Discussion and conclusions
N. meningitidis (Nm) is a well-known pathogen in meningitis and sepsis, but other end-organ manifestations of IMD such as pneumonia and septic arthritis are also described. Meningococcal epidemiology is unpredictable and not completely understood leading to a high variability in the incidence of IMD [
10]. RT-PCR is approximately 3-times more sensitive than culture in identifying
N. meningitidis from biological samples, therefore meningococcal infections might be underdiagnosed when using culture-based methods alone, especially in the event of an unusual presentation such as arthritis [
9,
11‐
15]. Meningococcal arthritis is a recognized complication of meningococcal infections reported in up to 7.5% of cases in association with IMD. Nevertheless, PMA is an unusual presentation reported in 2.6% of meningococcal infections and has an excellent prognosis [
1,
16]. According to Barahona et al. [
1], PMA is considered a rare entity, accounting for 1.5–1.8% of all pediatric cases of pyogenic arthritis isolated by synovial fluid culture [
17].To our knowledge, less than 50 cases are described in the literature, combining adult and pediatric patients [
1‐
7,
17,
18]. PMA is defined as the presence of septic arthritis without meningeal signs or meningococcaemia and the detection of
N. meningitidis in synovial fluid and/or blood analysis. The knee is described as the most affected joint followed by the ankle. Approximately 50% of patients were children less than 4 years of age [
18]. Despite its unusual presentation it is important not to miss a diagnosis of meningococcal septic arthritis as appropriate treatment and prophylaxis for contacts are required.
When facing uncommon or no specific presentations (e.g., pneumonia, septic arthritis), clinicians are less likely to suspect meningococcal disease and thus to submit clinical specimens for laboratory confirmation than in classic IMD cases (meningitis or sepsis). Moreover, in the context of an unusual presentation is more likely to collect specimens for microbiological identification after having started empirical antimicrobial treatment, reducing the likelihood for the pathogen isolation. This suggests that a proportion of laboratory diagnosis of PMA might be lost and that disease burden PMA might be underestimated. RT-PCR improves the diagnostic rates after having started antibiotic treatment and also allows the characterization of the Nm serogroups, which contributes to a better understanding of the meningococcal disease epidemiology.
A rise in the number of NmY infections has been observed in the last 20 years in several countries [
19,
20]. In Italy, despite an overall invariable incidence of IMD of 0.3 cases/100,000 inhabitants since 2007, an increased proportion of NmY has been observed [
21]. Similarly, to other European countries, serogroup B and C are responsible for the majority of cases, although the proportion of NmY IMD cases has steadily increased over the years [
20], surging from 2% in 2007 to 17% in 2013, in particular among 5- to 14-year-old patients, which is reported to be the most affected group since 2008 [
21].
In our laboratory, we routinely use RT-PCR tests on blood and other normally sterile fluids – as previously described [
9] – in association with culture to enhance the reliability of the IMD laboratory diagnosis. In the cases we presented, even though arthrocentesis was performed after having started antimicrobial therapy, RT-PCR on synovial fluid was able to detect NmY ST23/clusterA3, whereas the cultures resulted negative.
According to the pubMLST database, among invasive NmY the ST-23/cluster A3 complex (cc23) is the major cluster complex (cc) reported in Italy. The ST-23/cluster A3 complex could account for more than 85% of Italian IMD cases caused by NmY (
http://pubmlst.org/neisseria) and five of the total of six cases of meningococcal arthritis caused by NmY are reported (from 2011 to 2018) in Europe were characterized as ST-23/cluster A3 complex (cc23). A limitation of this analysis is that the submission of isolates to the database is voluntary, which might represent a selection bias and underrepresent the real incidence rate.
In conclusion, our report aims to raise awareness among physicians of the atypical presentations of IMD and highlights the diagnostic sensitivity improvements added by the routine use of RT-PCR for IMD, also in the event of unusual presentations, such as PMA. Better quality in laboratory confirmation of IMD is necessary to improve the understanding of the epidemiological features of Nm disease. Currently NmY is not part of the Italian Immunization Program for children under 11-years-old and, based on our limited data we cannot draw conclusions about a dedicated national vaccination strategy. However, we believe that a more accurate surveillance based on cultural and molecular methods would better frame the diffusion of the different meningococcal serogroups allowing a review of the current vaccination strategies. A better estimation of IMD rates, based on active and appropriate surveillance, would likely help in the development of an effective national vaccination program, which remains the best control strategy to prevent invasive meningococcal disease.