Meningococcal invasive disease by serogroup W and use of ACWY conjugate vaccines as control strategy in Chile

doi:10.1016/j.vaccine.2019.09.050

Vaccine

Volume 37, Issue 46, 31 October 2019, Pages 6915-6921

https://doi.org/10.1016/j.vaccine.2019.09.050 Get rights and content

Abstract

Background

Serogroup causing invasive meningococcal disease (IMD) can change abruptly, as it occurred in Chile when serogroup predominance switched from MenB to MenW in 2012. As a response, a national vaccination strategy was implemented since 2012 using tetravalent meningococcal-conjugate vaccines (MCV–ACWY) in children 9 months through 4 years of age. The aim of this study was to describe IMD cases by MenW in Chile 2009–2016, and to analyse its trend after the introduction of MCV-ACWY.

Methods

Descriptive study of IMD cases in Chile, period 2009–2016. Cumulative incidence and mortality rate per 100,000 inhabitants, and case fatality rate (CRF) were used for descriptive analysis. Linear regression was used for post-intervention trend analysis.

Results

In 2012, MenW, mainly ST-11 cc, became predominant. MenW incidence rose from 0.01/100,000 inhabitants in 2009 to a maximum of 0.6/100,000 in 2015. Infants and adults 80 years of age and older were mostly affected, with an incidence peak of 9.7/100,000 and 1.6/100,000, respectively, in 2015. In the group of children from 1 to 4 years of age MenW incidence declined from 1.3/100,000 in 2012 to 0.1/100,000 in 2016, a 92.3% reduction after vaccination implementation. In the same period and age-cohort, CFR decreased from 23% to 0%. High mortality rates concentrated in infants and adults 80 years of age and over.

Conclusion

MenW became predominant in Chile since 2012. IMD cases increased steadily from 2009 to 2016, with higher incidence, CFR and mortality concentrating in infants and people 80 years of age and older. MCV–ACWY provided direct protection against MenW, reducing its incidence after mass meningococcal vaccine implementation. Indirect effects of vaccination are not yet observed.

Section snippets

Background

Invasive meningococcal disease (IMD) is a major public health problem, as it is one of the main causes of sepsis and meningitis worldwide. IMD is of unpredictable occurrence, abrupt clinical manifestations, and associated with high case-fatality rate (CFR) [1], [2]. The majority of invasive disease reported worldwide is caused by six Neisseria meningitidis serogroups: A, B, C, W, X and Y. The distribution of serogroups causing disease varies with age group and geographical location [3], while

Methods

Overall study design. Descriptive analysis of IMD cases registered in Chile, regarding incidence, CFR and mortality from 2009 to 2016, and IMD trend analysis after the introduction of MCV-ACWY. Epidemiologic data was obtained from the National IMD Surveillance and Control Program of the Ministry of Health. Every suspect IMD case must immediately be notified to the regional sanitary authority (SEREMI) by phone call and electronically. SEREMI notifies the Epidemiology Department within the MoH.

Results

Cases description: In the 2009–2016 period, 902 IMD cases were reported to the surveillance system. Microbiologic confirmation achieved 84% (n = 759), with 13.6% (n = 103) confirmation by PCR-based techniques only.

Total MenW cases increased steadily between 2009 and 2014, from 1 to 100 cases respectively, followed by a decline in 2015 and 2016 of about 30%. By age group, 25% of MenW cases in the study period occurred in infants (n = 102), 8% (n = 32) in children 1 to 4 years of age, 8% (n = 32)

Discussion

IMD is a major cause of meningitis and septicaemia worldwide. The ever changing IMD epidemiology together with sudden switches in serogroup predominance contribute to the unpredictable nature of IMD, with significant health, social and economic impact due to high CFR and long-term sequelae [1], [2], [20], [21], [22], [23]. The potential epidemic nature of IMD is the main reason for primary prevention through mass vaccination strategies, as they have been implemented against serogroups A, B and

Declaration of Competing Interest

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Rodolfo Villena has received grants to support research projects from GSK and consultancy fee from Pfizer and Sanofi Pasteur. María Teresa Valenzuela does not report any conflicts of interest. Magdalena Bastías does not report any conflicts of interest. María Elena Santolaya has received grants to support research projects in Men B vaccine from GSK.

Acknowledgements

We greatly appreciate the cooperation of National IMD Surveillance and Control Program of the Ministry of Health, Public Health Institute, and National Immunization Program of Chile for their data contribution.

Funding

No funding was received.

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MenW belonged to a hypervirulent genetic linage P1.5, 2:ST-11, clonal complex 11 (cc11), which became the main cause of IMD [11–14]. Confronted with the MenW outbreak and as part of a comprehensive control strategy, the Chilean MoH implemented a mass meningococcal vaccination campaign using meningococcal ACWY conjugate vaccines (MCV–ACWY) in accordance with approval and license for use at the time [11,15]. The vaccination campaign was implemented in October 2012 through December 2013, targeting children 9 months to 4 years of age.
A serogroup W (MenW) outbreak in Chile prompted a meningococcal vaccination campaign using tetravalent meningococcal-conjugate vaccines (MCV–ACWY) in children since 2012, followed by its introduction into the National Immunization Program (NIP) in toddlers from 2014. Direct protection was observed, but no indirect effects in other age-groups were evidenced. The aim of this study was to describe invasive meningococcal disease (IMD) cases in Chile between 2009 and 2019, and its trend after the introduction of MCV–ACWYs.
IMD cases, cumulative incidence per 100,000 inhabitants, CFR, and vaccination uptake were described. Data were obtained from the Public Health Institute and NIP.
Overall-IMD cases increased in 2009–2014 period, followed by a decline in 2015–2019, focused in infants, children <5 years and people ≥60 years. Serogroup B (MenB) and MenW alternate its predominance. Median overall incidence was 0.6/100,000, increasing from 0.6/100,000 in 2009 to 0.8/100,000 in 2014, later decreasing to 0.4/100,000 in 2019. Median incidences for MenB, serogroup C (MenC) and Y (MenY) were 0.25/100,000, <0.01/100,000 and <0.01/100,000, respectively. Median MenW incidence was 0.53/100,000, increasing from 0.01/100,000 in 2009 to 0.56/100,000 in 2014, followed by a constant decline to 0.12 in 2019. Infants, children <5 years and adults ≥60 years were affected the most, with median incidences of 9.7, 0.9 and 0.93, decreasing to 1.3, 0.1 and 0.1/100,000 in 2019, respectively. Median overall-CFR was 19%, 7.5% for MenB and 24.5% for MenW. Median MCV–ACWY uptake was 93%
Overall-IMD, MenW cases and incidence declined since 2015 after the MCV-ACWY introduction, while MenB, MenC and MenY have been stable. MenW incidence declined in all age groups, including non-immunized infants and people >60 years. Further analysis and a longer period of observation are needed to have a more robust conclusion about this epidemiological trend. By 2019, CFR remains high.
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The bacterium Neisseria meningitidis, a strictly human pathogen, can cause meningitis, meningococcemia, sepsis, and death; repeatedly it scause outbreaks around the world. The frequency of asymptomatic carriage is often high in adolescents and young adults, increasing the invasive meningococcal disease risk and likelihood of transmission. However, detailed analyses of meningococcal carriage in this population in Colombia, particularly in coastal areas, are lacking. In this study, the prevalence and characteristics of Neisseria meningitidis carriage were evaluated in asymptomatic adolescents and young adults (11-25 years old) in Cartagena, Colombia. Oropharynx samples were collected from participants between August and December 2019. The phenotypic identification of bacteria was performed by conventional methods and biochemical testing. Molecular identification to the species level was performed by 16S rRNA gene sequencing. In total, 12 of 648 samples were positive for Neisseria meningitidis by 16S rRNA sequencing, indicating a prevalence of 1.9%. Isolates were classified into four invasive serogroups (A, B, C, and W) by a comparative sequence analysis of the ribosomal gene. Despite the occurrence of meningococcal disease in Cartagena city in the last several years, the frequency of oropharyngeal carriage in adolescents and young adults was low. Serogroup A had not been previously reported in nasopharyngeal samples in Colombia. This is the first report of Neisseria meningitidis on the Colombian Caribbean coast based on 16S rRNA sequencing and is expected to guide the development of vaccination and follow-up strategies.
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Data were obtained from national surveillance systems from 2005 to 2018. Age-stratified incidence and mortality rates were calculated and a descriptive time-series analysis was performed comparing rates in the pre-(2005–2009) and post-vaccination (2011–2018) periods; MD due to specific meningococcal serogroups were analyzed in the pre-(2007–2009) and post-vaccination (2011–2018) periods.
From 2005 to 2018, 31,108 MD cases were reported with 6496 deaths; 35% of cases and deaths occurred in children < 5 years. Incidence and mortality rates declined steadily since 2012 in all age-strata, with significantly lower incidence and mortality in the post-vaccine introduction period in children aged < 1-year, 1–4 years, 5–9 years and 10–14 years. A significant decline in MenC disease in children < 5 years was observed following MenC vaccine introduction; infants < 1 year, from 3.30/100,000 (2007–2009) to 1.08/100,000 (2011–2018) and from 1.44/100,000 to 0.42/100,000 in 1–4-year-olds for these periods. Reductions in MenB disease was also observed. MenW remains an important cause of MD with 748 cases reported across 2005–2018. While initial infant vaccination coverage was high (>95% nationwide), this has since declined (to 83% in 2018); adolescent uptake was < 20% in 2017/18). Regional variations in outcomes and vaccine coverage were observed.
A substantial decline in incidence and mortality rates due to MD was seen following MenC vaccine introduction in Brazil, especially among children < 5 years chiefly driven by reductions in MenC serogroup. While these benefits are considerable, the prevalence of MD due to other serogroups such as MenW and MenB remains a concern. A video summary linked to this article can be found on Figshare: https://doi.org/10.6084/m9.figshare.13379612.v1
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In Chile, after a long period of MenB predominance and stable incidence rates, IMD incidence doubled in 2012 (0.8/100,000) comparing to 2011, associated with the emergence of a hypervirulent genetic lineage MenW: P1.5, 2:ST-11, responsible for >80% of the identified cases. In addition, unusual clinical presentations including gastrointestinal symptoms, increased morbidity, and CFR as high as 28% have been reported for the South American MenWcc11 sublineage.84 In 2012, Chile implemented a reactive immunization campaign with MenACWY conjugate vaccines, initially targeting children aged 9 months to 5 years and, after 2014, as a one-dose schedule at 12 months of age.
Neisseria meningitidis is a major cause of bacterial meningitis and septicaemia worldwide and is associated with high case fatality rates and serious life-long complications among survivors. Twelve serogroups are recognised, of which six (A, B, C, W, X and Y) are responsible for nearly all cases of invasive meningococcal disease (IMD). The incidence of IMD and responsible serogroups vary widely both geographically and over time. For the first time, effective vaccines against all these serogroups are available or nearing licensure. Over the past two decades, IMD incidence has been declining across most parts of the world through a combination of successful meningococcal immunisation programmes and secular trends. The introduction of meningococcal C conjugate vaccines in the early 2000s was associated with rapid declines in meningococcal C disease, whilst implementation of a meningococcal A conjugate vaccine across the African meningitis belt led to near-elimination of meningococcal A disease. Consequently, other serogroups have become more important causes of IMD. In particular, the emergence of a hypervirulent meningococcal group W clone has led many countries to shift from monovalent meningococcal C to quadrivalent ACWY conjugate vaccines in their national immunisation programmes. Additionally, the recent licensure of two protein-based, broad-spectrum meningococcal B vaccines finally provides protection against the most common group responsible for childhood IMD across Europe and Australia. This review describes global IMD epidemiology across each continent and trends over time, the serogroups responsible for IMD, the impact of meningococcal immunisation programmes and future needs to eliminate this devastating disease.
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Meningococcal invasive disease by serogroup W and use of ACWY conjugate vaccines as control strategy in Chile

Abstract

Background

Methods

Results

Conclusion

Section snippets

Background

Methods

Results

Discussion

Declaration of Competing Interest

Acknowledgements

Funding

Lancet

Vaccine.

Lancet Neurol

Vaccine

Vaccine

Vaccine

Lancet

Vaccine

Vaccine

J Infect Public Health

Lancet

Meningococcal disease

N Engl J Med

Invasive meningococcal disease in the vaccine era

Front Pediatr

Neisseria meningitidis: Biology, microbiology, and epidemiology

Methods Mol Biol

Historia y epidemiología del meningococo

Rev Chil Pediatr

Laboratory surveillance for invasive meningococcal disease in Chile, 2006–2012

Rev Chil Infectología

Neisseria meningitidis ST-11 clonal complex, Chile, 2012

Emerg Infect Dis