A European approach to infection prevention and control goals.

The current pandemic caused by COVID-19 has underlined the importance of a joint effort and approach to ensure patient and health care worker safety in medical care throughout Europe. In addition, the recent flood disasters in Germany and other countries called for immediate joint action, in this case with regard to the prevention of water-borne infections. Environmental disasters will increase with consequences for hospitals and nursing homes. Cooperative efforts are needed for preventing and controlling associated infection outbreaks, new pathogens will appear and a geographic shift of infectious diseases previously not detected in certain areas has already been observed. This approach to infection prevention and control must entail structural as well as regulatory aspects. The principle of equal protection against infections in all European countries must be implemented. Prevention and control of infections, including nosocomial infections, infections caused by antibiotic-resistant bacteria as well as pandemics, need to be based on equal standards in all of Europe. Protection against infections and other public health risks in all European countries is the best guarantor for building trust and identification of citizens in our common Europe. Experts in the fields of hygiene, microbiology, infectiology and epidemiology have to pool the expertise on the prevention and control of infections from different European countries and define key targets for achieving a high standard of hygiene measures throughout Europe. The participants of the Rudolf Schülke Foundation International Symposium call for immediate action and priority to be given to the realization of the proposed 16-point plan.

Chemical disinfection in healthcare settings: critical aspects for the development of global strategies.

Chemical disinfection is an indispensable means of preventing infection. This holds true for healthcare settings, but also for all other settings where transmission of pathogens poses a potential health risk to humans and/or animals. Research on how to ensure effectiveness of disinfectants and the process of disinfection, as well as on when, how and where to implement disinfection precautions is an ongoing challenge requiring an interdisciplinary team effort. The valuable resources of active substances used for disinfection must be used wisely and their interaction with the target organisms and the environment should be evaluated and monitored closely, if we are to reliable reap the benefits of disinfection in future generations. In view of the global threat of communicable diseases and emerging and re-emerging pathogens and multidrug-resistant pathogens, the relevance of chemical disinfection is continually increasing. Although this consensus paper pinpoints crucial aspects for strategies of chemical disinfection in terms of the properties of disinfectant agents and disinfection practices in a particularly vulnerable group and setting, i.e., patients in healthcare settings, it takes a comprehensive, holistic approach to do justice to the complexity of the topic of disinfection.

Antibiotic resistance: What is so special about multidrug-resistant Gram-negative bacteria?

In the past years infections caused by multidrug-resistant Gram-negative bacteria have dramatically increased in all parts of the world. This consensus paper is based on presentations, subsequent discussions and an appraisal of current literature by a panel of international experts invited by the Rudolf Schülke Stiftung, Hamburg. It deals with the epidemiology and the inherent properties of Gram-negative bacteria, elucidating the patterns of the spread of antibiotic resistance, highlighting reservoirs as well as transmission pathways and risk factors for infection, mortality, treatment and prevention options as well as the consequences of their prevalence in livestock. Following a global, One Health approach and based on the evaluation of the existing knowledge about these pathogens, this paper gives recommendations for prevention and infection control measures as well as proposals for various target groups to tackle the threats posed by Gram-negative bacteria and prevent the spread and emergence of new antibiotic resistances.

Lesser-known or hidden reservoirs of infection and implications for adequate prevention strategies: Where to look and what to look for.

In developing hygiene strategies, in recent years, the major focus has been on the hands as the key route of infection transmission. However, there is a multitude of lesser-known and underestimated reservoirs for microorganisms which are the triggering sources and vehicles for outbreaks or sporadic cases of infection. Among those are water reservoirs such as sink drains, fixtures, decorative water fountains and waste-water treatment plants, frequently touched textile surfaces such as private curtains in hospitals and laundry, but also transvaginal ultrasound probes, parenteral drug products, and disinfectant wipe dispensers. The review of outbreak reports also reveals Gram-negative and multiple-drug resistant microorganisms to have become an increasingly frequent and severe threat in medical settings. In some instances, the causative organisms are particularly difficult to identify because they are concealed in biofilms or in a state referred to as viable but nonculturable, which eludes conventional culture media-based detection methods. There is an enormous preventative potential in these insights, which has not been fully tapped. New and emerging pathogens, novel pathogen detection methods, and hidden reservoirs of infection should hence be given special consideration when designing the layout of buildings and medical devices, but also when defining the core competencies for medical staff, establishing programmes for patient empowerment and education of the general public, and when implementing protocols for the prevention and control of infections in medical, community and domestic settings.

The role of surface disinfection in infection prevention.

BACKGROUND: The Rudolf Schuelke Foundation addresses topics related to hygiene, infection prevention and public health. In this context a panel of scientists from various European countries discussed "The Role of Surface Disinfection in Infection Prevention". The most important findings and conclusions of this meeting are summarised in the present consensus paper. AIM: Although the relevance of surface disinfection is increasingly being accepted, there are still a number of issues which remain controversial. In particular, the following topics were addressed: Transferral of microbes from surface to patients as a cause of infection, requirements for surface disinfectants, biocidal resistance and toxicity, future challenges. METHODS AND FINDINGS: After discussion and review of current scientific literature the authors agreed that contaminated surfaces contribute to the transmission of pathogens and may thus pose an infection hazard. Targeted surface disinfection based on a risk profile is seen as an indispensable constituent in a multibarrier approach of universal infection control precautions. Resistance and cross-resistance depend on the disinfectant agent as well as on the microbial species. Prudent implementation of surface disinfection regimens tested to be effective can prevent or minimize adverse effects. CONCLUSIONS: Disinfection must be viewed as a holistic process. There is a need for defining standard principles for cleaning and disinfection, for ensuring compliance with these principles by measures such as written standard operating procedures, adequate training and suitable audit systems. Also, test procedures must be set up in order to demonstrate the efficacy of disinfectants including new application methods such as pre-soaked wipes for surface disinfection.

Pharmacokinetics of linezolid in septic patients with and without extended dialysis.

PURPOSE: Linezolid is an option for the treatment of infections caused by multiresistant Gram-positive bacteria. The survival of critically ill patients with acute renal failure (ARF) can be improved by increasing the dose of renal replacement therapy. Extended (daily) dialysis (ED) is a new and important approach to renal replacement therapy in intensive care units. The aim of the study was to evaluate the pharmacokinetics of linezolid in septic patients without ED and on ED, respectively. METHODS: We studied the pharmacokinetics of linezolid in adult intensive care patients with sepsis (n = 5) and anuric septic patients with ARF being treated with ED (n = 10). Linezolid 600 mg was administered intravenously twice daily. The pharmacokinetic parameters, their variability, and possible covariates were analyzed using NONMEM. RESULTS: The pharmacokinetics of linezolid followed a two-compartment model with clearance (Cl) = 0.159 L h(-1) kg(-1) +/- 51% (population mean +/- interindividual variability), central volume of distribution (V(1)) = 0.273 L/kg +/- 21%, intercompartmental clearance (Q) = 0.369 L h(-1) kg(-1), and peripheral volume of distribution (V(2)) = 0.271 L/kg. The clearance in ED patients while on dialysis was increased by 3.5 L/h, and patients with liver transplantation/resection had their clearance reduced by 60%. Intra-individual variability was much smaller than inter-individual variability. CONCLUSIONS: Our results suggest that linezolid pharmacokinetics in critically ill patients with ARF undergoing ED is not comparable to that in healthy subjects and patients without ARF. The best method of managing linezolid dosage in such a complex group of patients, whose physiology can vary daily, would be to use therapeutic drug monitoring.

Implementation of practice guidelines for antifungal therapy in a surgical intensive care unit and its impact on use and costs.

BACKGROUND: Considering the complexity of diagnosis, high costs of therapy and high morbidity and mortality of systemic fungal infections, antifungal therapy of intensive care patients should follow clearly defined guidelines. We outline the impact of a standardised practice of antifungal treatment in an interdisciplinary surgical intensive care unit of a university hospital. METHODS: Therapy was intended to be optimised by implementation of standardised practice guidelines supported by the clinical pharmacist. Costs for antifungal agents during a period of 18 months before and after implementation of the practice guidelines were compared, respectively. RESULTS: The intervention was associated with a significant decrease in use of antifungal agents. Analysis of data revealed a reduction in costs by 50%. This could substantially be attributed to the implementation of the practice guidelines. CONCLUSION: The implementation of standardised practice guidelines for antifungal therapy in intensive care units decreased the use of selected antifungal agents and resulted in substantial reduction in expenditure on antifungal agents.

Tissue penetration of moxifloxacin into human gallbladder wall in patients with biliary tract infections.

OBJECTIVES: Moxifloxacin, the newest fourth-generation fluoroquinolone, has a broad spectrum of antibacterial activity covering both Gram-positive and Gram-negative aerobic and anaerobic bacteria and is therefore very well suited for the treatment of biliary tract infections. The present study aimed to determine the penetration of moxifloxacin into gallbladder tissue to evaluate its antibiotic potential in this indication. PATIENTS AND METHODS: Hospitalized patients with acute cholecystitis received a single, 1 h infusion of 400 mg of moxifloxacin before cholecystectomy. Serum and gallbladder wall tissue samples were collected during surgery, and the moxifloxacin concentrations were measured by HPLC. RESULTS: Sixteen patients (eight men and eight women) were included between January 2007 and April 2008. The time between start of infusion and gallbladder removal ranged from 50 min to 21 h 10 min. The serum concentration at the time of cholecystectomy was between 0.39 and 4.37 mg/L, and the tissue concentration between 1.73 and 17.08 mg/kg. The tissue-to-serum concentration ratio ranged from 1.72 to 6.33. CONCLUSIONS: The results show that moxifloxacin penetrates well into gallbladder tissue and is therefore a therapeutic option for biliary tract infection. The highest concentrations in serum and gallbladder tissue were measured shortly after the end of a 1 h infusion. As perioperative prophylaxis, moxifloxacin should therefore be administered 30-60 min before the first surgical incision.

Survey of attitudes towards curriculum reforms among medical teachers in different socio-economic and cultural environments.

BACKGROUND: Curriculum reforms in medical schools require cultural and conceptual changes from the faculty. AIMS AND METHODS: We assessed attitudes towards curriculum reforms in different academic, economic, and social environments among 776 teachers from 2 Western European medical schools (Belgium and Denmark) and 7 medical schools in 3 countries in post-communist transition (Croatia, Slovenia, Bosnia and Herzegovina). The survey included a 5-point Likert-type scale on attitudes towards reforms in general and towards reforms of medical curriculum (10 items each). RESULTS: Teaching staff from medical schools in Bosnia and Herzegovina had a more positive attitude towards reforms of medical curriculum (mean score 36.8 out of maximum 50 [95% CI 36.1 to 37.3]) than those from medical schools in Croatia or Slovenia (30.7 [29.8 to 31.6]) or Western Europe (27.7 [27.1 to 28.3]) (P < 0.001, ANOVA). Significant predictors of positive attitudes towards medical curriculum reform in post-communist transition countries, but not in Western European schools, was younger age, as well as female gender in Bosnia and Herzegovina. CONCLUSIONS: Factors influencing faculty attitudes may not be easy to identify and may be specific for different settings. Their identification and management is necessary for producing sustainable curriculum reform.

Prevention is in! Surveillance is out!

There has been a major change in the basic approach taken to hospital hygiene practices, and indeed to infection control within the hospital on the whole. Whereas as recently as the 1990s lectures on the topic of hand disinfection at international congresses were confined to "the periphery of the congress", today several keynote speakers address this issue with the full attention of the audience. This trend is also reflected in publications, and going beyond the domain of hand disinfection, has highlighted the important role of surface disinfection as well as of instrument disinfection in the prevention of nosocomial infections. The role of preventive as opposed to evidence-based hospital hygiene measures has for decades triggered lively discussions. The enormous rise in nosocomial infections due to antibiotic-resistant infections (MRSA, VRE, ESBL, etc.) will, no doubt, have made a significant contribution to bringing about a change in attitude. Even if of all the transmission channels implicated, the hands are the chief vehicles, there is in the meantime widespread evidence that contaminated instruments and surfaces can play a role in transmission. Surveillance is no doubt suitable for analyzing pathogenic transmission channels or shortcomings in infection control measures, but it is no substitute for the requisite preventive use of disinfection measures, since as a rule by the time the results of infectiology diagnostic measures are available, microbial spread will already have taken place. Prevention has had a long tradition in Germany and, in respect of infectious diseases, can be traced back to the 1880s (Robert Koch). It was therefore not surprising that it was Germany, where such efforts were initiated already in already in 1959, that began to formulate guidelines for efficacy testing of disinfection procedures. Since 1989 such guidelines have been compiled for the whole of Europe, thus assuring the preconditions for provision of high-quality disinfectants and, above all, for disinfection procedures whose efficacy has been verified. For the future it must be advocated that industry, on the one hand, will continue to develop more environmentally compatible disinfectants with broader spectra of action and that, on the other hand, the test methods for efficacy testing will be further improved in order to meet the requirements for efficacy testing of such agents.

A comprehensive assessment of medical schools in Bosnia and Herzegovina.

OBJECTIVES: To perform internal and external evaluations of all 5 medical schools in Bosnia and Herzegovina against international standards. METHODS: We carried out a 2-stage survey study using the same 5-point Likert scale for internal and external evaluations of 5 medical schools in Bosnia and Herzegovina (Banja Luka, Foca/East Sarajevo, Mostar, Sarajevo and Tuzla). Participants consisted of managerial staff, teaching staff and students of medical schools, and external expert assessors. Main outcome measures included scores on internal and external evaluation forms for 10 items concerning aspects of school curriculum and functioning: 'School mission and objectives'; 'Curriculum'; 'Management'; 'Staff'; 'Students'; 'Facilities and technology'; 'Financial issues'; 'International relationships'; 'Internal quality assurance', and 'Development plans'. RESULTS: During internal assessment, schools consistently either overrated their overall functioning (Foca/East Sarajevo, Mostar and Tuzla) or markedly overrated or underrated their performance on individual items on the survey (Banja Luka and Sarajevo). Scores for internal assessment differed from those for external assessment. These differences were not consistent, except for the sections 'School mission and objectives', 'Curriculum' and 'Development plans', which were consistently overrated in the internal assessments. External assessments was more positive than internal assessments on 'Students' and 'Facilities and technology' in 3 of 5 schools. CONCLUSIONS: This assessment exercise in 5 medical schools showed that constructive and structured evaluation of medical education is possible, even in complex and unfavourable conditions. Medical schools in Bosnia and Herzegovina have successfully formed a national consortium for formal collaboration in curriculum development and reform.

Reproducibility and workability of the European test standard EN 12791 regarding the effectiveness of surgical hand antiseptics: a randomized, multicenter trial.

OBJECTIVES: To evaluate the reproducibility and workability of the in vivo test model of the European test standard EN 12791 regarding the effectiveness of surgical hand antiseptics and, as a secondary objective, to evaluate the power of the model to discriminate between the effectiveness of various formulations of surgical hand antiseptics. DESIGN: Prospective, randomized, multicenter study with a Latin square design. SETTING: Five laboratories at 2 universities, 2 disinfectant manufacturers, and 1 private testing institution. PARTICIPANTS: Twenty healthy adults in each laboratory. INTERVENTION: Surgical hand antisepsis was performed by scrubbing with chlorhexidine gluconate 4% detergent (CHG) or by rubbing the hands with propan-2-OL (70% by volume; Iso 70) or ethanol 85% (E 85); rubbing the hands and forearms for 3 minutes with propan-1-OL (N 60) was used as the reference disinfection procedure. We deliberately chose to use these antiseptics at the given concentrations because they were intended to cover the range of typical antiseptics submitted for approval according to EN 12791. METHODS: In once-weekly tests, the immediate effects of the 4 antiseptics were established according to the method laid down in EN 12791 by assessing the release of skin flora from the fingertips as viable bacteria counts per milliliter of sampling fluids before treatment and viable bacteria counts immediately after treatment, separately for both hands, such that after 4 weeks each volunteer had used every formulation once. RESULTS: The mean log reduction factor (RF) for the release of bacterial skin flora (the log RF was calculated as the log count before treatment minus the log count after treatment) and corresponding standard deviations for the 4 hand antisepsis formulations were as follows: for CHG, 1.1+/-0.3 colony-forming units (cfu) per milliliter of sampled fluid; for Iso 70, 1.7+/-0.3 cfu/mL; for E 85, 2.1+/-0.3 cfu/mL; and for N 60, 2.4+/-0.4 cfu/mL. The differences between these values proved significant (P<.001) by analysis of variance and in Tukey's "honestly significantly different" (HSD) post hoc test. Although, with regard to their immediate antibacterial activity, the same ranking of these antiseptics was found at all laboratories, the levels of efficacy were significantly different across laboratories (P<.001); no statistical difference was found between left and right hands (P>.01). Relating the log RF values of the other 3 formulations to those of the reference formulation (N 60) abolished differences between laboratories (P=.16); in addition, the interclass correlation coefficient decreased from 9.1% to 4.5%. With 20 volunteers, a minimum difference of 0.47 log between the mean log RFs of the reference formulation and an inferior test formulation will be detected as significant at an alpha of .05 (1-sided) and a 1- beta value of .8. CONCLUSION: The test method described in EN 12791 yielded the same conclusion on the effectiveness of the tested formulations in every laboratory and proved, therefore, reproducible and workable.

Can soda fountains be recommended in hospitals?

Mineral water (soda water) is very popular in Germany. Therefore, soda fountains were developed as alternatives to the traditional deposit bottle system. Nowadays, different systems of these devices are commercially available. For several years, soda fountains produced by different companies have been examined at the University Hospital of Heidelberg. In 1998, it was possible for the first time to observe and evaluate one of these systems over a period of 320 days in a series of microbiological examinations. The evaluation was implemented on the basis of the German drinking water regulation (Anonymous, 1990. Gesetz über Trinkwasser und Wasser für Lebensmittelbetriebe (Trinkwasserverordnung - TrinkwV) vom 12. Dezember 1990. Bundesgesetzblatt 66, 2613ff). Initially, the bacteria counts exceeded the reference values imposed by the German drinking water regulation in almost 50% of the analyses. Pseudomonas aeruginosa was also detected in almost 38% of the samples. After a re-arrangement of the disinfection procedure and the removal of the charcoal filter, Pseudomonas aeruginosa was not detectable any more. However, the bacteria counts still frequently exceeded the reference values of the German drinking water regulation. Following our long-term analysis, we would not recommend soda fountains in high-risk areas of hospitals. If these devices are to be used in hospitals, the disinfection procedures should be executed in weekly or fortnightly intervals and the water quality should be examined periodically.

Bacterial contamination of preserved and non-preserved metal working fluids.

Metal working fluids (MWFs) are important facilities for certain industrial processes. Besides their advantage concerning the effective technical applicability it is disadvantageous that they are excellent culture media for bacterial and fungal growth and may therefore act as an infectious source for employees getting in contact with them. As a matter of prevention most of MWFs are nowadays treated with preservatives to eliminate the contamination of possible human pathogenic bacteria and fungi. Own investigations were concerned with the objectives of the actual and long-term study of the bacterial contamination of preserved and non-preserved MWFs from different MWF systems, the development of a standardized bacterial biotope in non-preserved MWFs and its efficacy to eliminate bacteria which caused infectious diseases in humans, the development of bacterial resistance against preservatives in preserved MWFs and the occurrence of infections and allergies in employees working with MWFs. Our results show: high numbers of different bacteria can be found in non-preserved as well as preserved MWFs; bacteria with a possible human pathogenic potential (category 2, TRBA 466) could almost exclusively be found in preserved MWFs. Those bacteria besides others were able to develop resistance against biocides and could therefore be detected in preserved MWFs for weeks and months; non-preserved MWFs develop stable bacterial biotopes which can be controlled by an artificial inoculation of bacteria. Those biotopes are able to eliminate bacteria which induce infectious diseases in humans; there are only very few data published concerning MWF caused infections or allergies. According to our results of a questionnaire 10% of employees getting in contact with MWFs, complain skin irritations/reactions. There was no difference working with preserved or non-preserved MWFs nor a clear cut correlation to the MWF contact. These data may motivate for more intensive epidemiological studies in this field. The results of our investigations point out that taking into consideration safe working conditions non-preserved MWFs even contaminated with a standardized combination of waterborne bacteria like Pseudomonas spec. up to 10(8) CFU/ml are an alternative to preserved MFWs.

Temptation of academic medicine: second alma mater and "shared employment' concepts as possible way out?

Apparently, in developing and in well-developed societies we are confronted with a crisis of academic medicine in all aspects: health care, teaching, and research. Health care providers in teaching hospitals are under pressure to generate revenues, academic research is pressed to keep pace with institutions devoted solely to research, and teaching is often understood not as privilege and honor but as burden and nuisance. The key problem and the principal cause of the crisis are low interest of the best young graduates to follow an academic career in a world where the benefits and values of the private sector are prevailing. Confronted with these circumstances and the continuous perils of permanent brain-drain, we developed an innovative concept of "shared employment' where two academic institutions (one in a developed and one in a developing country) will collaborate in development and support of fresh talents, building elite academic staff. Most academic exchange programs developed so far have proved to be ineffective and of poor vitality, in spite of loud exclamations, high expectations, and a huge amount of good will involved. In contrast, the suggested cooperation will be based exclusively on mutual interest and clearly defined benefits for all involved parties.

Reform of medical education in Bosnia-Herzegovina: luxury or necessity?

We present the current status of medical education in Bosnia-Herzegovina to set the stage for the curriculum reform. Two principal questions are asked: is the reform necessary, and is it possible? In spite of the differences in size and tradition of medical schools in Bosnia and Herzegovina (BH), they have more features in common than not: all of them are under internal and external pressures for change and reform, which will eventually be inevitable. The history and strategy of reform in Heidelberg, Germany, and Vienna, Austria, are described and recommendations are made on the basis of their experience. The consensus on the need for reforms has to be reached by all parties involved, ie, faculty, administration, students, and the medical community. After that, the reform process must proceed according to the agreed timetable. The job should be delegated to a dedicated task force and work coordinated through the ongoing "Dictum" project, directed exclusively at reform of medical curricula in BH. The project is funded by a European Union TEMPUS program.

Description of new mutations in the rpoB gene in rifampicin-resistant Neisseria meningitidis selected in vitro in a stepwise manner.

Fourteen meningococcal strains were selected towards rifampicin resistance in a stepwise manner in vitro; final MICs were between 8 and >256 microg ml(-1). Sequence analysis of a 295 bp subgenic fragment of the RNA polymerase beta-subunit (rpoB) gene from the original and the fully resistant strains revealed that, with one exception, the strain pairs differed by just one position in the deduced amino acid sequence. Transformation of a PCR-amplified subgenic rpoB fragment harbouring the mutated site into a susceptible strain demonstrated the resistance-conferring mechanism.

Disinfection of surfaces by photocatalytic oxidation with titanium dioxide and UVA light.

Particularly in microbiological laboratories and areas in intensive medical use, regular and thorough disinfection of surfaces is required in order to reduce the numbers of bacteria and to prevent bacterial transmission. The conventional methods of disinfection with wiping are not effective in the longer term, cannot be standardized, are time- and staff-intensive and use aggressive chemicals. Disinfection with hard ultraviolet C (UVC) light is usually not satisfactory, as the depth of penetration is inadequate and there are occupational medicine risks. Photocatalytic oxidation on surfaces coated with titanium dioxide (TiO2) might offer a possible alternative. In the presence of water and oxygen, highly reactive OH-radicals are generated by TiO2 and mild ultraviolet A (UVA). These radicals are able to destroy bacteria, and may therefore be effective in reducing bacterial contamination. Direct irradiation with UVC however can produce areas of shadow in which bacteria are not inactivated. Using targeted light guidance and a light-guiding sheet (out of a UVA-transmittant, Plexiglas, for example), as in the method described in the present study, bacterial inactivation over the entire area is possible. The effectiveness of the method was demonstrated using bacteria relevant to hygiene such as Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Enterococcus faecium. For these bacteria, a reduction efficiency (RE) more than 6log10 steps in 60 min was observed. Using Candida albicans, a RE of 2log10 steps in 60 min was seen. Light and scanning electron microscopic examinations suggest that the germ destruction achieved takes place through direct damage to cell walls caused by OH-radicals.

Immunogenicity of recombinant L7/L12 ribosomal protein of Neisseria meningitidis--high prevalence of specific antibodies in humans but limited immunogenicity for T cells.

The rplL gene, coding for ribosomal protein L7/L12 of Neisseria meningitidis was cloned and expressed as a fusion protein. The recombinant protein was used in Western blots and lymphocyte proliferation assays to study the prevalence of specific antibodies in human sera and the immunogenicity for the cellular immune system. Most of the serum samples studied were found to be positive for L7/L12-specific antibodies. A number of peripheral blood mononuclear cell preparations tested displayed activation in lymphocyte proliferation assays. The magnitude of activation (stimulation index) was moderate, and there was no correlation with a history of meningococcal disease. The high prevalence of specific antibodies is explained by the high carriage rate of meningococci in the normal population or cross-reactivity to ribosomal proteins of other bacteria, thus indicating immunogenicity. However, meningococcal L7/L12 does not seem to be a potential T cell antigen.