Search Results (11)

Neisseria meningitidis is commensal of the human pharynx and occasionally invades the host, causing the life-threatening illness invasive meningococcal disease. The meningococcus is a highly diverse and adaptable organism thanks to natural competence, a propensity for recombination, and a highly repetitive genome. These mechanisms together result in a high level of antigenic variation to invade diverse human hosts and evade their innate and adaptive immune responses. This review explores the ways in which this diversity contributes to the evolutionary history and population structure of the meningococcus, with a particular focus on microevolution. It examines studies on meningococcal microevolution in the context of within-host evolution and persistent carriage; microevolution in the context of meningococcal outbreaks and epidemics; and the potential of microevolution to contribute to antimicrobial resistance and vaccine escape. A persistent theme is the idea that the process of microevolution contributes to the development of new hyperinvasive meningococcal variants. As such, microevolution in this species has significant potential to drive future public health threats in the form of hypervirulent, antibiotic-resistant, vaccine-escape variants. The implications of this on current vaccination strategies are explored. Full article

The meningococcal meningitis (MM) vaccine reduces the incidence of MM significantly; however, outbreaks still occur in communities with high vaccine coverage. We aimed to analyze the driving factors of infection from a community outbreak. A total of 266 children aged 9 to 15 years old from the three junior high schools of Tongzi county were identified. We documented infection cases using laboratory tests and analyzed attack rates, infection rates and risk factors for transmission. The index case in School A was identified, and the attack rate in School A was 0.03%. Children showed a significantly low infection rate of MenC in School A (13.2% vs. 19.5% in total children, p = 0.002), while exhibiting significantly high infection rates of MenA in School B (44.1% vs. 24.8% in total children, p < 0.001) and MenB in School C (11.1% vs. 4.1% in total children, p = 0.015). The infection rate of MenA for females (30.0%) was higher (p = 0.055) than for males (19.9%). In School A, 63.19% of children were vaccinated against MenC, while in School B the rate was 42.65% and in School C, it was 59.26%. Three male MenC infection cases were detected as breakthrough infection cases in addition to the index case. The findings suggest that the current full-course immunization has limited long-term effectiveness and is inefficient in preventing the transmission of MM among older children. Full article

Background: Based on previous studies (regional and national), Tijuana, Baja California, Mexico (across the border from San Diego, California, USA), has been shown to have the highest rate of meningococcal meningitis (MeM) in the country. However, the reason for this high incidence has not yet been established. To explain this regional/endemic public health problem, we aimed to evaluate whether there is a climatic association with MeM in the region. In the “African Meningitis Belt,” the Harmattan seasons are associated with MeM outbreaks; similarly, the Santa Ana winds (SAWs) seasons are characterized by hot and dry winds (similar to Harmattan seasons) that occur seasonally in Southwest California, USA, and Northwest Baja California, Mexico. Objectives: We aimed to determine a potential association of SAWs with MeM in Tijuana, Baja California, Mexico, which in turn may partially explain the high rate of this disease in the region. Methods: Based on our previously published data obtained from thirteen years of active surveillance of MeM and a 65-year review showing the seasonal occurrence of SAWs, we estimated the risk ratio (RR) for the total case numbers of MeM (51 cases of children < 16 years old) vs. bacterial meningitis not caused by Neisseria meningitidis (NMeM, 30 cases, same age group) during seasons with and without SAWs. Results: We found an association between SAWs and MeM, but not with NMeM (RR = 2.06, p = 0.02 (95% CI 1.1 to 3.8), which may partially explain the high endemicity of this deadly disease in this part of the globe. Conclusion: This study shows a new potential climatic association with MeM and provides more information that justifies universal meningococcal vaccination in Tijuana, Mexico. Full article

Understanding trends in vaccine refusal is critical to monitor as small declines in vaccination coverage can lead to outbreaks of vaccine-preventable diseases. Using electronic heath record (EHR) data from the Children’s Hospital of Philadelphia’s 31 outpatient primary care sites, we created a cohort of 403,448 children less than age 20 years who received at least one visit from 1 January 2013 through 31 December 2020. The sample represented 1,449,061 annualized patient and 181,131 annualized preventive vaccination visits per year. We characterized trends in vaccine refusal and acceptance using a repeated cross-sectional observational analysis of electronic health records (EHR) data using a single annual merged observation measure for patients seen multiple times for preventive healthcare within a calendar year. Refusals were identified for 212,900 annualized patient-visit year observations, which represented 14.6% of annualized patient-visit year observations and 25.1% of annualized vaccine patient-year observations. The odds of having a refusal marker were significantly increased in patients seen in suburban practices (aOR [CI]: 2.35 [2.30–2.40, p < 0.001]), in patients with increased age 11–17 years (aOR [CI]: 3.85 [3.79–3.91], p < 0.001), and those eligible for the VFC program (aOR [CI]: 1.10 [1.08–1.11]. Parental refusal (61.0%) and provider decisions (32.0%) were the most common documented in progress notes for not administering vaccines, whereas contraindications (2.5%) and supply issues (1.8%) were the least common. When offered, vaccine acceptance increased for human papillomavirus, hepatitis B, measles-mumps-rubella-containing and varicella-containing vaccines and decreased for hepatitis A and meningococcal vaccines. Repeated offering of vaccines was central to increasing acceptance, in part due to increased opportunities to address specific concerns. Full article

Towards achieving the goal of eliminating epidemic outbreaks of meningococcal disease in the African meningitis belt, a pentavalent glycoconjugate vaccine (NmCV-5) has been developed to protect against Neisseria meningitidis serogroups A, C, Y, W and X. MenA and X polysaccharides are conjugated to tetanus toxoid (TT) while MenC, Y and W polysaccharides are conjugated to recombinant cross reactive material 197 (rCRM₁₉₇), a non-toxic genetic variant of diphtheria toxin. This study describes quality control testing performed by the manufacturer, Serum Institute of India Private Limited (SIIPL), and the independent control laboratory of the U.K. (NIBSC) on seven clinical lots of the vaccine to ensure its potency, purity, safety and consistency of its manufacturing. In addition to monitoring upstream-manufactured components, samples of drug substance, final drug product and stability samples were evaluated. This paper focuses on the comparison of the vaccine’s critical quality attributes and reviews key indicators of its stability and immunogenicity. Comparable results were obtained by the two laboratories demonstrating sufficient levels of polysaccharide O-acetylation, consistency in size of the bulk conjugate molecules, integrity of the conjugated saccharides in the drug substance and drug product, and acceptable endotoxin content in the final drug product. The freeze-dried vaccine in 5-dose vials was stable based on molecular sizing and free saccharide assays. Lot-to-lot manufacturing consistency was also demonstrated in preclinical studies for polysaccharide-specific IgG and complement-dependent serum bactericidal activity for each serogroup. This study demonstrates the high quality and stability of NmCV-5, which is now undergoing Phase 3 clinical trials in Africa and India. Full article

Infectious respiratory diseases are highly contagious and very common, and thus can be considered as one of the leading causes of morbidity and mortality worldwide. We followed up the incidence rates (IRs) of eight infectious respiratory diseases, including chickenpox, measles, pertussis, mumps, invasive pneumococcal disease, scarlet fever, rubella, and meningococcal disease, after COVID-19 mitigation measures were implemented in South Korea, and then compared those with the IRs in the corresponding periods in the previous 3 years. Overall, the IRs of these diseases before and after age- or sex-standardization significantly decreased in the intervention period compared with the pre-intervention periods (p < 0.05 for all eight diseases). However, the difference in the IRs of all eight diseases between the IRs before and after age-standardization was significant (p < 0.05 for all periods), while it was not significant with regard to sex-standardization. The incidence rate ratios for eight diseases in the pre-intervention period compared with the intervention period ranged from 3.1 to 4.1. These results showed the positive effects of the mitigation measures on preventing the development of respiratory infectious diseases, regardless of age or sex, but we need to consider the age-structure of the population to calculate the effect size. In the future, some of these measures could be applied nationwide to prevent the occurrence or to reduce the transmission during outbreaks of these infections. This study provides evidence for strengthening the infectious disease management policies in South Korea. Full article

Despite advances in the development and introduction of vaccines against the major bacterial causes of meningitis, the disease and its long-term after-effects remain a problem globally. The Global Roadmap to Defeat Meningitis by 2030 aims to accelerate progress through visionary and strategic goals that place a major emphasis on preventing meningitis via vaccination. Global vaccination against Haemophilus influenzae type B (Hib) is the most advanced, such that successful and low-cost combination vaccines incorporating Hib are broadly available. More affordable pneumococcal conjugate vaccines are becoming increasingly available, although countries ineligible for donor support still face access challenges and global serotype coverage is incomplete with existing licensed vaccines. Meningococcal disease control in Africa has progressed with the successful deployment of a low-cost serogroup A conjugate vaccine, but other serogroups still cause outbreaks in regions of the world where broadly protective and affordable vaccines have not been introduced into routine immunization programs. Progress has lagged for prevention of neonatal meningitis and although maternal vaccination against the leading cause, group B streptococcus (GBS), has progressed into clinical trials, no GBS vaccine has thus far reached Phase 3 evaluation. This article examines current and future efforts to control meningitis through vaccination. Full article

Neisseria meningitidis, carried in the human nasopharynx asymptomatically by ~10% of the population, remains a leading cause of meningitis and rapidly fatal sepsis, usually in otherwise healthy individuals. The epidemiology of invasive meningococcal disease (IMD) varies substantially by geography and over time and is now influenced by meningococcal vaccines and in 2020–2021 by COVID-19 pandemic containment measures. While 12 capsular groups, defined by capsular polysaccharide structures, can be expressed by N. meningitidis, groups A, B, and C historically caused most IMD. However, the use of mono-, bi-, and quadrivalent-polysaccharide-conjugate vaccines, the introduction of protein-based vaccines for group B, natural disease fluctuations, new drugs (e.g., eculizumab) that increase meningococcal susceptibility, changing transmission dynamics and meningococcal evolution are impacting the incidence of the capsular groups causing IMD. While the ability to spread and cause illness vary considerably, capsular groups W, X, and Y now cause significant IMD. In addition, group E and nongroupable meningococci have appeared as a cause of invasive disease, and a nongroupable N. meningitidis pathotype of the hypervirulent clonal complex 11 is causing sexually transmitted urethritis cases and outbreaks. Carriage and IMD of the previously “minor” N. meningitidis are reviewed and the need for polyvalent meningococcal vaccines emphasized. Full article

Neisseria meningitidis is the main cause of meningitis and sepsis, potentially life-threatening conditions. Thanks to advancements in vaccine development, vaccines are now available for five out of six meningococcal disease-causing serogroups (A, B, C, W, and Y). Vaccination programs with monovalent meningococcal serogroup C (MenC) conjugate vaccines in Europe have successfully decreased MenC disease and carriage. The use of a monovalent MenA conjugate vaccine in the African meningitis belt has led to a near elimination of MenA disease. Due to the emergence of non-vaccine serogroups, recommendations have gradually shifted, in many countries, from monovalent conjugate vaccines to quadrivalent MenACWY conjugate vaccines to provide broader protection. Recent real-world effectiveness of broad-coverage, protein-based MenB vaccines has been reassuring. Vaccines are also used to control meningococcal outbreaks. Despite major improvements, meningococcal disease remains a global public health concern. Further research into changing epidemiology is needed. Ongoing efforts are being made to develop next-generation, pentavalent vaccines including a MenACWYX conjugate vaccine and a MenACWY conjugate vaccine combined with MenB, which are expected to contribute to the global control of meningitis. Full article

Background: Major intercontinental outbreaks of invasive meningococcal disease associated with the Hajj occurred in 1987, 2000, and 2001. Mandatory meningococcal vaccination for all pilgrims against serogroups A and C and, subsequently, A, C, W, and Y controlled the epidemics. Overseas pilgrims show excellent adherence to the policy; however, vaccine uptake among domestic pilgrims is suboptimal. This survey aimed to evaluate meningococcal vaccine uptake among Hajj pilgrims and to identify key factors affecting this. Methods: An anonymous cross-sectional survey was conducted among pilgrims in Greater Makkah during the Hajj in 2017–2018. Data on socio-demographic characteristics, vaccination status, cost of vaccination, and reasons behind non-receipt of the vaccine were collected. Results: A total of 509 respondents aged 13 to 82 (median 33.8) years participated in the survey: 86% male, 85% domestic pilgrims. Only 389/476 (81.7%) confirmed their meningococcal vaccination status; 64 individuals (13.4%), all domestic pilgrims, did not receive the vaccine, and 23 (4.8%) were unsure. Among overseas pilgrims, 93.5% certainly received the vaccine (6.5% were unsure) compared to 80.9% of domestic pilgrims (p < 0.01). Being employed and having a tertiary qualification were significant predictors of vaccination adherence (odds ratio (OR) = 2.2, 95% confidence interval (CI) = 1.3–3.8, p < 0.01; and OR = 1.7, CI = 1–2.5, p < 0.05, respectively). Those who obtained pre-Hajj health advice were more than three times as likely to be vaccinated than those who did not (OR = 3.3, CI = 1.9–5.9, p < 0.001). Lack of awareness (63.2%, 36/57) and lack of time (15.8%, 9/57) were the most common reasons reported for non-receipt of vaccine. Conclusion: Many domestic pilgrims missed the compulsory meningococcal vaccine; in this regard, lack of awareness is a key barrier. Being an overseas pilgrim (or living at a distance from Makkah), receipt of pre-Hajj health advice, and employment were predictors of greater compliance with the vaccination policy. Opportunities remain to reduce the policy–practice gap among domestic pilgrims. Full article

A literature review was conducted to identify evidence of cases and outbreaks of vaccine-preventable diseases (VPDs) that have been reported from on board ships and the methods applied on board for prevention and control, worldwide, in 1990 to April 2019. Moreover, evidence from seroprevalence studies for the same diseases were also included. The literature review was conducted according to Preferred Reporting Items for Systematic reviews (PRISMA) guidelines. A total of 1795 cases (115 outbreaks, 7 case reports) were identified, the majority were among crew (1466/1795, 81.7%) and were varicella cases (1497, 83.4%). The origin of crew cases was from sub-tropical countries in many reports. Measles (40 cases, 69% among crew), rubella (47, 88.7%), herpes zoster (9, 69.2%) and varicella cases (1316, 87.9%) were more frequent among crew. Mumps cases were equal among passengers and crew (22/22). Hepatitis A (73/92, 70.3%), meningococcal meningitis (16/29, 44.8%), and pertussis (9/9) were more frequent among passengers. Two outbreaks resulted in 262 secondary measles cases on land. Review results were used to draft a new chapter for prevention and control of VPDs in the European Manual for Hygiene Standards and Communicable Disease Surveillance on Passenger Ships. Despite past and current evidence for cross-border VPD transmission and maritime occupational risks, documented pre-employment examination of immune status, vaccination of seafarers, and travel advice to passengers are not yet regulated. Full article