Serogroup B meningococcal disease in persons previously vaccinated with a serogroup B meningococcal vaccine – United States, 2014–2019

Since serogroup B meningococcal (MenB) vaccines became available in the United States, six serogroup B meningococcal disease cases have been reported in MenB-4C (n = 4) or MenB-FHbp (n = 2) recipients. Cases were identified and characterized through surveillance and health record review. All five available isolates were characterized using whole genome sequencing; four isolates (from MenB-4C recipients) were further characterized using flow cytometry, MenB-4C-induced serum bactericidal activity (SBA), and genetic Meningococcal Antigen Typing System (gMATS). Three patients were at increased meningococcal disease risk because of an outbreak or underlying medical conditions, and only four of the six patients had completed a full 2-dose MenB series. Isolates were available from 5 patients, and all contained sub-family A FHbp. The four isolates from MenB-4C recipients expressed NhbA but were mismatched for the other MenB-4C vaccine antigens. These four isolates were relatively resistant to MenB-4C-induced SBA, but predicted by gMATS to be covered. Overall, patient risk factors, incomplete vaccine series completion, waning immunity, and strain resistance to SBA likely contributed to disease in these six patients.     

Increase in penicillin-resistant invasive meningococcal serogroup W ST-11 complex isolates in England

IntroductionInvasive meningococcal disease (IMD) caused by serogroup W meningococci belonging to the ST-11 complex (MenW:cc11) has been increasing globally since the early 2000s. Penicillin resistance among meningococci due to the production of beta-lactamase remains relatively rare. Isolates displaying resistance and reduced susceptibility to penicillin due to alterations in the penA gene (encoding Penicillin Binding Protein 2) are increasingly reported. In 2016, a penicillin-resistant clade of MenW:cc11 isolates with altered penA genes was identified in Australia. More recently, an increase in penicillin-resistant invasive MenW:cc11 isolates was observed in England. Here, we investigate the distribution of penicillin resistance among English invasive MenW:cc11 isolates.MethodsIsolates from IMD cases in England from July 2010 to August 2019 underwent whole genome sequencing and antibiotic susceptibility testing as part of routine surveillance. The PubMLST Neisseria database was used to determine the distribution of penicillin resistance among English MenW:cc11 isolates and to identify other closely related isolates.ResultsTwenty-five out of 897 English invasive MenW:cc11 isolates were resistant to penicillin; identified among six distinct sublineages and a singleton. Expansion of the Australian penicillin-resistant clade included isolates from several new countries as well as 20 English isolates. A newly identified penicillin resistance-associated lineage was also identified among several countries.ConclusionPenicillin resistance among diverse MenW:cc11 isolates is increasing. Surveillance of antibiotic resistance among meningococci is essential to ensure continued effective use.     

Molecular Characteristics of Neisseria meningitidis Isolated during an Outbreak in a Jail: Associatition with the Spread and Distributition of ST-4821 Complex Serogroup C Cltione in China

Objective To characterize the meningococcal strains isolated from cases and close contacts with meningococcal disease associated with an outbreak in a jail in May 2010 by investigating the national distribution of hyperinvasive ST-4821 serogroup C clone associated with this outbreak. Methods The cases were described based on the clinical symptoms and laboratory results. Pharyngeal swabs were cultured for N. meningitidis from men in the jail. Meningococcal isolates were identified by serogrouping, pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST), respectively. Four hundred and sixteen serogroup C N. meningitidis strains were collected from 27 provinces between 2003 and 2010 for a nationwide survey and analyzed by PFGE and MLST. Results Three persons in a jail system were infected with invasive N. meningitidis serogroup C. All isolates tested had matching PFGE patterns and belonged to the multilocus sequence type (ST) 4821 clonal complex. All 47 N. meningitidis strains were identified from the pharyngeal swabs of 166 peoples in the jail, and 26 of them belonged to ST-4821 serogroup C clone, and 90.14% (375/416) serogroup C strains identified in the nationwide survey belonged to the ST-4821 complex. The ST-4821 serogroup C clone was spread nationwide, distributed in 24 provinces, especially in eastern provinces between 2003 and 2010. Conclusion Endemic transmission and carriage rate of ST-4821 serogroup C clone are high in this jail system. The ST-4821 serogroup C clone is spreading in China and nationwide distributed despite the existence of some effective vaccines.     

National survey of physicians in Japan regarding their use of diagnostic tests for legionellosis

IntroductionBacterial culture remains the gold standard for the diagnosis of legionellosis. However, past reports indicate that most physicians use the urinary antigen test (UAT) alone. Combining it with other tests is important, especially in patients with negative UAT results. The aim of this study was to investigate the current situation of legionellosis diagnostics and clarify the issues that need to be addressed.MethodsBetween March 1, 2021 and April 30, 2021, a questionnaire survey was conducted in an anonymous manner among physicians working in Japan. Questionnaires were generated on a website and asked questions in a multiple-choice format.ResultsValid responses were received from 309 physicians during the study period. Most (92.9%) physicians reported using UAT as the initial test for patients suspected of having legionellosis, and <10% reported using other tests (e.g., culture, nucleic acid amplification test [NAAT], Gimenez staining, and serum antibody titer measurement [ATM]). When the initial test result was negative, 63% of physicians reported not conducting additional tests. Even when they chose to run additional tests, at most 27.8%, 23.6%, 12.3%, and 10.4% of all physicians used NAAT, culture, Gimenez staining, and serum ATM, respectively. The major reasons for not using tests other than UAT were “unavailability in the medical facility,” “long turn-around time,” and “difficult to collect sputum.”ConclusionsThe present survey revealed that most physicians in Japan used UAT alone for diagnosing legionellosis. Eliminating barriers to creating a reasonable environment and edification of physicians are needed to improve the current situation.     

安徽怀远县1970～2003年钩端螺旋体病流行病学分析

目的了解怀远县乃至安徽省钩端螺旋体病(以下简称“钩体病”)其流行趋势,以制定科学有效的控制措施。方法根据怀远县1970-2003年疫情资料及检验结果进行汇总统计,并加以整理分析。结果怀远县1970-2003年平均发病率为1.79/10万,1970～2001年全县发生的钩体病以波摩那群为主,2002～2003年以黄疸出血群为主;流行形式上,以爆发为主,常伴有散发病例,爆发病例共549例,占总报告病例的88.12％;时间分布上,无明显周期性,除3次爆发出现明显的年度高峰外,其余年份病例数无明显差异,呈散发,以7～10月份发病为多,占报告病例总数的93.10％,去除爆发因素,则以1月份和7、8月份相对较多;男性明显高于女性,男女性别发病数之比为2.09∶1,以10～44岁发病数较高,形成较为明显的年龄高峰,75岁以上无发病;地区分布上,除爆发乡镇病例明显高于其它乡镇外,其余乡镇无明显差异,但从河流分布看,涡河以南明显高于涡河以北,若去除爆发因素,两者无明显改变。2003年的8～9月份钩体病现状调查显示,我县涡河以南钩体病感染率明显高于涡河以北(x~2=17.32,P<0.01)。结论我县钩体疫源地类型已由既往的经济疫源地向自然疫源地过渡,为混合型疫源地,流行形式已由洪水型向稻田型过渡,目前与稻田型一致,以黄疸出血群为主,黑线姬鼠为主要动物宿主,流行菌群发生变迁,并从血清学及病原学方面证实了“南黄北移”现象的存在。     

Preclinical immunogenicity study of trivalent meningococcal AWX-OMV vaccines for the African meningitis belt

In the recent decade, epidemic meningitis in the African meningitis belt has mostly been caused by Neisseria meningitidis of serogroups A, W and X (MenA, MenW and MenX, respectively). There is at present no licensed vaccine available to prevent MenX meningococcal disease. To explore a trivalent MenAWX vaccine concept, we have studied the immunogenicity in mice of MenX outer membrane vesicles (X-OMV) or MenX polysaccharide (X-PS) when combined with a bivalent A-OMV and W-OMV (AW-OMV) vaccine previously shown to be highly immunogenic in mice. The vaccine antigens were produced from three representative wild type strains of MenA (ST-7), MenW (ST-11) and MenX (ST-751) isolated from patients in the African meningitis belt. Groups of mice were immunized with two doses of X-OMV or X-PS combined with the AW-OMV vaccine or as individual components. All vaccine preparations were adsorbed to Al(OH)₃. Sera from immunized mice were tested by ELISA and immunoblotting. Functional antibody responses were measured as serum bactericidal activity (SBA) and opsonophagocytic activity (OPA). Immunization of mice with X-OMV, alone or in combination with AW-OMV induced high levels of anti-X OMV IgG. Moreover, X-OMV alone or in combination with the AW-OMV vaccine induced high SBA and OPA titers against the MenX target strain. X-PS alone was not immunogenic in mice; however, addition of the AW-OMV vaccine to X-PS increased the immunogenicity of X-PS. Both AWX vaccine formulations induced high levels of IgG against A- and W-OMV and high SBA titers against the MenA and MenW vaccine strains. These results suggest that a trivalent AWX vaccine, either as a combination of OMV or OMV with X-PS, could potentially prevent the majority of meningococcal disease in the meningitis belt.     

Economic evaluation of meningococcal serogroup B childhood vaccination in Ontario,Canada

Objective

Invasive Neisseria meningitidis serogroup B (MenB) disease is a low incidence but severe infection (mean annual incidence 0.19/100,000/year, case fatality 11%, major long-term sequelae 10%) in Ontario, Canada. This study assesses the cost-effectiveness of a novel MenB vaccine from the Ontario healthcare payer perspective.

Methods

A Markov cohort model of invasive MenB disease based on high quality local data and data from the literature was developed. A 4-dose vaccination schedule, 97% coverage, 90% effectiveness, 66% strain coverage, 10-year duration of protection, and vaccine cost of C$75/dose were assumed. A hypothetical Ontario birth cohort (n = 150,000) was simulated to estimate expected lifetime health outcomes, quality-adjusted life years (QALYs), and costs, discounted at 5%.

Results

A MenB infant vaccination program is expected to prevent 4.6 invasive MenB disease cases over the lifetime of an Ontario birth cohort, equivalent to 10 QALYs gained. The estimated program cost of C$46.6 million per cohort (including C$318,383 for treatment of vaccine-associated adverse events) were not offset by healthcare cost savings of C$150,522 from preventing MenB cases, resulting in an incremental cost of C$4.76 million per QALY gained. Sensitivity analyses showed the findings to be robust.

Conclusions

An infant MenB vaccination program significantly exceeds commonly used cost-effectiveness thresholds and thus is unlikely to be considered economically attractive in Ontario and comparable jurisdictions.     

Outbreak-specific monovalent/bivalent vaccination to control and eradicate virulent ovine footrot

Footrot is a contagious disease of small ruminants which is caused by the bacterium Dichelobacter nodosus. In its virulent form there are severe economic losses and a very significant animal welfare issue. Sheep and goats can be vaccinated for treatment and prevention of the disease. There are 10 different serogroups of D. nodosus (A–I and M) and immunity is serogroup-specific. When all 10 serogroups are presented together in a vaccine, protection persists for only a few months due to “antigenic competition”. Consequently we evaluated the use of sequential monovalent or bivalent vaccines to control/eliminate/eradicate virulent footrot in a longitudinal intervention study on 12 commercial farms in southeast Australia with flock sizes of approximately 1200–4200 sheep. Overall, virulent footrot was eradicated from 4 of the flocks, 2 of which had 2 serogroups, and the others 4 or 5 serogroups. Where there were only 1 or 2 serogroups (3 farms) the clinical response was rapid and dramatic; prevalence was reduced from 45 to 50% before vaccination to 0% (2 farms) or 0.4% (1 farm) after one round of vaccination. In the remaining 9 flocks there were more than 2 serogroups and successive bivalent vaccines were administered leading to eradication of virulent footrot on 2 farms over 4 years and control of the disease on all but 3 of the others. Of the latter farms, 1 discontinued, and 2 initially had poor response to vaccine due to misdiagnosis of serogroup ‘M’, which was previously unknown in Australia. Control was achieved after administration of a serogroup M vaccine. These results provide clear evidence for control, elimination and eradication of virulent footrot by outbreak-specific vaccination in Australia.