Neisseria meningitidis is the major worldwide cause of meningitis and rapidly fatal sepsis in healthy individuals. The risk of meningococcal disease is higher among those with complement deficiencies, asplenia and other underlying conditions. N. meningitidis is the only agent among the major bacterial agents causing meningitis that causes epidemic as well as endemic disease. The meningococcus is carried in the human nasopharynx asymptomatically by 5% to 10% of adults in non-epidemic periods. N. meningitidis accounts for morbidity and mortality within the cases and may result in sequelae. In addition, it is responsible for other infections, such as arthritis, osteomyelitis and cellulitis. Meningococci are usually assorted according to serologic typing systems based on structural differences of capsule (serogroup), major outer membrane porin proteins (serotype), other outer membrane proteins (serosubtype) and lipooligosaccharide (immunotype). Meningococcal disease surveillance is paramount and aims at different targets: early detection of cases to activate public health response (namely identification of close contacts and administration of chemoprophylaxis to prevent secondary cases of the disease, to evaluate trends and to act in outbreaks), surveillance with vaccination purposes and the estimation of the burden of meningococcal disease. Meningococcal surveillance systems are partially based on laboratory diagnoses, therefore, there is a need for accuracy and proficiency in surveillance laboratory performance. ECDC promotes the performance of External Quality Assurance (EQA) schemes, in which laboratories are sent simulated clinical specimens or bacterial isolates for testing by routine and/or reference laboratory methods. EQA schemes or proficiency laboratory testing provides information about the accuracy of different characterisation and typing methods as well as antimicrobial susceptibility testing, and the sensitivity of the methods in place to detect a certain pathogen or novel resistance patterns. This means that quality assurance enables a laboratory performance to be assessed in comparison to reference methods and to other peer laboratories. In March 2009, a collection of six viable isolates of N. meningitidis of the major disease-causing serogroups (A, B, C, Y and W-135) together with six simulated blood (non-culture) samples for molecular studies, was sent by UKNEQAS to 27 participating Reference Laboratories (Annex 1) in the IBD-Labnet surveillance network for quality assurance testing. The laboratories were asked to perform phenotypic characterisation of viable isolates: serogroup, serotype, serosubtype and antimicrobial susceptibility testing (MIC results) on the viable isolates, and molecular characterisation both of the viable isolates and non-culture simulated septicaemia samples. Overall, the EQA performance has shown that European Meningococcus Reference Laboratories differ in the level of characterisation of the strains. The phenotypic characterisation of viable isolates was quite successful with reports for serogroup received from all 27 participating laboratories for each sample. However, the phenotypic serotyping and serosubtyping reports demonstrated limited discrimination due mainly to the limited resources or reactivity of the reagents. The EQA exercise pointed out that this is an area in which further work needs to be done. The antimicrobial susceptibility testing exercise and determination of the minimum inhibitory concentration (MIC) pointed out that there are two major areas for consideration: the designated and reported MIC of the antimicrobial and the interpretation of susceptibility or resistance. The European Monitoring Group on Meningococci (EMGM) has recommended the utility of gradient diffusion methodology (such as by Etest) and a standardised agar plate medium (Mueller Hinton plus blood), but it seems that a number of laboratories may be using different methodologies, making comparisons more difficult. The range of MIC values and calculated modes suggest that laboratories are not all using Etest strips. It is also apparent that the laboratories used a number of different guidelines to interpret the MICs as susceptible, intermediate or resistant. From the epidemiological point of view, it would be advisable to collect MIC values and then interpret them according to only one guideline for consistency. The MIC EQA reports suggest that CLSI currently predominates but a standardised methodology and the use of EUCAST breakpoints would be an appropriate future aim. The MLST analysis of non-culture samples revealed more problems than the viable isolates MLST. In conclusion, the results of the EQA exercise proved that the establishment of a regular EQA scheme for the reference laboratories is required in order to maintain the movement towards improved quality of epidemiological reports. It was also concluded that training might be requested to assist the laboratories setting up different techniques according to their particular needs.
