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Two unvaccinated infants residing in the same borough of New York, New York, USA, had Haemophilus influenzae type b meningitis develop 1 year apart. Whole-genome sequencing and phylogenetic analysis revealed the isolates shared a previously undescribed multilocus sequence type and were more closely related to each other than to other sequenced strains.

•An active surveillance through a phased introduction of the Hib vaccine in Japan was studied.•Hib disease incidence decreased significantly after vaccine introduction.•Hif and non-typeable H. influenzae were isolated from a few cases.•Serotype replacement was not observed after the introduction of the Hib vaccine.•Continuous capsular typing and strain identification surveillance is important. Haemophilus influenzae type b (Hib) vaccine was introduced as a voluntary vaccine in December 2008 and was included in the national routine immunization program in April 2013 in Japan. Currently, no nationwide data are available to evaluate the effectiveness of Hib vaccine in Japan. To evaluate the effectiveness of Hib vaccine in Japan, nationwide active population-based surveillance of culture-proven invasive infections caused by H. influenzae in children was performed in 2008–2017 in 10 prefectures in Japan (covering approximately 23% of the total Japanese population). Clinical data were recorded on a standardized case report form. Capsular type and antimicrobial susceptibility of the H. influenzae isolates were examined. The incidence rate ratio (IRR) and its confidence interval (CI) were calculated to compare data from 5 years before and that from after the introduction of the national routine Hib vaccine immunization program. During the 10-year study period, 566 invasive H. influenzae disease cases including 336 meningitis cases were identified. The average number of invasive H. influenzae disease cases among children <5 years of age during 2013–2017 decreased by 93% (IRR: 0.07, 95%CI 0.05–0.10, p < 0.001) compared with those occurring during 2008–2012. Hib strains have not been isolated from invasive H. influenzae disease cases since 2014; however, non-typeable H. influenzae and H. influenzae type f isolates have been noted as causes of invasive H. influenzae diseases among children <5 years in the post-Hib vaccine era. After the governmental subsidization of the Hib vaccine, invasive Hib disease cases decreased dramatically in the study population, as per our surveillance. Continuous surveillance is necessary to monitor the effectiveness of Hib vaccine and for detecting any emerging invasive capsular types.

The current coronavirus disease 2019 (COVID-19) outbreak has caused a persistent decline in childhood vaccination coverage, including Haemophilus influenzae type b (Hib) vaccine, in some countries. Our objective was to evaluate the impact of decreased Hib vaccination due to COVID-19 on invasive Hib disease burden in Japan. Using a deterministic dynamic transmission model (susceptible-carriage-infection-recovery model), the incidence rates of invasive Hib disease in under 5 year olds in rapid vaccination recovery and persistent vaccination declined scenarios were compared for the next 10 years after 2020. The national Hib vaccination rate after the impact of COVID-19 reduced to 87% and 73% in 2020 from approximately 97% each in 2013–2019 for primary and booster doses. While the persistent decline scenarios revealed an increase in invasive Hib disease incidence to 0.50/100,000 children under 5 years old, the incidence of the rapid recovery scenario slightly increased with a consistent decline of incidence after 2021. The shorter the duration of the decline in vaccination rate was, the smaller the incremental disease burden observed in the model. Compared to the rapid recovery scenario, the permanent decline scenario showed a 296.87 cumulative incremental quality-adjusted life years (QALY) loss for the next 10 years. The persistent decline of Hib vaccination rate due to COVID-19 causes an incremental disease burden irrespective of the possible decline of Hib transmission rate by COVID-19 mitigation measures. A rapid recovery of vaccination coverage rate can prevent this possible incremental disease burden.

The majority of conjugate vaccines focus on inducing an antibody response to the polysaccharide antigen and the carrier protein is present primarily to induce a T-cell dependent response. In this study conjugates consisting of poly(ribosylribitolphosphate) (PRP) purified from Haemophilus influenzae Type b bound to Hepatitis B virus surface antigen (HBsAg) virus like particles were prepared with the aim of inducing an antibody response to not only the PRP but also the HBsAg. A conjugate consisting of PRP bound to HBsAg via an adipic acid dihydrazide (ADH) spacer induced strong IgG antibodies to both the PRP and HBsAg. When conjugation was performed without the ADH spacer the induction of an anti-PRP response was equivalent to that seen by conjugate with the ADH spacer, however, a negligible anti-HBsAg response was induced. For comparison, PRP was conjugated to diphtheria toxoid (DT) and Vi polysaccharide purified from Salmonella Typhi conjugated to HBsAg both using an ADH spacer. The PRPAH–DT conjugate induced strong anti-PRP and anti-DT responses, the Vi–AHHBsAg conjugate induced a good anti-HBsAg response but not as strong as that induced by the PRPAH–HBsAg conjugate. This study demonstrated that in mice it was possible to induce robust antibody responses to both polysaccharide and carrier protein provided the conjugate has certain physico-chemical properties. A PRPAH–HBsAg conjugate with the capacity to induce anti-PRP and anti-HBsAg responses could be incorporated into a multivalent pediatric vaccine and simplify formulation of such a vaccine.

Capsular polysaccharide produced by Haemophilus influenzae b (Hib) is the main virulent agent and used as the antigen in the vaccine formulation. In this study, an improved process of polysaccharide purification was established based on tangential flow ultrafiltration using detergents (cocamidopropyl betaine and sodium deoxycholate), two selective ethanol precipitations steps, and extensive enzymatic hydrolysis as strategy. The relative purity (RP) related to protein and nucleic acids were 122∼263 and 294∼480, respectively, and compatible with the specifications established by the World Health Organization for Hib vaccine, RP ≥ 100. These results make this process simple, cheaper, efficient, environmentally friendly, and prone to be scaled up.

Background. Many bacteria responsible for clinically relevant disease reside harmlessly in a large fraction of humans. Three explanations have been proposed to account for why these normally commensal bacteria occasionally cause invasive disease: host susceptibility, stochasticity in the host-bacteria interaction, and the evolution of invasive mutants in colonized hosts. Here we test the third of these hypotheses for the rare invasiveness of commensal bacteria: within-host evolution. Methods and Results. Using neonatal rats intranasally colonized with pairs of marked Haemophilus influenzae type b strains, we demonstrate that the resulting bacteremias are derived from single organisms. To test the withinhost evolution hypothesis we explored the relative ability of bacteria isolated from the blood and nasal passages of bacteremic rats to colonize the nasopharynx and invade the bloodstream. Conclusions. Our results provide support for within-host evolution as one but not the sole explanation for the invasiveness of these bacteria. We discuss the implications of these results for both the rare invasiveness of commensal bacteria and the general observation that bacteria isolated from the sites of human invasive disease are almost invariably monoclonal.

Background The bacteria Streptococcus pneumoniae (pneumococcus) and Haemophilus influenzae type b (Hib) are leading causes of childhood pneumonia and meningitis and are major contributors to worldwide mortality in children younger than 5 years of age. Asymptomatic nasopharyngeal carriage of pneumococcus and Hib was determined for healthy children in Shanghai in 2009. Methods Children from 5 immunization clinics were enrolled in this study. Specimens from the nasopharynx were collected and cultured in Columbia and chocolate agar to identify pneumococcal and Hib carriage. Pneumococcal specimens were serotyped with the Neufeld test, and antibiotic resistance for pneumococcal and Hib specimens used the E-test method. Significance of risk factors for carriage was assessed through chi-square tests. Results Among 614 children, 16.6 % had pneumococcal carriage and 8.0 % Hib carriage. The predominant serotype of pneumococcus that was isolated was 19 F (52.9 %); serotype coverage was 68.6 % for both 7-valent pneumococcal conjugate vaccine (PCV) and PCV-10, and 82.3 % for PCV-13. Household residency and father’s education were both significantly related to pneumococcal and Hib carriage. The majority of S. pneumoniae isolates were sensitive to most antimicrobials but there were high levels of resistance to azithromycin (51.0 %) and erythromycin (51.0 %). Haemophilus influenzae isolates were sensitive to almost all antimicrobials tested although 12.2 % of isolates were resistant to ampicillin. Conclusions The pneumococcal and Hib vaccines require payment, and the children with the highest burden of disease may not be receiving these vaccines. Moreover, the presence of high antibiotic susceptibility towards pneumococcus, and to a lesser extent towards Hib, underscores the need for preventive protection against these diseases. Public funding of pneumococcal and Hib vaccines would be one mechanism to increase uptake of these vaccines.

This article presents the World Health Organizations (WHO) evidence and recommendations for the use of Haemophilus influenzae type b vaccination from the WHO position paper on H. influenzae type b (Hib) Vaccination – July 2013 recently published in the Weekly Epidemiological Record [1]. This position paper summarizes the WHO position on the inclusion of Hib vaccines in all national immunization programmes, recent developments in the field and the potential of different Hib immunization schedules to further reduce morbidity and mortality. The current document replaces the position paper on the use of Hib vaccines published in 2006 [2]. Footnotes to this paper provide a number of core references. In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO's current position on the use of vaccines in the global context. This paper reflects the recommendations of WHO's Strategic Advisory Group of Experts (SAGE) on immunization. These recommendations were discussed by SAGE at its April 2013 meeting. Evidence presented at the meeting can be accessed at http://www.who.int/immunization/sage/previous/en/index.html.

Adoption of new vaccines in developing countries is critical to reducing child mortality and meeting Millennium Development Goal 4. However, such introduction has historically suffered from significant delays that can be attributed to various factors including (i) lack of recognition of the value of a vaccine, (ii) factors related to weak health systems, and (iii) policy considerations. Recently, the Global Alliance for Vaccines and Immunization (GAVI) supported efforts to accelerate the introduction of Haemophilus influenzae type b (Hib) vaccines in developing countries, which resulted in a significant surge in vaccine adoption by these countries. The experience with Hib vaccines, as well as similar efforts by GAVI to support the introduction of new pneumococcal and rotavirus vaccines, provides a strategy for new vaccine adoption that is reviewed in this paper, providing a useful model to help accelerate the uptake of other life-saving vaccines. This strategy addresses barriers for vaccine adoption by focusing on three major areas: (i) communications to increase awareness about the various factors needed for evidence-based decisions that meet a country's health goals; (ii) research activities to answer key questions that support vaccine introduction and long-term programme sustainability; and (iii) coordination with the various stakeholders at global, regional and country levels to ensure successful programme implementation.

Most invasive Haemophilus influenzae type b strains possess a duplication of the capsulation locus. Further amplification resulting in as many as 5 copies has been described. To verify whether amplification is involved in vaccine failure, the number of copies of the locus was determined by Southern blotting in 90 strains from children with true vaccine failure (TVF) between 1993 and 1999 and in 139 strains from unvaccinated children (50 collected between 1993 and 1999 and 89 collected between 1991 and 1992, before routine immunization was introduced). A significantly greater proportion of strains from TVFs contained multiple copies, compared with strains from control children (24% vs. 10%; P=.0379), which suggests that amplification of the capb locus may be a contributory factor in vaccine failure. The presence of multiple-copy strains was associated with disease other than meningitis