Australian Meningococcal Surveillance Programme annual report, 2019.

Invasive meningococcal disease (IMD) is a notifiable disease in Australia, and both probable and laboratory-confirmed cases of IMD are reported to the National Notifiable Diseases Surveillance System (NNDSS). In 2019, there were 206 notifications of IMD. Of these, 202 were laboratory-confirmed cases analysed by the reference laboratories of the Australian National Neisseria Network (NNN). Of the 202 laboratory-confirmed cases of IMD, 167 were confirmed by bacterial culture and 35 by nucleic acid amplification testing, and all had the serogroup determined. Fine typing was available on 146 samples (146/202, 72%). Neisseria meningitidis serogroup B (MenB) infections accounted for 50.0% (101/202); MenW for 26.2% (53/202); MenY for 20.8% (42/202) and MenC for 3.0% of cases (6/202). Of the MenW cases, 88% were PorA antigen type P1.5,2, and 65% of these (24/37) were sequence type 11, the hypervirulent strain reported in recent outbreaks in Australia and overseas. The primary peaks of IMD notifications in Australia in 2019 were observed in infants less than 1 year of age (36/202, 18%) and in adults aged 65 years or older (39/202, 19%). MenB infections predominated in those aged less than 5 years and those aged 15-19 years, whereas MenW and MenY infections predominated in those aged 45 years or more. All 167 IMD isolates were tested for antimicrobial susceptibility. One isolate out of these 167 (0.6%) was resistant to penicillin with an MIC ≥ 1mg/L; 154/167 isolates (92%) had decreased susceptibility to penicillin. All isolates were susceptible to ceftriaxone and ciprofloxacin, and one isolate was resistant to rifampicin.

[About the Chilean meningococcal epidemic (1941-1942): The children with septic shock 80 years ago from a medical and social perspective]. / A propósito de la epidemia meningocóccica chilena (1941-1942): El niño con shock séptico hace 80 años desde la perspectiva médica y social.

In our country, meningococcal disease has a low endemic and high lethality, with epidemic out breaks; some of them of historical character, like the one happened during the first half of the last century. The action of a group of doctors, pioneers in clinical, research and teaching aspects, together with the health personnel that constituted their team, immersed in a successful public health policy, allowed to consolidate the necessary care of the sick child of this serious pathology, as well as many others, thus enabling the development of a structured and scientific proposal, in the light of the knowledge available at that time. Therefore, after 80 years, it is important to review the various clini cal, pathophysiological and therapeutic aspects, in addition to the hospital and social context, of this successful history of the Chilean public health system.

A propósito de la epidemia meningocóccica chilena (1941-1942): el niño con shock séptico hace 80 años desde la perspectiva médica y social / About the Chilean meningococcal epidemic (1941-1942): the children with septic shock 80 years ago from a medical and social perspective

Resumen: En nuestro país, la enfermedad meningocóccica presenta una baja endemia y alta letalidad, con exis tencia de brotes epidémicos, algunos de ellos de carácter histórico, como el acaecido durante la pri mera mitad del siglo pasado. La acción de un grupo de médicos, pioneros en los aspectos clínicos, de investigación y docencia, junto al personal de salud que constituía su equipo, inmersos en una política pública sanitaria exitosa, permitieron consolidar el cuidado necesario del niño enfermo de esta grave patología, como también de muchas otras, posibilitando así el desarrollo de una propuesta estructurada y científica a la luz del conocimiento disponible en aquella época. Por ello, luego de 80 años, es importante revisar los diversos aspectos clínicos, fisiopatológicos y terapéuticos, además del contexto hospitalario y social de esta exitosa historia del sistema de salud público chileno.

Abstract: In our country, meningococcal disease has a low endemic and high lethality, with epidemic out breaks; some of them of historical character, like the one happened during the first half of the last century. The action of a group of doctors, pioneers in clinical, research and teaching aspects, together with the health personnel that constituted their team, immersed in a successful public health policy, allowed to consolidate the necessary care of the sick child of this serious pathology, as well as many others, thus enabling the development of a structured and scientific proposal, in the light of the knowledge available at that time. Therefore, after 80 years, it is important to review the various clini cal, pathophysiological and therapeutic aspects, in addition to the hospital and social context, of this successful history of the Chilean public health system.

Standing on the shoulders of giants: two centuries of struggle against meningococcal disease.

Meningococcal disease was first clinically characterised by Gaspard Vieusseux in 1805, and its causative agent was identified by Anton Weichselbaum in 1887, who named it Diplococcus intracellularis menigitidis. From the beginning, the disease was dreaded because of its epidemic nature, predilection for previously healthy children and adolescents, and high mortality. In the last decade of the 19th century, the concept of serum therapy for toxin-related bacterial diseases was identified. This concept was applied to meningococcal disease therapy, in an independent way, by Wilhelm Kolle, August von Wasserman, and Georg Jochmann in Germany, and Simon Flexner in the USA, resulting in the first successful approach for the treatment of meningococcal disease. During the first three decades of the 20th century, serum therapy was the standard treatment for meningococcal disease. With the advent of sulphamides first and then antibiotics, serum therapy was abandoned. The great challenges that infectious diseases medicine is facing and the awaiting menaces in the future in terms of increasing antibiotic resistance, emergence of new pathogens, and re-emergence of old ones without effective therapy, make passive immunotherapy a promising tool. Acknowledging the achievements of our predecessors might teach us some lessons to bring light to our future.

Neonatal Conjunctivitis Caused by Neisseria meningitidis US Urethritis Clade, New York, USA, August 2017.

We characterized a case of neonatal conjunctivitis in New York, USA, caused by Neisseria meningitidis by using whole-genome sequencing. The case was a rare occurrence, and the isolate obtained belonged to an emerging clade (N. meningitidis US nongroupable urethritis) associated with an increase in cases of urethritis since 2015.

University-Based Outbreaks of Meningococcal Disease Caused by Serogroup B, United States, 2013-2018.

We reviewed university-based outbreaks of meningococcal disease caused by serogroup B and vaccination responses in the United States in the years following serogroup B meningococcal (MenB) vaccine availability. Ten university-based outbreaks occurred in 7 states during 2013-2018, causing a total of 39 cases and 2 deaths. Outbreaks occurred at universities with 3,600-35,000 undergraduates. Outbreak case counts ranged from 2 to 9 cases; outbreak duration ranged from 0 to 376 days. All 10 universities implemented MenB vaccination: 3 primarily used MenB-FHbp and 7 used MenB-4C. Estimated first-dose vaccination coverage ranged from 14% to 98%. In 5 outbreaks, additional cases occurred 6-259 days following MenB vaccination initiation. Although it is difficult to predict outbreak trajectories and evaluate the effects of public health response measures, achieving high MenB vaccination coverage is crucial to help protect at-risk persons during outbreaks of meningococcal disease caused by this serogroup.

Hospitalization rates and outcome of invasive bacterial vaccine-preventable diseases in Tuscany: a historical cohort study of the 2000-2016 period.

BACKGROUND: Invasive bacterial diseases (IBD) are a serious cause of hospitalization, sequelae and mortality. Albeit a low incidence, an increase in cases due to H. influenzae was registered in the past 4 years and, in the Tuscany region, an excess of cases due to N. meningitidis since 2015 is alarming. The purpose of this study is to deepen the knowledge of IBD epidemiology in Tuscany with particular attention to temporal trends. METHODS: Tuscan residents hospitalized for IBD from January 1st 2000 to March 18th 2016 were selected from the regional hospital discharge database based on ICD-9-CM codes. Age-specific and standardized hospitalization rates were calculated together with case-fatality rates (CFRs). A time-trend analysis was performed; whereas, prognostic factors of death were investigated through univariable and multivariable analyses. RESULTS: The average standardized hospitalization rates for invasive meningococcal diseases (IMD), invasive pneumococcal diseases and invasive diseases due to H. influenzae from 2000 to 2016 were 0.6, 1.8, and 0.2 per 100,000, respectively. The average CFRs were 10.5%, 14.5% and 11.5% respectively with higher values in the elderly. Older age was significantly associated with higher risk of death from all IBD. A significant reduction in hospitalization rates for IMD was observed after meningococcal C conjugate vaccine introduction. The Annual Percentage Change (APC) was -13.5 (95% confidence interval (CI) -22.3; -3.5) in 2005-2013 but has risen since that period. Furthermore, a significant increasing trend of invasive diseases due to H. influenzae was observed from 2005 onwards in children 1-4 years old (APC 13.3; 95% CI 0; 28.3). CONCLUSIONS: This study confirms changes in the epidemiology of invasive diseases due to H. influenzae and IMD. Furthermore, attention is called to the prevention of IBD in the elderly because of the age group's significantly higher rate of hospitalizations and deaths for all types of IBD.

Novel approaches to Neisseria meningitidis vaccine design.

A range of vaccines is available for preventing life-threatening diseases caused by infection with Neisseria meningitidis (meningococcus, Men). Capsule polysaccharide (CPS)-conjugate vaccines are successful prophylactics for serogroup MenA, MenC, MenW and MenY infections, and outer membrane vesicle (OMV) vaccines have been used successfully for controlling clonal serogroup MenB infections. MenB vaccines based on recombinant proteins identified by reverse vaccinology (Bexsero™) and proteomics (Trumenba™) approaches have recently been licensed and Bexsero™ has been introduced into the UK infant immunisation programme. In this review, we chart the development of these licensed vaccines. In addition, we discuss the plethora of novel vaccinology approaches that have been applied to the meningococcus with varying success in pre-clinical studies, but which provide technological platforms for application to other pathogens. These strategies include modifying CPS, lipooligosaccharide and OMV; the use of recombinant proteins; structural vaccinology approaches of designing synthetic peptide/mimetope vaccines, DNA vaccines and engineered proteins; epitope presentation on biological and synthetic particles; through vaccination with live-attenuated pathogen(s), or with heterologous bacteria expressing vaccine antigens, or to competitive occupation of the nasopharyngeal niche by commensal bacterial spp. After close to a century of vaccine research, it is possible that meningococcal disease may be added, shortly, to the list of diseases to have been eradicated worldwide by rigorous vaccination campaigns.

Emergency Meningococcal ACWY Vaccination Program for Teenagers to Control Group W Meningococcal Disease, England, 2015-2016.

During the first 12 months of an emergency meningococcal ACWY vaccination program for teenagers in England, coverage among persons who left school in 2015, the first cohort to be vaccinated, was 36.6%. There were 69% fewer group W meningococcal cases than predicted by trend analysis and no cases in vaccinated teenagers.

Australian Meningococcal Surveillance Programme annual report, 2016.

In 2016, there were 243 laboratory-confirmed cases of invasive meningococcal disease analysed by the Australian National Neisseria Network. This number was the highest number of laboratory confirmed cases since 2008. Probable and laboratory confirmed invasive meningococcal disease (IMD) are notifiable in Australia, and there were 252 IMD cases notified to the National Notifiable Diseases Surveillance System in 2016, the highest number reported since 2010. Meningococcal serogrouping was able to be determined for 98% (237/243) of laboratory confirmed IMD cases. Serogroup B infections accounted for 87 cases (37%), the lowest number and proportion reported since inception of the Australian Meningococcal Surveillance Programme (AMSP) in 1997. In contrast, the number and proportion of serogroup W infections (44%, 107 cases) in 2016 was the highest since the AMSP began. In addition, the number and proportion of serogroup Y infections (16%, 40 cases) was also the highest recorded by the AMSP. Molecular typing results were available for 225 of the 243 IMD cases. Of the serogroup W IMD strains that were able to be genotyped, 92% (97/105) have the PorA antigen encoding gene type P1.5,2 and of these, 72% (70/97) were sequence type 11, the same type as the hypervirulent serogroup W strain that has been circulating in the UK and South America since 2009. The primary IMD age peak was observed in adults aged 45 years or more, whilst secondary disease peaks were observed in those aged less than 5 years, and in adolescents aged 15-19 years. Serogroup B infections predominated in the age groups less than 1 year and 20-24 years, whereas serogroup W infections predominated in those aged 45 years or more. For all other age groups, distribution of serogroup B and W infections was roughly equal. Of the IMD isolates tested for antimicrobial susceptibility, 6% (11/189) were resistant to penicillin, and decreased susceptibility to penicillin was observed in a further 90% (170/189) of isolates. One Men W isolate demonstrated an elevated minimum inhibitory concentration (MIC) to ceftriaxone (0.125mg/L), the highest reported in Australia. All isolates tested were susceptible to rifampicin and ciprofloxacin.

Australian Meningococcal Surveillance Programme annual report, 2014.

In 2014 there were 165 laboratory-confirmed cases of invasive meningococcal disease analysed by the Australian National Neisseria Network. This number was higher than the number reported in 2013, but was the second lowest reported since inception of the Australian Meningococcal Surveillance Programme in 1994. Probable and laboratory confirmed invasive meningococcal disease (IMD) are notifiable in Australia, and there were 170 IMD cases notified to the National Notifiable Diseases Surveillance System (NNDSS) in 2014. This was also higher than in 2013, but was the second lowest number of IMD cases reported to the NNDSS. The meningococcal serogroup was determined for 161/165 (98%) of laboratory confirmed IMD cases. Of these, 80.1% (129 cases) were serogroup B infections; 1.9% (3 cases) were serogroup C infections; 9.9% (16 cases) were serogroup W135; and 8.1% (13 cases) were serogroup Y. Primary and secondary disease peaks were observed in those aged 4 years or less, and in adolescents (15-19 years) respectively. Serogroup B cases predominated in all jurisdictions and age groups, except for those aged 65 years or over, where serogroups Y and W135 combined predominated. The overall proportion and number of IMD caused by serogroup B was higher than in 2013, but has decreased from previous years. The number of cases of IMD caused by serogroup C was the lowest reported to date. The number of IMD cases caused by serogroup Y was similar to previous years, but the number of IMD cases caused serogroup W135 was higher than in 2013. The proportion of IMD cases caused by serogroups Y and W135 has increased in recent years, whilst the overall number of cases of IMD has decreased. Molecular typing was able to be performed on 106 of the 165 IMD cases. In 2014, the most common porA genotypes circulating in Australia were P1.7-2,4 and P1.22,14. All IMD isolates tested were susceptible to ceftriaxone and ciprofloxacin. There were 2 isolates that were resistant to rifampicin. Decreased susceptibility to penicillin was observed in 88% of isolates.

The Burden of Pediatric Invasive Meningococcal Disease in Spain (2008-2013).

BACKGROUND: Invasive meningococcal disease remains a rare infectious disease not only with high mortality but also with important morbidity. Until recently no universal vaccine existed against serogroup B, which explains most of the cases in settings like Europe. The objective of this study was to analyze the clinical course and sequelae of meningococcal disease in Spain. METHODS: Retrospective review of all children younger than 15 years admitted to any of the 36 hospitals in the MENDICOS Spanish network (www.mendicos.org) with confirmed or probable invasive meningococcal disease in children between January 2008 and December 2013. RESULTS: A total of 458 cases were identified across the country, most of them occurring in previously healthy children (91.5%; n = 419/458). Median (interquartile range) age was 1.7 (0.7 and 4.6) years, with 53.1% of the cases occurring in children younger than 2 years; 82.1% (n = 368) were laboratory confirmed cases; 95.2% (n = 256) of those serogrouped were serogroup B. The diagnosis was meningitis in 24.9% (n = 114) of the cases, sepsis in 37.1% (n = 170) and both in 38.0% (n = 174). Mean hospital length of stay was 11.6 (10.9) days; 79.2% (n = 354) of the patients required pediatric intensive care unit admission, with a mean pediatric intensive care unit stay of 3.9 (4.9) days; 3.5% (n = 16) died; 12.9% (n = 59) of the survivors were discharged with some kind of physical sequelae, mainly neurological (n = 23). CONCLUSIONS: Serogroup B invasive meningococcal infection explains substantial morbidity and mortality in Spain, occurring mainly in infants. The recent availability of a vaccine against serogroup B may change this scenario. Given that the vast majority of the cases occur in otherwise healthy children, inclusion of the meningococcal B vaccine in the national immunization program should be carefully considered.

Carriage of Neisseria meningitidis in the Hajj and Umrah mass gatherings.

Meningococcal disease is a serious public health threat, especially during mass gatherings such as Hajj and Umrah which provide optimal conditions for disease transmission. The disease is caused by Neisseria meningitidis and transmitted mainly via asymptomatic carriers. A review of the literature on asymptomatic N. meningitidis carriage among Hajj and Umrah pilgrims and their household contacts was performed. Carriage studies reported carriage rates to be higher in Hajj pilgrims compared to Umrah pilgrims and that these events promote acquisition of carriage among pilgrims. With some outliers, most studies found carriage rates among pilgrims to be comparable to those in populations under non-epidemic settings. However, these results should be interpreted with caution, taking into account the limitations within the studies identified. A wide variety of N. meningitidis serogroups appear to be circulating among Hajj and Umrah pilgrims, with serogroups W135 and B being most prominent. Current Hajj and Umrah meningococcal disease preventative measures do not necessarily prevent carriage and transmission, which may result in local and international outbreaks among susceptible populations. Monitoring carriage states of visitors and local inhabitants in the Kingdom of Saudi Arabia, as well as the implementation of preventive measures that impact carriage, are warranted to reduce the risk of Hajj and Umrah-related meningococcal disease outbreaks.

Rise in invasive serogroup W meningococcal disease in Australia 2013-2015.

Since 2013, there has been an increase in the number of notified cases of invasive meningococcal disease (IMD) due to serogroup W (MenW) in Australia. In response to this observed increase, the Communicable Diseases Network Australia convened a working group in 2015 to collate and analyse the epidemiology of MenW disease nationally. Enhanced surveillance data collected by jurisdictions were collated and analysed, and whole genome sequencing (WGS) of MenW isolates assessed the genomic relatedness of strains between 2012 and 2015. This report describes that epidemiology. Since 2013, the incidence and proportion of MenW has increased in Australia, rising from an average of 2% of all IMD cases annually (range 0% to 5%) between 1991 and 2012; to 8% (12/149) of cases in 2013, 10% (17/169) in 2014, and 19% (34/182) in 2015. Victoria has been the main affected state, with 50% (17/34) of national cases in 2015. MenW has affected older populations, with a median age between 2003 and 2015 being 44 years. During this period, case fatality was 10.7% (17/159), 2.3 times higher than for all IMD serogroups combined (4.7%, 173/3720). There were 7 deaths due to MenW in 2015 (CFR 21%). WGS has found the majority of Australian isolates cluster within a group of W:P1.5,2:F1-1:ST11 isolates from the United Kingdom and South America, regions where rapid spread and endemic transmission has occurred since 2009. The recent increase in incidence of MenW in Australia is evolving and is being closely monitored. Lessons learned from the international experience will be important in informing the public health response.