Invasive meningococcal disease in patients with complement deficiencies: a case series (2008\u20132017)

Xilian Bai,Helen Campbell,Mary Ramsay,Sydel Parikh,Jay Lucidarme,Stephen A. Clark,Steve Gray,Shamez N. Ladhani,Ray Borrow,Sima Patel,Aiswarya Lekshmi,Laura Willerton,Andrew Walker

doi:10.1186/s12879-019-4146-5

Abstract

BackgroundTo describe patients with inherited and acquired complement deficiency who developed invasive meningococcal disease (IMD) in England over the last decade.MethodsPublic 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.ResultsA 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.ConclusionsIn 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.

Highlights

To describe patients with inherited and acquired complement deficiency who developed invasive meningococcal disease (IMD) in England over the last decade
In three of the four patients with repeat IMD episodes, the infections were due to different capsular groups; interestingly, all three involved one episode each of group B and group W IMD
The two IMD episodes occurred more than 2 years apart and were caused by a NG(B) strain that was confirmed by PCR only; the 2 NG(B) strains were indistinguishable in terms of PorA (P1.7–1,1) and fHbp

Summary

Introduction

To describe patients with inherited and acquired complement deficiency who developed invasive meningococcal disease (IMD) in England over the last decade. Individuals with primary immunodeficiencies such as the autosomal recessive terminal complement pathway deficiencies have a 7000–10,000 fold higher risk of IMD compared to the general population and more than half of these patients develop recurrent episodes of IMD [6]. In addition to inherited deficiencies of the terminal complement pathway, a number of medical conditions and treatments can lead to acquired or secondary complement deficiency. Eculizumab binds with high affinity to human complement C5 and blocks the generation of C5a and C5b-9, which prevents the formation of membrane attack complexes and activation of the pro-inflammatory pathway, protecting against end-organ damage [7]

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Discussion

Conclusion