Prevention strategies for invasive meningococcal infections in the APAC region

Overview of IMD
IMD is a severe infection caused by Neisseria meningitidis, which colonizes the upper respiratory tract and can enter the bloodstream, leading to meningitis, septicaemia, or both. Most colonization occurs asymptomatically (the ‘carriage’ state), particularly in infants, toddlers, adolescents and young adults, who act as reservoirs for transmission, some of whom may develop IMD. [Epidemiol In­fect 2023:151:e57; Eur J Clin Microbiol Infect Dis 2020;39:1703-1709]

Patients infected with N. menin­gitidis typically present with nonspe­cific symptoms such as fever, myal­gia, nausea and vomiting at the early stage, making identification and diag­nosis of IMD difficult. Approximately 40–70 percent present with meningo­coccal septicaemia, exhibiting circu­latory insufficiency, shock, and a pur­puric rash. The disease can progress rapidly within 12–24 hours, leading to serious clinical sequelae, with a fatality rate of about 10 percent. Among sur­vivors, 10–20 percent may experience lifelong disabilities. [J Adolesc Health 2016;59:S21-8; BMC Fam Pract 2021;22:240; Expert Rev Anti Infect Ther 2017:689-701]

“Unfortunately, resistance to anti­microbials, including chloramphenicol, ciprofloxacin, penicillin and azithromy­cin, has been documented in strains of N. meningitidis in the APAC region, complicating the management of IMD,” stated Kwan. [IJID Reg 2023:10:52- 59; Antimicrob Agents Chemother 2023;67:e0074423]

Epidemiology and trends of IMD
N. meningitidis is classified into several serogroups based on their surface antigens, namely, the poly­saccharide capsules surrounding the bacterial cell. Of the various identified meningococcal serogroups, five (A, B, C, W, and Y) are responsible for the majority of IMD. [Epidemiol Infect 2023:151:e57]

A systematic review and meta-analysis of 102 studies on N. meningitidis serogroups in IMD in­dicated that the seroprevalence varies noticeably across countries and age groups. Globally, serogroup B (MenB) was responsible for the highest pro­portion of cases (48.5 percent), fol­lowed by MenC (21.7 percent). In paediatric patients, MenC account­ed for 9.7 percent of cases among those aged 1–4 years, while MenB accounted for 9.5 percent of cases in infants <1 year of age. Time trends in seroprevalence showed an increase in the proportions of MenB and MenC in the Western Pacific or APAC region and a marked decrease in MenC in Europe and North America. [Microb Pathog 2019:134:103571]

In the APAC region, the reported prevalence of IMD is generally low, at approximately 0.01–0.2 cases per 100,000 population, with higher rates observed among younger patients (<5 years of age). Additionally, sero­prevalence data indicate that MenB is predominant in many countries within the APAC region. (Table 1) Howev­er, incidence rates can be sporadic across the region, with periodic re­ports of endemic IMD. [Epidemiol In­fect 2011;139:967-985]

“During the COVID-19 pandemic, similar to some infectious diseases, IMD incidence and mortality rates declined in many regions, likely due to public health measures, which at the same time disrupted IMD vac­cination programmes, leading to reduced vaccine uptake. Following the easing of pandemic restrictions, a worldwide resurgence in IMD inci­dence, particularly MenB, has been observed,” noted Kwan. “The pan­demic has also exacerbated antibi­otic resistance from the widespread use of broad-spectrum antibiotics for coinfections in patients with SARS-CoV-2, posing additional challenges in managing IMD. This underscores the urgent need to implement and prioritize vaccination programmes targeting prevalent serogroups in pa­tients at risk of IMD.” [Infect Dis Ther 2024;13:2489-2507; Infect Dis Ther 2023;12:2649-2663; Int J Antimicrob Agents 2021;57:106324]

Real-world evidence on meningococcal vaccines
Quadrivalent glycoconjugate me­ningococcal ACWY (MenACWY) and recombinant protein-based MenB vac­cines are widely available in the APAC region for protection against IMD.

Studies of MenACWY-TT, MenACWY-D and MenACWY-CRM vaccines used as part of immuniza­tion programmes targeting toddlers, adolescents, young adults and mili­tary recruits have shown effectiveness ranging from 69–94 percent, with ex­cellent safety profiles. [Hum Vaccin Immunother 2023;19:2251825; Ex­pert Rev Vaccines 2024;23:845-861; Vaccine 2020;38:730-732]

Real-world data also confirm that MenB vaccines produce a robust immune response in infants, adoles­cents and young adults, including during outbreaks. An observational retrospective study collected data between 2006 and 2018 in two re­gions of Italy. In Tuscany, prevaccine incidence was 1.96 and dropped to 0.62 in the post-4CMenB era. Eval­uating only vaccinated children, post-4CMenB incidence was 0.12. In Veneto, prevaccine incidence was 1.94 and dropped to 1.34 in the post-4CMenB era, with an incidence of 0.53 in the vaccinated population. In the vaccinated population, the rel­ative case reduction was 91 percent in Tuscany and 80 percent in Veneto. Vaccine effectiveness was 93.6 per­cent in Tuscany and 91.0 percent in Veneto, with mean vaccine coverage of 83.9 and 81.7 percent, respective­ly. [Vaccines (Basel) 2020;8:469]

In Canada, 4CMenB was im­plemented in a mass vaccination campaign in 2014 in the Saguenay-Lac-Saint-Jean region, targeting in­dividuals aged 2 months to 20 years due to a MenB outbreak that began in 2003. Between 2015 and 2016, no cases of MenB IMD were report­ed among vaccinated individuals, of whom 82 percent received at least one dose. Over the 5-year postcam­paign period (2014–2019), MenB IMD incidence decreased in the target­ed age group, from 11.4 to 0.7 per 100,000 person-years (p=0.0001). The incidence decreased by 100 percent in the vaccine-eligible popu­lation during the first 2 years of the programme (p<0.0001), by 96 per­cent after 4 years (p=0.0013), and by 94 percent after 5 years (p<0.06). [J Infect 2021;83:17-26]

“International evidence support­ing the effectiveness of MenB vac­cines highlights the need for mass immunization of infants and targeted vaccination for adolescents to reduce MenB IMD,” emphasized Kwan.

Meningococcal vaccination policies and recommendations
In April 2024, experts from the APAC region convened to review recent epidemiological data on the burden of IMD, assess evidence for vaccination, identify barriers to vac­cination, and formulate consensus statements on IMD surveillance and vaccination programmes for the re­gion in the postpandemic era.

“During the meeting, the advi­sory group noted that many coun­tries do not include meningococcal vaccines in their routine vaccination programmes. There is also substan­tial variation in the types of samples tested [blood or cerebrospinal fluid] and the methods used [culture or polymerase chain reaction (PCR)]. In addition, epidemiological data may be underestimated in certain areas due to early antibiotic treatment and inconsistent surveillance approach­es. Nations should consider adding meningococcal vaccines to their im­munization programmes,” Kwan re­marked. “The final APAC consensus statement is currently being prepared and will be published soon.” (Table 2) [Kwan M, 2024]

Overcoming vaccine hesitancy
“Vaccine hesitancy [ie, reluctance or refusal to vaccinate] is a growing phenomenon in Asia, including Hong Kong. It is driven by concerns about safety, mistrust of manufacturers and regulators, and lack of IMD aware­ness and vaccine availability,” Kwan suggested. [Isr J Health Policy Res 2023;12:11] “To overcome these bar­riers, it is essential to educate par­ents, adolescents and young adults about IMD’s prevalence and the ben­efits of vaccination. Encouraging lo­cal healthcare providers to advocate vaccination can help change public perception, as they are trusted sourc­es of health information that can address the public’s concerns and misconceptions.”

Although MenB is becoming the predominant strain globally, it is not included in Hong Kong’s vaccination scheme. Therefore, private doctors play a vital role in educating patients and parents about IMD protection, es­pecially for children <5 years of age and individuals travelling to high-risk areas.

Conclusion
IMD is a severe infection that may lead to serious clinical sequelae. It is important to overcome vaccine hesitancy by raising public aware­ness of meningococcal vaccines’ effectiveness in preventing IMD in children, adolescents, young adults and individuals at risk, which is con­firmed by real-world evidence. Local healthcare providers may consider including both MenACWY and MenB vaccines in national immunization programmes.

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