Invasive meningococcal disease (IMD) is a severe infection caused by Neisseria meningitidis, with mortality rates ranging from 10% to 40%. IMD has been confirmed to be an endemic disease in Tijuana, Mexico, right across the border from San Diego, California. To date, coronavirus disease 2019 (COVID-19) is the most severe pandemic, causing more than 5.5 million deaths globally. Prior or co-infections of influenza with IMD has been reported previously; however, the participation of other respiratory viruses facilitating the invasiveness of N. meningitidis is either not shown or remains unclear. Here, we report the case of an unvaccinated (for IMD and COVID-19) seven-year-old child who had confirmed fatal IMD caused by N. meningitidis, serogroup C, and was co-infected by severe acute respiratory syndrome coronavirus 2.

Neisseria meningitidis serogroup W has emerged as an increasingly common cause of invasive meningococcal disease worldwide; the average case-fatality rate is 10%. In 2017, an unprecedented outbreak of serogroup W infection occurred among the Indigenous pediatric population of Central Australia; there were 24 cases over a 5-month period. Among these cases were atypical manifestations, including meningococcal pneumonia, septic arthritis, and conjunctivitis. The outbreak juxtaposed a well-resourced healthcare system against unique challenges related to covering vast distances, a socially disadvantaged population, and a disease process that was rapid and unpredictable. A coordinated clinical and public health response included investigation of and empiric treatment for 649 febrile children, provision of prophylactic antimicrobial drugs for 465 close contacts, and implementation of a quadrivalent meningococcal ACWY conjugate vaccine immunization program. The response contained the outbreak within 6 months; no deaths and only 1 case of major illness were recorded.

A 36-week-2-day-old male infant was admitted to the neonatal unit with respiratory distress, hypoglycaemia and suspected early onset neonatal sepsis for respiratory support, monitoring and intravenous antibiotics. His initial C-reactive protein was 12 mg/L, this increased to 66 mg/L at 24 hours. Blood cultures at 48 hours confirmed Neisseria meningitidis serogroup B. As the isolate was sensitive to benzylpenicillin the same antibiotic was continued for a total of 7 days. His mother remained asymptomatic but was monitored closely. Ciprofloxacin chemoprophylaxis was given to close family contacts. Neisseria meningitidis causing early onset neonatal sepsis is extremely rare and neonates may have minimal symptoms at presentation. A table reviewing all documented cases of early onset neonatal sepsis caused by Neisseria meningitidis over a 102-year time period is included. There is need for early identification and initiation of empirical antibiotic therapy pending confirmation and sensitivities.

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.

Paroxysmal nocturnal haemoglobinuria (PNH) is a rare acquired haematopoietic stem cell disease which causes defects in complement inhibiting proteins. The disease presents classically with the triad of haemolytic anaemia, pancytopenia and thrombosis. Eculizumab, a humanized antibody that blocks the cleavage of complement factor 5, was approved for PNH treatment in 2007 and has improved patients\' survival since then. However, several cases of invasive meningococcal disease (IMD) have been reported in eculizumab-treated patients, mostly caused by serogroup B infection which was not covered by the previously administered vaccine (MenACWY). We report a rare case of septic shock due to infection with Neisseria meningitis serogroup B despite prior vaccination with 4CMenB in a young PNH patient treated with eculizumab. There are increasing doubts over whether vaccination ensures sufficient immunoprotection against IMD in patients receiving eculizumab. Therefore, besides monitoring the immune response, lifelong chemoprophylaxis should be considered.

There is a need for easy-to-use molecular assays for diagnosis of invasive meningococcal disease. Here, we report the rapid identification of Neisseria meningitidis in a cerebrospinal fluid sample from a patient with purulent meningitis using a commercially available loop-mediated isothermal amplification assay, resulting in a prompt de-escalation of the initial empiric antibiotic therapy.

We present a 4-year-old girl who developed invasive meningococcal disease (IMD) caused by Neisseria meningitidis serogroup C sequence type (ST)-4821. She was hospitalized due to fever, vomiting, rash and altered consciousness. Serogroup C N. meningitidis was isolated from blood culture taken on admission and was confirmed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry, a biochemical test, and molecular microbiological analysis. The patient was successfully treated with 50 mg/kg ceftriaxone every 12 hours for 7 days without any complications. The isolate was susceptible to a wide variety of β-lactams and rifampin but was resistant to ciprofloxacin. The isolate harbored gyrA T91I and parC S87I mutations at the quinolone-resistance-determining regions. Multi-locus sequence typing revealed the isolates as ST-4821, which was identical to an endemic clone frequently detected in China. However, neither the patient nor her family members had traveled abroad. To our knowledge, this report is the first to describe an IMD patient caused by ciprofloxacin-resistant N. meningitidis ST-4821 in Japan, and is the first community-acquired IMD case due to this strain outside of China. The high proportion of ciprofloxacin resistance and hypervirulent features of this ST-4821 strain raise special public health concerns. We still consider ciprofloxacin is still appropriate drug for post-exposure chemoprophylaxis in Japan. However, nationwide surveillance for susceptibility of IMD isolates is necessary to establish the regional antibiogram, and thereby to avoid chemoprophylaxis failure.

Atypical clinical presentations associated with group W meningococcal disease (MenW) are well-described and include pneumonia, septic arthritis, endocarditis and epiglottitis/supraglottitis. Following anecdotal reports of teenagers presenting with predominantly gastrointestinal symptoms, we undertook a case review of MenW cases in 15 to 19 year-olds diagnosed in England between July 2015 and January 2016. Of the 15 cases, seven presented with a short history of nausea, vomiting and diarrhoea; five of these seven cases died within 24 hours of presentation to hospital.