Safety Observation Study on Haemophilus Influenza Type B Conjugate Vaccines Injected at Different Sites in Chinese Infants

In the present study, the safety of Hoemophilus influenza type b conjugate vaccines inoculated in the upper arm deltoid and vastus lateralis muscle was evaluated. 680 infants aged 2-5 months and 6-12 months were selected to be the research subjects in whom the Hib conjugate vaccines were inoculated by injection in the upper arm deltoid and vastus lateralis muscle, respectively. The safety analysis indicated that there were no statistic differences in the incidence rates of adverse reactions when the Hib conjugate vaccines were inoculated at different sites. So we concluded that the safety of inoculation injection of Hib conjugate vaccines in vastus lateralis muscle was the same as that inoculated in the upper arm deltoid.

Clinical Characteristics of Haemophilus influenzae at General Hospital in the Central Region of Japan

Haemophilus influenzae is an important pathogen that caused several infection diseases, such as sinusitis, otitis media, sepsis, and meningitis. This study was conducted to find out the prevalence and antimicrobial susceptibility pattern of Haemophilus influenzae isolates at general hospital in the central region of Japan from December 2015 to January 2016. Haemophilus influenzae was identified by standard laboratory procedure. Antimicrobial susceptibility testing was performed by micro dilution assay according to CLSI recommendation. One hundred ninety-one Haemophilus influenzae were isolated, among which 95 (49.7%) were from male and 96 (50.3%) were from female. The age incidence of (0) years, (≤2) years, (≤5) years, and (6≤) years groups were 22(11.5%), 92(48.2%), 61(31.9%), and 16(8.4%), respectively. Positive samples were received mostly from the nasal discharge (177/92.7%), sputum (6/3.1%), tonsillar (6/3.1%), and pharynx (2/1.0%). Ceftriaxone was the most active antibiotics with 100% susceptible rates, followed by ciprofloxacin (99.5%) and minocycline (99%) in our study. Furthermore, we categorized four patterns: beta lactamase-negative ampicillin-sensitive strain (BLNAS), beta lactamase-negative ampicillin-re- sistant strain (BLNAR), beta lactamase-positive ampicillin resistant strain (BLPAR), and beta lactamase-positive amoxicillin-clavulanic acid-resistant strain (BLPACR) from those ampicillin susceptible results. The numbers of female were significant greater than those of male in BLPAR (p = 0.0336). With respect to antimicrobial susceptible pattern, there was no minocycline and piperacillin resistant strain in both BLNAS and BLNAR (p

Report of Haemophilus Influenzae serotype a intracranial infections in older children

Introduction:Haemophilus influenzae(Hi)is subdivided into typeable(a-f)and non-typeable groups.Hi serotype b(Hib)has historically been one of the important pathogens responsible for invasive infection.However,after widespread Hib vaccination,the emergence of other Hi serotypes,specifically Hi serotype a(Hia),was noted during the last few decades,mostly in children younger than 5 years of age.Case presentation:We present two cases of severe intracranial infections with detected Hia in patients>5 years of age within a short time frame and within the same geographic area.Conclusion:Epidemiological studies and surveillance on Hia-related illnesses in all age groups worldwide are needed to better understand the clinical and epidemiological characteristics of Hia.This can establish a platform to develop a candidate vaccine against Hia that might protect children of all ages.

Can non-typeable Haemophilus influenzae carriage surveillance data infer antimicrobial resistance associated with otitis media?

Importance:In remote communities of the Northern Territory,Australia,children experience high rates of otitis media(OM),commonly caused by non-typeable Haemophilus influenzae(NTHi).Few data exist on antibiotic susceptibility of NTHi from OM.Objective:To determine whether population-level nasopharyngeal NTHi antibiotic susceptibility data could inform antibiotic treatment for OM.Methods:NTHi isolates(n=92)collected from ear discharge between 2003 and 2013 were selected to time-and age-match NTHi isolates from the nasopharyngeal carriage(n=95).Antimicrobial susceptibility were tested.Phylogenomic trees and a genome-wide association study(GWAS)were performed to determine the similarity of nasopharyngeal and ear isolates at a population level.Results:Among 174 NTHi isolates available for antimicrobial susceptibility testing,10.3%(18/174)were resistant to ampicillin and 9.2%(16/174)were resistant to trimethoprim-sulfamethoxazole.Small numbers of isolates(≤3)were resistant to tetracycline,chloramphenicol,or amoxicillin-clavulanic acid.There was no statistical difference in the proportion of ampicillin-resistant(P=0.11)or trimethoprim-sulfamethoxazole-resistant isolates(P=0.70)between ear discharge and nasopharynx-derived NTHi isolates.Three multi-drug resistant NTHi isolates were identified.Phylogenomic trees showed no clustering of 187 Haemophilus influenzae isolates based on anatomical niche(nasopharynx or ear discharge),and no genetic variations that distinguished NTHi derived from ear discharge and nasopharyngeal carriage were evident in the GWAS.Interpretation:In this population-level study,nasopharyngeal and ear discharge isolates did not represent distinct microbial populations.These results support tracking of population-level nasopharyngeal NTHi antibiotic resistance patterns to inform clinical management of OM in this population.

Activity of ciprofloxacin and azithromycin on biofilms produced in vitro by Haemophilus influenzae

Background It is recognized that Haemophilus influenzae isolated from patients with otitis media forms biofilms both in vitro and in vivo, suggesting that biofilm formation in vivo might play an important role in the pathogenesis and chronicity of otitis media, but the effect of antibiotics on biofilm has not been well studied. We investigated the impact of ciprofloxacin and azithromycin on bacterial biofilms formed by Haemophilus influenzae in vitro in this study. Methods Eleven strains of Haemophilus influenzae were isolated from sputum specimens collected from patients with acute exacerbation of chronic obstructive pulmonary diseases. Formation of bacterial biofUm was examined by crystal violet assay and a scanning electron microscope. Alterations of biofilms were measured under varying concentrations of azithromycin and ciprofloxacin. Results Striking differences were observed among strains with regard to the ability to form biofilm. Typical membrane-like structure formed by bacterial cells and extracellular matrix was detected. Initial biofilm synthesis was inhibited by azithromycin and ciprofloxacin at concentrations higher than two-fold minimal inhibitory concentration. Disruption of mature biofilms could be achieved at relatively higher concentration, and ciprofloxacin displayed more powerful activity. Conclusions Haemophilus influenzae is capable of forming biofilm in vitro. Sufficient dosage might control early formation of biofilms. Ciprofloxacin exerts better effects on breakdown of biofilm than azithromycin at conventional concentration in clinics.

Determination of ribose and phosphorus contents in Haemophilus influenzae type b capsular polysaccharide by a quantitative NMR method using a single internal standard

The ribose and phosphorus contents in Haemophilus influenzae type b(Hib)capsular polysaccharide(CPS)are two important chemical indexes for the development and quality control of Hib conjugate vaccine.A quantitative ^(1)H-and ^(31)P-NMR method using a single internal standard was developed for simultaneous determination of ribose and phosphorus contents in Hib CPS.Hexamethylphosphoramide(HMPA)was successfully utilized as an internal standard in quantitative ^(1)H-NMR method for ribose content determination.The ribose and phosphorus contents were found to be affected by the concentration of polysaccharide solution.Thus,15–20 mg·L^(−1) was the optimal concentration range of Hib CPS in D_(2)O solution for determination of ribose and phosphorus contents by this method.The ribose and phosphorus contents obtained by the quantitative NMR were consistent with those obtained by traditional chemical methods.In conclusion,this quantitative ^(1)H-and ^(31)P-NMR method using a single internal standard shows good specificity,accuracy and precision,providing a valuable approach for the quality control of Hib glycoconjugate vaccines.

Nasopharyngeal colonization of otopathogens in South Indian children with acuteotitis media -- A case control pilot study

Background: Acute otitis media (AOM) is an inflammatory disease of the middle ear causing significantmorbidity in early childhood. A pilot study was undertaken to identify the role of various risk factorsSouth Indian children with AOM, especially the role of nasopharyngeal otopathogens.Methodology: A prospective case control pilot study was conducted in children aged below six years,presenting to a single tertiary care from 2018 to 2019. Fifty cases with AOM and 45 age and gendermatched controls were recruited. Two nasopharyngeal swabs were collected, one was processed forbacterial culture. The other swab was processed according to the CDC recommended broth enrichmentmethod to identify carriage of S. pneumoniae. Subsequent serotyping was done by Quellung method andconventional sequential multiplex PCR.Result: Otalgia was the major presentation seen in 92% of the children with AOM. None of the clinical anddemographic characteristics were found to be statistically significant between the cases and controls. Themost common otopathogen was S. pneumoniae (55%) followed by H. influenza (29%). The commonS. pneumoniae serotypes encountered were 11A and 19F.Nasopharyngeal colonization with S. pneumoniae[OR 6.57, p < 0.003] and H. influenzae [OR14.18, p < 0.003] were significant risk factors for AOM inchildren. The risk increased with co-colonization (OR 13.89,p < 0.003).Conclusion: This study strengthens the significant association between nasopharyngeal colonization ofotopathogens and AOM as a risk factor that is enhanced by co-colonization.S. pneumoniae was the mainotopathogen in this population, serotypes 11A and 19F being the most common.

Prevalence and factors associated with pentavalent vaccination:a cross-sectional study in Southern China

Background Immunization is one of the most far-reaching and cost-effective strategies for promoting good health and saving lives.A complex immunization schedule,however,may be burdensome to parents and lead to reduced vaccine compliance and completion.Thus,it is critical to develop combination vaccines to reduce the number of injections and simplify the immunization schedule.This study aimed to investigate the current status of the pentavalent diphtheria-tetanus-acellular pertussis inactivated poliomyelitis andHaemophilus influenzae type B conjugate(DTaP-IPV/Hib)vaccination in Southern China as well as explore the factors in the general population associated with uptake and the differences between urban and rural populations.Methods A cross-sectional study was conducted with recently enrolled kindergarten students in Hainan Province between December 2022 and January 2023.The study employed a stratified multistage cluster random sampling method.Information regarding the demographic characteristics and factors that influence decisions were collected from the caregivers of children via an online questionnaire.Multivariate logistic regression was used to determine the factors associated with the status of DTap-IPV/Hib vaccinations.Results Of the 4818 valid responses,95.3%of children were aged 3-4 years,and 2856(59.3%)held ruralhukou.Coverage rates of the DTaP-IPV/Hib vaccine,from 1 to 4 doses,were 24.4%,20.7%,18.5%,and 16.0%,respectively.Caregivers who are concerned about vaccine efficacy[adjusted odds ratio(aOR)=1.53,95%confidence interval(CI):1.30-1.79],the manufacturer(aOR=2.05,95%CI:1.69-2.49),and a simple immunization schedule(aOR=1.26,95%CI:1.04-1.54)are factors associated with a higher likelihood of vaccinating children against DTaP-IPV/Hib.In addition,caregivers in urban areas showed more concern about the vaccine price(P=0.010)and immunization schedule(P=0.022)in regard to vaccinating children.Conclusions The DTaP-IPV/Hib vaccine coverage rate in Hainan Province remains low.Factors such as lower socioeconomic status,cultural beliefs,concerns about vaccine safety,and cost may hinder caregivers from vaccinating their children.Further measures,such as health education campaigns to raise knowledge and awareness,and encouragement of domestic vaccine innovation,which would reduce out-of-pocket costs,could be implemented to improve the coverage of DTap-IPV/Hib vaccination.

Synergistic and feedback signaling mechanisms in the regulation of inflammation in respiratory infections

Pneumonia, the most typical and frequent lower respiratory tract infection （LRTI）, is a leading cause of health problems in the United States. Bacteria represent the most prevailing cause of pneumonia in both children and adults. Although pneumonia with a single bacterial infection is common, a significant portion of patients with pneumonia is polymicrobial. This infection is often complexed with other physiological factors such as cytokines and growth factors. Nontypeable Haemophilus influenzae （NTHi） is the most frequently recovered Gram-negative bacterial pathogen in the respiratory system and induces strong inflammatory responses. NTHi also synergizes with other respiratory pathogens, such as Streptococcus pneumoniae and respiratory viruses and pro-inflammatory cytokines, such as tumor necrosis factor-alpha （TNF-α）. It is noteworthy that NTHi not only synergizes with growth factors such as transforming growth factor-beta （TGF-β）, but also utilizes growth factor receptors such as TGF-β receptor and epidermal growth factor receptor （EGFR）, to enhance inflammatory responses. Although appropriate inflammation is a protective response against invading pathogens, an uncontrolled inflammatory response is often detrimental to the host. Thus, inflammation must be tightly regulated. The human immune system has evolved strategies for controlling overactive inflammatory response. One such important mechanism is via regulation of negative feedback regulators for inflammation. CYLD, a multifunctional deubiquitinase, was originally reported as a tumor suppressor, but was recently identified as a negative regulator for nuclear factor-kappa B （NF-κB） signaling. It is induced by NTHi and TNF-α via a NF-κB-dependent mechanism, thereby serving as an inducible negative feedback regulator for tightly controlling inflammation in NTHi infection.

Polysaccharide conjugate vaccine:A kind of vaccine with great development potential

Diseases caused by microbial bacteria such as Haemophilus influenzae type b(Hib),Streptococcus pneumoniae and Neisseria meningitidis are still very serious disease,which has brought a lot of burden to many countries.Development of vaccine has brought hope for the prevention of such diseases.Polysaccharide conjugate vaccines have been shown to have very good effects in preventing such diseases.The polysaccharide co njugate vaccine adds the positive characteristics of protein antigens to the polysaccharide antigen,thereby improving the immunogenicity of the polysaccharide antigen,solving the problem that the polysaccharide vaccine cannot be effectively applicated in toddler or children,which greatly promoting the development of this vaccine.This review introduces the progress of polysaccharide conjugate vaccines.We introduce the typical polysaccharide conjugate vaccines currently on the market firstly,and then elucidate the protein carriers,the coupling chemistry methods and quality control that required in the preparation of polysaccharide conjugate vaccines.We can see that polysaccharide conjugate vaccine is a kind of vaccine with great development potential,which can be a sharp edge for us to prevent diseases.