Relationships Between Clinico-Epidemiological Patterns of Invasive Meningococcal Infections and Complement Deficiencies in French South Pacific Islands (New Caledonia)

Daurès, Maguy; John, Michéle; Balter, Cécile Veysseyre; Simon, Olivier; Barguil, Yann; Missotte, Isabelle; Grangeon, Jean-Paul; Laumond-Barny, Sylvie; Noël, Martine; Besson-Leaud, L.; Spasic, Pierre-Emmanuel; Suremain, Aurélie de; Gourinat, Ann-Claire; Descloux, Élodie

doi:10.1007/s10875-014-0104-6

Cited by 5 publications

(2 citation statements)

References 33 publications

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“…Patients enrolled in a French monocentric survey in New Caledonia on meningococcal infection were also enrolled if they completed the inclusion criteria. 12 The inclusion criteria for the study were 1 age >15 years, 2 complement deficiency, and 3 clinical infection. Both inpatients and outpatients were included.…”

Section: Methodsmentioning

confidence: 99%

Infections Revealing Complement Deficiency in Adults

et al. 2016

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Complement system is a part of innate immunity, its main function is to protect human from bacterial infection. As genetic disorders, complement deficiencies are often diagnosed in pediatric population. However, complement deficiencies can also be revealed in adults but have been poorly investigated. Herein, we describe a case series of infections revealing complement deficiency in adults to study clinical spectrum and management of complement deficiencies.A nationwide retrospective study was conducted in French university and general hospitals in departments of internal medicine, infectious diseases enrolling patients older than 15 years old who had presented at least one infection leading to a complement deficiency diagnosis.Forty-one patients included between 2002 and 2015 in 19 different departments were enrolled in this study. The male-to-female ratio was 1.3 and the mean age at diagnosis was 28 ± 14 (15–67) years. The main clinical feature was Neisseria meningitidis meningitis 75% (n = 31/41) often involving rare serotype: Y (n = 9) and W 135 (n = 7). The main complement deficiency observed was the common final pathway deficiency 83% (n = 34/41). Half of the cohort displayed severe sepsis or septic shock at diagnosis (n = 22/41) but no patient died. No patient had family history of complement deficiency. The mean follow-up was 1.15 ± 1.95 (0.1–10) years. Half of the patients had already suffered from at least one infection before diagnosis of complement deficiency: meningitis (n = 13), pneumonia (n = 4), fulminans purpura (n = 1), or recurrent otitis (n = 1). Near one-third (n = 10/39) had received prophylactic antibiotics (cotrimoxazole or penicillin) after diagnosis of complement deficiency. The vaccination coverage rate, at the end of the follow-up, for N meningitidis, Streptococcus pneumonia, and Haemophilius influenzae were, respectively, 90% (n = 33/37), 47% (n = 17/36), and 35% (n = 14/34).This large study emphasizes that complement deficiencies can be revealed in adults by infectious episodes. Most of them were meningococcal infections revealing common final pathway deficiency. To avoid undiagnosis or late diagnosis, adult displaying first episode of N meningitidis infection should be tested for complement deficiency.

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Section: Methodsmentioning

confidence: 99%

Infections Revealing Complement Deficiency in Adults

et al. 2016

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“…For instance, IMD is three-fold more common in New Caledonia than in France. This was found to be due to a high prevalence of complement deficiency status (C-deficiency) in Melanesian patients, particularly those originating from the Loyalty Islands (Daures et al, 2015). In New Zealand, the ethnic groups with the highest rates of disease in 2018 were Pacific peoples (5.1 cases per 100 000) and Māori (4.7 cases per 100 000) (ESR, 2018b).…”

Section: Risk Factors For Imdmentioning

confidence: 99%

Identification of a meningococcal adhesin that inhibits epithelial cell migration

Greig¹

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<p>Neisseria meningitidis virulence is polygenic, therefore comparing many genomes may not yield strictly disease-associated virulence factors. An alternative approach is comparing closely related isolates, such as those from household contacts. Disease isolates have been shown to inhibit epithelial cell wound repair, while many carriage isolates do not. In this study, bacteria collected from disease patients and healthy household contacts were compared to identify the meningococcal factor responsible for wound repair inhibition and investigate how it contributes to invasive disease. Host cell wound repair inhibition was compared between disease-associated meningococcal isolate, NZ97/052, and isolates NZCM111 and NZCM112, from asymptomatic household contacts. Migrating bronchial airway cells were infected with meningococcal isolates and wound closure was evaluated by microscopy. NZ97/052 and NZCM111 both inhibited wound repair, whereas NZCM112 did not. To investigate if this was due to bacterial consumption of an important nutrient, infected cells were supplemented with nutrients known to be important for meningococcal growth and cell migration. Iron supplementation resulted in carriage associated isolates gaining the ability to inhibit wound repair. Genome and transcriptome comparisons were completed between NZ97/052 and NZCM112, which differ in wound repair inhibition. This analysis identified a frameshift mutation in NZCM112 in the haptoglobin-haemoglobin utilization gene, hpuA, which caused complete loss of expression. The hpuA gene was deleted by allelic replacement from NZ97/052, nullifying its ability to inhibit host cell migration. Furthermore, bacterial association and fluorescence microscopy assays suggested that HpuA contributes to meningococcal attachment to bronchial epithelial cells, as the hpuA mutant had significantly lower cell association. Heterologous expression of HpuA in E. coli resulted in higher levels of cell association, indicating that HpuA is sufficient to mediate bacterial adhesion to human bronchial epithelial cells. This work reveals novel roles for HpuA as a meningococcal adhesin and a bacterial factor that inhibits host cell migration.</p>

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