{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T18:30:51Z","timestamp":1777401051015,"version":"3.51.4"},"reference-count":23,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Atypical hemolytic uremic syndrome (aHUS) is a rare, life-threatening thrombotic microangiopathy caused by dysregulation of the alternative complement pathway, often related to genetic mutations or autoantibodies. The introduction of complement C5 inhibitors, such as eculizumab and ravulizumab, has significantly improved renal and overall outcomes. However, complement inhibition impairs host defense against encapsulated bacteria, markedly increasing the risk of invasive infections, particularly Neisseria meningitidis. Vaccination against meningococcal groups ACWY and B, along with temporary antibiotic prophylaxis, is therefore recommended before initiating anti-C5 therapy. Methods: We report the clinical course of a 13-year-old boy with aHUS secondary to anti\u2013complement factor H (CFH) autoantibodies and CFHR3\u2013CFHR1 homozygous deletion, treated with C5 inhibitors. Results: Despite complete meningococcal vaccination and a previous course of antibiotic prophylaxis, the patient developed meningitis during ongoing complement inhibitor therapy. Conclusions: This case highlights that breakthrough invasive infections may occur despite adherence to recommended preventive strategies. It underscores the need for sustained clinical vigilance, timely vaccine boosters, and careful reassessment of the risk\u2013benefit balance of continued complement inhibition therapy.<\/jats:p>","DOI":"10.3390\/jcm15083048","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T14:05:36Z","timestamp":1776348336000},"page":"3048","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Beyond Vaccination: Persistent Meningococcal Risk in Anti-C5\u2013Treated aHUS\u2014Case Report and Review of Literature"],"prefix":"10.3390","volume":"15","author":[{"given":"Simona","family":"Matarese","sequence":"first","affiliation":[{"name":"Pediatric Emergency Room and Emergency Medicine Unit, Emergency Department, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7992-0181","authenticated-orcid":false,"given":"Giacomo","family":"Brisca","sequence":"additional","affiliation":[{"name":"Neonatal and Pediatric Intensive Care Unit and Intermediate Care Unit, IRCCS Istituto Giannina Gaslini, Via Gerolamo Gaslini 5, 16147 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7839-317X","authenticated-orcid":false,"given":"Andrea","family":"Moscatelli","sequence":"additional","affiliation":[{"name":"Neonatal and Pediatric Intensive Care Unit and Intermediate Care Unit, IRCCS Istituto Giannina Gaslini, Via Gerolamo Gaslini 5, 16147 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Romanengo","sequence":"additional","affiliation":[{"name":"Neonatal and Pediatric Intensive Care Unit and Intermediate Care Unit, IRCCS Istituto Giannina Gaslini, Via Gerolamo Gaslini 5, 16147 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0593-4112","authenticated-orcid":false,"given":"Alessio","family":"Mesini","sequence":"additional","affiliation":[{"name":"Pediatric Infectious Diseases Unit, Department of Pediatrics, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2989-7301","authenticated-orcid":false,"given":"Marcello","family":"Mariani","sequence":"additional","affiliation":[{"name":"Pediatric Infectious Diseases Unit, Department of Pediatrics, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriele","family":"Mortari","sequence":"additional","affiliation":[{"name":"UOC Nephrology, Dialysis and Transplantation, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5336-8429","authenticated-orcid":false,"given":"Elio","family":"Castagnola","sequence":"additional","affiliation":[{"name":"Pediatric Infectious Diseases Unit, Department of Pediatrics, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Micaela","family":"Gentile","sequence":"additional","affiliation":[{"name":"UOC Nephrology, Guglielmo da Saliceto Hospital, AUSL Piacenza, 29121 Piacenza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrico","family":"Verrina","sequence":"additional","affiliation":[{"name":"UOC Nephrology, Dialysis and Transplantation, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianluigi","family":"Ardissino","sequence":"additional","affiliation":[{"name":"Center for HUS Prevention Control and Management, Pediatric Nephrology Dialysis, Transplant Unit Fondazione, IRCCS Ca\u2019 Granda-Ospedale Maggiore Policlinico, 20122 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edoardo","family":"La Porta","sequence":"additional","affiliation":[{"name":"UOC Nephrology, Dialysis and Transplantation, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1016\/S0140-6736(22)01202-8","article-title":"Haemolytic uraemic syndrome","volume":"400","author":"Michael","year":"2022","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1007\/s40620-023-01873-9","article-title":"Outcome of atypical hemolytic uremic syndrome: Role of triggers and complement abnormalities in the response to C5 inhibition","volume":"37","author":"Ardissino","year":"2024","journal-title":"J. Nephrol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1182\/hematology.2024000543","article-title":"Atypical hemolytic uremic syndrome: Diagnosis, management, and discontinuation of therapy","volume":"2024","author":"Java","year":"2024","journal-title":"Hematology"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Barratt, J., and Weitz, I. (2021). Complement Factor D as a Strategic Target for Regulating the Alternative Complement Pathway. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.712572"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1097\/QCO.0000000000000279","article-title":"Infections associated with the use of eculizumab: Recommendations for prevention and prophylaxis","volume":"29","author":"Benamu","year":"2016","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"734","DOI":"10.15585\/mmwr.mm6627e1","article-title":"High Risk for Invasive Meningococcal Disease Among Patients Receiving Eculizumab (Soliris) Despite Receipt of Meningococcal Vaccine","volume":"66","author":"McNamara","year":"2017","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1182\/blood.2022018833","article-title":"Atypical hemolytic uremic syndrome in the era of terminal complement inhibition: An observational cohort study","volume":"142","author":"Brocklebank","year":"2023","journal-title":"Blood"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15585\/mmwr.rr6909a1","article-title":"Meningococcal Vaccination: Recommendations of the Advisory Committee on Immunization Practices, United States, 2020","volume":"69","author":"Mbaeyi","year":"2020","journal-title":"MMWR Recomm. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1136\/pn-2025-004651","article-title":"Ravulizumab-related meningococcal sepsis post rituximab","volume":"25","author":"Kline","year":"2025","journal-title":"Pract. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.cmi.2017.07.011","article-title":"Post-eculizumab meningococcaemia in vaccinated patients","volume":"24","author":"Lebel","year":"2018","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1111\/ajt.12032","article-title":"Meningococcal Sepsis Complicating Eculizumab Treatment Despite Prior Vaccination","volume":"13","author":"Struijk","year":"2013","journal-title":"Am. J. Transplant."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e1506","DOI":"10.1542\/peds.2014-3503","article-title":"Case Report: Benefits and Challenges of Long-term Eculizumab in Atypical Hemolytic Uremic Syndrome","volume":"135","author":"Cullinan","year":"2015","journal-title":"Pediatrics"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"106228","DOI":"10.1016\/j.jinf.2024.106228","article-title":"Effectiveness and duration of protection of primary and booster immunisation against meningococcal serogroup C disease with meningococcal conjugate C and ACWY vaccines: Systematic review","volume":"89","author":"Griskaitis","year":"2024","journal-title":"J. Infect."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2304","DOI":"10.4161\/hv.25505","article-title":"Persistence of antibodies in adolescents 18-24 months after immunization with one, two, or three doses of 4CMenB meningococcal serogroup B vaccine","volume":"9","author":"Santolaya","year":"2013","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1093\/cid\/ciy958","article-title":"Disseminated Gonococcal Infections in Patients Receiving Eculizumab: A Case Series","volume":"69","author":"Crew","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1182\/blood-2017-05-781450","article-title":"Eculizumab treatment and impaired opsonophagocytic killing of meningococci by whole blood from immunized adults","volume":"130","author":"Konar","year":"2017","journal-title":"Blood"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1093\/ndt\/gfy225","article-title":"Failure of first meningococcal vaccination in patients with atypical haemolytic uraemic syndrome treated with eculizumab","volume":"35","author":"Rohn","year":"2020","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"S21","DOI":"10.1016\/j.cmi.2018.02.002","article-title":"ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: An infectious diseases perspective (Soluble immune effector molecules [II]: Agents targeting interleukins, immunoglobulins and complement factors)","volume":"24","author":"Winthrop","year":"2018","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2507","DOI":"10.1016\/j.vaccine.2018.03.087","article-title":"A rare case of septic shock due to Neisseria meningitidis serogroup B infection despite prior vaccination in a young adult with paroxysmal nocturnal haemoglobinuria receiving eculizumab","volume":"36","author":"Reher","year":"2018","journal-title":"Vaccine"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3615","DOI":"10.1182\/bloodadvances.2020002497","article-title":"Eculizumab impairs Neisseria meningitidis serogroup B killing in whole blood despite 4CMenB vaccination of PNH patients","volume":"4","author":"Langereis","year":"2020","journal-title":"Blood Adv."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.jinf.2019.11.015","article-title":"Antibiotic prophylaxis in vaccinated eculizumab recipients who developed meningococcal disease","volume":"80","author":"Crew","year":"2020","journal-title":"J. Infect."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1053\/j.ajkd.2014.01.434","article-title":"Discontinuation of eculizumab maintenance treatment for atypical hemolytic uremic syndrome: A report of 10 cases","volume":"64","author":"Ardissino","year":"2014","journal-title":"Am. J. Kidney Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"50","DOI":"10.2215\/CJN.06440616","article-title":"Pathogenic Variants in Complement Genes and Risk of Atypical Hemolytic Uremic Syndrome Relapse after Eculizumab Discontinuation","volume":"12","author":"Fakhouri","year":"2017","journal-title":"Clin. J. Am. Soc. Nephrol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/8\/3048\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:20:35Z","timestamp":1777371635000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/8\/3048"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,16]]},"references-count":23,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["jcm15083048"],"URL":"https:\/\/doi.org\/10.3390\/jcm15083048","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,16]]}}}