Invasive meningococcal disease in patients with complement deficiencies: a case series (2008–2017)

Abstract

Background To describe patients with inherited and acquired complement deficiency who developed invasive meningococcal disease (IMD) in England over the last decade. Methods Public Health England conducts enhanced surveillance of IMD in England. We retrospectively identified patients with complement deficiency who developed IMD in England during 2008–2017 and retrieved information on their clinical presentation, vaccination status, medication history, recurrence of infection and outcomes, as well as characteristics of the infecting meningococcal strain. Results A total of 16 patients with 20 IMD episodes were identified, including four with two episodes. Six patients had inherited complement deficiencies, two had immune-mediated conditions associated with complement deficiency (glomerulonephritis and vasculitis), and eight others were on Eculizumab therapy, five for paroxysmal nocturnal haemoglobinuria and three for atypical haemolytic uraemic syndrome. Cultures were available for 7 of 11 episodes among those with inherited complement deficiencies/immune-mediated conditions and the predominant capsular group was Y (7/11), followed by B (3/11) and non-groupable (1/11) strains. Among patients receiving Eculizumab therapy, 3 of the 9 episodes were due to group B (3/9), three others were NG but genotypically group B, and one case each of groups E, W and Y. Conclusions In England, complement deficiency is rare among IMD cases and includes inherited disorders of the late complement pathway, immune-mediated disorders associated with low complement levels and patients on Eculizumab therapy. IMD due to capsular group Y predominates in patient with inherited complement deficiency, whilst those on Eculizumab therapy develop IMD due to more diverse capsular groups including non-encapsulated strains.

Retrospective analysis of the etiology, clinical characteristics and outcomes of community-acquired bacterial meningitis in the University Infectious Diseases Centre in Lithuania

“…Unlike most previously reported outbreaks of invasive meningococcal disease that were associated with serotype B [20], we found that all our cases of meningococcal meningitis were sporadic. According to other studies, L. monocytogenes is the third most common causative agent of CABM and is associated with older age and immunodeficiency [15,[21][22][23][24]. In our study, L. monocytogenes meningitis was the third most common etiological factor and 40% of L. monocytogenes meningitis in our study occurred in adults under the age of 50 without specific risk factors.…”

“…The strongest risk factors in our study for an unfavorable outcome were an older age, coexisting pneumonia and a low platelet count at presentation. According to other studies, impaired consciousness, low white-cell count, a delay in antibiotic therapy initiation and other comorbidities may also lead to a more severe course of meningitis [21,22,31,43].…”

Impact of COVID-19 pandemic and the lockdown on invasive meningococcal disease

“…An additional interference between COVID-19 and IMD may originate from the use of anti-complement drugs that are explored to control COVID-19 by lowering complement mediated pro-inflammatory response [ 16 ]. These drugs such as anti-complement compounded 5 (C5) are known to increase the risk for IMD [ 17 ].…”

Detection of the United States Neisseria meningitidis urethritis clade in the United Kingdom, August and December 2019 – emergence of multiple antibiotic resistance calls for vigilance

“…This includes disease caused by unencapsulated strains, such as the US_NmUC strain, that would not normally cause disease in healthy individuals [15]. These individuals are recommended to receive meningococcal vaccination and long-term penicillin prophylaxis [16]. To account for the existence of relatively rare penicillin-resistant strains, ciprofloxacin may also be prescribed as a back-up should the patient experience symptoms of invasive meningococcal disease.…”