Sex: U
Vaccine: MEN
Symptoms: Meningococcal infection, Neisseria test positive
Clinical narrative: Non-groupable meningococcal disease; This case was reported in a literature article and described the occurrence of meningococcal infection in a adult subject who received Meningococcal B vaccine for prophylaxis.   On an unknown date, unknown after receiving Meningococcal B vaccine, the subject developed meningococcal infection. Serious criteria included hospitalization and GSK medically significant. The outcome of meningococcal infection was unknown.   The investigator considered that there was a reasonable possibility that the meningococcal infection may have been caused by Meningococcal B vaccine.   Relevant Tests: Lab tests were performed on unspecified dates between 2011 and 2016. The disease was culture confirmed. The patient's isolates normally sterile site were found to be nongroupable Neisseria meningitidis by slide agglutination that was tested twice. Symptoms were not associated with isolate genogroup or CC.   Diagnostic results (unless otherwise stated, normal values were not provided):  On an unknown date, Blood culture result was see text . On an unknown date, Neisseria test positive result was nongroupable Neisseria meningitidis .  Additional information was provided.  This case was reported in a literature article and described the occurrence of non-groupable meningococcal disease in a patient aged between 17 years and 25 years of unspecified gender who was vaccinated with unspecified meningococcal B vaccine (manufacturer unknown) for prophylaxis.   The patient was the part of study that conducted a medical record review of nongroupable meningococcal disease cases identified in Active Bacterial Core surveillance (ABCs) sites in 2011-2016 and molecular analysed the isolates to characterize these cases and inform prevention and control strategies. [In this study, twenty-two nongroupable meningococcal disease cases were identified, 7 were female, 15 were male. Three patients were taking eculizumab; 2 for Paroxysmal nocturnal hemoglobinuria (PNH) and 1 for atypical hemolytic uremic syndrome (aHUS). No eculizumab recipients had documented receipt of antibiotic prophylaxis for meningococcal disease. Information on complement deficiency diagnosis or complement deficiency testing that included terminal complement components was available for 4 additional nongroupable cases. All complement deficiency testing was initiated after meningococcal disease onset. Both the C6- and C7-deficient patients reported previous episodes of bacterial meningitis (1 meningococcal, 1 unknown organism) within the past 3 years. Four additional patients had other underlying conditions, including 1 with asplenia (Patient also had diabetes, chronic obstructive pulmonary disease, cirrhosis, endocarditis, and end-stage renal disease) and 1 with an intraoperative CSF leak (CSF leak during transphenoidal surgery days before meningococcal disease onset. Patient also had Rathke's pouch cyst, hypogonadism, and pituitary macroadenoma.). One patient had asthma; 1 had atherosclerotic cardiovascular disease, congestive heart failure, Turner's syndrome, and syndrome of inappropriate antidiuretic hormone secretion. Of the 3 patients who died, 1 had asthma; the others had no identified underlying conditions. Two patients, 1 with unspecified complement deficiency and 1 without documented complement testing, had a family history of meningococcal disease]. The patient was a military barracks resident. No information on patient's medical or family history or concurrent condition or concomitant medication was provided.  On an unspecified date, the patient received 1 dose of unspecified meningococcal B vaccine (administration route and site unspecified; batch number not provided). The age of vaccination was not provided.  On an unspecified date between 2011 and 2016, an unknown period after vaccination, the patient developed invasive non-groupable Meningococcal disease. The disease was culture confirmed. The patient's isolates normally sterile site were found to be nongroupable Neisseria meningitidis by slide agglutination that was tested twice. Symptoms were not associated with isolate genogroup or CC.  [In this study, Nongroupable meningococcal disease cases were defined as isolation of Neisseria meningitidis from normally sterile. Isolate capsule polysaccharide synthesis (cps) loci, clonal complex (CC), and sequence type (ST) were characterized by whole-genome sequencing (WGS). CCs 11, 32, 41/44, and 269 were classified as hyperinvasive. 14 had meningitis based on clinical presentation, 19 had bacteraemia (isolation of N. meningitidis from blood), 8 had developed septic shock. Fever, rash, vomiting, and headache were the most common symptoms; 36% of patients had diarrhoea. Three patients died. Isolate capsule polysaccharide synthesis (cps) loci were characterized to understand the genetic basis of the nongroupable phenotype. One isolate had a capsule null locus (cnl); the remaining isolates were assigned togenogroups B, C, E, or Y based on serogroup-specific genes. Four isolates had no cps locus mutations despite absent capsule expression. Two genogroup B isolates had a phase variable off capsule polymerase allele as the only detected cps mutation, 3 isolates had insertion element 1301 (IS1301) within the cps locus, 5 had internal stop codons and/or truncated cps genes, and 8 were missing 1 or more cps genes. The 22 isolates belonged to 19 STs and 10 CCs; CC was unassigned for 1 isolate. Six isolates belonged to hyperinvasive CCs (2 CC11 and 4 CC41/44. Patients genogroup of the infection were inferred from polymerase chain reaction and slide agglutination results for serogroupable isolates (6 patient had genogroup type B infection, 3 had genogroup type C, 7 had genogroup type E, 5 had genogroup type Y, cnl for 1). Six of 8 patients with isolates missing capsule genes had eculizumab use, complement deficiency, or another serious medical condition. Two of the 3 fatal cases were caused by isolates with missing capsule genes; the third was caused by a phase variable off genogroup B isolate]. The patient was hospitalised. [In this study, all patients were hospitalized except 1, who died in the emergency department. 12 patients were admitted to an intensive care unit].  This case has been considered as serious due hospitalisation.  Treatment was unknown.   The outcome of the event was not reported [In this study, 3 patients died. 2 patients had sequelae: 1 had seizures, and 1 had finger and bilateral below-knee amputations].   The authors did not comment on the relationship between the Nongroupable meningococcal disease and unspecified meningococcal B vaccine.   The author stated, "The nongroupable cases in this chart review had a case fatality rate, presentation, and risk of sequelae comparable to those for meningococcal disease caused by serogroupable strains. Collectively, these cases demonstrate that although nongroupable meningococci are an uncommon cause of illness, they can cause serious invasive disease. Although all nongroupable isolates were tested twice by slide agglutination to confirm nongroupable phenotype, 4 isolates had no cps locus mutations, and 5 had only phase variable off mutations or IS1301 insertion, both of which are potentially reversible. It is possible that some of these strains may have expressed capsule while causing invasive disease or may have expressed capsule in vitro at a level undetectable by slide agglutination. However, 2 isolates with IS1301 insertions as the only cps locus mutations were genogroup E, which infrequently causes invasive disease even when expressing capsule. Furthermore, most cases were caused by strains with cps mutations unlikely to be readily reversible, including 8 isolates missing 1 or more capsule locus genes. Clinical and epidemiologic characteristics were similar among patients with disease caused by strains with reversible vs less reversible cps mutations, but the small number of cases limited power to detect differences. All 4 patients with documented complement deficiency testing had either a diagnosed complement deficiency (3) or low CH50 results (1). Three additional patients were taking eculizumab. Terminal complement deficiency is a known risk factor for disease due to nongroupable meningococcal strains. Unfortunately, as most cases lacked complement testing results, it is unclear how many cases may be attributable to this risk factor. More routine complement testing for meningococcal disease patients, particularly those with nongroupable meningococcal disease, would both promote appropriate vaccination for patients and their families, who may be at risk of recurrent disease, and help define the contribution of this risk factor to meningococcal disease incidence in the a specific country".       Lab Comments: Lab tests were performed on unspecified dates between 2011 and 2016. The disease was culture confirmed. The patient's isolates normally sterile site were found to be nongroupable Neisseria meningitidis by slide agglutination that was tested twice. Symptoms were not associated with isolate genogroup or CC.