[Historical review of the epidemic situation, prevention and control of epidemic cerebrospinal meningitis during 1966 to 1967].

During the winter and spring of 1966 to 1967, the nationwide revolution networking not only exerted great pressure on food, housing and transportation, but also triggered the most serious nationwide epidemic cerebrospinal meningitis outbreak in history. The students of the revolution networking were the disseminators of the disease and the first group of patients. The unprecedented scale and scope of the epidemic, the destroyed medical and health order and other factors exacerbated the epidemic situation. Zhou Enlai restarted the " prevention and treatment by masses " mode to gradually control the epidemic. Fifty years later, looking back on the history of the epidemic situation and prevention and control of epidemic cerebrospinal meningitis, many problems are worth pondering deeply.

A New Sequence Type of Neisseria meningitidis Serogroup C Associated With a 2016 Meningitis Outbreak in Mali.

In 2016, Mali reported a bacterial meningitis outbreak consisting of 39 suspected cases between epidemiologic weeks 9 and 17 with 15% case fatality ratio in the health district of Ouéléssebougou, 80 kilometers from the capital Bamako. Cerebrospinal fluid specimens from 29 cases were tested by culture and real-time polymerase chain reaction; 22 (76%) were positive for bacterial meningitis pathogens, 16 (73%) of which were Neisseria meningitidis (Nm). Of the Nm-positive specimens, 14 (88%) were N meningitidis serogroup C (NmC), 1 was NmW, and 1 was nongroupable. Eight NmC isolates recovered by culture from the outbreak were characterized using whole genome sequencing. Genomics analysis revealed that all 8 isolates belonged to a new sequence type (ST) 12446 of clonal complex 10217 that formed a distinct clade genetically similar to ST-10217, a NmC strain that recently caused large epidemics of meningitis in Niger and Nigeria. The emergence of a new ST of NmC associated with an outbreak in the African meningitis belt further highlights the need for continued molecular surveillance in the region.

Neisseria meningitidis Serogroup W Meningitis Epidemic in Togo, 2016.

BACKGROUND: During 2014, 4 regions in Togo within the African meningitis belt implemented vaccination campaigns with meningococcal serogroup A conjugate vaccine (MACV). From January to July 2016, Togo experienced its first major Neisseria meningitidis serogroup W (NmW) outbreak. We describe the epidemiology, response, and management of the outbreak. METHODS: Suspected, probable, and confirmed cases were identified using World Health Organization case definitions. Through case-based surveillance, epidemiologic and laboratory data were collected for each case. Cerebrospinal fluid specimens were analyzed by polymerase chain reaction, culture, or latex agglutination. Vaccination campaigns were conducted in affected districts. RESULTS: From January 11 to July 5, 2016, 1995 suspected meningitis cases were reported, with 128 deaths. Among them, 479 (24.0%) were confirmed by laboratory testing, and 94 (4.7%) and 1422 (71.3%) remained as probable and suspected cases, respectively. Seven epidemic districts had cumulative attack rates greater than 100 per 100 000 population. Of the confirmed cases, 91.5% were NmW; 39 of 40 available NmW isolates were sequence type-11/clonal complex-11. CONCLUSIONS: This outbreak demonstrates that, although high coverage with MACV has reduced serogroup A outbreaks, large meningococcal meningitis outbreaks due to other serogroups may continue to occur; effective multivalent meningococcal conjugate vaccines could improve meningococcal disease prevention within meningitis belt populations.

Development and Implementation of a Cloud-Based Meningitis Surveillance and Specimen Tracking System in Burkina Faso, 2018.

Nationwide case-based meningitis surveillance was established in Burkina Faso following the introduction of meningococcal serogroup A conjugate vaccine in 2010. However, timely tracking and arrival of cerebrospinal fluid specimens for confirmation at national reference laboratories remained suboptimal. To better understand this gap and identify bottlenecks, the Burkina Faso Ministry of Health, along with key partners, developed and implemented a cloud-based System for Tracking Epidemiological Data and Laboratory Specimens (STELAB), allowing for timely nationwide data reporting and specimen tracking using barcodes. STELAB was adapted to Burkina Faso's infrastructure to ensure suitability, functionality, flexibility, and sustainability. We describe the design, development, and implementation of STELAB. In addition, we discuss strategies used to promote sustainability, lessons learned during the first year of implementation, and future directions. STELAB's novel design and country-driven approach has the potential to achieve sustainable real-time data reporting and specimen tracking for the first time in sub-Saharan Africa.

Meningococcal Meningitis Outbreaks in the African Meningitis Belt After Meningococcal Serogroup A Conjugate Vaccine Introduction, 2011-2017.

BACKGROUND: In 2010-2017, meningococcal serogroup A conjugate vaccine (MACV) was introduced in 21 African meningitis belt countries. Neisseria meningitidis A epidemics have been eliminated here; however, non-A serogroup epidemics continue. METHODS: We reviewed epidemiological and laboratory World Health Organization data after MACV introduction in 20 countries. Information from the International Coordinating Group documented reactive vaccination. RESULTS: In 2011-2017, 17 outbreaks were reported (31 786 suspected cases from 8 countries, 1-6 outbreaks/year). Outbreaks were of 18-14 542 cases in 113 districts (median 3 districts/outbreak). The most affected countries were Nigeria (17 375 cases) and Niger (9343 cases). Cumulative average attack rates per outbreak were 37-203 cases/100 000 population (median 112). Serogroup C accounted for 11 outbreaks and W for 6. The median proportion of laboratory confirmed cases was 20%. Reactive vaccination was conducted during 14 outbreaks (5.7 million people vaccinated, median response time 36 days). CONCLUSION: Outbreaks due to non-A serogroup meningococci continue to be a significant burden in this region. Until an affordable multivalent conjugate vaccine becomes available, the need for timely reactive vaccination and an emergency vaccine stockpile remains high. Countries must continue to strengthen detection, confirmation, and timeliness of outbreak control measures.

Improving Case-Based Meningitis Surveillance in 5 Countries in the Meningitis Belt of Sub-Saharan Africa, 2015-2017.

BACKGROUND: The MenAfriNet consortium was established in 2014 to support implementation of case-based meningitis surveillance in 5 countries in the meningitis belt of sub-Saharan Africa: Burkina Faso, Chad, Mali, Niger, and Togo. Assessing surveillance performance is critical for interpretation of the collected data and implementation of future surveillance-strengthening initiatives. METHODS: Detailed epidemiologic and laboratory data were collected on suspected meningitis cases through case-based meningitis surveillance in participating districts in 5 countries. Performance of case-based surveillance was evaluated through sensitivity of case ascertainment in case-based versus aggregate meningitis surveillance and an analysis of surveillance indicators. RESULTS: From 2015 to 2017, 18 262 suspected meningitis cases were identified through case-based surveillance and 16 262 were identified through aggregate surveillance, for a case ascertainment sensitivity of 112.3%. Among suspected cases, 16 885 (92.5%) had a cerebrospinal fluid (CSF) specimen collected, 13 625 (80.7%) of which were received at a national reference laboratory. Among these, 13 439 (98.6%) underwent confirmatory testing, and, of those tested, 4371 (32.5%) were confirmed for a bacterial pathogen. CONCLUSIONS: Overall strong performance for case ascertainment, CSF collection, and laboratory confirmation provide evidence for the quality of MenAfriNet case-based surveillance in evaluating epidemiologic trends and informing future vaccination strategies.

Vaccine Development and Collaborations: Lessons from the History of the Meningococcal A Vaccine (1969-73).

Based on a wide range of historical sources, including published scientific literature and archives (Institut Mérieux, WHO and IMTSSA), this article examines the history of the development of the meningococcal A vaccine between 1969 and 1973. It explores the social factors of vaccine development including various collaborations, informal discussions, the circulation of products and materials, formal meetings, trials and setbacks to highlight the complex reality of the development, production and use of the vaccine. Inscribed in a 'Golden Age' of vaccine development and production, this episode not only adds to the scholarship on the history of vaccines, which has tended to focus on a narrative of progress, but also considers the sharing of knowledge through collaborations, and the risks involved in the development of a vaccine. Finally, this perspective reveals the uncertainties and difficulties underlying the production of an effective vaccine.

Vaccine development as a 'doable problem': The case of the meningococcal A vaccines 1962-1969.

During the period from 1962 to 1967, the development of a meningococcal A vaccine could be considered as feasible despite all the drawbacks of working with cerebrospinal meningitis A. In this paper, I analyse why and how this programme for vaccine development was put into place, and in particular how the problem was perceived as feasible. Deploying the concept of Doable Problems developed by Joan Fujimura, I examine the complex range of factors that led to the outcome of the trial in Yako in 1967. Thus I show how the different protagonists were mobilized and their work organized at different levels in order to produce and test a vaccine. Indeed, a number of elements seemed to stand in the way of successfully producing a vaccine, but the collaboration of the different actors under the aegis of the WHO provides interesting lessons about the management of this kind of project. Seen in a wider historical context, this approach could provide ideas and lessons for approaching current questions in vaccination from a new perspective.

A probable prehistoric case of meningococcal disease from San Francisco Bay: Next generation sequencing of Neisseria meningitidis from dental calculus and osteological evidence.

Next Generation Sequencing (NGS) of ancient dental calculus samples from a prehistoric site in San Francisco Bay, CA-SCL-919, reveals a wide range of potentially pathogenic bacteria. One older adult woman, in particular, had high levels of Neisseria meningitidis and low levels of Haemophilus influenzae, species that were not observed in the calculus from three other individuals. Combined with the presence of incipient endocranial lesions and pronounced meningeal grooves, we interpret this as an ancient case of meningococcal disease. This disease afflicts millions around the globe today, but little is known about its (pre)history. With additional sampling, we suggest NGS of calculus offers an exciting new window into the evolutionary history of these bacterial species and their interactions with humans.

Evolution of Sequence Type 4821 Clonal Complex Meningococcal Strains in China from Prequinolone to Quinolone Era, 1972-2013.

The expansion of hypervirulent sequence type 4821 clonal complex (CC4821) lineage Neisseria meningitidis bacteria has led to a shift in meningococcal disease epidemiology in China, from serogroup A (MenA) to MenC. Knowledge of the evolution and genetic origin of the emergent MenC strains is limited. In this study, we subjected 76 CC4821 isolates collected across China during 1972-1977 and 2005-2013 to phylogenetic analysis, traditional genotyping, or both. We show that successive recombination events within genes encoding surface antigens and acquisition of quinolone resistance mutations possibly played a role in the emergence of CC4821 as an epidemic clone in China. MenC and MenB CC4821 strains have spread across China and have been detected in several countries in different continents. Capsular switches involving serogroups B and C occurred among epidemic strains, raising concerns regarding possible increases in MenB disease, given that vaccines in use in China do not protect against MenB.

Genomic Surveillance of 4CMenB Vaccine Antigenic Variants among Disease-Causing Neisseria meningitidis Isolates, United Kingdom, 2010-2016.

In September 2015, 4CMenB meningococcal vaccine was introduced into the United Kingdom infant immunization program without phase 3 trial information. Understanding the effect of this program requires enhanced surveillance of invasive meningococcal disease (IMD) Neisseria meningitidis isolates and comparison with prevaccination isolates. Bexsero Antigen Sequence Types (BASTs) were used to analyze whole-genome sequences of 3,073 prevaccine IMD N. meningitidis isolates obtained during 2010-2016. Isolates exhibited 803 BASTs among 31 clonal complexes. Frequencies of antigen peptide variants were factor H binding protein 1, 13.4%; Neisserial heparin-binding antigen 2, 13.8%; Neisseria adhesin A 8, 0.8%; and Porin A-VR2:P1.4,10.9%. In 2015-16, serogroup B isolates showed the highest proportion (35.7%) of exact matches to >1 Bexsero components. Serogroup W isolates showed the highest proportion (93.9%) of putatively cross-reactive variants of Bexsero antigens. Results highlighted the likely role of cross-reactive antigens. BAST surveillance of meningococcal whole-genome sequence data is rapid, scalable, and portable and enables international comparisons of isolates.

Current status of cerebrospinal meningitis and impact of the 2015 meningococcal C vaccination in Kebbi, Northwest Nigeria.

INTRODUCTION: Following the significant reduction of Neisseria meningitidis A (NmA) in most parts of northern Nigeria, a new strain of Neisseria meningitidis C (NmC) emerged in 2013 causing outbreaks in the north and recently spreading to southern parts of the Nigeria. This study provides detailed epidemiological investigation in the last four years. METHODS: Analysis of confirmed and suspected cases of meningitis in Kebbi, Nigeria from 2014 to June 2017 detected through Integrated Disease Surveillance and Response. RESULTS: Of the 2776 cases, 1568 were males, and 1208 females. The median age of males and females was 10 and 11 years (Interquartile range of ages is 9 years) respectively. The attack rate (AR) per 100,000 in the state between 2014 and 2017 was 13.2, 46.7, 2.2 and 3.2 respectively. Case fatality rate (CFR) in 2014 was highest in the 4 years analysed at 13.8%. Binary logistic regression analysis suggests that the odds of confirmation of meningitis was 3.6 (Odds ratio, OR 3.60, 95% CI 1.58-8.2; p = 0.002) times as high in the age group 6-10 years and 2.4 times in the age group 11-19 years compared to the age group 0-5 years (OR 2.44, 95% CI 1.09-5.48; p = 0.03). An epidemic of NmC in 2015, led to a reactive vaccination campaign in selected wards in Aliero and Jega targeting age groups 1-29 years old, with a coverage of 72% and 51% respectively. In 2016-2017 Aliero and Jega local government areas (LGA) had no recorded deaths due to meningitis, a significant improvement over 2015 mortality rates (MR) per 100,000 of 33.4 and 12.2 respectively. CONCLUSION: The CFR in the state is still very high, suggesting the need for a more coordinated approach aimed at improving disease notification and early treatment. Vaccination in Aliero and Jega LGAs have demonstrated the usefulness of meningococcal C vaccine in reduction of morbidity and mortality.

Deep coal mining and meningococcal meningitis in England and Wales, 1931-38: Ecological study, with implications for deep shaft mining activities worldwide.

The hypothesized role of deep coal mining in the development of community-based outbreaks of meningococcal meningitis has gone largely unexplored. Taking the coalfields of Britain as a historical testbed, techniques of linear and binomial logistic regression were used to assess the association between meningococcal meningitis rates and male occupation rates for coal mining in England and Wales during the national epidemic of 1931-32 and in its aftermath. Adjusting for the epidemiological effects of age, residential density, recent changes in the number of families, housing stock and low social class, the analysis yielded evidence of a significant and positive association between coal mining occupation rates and notified levels of meningitis activity in the epidemic period. Communities in areas of the world that currently maintain substantial deep coal extraction industries may be at increased risk for the epidemic transmission of meningococcal meningitis.

Serogroup B Meningococcal Disease Vaccine Recommendations at a University, New Jersey, USA, 2016.

In response to a university-based serogroup B meningococcal disease outbreak, the serogroup B meningococcal vaccine Trumenba was recommended for students, a rare instance in which a specific vaccine brand was recommended. This outbreak highlights the challenges of using molecular and immunologic data to inform real-time response.

Adverse events following quadrivalent meningococcal CRM-conjugate vaccine (Menveo®) reported to the Vaccine Adverse Event Reporting system (VAERS), 2010-2015.

BACKGROUND: Limited data are available describing the post-licensure safety of meningococcal vaccines, including Menveo®. We reviewed reports of adverse events (AEs) to the Vaccine Adverse Event Reporting System (VAERS) to assess safety in all age groups. METHODS: VAERS is a national spontaneous vaccine safety surveillance system co-administered by the Centers for Disease Control and Prevention and the US Food and Drug Administration. We searched the VAERS database for US reports of adverse events in persons who received Menveo from 1 January 2010 through 31 December 2015. We clinically reviewed reports and available medical records for serious AEs, selected pre-specified outcomes, and vaccination during pregnancy. We used empirical Bayesian data mining to identify AEs that were disproportionately reported after receipt of Menveo. RESULTS: During the study period, VAERS received 2614 US reports after receipt of Menveo. Of these, 67 were classified as serious, including 1 report of death. Adolescents (aged 11-18years) accounted for 74% of reports. Most of the reported AEs were non-serious and described AEs consistent with data from pre-licensure studies. Anaphylaxis and syncope were the two most common events in the serious reports. We did not identify any new safety concerns after review of AEs that exceeded the data mining threshold, although we did observe disproportionate reporting for terms that were not associated with an adverse event (e.g., "incorrect drug dosage form administered", "wrong technique in drug usage process"). Although reports were limited, we did not find any evidence for concern regarding the use of Menveo during pregnancy. CONCLUSIONS: In our review of VAERS reports, findings of AEs were consistent with the data from pre-licensure studies. Vaccine providers should continue to emphasize and adhere to proper administration of the vaccine.

Sequence Type 4821 Clonal Complex Serogroup B Neisseria meningitidis in China, 1978-2013.

Serogroup B Neisseria meningitidis strains belonging to sequence type 4821 clonal complex (CC4821), a hyperinvasive lineage first identified for serogroup C in 2003, have been increasingly isolated in China. We characterized the outer membrane protein genes of 48 serogroup B and 214 serogroup C strains belonging to CC4821 and analyzed the genomic sequences of 22 strains. Four serogroup B strains had porin A (i.e., PorA), PorB, and ferric enterobactin transport (i.e., FetA) genotypes identical to those for serogroup C. Phylogenetic analysis of the genomic sequences showed that the 22 CC4821 strains from patients and healthy carriers were unevenly clustered into 2 closely related groups; each group contained serogroup B and C strains. Serogroup B strains appeared variable at the capsule locus, and several recombination events had occurred at uncertain breakpoints. These findings suggest that CC4821 serogroup C N. meningitidis is the probable origin of highly pathogenic CC4821 serogroup B strains.

Neisseria meningitidis ST-11 clonal complex, Chile 2012.

Serogroup W Neisseria meningitidis was the main cause of invasive meningococcal disease in Chile during 2012. The case-fatality rate for this disease was higher than in previous years. Genotyping of meningococci isolated from case-patients identified the hypervirulent lineage W:P1.5,2:ST-11, which contained allele 22 of the fHbp gene.

Prevalence of meningococcal meningitis in China from 2005 to 2010.

BACKGROUND: We aimed to estimate the prevalence and epidemiologic characteristics of meningococcal meningitis (MM) in mainland China (excluding Taiwan, Hong Kong, and Macau) and to provide reference data for controlling the outbreak and prevalence of MM. METHODS: Data from the National Notifiable Diseases Registry System and the MM case information reporting system from 2005 to 2010 as well as data from the MM Surveillance System were used. RESULTS: The morbidity of MM for the whole country was, on average, 0.09 cases per 100,000 (range 0.02 [2010]-0.18 [2005] cases per 100,000) from 2005 to 2010, the incidence rate was highest in the Xinjiang autonomous region (average 0.56 cases per 100,000), and the majority of cases came from Anhui province (average 0.32 cases per 100,000). Morbidity was highest in children under 1 year old (average 0.60 cases per 100,000). The proportion of laboratory-confirmed cases of serogroups A, B, and C were 37.2, 11.5 and 42.7, respectively, from 2005 to 2010. CONCLUSIONS: The incidence level declined year-to-year in mainland China. Children and students are the most at risk groups. The proportion of serogroup C cases has increased year-to-year, and new cases of serogroup W135 have been found. Controlling the epidemic of serogroup C and preventing outbreaks of serogroup B and W135 represent major future challenges.

Neisseria meningitidis serogroup W, Burkina Faso, 2012.

In 2010, Burkina Faso became the first country to introduce meningococcal serogroup A conjugate vaccine (PsA-TT). During 2012, Burkina Faso reported increases in Neisseria meningitidis serogroup W, raising questions about whether these cases were a natural increase in disease or resulted from serogroup replacement after PsA-TT introduction. We analyzed national surveillance data to describe the epidemiology of serogroup W and genotyped 61 serogroup W isolates. In 2012, a total of 5,807 meningitis cases were reported through enhanced surveillance, of which 2,353 (41%) were laboratory confirmed. The predominant organism identified was N. meningitidis serogroup W (62%), and all serogroup W isolates characterized belonged to clonal complex 11. Although additional years of data are needed before we can understand the epidemiology of serogroup W after PsA-TT introduction, these data suggest that serogroup W will remain a major cause of sporadic disease and has epidemic potential, underscoring the need to maintain high-quality case-based meningitis surveillance after PsA-TT introduction.

Typhus syncopalis: an epidemic in Connecticut in 1823.

In 1825 Dr. Thomas Miner wrote about an epidemic that occurred in Middletown, Connecticut in 1823. He called this disease "Typhus syncopalis," sinking typhus, or New England spotted fever. Differences in the understanding of disease processes in the early 19th century preclude a definitive modern equivalent fortyphus syncopalis. In addition, there are disagreements among Dr. Miners' contemporaries with regard to fever classification systems. Examination of the symptoms and physical findings as described by Dr. Miner suggest the presence of encephalitis or meningitis as well as a syndrome resembling a shock-like state. Based on symptom comparisons, this paper suggests that typhus syncopalis was likely meningococcemia caused by Neisseria meningiditis.