Hib Vaccine Research Articles

Motivational interviewing and vaccine acceptance in children: The MOTIVE study

Background and ObjectiveVaccine coverage have been less than desired in young children in part due to parental vaccine hesitancy. Addressing health beliefs through patient-centered communication approaches such as motivational interviewing (MI) may improve vaccine confidence. Thus, the objective of this study was to determine the difference in paediatric vaccination coverage rates based on the Advisory Committee on Immunization Practices (ACIP) and Centers for Disease Control and Prevention (CDC) recommended schedule in children 0–6 years of age after an educational intervention for providers and integration of an MI-based communication tool, MOTIVE (MOtivational Interviewing Tool to Improve Vaccine AcceptancE). MethodsPaediatric and family practice providers in a federally qualified health center in the United States completed an educational intervention regarding vaccine hesitancy and use of the MOTIVE tool. Providers then implemented the MOTIVE tool to address common health beliefs using strong, presumptive vaccine recommendations and an MI framework during encounters with patients 0–6 years of age. Data were collected from 1-year pre-educational intervention (July 2018-June 2019, N = 2504) and post-intervention (July 2019-March 2020, N = 1954) to examine differences in vaccination coverage rates and documented vaccine refusals. ResultsUse of the MOTIVE tool was associated with a statistically significant increase in IIV vaccination coverage rate in children 6 months to 6 years of age (32.4% versus 43.9%, p < 0.01). A significantly increased Hib vaccination coverage rate was observed in children 0–18 months of age. Patients with commercial insurance also had significantly higher vaccination coverage rates for the DTaP, IPV, and VAR vaccines during the intervention period. Use of the MOTIVE tool was associated with a decrease in documented vaccine refusals per 100 patients in children 0–6 years of age (31.5 versus 17.6, p < 0.01). ConclusionUse of an MI-based communication tool may decrease vaccine refusals and improve childhood vaccination coverage rates, particularly for IIV.Clinical Trial Registration: ClinicalTrials.gov, NCT03934008, https://clinicaltrials.gov/ct2/show/NCT03934008, deidentified individual participant data will not be made available.

Establishment of the national reference for heamophilus influenza type b vaccine

Vietnam still lacks the national standard Hib vaccine to determine the content of Polyribosyl Ribitol Phosphate, an indicator to assess the protective ability of vaccines against the diseases caused by Heamophilus influenza type b (Hib) bacteria. National Institute for Control of Vaccines and Biologicals has developed the specifications of the national standard Hib vaccine, produced a candidate batch, calibrated the candidate to the international standards to determine its value. The results show that the candidate meets the requirements, has been recognized as a national reference standard, namely MCQG.Hib.01, with a content of (5.00 - 5.74) mg PRP/vial.

Safety and Immunogenicity of a Shigella Bivalent Conjugate Vaccine (ZF0901) in 3-Month- to 5-Year-Old Children in China.

No licensed Shigella vaccine is presently available globally. A double-blinded, randomized, placebo-controlled, age descending phase II clinical trial of a bivalent conjugate vaccine was studied in China. The vaccine ZF0901 consisted of O-specific polysaccharides purified and detoxified from lipopolysaccharide (LPS) of S. flexneri 2a and S. sonnei and covalently bonded to tetanus toxoid. A total of 224, 310, and 434 children, consented by parents or guardians, aged 3 to 6 and 6 to 12 months and 1 to 5 years old, respectively, were injected with half or full doses, with or without adjuvant or control Hib vaccine. There were no serious adverse reactions in all recipients of ZF0901 vaccine independent of age, dosage, number of injections, or the adjuvant status. Thirty days after the last injection, ZF0901 induced robust immune responses with significantly higher levels of type-specific serum antibodies (geometric mean concentrations (GMCs) of IgG anti-LPS) against both serotypes in all age groups compared with the pre-immune or the Hib control (p < 0.0001). Here, we demonstrated that ZF0901 bivalent Shigella conjugate vaccine is safe and immunogenic in infants and young children and is likely suitable for routine immunization.

Nasopharyngeal carriage of Haemophilus influenzae among adults with co-morbidities

After the widespread use of Haemophilus influenzae type b (Hib) vaccine, H. influenzae invasive disease is now commonly due to non-encapsulated (NTHi), affecting mostly the youngest and the elderly. The objective of this study was to investigate H. influenzae nasopharyngeal carriage rate in adults with co-morbidities and possible associated risk factors. MethodsPatients aged >50 years with co-morbidities attending medical centres were examined. A nasopharyngeal swab was analysed for H. influenzae presence by cultural and molecular methods (RT-PCR). Univariable and multivariable analysis of risk factors for H. influenzae carriage were performed. Serotype of isolates was determined by PCR capsular genotyping. Minimum inhibitory concentration (MIC) was determined by MIC gradient test and β-lactamase production was detected by the nitrocephin test. Genotyping was performed by Multilocus sequence typing (MLST). Phylogenetic relationships among carriage and invasive NTHi strains were assessed. ResultsAmong 248 enrolled patients (median age: 73 years), the carriage rate was 5.6% and 10.5% by cultural method or RT-PCR, respectively. Colonization with H. influenzae was significantly associated with the presence of acute respiratory symptoms (adjusted OR = 12.16, 95% CI: 3.05–48.58, p < 0.001). All colonizing isolates were NTHi. Three isolates (3/14, 21.4%) were resistant to ampicillin and beta-lactamase positive. MLST revealed a high degree of genetic diversity, with 11 different STs from 14 isolates. Eight out of the 11 (72.7%) STs were shared among carriage and invasive isolates. ConclusionsAdults ≥50 years old with co-morbidities are occasionally colonized by H. influenzae, even if the presence of co-morbidities is not a risk factor for colonization. The presence of acute respiratory symptoms is the only factor associated with H. influenzae colonization. Colonizing H. influenzae are all NTHi. Colonizing H. influenzae often belong to the same STs of invasive disease isolates.

Ampicillin &amp; Gentamicin V/S 3rd Generation Cephalosporin for the Management of Community-Acquired Pneumonia in Children; A Comparative Analysis

Background: Community acquired pneumonia (CAP) is a common cause of childhood morbidity, attributed to every 1 in 500 hospitalization of children under the age of 5 years. While science made therapeutic advancements to battle CAP, the pathogens too have acquired resistance to many drugs. In this fight for dominance, Ampicillin plus Gentamicin and 3rd Gen Cephalosporins are nowadays the cornerstone of treatment. However, their efficacy varies in different parts of the world owing to differing levels of drug resistance.&#x0D; Objective: To compare the effect of Ampicillin and Gentamicin vs. third generation cephalosporin in treatment of severe community acquired pneumonia.&#x0D; Methodology: This Randomized Controlled Trial was conducted at the Dept. of Pediatrics (Ziauddin University Hospital) upon a sample of 74 patients (in two equal groups) of either gender, aged 2 months to 5 years, presenting with CAP. After taking written informed consent, data was recorded onto a pre-structured questionnaire containing inquiries pertaining to basic biodata, sociodemographic details, presenting complaints, immunization status of the pneumococcal and HIB vaccine, laboratory values, and treatment outcome.&#x0D; Results: The mean age of the sample stood at 15 months (SD ± 3) with a majority of the sample comprising of male children (52.7%). The mean weight stood at 8.7 kg (SD ± 0.9) and the mean height was recorded to be 74.2 cm (SD ± 11). The commonest symptoms included fever, fast breathing, chest in-drawing and added sounds. It was revealed that both treatments achieved successful treatment outcomes in all patients with no mortality. The resolution of symptoms however varied with faster resolution observed in the Cephalosporin group.&#x0D; Conclusion: After careful consideration, it can be concluded that 3rd generation cephalosporins is more efficacious at treatment of CAP with significantly faster resolution of disease symptoms.

1147. Sentinel Surveillance of Bacterial Pneumonia in Children Under 5 years Treated in HOMI - Fundación Hospital pediatrico la Misericordia in Bogotá, Colombia 2016-2020

BackgroundPneumonia is one of the leading causes of hospitalization and death in children under 5y. The main causes of bacterial pneumonia (BP) are Streptococcus pneumoniae (Spn) and Haemophilus influenzae (Hi). Colombia implemented the Hib vaccine in 1997 with a 3 + 0 scheme and the PCV10 vaccine in 2012, using a 2 + 1 scheme. Sentinel surveillance of BP is carried out at HOMI - Fundación Hospital Pediátrico La Misericordia, which is part of the invasive bacterial vaccine preventable disease surveillance network. MethodsA daily active search for cases that met the definitions established in the protocol of the Pan American Health Organization was carried out. All hospitalized patients under 5 years of age with a diagnosis of community acquired pneumonia (ICD10 J10 to J22) were classified as suspected cases, while all suspected cases in which chest X-ray showed a radiological pattern compatible with bacterial pneumonia were considered a probable case. Blood cultures were taken from probable cases; if results were positive (Spn, Hi), the samples were sent to the district and national reference laboratories for confirmation and serotyping. The data obtained in the period January 2016 to December 2020 were analyzed.Results5272 suspected cases of bacterial pneumonia were found, of which 60% were < 2 y. The highest incidence occurred from March to June (Figure 1). Blood cultures were performed in 2223 (92%) of the 2432 (46.1%) probable cases, confirming 127 (5.2%) cases. Spn, Hi, and other bacteria were found in 55, 27, and 28 cases, respectively (Table 1). Serotyping was performed in 85.4% of the Spn isolates and 77.7% of Hi isolates. The most frequent Spn serotypes were Spn19A in 19 cases (40.4%), Spn3 in 12 cases (25.5%), and Spn14 in 4 cases (8.5%). The presence of Spn19A has increased over time (Figure 2). The most frequent Hi was non-typeable in 13 patients (61.9%), followed by serotype b 6 (28.5%) and serotype a 2 (9.5%). The rate of hospitalization for BP was 9/1000 children < 5 years, and 43 patients died. Case fatality rate was 1.7% among probable cases.Graph 1. Trend of suspected bacterial pneumonia cases in children under 5 years old. HOMI. 2016-2020 Table 1. Bacterial pneumonia isolates. HOMI. 2016 - 2020 Graph 2. Bacterial pneumonia serotypes. HOMI. January 2016 - December 2020 ConclusionBP mainly occurs in 2-year-old children. Spn 19A is the most common bacteria. Although the most frequent Hi is non-typeable, cases of Hib are still observed. Sentinel surveillance allows measuring the impact of public health interventions on this disease.Disclosures German Camacho Moreno, n/a, Pfizer and MSD (Research Grant or Support, Speaker’s Bureau, Other Financial or Material Support, Has received support from Pfizer for participation in congresses)

COVID-19: Cross Reactive Immunity, Herd Immunity, and Convalescent Serum Therapy

Objective: To present various types of vaccines and viral infections which can induce cross-reactive immunity against COVID-19. In addition, this article discusses the role of herd immunity and convalescent serum therapy in preventing and controlling SARS CoV-2. The study also determined the claims and counterclaims about their protective and therapeutic effects.&#x0D; Method: Non-systematic review was done using different articles done on cross-reactive immunity against COVID-19 through vaccinations, previous infections, herd immunity and the therapeutic effects of convalescence serum. The search was done on the PubMed, Google Scholar, and Science Direct, WHO, Euro-surveillance, CDC databases. &#x0D; Results: Many observational correlational studies reported that BCG decreases the incidence and mortality from COVID-19. Furthermore, homology between the COVID-19 virus and the measles, mumps, and rubella (MMR) viruses was discovered. Few studies suggested the presence of cross-immunity between MMR vaccine and SARS-CoV-2. Similarly, few studies suggested protective effects of Oral Polio Vaccine (OPV) against SARS-CoV-2; since both viruses are positive-single-strand RNA (+ssRNA). Diphtheria, pertussis, and tetanus (DPT) vaccines, particularly those that include inactivated whole pertussis vaccine, might induce B and T cell cross-reactive immunity against SARS-CoV-2. Other vaccines against Streptococcus pneumonia, Haemophilus influenza, and Meningococcal meningitis vaccines are suggested also to induce some immunity against Covid-19. It is hypothesized that infections with other Coronaviruses may cause protection against SARS-CoV-2. However, the studies done on these suggestions were mostly observational that can carry a high chance of inherent biases. There are also claims and counterclaims about the effect of herd immunity and convalescence serum on the prevention and control of Covid-19. So, appropriately designed RCTs are needed to prove or disprove their protective and therapeutic effects.&#x0D; Conclusions: There are claims and counterclaims about the protective effects of different vaccines, previous infections, and herd immunity and regarding the therapeutic effects of convalescence serum. Comparing with other vaccines, BCG was suggested to have the highest cross-reactive epitopes against SARS-Cov-2 virus. MMR, OPV, DPT, Influenza, Pneumococcal and meningococcal vaccines are suggested to protect against Covid-19. Previous infection with other Corona viruses, herd immunity and convalescence serum may play roles in the prevention and control of Covid-19. Many large clinical trials are undergoing nowadays and their results are needed to prove or disprove the cross-immunity related to SARS-CoV-2 and the effect of convalescence serum.

Impact of Haemophilus influenza immunization on hospitalized acute respiratory infections

Abstract Background Immunization is the most cost-effective measure to combat communicable diseases in childhood. Haemophilus influenza (Hib) vaccine was included in the Tunisian expanded program of immunization for the first time in 2002 (Hib Vaccine monovalent) and is currently combined with the pneumococcal vaccine(Hib vaccine pentavalent combination) since April 2019. We aimed to assess impact of Hib vaccine on Respiratory Infection(RI) admissions in children aged up to 3 years. Methods It was a cohort study from January 1, 2002 to December 31, 2013. All Respiratory Infection (RI) admissions in children aged up to 3 years in the university hospital of Monastir(Tunisia) were enrolled. Results Admissions for RI represented 17.6% (CI95%: 17.3-18.1) of all communicable diseases hospitalizations (n = 6 061/34 289). The median age was 22 years (IQR: 3-52). Admission for Pneumonia with Streptococcus Pneumoniae (SP) increased significantly during study period (b = 25.9 (p &amp;lt; 0.0001)) especially in children up to 5 years old (b = 10.6) and in elderly (b = 6.0). Among children up to 3 years old, the Crude incidence rate per 100,000 for Hib pneumonia admission were 11.6 in Non-Vaccinated Cohort (NVC), 10.6 in Vaccinated Cohort (VC) by protocol 1 (Hib Vaccine monovalent) and 0.80 in VC by protocol 2 (Hib vaccine pentavalent combination).The relative risk reduction was 99% for protocol 2 (p &amp;lt; 0.001). Conclusions Admissions for RI in a tertiary level hospital were common with an increasing trend. The Hib immunization program, in particular the second protocol (pentavalent combination), has had a positive impact on the reduction of related acute diseases. Key messages The Hib immunization program, has had a positive impact on the reduction of related acute diseases. The “Hib vaccine pentavalent combination “is more efficient than “Hib Vaccine monovalent”.

“Missed a vaccine?” Survey on vaccine hesitancy of high-risk categories in Bologna

Abstract Background Vaccine Hesitancy (VH) is considered by the WHO to be one of the ten threats of the 21st century. The Italian National Plan for Vaccine Prevention, as well as the European Action Plan, have among their objectives that of increasing the adherence to vaccinations both in general population and in categories at higher risk. It is precisely to these latter groups that the action of the Bologna Local Health Authority (LHA) has addressed targeted vaccination campaigns in recent years (e.g., DTP, HepB, PCV/PPV, RZV). Aim of our study was to investigate adherence to the proposed vaccination campaigns. Methods An anonymous QR-code scanned survey was administered to adults during the COVID-19 vaccine campaign in February in Bologna, a city in Northern Italy. Results A total of 2,321 participants were enrolled, 59% of whom were female. Among healthcare workers (n = 1,417), VH was 45.6% for Hib in 2020, 60.3% in 2019, and 68.3% in 2018; and 14.9% for HepB. Among people with chronic conditions (n = 149), 36.6% did not get the PCV/PPV vaccine. Among RZV vaccine recipients (n = 406), only 11.1% reported having been vaccinated. Women who were at least once pregnant in the last 5 years (n = 124), did not get the anti-pertussis vaccine in 41.9% of cases, and 71.8% of them refused the Hib vaccine. In general, the reasons most often given for missed vaccinations were ‘I did not inform myself enough about this specific vaccine' (ranging from 16.0% for Hib for healthcare workers to 44.8% for RZV), ‘I am not informed about the vaccinations I am entitled to' (27.3% for RZV, 31.8% for PCV/PPV), and ‘I do not find it useful' (46.2% for Hib in healthcare workers). Conclusions Our findings show that even in those who accept the COVID-19 vaccine, VH is high for other vaccinations campaigns run by the Bologna LHA. Targeted awareness and designed catch-up actions are needed, especially regarding this group that does not totally stand in the ranks of the so-called ‘no vax'. Key messages Vaccine Hesitancy toward other vaccines remains high among those who accept the anti-COVID-19 vaccination. A large number of hesitant respondents report either not being aware of the possibility of vaccination or not being adequately informed about the specific vaccine.

Sentinel surveillance for bacterial pneumonia and meningitis in children under the age of 5 in a tertiary pediatric hospital in Colombia - 2016.

:Introduction: Bacterial pneumonia and meningitis are vaccine-preventable diseases. Sentinel surveillance provides relevant information about their behavior.Objective: To present the data from sentinel surveillance carried out at the Fundación HOMI, Fundación Hospital Pediátrico La Misericordia in 2016.Materials and methods: We conducted a descriptive study from January 1 to December 31, 2016, on the daily surveillance of patients under 5 years of age diagnosed with pneumonia or bacterial meningitis according to PAHO's definitions. We identified the microorganisms using the automated VITEKTM 2 system. Bacterial isolates were sent to the Microbiology Group at the Colombian Instituto Nacional de Salud for confirmation, serotyping, phenotypic, and genotypic characterization. Antimicrobial susceptibility profiles were established.Results: From 1,343 suspected cases of bacterial pneumonia, 654 (48.7%) were probable, 84% had complete Hib vaccination schedules, and 87% had complete pneumococcal vaccination schedules for age. Blood culture was taken in 619 (94.6%) and 41 (6.6%) were positive while S. pneumoniae was isolated in 17 (41%) of them. The most frequent serotype was 19A in five cases (29.4%), and four 19A serotypes were associated with the reference isolate ST320. The incidence rate of probable bacterial pneumonia was 7.3 cases/100 hospitalized patients, and lethality was 2.1%. As for bacterial meningitis, 22 suspected cases were reported, 12 (54%) were probable, four (33%) were confirmed: two by Escherichia coli and two by group C N. meningitidis. The incidence of probable bacterial meningitis was 0.14 cases/100 hospitalized patients.Conclusion:Streptococcus pneumoniae serotypes 19A and 3 were the most frequent cause of pneumonia. Spn19A is related to the multi-resistant clone ST320. Strengthening and continuing this strategy will allow understanding the impact of vaccination.

Усовершенствование процесса получения полисахарида полирибозилрибитолфосфата, используемого в производстве вакцин против гемофильной инфекции

The production of vaccines requires constant improvement of methods and tools, revision and modernization of the current technology with the aim to improve quality of the product made for the benefit of public health. The purposяe of this work was to improve the process of production of polysaccharide polyribosyl ribitol phosphate (PRP), which is the active agent of Haemophilus influenzae type b (Hib) vaccines. We investigated how PRP yield depends on the following factors: concentration of dissolved oxygen in the culture liquid, glucose concentration control method applied in cultivation, source of protein for the producer microorganism, stability of the polysaccharide at the culture liquid inactivation stage. As a result, we managed to increase the PRP yield in the culture liquid by 10%, ensured a 25% boost of the biomass accumulation rate during cultivation in the fermenter and reduced the cultivation time by 6.5 hours. The PRP loss rate at the culture liquid inactivation stage was reduced by 80%. Relying on the patented composition, we invented a new composition of the nutrient medium that meets the current regulatory requirements.

Hib Vaccines: Their Impact on Haemophilus influenzae Type b Disease.

Haemophilusinfluenzae serotype b (Hib) is an important cause of serious, invasive infections, particularly in young children. Since 1985, a series of vaccines composed of the type b capsular polysaccharide polyribosylribitol phosphate (PRP), followed by PRP conjugated to various proteins, have been licensed for use in the United States and worldwide. The conjugated vaccines offer increased immunogenicity and prolonged durability of immune protection compared to the plain PRP vaccine and increasingly are combined with other childhood vaccines for decreased cost and increased ease of vaccination. Hib vaccines have a very favorable safety profile, have been found to be either cost-saving or cost-effective by many public health agencies, and, in most countries, are initiated during early infancy as part of routine childhood immunization programs. As a result of widespread use of the vaccines, the incidence of Hib infections, and their associated morbidity and mortality, has fallen dramatically across the globe. Yet, many children remain unimmunized or underimmunized against Hib, particularly in limited-resource countries. Future efforts to further reduce the disease burden of Hib infections remain a high priority.

Impact of Vaccination on Haemophilus influenzae Type b Carriage in Healthy Children Less Than 5 Years of Age in an Urban Population in Nepal.

BackgroundReduction in detection of asymptomatic carriage of Haemophilus influenzae type b (Hib) can be used to assess vaccine impact. In Nepal, routine vaccination against Hib in children at 6, 10, and 14 weeks of age was introduced in 2009. Before vaccine introduction, Hib carriage was estimated at 5.0% among children aged <13 years in Nepal, with higher rates among children under 5. Large-scale evaluation of Hib carriage in children has not been investigated since the introduction of the pentavalent diphtheria-tetanus-pertussis/Hib/hepatitis B (DTP-Hib-HepB) vaccine in Nepal.MethodsA total of 666 oropharyngeal swabs were collected between August and December 2018 from healthy children between 6 months and 5 years of age attending the vaccination clinic at Patan Hospital, Kathmandu, Nepal. Of these 666 swabs, 528 (79.3%) were tested for Hib by culture. Demographic and vaccination data were collected.ResultsAmong 528 swabs tested for Hib, 100% came from fully vaccinated children. No swabs were positive for Hib (95% confidence interval, .0–.7). The absence of Hib in 2018 suggests vaccine-induced protection against Hib carriage 9 years after vaccine introduction.ConclusionsFollowing 3 doses of pentavalent DTP-Hib-HepB vaccine, Hib carriage in children under the age of 5 years in Nepal is no longer common. Ongoing high coverage with Hib vaccine in early childhood is expected to maintain protection against Hib disease in Nepal.

Cost-Minimization and Budget Impact Analysis of a Hexavalent Vaccine (Hexaxim®) in the Colombian Expanded Program on Immunization

ObjectivesTo evaluate cost implications of a hexavalent vaccine (diphtheria, tetanus, and acellular pertussis [DTaP]–inactivated polio vaccine [IPV]–hepatitis B [HB]–Haemophilus influenzae type B [Hib] polysaccharide conjugated to T protein [PRP∼T]) as an alternative to DT-whole-cell pertussis (wP)–HB//Hib, DTwP, IPV, and oral polio vaccines in the Expanded Program on Immunization schedule in Colombia. MethodsPrimary vaccination (DTaP–IPV–HB–PRP∼T or DTwP–HB–Hib + IPV [2, 4, 6 months]) and booster (DTaP–IPV–HB–PRP∼T or DTwP + oral polio vaccine [18 months]) (scenario 1) and primary vaccination only (DTaP–IPV–HB–PRP∼T or DTwP–HB–Hib + IPV) (scenario 2) were evaluated. An estimated cost-minimization analysis was based on a micro costing technique for vaccination-associated activities. Adverse event (AE)-associated costs, out-of-pocket costs, and productivity losses for caregivers were included. A budget impact (12-month temporal horizon) was estimated according to the distribution of full-term and premature infants. A 5% annual discount rate was used. A 2-way univariate (tornado) analysis evaluated which variables had the greatest impact on the overall cost. ResultsDTaP–IPV–HB–PRP∼T resulted in a cost increase of 29.38% (scenario 1) and 22.19% (scenario 2) for full-term infants and a decrease of 0.99% (scenario 1) and 18.88% (scenario 2) for premature infants, probably because of the higher incidence of wP-related AEs and associated costs in premature infants. With a 100% replacement rate, the budget impact for full-term infants and full-term plus premature infants was 23.73% and 21.80% (scenario 1), respectively, and 13.02% and 11.14% (scenario 2), respectively, of the national immunization program budget. The variables with most impact were the hexavalent vaccine price and costs associated with the pentavalent safety profile. ConclusionsIncorporation of the hexavalent vaccine in the Expanded Program on Immunization schedule would lead to an increase in spending largely mitigated by reduced AE incidence and reduced logistic and social costs.

National and provincial impact and cost-effectiveness of Haemophilus influenzae type b conjugate vaccine in China: a modeling analysis

BackgroundGlobally, Haemophilus influenzae type b (Hib) vaccine has substantially reduced the burden of Hib invasive disease. However, China remains the only country not to include Hib vaccine into its national immunization program (NIP), although it accounts for 11% of global Hib deaths. We aimed to assess the cost-effectiveness of including Hib vaccine in China’s NIP at the national and provincial levels.MethodsUsing a decision-tree Markov state transition model, we estimated the cost-effectiveness of Hib vaccine in the NIP compared to the status quo of Hib vaccine in the private market for the 2017 birth cohort. Treatment costs and vaccine program costs were calculated from Chinese Center for Disease Control and Prevention (CDC) and national insurance databases. Epidemiological data and other model parameters were obtained from published literature. Cases and deaths averted, quality-adjusted life years (QALYs) gained, and incremental cost-effectiveness ratios (ICER) were predicted by province. Deterministic and probabilistic sensitivity analyses were performed to explore model uncertainty.ResultsIncluding Hib vaccine in the NIP was projected to prevent approximately 2700 deaths (93% reduction) and 235,700 cases of Hib disease (92% reduction) for the 2017 birth cohort at the national level. Hib vaccine was cost-effective nationally (US$ 8001 per QALY gained) compared to the GDP per capita and cost-effective in 15 of 31 provinces. One-way and scenario sensitivity analyses indicated results were robust when varying model parameters, and in probabilistic sensitivity analysis, Hib vaccine had a 64% probability of being cost-effective nationally.ConclusionIntroducing Hib vaccine in China’s NIP is cost-effective nationally and in many provinces. Less socioeconomically developed provinces with high Hib disease burden and low access to Hib vaccine in the current private market, such as those in the west region, would benefit the most from adding Hib vaccine to the NIP. In the absence of a national policy decision on Hib vaccine, this analysis provides evidence for provincial governments to include Hib vaccine into local immunization programs to substantially reduce disease burden and treatment costs.

Haemophilus influenzae type b (Hib) seroprevalence in France: impact of vaccination schedules

BackgroundHaemophilus influenzae serotype b (Hib) conjugate vaccine was introduced in France in 1992 as a 3 + 1 scheme at 2, 3, and 4 months (primary vaccination) with a booster at the age of 16–18 months. The vaccination was simplified in 2013 to a 2 + 1 scheme at 2 and 4 months (primary immunization) and a booster at the age of 11 months. The coverage was 95.4% in France at 24 months in 2017. During the period 2017–2019 the number of Hib invasive infections increased with several cases of vaccine failure.MethodsThe numbers and proportions of Hib invasive isolates during the period 2017–2019 were compared and vaccine failure cases were explored. A seroprevalence study was performed by measuring anti-polyribosyl-ribitol phosphate (PRP) IgG concentrations by ELISA among children < 5 years of age at the time of sampling covering the periods of the 3 + 1 or 2 + 1 schemes of Hib vaccination. A collection of residual 232 sera was tested (group 3 + 1 n = 130) and (group 2 + 1, n = 102) was used.ResultsAnti-PRP IgG concentrations were significantly higher in toddlers of 2 years (median 2.9 μg/ml) in the 3 + 1 group while these concentrations showed a median of 0.58 μg/ml among children in 2 + 1 group. The proportion of children of 2 years of age who achieved 1 μg/ml threshold (56%) was higher in the 3 + 1 group than that observed in the 2 + 1 group (25%). All the detected cases of vaccine failure received the 2 + 1 scheme and anti-PRP IgG levels were less than 1 μg/ml at the admission. However, these levels increased significantly 1 month after the admission suggesting a secondary immune response to the Hib infection.ConclusionsThe simplification of the vaccination to a 2 + 1 scheme seems to reduce the level of anti PRP IgG. Hib antibodies wane rapidly after the 11 months booster and may not be enough to ensure long term protection. Surveillance of cases and monitoring of titres need to be continued to inform future vaccination policy.

The Impact of Haemophilus Influenzae and Streptococcus Pneumoniae Vaccination in Bacterial Meningitis in a Pediatric Referral Hospital in Mexico

Abstract Objective This study aimed to compare the epidemiology of bacterial meningitis (BM) before and after vaccination, and identify possible risk factors associated with mortality. Methods The medical and microbiologic records of children (1 month–18 years) with a discharge diagnosis of BM in a third level children's hospital in Mexico from 1990 to 2018 were reviewed. The epidemiology, pathogens, and outcomes were compared before and after introducing Haemophilus influenzae type b (Hib) and pneumococcal conjugate vaccines to the Mexican immunization schedule. Risk factors associated with mortality were determined. Results In the 28-year period, 226 cases with BM were included 55.8% (1990–1999), 27.4% (2000–2008), and 16.8% (2009–2018) (p = 0.0001). The most frequent pathogen was Hib, documented in 39% of cases. There was a reduction in neurological complications after introducing the Hib conjugate vaccine (59 vs. 39%; p = 0.003) and sequelae after the Streptococcus pneumoniae conjugate vaccine (43 vs. 35%; p = 0.05). Independent risk factors associated with mortality were coma (odds ratio [OR]: 15 [2.9–78]), intracerebral bleeding (OR: 3.5 [1.4–12]), and pneumococcal meningitis (OR: 9.4 [2.2–39]). Conclusion Since the introduction of Hib and pneumococcal conjugate vaccines to the national immunization schedule, there was a reduction in BM cases, mainly associated with the Hib vaccine, with the consequent reduction of neurological complications and sequelae.

Immunogenicity and Efficacy of Pneumococcal Conjugate Vaccine (Prevenar13®) in Preventing Acquisition of Carriage of Pneumococcal Vaccine Serotypes in Tanzanian Children With HIV/AIDS.

In every year, up to one million children die due to pneumococcal disease. Children infected with Human Immunodeficiency Virus (HIV) are mostly affected, as they appear to have higher rates of pneumococcal carriage and invasive disease. Successful immunity is dependent on mounting a sufficient immune response to the vaccine. We conducted a double blinded crossover randomised controlled trial to determine the serum antibody response (≥4-fold and geometric mean concentration) to pneumococcal vaccine (PCV13) serotypes at 3 months after second vaccination. We also determined the number and proportion of children carrying new (not present at baseline) vaccine serotypes of S. pneumoniae isolated from nasopharynx at 6 months post initial vaccination in recipients of Prevenar13® compared with those given Haemophilus influenzae-type b (Hib) vaccine (control). The study was conducted at St Augustine's also known as Teule Hospital in Muheza, Tanga Tanzania. 225 HIV infected children aged 1-14 years were enrolled from Jan 2013 to Nov 2013 and randomised to Prevenar13® or Hib vaccines each given at baseline and 2-3 months later. Nasopharyngeal and serum samples were collected at baseline and 4-6 months later. Serotyping was done by Quellung Reaction using Staten antisera. Serum antibodies were ELISA quantified. The study revealed a non-significant reduction in the acquisition of new vaccine serotypes of S. pneumoniae in the recipients of PCV13 by nearly a third compared to those who received Hib vaccine. The vaccine efficacy was 30.5% (95% confidence interval [CI] –6.4-54.6%, P = 0.100)]. The antibody response was not enough to induce a 4-fold rise in GMC in 7 of the 13 vaccine serotypes. When combining the effects of preventing new acquisition and clearing existing vaccine type carriage, the overall efficacy was 31.5% (95% CI 1.5-52.4%, P = 0.045). In the PCV13 group, the proportion of participants carrying vaccine serotype was significantly lower after 2 doses of PCV13 (30%; 32/107), compared with the baseline proportion (48%; 51/107). The introduction of PCV13 targeting HIV-positive children in a setting similar to Tanzania is likely to be associated with appreciable decrease in the acquisition and carriage of pneumococci, which is an important marker of the likely effect of the vaccine on pneumococcal disease.Clinical Trial Registration https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=335579, identifier ACTRN12610000999033.

Cloning and Characterization of Immunological Properties of Haemophilus influenzae Enolase.

Haemophilus influenzae is a common organism of the human upper respiratory tract; this bacterium is responsible of a wide spectrum for respiratory infections and can generate invasive diseases such as meningitis and septicemia. These infections are associated with H. influenzae encapsulated serotype b. However, the incidence of invasive disease caused by nontypeable H. influenzae (NTHi) has increased in the post-H. influenzae serotype b (Hib) vaccine era. Currently, an effective vaccine against NTHi is not available; due to this, it is important to find an antigen capable to confer protection against NTHi infection. In this study, 10 linear B cell epitopes and 13 CTL epitopes and a putative plasminogen-binding motif (252FYNKENGMY260) and the presence of enolase on the surface of different strains of H. influenzae were identified in the enolase sequence of H. influenzae. Both in silico and experimental results showed that recombinant enolase from H. influenzae is immunogenic that could induce a humoral immune response; this was observed mediating the generation of specific polyclonal antibodies anti-rNTHiENO that recognize typeable and nontypeable H. influenzae strains. The immunogenic properties and the superficial localization of enolase in H. influenzae, important characteristics to be considered as a new candidate for the development of a vaccine, were demonstrated.

A Laboratory-Based Surveillance Study of Invasive Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae Diseases in a Serbian Pediatric Population-Implications for Vaccination.

The aim of this study was to present the epidemiology of invasive diseases caused by Neisseria meningitidis and Streptococcus pneumoniae in the pre-vaccine period, and Haemophilus influenzae in the post-vaccine period in a pediatric population from Serbia. Among the meningococci, serogroup B dominated (83%), followed by serogroup C (11.3%). High antigenic diversity was found, with fine type P1.5-1,10-4 being the most frequent. Moderate susceptibility to penicillin was common (55%). Within pneumococci, serotypes 19F, 14, 6B, 6A, 18C, 23F, 3, and 7F prevailed, while 19A was rare (3.6%). The coverages of PCV10 and PCV13 were 68% and 84%, respectively. Major sequence types were ST320, ST15, ST273, ST271, and ST81. Non-susceptibility to penicillin (66.7%), cefotaxime (37%), and macrolides (55%) was predominantly detected in vaccine-related serotypes. Among the 11 invasive H. influenzae isolates collected, there were six Hib, three non-type b, and two non-typeable strains (ntHi) that were antibiotic susceptible. These results imply a potential benefit of future Men-B vaccine implementations. For pneumococci, as PCV10 was recently introduced, a significant reduction of morbidity and antibiotic resistance might be expected. The efficiency of Hib vaccination is evident, but a shift towards non-type b and ntHi strains may be anticipated.