Explore the vast range of titles available.

Although invasive meningococcal disease caused by serogroup A is not prevalent in developed countries, a considerable number of cases were recently recorded in Greece. In this study, serogroup A meningococcal disease was compared prospectively with meningococcal disease caused by other serogroups, using similar settings of testing and management during a 5-year period between 1999 and 2003. The Neisseria meningitidis serogroup was determined in 262 cases. Serogroup B predominated, accounting for 158 (60%) of the cases. Serogroup A was second most frequent (19%), followed by serogroups W135 (11%), C (8%), and Y (2%). No cases due to serogroup C were recorded during the last year of the study. Patients with serogroup A disease were older and had a milder course compared to patients infected with serogroups B or C. Toxic appearance, purpura, thrombocytopenia, abnormal coagulation tests, and the need for admission to the intensive care unit, fluid resuscitation, inotropic drugs, and mechanical ventilation were less common. Although morbidity and mortality were lower in these patients, the differences were not significant. Serogroup B is predominant in our area, and the introduction of an effective vaccine against it is a priority. Serogroup A has emerged as the second most common serogroup, but the illness associated with it is milder.

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. We reviewed epidemiological and laboratory World Health Organization data after MACV introduction in 20 countries. Information from the International Coordinating Group documented reactive vaccination. 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). 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.

A novel meningococcal serogroup A conjugate vaccine (MACV [MenAfriVac]) was developed as part of efforts to prevent frequent meningitis outbreaks in the African meningitis belt. The MACV was first used widely and with great success, beginning in December 2010, during initial deployment in Burkina Faso, Mali, and Niger. Since then, MACV rollout has continued in other countries in the meningitis belt through mass preventive campaigns and, more recently, introduction into routine childhood immunization programs associated with extended catch-up vaccinations. We reviewed country reports on MACV campaigns and routine immunization data reported to the World Health Organization (WHO) Regional Office for Africa from 2010 to 2018, as well as country plans for MACV introduction into routine immunization programs. By the end of 2018, 304 894 726 persons in 22 of 26 meningitis belt countries had received MACV through mass preventive campaigns targeting individuals aged 1-29 years. Eight of these countries have introduced MACV into their national routine immunization programs, including 7 with catch-up vaccinations for birth cohorts born after the initial rollout. The Central African Republic introduced MACV into its routine immunization program immediately after the mass 1- to 29-year-old vaccinations in 2017 so no catch-up was needed. From 2010 to 2018, successful rollout of MACV has been recorded in 22 countries through mass preventive campaigns followed by introduction into routine immunization programs in 8 of these countries. Efforts continue to complete MACV introduction in the remaining meningitis belt countries to ensure long-term herd protection.

Analysis of meningococcal strains recovered from outbreaks and epidemics in the African meningitis belt, using molecular methods, has demonstrated for nearly 20 years the dominance among serogroup A organisms of a single clone complex, the sequence type 5 (ST-5) complex. However, a shift was observed since the mid-1990s when ST-5 gradually was replaced by ST-7 in all countries of the region. Since 2001, outbreaks caused by serogroup W135 strains belonging to the ST-11 complex became an additional problem. Monitoring of the clones responsible for meningococcal disease provides important insights on the biology and epidemiology of this most serious pathogen.

In the African “meningitis belt,” outbreaks of meningococcal meningitis occur in cycles, representing a model for the role of host-pathogen interactions in epidemic processes. The periodicity of the epidemics is not well understood, nor is it currently possible to predict them. In our longitudinal colonization and disease surveys, we have observed waves of clonal replacement with the same serogroup, suggesting that immunity to noncapsular antigens plays a significant role in natural herd immunity. Here, through comparative genomic analysis of 100 meningococcal isolates, we provide a high-resolution view of the evolutionary changes that occurred during clonal replacement of a hypervirulent meningococcal clone (ST-7) by a descendant clone (ST-2859). We show that the majority of genetic changes are due to homologous recombination of laterally acquired DNA, with more than 20% of these events involving acquisition of DNA from other species. Signals of adaptation to evade herd immunity were indicated by genomic hot spots of recombination. Most striking is the high frequency of changes involving the pgl locus, which determines the glycosylation patterns of major protein antigens. High-frequency changes were also observed for genes involved in the regulation of pilus expression and the synthesis of Maf3 adhesins, highlighting the importance of these surface features in host-pathogen interaction and immune evasion. IMPORTANCE While established meningococcal capsule polysaccharide vaccines are protective through the induction of anticapsular antibodies, findings of our longitudinal studies in the African meningitis belt have indicated that immunity to noncapsular antigens plays a significant role in natural herd immunity. Our results show that meningococci evade herd immunity through the rapid homologous replacement of just a few key genomic loci that affect noncapsular cell surface components. Identification of recombination hot spots thus represents an eminent approach to gain insight into targets of protective natural immune responses. Moreover, our results highlight the role of the dynamics of the protein glycosylation repertoire in immune evasion by Neisseria meningitidis . These results have major implications for the design of next-generation protein-based subunit vaccines. While established meningococcal capsule polysaccharide vaccines are protective through the induction of anticapsular antibodies, findings of our longitudinal studies in the African meningitis belt have indicated that immunity to noncapsular antigens plays a significant role in natural herd immunity. Our results show that meningococci evade herd immunity through the rapid homologous replacement of just a few key genomic loci that affect noncapsular cell surface components. Identification of recombination hot spots thus represents an eminent approach to gain insight into targets of protective natural immune responses. Moreover, our results highlight the role of the dynamics of the protein glycosylation repertoire in immune evasion by Neisseria meningitidis . These results have major implications for the design of next-generation protein-based subunit vaccines.

Although Neisseria meningitidis is a highly variable organism, most invasive disease is caused by a minority of genotypes. Hypervirulent lineages have been identified and their pandemic spread has been traced. During a longitudinal meningococcal colonization study in a district of northern Ghana clonal waves of carriage and disease were observed. Genetic diversification of genoclouds was analysed by pulsed field gel electrophoretic (PFGE) analysis of isolates from healthy carriers and from meningitis patients. Even during the limited time of persistence in the district, microevolution of the dominating genoclouds took place. Population genomic analyses are required to understand the genetic basis for the emergence of new lineages with epidemic potential, which is of crucial importance for the development of long-term global vaccination strategies against meningococcal disease.

Abstract In particular in the ‘meningitis belt’ of sub-Saharan Africa, epidemic meningococcal meningitis is a severe public health problem. In the past decades, serogroup A lineages have been the dominant etiologic agents, but also other serogroups have caused outbreaks. A comprehensive vaccine based on subcapsular outer membrane proteins (OMPs) is not available. Here, we have investigated whether meningococcal populations overcome herd immunity by changing antigenic properties of their OMPs. Meningococcal isolates were collected in the context of longitudinal studies in Ghana between 2002 and 2008 and in Burkina Faso between 2006 and 2007. Serogroup A strains isolated during two clonal waves of colonization and disease showed no diversification in the genes encoding their PorA, PorB, and FetA proteins. However, we detected occasional allelic exchange of opa genes, as well as wide variation in the number of intragenic tandem repeats, showing that phase variation of Opa protein expression is a frequent event. Altogether we observed a remarkable antigenic stability of the PorA, PorB and FetA proteins over years. Our results indicate that while herd immunity may be responsible for the disappearance of meningococcal clones over time, it is not a strong driving force for antigenic diversification of the major OMPs analyzed here. This very interesting study compares outer membrane protein sequences in a number of Neisseria meningitidis serogroup. A disease and carriage isolates from a defined region or subsaharan Africa between 2002 and 2008. It concludes that there is a remarkable antigenic stability in this population and that herd immunity is not a strong driving force for antigenic diversification. The study is well conceived and carried out, the results are clearly presented and the conclusions pertinent. This is important and useful information

Neisseria meningitidis is a common commensal bacterium of the nasopharynx that can cause invasive meningococcal disease (IMD). In comparison, N. gonorrhoeae is always a pathogen usually limited to mucosal sites. However, increased evidence for overlapping clinical syndromes is emerging. We compared N. meningitidis samples from a urogenital outbreak in Australia with sequences from the United States and other countries. We conducted phylogenetic analyses to assess relatedness and examine for genomic changes associated with meningococcal adaptation; we collated a total of 255 serogroup Y (MenY), sequence type (ST) 1466 isolate assemblies. Most urogenital isolates originated from Australia; those isolates formed a distinct clade, most closely related genomically to recent US IMD isolates. No specific genomic changes suggested niche adaptation or associated clinical manifestations. The MenY ST1466 N. meningitidis isolates circulating in Australia and the United States are capable of causing both urethritis and invasive meningococcal disease.

A novel multicomponent vaccine against meningococcal capsular group B (MenB) disease contains four major components: factor-H-binding protein, neisserial heparin binding antigen, neisserial adhesin A, and outer-membrane vesicles derived from the strain NZ98/254. Because the public health effect of the vaccine, 4CMenB (Novartis Vaccines and Diagnostics, Siena, Italy), is unclear, we assessed the predicted strain coverage in Europe. We assessed invasive MenB strains isolated mainly in the most recent full epidemiological year in England and Wales, France, Germany, Italy, and Norway. Meningococcal antigen typing system (MATS) results were linked to multilocus sequence typing and antigen sequence data. To investigate whether generalisation of coverage applied to the rest of Europe, we also assessed isolates from the Czech Republic and Spain. 1052 strains collected from July, 2007, to June, 2008, were assessed from England and Wales, France, Germany, Italy, and Norway. All MenB strains contained at least one gene encoding a major antigen in the vaccine. MATS predicted that 78% of all MenB strains would be killed by postvaccination sera (95% CI 63–90, range of point estimates 73–87% in individual country panels). Half of all strains and 64% of covered strains could be targeted by bactericidal antibodies against more than one vaccine antigen. Results for the 108 isolates from the Czech Republic and 300 from Spain were consistent with those for the other countries. MATS analysis showed that a multicomponent vaccine could protect against a substantial proportion of invasive MenB strains isolated in Europe. Monitoring of antigen expression, however, will be needed in the future. Novartis Vaccines and Diagnostics.

Meningococci spread via respiratory droplets, whereas the closely related gonococci are transmitted sexually. Several outbreaks of invasive meningococcal disease have been reported in Europe and the United States among men who have sex with men (MSM). We recently identified an outbreak of serogroup C meningococcal disease among MSM in Germany and France. In this study, genomic and proteomic techniques were used to analyze the outbreak isolates. In addition, genetically identical urethritis isolates were recovered from France and Germany and included in the analysis. Genome sequencing revealed that the isolates from the outbreak among MSM and from urethritis cases belonged to a clade within clonal complex 11. Proteome analysis showed they expressed nitrite reductase, enabling anaerobic growth as previously described for gonococci. Invasive isolates from MSM, but not urethritis isolates, further expressed functional human factor H binding protein associated with enhanced survival in a newly developed transgenic mouse model expressing human factor H, a complement regulatory protein. In conclusion, our data suggest that urethritis and outbreak isolates followed a joint adaptation route including adaption to the urogenital tract.