Discussion

Key Findings

Despite a reduction in the number of cases of IMD since the MenB epidemic, the incidence of IMD in New Zealand remains double that of other high-income countries^[3,5]. Although MenB remains the most common serogroup in children, the epidemic B:P1.7–2,4 strain no longer dominates in the Auckland region. Rates of pediatric IMD increased in Auckland and nationally in 2014–2019, partly because of an observed global increase in MenW^[3,5]. Mirroring international trends in invasive bacterial disease during the COVID-19 pandemic^[26–28], there was a sharp decrease in cases of pediatric IMD in NZ in 2020 after national COVID-19 control measures began, and that decrease continued through 2021^[29]. Future patterns of pediatric IMD remain uncertain; however, there is a risk of resurgent disease exacerbated by rising poverty and socioeconomic inequity^[30].

Our findings highlight the severity of IMD. One third of the cases we studied included admission to an ICU, comparable with data for international cohorts^[8,31]. Over half of those cases required invasive ventilation or inotropic/vasopressor support. The CFR in our cohort was 4.1%, which compares to rates for other high-income settings of 2%–12%^[1]. Sequelae occurred in 23.6% of survivors. Because outcome was classified as unknown for 48 cases that lacked audiologic data but had no other reported sequelae, we might have overestimated the proportion of survivors with sequelae. Our study revealed that 1 in 4 children did not receive an audiology assessment after meningococcal meningitis. Given this finding, we strongly recommend that children in New Zealand who are diagnosed with meningococcal meningitis receive audiology assessment before hospital discharge. Active follow-up for survivors of IMD should focus on confirming audiology assessment and screening for neurologic, developmental, and psychological effects^[2,9]. Our lack of access to mental health and educational data and shorter follow-up durations of ≥3 months might have underestimated the prevalence of long-term neurocognitive and psychological effects. Urgent action is needed to honor the nation’s commitment to Te Tiriti o Waitangi, the 1840 founding document that established bicultural partnership between indigenous Māori and the British Crown.

Our data demonstrate the usefulness of PCR for diagnosing culture-negative IMD^[32,33]. Blood culture results were negative in 79% of children who received prehospital antibiotics. However, when performed, N. meningitidis blood PCR was positive in all those cases. Drew et al. similarly reported positive blood PCR in 25 of 28 IMD cases that had a negative blood culture after intramuscular penicillin^[32]. We suggest that clinicians consider using N. meningitidis PCR testing, especially in the context of prior antibiotic administration. We found no statistically significant differences in clinical outcomes between children who received prehospital parenteral antibiotics and those who did not; however, our study was not powered to detect a difference in those outcomes.

In our cohort, bacteremia and meningitis coexisted in 44.2% of cases; we propose that CSF testing be carefully considered for those with proven meningococcal bacteremia, especially in infants. In cases with bacteremia, 85.9% had a rash at first examination; rash characteristics included purpura (50.7%), petechiae without purpura (40.4%), and blanching only (8.9%), findings similar to those reported for a pediatric cohort in Ireland^[9]. Whereas a classic purpuric or petechial rash can suggest IMD, rash at presentation might be nonspecific or absent. It is therefore important for clinicians to maintain a high index of suspicion of IMD in children with suspected sepsis without rash.

In our cohort, we noted an increase over time in the proportion of isolates with reduced penicillin susceptibility. Similar trends have been reported among adults in Auckland, as well as in Spain and Australia^[34–36]. Earlier literature reported an association between reduced penicillin susceptibility and increased complications^[37]; however, no difference in outcomes were noted for our pediatric cohort or for the Auckland adult cohort^[34]. New Zealand guidelines recommend a third-generation cephalosporin for empiric treatment of sepsis in children^[38]. Because all isolates we studied were ceftriaxone-susceptible, reduced penicillin susceptibility is unlikely to have clinical significance for empiric therapy in New Zealand.

Our study illustrates the considerable inequity of IMD in the Auckland region of New Zealand. Māori and Pacific children had disproportionately higher rates of IMD and were more likely to experience complications. All but 1 death occurred in Māori or Pacific children. Children living in Auckland’s most deprived 20% of neighborhoods had rates of IMD 17 times higher than those in the least deprived 20% of neighborhoods. The relationship between ethnicity, socioeconomic deprivation, and the risk of severe childhood infections is not well understood but is likely rooted in the ongoing effects of colonization and structural racism^[39]. Recent findings from a nationally representative longitudinal study, Growing Up in New Zealand^[40], indicate that disparities in infectious disease hospitalizations among infants of Māori or Pacific peoples can be only partly explained by socioeconomic deprivation factors. Nonetheless, household crowding has been shown to be strongly associated with epidemic IMD in New Zealand^[41].

Addressing the upstream determinants of health is important, but vaccination remains the best strategy to control IMD and is a key method for reducing inequity^[4,5,42]. Although New Zealand’s universal vaccination programs have not yet resulted in equitable uptake, prioritizing delivery and implementation might improve coverage and outcomes for those most at risk^[43]. Despite having the highest rate of MenB in the world and some prior success with MeNZB immunization, New Zealand has not yet included 4CMenB in the National Immunization Schedule nor funded vaccine for children at highest risk of disease. The real-world evidence for 4CMenB is clear and demonstrates that control of IMD in New Zealand is within reach^[15].

In conclusion, IMD remains a severe, life-threatening disease in young children in New Zealand; Māori and Pacific infants and those living in areas of socioeconomic deprivation are at greatest risk. The recent increase in incidence of MenB IMD highlights the urgent case for inclusion of 4CMenB in the National Immunization Schedule. Using N. meningitidis PCR to aid diagnosis of culture-negative, clinically suspected IMD, along with routine inpatient audiology assessment after cases of meningococcal meningitis, may improve clinical outcomes.