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Neisseria meningitidis (the meningococcus) is a major human pathogen with a history of high invasive disease burden, particularly in sub-Saharan Africa. Our current understanding of the evolution of meningococcal genomes is limited by the rarity of large-scale genomic population studies and lack of in-depth investigation of the genomic events associated with routine pathogen transmission. Here, we fill this knowledge gap by a detailed analysis of 2839 meningococcal genomes obtained through a carriage study of over 50,000 samples collected systematically in Burkina Faso, West Africa, before, during, and after the serogroup A vaccine rollout, 2009-2012. Our findings indicate that the meningococcal genome is highly dynamic, with highly recombinant loci and frequent gene sharing across deeply separated lineages in a structured population. Furthermore, our findings illustrate how population structure can correlate with genome flexibility, as some lineages in Burkina Faso are orders of magnitude more recombinant than others. We also examine the effect of selection on the population, in particular how it is correlated with recombination. We find that recombination principally acts to prevent the accumulation of deleterious mutations, although we do also find an example of recombination acting to speed the adaptation of a gene. In general, we show the importance of recombination in the evolution of a geographically expansive population with deep population structure in a short timescale. This has important consequences for our ability to both foresee the outcomes of vaccination programs and, using surveillance data, predict when lineages of the meningococcus are likely to become a public health concern.
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Today's world is characterized by increasing population density, human mobility, urbanization, and climate and ecological change. This global dynamic has various effects, including the increased appearance of emerging infectious diseases (EIDs), which pose a growing threat to global health security.Outbreaks of EIDs, like the 2013-2016 Ebola outbreak in West Africa or the current Ebola outbreak in Democratic Republic of the Congo (DRC), have not only put populations in low- and middle-income countries (LMIC) at risk in terms of morbidity and mortality, but they also have had a significant impact on economic growth in affected regions and beyond.The Coalition for Epidemic Preparedness Innovation (CEPI) is an innovative global partnership between public, private, philanthropic, and civil society organizations that was launched as the result of a consensus that a coordinated, international, and intergovernmental plan was needed to develop and deploy new vaccines to prevent future epidemics.CEPI is focusing on supporting candidate vaccines against the World Health Organization (WHO) Blueprint priority pathogens MERS-CoV, Nipah virus, Lassa fever virus, and Rift Valley fever virus, as well as Chikungunya virus, which is on the WHO watch list. The current vaccine portfolio contains a wide variety of technologies, ranging across recombinant viral vectors, nucleic acids, and recombinant proteins. To support and accelerate vaccine development, CEPI will also support science projects related to the development of biological standards and assays, animal models, epidemiological studies, and diagnostics, as well as build capacities for future clinical trials in risk-prone contexts.
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Doenças Transmissíveis Emergentes , Epidemias , Vacinas , África Ocidental , Animais , Surtos de Doenças , Alemanha , HumanosRESUMO
In the original publication of this article, the author name Richard Hatchett was incorrectly published.
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OBJECTIVE: To review the findings of studies of pharyngeal carriage of Neisseria meningitidis and related species conducted in the African meningitis belt since a previous review published in 2007. METHODS: PubMed and Web of Science were searched in July 2018 using the terms 'meningococcal OR Neisseria meningitidis OR lactamica AND carriage AND Africa', with the search limited to papers published on or after 1st January 2007. We conducted a narrative review of these publications. RESULTS: One hundred and thirteen papers were identified using the search terms described above, 20 of which reported new data from surveys conducted in an African meningitis belt country. These papers described 40 surveys conducted before the introduction of the group A meningococcal conjugate vaccine (MenAfriVacR ) during which 66 707 pharyngeal swabs were obtained. Carriage prevalence of N. meningitidis varied substantially by time and place, ranging from <1% to 24%. The mean pharyngeal carriage prevalence of N. meningitidis across all surveys was 4.5% [95% CI: 3.4%, 6.8%] and that of capsulated N. meningitidis was 2.8% [95% CI: 1.9%; 5.2%]. A study of households provided strong evidence for meningococcal transmission within and outside households. The introduction of MenAfriVac® led to marked reductions in carriage of the serogroup A meningococcus in Burkina Faso and Chad. CONCLUSIONS: Recent studies employing standardised methods confirm the findings of older studies that carriage of N. meningitidis in the African meningitis belt is highly variable over time and place, but generally occurs with a lower prevalence and shorter duration than reported from industrialised countries.
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Portador Sadio/epidemiologia , Meningite Meningocócica/epidemiologia , Neisseria meningitidis/isolamento & purificação , África , Humanos , Vacinação em Massa , Meningite Meningocócica/prevenção & controle , Vacinas Meningocócicas/administração & dosagem , Neisseria meningitidis Sorogrupo ARESUMO
BACKGROUND: The introduction of a conjugate vaccine for serogroup A Neisseria meningitidis has dramatically reduced disease in the African meningitis belt. In this context, important questions remain about the performance of different vaccine policies that target remaining serogroups. Here, we estimate the health impact and cost associated with several alternative vaccination policies in Burkina Faso. METHODS AND FINDINGS: We developed and calibrated a mathematical model of meningococcal transmission to project the disability-adjusted life years (DALYs) averted and costs associated with the current Base policy (serogroup A conjugate vaccination at 9 months, as part of the Expanded Program on Immunization [EPI], plus district-specific reactive vaccination campaigns using polyvalent meningococcal polysaccharide [PMP] vaccine in response to outbreaks) and three alternative policies: (1) Base Prime: novel polyvalent meningococcal conjugate (PMC) vaccine replaces the serogroup A conjugate in EPI and is also used in reactive campaigns; (2) Prevention 1: PMC used in EPI and in a nationwide catch-up campaign for 1-18-year-olds; and (3) Prevention 2: Prevention 1, except the nationwide campaign includes individuals up to 29 years old. Over a 30-year simulation period, Prevention 2 would avert 78% of the meningococcal cases (95% prediction interval: 63%-90%) expected under the Base policy if serogroup A is not replaced by remaining serogroups after elimination, and would avert 87% (77%-93%) of meningococcal cases if complete strain replacement occurs. Compared to the Base policy and at the PMC vaccine price of US$4 per dose, strategies that use PMC vaccine (i.e., Base Prime and Preventions 1 and 2) are expected to be cost saving if strain replacement occurs, and would cost US$51 (-US$236, US$490), US$188 (-US$97, US$626), and US$246 (-US$53, US$703) per DALY averted, respectively, if strain replacement does not occur. An important potential limitation of our study is the simplifying assumption that all circulating meningococcal serogroups can be aggregated into a single group; while this assumption is critical for model tractability, it would compromise the insights derived from our model if the effectiveness of the vaccine differs markedly between serogroups or if there are complex between-serogroup interactions that influence the frequency and magnitude of future meningitis epidemics. CONCLUSIONS: Our results suggest that a vaccination strategy that includes a catch-up nationwide immunization campaign in young adults with a PMC vaccine and the addition of this new vaccine into EPI is cost-effective and would avert a substantial portion of meningococcal cases expected under the current World Health Organization-recommended strategy of reactive vaccination. This analysis is limited to Burkina Faso and assumes that polyvalent vaccines offer equal protection against all meningococcal serogroups; further studies are needed to evaluate the robustness of this assumption and applicability for other countries in the meningitis belt.
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Análise Custo-Benefício , Programas de Imunização/economia , Vacinas Meningocócicas/economia , Vacinação/economia , Burkina Faso , Política de Saúde/economia , Modelos Teóricos , Vacinação/legislação & jurisprudência , Vacinação/métodos , Vacinas Conjugadas/economiaRESUMO
BACKGROUND: Meningococcal colonization is a prerequisite for transmission and disease, but the bacterium only very infrequently causes disease while asymptomatic carriage is common. Carriage is highly dynamic, showing a great variety across time and space within and across populations, but also within individuals. The understanding of genetic changes in the meningococcus during carriage, when the bacteria resides in its natural niche, is important for understanding not only the carriage state, but the dynamics of the entire meningococcal population. RESULTS: Paired meningococcal isolates, obtained from 50 asymptomatic carriers about 2 months apart were analyzed with whole genome sequencing (WGS). Phylogenetic analysis revealed that most paired isolates from the same individual were closely related, and the average and median number of allelic differences between paired isolates defined as the same strain was 35. About twice as many differences were seen between isolates from different individuals within the same sequence type (ST). In 8%, different strains were detected at different time points. A difference in ST was observed in 6%, including an individual who was found to carry three different STs over the course of 9 weeks. One individual carried different strains from the same ST. In total, 566 of 1605 cgMLST genes had undergone within-host genetic changes in one or more pairs. The most frequently changed cgMLST gene was relA that was changed in 47% of pairs. Across the whole genome, pilE, differed mostly, in 85% of the pairs. The most frequent mechanisms of genetic difference between paired isolates were phase variation and recombination, including gene conversion. Different STs showed variation with regard to which genes that were most frequently changed, mostly due to absence/presence of phase variation. CONCLUSIONS: This study revealed within-host genetic differences in meningococcal isolates during short-term asymptomatic carriage. The most frequently changed genes were genes belonging to the pilin family, the restriction/modification system, opacity proteins and genes involved in glycosylation. Higher resolution genome-wide sequence typing is necessary to resolve the diversity of isolates and reveals genetic differences not discovered by traditional typing schemes, and would be the preferred choice of technology.
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Doenças Assintomáticas , Interações Hospedeiro-Patógeno/genética , Neisseria meningitidis/genética , Neisseria meningitidis/fisiologia , Sequenciamento Completo do Genoma , Adolescente , Adulto , Alelos , Criança , Pré-Escolar , Etiópia , Feminino , Humanos , Lactente , Masculino , Orofaringe/microbiologia , Filogenia , Polimorfismo de Nucleotídeo Único , Sorogrupo , Adulto JovemRESUMO
BACKGROUND: Neisseria meningitidis colonizes humans and transmits mainly by asymptomatic carriage. We sought to determine the prevalence and epidemiology of meningococcal carriage in Ethiopia prior to the introduction of MenAfriVac, a serogroup A meningococcal conjugate vaccine. METHODS: A cross-sectional meningococcal carriage study was conducted in Arba Minch, southern Ethiopia. A total of 7479 oropharyngeal samples were collected from 1 to 29 year old volunteers, between March and October, 2014. The swabs were cultured for N. meningitidis and Neisseria lactamica in Ethiopia. N. meningitidis isolates were confirmed and characterized by their serogroup, sequence type (ST) and PorA:FetA profile in Norway. RESULTS: Overall carriage prevalence was 6.6 %. There was no significant difference in overall carriage between male (6.7 %) and female (6.4 %) participants. Highest carriage prevalence (10.9 %) for females was found in the 15-19 years of age, while prevalence among males was highest (11.3 %) in the 20-24 age group. Non-groupable isolates dominated (76.4 %), followed by serogroups X (14.0 %) and W (5.9 %) isolates. No serogroup A was found. Most non-groupable isolates were ST-192. Serogroup W isolates were assigned to the ST-11 clonal complex, and serogroup X isolates to the ST-181 and ST-41/44 clonal complexes. Overall carriage prevalence of N. lactamica was 28.1 %. Carriage of N. meningitidis and N. lactamica varied depending on age and geographic area, but there was no association between carriage of the two species. CONCLUSIONS: Epidemic strains of serogroups W and X were circulating in this area of Ethiopia. As no serogroup A was found among the carriage isolates the immediate impact of mass-vaccination with MenAfriVac on transmission of N. meningitidis in this population is expected to be marginal.
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Portador Sadio/epidemiologia , Portador Sadio/microbiologia , Infecções Meningocócicas/epidemiologia , Infecções Meningocócicas/microbiologia , Vacinas Meningocócicas/administração & dosagem , Neisseria meningitidis/isolamento & purificação , Vacinas Conjugadas/administração & dosagem , Adolescente , Adulto , Técnicas de Tipagem Bacteriana , Criança , Pré-Escolar , Estudos Transversais , Etiópia/epidemiologia , Feminino , Humanos , Lactente , Masculino , Vacinação em Massa , Infecções Meningocócicas/prevenção & controle , Prevalência , Adulto JovemRESUMO
BACKGROUND: During the first introduction of a group A meningococcal vaccine (PsA-TT) in 2010-2011 and its rollout from 2011 to 2013, >150 million eligible people, representing 12 hyperendemic meningitis countries, have been vaccinated. METHODS: The new vaccine effectiveness evaluation framework was established by the World Health Organization and partners. Meningitis case-based surveillance was strengthened in PsA-TT first-introducer countries, and several evaluation studies were conducted to estimate the vaccination coverage and to measure the impact of vaccine introduction on meningococcal carriage and disease incidence. RESULTS: PsA-TT implementation achieved high vaccination coverage, and results from studies conducted showed significant decrease of disease incidence as well as significant reduction of oropharyngeal carriage of group A meningococci in vaccinated and unvaccinated individuals, demonstrating the vaccine's ability to generate herd protection and prevent group A epidemics. CONCLUSIONS: Lessons learned from this experience provide useful insights in how to guide and better prepare for future new vaccine introductions in resource-limited settings.
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Portador Sadio/epidemiologia , Portador Sadio/prevenção & controle , Transmissão de Doença Infecciosa/prevenção & controle , Infecções Meningocócicas/epidemiologia , Infecções Meningocócicas/prevenção & controle , Vacinas Meningocócicas/administração & dosagem , Vacinas Meningocócicas/imunologia , Adolescente , Adulto , África/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Masculino , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: The objective of this study was to evaluate the carriage of Neisseria meningitidis (Nm) serogroups X and Y in the health district of Kaya before the introduction of a serogroup A meningococcal conjugate vaccine in Burkina Faso. METHODS: A repeated cross-sectional meningococcal carriage study was conducted in 2009 in eight randomly selected villages in the health district of Kaya, Burkina Faso. In each of 4 sampling rounds at least 1,500 people were enrolled within a 1-month period. RESULTS: From a total of 6,686 throat swabs we identified 419 Nm isolates (6.27%). The dominating serogroups were Y (3.19%) and X (1.05%). Overall carriage was higher in the dry season compared with the rainy season (OR, 1.51; 95% CI, 1.06-2.16). Carriage prevalence of serogroups Y and X varied by round and was highest at the end of the dry season (4.92% and 1.22%, respectively). The only risk factor associated with NmX carriage was vaccination status in contrast to serogroup Y, which was associated with age groups 5-9 years and 10-14 years. CONCLUSION: The presence of Nm serogroups X and Y, which could replace or be added to the serogroup A, is a warning sign. There is a need to strengthen surveillance and laboratory diagnosis of the various meningococcal serogroups circulating in Africa.
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Infecções Meningocócicas/epidemiologia , Vacinas Meningocócicas/administração & dosagem , Neisseria meningitidis/imunologia , Adolescente , Burkina Faso/epidemiologia , Portador Sadio , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Masculino , Infecções Meningocócicas/microbiologia , Infecções Meningocócicas/prevenção & controle , Neisseria meningitidis/classificação , Fatores de Risco , SorogrupoRESUMO
BACKGROUND: The conjugate vaccine against serogroup A Neisseria meningitidis (NmA), MenAfriVac, is currently being introduced throughout the African meningitis belt. In repeated multicentre cross-sectional studies in Burkina Faso we demonstrated a significant effect of vaccination on NmA carriage for one year following mass vaccination in 2010. A new multicentre carriage study was performed in October-November 2012, two years after MenAfriVac mass vaccination. METHODS: Oropharyngeal samples were collected and analysed for presence of N. meningitidis (Nm) from a representative selection of 1-29-year-olds in three districts in Burkina Faso using the same procedures as in previous years. Characterization of Nm isolates included serogrouping, multilocus sequence typing, and porA and fetA sequencing. A small sample of invasive isolates collected during the epidemic season of 2012 through the national surveillance system were also analysed. RESULTS: From a total of 4964 oropharyngeal samples, overall meningococcal carriage prevalence was 7.86%. NmA prevalence was 0.02% (1 carrier), significantly lower (OR, 0.05, P = 0.005, 95% CI, 0.006-0.403) than pre-vaccination prevalence (0.39%). The single NmA isolate was sequence type (ST)-7, P1.20,9;F3-1, a clone last identified in Burkina Faso in 2003. Nm serogroup W (NmW) dominated with a carriage prevalence of 6.85%, representing 87.2% of the isolates. Of 161 NmW isolates characterized by molecular techniques, 94% belonged to the ST-11 clonal complex and 6% to the ST-175 complex. Nm serogroup X (NmX) was carried by 0.60% of the participants and ST-181 accounted for 97% of the NmX isolates. Carriage prevalence of serogroup Y and non-groupable Nm was 0.20% and 0.18%, respectively. Among the 20 isolates recovered from meningitis cases, NmW dominated (70%), followed by NmX (25%). ST-2859, the only ST with a serogroup A capsule found in Burkina Faso since 2004, was not found with another capsule, neither among carriage nor invasive isolates. CONCLUSIONS: The significant reduction of NmA carriage still persisted two years following MenAfriVac vaccination, and no cases of NmA meningitis were recorded. High carriage prevalence of NmW ST-11 was consistent with the many cases of NmW meningitis in the epidemic season of 2012 and the high proportion of NmW ST-11 among the characterized invasive isolates.
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Portador Sadio/epidemiologia , Infecções Meningocócicas/epidemiologia , Vacinas Meningocócicas/uso terapêutico , Neisseria meningitidis Sorogrupo A/isolamento & purificação , Adolescente , Adulto , Infecções Assintomáticas/epidemiologia , Proteínas da Membrana Bacteriana Externa/genética , Burkina Faso/epidemiologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Masculino , Vacinação em Massa , Meningite Meningocócica/epidemiologia , Infecções Meningocócicas/prevenção & controle , Tipagem de Sequências Multilocus , Neisseria meningitidis Sorogrupo A/genética , Orofaringe/microbiologia , Porinas/genética , Prevalência , Vacinação , Adulto JovemRESUMO
Rapid diagnostic tests (RDTs) are critical for preparedness and response against an outbreak or pandemic and have been highlighted in the 100 Days Mission, a global initiative that aims to prepare the world for the next epidemic/pandemic by driving the development of diagnostics, vaccines and therapeutics within 100 days of recognition of a novel Disease X threat.RDTs play a pivotal role in early case identification, surveillance and case management, and are critical for initiating deployment of vaccine and monoclonal antibodies. Currently available RDTs, however, have limited clinical sensitivity and specificity and inadequate validation. The development, validation and implementation of RDTs require adequate and sustained financing from both public and private sources. While the World Health Assembly recently passed a resolution on diagnostic capacity strengthening that urges individual Member States to commit resources towards this, the resolution is not binding and implementation will likely be impeded by limited financial resources and other competing priorities, particularly in low-income countries. Meanwhile, the diagnostic industry has not sufficiently invested in RDT development for high priority pathogens.Currently, vaccine development projects are getting the largest funding support among medical countermeasures. Yet vaccines are insufficient tools in isolation, and pandemic preparedness will be incomplete without parallel investment in diagnostics and therapeutics.The Pandemic Fund, a global financing mechanism recently established for strengthening pandemic prevention, preparedness and response, may be a future avenue for supporting diagnostic development.In this paper, we discuss why RDTs are critical for preparedness and response. We also discuss RDT investment challenges and reflect on the way forward.
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Surtos de Doenças , Preparação para Pandemia , Testes de Diagnóstico Rápido , Humanos , Surtos de Doenças/prevenção & controle , Saúde Global , Pandemias/prevenção & controleRESUMO
BACKGROUND: The conjugate vaccine against serogroup A Neisseria meningitidis (NmA), MenAfriVac, was first introduced in mass vaccination campaigns of 1-29-year-olds in Burkina Faso in 2010. It is not known whether MenAfriVac has an impact on NmA carriage. METHODS: We conducted a repeated cross-sectional meningococcal carriage study in a representative portion of the 1-29-year-old population in 3 districts in Burkina Faso before and up to 13 months after vaccination. One district was vaccinated in September 2010, and the other 2 were vaccinated in December 2010. We analyzed 25 521 oropharyngeal samples, of which 22 093 were obtained after vaccination. RESULTS: In October-November 2010, NmA carriage prevalence in the unvaccinated districts was comparable to the baseline established in 2009, but absent in the vaccinated district. Serogroup X N. meningitidis (NmX) dominated in both vaccinated and unvaccinated districts. With 4 additional sampling campaigns performed throughout 2011 in the 3 districts, overall postvaccination meningococcal carriage prevalence was 6.95%, with NmX dominating but declining for each campaign (from 8.66% to 1.97%). Compared with a baseline NmA carriage prevalence of 0.39%, no NmA was identified after vaccination. Overall vaccination coverage in the population sampled was 89.7%, declining over time in 1-year-olds (from 87.1% to 26.5%), as unvaccinated infants reached 1 year of age. NmA carriage was eliminated in both the vaccinated and unvaccinated population from 3 weeks up to 13 months after mass vaccination (P = .003). CONCLUSIONS: The disappearance of NmA carriage among both vaccinated and unvaccinated populations is consistent with a vaccine-induced herd immunity effect.
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Imunidade Coletiva , Meningite Meningocócica/prevenção & controle , Vacinas Meningocócicas/administração & dosagem , Neisseria meningitidis/isolamento & purificação , Adolescente , Adulto , Burkina Faso , Criança , Pré-Escolar , Estudos Transversais , Surtos de Doenças/prevenção & controle , Feminino , Humanos , Imunidade Coletiva/imunologia , Lactente , Masculino , Meningite Meningocócica/imunologia , Meningite Meningocócica/microbiologia , Neisseria meningitidis/imunologia , Prevalência , Vacinação , Adulto JovemRESUMO
BACKGROUND: The conjugate vaccine against serogroup A Neisseria meningitidis (NmA), MenAfriVac, was first introduced in mass vaccination campaigns of the 1-29-year-olds in Burkina Faso in 2010. The aim of this study was to genetically characterize meningococcal isolates circulating in Burkina Faso before and up to 13 months after MenAfriVac mass vaccination. METHODS: A total of 1,659 meningococcal carriage isolates were collected in a repeated cross-sectional carriage study of the 1-29-year-olds in three districts of Burkina Faso in 2010 and 2011, before and up to 13 months after mass vaccination. Forty-two invasive isolates were collected through the national surveillance in Burkina Faso in the same period. All the invasive isolates and 817 carriage isolates were characterized by serogroup, multilocus sequence typing and porA-fetA sequencing. RESULTS: Seven serogroup A isolates were identified, six in 2010, before vaccination (4 from carriers and 2 from patients), and one in 2011 from an unvaccinated patient; all were assigned to sequence type (ST)-2859 of the ST-5 clonal complex. No NmA carriage isolate and no ST-2859 isolate with another capsule were identified after vaccination. Serogroup X carriage and disease prevalence increased before vaccine introduction, due to the expansion of ST-181, which comprised 48.5% of all the characterized carriage isolates. The hypervirulent serogroup W ST-11 clone that was responsible for most of meningococcal disease in 2011 and 2012 was not observed in 2010; it appeared during the epidemic season of 2011, when it represented 40.6% of the serogroup W carriage isolates. CONCLUSIONS: Successive clonal waves of ST-181 and ST-11 may explain the changing epidemiology in Burkina Faso after the virtual disappearance of NmA disease and carriage. No ST-2859 strain of any serogroup was found after vaccination, suggesting that capsule switching of ST-2859 did not occur, at least not during the first 13 months after vaccination.
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Infecções Meningocócicas/microbiologia , Vacinas Meningocócicas/administração & dosagem , Neisseria meningitidis/isolamento & purificação , Adolescente , Adulto , Antibacterianos/farmacologia , Cápsulas Bacterianas/genética , Burkina Faso , Portador Sadio/microbiologia , Criança , Pré-Escolar , Estudos Transversais , Genótipo , Humanos , Lactente , Vacinação em Massa , Infecções Meningocócicas/prevenção & controle , Testes de Sensibilidade Microbiana , Neisseria meningitidis/efeitos dos fármacos , Neisseria meningitidis/genética , FenótipoRESUMO
Reference materials are critical in assay development for calibrating and assessing their suitability. The devasting nature of the COVID-19 pandemic and subsequent proliferation of vaccine platforms and technologies has meant that there is even a greater need for standards for immunoassay development, which are critical to assess and compare vaccines' responses. Equally important are the standards needed to control the vaccine manufacturing processes. Standardized vaccine characterization assays throughout process development are essential for a successful Chemistry, Manufacturing and Controls (CMC) strategy. In this perspective paper, we advocate for reference material incorporation into assays and their calibration to International Standards from preclinical vaccine development through control testing and provide insight into why this is necessary. We also provide information on the availability of WHO international antibody standards for CEPI-priority pathogens.
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Neisseria lactamica is a true commensal bacterium occupying the same ecological niche as the pathogenic Neisseria meningitidis, which is responsible for outbreaks and large epidemics, especially in sub-Saharan Africa. To better understand the epidemiology of N. lactamica in Africa and its relationship to N. meningitidis, we studied N. lactamica carriage in 1- to 29-year-old people living in three districts of Burkina Faso from 2009 to 2011. N. lactamica was detected in 18.2% of 45,847 oropharyngeal samples. Carriage prevalence was highest among the 2-year-olds (40.1%) and decreased with age. Overall prevalence was higher for males (19.1%) than females (17.5%) (odds ratio [OR], 1.11; 95% confidence interval [CI], 1.04 to 1.18), while among the 18- to 29-year-olds, carriage prevalence was significantly higher in women (9.1%) than in men (3.9%) (OR, 2.49; 95% CI, 1.94 to 3.19). Carriage prevalence of N. lactamica was remarkably homogeneous in the three districts of Burkina Faso and stable over time, in comparison with carriage of N. meningitidis (P. A. Kristiansen et al., Clin. Vaccine Immunol. 18:435-443, 2011). There was no significant seasonal variation of N. lactamica carriage and no significant change in carriage prevalence after introduction of the serogroup A meningococcal conjugate vaccine, MenAfriVac. Multilocus sequence typing was performed on a selection of 142 isolates. The genetic diversity was high, as we identified 62 different genotypes, of which 56 were new. The epidemiology of N. lactamica carriage and the molecular characteristics of carried isolates were similar to those reported from industrialized countries, in contrast to the particularities of N. meningitidis carriage and disease epidemiology in Burkina Faso.
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Portador Sadio/epidemiologia , Neisseria lactamica/isolamento & purificação , Infecções por Neisseriaceae/epidemiologia , Adolescente , Adulto , Burkina Faso/epidemiologia , Portador Sadio/microbiologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Variação Genética , Humanos , Lactente , Masculino , Epidemiologia Molecular , Tipagem de Sequências Multilocus , Neisseria lactamica/classificação , Neisseria lactamica/genética , Infecções por Neisseriaceae/microbiologia , Orofaringe/microbiologia , Prevalência , Adulto JovemRESUMO
PURPOSE OF REVIEW: The emergence of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has affected lives of billions of individuals, globally. There is an urgent need to develop interventions including vaccines to control the ongoing pandemic. RECENT FINDINGS: Development of tools for fast-tracked testing including small and large animal models for vaccine efficacy analysis, assays for immunogenicity assessment, critical reagents, international biological standards, and data sharing allowed accelerated development of vaccines. More than 300 vaccines are under development and 9 of them are approved for emergency use in various countries, with impressive efficacy ranging from 50 to 95%. Recently, several new SARS-CoV-2 variants have emerged and are circulating globally, and preliminary findings imply that some of them may escape immune responses against previous variants and diminish efficacy of current vaccines. Most of these variants acquired new mutations in their surface protein (Spike) which is the antigen in most of the approved/under development vaccines. SUMMARY: In this review, we summarize novel and traditional approaches for COVID-19 vaccine development including inactivated, attenuated, nucleic acid, vector and protein based. Critical assessment of humoral and cell-mediated immune responses induced by vaccines has shown comparative immunogenicity profiles of various vaccines in clinical phases. Recent reports confirmed that some currently available vaccines provide partial to complete protection against emerging SARS-CoV-2 variants. If more mutated variants emerge, current vaccines might need to be updated accordingly either by developing vaccines matching the circulating strain or designing multivalent vaccines to extend the breadth.
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BACKGROUND: In the first 2 years after a nationwide mass vaccination campaign of 1-29-year-olds with a meningococcal serogroup A conjugate vaccine (MenAfriVac) in Burkina Faso, carriage and disease due to serogroup A Neisseria meningitidis were nearly eliminated. We aimed to assess the long-term effect of MenAfriVac vaccination on meningococcal carriage and herd immunity. METHODS: We did four cross-sectional studies of meningococcal carriage in people aged 9 months to 36 years in two districts of Burkina Faso between May 2, 2016, and Nov 6, 2017. Demographic information and oropharyngeal swabs were collected. Meningococcal isolates were characterised using whole-genome sequencing. FINDINGS: Of 14â295 eligible people, 13â758 consented and had specimens collected and laboratory results available, 1035 of whom were meningococcal carriers. Accounting for the complex survey design, prevalence of meningococcal carriage was 7·60% (95% CI 5·67-9·52), including 6·98% (4·86-9·11) non-groupable, 0·48% (0·01-0·95) serogroup W, 0·10% (0·01-0·18) serogroup C, 0·03% (0·00-0·80) serogroup E, and 0% serogroup A. Prevalence ranged from 5·44% (95% CI 4·18-6·69) to 9·14% (6·01-12·27) by district, from 4·67% (2·71-6·64) to 11·17% (6·75-15·59) by round, and from 3·39% (0·00-8·30) to 10·43% (8·08-12·79) by age group. By clonal complex, 822 (88%) of 934 non-groupable isolates were CC192, all 83 (100%) serogroup W isolates were CC11, and nine (69%) of 13 serogroup C isolates were CC10217. INTERPRETATION: Our results show the continued effect of MenAfriVac on serogroup A meningococcal carriage, for at least 7 years, among vaccinated and unvaccinated cohorts. Carriage prevalence of epidemic-prone serogroup C CC10217 and serogroup W CC11 was low. Continued monitoring of N meningitidis carriage will be crucial to further assess the effect of MenAfriVac and inform the vaccination strategy for future multivalent meningococcal vaccines. FUNDING: Bill & Melinda Gates Foundation and Gavi, the Vaccine Alliance.
Assuntos
Vacinação em Massa , Infecções Meningocócicas/prevenção & controle , Vacinas Meningocócicas/imunologia , Neisseria meningitidis/isolamento & purificação , Adolescente , Adulto , Burkina Faso/epidemiologia , Portador Sadio , Criança , Pré-Escolar , Estudos Transversais , Humanos , Lactente , Infecções Meningocócicas/epidemiologia , Adulto JovemRESUMO
Neisseria meningitidis colonizes the human oropharynx and transmits mainly via asymptomatic carriage. Actual outbreaks of meningococcal meningitis are comparatively rare and occur when susceptible populations are exposed to hypervirulent clones, genetically distinct from the main carriage isolates. However, carriage isolates can evolve into pathogens through a limited number of recombination events. The present study examines the potential for the sequence type (ST)-192, by far the dominant clone recovered in recent meningococcal carriage studies in sub-Saharan Africa, to evolve into a pathogen. We used whole-genome sequencing on a collection of 478 meningococcal isolates sampled from 1- to 29- year-old healthy individuals in Arba Minch, southern Ethiopia in 2014. The ST-192 clone was identified in nearly 60â% of the carriers. Using complementary short- and long-read techniques for whole-genome sequencing, we were able to completely resolve genomes and thereby identify genomic differences between the ST-192 carriage strain and known pathogenic clones with the highest possible resolution. We conclude that it is possible, but unlikely, that ST-192 could evolve into a significant pathogen, thus, becoming the major invasive meningococcus clone in the meningitis belt of Africa following upcoming mass vaccination with a polyvalent conjugate vaccine that targets the A, C, W, Y and X capsules.