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Table 1.  

Variable

Total no. (missing data)

No. (%) cases/y

Average incidence, cases/100,000 population/y

Age, y 319 (0)    
   <1 y   118 (37.0) 31.5
   1–4   120 (37.6) 8.2
   5–9   46 (14.4) 2.6
   10–14   35 (11.0) 2.0
Sex 319 (0)    
   F   125 (39.2) 4.8
   M   194 (60.8) 7.0
Ethnicity, prioritized 319 (0)    
   Māori   114 (35.7) 11.6
   Pacific   140 (43.9) 13.4
   Non-Māori, non-Pacific   65 (20.4) 1.9
New Zealand Index of Deprivation Quintile† 317‡    
   1   11 (3.5) NA
   2   21 (6.6) NA
   3   42 (13.2) NA
   4   54 (17.0) NA
   5   189 (59.6) NA
Clinical manifestations 319 (0)    
   Bacteremia only   108 (33.9) NA
   Meningitis only   63 (19.7) NA
   Meningitis with bacteremia   138 (42.3) NA
   Septic arthritis only   5 (1.6) NA
   Septic arthritis with bacteremia   2 (0.6) NA
   Meningitis and septic arthritis with bacteremia   3 (0.9) NA
Vital signs on first presentation      
   Temperature >38·5°C or <36°C 314 (5) 150 (47.7) NA
   Systolic hypotension for age 218 (101) 84 (38.5) NA
   Impaired level of consciousness 291 (28) 99 (34.0) NA
Clinical signs at first presentation      
   Rash in cases with bacteremia 248 (3) 213 (85.9) NA
   Includes purpura 213 (3) 108 (50.7) NA
   Includes petechiae without purpura 213 (3) 86 (40.4) NA
   Blanching only 213 (3) 19 (8.9) NA
   Meningism in cases with meningitis 184 (20) 111 (60.3) NA
   Bulging fontanelle in infants with meningitis 43 (39) 19 (44.2) NA
   Arthritis during admission 314 (5) 19 (6.1) NA
   Arthralgia during admission 314 (5) 23 (7.3) NA

Table 1. Demographic and clinical factors of 319 confirmed cases of invasive meningococcal disease in children <15 years of age, Auckland, New Zealand, 2004–2020*

*NA, not applicable.
†Each NZDep quintile contains ≈20% of the population. 1 = least deprived; 5 = most deprived.
‡Two overseas cases were excluded.

Table 2.  

Outcome

No. cases/total no. (%)

Died 13/319 (4.1)
Cure, complete outcome data 258/306 (84.3)
Cure, incomplete outcome data 48/306 (15.6)
Cure without sequelae 197/258 (76.4)
Cure with sequelae 61/258 (23.6)
Sequelae
   Neurodevelopmental 35/258 (13.6)
   Sensorineural hearing loss 32/258 (12.4)
   Skin scarring 16/258 (6.2)
   Loss of limbs or digits 7/258 (2.7)
   Chronic kidney disease 1/258 (0.4)
   Other sequelae* 5/258 (1.9)
Neurodevelopmental sequelae
   Delayed development 20/258 (7.8)
   Cerebral ischemia 13/258 (5)
   Epilepsy 8/258 (3.1)
   Learning, concentration, behavior, psychological 8/258 (3.1)
   Other† 10/258 (3.9)

Table 2. Outcomes of 319 confirmed cases of invasive meningococcal disease in children <15 years of age, Auckland, New Zealand, 2004–2020

*Other: bone growth arrest 2/258 (0.8%); cardiomyopathy 1/258 (0.4%); gastrointestinal hemorrhage 1/258 (0.4%); panniculitis 1/258 (0.4%). †Other neurodevelopmental: chronic hydrocephalus 2/258 (0.8%); autism spectrum disorder 1/258 (0.4%); ataxia 1/258 (0.4%); carotid artery narrowing 1/258 (0.4%); chronic headache 1/258 (0·4%); cranial nerve palsy 1/258 (0.4%); encephalomalacia 1/258 (0.4%); hypertonia 1/258 (0.4%); syringomyelia 1/258 (0.4%).

Table 3.  

Variable

No. cases (%)

OR (95% CI)

p value

Ethnicity, compared with non-Māori, non-Pacific population
   Pacific 38/118 (32.2) 2.91 (1.31–7.18) 0.0128
   Māori 28/96 (29.2) 2.52 (1.10–6.35) 0.0366
Reduced penicillin susceptibility 12/64 (18.8) 0.548 (0.25–1.14) 0.117
NZDep quintile† 271 1.21 (0.95–1.58) 0.142
Age, mo† 271 0.996 (0.99–1.00) 0.157
Serogroup, compared with MenB
   MenC 7/18 (38.9) 1.80 (0.64–4.82) 0.247
   MenW 6/25 (24.0) 0.89 (0.31–2.24) 0.822
   MenY 3/8 (37.5) 1.70 (0.34–7.16) 0.478
Male sex, compared with female 50/168 (29.8) 1.39 (0.80–2.48) 0.248
Season, compared with autumn
   Spring 23/76 (30.3) 1.47 (0.64–3.60) 0.374
   Summer 11/35 (31.4) 1.56 (0.57–4.31) 0.386
   Winter 30/116 (25.9) 1.19 (0.54–2.79) 0.683
MeNZB vaccination, compared with fully vaccinated
   Unvaccinated 43/166 (25.9) 0.76 (0.39–1.51) 0.425
   Partially vaccinated 12/41 (29.3) 0.90 (0.37–2.17) 0.817
Prehospital parenteral antibiotic treatment 10/44 (22.7) 0.79 (0.35–1.64) 0.537
Sepsis criteria 39/145 (26.9) 1.14 (0.51–2.77) 0.751

Table 3. Univariate logistic regression for combined outcome of death or sequelae in 271 confirmed cases of invasive meningococcal disease in children <15 years of age, Auckland, New Zealand, 2004–2020*

*Men, Neisseria meningitidis serogroup; OR, odds ratio; NZDep, New Zealand Index of Deprivation
†Continuous variable; OR represents increase in odds for each unit increase in variable.

CME / ABIM MOC

A New Study Highlights the Need for the Meningitis B Vaccine for Children in New Zealand

  • Authors: Cameron Burton, MBChB; Emma Best, MBChB; Matthew Broom, MBChB; Helen Heffernan, BSc (Hons 1); Simon Briggs, MBChB; Rachel Webb, MD
  • CME / ABIM MOC Released: 3/16/2023
  • Valid for credit through: 3/16/2024
Start Activity

  • Credits Available

    Physicians - maximum of 1.00 AMA PRA Category 1 Credit(s)™

    ABIM Diplomates - maximum of 1.00 ABIM MOC points

    You Are Eligible For

    • Letter of Completion
    • ABIM MOC points

Target Audience and Goal Statement

This activity is intended for primary care physicians, pediatricians, infectious disease specialists, and other clinicians who treat and manage children at risk for infection with Neisseria meningitidis.

The goal of this activity is for learners to be better able to evaluate the epidemiology, clinical features, and outcomes of pediatric invasive meningococcal disease.

Upon completion of this activity, participants will:

  • Assess the global epidemiology of invasive meningococcal disease
  • Analyze the epidemiology of invasive meningococcal disease among children in Aotearoa New Zealand
  • Evaluate clinical features of invasive meningococcal disease in the current study
  • Distinguish outcomes of invasive meningococcal disease in the current study


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Faculty

  • Cameron Burton, MBChB

    Te Whatu Ora Counties Manukau
    University of Auckland 
    Auckland, New Zealand

  • Emma Best, MBChB

    Te Whatu Ora Te Toka Tumai Auckland
    University of Auckland
    Auckland, New Zealand

  • Matthew Broom, MBChB

    Te Whatu Ora Te Toka Tumai Auckland
    University of Auckland
    Auckland, New Zealand

  • Helen Heffernan, BSc (Hons 1)

    Institute of Environmental Science and Research
    Wellington, New Zealand

  • Simon Briggs, MBChB

    Te Whatu Ora Te Toka Tumai Auckland
    University of Auckland
    Auckland, New Zealand

  • Rachel Webb, MD

    Te Whatu Ora Te Toka Tumai Auckland
    University of Auckland
    Auckland, New Zealand

CME Author

  • Charles P. Vega, MD

    Health Sciences Clinical Professor of Family Medicine
    University of California, Irvine School of Medicine
    Irvine, California

    Disclosures

    Charles P. Vega, MD, has the following relevant financial relationships:
    Consultant or advisor for: GlaxoSmithKline; Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Editor

  • Cheryl Salerno, BA

    Copyeditor
    Emerging Infectious Diseases

    Disclosures

    Cheryl Salerno, BA, has no relevant financial relationships.

Compliance Reviewer

  • Yaisanet Oyola, MD

    Associate Director, Accreditation and Compliance, Medscape, LLC

    Disclosures

    Yaisanet Oyola, MD, has no relevant financial relationships.


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CME / ABIM MOC

A New Study Highlights the Need for the Meningitis B Vaccine for Children in New Zealand: Results

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Results

Case Numbers

We reviewed data from 331 cases, excluding 12 cases (6 in nonresidents, 5 that were noninvasive disease, and 1 that lacked sufficient data). The remaining 319 cases of laboratory-confirmed IMD occurred in 318 children. One child had 2 unrelated episodes of IMD that occurred in 2006 and 2017. There were no documented relapses after treatment in the cohort. The average annual incidence of IMD across the study period was 5.9/100,000 population. Incidence rates declined from the tail end of the epidemic in 2004 to a nadir in 2014, then increased to a second peak in 2019 (Figure 1). Overall, we found a trend toward reduced incidence over the study period (Poisson coefficient −0.07 [95% CI −0.14 to −0.01; p<0.01]; rate ratio 0.92 [95% CI 0.90–0.95]). Cases were more common in winter (135/319, 42.3%), followed by spring (87/319, 27.3%), autumn (52/319, 16.3%), and summer (45/319, 14.1%) (p<0.0001).

Enlarge

Figure 1. Timeline of 319 cases of confirmed invasive meningococcal disease in children <15 year of age, by serogroup, reported by year, Auckland, New Zealand, 2004–2020. Numbers along data line indicate exact rates for all cases by year. Men, Neisseria meningitidis serogroup.

Demographic Factors

Median age at time of diagnosis was 18 months (interquartile range [IQR] 7–60 months). The highest average incidence rates were among infants <1 year of age (31.5/100,000 population/year), followed by those 1–4 years of age (8.2/100,000 population/year), 5–9 years of age (2.6/100,000 population/year), and 10–14 years of age (2.0/100,000 population/year) (Table 1). Average incidence rates by ethnic group were highest in Pacific peoples (13.4/100,000 population/year), followed by Māori (11.6/100,000 population/year) and those who were neither Māori or Pacific (1.9/100,000 population/year) (Table 1). Based on census data and compared with non-Māori and non-Pacific groups, the unadjusted relative risk of IMD was 5.9 (95% CI 4.4–8.1) for Māori (p<0.0001) and 6.9 (95% CI 5.1–9.3) for Pacific peoples (p<0.0001). Most children (189/317, 59.6%) lived in NZDep quintile 5 (most deprived 20%) areas. The unadjusted relative risk of IMD for children living in NZDep quintile 5 areas compared with quintile 1 areas was 17.2 (95% CI 9.7–33.2; p<0.0001).

Microbiology and Laboratory Features

Of the 319 cases, we confirmed a microbiological diagnosis by both culture and PCR for 81 (25.4%), on culture alone for 114 (35.7%), and on PCR alone for 124 (38.9%). We compared N. meningitidis culture and PCR from blood and from CSF (Appendix Table 1). Blood culture was negative for 56 (78.9%) of 71 cases in children who received antibiotics before hospital admission (odds ratio 5.1 [95% CI 2.7–9.5]) compared with no prehospital antibiotics (p<0.0001). Of those 56 cases, N. meningitidis blood PCR was positive in all 50 cases tested. CSF analysis was performed in 138 (67.6%) of the 204 cases classified as meningitis (Appendix Table 2). CSF leukocytosis for age was present in 130 (97.7%) of 133 cases of meningitis where a CSF leukocyte count was performed. The serogroup was identified for 301 (94.4%) of the 319 cases: 245 (81.4%) were MenB, 26 (8.6%) MenW, 19 (6.3%) MenC, and 11 (3.7%) serogroup Y. Beginning in 2017, there was an increase in disease caused by MenW, which accounted for 8 (29.6%) of the 27 cases serogrouped in 2019; MenB was the remaining predominant serogroup (Figure 2). The epidemic B:P1.7–2,4 strain accounted for 135 cases (44.9%), waning over time, from 42 cases (14.0/100,000 population) in 2004 to 3 cases (0.90/100,000 population) in 2020 (Poisson coefficient −0.20 [95% CI −0.28 to −0.11]; p<0.01; rate ratio 0.82 [95% CI 0.78–0.85]). The proportion of isolates with reduced penicillin susceptibility increased during the study period. A MIC of >0.06 mg/L was identified in 28 (22.6%) of 124 isolates in 2004–2012 and 47 (66.2%) of 71 isolates in 2013–2020 (p<0.0001). Reduced penicillin susceptibility was identified in 20 (76.9%) of 26 MenW isolates compared with 55 (32.5%) of 169 non-MenW isolates (p = 0.012). All isolates were susceptible to ceftriaxone, ciprofloxacin, and rifampin.

Enlarge

Figure 2. Timeline of 319 cases of confirmed invasive meningococcal disease in children <15 years of age by age group (A) and prioritized ethnicity (B), reported by year, Auckland, New Zealand, 2004–2020.

Clinical Features

The median duration of illness before care was sought was 1 day (IQR 1–3 days). Bacteremia was present in 251 cases (78.7%), meningitis in 204 (63.9%), and septic arthritis in 10 (3.1%) (Table 1). Concomitant bacteremia and meningitis occurred in 141 (44.2%) cases. No cases of chronic meningococcemia were recorded. Sepsis occurred in 172 (80.8%) of the 213 cases with complete systemic inflammatory response syndrome data.

Treatment

Of the 319 cases, 317 (99%) were treated in a hospital; 2 children (0.6%) died before arrival. The median duration of hospitalization was 5 nights (IQR 3–7 nights). Prehospital parenteral antibiotics were administered in 52 (16.3%) cases. In the hospital, empiric antibiotics included a third-generation cephalosporin in 294 (92.7%) cases. There were 303 children who completed a full targeted treatment course of antibiotics, which included a third-generation cephalosporin in 230 cases (75.9%), benzylpenicillin in 67 cases (22.1%), amoxicillin in 8 cases (2.6%), and another antibiotic in 4 cases (1.3%). The median duration of antibiotic treatment was 5 days (IQR 5–7 days). Dexamethasone was administered in 47 (23%) of the 204 meningitis cases. Of the 100 (31.3%) children who were admitted to an ICU (median duration of stay 1 night [IQR 1–3 nights]), 55 received ≥1 life-saving measure: 46 received invasive ventilation, 44 received inotropic/vasopressor support, and 7 received renal replacement therapy. Plastic surgical procedures were performed in 12 (3.8%) cases, orthopedic procedures in 12 (3.8%), and neurosurgical procedures in 6 (1.9%).

Outcomes

Thirteen children died, resulting in a CFR of 4.1% (Table 2). The average death rate over the study period was 0.24/100,000 population/year. Of the 13 children who died (Appendix Table 3), 12 (92.3%) were Māori or Pacific peoples, 11 (84.6%) were living in NZDep quintile 5 areas, and 9 (69.2%) were infants <1 year of age. Ten deaths (76.9%) occurred in the community or within the first 48 hours of hospitalization. Of the 306 survivors, outcome data were complete for 258 cases (84.3%): cure without sequelae occurred in 197 (76.4%) and cure with sequelae 61 (23.6%). We classified outcome as unknown in 48 cases; all had meningitis with no available audiometry results (none had other sequelae identified on follow-up). Documented audiologic assessment occurred in 143 (72.6%) of 197 cases after meningitis. Of the 142 cases with audiometry results available, 32 (22.5%) had sensorineural impairment. Māori children with IMD had 2.5 (95% CI 1.1–6.4) times the odds for death or sequelae compared with non-Māori, non-Pacific peoples (p = 0.0366) (Table 3). Pacific peoples with IMD had 2.9 (95% CI 1.3–7.2) times the odds for death or sequelae compared with non-Māori, non-Pacific peoples (p = 0.0128). Results of univariate comparisons of age, sex, NZDep quintile, season, MeNZB vaccination status, sepsis criteria, serogroup, reduced penicillin susceptibility, and prehospital parenteral antibiotics were not significant.

MeNZB Vaccination

Of the 163 children with complete vaccination records who were eligible for MeNZB, 114 (69.9%) had received ≥1 dose and 64 (39.3%) were fully vaccinated at time of hospital admission. For the 97 eligible children with vaccine subtype IMD, 55 (56.7%) had received ≥1 dose and 31 (32%) were fully vaccinated at time of hospital admission. The mean number of days between the date of last MeNZB vaccine and IMD onset increased with the number of doses received (p<0.00027) (Appendix Table 4).