Serum bactericidal titres for monitoring antimicrobial therapy: current status and potential role in the management of multidrug-resistant Gram-negative infections.

BACKGROUND: Serum bactericidal titres (SBTs) were widely used in the 1970s and 1980s to monitor antimicrobial therapy but are now seldom recommended. It is the only laboratory test that integrates drug pharmacodynamics, host pharmacokinetics and synergistic or antagonistic interactions of antimicrobial combinations into a single index of antimicrobial activity. We hypothesized that SBTs could play a renewed role in monitoring antibiotic treatment of multidrug-resistant Gram-negative infections. However, the last critical appraisal of the test was published over 30 years ago. OBJECTIVES: This narrative review provides an updated assessment of the SBT test and its methodological limitations. We performed a diagnostic meta-analysis to estimate the value of SBTs for predicting clinical failure or death during antibiotic treatment. SOURCES: A comprehensive literature search of PubMed including all English publications was performed in December 2019 using the Medical Subject Headings (MeSH search terms "serum", "bactericidal", "inhibitory", "titre", "monitoring", "anti-infective agents" "antimicrobial therapy" and "therapeutic drug monitoring"). CONTENT: Although standardized methods for performing SBTs were approved in 1999, the test remains labour intensive, and results may not be available until 72 hr. However, the use of non-culture-based endpoints (i.e. spectrophotometric or fluorescent) may shorten test time to 24 hr. Despite considerable heterogeneity in published studies, a meta-analysis of 11 evaluable studies published from 1974 to 2007 indicated a critical SBT result (peak SBT ≤1:8 or trough ≤1:2) is associated with a diagnostic odds ratio for clinical failure during antibiotic treatment of 12.27 (95% confidence interval 5.28-28.54) and a 5.32 (95% 1.32-21.42) odds of death. IMPLICATIONS: SBTs have prognostic value for identifying patients at high risk for antibiotic treatment failure, but the slow turnaround time of the current test limits its clinical utility. Standardization of a more rapid SBT testing method is needed.

Altitudinal Effects on Innate Immune Response of a Subterranean Rodent.

Immune defense is costly to maintain and deploy, and the optimal investment into immune defense depends on risk of infection. Altitude is a natural environmental factor that is predicted to affect parasite abundance, with lower parasite abundance predicted at higher altitudes due to stronger environmental stressors, which reduce parasite transmission. Using high and low altitude populations of the Turkish blind mole-rat (TBMR) Nannospalax xanthodon, we tested for effects of altitude on constitutive innate immune defense. Field studies were performed with 32 wild animals in 2017 and 2018 from two low- and one high-altitude localities in the Central Taurus Mountains, at respective altitudes of 1010 m, 1115 m, and 2900 m above sea level. We first compared innate standing immune defense as measured by the bacteria-killing ability of blood serum. We then measured corticosterone stress hormone levels, as stressful conditions may affect immune response. Finally, we compared prevalence and intensity of gastrointestinal parasites of field-captured TBMR. We found that the bacteria-killing ability of serum is greater in the mole-rat samples from high altitude. There was no significant difference in stress (corticosterone) levels between altitude categories. Coccidian prevalence and abundance were significantly higher in 2017 than 2018 samples, but there was no significant difference in prevalence, abundance, or intensity between altitudes, or between sexes. Small sample sizes may have reduced power to detect true differences; nevertheless, this study provides support that greater standing innate immunity in high altitude animals may reflect greater investment into constitutive defense.

Is it possible to shorten serum bactericidal testing?

Serum bactericidal test represents an alternative possibility for optimization of antibiotic treatment. The paper aimed to confirm non-inferiority of bactericidal testing using the broth dilution method according to the CLSI method (M21A) in comparison with turbidimetric and colorimetric modifications. We tested human blood sera (n = 76) of ten hematological patients, their blood was withdrawn prior to and during the course of antibiotic therapy. Testing employed the reference strain Escherichia coli ATCC 25922. The results of the modified turbidimetric method did not differ in a statistically significant way with the use of the wavelengths of 620 nm or 405 nm and the break-point <30% turbidity change after 24-hour incubation. The colorimetric method was also non-inferior from the CLSI method when resazurin was applied after 8-hour incubation and the results of subculture were read after 24-hour incubation. Both tested modifications can represent a shorter alternative to the CLSI reference method.

Exposure to fluctuating temperatures leads to reduced immunity and to stress response in rattlesnakes.

Ectothermic organisms often experience considerable variation in their body temperature throughout the circadian cycle. However, studies focusing on the measurement of physiological traits are usually performed under constant temperature regimes. This mismatch between thermal exposure in the field and experimental conditions could act as a stressor agent, as physiological functions are strongly influenced by temperature. Herein, we asked the question whether constant thermal regimes would cause a stress response and impact the immunity of the South American rattlesnake (Crotalus durissus) when compared with a fluctuating thermal regime. We addressed this question by determining heterophil:lymphocyte (H:L) ratio, plasma bacteria-killing ability (BKA) and corticosterone (CORT) levels in snakes kept under a constant temperature regime at 30°C, and under a fluctuating regime that oscillated between 25°C at night and 35°C during the day. The experiments had a mirrored design, in which half of the snakes were subjected to a fluctuating-to-constant treatment, while the other half was exposed to a constant-to-fluctuating treatment. The shift from constant to fluctuating thermal regime was accompanied by an increase in plasma CORT levels, indicating the activation of a stress response. Exposure to a fluctuating thermal regime at the onset of the experiments induced a decrease in the BKA of rattlesnakes. H:L ratio was not affected by treatments and, therefore, the shift between thermal regimes seems to have acted as a low-intensity stressor. Our results suggest that removal from temperatures close to the snake's preferred body temperature triggers a stress response in rattlesnakes.

The bivalent factor H binding protein meningococcal serogroup B vaccine elicits bactericidal antibodies against representative non-serogroup B meningococci.

MenB-FHbp (Trumenba®; bivalent rLP2086) is a meningococcal serogroup B vaccine containing 2 variants of the recombinant lipidated factor H binding protein (FHbp) antigen. The expression of FHbp, an outer membrane protein, is not restricted to serogroup B strains of Neisseria meningitidis (MenB). This study investigated whether antibodies elicited by MenB-FHbp vaccination also protect against non-MenB strains. Immunological responses were assessed in serum bactericidal assays using human complement (hSBAs) with non-MenB disease-causing test strains from Europe, Africa, and the United States. Importantly, FHbp variant distribution varies among meningococcal serogroups; therefore, strains that code for serogroup-specific prevalent variants (ie, representative of the 2 antigenically distinct FHbp subfamilies, designated subfamily A and subfamily B) and with moderate levels of FHbp surface expression were selected for testing by hSBA. After 2 or 3 doses of MenB-FHbp, 53% to 100% of individuals had bactericidal responses (hSBA titers ≥ 1:8) against meningococcal serogroup C, W, Y, and X strains, and 20% to 28% had bactericidal responses against serogroup A strains; in fact, these bactericidal responses elicited by MenB-FHbp antibodies against non-MenB strains, including strains associated with emerging disease, were greater than the serological correlate of protection for meningococcal disease (ie, hSBA titers ≥ 1:4). This is in comparison to a quadrivalent polysaccharide conjugate vaccine, MCV4 (Menactra®, targeting meningococcal serogroups A, C, W, and Y), which elicited bactericidal responses of 90% to 97% against the serogroup A, C, W, and Y strains and had no activity against serogroup X. Together, these results provide clinical evidence that MenB-FHbp may protect against meningococcal disease regardless of serogroup.

Validation of a Host Response Assay, SeptiCyte LAB, for Discriminating Sepsis from Systemic Inflammatory Response Syndrome in the ICU.

RATIONALE: A molecular test to distinguish between sepsis and systemic inflammation of noninfectious etiology could potentially have clinical utility. OBJECTIVES: This study evaluated the diagnostic performance of a molecular host response assay (SeptiCyte LAB) designed to distinguish between sepsis and noninfectious systemic inflammation in critically ill adults. METHODS: The study employed a prospective, observational, noninterventional design and recruited a heterogeneous cohort of adult critical care patients from seven sites in the United States (n = 249). An additional group of 198 patients, recruited in the large MARS (Molecular Diagnosis and Risk Stratification of Sepsis) consortium trial in the Netherlands ( www.clinicaltrials.gov identifier NCT01905033), was also tested and analyzed, making a grand total of 447 patients in our study. The performance of SeptiCyte LAB was compared with retrospective physician diagnosis by a panel of three experts. MEASUREMENTS AND MAIN RESULTS: In receiver operating characteristic curve analysis, SeptiCyte LAB had an estimated area under the curve of 0.82-0.89 for discriminating sepsis from noninfectious systemic inflammation. The relative likelihood of sepsis versus noninfectious systemic inflammation was found to increase with increasing test score (range, 0-10). In a forward logistic regression analysis, the diagnostic performance of the assay was improved only marginally when used in combination with other clinical and laboratory variables, including procalcitonin. The performance of the assay was not significantly affected by demographic variables, including age, sex, or race/ethnicity. CONCLUSIONS: SeptiCyte LAB appears to be a promising diagnostic tool to complement physician assessment of infection likelihood in critically ill adult patients with systemic inflammation. Clinical trial registered with www.clinicaltrials.gov (NCT01905033 and NCT02127502).

Serologic response to meningococcal vaccination in patients with paroxysmal nocturnal hemoglobinuria (PNH) chronically treated with the terminal complement inhibitor eculizumab.

Eculizumab is indicated for the therapy of patients with symptomatic paroxysmal nocturnal hemoglobinuria (PNH). Due to inhibition of terminal complement cascade, patients on eculizumab are susceptible to Neisseria meningitidis infections. The two mainstays to reduce the risk of infection are vaccination and antibiotic prophylaxis. In this retrospective study, serologic response was analyzed after vaccination with a meningococcal vaccine in 23 PNH patients (median age 36 years; range 25 - 88 years; 15 males, 8 females) by measuring serum bactericidal assay (SBA) using rabbit complement (rSBA) titers against meningococcal serogroups A, C, W, and Y. Serologic protection was defined by an rSBA titer ≥1:8. Forty-three percent (10/23) were vaccinated more than once due to chronic eculizumab treatment. Overall serologic response for the meningococcal serogroups was A: 78% (18/23), C: 87% (20/23), W: 48% (11/23), and Y: 70% (16/23). No meningococcal infections have been observed. As immunological response to vaccines varies, the use of serologic response analyses is warranted. Re-vaccination with a tetravalent conjugate vaccine under eculizumab therapy every 3 years is essential or should be based on response rates. If meningococcal infection is suspected, standby therapy with ciprofloxacin and immediate medical evaluation are recommended. The novel vaccines covering serogroup B may even further reduce the risk for infection.

Repeatability and sources of variation of the bacteria-killing assay in the common snapping turtle.

Research on reptile ecoimmunology lags behind that on other vertebrates, despite the importance of such studies for conservation and evolution. Because the innate immune system is highly conserved across vertebrate lineages, assessments of its performance may be particularly useful in reptiles. The bacteria-killing assay requires a single, small blood sample and quantifies an individual's ability to kill microorganisms. The assay's construct validity and interpretability make it an attractive measure of innate immunity, but it requires proper optimization and sample storage. We optimized this assay for the common snapping turtle (Chelydra serpentina) to assess the repeatability of the assay and the effects of freezing and thawing on bactericidal capacity. We determined whether age (adult female and hatchlings) or incubation temperature influenced bactericidal capacity. We found that the assay was repeatable and that freezing plasma samples for 6 weeks at -80°C did not decrease bactericidal capacity nor did a single 30-min thaw and subsequent refreezing. However, we detected subtle interassay variation and results from one assay were 5-6% greater than those from the other two. Adult females had significantly greater bactericidal ability than hatchlings and we found no relationship between incubation temperature and bactericidal capacity. This assay is a useful tool in snapping turtles and may have applicability in other reptiles. However, species-specific optimization is required to ensure that variation among individuals exceeds interassay variation. Consideration should be given to optimization conditions that facilitate comparisons between or within groups, particularly groups that differ considerably in bactericidal capacity.

Adenosine receptor antagonists effect on plasma-enhanced killing.

Previous studies demonstrated that naive plasma has inherent capabilities to enhance bacterial opsonization and phagocyte killing, but not all plasma is equally effective. This raised the question of whether plasma constituents other than opsonins may play a role. Adenosine receptor antagonists have been shown to modulate cytokine response and survival in mice after a bacterial challenge. We investigated whether selective adenosine receptor blockade would influence the ability of naive plasma to effectively control bacterial growth. Colonic bacteria- and thioglycollate-elicited peritoneal macrophages and neutrophils were obtained from naive mice. Stock murine plasma from naive was purchased and categorized as having high plasma-enhanced bacterial killing capacity using our previously described methods. Bacteria and plasma were incubated to allow for opsonization and then added to macrophages previously exposed to selected adenosine receptor antagonists: ZM 241385: A2A, MRS1754: A2B, DPCPX: A1, and MRS1220: A3. The final mixture was plated on blood agar plates in aerobic and anaerobic conditions and bacterial colony-forming units quantified after 24 h. This study demonstrated that exogenous adenosine was able to significantly decrease phagocyte killing of cecal bacteria. Blocking adenosine receptors with selective antagonists altered the bacterial killing capacity of plasma. Selectively blocking the A1, A2A, or A2B receptors proved most beneficial at reversing the effect of adenosine. Consistent with previous work, only macrophage killing of bacteria could be modulated by adenosine receptor blockade because neutrophils were unaffected. These data demonstrate that adenosine decreases macrophage killing of enteric bacteria and that this effect is mediated through the adenosine receptors.

Swarming growth and resistance of Proteus penneri and Proteus vulgaris strains to normal human serum.

BACKGROUND: Proteus sp. strains isolated from patients with urinary tract infection (UTI) are often insensitive to the bactericidal action of normal human serum (NHS) which poses a clinical problem. The swarming phenomenon is an especially important factor in cases of UTIs gained through the ascending route. Both these virulence factors are connected with the cell surface components of bacteria, including lipopolysaccharide (LPS). OBJECTIVES: The resistance of Proteus bacilli to the bactericidal activity of NHS and the swarming phenomenon were investigated as well as the possible relationships between these virulence factors and the chemical structure of LPS. MATERIAL AND METHODS: The research was carried out on P. penneri and P. vulgaris species. Two preparations of sera were tested with respect to the bactericidal action of NHS. The ability of bacteria to swarm was checked on broth agar plates. The length of the O-specific part of LPS was estimated after poliacrylamide gel electrophoresis (PAGE) and staining with silver nitrate. RESULTS: Among the 62 tested Proteus strains, over 62% of Proteus vulgaris and 50% of Proteus penneri strains were sensitive to the bactericidal action of NHS. However, the number of resistant strains grew dramatically when serum with blocked complement activation via the alternative pathway was used. From 102 of the Proteus sp. Strains, only few were unable to swarm over the solid surface of the media. The remaining showed diverse ability to translocate. CONCLUSIONS: There was no definite correlation between the chemical structure of the O-specific chains of lipopolysaccharides and sensitivity or resistance of the Proteus sp. strains to NHS. Also, no significant relationships were found between the length or the chemical structure of the O-specific chains of the bacterial LPSs and the swarming phenomenon.

[Methods for studying the in vitro susceptibility of Candida spp. to antifungals]. / Méthodes d'étude de la sensibilité in vitro de Candida spp. aux antifongiques.

In recent years, an increase of systemic Candida infections was noted. Thus, identification and susceptibility testing to antifungals became of considerable importance. The technique of dilution in liquid medium developed by « National committee for clinical laboratory standards ¼ NCCLS or more recently named CLSI « Clinical and laboratory standards institute ¼ is the reference method most used. The European committee "European committee on antibiotic susceptibility testing" or EUCAST has made progress by determining the susceptibility of strains within a shorter time. However, the use of these techniques is limited especially in clinical microbiology laboratories. Other techniques for determining antifungal sensitivity have been developed such as those based on agar diffusion (E-test and disk diffusion), on microdilution (Sensititre yeastOne, Vitek 2 AST-YS01), on flow cytometry techniques and the MALDI-TOF.

Anti-anaerobic activity of serum from patients treated with tigecycline for skin/soft tissue infections.

To gain additional data concerning the anti-anaerobic activity of tigecycline in serum, we analyzed blood samples from six patients with a complicated skin/soft tissue infection who were receiving IV tigecycline 50 mg every 12 h. Venous blood samples were obtained after multiple doses of tigecycline at 1, 6 and 12 h after the initiation of a 1 h IV infusion. Sera from these samples were tested to determine serum inhibitory and bactericidal activity over time against 4 anaerobic bacteria (Bacteroides fragilis, Peptoniphilus asaccharolyticus, Prevotella bivia and Finegoldia magna). An analysis of serum titers found that tigecycline exhibited early (1 h) and prolonged (12 h) inhibitory activity against each study isolate. Moreover, it provided bactericidal activity for 12 h against these strains with the exception of F. magna. Tigecycline was found to exhibit antibacterial activity at serum concentrations below the MICs of the anaerobic bacteria tested. This finding further supports that the antimicrobial activity of tigecycline can be greater than that suggested by the free fraction of drug and that serum appears to enhance this antibacterial activity.

Microbiological equivalence of serum bacteriostatic and bactericidal activities of the sera from healthy volunteers receiving original meropenem (Meronem) and generic meropenem (Mero).

BACKGROUND: Several generic meropenem formulations have been approved by Thai Food and Drug Administration, Ministry of Public Health since 2008. Meropenem is a parenteral drug. Therefore, a study demonstrating a biological equivalence of generic meropenem is not required for drug registration in Thailand. The objective of the study was to determine microbiological equivalence of serum bacteriostatic and bactericidal activities of the sera from healthy volunteers receiving original meropenem (Meronem) and generic meropenem (Mero). MATERIAL AND METHOD: This was a randomized crossover study in 16 adult healthy volunteers. Each subject received one gram of Meronem and Mero in 50 ml of normal saline via intravenous infusion for 30 minutes. The blood samples were drawn at baseline prior to receiving the study drug, at 30 minutes after initiating infusion, and at 8 hours after initiating infusion. The serum bacteriostatic activity against E. coli ATCC 25922, K. pneumoniae, P. aeruginosa ATCC 27853 and A. baumannii was performed by disk diffusion. The serum bactericidal activity against E. coli ATCC 25922 was performed by Serum Bactericidal Titre. RESULTS: The average inhibition zone diameter of the serum samples from the subjects while receiving Mero against each tested organisms was < 1 mm smaller than that while receiving Meronem and such difference was not significantly different. All serum samples taken at 30 minutes after initiating Meronem and Mero had bactericidal titres against E. coli ATCC 25922 > or = 1:256. Only 3 serum samples taken from the subjects while receiving Mero at 8 hours had less bactericidal titre for 1-fold dilution when compared with that of Meronem. CONCLUSION: The sera from healthy volunteers receiving Meronem and Mero had microbiological equivalence in terms of serum bacteriostatic and bactericidal activities.

Strain specificity of antimycobacterial immunity in whole blood culture after cure of tuberculosis.

Bactericidal assays have facilitated development of most modern vaccines, and have been proposed as indicators of protection after vaccination against tuberculosis. We examined control of intracellular growth of Mycobacterium tuberculosis in whole blood cultures of cured TB patients and tuberculin-negative healthy volunteers. Cured patients showed superior restriction of growth of the strain with which they had been infected. They similarly showed superior control of growth of a clinical strain (MP-28) that had become attenuated during passage. However, patients and healthy volunteers did not differ with regard to control of M. tuberculosis H37Ra. The ability of cured patients to control growth of the strain with which they had been infected correlated with MP-28, but not with H37Ra. These findings indicate M. tuberculosis MP-28 may be suitable to assess mycobacterial immunity as growth inhibition in whole blood culture, whereas H37Ra is not. However, additional studies will be required to confirm these observations in additional patient and microbial populations that are distinct according to geography and microbial and host genetics.

[Monitoring of chemotherapy in patients with pulmonary tuberculosis by the blood bacteriostatic activity-determining test].

The paper gives the results of studies to determine blood bacteriostatic activity (BBA) in the use of a patient's autostrain and semiliquid medium versus the clinical and laboratory parameters of the course of a process in 101 patients with pulmonary tuberculosis. There is evidence for the relationship of the BBA to the sensitivity to isoniazid and the structure of drug resistance. The zero values of BBA correspond to the severest course of the disease. The efficiency of treatment is much higher in patients with high and moderate BBA. The latter's determination using the semiliquid medium permits an objective evaluation of the efficiency of chemotherapy, identification of patients with a poor prognosis, and then choice of an individual treatment regimen on day 7 after the test just before obtaining the data on drug sensitivity.

Inhaled aztreonam lysine for chronic airway Pseudomonas aeruginosa in cystic fibrosis.

RATIONALE: The effectiveness and safety of aztreonam lysine for inhalation (AZLI) in patients with cystic fibrosis (CF) on maintenance treatment for Pseudomonas aeruginosa (PA) airway infection was evaluated in this randomized, double-blind, placebo-controlled study. OBJECTIVES: To evaluate the safety and efficacy of inhaled aztreonam lysine in controlling PA infection in patients with CF. METHODS: After randomization and a 28-day course of tobramycin inhalation solution (TIS), patients (n = 211; > or =6 yr; > or =3 TIS courses within previous year; FEV(1) > or = 25% and < or =75% predicted values) were treated with 75 mg AZLI or placebo, twice or three times daily for 28 days, then monitored for 56 days. The primary efficacy endpoint was time to need for additional inhaled or intravenous antipseudomonal antibiotics. Secondary endpoints included changes in respiratory symptoms (CF Questionnaire-Revised [CFQ-R] Respiratory Scale), pulmonary function (FEV(1)), and sputum PA density. Adverse events and minimum inhibitory concentrations of aztreonam for PA were monitored. MEASUREMENTS AND MAIN RESULTS: AZLI treatment increased median time to need for additional antipseudomonal antibiotics for symptoms of pulmonary exacerbation by 21 days, compared with placebo (AZLI, 92 d; placebo, 71 d; P = 0.007). AZLI improved mean CFQ-R respiratory scores (5.01 points, P = 0.02), FEV(1) (6.3%, P = 0.001), and sputum PA density (-0.66 log(10) cfu/g, P = 0.006) compared with placebo; no AZLI dose-response was observed. Adverse events reported for AZLI and placebo were comparable and consistent with CF lung disease. Susceptibility of PA to aztreonam at baseline and end of therapy were similar. CONCLUSIONS: AZLI was effective in patients with CF using frequent TIS therapy. AZLI delayed time to need for inhaled or intravenous antipseudomonal antibiotics, improved respiratory symptoms and pulmonary function, and was well tolerated. Clinical trial registered with www.clinicaltrials.gov (NCT 00104520).

Serum bactericidal antibody responses to meningococcal polysaccharide vaccination as a basis for clinical classification of common variable immunodeficiency.

Common variable immunodeficiency (CVID) is a heterogeneous group of disorders characterized by hypogammaglobulinemia and increased susceptibility to recurrent pyogenic infections. This study was performed to subclassify CVID on the basis of the bactericidal antibody responses of patients to polysaccharide meningococcal vaccine. Twenty-five patients with CVID (18 male and 7 female) and 25 healthy volunteers received meningococcal polysaccharide vaccine A + C. Serum bactericidal antibody (SBA) titers were measured at baseline and after 3 weeks. Response was correlated with clinical and immunological manifestations of CVID. Twenty-four (96%) of the 25 normal controls had a protective SBA titer of > or = 8 postvaccination, whereas only 16 (64%) of the 25 CVID patients had a protective titer (P value = 0.013). Among the patients with CVID who were nonresponders, there were significantly increased rates of bronchiectasis (P = 0.008), splenomegaly (P = 0.016), and autoimmunity (P = 0.034) in comparison with patients who had protective SBA titers. A reversed CD4/CD8 ratio was more common in the nonresponder group of patients (P = 0.053). We conclude that individuals with CVID who cannot produce protective postvaccination titers after receiving meningococcal polysaccharide vaccine are more likely to exhibit bronchiectasis, splenomegaly, and autoimmune diseases. Vaccination response may define subgroups of patients with CVID, enabling more effective monitoring and therapeutic strategies.

Issues surrounding standardization of meningococcal group W135 serology.

Group W135 polysaccharide vaccines were licensed without efficacy trials using the serum bactericidal antibody (SBA) assay as a surrogate of protection. Standardization of group A and C SBA assays has been largely achieved. However, no such efforts have been focussed on W135. Although W135 strains have been recommended by WHO for polysaccharide production, no such recommendation are in place for use in immunoassays. Strain characterization is of importance as W135 strains may possess either an O-acetylated or de-O-acetylated polysaccharide capsule and the human immune response can vary according to the O-acetylation of the target antigen. Following conjugate or polysaccharide vaccination, few data are published with respect to complement source comparisons although both human and baby rabbit sera have been utilized with similar end points. In studies of natural immunity subcapsular antigens are primarily the target antigens and thus strain choice for use in the SBA assay is important. International standardization of assays is necessary to allow for comparisons of data over time and place.

An evaluation of the immunogenicity and safety of a new trivalent meningococcal polysaccharide vaccine.

The immunogenicity and safety of a meningococcal trivalent A/C/W135 polysaccharide vaccine was compared with that of a tetravalent A/C/Y/W135 polysaccharide vaccine in a randomised, double blind trial. The study included 360 adults, who received either a trivalent or tetravalent polysaccharide meningococcal vaccine. Antibody responses were determined by serum bactericidal antibody (rSBA) assays prior to vaccination and on day 28 and month 11 after vaccination. The percentage of participants in the trivalent vaccine group who had rSBA titres >or=8 on day 28 post-vaccination against serogroups A, C and W135 meningococci were 99, 98 and 91%, respectively. The corresponding figures in the tetravalent vaccine group were 99, 99 and 90%. The percentage of participants with various cut off levels of rSBA against serogroups A, W135 and C meningococci on day 28 and 11-month post-vaccination and the incidence of adverse events did not differ significantly between the two groups.