tertiary care medical center and community. PARTICIPANTS: Eighty-seven persons with recent SCI. INTERVENTION: Participants were randomized to receive either placebo or pneumococcal vaccine at 16 to 18 days versus 4 to 6 months postinjury. MAIN OUTCOME MEASURES: Antibody concentrations were measured prior to intervention and 1, 2, and 12 months afterward to evaluate the immune response to five serotypes of Streptococcus pneumoniae. Effects of demographic and injury-related variables on immune response were also evaluated. RESULTS: Timing of vaccination did not influence mean antibody concentrations for any serotype (p > .05). Ninety-five percent of vaccinated persons had twofold or greater increases in antibody concentration for at least one serotype when measured 1 month after vaccination versus 35% of placebo groups (p < .01). After 12 months, 93% of vaccinated persons in both groups maintained antibody concentrations twofold or greater than baseline values. CONCLUSIONS: Most participants developed an immune response to at least one serotype that was maintained for at least 12 months. Immune response varied according to serotype. Given the favorable immune response and no effect of timing, persons with SCI should receive pneumococcal vaccine during initial hospitalization.     

Antibody responses of three Haemophilus influenzae type b conjugate vaccines after one, two and three doses in Filipino children

Differences in the magnitude of antibody response after one, two or three doses of Haemophilus influenzae type b conjugate vaccines have been reported which may influence decision-making regarding which vaccine should be used. This is of particular importance in developing countries where children may not receive a full immunization series and the vaccination schedule may be delayed. Serum antibody responses to three Hib capsular polysaccharide protein conjugate vaccines (PRP-OMP, HbOC and PRP-T) were evaluated in 102 Filipino infants. Vaccination was carried out at 6, 10 and 14 weeks of age based on the national Expanded Programme on Immunization (EPI) schedule together with diphtheria-tetanus-pertussis, hepatitis B and oral poliomyelitis vaccines. Sera were collected at 6 weeks and 1 month after each vaccination. Anti-Hib polysaccharide antibody concentrations were determined by Farrtype radioimmunoassay (RIA) and enzymeimmunoassay (EIA), Following the first dose, the geometric mean concentrations (GMC, micrograms ml-1) for PRP-OMP, HbOC and PRP-T were 0.69, 0.27 and 0.38, respectively. After two doses, there was a significant response (P < 0.05) to PRP-OMP and PRP-T (0.89 and 1.47) but not for HbOC (0.37). Differences in the GMC after the primary series were significant (pairwise P < 0.05): GMC was highest for PRP-T (4.0), followed by HbOC (1.6) and PRP-OMP (1.1). All three Hib vaccines were immunogenic when given in the local EPI schedule in Filipino infants although significant differences in the kinetics and magnitude of antibody responses were noted. The anti-Hib antibody concentrations determined by RIA and EIA were also compared in order to validate the latter for use in laboratories where it is feasible. There was a good correlation (r2 = 76%; P = 0.0001) in the Hib antibody titres obtained by both assays.     

Antibody responses to capsular polysaccharide backbone and O-acetate side groups of Streptococcus pneumoniae type 9V in humans and rhesus macaques

Streptococcus pneumoniae is responsible for high rates of pneumococcal bacteremia, meningitis, pneumonia, and acute otitis media worldwide. Protection from disease is conferred by antibodies specific for the polysaccharide (Ps) capsule of the bacteria. Of the four types of group 9 pneumococci, types 9N and 9V cause the most disease, and both types are included in the polyvalent pneumococcal vaccine. The type 9V capsule consists of repeating pentasaccharide units linearly arranged, with an average of 1 to 2 mol of O-acetate side chains per mol of repeat units, added in a complex pattern in which not all repeat units are alike. alpha-GlcA residues may be O-acetylated in the 2 (17%) or 3 (25%) position and beta-ManNAc residues may be O-acetylated in the 4 (6%) or 6 (55%) position. Under certain conditions, the O-acetate side chains are subject to oxidation, which results in subsequent de-O-acetylation of a significant number of the repeat units. This de-O-acetylation could adversely affect the efficacy of a vaccine containing the 9V Ps. A study was undertaken to compare the relative contributions of O-acetate and Ps backbone epitopes in the immune response to S. pneumoniae 9V type-specific Ps. In both an infant rhesus monkey model and humans, antibodies against the non-O-acetylated 9V backbone as well as against O-acetylated 9V Ps were detected. Functional (opsonophagocytic) activity was observed in antisera in which the predominant species of antibody recognized de-O-acetylated 9V Ps. We concluded that the O-acetate side groups, while recognized, are not essential to the ability of the 9V Ps to induce functional antibody responses.     

Family practice and the advancement of medical understanding. The first 50 years

BACKGROUND: Few data exist on the persistence of measles antibodies after vaccination of West African infants. Therefore we examined measles antibody titers 5 to 7 years after children in rural Senegal had received high titer Edmonston-Zagreb (EZ-HT), high titer Schwarz (SW-HT) or standard titer Schwarz (SW-STD) measles vaccines in infancy. METHODS: Children had received either high titer vaccines at 5 months of age or standard titer at 10 months of age. Finger prick blood samples were tested for measles antibody 5 to 7 years later by the hemagglutinin inhibition test. RESULTS: Persistence of antibody after high titer vaccines was poor with the result that 39 and 50% of the EZ-HT and the SW-HT groups had low titers of hemagglutinin inhibition measles antibodies (< or =125 mIU/ml). Nineteen percent of the children in the SW-STD group had low titers which is a lower prevalence than in the high titer groups [relative risk (95% confidence intervals), 0.05 (0.28 to 0.88) vs. EZ-HT; relative risk, 0.38 (0.22 to 0.66) vs. SW-HT]. Geometric mean (95% confidence interval) antibody titers in children with detectable values were 616 (435 to 871) in the EZ-HT, 1106 (616 to 1866) in the SW-HT and 1271 (871 to 1741) mIU/ml in the SW-STD groups, respectively. Multivariant regression analysis showed that mean titers were 2.00 (1.03 to 3.89) times higher for children with low prevaccination antibody titers (< or =125 mIU/ml) and 3.06 (1.90 to 4.94) times higher if blood was collected in the rainy season. INTERPRETATION: Given the rapid decline in antibody titers over a 5- to 6-year period in an area where measles vaccine coverage was high, it seems likely that multiple dose immunization schedules will be needed in the future to maintain protective antibody concentrations (>125 mIU/ml) in West Africa. The role of subclinical boosting by exposure to natural measles and the possible role of malaria, which increases immunoglobulin turnover, in influencing long term antibody persistence after vaccination deserve further investigation.     

Passively acquired anti-tetanus and anti-Haemophilus antibodies and the response to Haemophilus influenzae type b-tetanus toxoid conjugate vaccine in infancy

OBJECTIVE: To study the influence of maternally inherited tetanus antitoxin (anti-TT) antibodies on the response to the Haemophilus influenzae type b (Hib) capsular polysaccharide (PS)-tetanus toxoid conjugate (PRP-T) vaccine. DESIGN: One hundred thirty healthy infants received their first dose of PRP-T in the same syringe with diphtheria-tetanus-pertussis vaccine (DTP) at 1 to 2 months, and 66 of them received a second dose at 3 to 4 months of age. RESULTS: Maternal anti-TT antibodies did not interfere with the anti-Hib PS response to the first PRP-T vaccination; the geometric mean concentration (GMC) of anti-Hib PS was 0.14 microgram/ml in those with the lowest preimmunization anti-TT (< 0.3 IU/ml, n = 15) and 0.13 microgram/ml in those with the highest anti-TT (> or = 3 IU/ml, n = 25). After the second dose of PRP-T there was a positive correlation (r = 0.37, P = 0.004) between the anti-Hib PS response and the preimmunization anti-TT; those with the lowest preimmunization anti-TT (< 0.3 IU/ml, n = 9) achieved GMC of anti-Hib PS of 1.22 micrograms/ml and those with anti-TT > or = IU/ml (n = 22) anti-Hib PS GMC of 2.67 micrograms/ml. High preimmunization anti-Hib PS antibodies did not interfere with the final antibody concentrations; the GMC of anti-Hib PS after the second dose of PRP-T was 1.60 micrograms/ml in those with a preimmunization titer > or = 1.0 microgram/ml (n = 12) and 1.57 micrograms/ml in those with a titer of < 1.0 microgram/ml (n = 53). CONCLUSION: The data suggest that infants can be safely vaccinated with PRP-T even though they have received high concentrations of anti-TT from their mother.     

Persistence of anti-mumps virus antibodies after a two-dose MMR vaccination. A nine-year follow-up

A two-dose vaccination program against measles, mumps, and rubella (MMR) viruses was started in Finland in 1982. In this program the trivalent MMR-II vaccine (MSD, USA) was offered to children at the ages of 14-18 months and 6 years followed by revaccination 4-5 years later. The vaccination coverage has been high (97%) and MMR infections have practically been eliminated in the Finnish population. In a serological follow-up program sequential serum samples were obtained from 254 children (127 14-18-month-old vaccinees and 127 6-year-old vaccinees) during a 9-year follow-up period. Anti-mumps virus antibody titers were determined by enzyme immunoassay using purified whole mumps viruses as the antigen. In seronegative (n = 120) 14-18-month-old vaccinees the seroconversion rate was 86% (geometric mean titer 1/1670 +/- 1/270). The antibody levels fell rapidly (significance p < 0.01) within the first year of follow-up (mean titer 1/1080 +/- 1/190), but remained relatively stable in subsequent years. After revaccination the seropositivity rate was 95% (mean titer 1/2310 +/- 1/260) and declined more slowly thereafter to 86% (mean titer 1/1510 +/- 1/210) at year 9 of follow-up. The mean antibody titer was significantly (p < 0.05) higher 4 years after the second MMR vaccination when compared with the corresponding time point after the first vaccination. In 6-year-old seronegative vaccinees the increase and decay of anti-mumps virus antibodies after the first MMR vaccination was similar to that seen in the group of younger vaccinees. A two-dose MMR vaccination protocol resulted in a high mumps immunity level in the vaccinated population.     

Pneumococcal immune complexes in the diagnosis of lower respiratory infections in children

BACKGROUND: In recent years serologic methods have been applied to assess pneumococcal etiology of pneumonia and other respiratory tract infections. Antigen and antibody assays have shown to be insensitive, especially in young children. The aim of this study was to evaluate the usefulness of circulating immune complexes in the diagnosis of pneumococcal lower respiratory infection in children. MATERIAL AND METHODS: Pneumococcal immune complexes (IC) containing antibodies to species-specific C-polysaccharide, to mixtures of type-specific capsular polysaccharides or to a protein antigen, pneumolysin, were studied in the sera of 449 children with lower respiratory tract infection. RESULTS: Circulating ICs were found in 68 (15%) children; 46 (68%) of them were demonstrated in acute and 43 in convalescent serum. In 5 (7%) of the 68 IC-positive patients pneumococcal antigen was present in acute serum; those patients formed 18% of the 28 cases with antigenemia. An antibody response between paired sera to any of the 3 pneumococcal antigens studied was observed in 14 (21%) IC-positive children; they formed 23% of the 60 cases with an antibody response. In total ICs were positive in 51% of all the 134 pneumococcal cases diagnosed by any method. CONCLUSIONS: We conclude that the measurement of circulating ICs is more sensitive than other serologic methods for the diagnosis of pneumococcal lower respiratory infection. In infants, however, it was as insensitive as antigen and antibody assays.     

Regulation of gelatinase B (MMP-9) in leukocytes by plant lectins

We compared the immunogenicity of 7-valent pneumococcal-conjugate vaccine plus 23-valent pneumococcal vaccine to immunization with 23-valent vaccine only in individuals > or = 2 years of age with sickle cell disease. IgG pneumococcal antibody concentrations were higher in the combined schedule group with no increase in side effects observed after immunization with 23-valent vaccine.