Modeling insights into Haemophilus influenzae type b disease, transmission, and vaccine programs.
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ABSTRACT:
SUBMITTER: Jackson ML
PROVIDER: S-EPMC3310093 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: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.
| S-EPMC8356460 | biostudies-literature
Project description:Haemophilus influenzae 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.
| S-EPMC8482018 | biostudies-literature
Project description:BackgroundAdoption of new and underutilized vaccines by national immunization programs is an essential step towards reducing child mortality. Policy decisions to adopt new vaccines in high mortality countries often lag behind decisions in high-income countries. Using the case of Haemophilus influenzae type b (Hib) vaccine, this paper endeavors to explain these delays through the analysis of country-level economic, epidemiological, programmatic and policy-related factors, as well as the role of the Global Alliance for Vaccines and Immunisation (GAVI Alliance).Methods and findingsData for 147 countries from 1990 to 2007 were analyzed in accelerated failure time models to identify factors that are associated with the time to decision to adopt Hib vaccine. In multivariable models that control for Gross National Income, region, and burden of Hib disease, the receipt of GAVI support speeded the time to decision by a factor of 0.37 (95% CI 0.18-0.76), or 63%. The presence of two or more neighboring country adopters accelerated decisions to adopt by a factor of 0.50 (95% CI 0.33-0.75). For each 1% increase in vaccine price, decisions to adopt are delayed by a factor of 1.02 (95% CI 1.00-1.04). Global recommendations and local studies were not associated with time to decision.ConclusionsThis study substantiates previous findings related to vaccine price and presents new evidence to suggest that GAVI eligibility is associated with accelerated decisions to adopt Hib vaccine. The influence of neighboring country decisions was also highly significant, suggesting that approaches to support the adoption of new vaccines should consider supply- and demand-side factors.
| S-EPMC2838745 | biostudies-literature
Project description:During 5 months in 2014, three Amish children in Missouri, USA, were diagnosed with invasive Haemophilus influenzae type b infection. Two were rural neighbors infected with a genetically similar rare strain, sequence type 45. One child had recently traveled, raising the possibility of maintenance of this strain among unvaccinated carriers in Amish communities.
| S-EPMC5176238 | biostudies-literature
Project description:The highest incidence of meningococcal disease occurs in infants younger than 1 year of age. However, in the US, prior to June 2012, there was no meningococcal vaccine licensed for use in this age group. In the US, where both serogroups C and Y contribute substantially to the overall epidemiology of invasive meningococcal disease, a vaccine combining these capsular polysaccharides was developed. We review the newly licensed HibMenCY-TT (MenHibrix™, GlaxoSmithKline Biologicals, Rixensart, Belgium), a novel vaccine containing Haemophilus influenzae type b (Hib) and serogroups C and Y Neisseria meningitidis conjugated to tetanus toxoid. We describe the vaccine, summarize the clinical trial data, and describe the patient populations recommended to receive HibMenCY-TT as their primary vaccination against Hib. Phase II and III clinical trials found HibMenCY-TT to be well tolerated, safe, and immunogenic when administered at 2, 4, 6, and 12-15 months of age for primary vaccination against both Hib and serogroups C and Y meningococcal disease. In October 2012, the Advisory Committee on Immunisation Practice in the US recommended HibMenCY-TT vaccination for infants at increased risk of meningococcal disease. HibMenCY-TT may be given concomitantly with other routine infant vaccines. It induces antibodies against Hib as well as bactericidal activity against meningococcal serogroup C and Y without increasing the number of injections required. As meningococcal disease epidemiology is dynamic, global surveillance remains essential. In the future, other countries may also benefit from the addition of HibMenCY-TT into their vaccine armamentarium against meningococcal disease.
| S-EPMC4108092 | biostudies-other
Project description: Not available
| S-EPMC4593434 | biostudies-literature
Project description:Transcriptome analysis of NTHi 86-028NPrpsL, NTHi 86-028NPrpsL∆fur, and NTHi 86-028NPrpsL∆fur(pT-fur) strains Nontypeable Haemophilus influenzae (NTHi) is a commensal microorganism of the normal human nasopharyngeal flora, yet also an opportunistic pathogen of the upper and lower respiratory tracts. Changes in gene expression patterns in response to host microenvironments are likely critical for survival. One such system of gene regulation is the ability to carefully regulate iron uptake. A central regulatory system that controls iron uptake, mediated by the ferric uptake regulator Fur, is present in multiple bacteria, including NTHi. To understand the regulation of iron homeostasis in NTHi, fur was deleted in the NTHi strain 86-028NPrpsL. Using RNA-Seq, we identified both protein-encoding and small RNA genes whose expression was repressed or activated by Fur. Overall design: These data comprise transcriptional anaylses of an rpsL mutant of 86-028NP, an isogenic fur mutant of 86-028NPrpsL and a complemented fur mutant strain. All strains were grown in defined medium containing 10 µg/ml human hemoglobin to mid-log phase. Cells were then harvested and RNA extracted. A total of three biological replicates were generated for these analyses.
2015-07-01 | GSE58890 | GEO
Project description:Vaccines to prevent acute otitis media (AOM) caused by non-typeable Haemophilus influenzae (NTHi) are under development. Because NTHi is highly variable and colonization rates are high, special vaccine characteristics and trial designs might be needed. We examined in mathematical models the equilibrium NTHi-caused AOM rate given hypothetical vaccines that generated immunity identical to corresponding maximal naturally acquired immunity. Vaccines were examined with single effects and combinations of immunity affecting (1) AOM rates given colonization (pathogenicity), (2) susceptibility to colonization, and (3) contagiousness given colonization. Percent reductions in AOM across all preschool children were (1) 34%, (2) 31%, (3) 9%, (1 and 2) 57%, (2 and 3) 50%, and (1, 2, and 3) 75%. Effects on children in daycare vs. not in daycare were (1) 18 vs. 48%, (2) -1 vs. 57%, (3) 13 vs. 5%, (1 and 2) 30 vs. 79%, (2 and 3) 33 vs. 60%, and (1, 2, and 3) 64 vs. 85%. Pure pathogenicity effects (1 alone) will need to be supplemented by transmission effects. The effects of susceptibility (2 alone) are diminished or negative because children protected against colonization have lower levels of immunity to (1) and (3) than unvaccinated children. For trials to predict population effects, both colonization and AOM outcomes must be studied and all three effects must be evaluated. This need arises because, unlike H. influenzae type B, high NTHi exposure diminishes cumulative vaccine effects and high colonization rates generate rapid accumulation of natural immunity that alters the indirect effects of vaccine immunity on transmission differently by age and daycare status.
| S-EPMC1852514 | biostudies-literature
Project description:The implementation of pneumococcal conjugate vaccines (PCVs) has led to a decline in vaccine-type disease. However, there is evidence that the epidemiology of non-typeable Haemophilus influenzae (NTHi) carriage and disease can be altered as a consequence of PCV introduction. We explored the epidemiological shifts in NTHi carriage using whole genome sequencing over a 5-year period that included PCV13 replacement of PCV7 in the UK's National Immunization Programme in 2010. Between 2008/09 and 2012/13 (October to March), nasopharyngeal swabs were taken from children <5 years of age. Significantly increased carriage post-PCV13 was observed and lineage-specific associations with Streptococcus pneumoniae were seen before but not after PCV13 introduction. NTHi were characterized into 11 discrete, temporally stable lineages, congruent with current knowledge regarding the clonality of NTHi. The increased carriage could not be linked to the expansion of a particular clone and different co-carriage dynamics were seen before PCV13 implementation when NTHi co-carried with vaccine serotype pneumococci. In summary, PCV13 introduction has been shown to have an indirect effect on NTHi epidemiology and there exists both negative and positive, distinct associations between pneumococci and NTHi. This should be considered when evaluating the impacts of pneumococcal vaccine design and policy.
| S-EPMC6202451 | biostudies-literature
Project description:A real-time PCR assay targeting the capsulation locus of Haemophilus influenzae type b (Hib) was developed. The linear detection range was from 1 to 10(6) microorganisms per reaction mixture. No H. influenzae other than Hib or any other control bacteria typically found in the upper respiratory tract was detected.
| S-EPMC497579 | biostudies-literature