Dataset Information

Outbreak of Neisseria meningitidis serogroup C outside the meningitis belt-Liberia, 2017: an epidemiological and laboratory investigation.

ABSTRACT: BACKGROUND:On April 25, 2017, a cluster of unexplained illnesses and deaths associated with a funeral was reported in Sinoe County, Liberia. Molecular testing identified Neisseria meningitidis serogroup C (NmC) in specimens from patients. We describe the epidemiological investigation of this cluster and metagenomic characterisation of the outbreak strain. METHODS:We collected epidemiological data from the field investigation and medical records review. Confirmed, probable, and suspected cases were defined on the basis of molecular testing and signs or symptoms of meningococcal disease. Metagenomic sequences from patient specimens were compared with 141 meningococcal isolate genomes to determine strain lineage. FINDINGS:28 meningococcal disease cases were identified, with dates of symptom onset from April 21 to April 30, 2017: 13 confirmed, three probable, and 12 suspected. 13 patients died. Six (21%) patients reported fever and 23 (82%) reported gastrointestinal symptoms. The attack rate for confirmed and probable cases among funeral attendees was 10%. Metagenomic sequences from six patient specimens were similar to a sequence type (ST) 10217 (clonal complex [CC] 10217) isolate genome from Niger, 2015. Multilocus sequencing identified five of seven alleles from one specimen that matched ST-9367, which is represented in the PubMLST database by one carriage isolate from Burkina Faso, in 2011, and belongs to CC10217. INTERPRETATION:This outbreak featured high attack and case fatality rates. Clinical presentation was broadly consistent with previous meningococcal disease outbreaks, but predominance of gastrointestinal symptoms was unusual compared with previous African meningitis epidemics. The outbreak strain was genetically similar to NmC CC10217, which caused meningococcal disease outbreaks in Niger and Nigeria. CC10217 had previously been identified only in the African meningitis belt. FUNDING:US Global Health Security.

SUBMITTER: Bozio CH

PROVIDER: S-EPMC6545567 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Outbreak of Neisseria meningitidis serogroup C outside the meningitis belt-Liberia, 2017: an epidemiological and laboratory investigation.

Bozio Catherine H CH Vuong Jeni J Dokubo E Kainne EK Fallah Mosoka P MP McNamara Lucy A LA Potts Caelin C CC Doedeh John J Gbanya Miatta M Retchless Adam C AC Patel Jaymin C JC Clark Thomas A TA Kohar Henry H Nagbe Thomas T Clement Peter P Katawera Victoria V Mahmoud Nuha N Djingarey Harouna M HM Perrocheau Anne A Naidoo Dhamari D Stone Mardia M George Roseline N RN Williams Desmond D Gasasira Alex A Nyenswah Tolbert T Wang Xin X Fox LeAnne M LM

The Lancet. Infectious diseases 20181015 12

<h4>Background</h4>On April 25, 2017, a cluster of unexplained illnesses and deaths associated with a funeral was reported in Sinoe County, Liberia. Molecular testing identified Neisseria meningitidis serogroup C (NmC) in specimens from patients. We describe the epidemiological investigation of this cluster and metagenomic characterisation of the outbreak strain.<h4>Methods</h4>We collected epidemiological data from the field investigation and medical records review. Confirmed, probable, and sus ...[more]

PMID: 30337259

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Project description:ObjectiveThe optimal long-term vaccination strategies to provide population-level protection against serogroup A Neisseria meningitidis (MenA) are unknown. We developed an age-structured mathematical model of MenA transmission, colonization, and disease in the African meningitis belt, and used this model to explore the impact of various vaccination strategies.MethodsThe model stratifies the simulated population into groups based on age, infection status, and MenA antibody levels. We defined the model parameters (such as birth and death rates, age-specific incidence rates, and age-specific duration of protection) using published data and maximum likelihood estimation. We assessed the validity of the model by comparing simulated incidence of invasive MenA and prevalence of MenA carriage to observed incidence and carriage data.ResultsThe model fit well to observed age- and season-specific prevalence of carriage (mean pseudo-R2 0.84) and incidence of invasive disease (mean R2 0.89). The model is able to reproduce the observed dynamics of MenA epidemics in the African meningitis belt, including seasonal increases in incidence, with large epidemics occurring every eight to twelve years. Following a mass vaccination campaign of all persons 1-29 years of age, the most effective modeled vaccination strategy is to conduct mass vaccination campaigns every 5 years for children 1-5 years of age. Less frequent campaigns covering broader age groups would also be effective, although somewhat less so. Introducing conjugate MenA vaccine into the EPI vaccination schedule at 9 months of age results in higher predicted incidence than periodic mass campaigns.DiscussionWe have developed the first mathematical model of MenA in Africa to incorporate age structures and progressively waning protection over time. Our model accurately reproduces key features of MenA epidemiology in the African meningitis belt. This model can help policy makers consider vaccine program effectiveness when determining the feasibility and benefits of MenA vaccination strategies.

Project description: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.

Project description:BackgroundNigeria reports high rates of mortality linked with recurring meningococcal meningitis outbreaks within the African meningitis belt. Few studies have thoroughly described the response to these outbreaks to provide strong and actionable public health messages. We describe how time delays affected the response to the 2016/2017 meningococcal meningitis outbreak in Nigeria.MethodsUsing data from Nigeria Centre for Disease Control (NCDC), National Primary Health Care Development Agency (NPHCDA), World Health Organisation (WHO), and situation reports of rapid response teams, we calculated attack and death rates of reported suspected meningococcal meningitis cases per week in Zamfara, Sokoto and Yobe states respectively, between epidemiological week 49 in 2016 and epidemiological week 25 in 2017. We identified when alert and epidemic thresholds were crossed and determined when the outbreak was detected and notified in each state. We examined response activities to the outbreak.ResultsThere were 12,535 suspected meningococcal meningitis cases and 877 deaths (CFR: 7.0%) in the three states. It took an average time of three weeks before the outbreaks were detected and notified to NCDC. Four weeks after receiving notification, an integrated response coordinating centre was set up by NCDC and requests for vaccines were sent to International Coordinating Group (ICG) on vaccine provision. While it took ICG one week to approve the requests, it took an average of two weeks for approximately 41% of requested vaccines to arrive. On the average, it took nine weeks from the date the epidemic threshold was crossed to commencement of reactive vaccination in the three states.ConclusionThere were delays in detection and notification of the outbreak, in coordinating response activities, in requesting for vaccines and their arrival from ICG, and in initiating reactive vaccination. Reducing these delays in future outbreaks could help decrease the morbidity and mortality linked with meningococcal meningitis outbreaks.

Dataset Information

Outbreak of Neisseria meningitidis serogroup C outside the meningitis belt-Liberia, 2017: an epidemiological and laboratory investigation.

Publications

Outbreak of Neisseria meningitidis serogroup C outside the meningitis belt-Liberia, 2017: an epidemiological and laboratory investigation.

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