Antibody Levels and Infection Status of Pertussis in the Population under Pertussis Resurgence in Guangxi in 2018:A Cross-Sectional Survey

Objective Pertussis cases have increased markedly since 2018 in Guangxi.The aim of this study was to evaluate antibody levels and the infection status of pertussis in the resident population.Method A total of 10,215 serum samples from residents were collected from August-November 2018 and tested for anti-pertussis IgG and toxin IgG using the enzyme-linked immunosorbent assay(ELISA).Results Of the collected samples,1,833(17.94%)tested positive for anti-pertussis IgG,with the median concentration of 16.06 IU/mL.Antibody level<10 IU/mL accounted for more than 60%in children under 4 years of age,but declined with age,whereas the percentages of the other three levels(10-40,40-50,and≥50 IU/mL)increased almost with age(P<0.001).Moreover,7,924 samples were selected for anti-pertussis toxin IgG,of which 653(8.24%)tested positive(≥40 IU/mL)with the median concentration of 5.89 IU/mL,and 204 participants(2.56%)had recent pertussis infection(≥100 IU/mL).Among the different age groups,the highest rates of positivity and recent infection were observed at 11-20 years of age,the lowest positivity rate at 5 years of age,and the lowest recent infection rate at 4 years of age(P<0.001,P=0.005,respectively).Conclusion The survey results showed that all age groups in Guangxi lacked immunity against pertussis,which was one of the main factors contributing to the resurgence of pertussis in 2018.In addition,the prevalence of pertussis is relatively high in Guangxi,and its incidence is seriously underestimated,especially in adolescents and adults.

The First Reported Case of Co-Infection with Neisseria Meningitidis and Bordetella Pertussis in the Cerebrospinal Fluid Specimen of a Normal Four-Year-Old Child

Pertussis is an acute and highly contagious respiratory disease caused by Bordetella pertussis(B.pertussis),which occurs in people of all ages and is most dangerous for young children,especially infants.The introduction of whole-cell pertussis vaccines(wPVs)in the 1950s dramatically reduced the incidence of pertussis worldwide[1].However,over the past two decades,many studies have reported the resurgence of pertussis in different countries[2].Epidemiological surveillance in Hubei Province over the last 3 years revealed a clear increasing trend in the incidence of pertussis during the coronavirus disease 2019(COVID-19)epidemic.

Characterization of two Achromobacter xylosoxidans isolates from patients with pertussis-like symptoms

Objective:To characterize two Achromobaeter xylosoxidans recovered from 2 patients diagnosed with pertussis during a Bordetella pertussis surveillance program.Methods:Nasopharyngeal swabs from 2 children under 1 year of age with clinical suspicion of pertussis were analyzed by culture and PCR.Results:Two Achromobaeter xylosoxidans A8,closely related to Bordetella spp.were recovered from 2 patients diagnosed of pertussis,both carrying the ptxA gene and IS418 the pertussis toxin encoding gene.Subsequently,antibiotic susceptibility was evaluated by disk-diffusion method and by PCR.Conclusions:Although more detailed studies are needed,the present data highlight the possibility that Achromobaeter xylosoxidans.closely related Bordetella pertussis microorganisms and not covered under the vaccine umbrella,might also result in cases of whooping cough.Thereby further surveillance is necessary to determine the extension and relevance of their pathogenic role in order to discriminate their real public health implication.

Epidemiological Characteristics and Risk Factors of the Pertussis in Infants < 12 Months of Age in Tianjin, China

The epidemiologic characteristics of 631 infant pertussis cases 〈 12 months, which accounted for 57.42% of the total cases, were analyzed by descriptive epidemiology in Tianjin, between 2010 and 2015. The incidence of infants was 104.66/100,000, which was 118 times higher than in other age groups （P 〈 0.001）. The primary type of pertussis simultaneously presented in households was adult-to-infant （70.51%）. The parents were identified as the source of infection in 80.18% of cases for infants. The positive rate of placental antibody transfer was 31.06% and 3.13% for 3-month-old infants. Infants presented the highest age-specific pertussis incidence. The most important reason was parents were the important sources of infection, and secondly the lower level of antibodies in neonates and the rapid waning of maternal antibody titer.

Risk factors for pertussis among children hospitalized for pertussis during 2016-2017, in Guizhou Province of China: a case-control study

Aim:Pertussis is a respiratory tract infection,the vaccine for which was introduced in the Expanded Programme on Immunization(EPI)in Guizhou Province of China(hereafter referred as Guizhou)in the 1980s.This vaccine rapidly decreased incidence rates of pertussis in the province,however,despite the wide high coverage of the diphtheria,tetanus and acellular pertussis(DTaP)combined vaccine,there has been a resurgence of pertussis since 2014.Even with this recent increase in disease transmission,risk factors for pertussis infection have not been evaluated in Guizhou.We aimed to provide information on pertussis risk factors and insight on designing targeted pertussis control policies and measures through this study.Methods:A 1:2 matched retrospective case-control study was conducted between 2016 and 2017,involving infants and children younger than 6 years old and parents of the participants.The enrolled cases included clinical and laboratory confirmed pertussis cases according to the WHO-recommended pertussis definition.Controls were selected from children in the same neighborhood who were not diagnosed with pertussis prior to our investigation and did not exhibit any clinical manifestations of pertussis.Results:The household size[Matched odds ratio(OR_(m)=1.4,95%confidence interval(Cl):1.1-1.7]and household members with antecedent cough(OR_(m)=3.6,95%CI:1.8-7.2)were significantly associated with their child’s pertussis onset.The parents’occupations were significantly associated with their child’s pertussis onset(ORm=9.4,95%CI:1.6-54.8,for mother side;ORm=4.5,95%CI:1.2-16.5,for father side),when they worked in the business and/or service industry.Having family members with a history of cough was an independent risk factor for pertussis[Adjusted odds ratio(AOR)=43.6,95%CI:2.7-694.0].Besides,the parents’demographic characteristics and DTaP doses were not found to be independent factors.Conclusion:Household exposure is an important risk factor for pertussis infection in infants and young children and should therefore be considered as a major factor during formulation of pertussis control policies and measures.

Research on pharmacological mechanism of the treatment of Asthma by oral Bordetella pertussis

Objective To examine the effect of oral Bordetella pertussis on the asthma mice sensitized by ovalbumin(OVA),and explore the possible mechanism.Methods Culture the B.pertussis in Bordet-Gengou agar containing 25% rabbit blood.Collect the bacteria and inactive them at 80 ℃ for 30 min to get whole killed B.pertussis.32 BALB/C mice were randomly divided into control group,model-control group,model group and treatment group.The mice were sensitized and challenged with OVA to establish asthma model.Asthma mice in treatment group were orally administrated with B.pertussis 7 days before sensitization.The mice in control group and model-control group were challenged with saline.After 24 hours of last challenge,bronchoaveolar lavage fluid(BALF)and peripheral blood were collected.The total cells and eosinophils were counted in BALF.Results Compared with the control group(2.03±0.42,0.33±0.82)×105 mL-1 and model-control group(2.16±0.48,0.16±0.41)×105 mL-1,the total cells(10.13±1.33)×105 mL-1 and eosinophils(11.83±4.573)×105 mL-1 in BALF were more in asthma mice(P<0.01).The number of total cells(5.50±1.55)×105 mL-1 and eosinophils(0.66±0.82)×105 mL-1 in BALF were reduced in asthma mice treated with B.pertussis compared with asthma mice(P<0.01).Conclusions Oral B.pertussis can inhabit airway inflammation of asthma mice and has the potential of treating asthma.

Aberration detection of pertussis from the Mazandaran province, Iran, from 2012 to 2018: Application of discrete wavelet transform

Objective:To define the level of alarm threshold for pertussisaberrations and to detect the aberrations of the reported suspectedcases of pertussis from the Mazandaran province in the north ofIran.Methods:The included cases were composed of the suspectedpertussis patients who came from Mazandaran province andregistered in the Center for Disease Control and Prevention from20 March 2012 to 20 March 2018.A discrete wavelet transformbasedmethod was used to detect the aberrations.All analyseswere performed using MATLAB Software version 2018a andExcel 2010.Results:A total of 1162 cases were recruited in the study,including 545(46.90%)males and 617(53.10%)females,withmedian age of 1.47(0.22-9.56)years.The median age of maleswas 1.18(0.21-8.24)years,while that of females was 1.82(0.21-10.75)years.Concerning the level of the alarm threshold,it was1.28 case/d when k=2,while it was 1.34 case/d when k=3.Thetotal detected aberration days were 123 d and 57 d by consideringk=2 and 3,respectively.The most defined alarm threshold wasrelated to spring(>2 cases/d)and summer(>1 case/d),respectively.Conclusions:The sensitivity of the surveillance system issubjected to a different time.Thus,determining the level of alarmthreshold periodically using different methods is recommended.

30 and 32 kDa outer membrane proteins of Bordetella pertussis as a modulator on promoting degranulation of mast cells

The correlation between the activities of the outer menbrane proteins （OMPs） of Bordetella pertussis and the lgE-mediated asthma was investigated in the present study, in which the OMPs of B. pertussis and their components were prepared by detergent treatment and chromatography, and the molecular weights of the OMPs components were determined by SDS-PAGE. The amounts of total as well as the ovalbumin （OVA）-specific IgE induced by dead B. pertussis whole bacterial vaccine on guinea pigs were detected by ELISA. Meanwhile, the effect of the OMPs and their components to promote the degranulation of guinea pig mast cells was observed by using the mast cell degranulation test, and ELISA assay was used to measure the histatmine levels in the supematants from the mast cell cultures. Histamine sensitive test was used to demonstrate the effects of the OMPs and their components to increase the histamine lethal sensitivity in mice. It was found that four components with molecular weights of 30, 32, 38 and 69 kDa could be obtained from the OMPs of B. pertussts, and the dead whole bacteria vaccine of B. pertussis had the ability to increase the levels of the total as well as the OVA-specific IgE in sera of guinea pigs. The OMPs and their 30 and 32 kDa components demonstrated significantly enhancing effect on the degranulation of guinea pig mast cells, and the histamine levels in the supematants from the mast cell culture treated with OMPs and their 30 and 32 kDa components were also significantly increased. It is evident that the strong adjuvant activity and the enhancing effect to degranulation of mast cells and the release of histamine of certain outer membrane components of B. pertussis could be demonstrated as revealed by the results of the present study, suggesting the possibility of a close relationship between the infection of vaccination with B. pertussis and the IgE-mediated asthma.

Resurgence of pertussis:reasons and coping strategies

Pertussis(whooping cough)is an acute and contagious respiratory disease caused by the pathogen Bordetella pertussis(B.pertussis).B.pertussis can infect individuals of all ages.Children with pertussis may experience severe and persistent coughing and paroxysms;for newborns and infants,pertussis may be life-threatening.The development and widespread administration of the pertussis vaccine had once successfully brought pertussis under control,maintaining it at a low level for many years.However,resurgence of pertussis has been reported in many countries even with high vaccination coverage recently.The resurgence of pertussis was first reported in the United States(USA)in 1993[1].During 2000–2016,the baseline incidence increased and the age distribution of pertussis changed in the USA[2].Other countries including Canada[3],Australia[4],European Union countries,and South Korea have also reported a rise in pertussis outbreaks[2,5].

A scoping review of studies on women's knowledge regarding Tdap vaccination during Pregnancy

This review aimed to determine and identify the knowledge and attitude of the mothers or pregnant women toward the Tdap vaccine during pregnancy.Whooping cough,Diphtheria disease and tetanus are infectious and pathogenic bacterial diseases that mainly affect children too young to complete basic vaccinations,and deaths associated with infectious diseases are frequent among them.Therefore,it is advisable for pregnant women to take the triple bacterial vaccine(tetanus,diphtheria and pertussis).This scoping review was conducted,and various electronic databases were searched,including Medline and PubMed.Moreover,Google Scholar,CDC,and immunization research group websites were searched to investigate the literature on the Tdap vaccine.As a result,13 studies were included in this review.Based on the findings of this review,the level of knowledge of ladies and pregnant women about the importance of the vaccine depended upon several factors,including education level,occupation,age,sources of vaccine information,maternal desire,being born outside the country,lower household income,religious misconception,residing in a province or area where the pertussis vaccine was not free,having given birth to live children in the past,and receiving maternity care from a midwife.Therefore,it can be concluded that the increase in the level of knowledge about the importance of Tdap vaccine increased the percentage of women who supported and accepted the vaccine.Studies have also shown that some mothers refused vaccination due to reservations about vaccine safety and efficacy since they did not have sufficient knowledge or experience.

Emergence of Erythromycin-Resistant and Pertactin-and Filamentous Hemagglutinin-Deficient Bordetella pertussis Strains—Beijing,China,2022-2023

What is already known about this topic?Pertussis has reemerged as a significant public health threat,primarily due to variations in Bordetella pertussis strains,antimicrobial resistance,and vaccine evasion.What is added by this report?All isolated strains were identified as ptxA1/ptxC2/ptxP3/prn150/fim2-1/fim3-1/fhaB1/tcfA2 type and exhibited resistance to erythromycin.

SDF-1/CXCR4在骨髓增生异常综合征患者中的生物学作用

本研究主要探讨骨髓增生异常综合征(MDS)及白血病患者中基质细胞衍生因子-1(SDF-1)在细胞凋亡、迁移和黏附中的作用及相关的信号转导。选取37例初发MDS患者〔低危组(IPSS≤1.0)22例,高危组(IPSS≥1.5)15例〕、10例初发白血病患者及14例良性贫血患者(作为对照组),通过流式细胞术检测骨髓CD34+细胞表面CXCR4的表达水平及CD34+细胞的凋亡情况。选取4例低危MDS患者和5例高危MDS患者,通过微孔细胞迁移实验检测SDF-1对细胞的趋化作用。通过CCK-8法检测SDF-1对细胞之间黏附能力的影响。结果表明,低危MDS组骨髓内CD34+细胞的凋亡率明显高于高危MDS组(21.33%vs 7.27%,p<0.001),同样低危MDS组骨髓内CD34+细胞的凋亡率明显高于白血病组(21.33%vs 7.53%,p<0.001),未发现CD34+细胞的凋亡率与患者年龄性别有相关性。SDF-1能够促进高表达CXCR4患者的细胞黏附于基质细胞并能诱导该细胞的迁移,诱导细胞形态发生极化,上述作用可以被G蛋白抑制剂pertussis toxin、PI3K抑制剂wortmannin及CXCR4拮抗剂AMD3100明显抑制;而对低表达CXCR4的患者细胞则无上述抑制作用。结论:SDF-1/CXCR4通过PI3K信号通路提高细胞的迁移及黏附能力,发挥抗凋亡作用,上述作用可以被PI3K途径抑制剂和G蛋白抑制剂所阻断。

Mechanisms mediating cholinergic antral circular smooth muscle contraction in rats

AIM:To investigate the pathway(s)mediating rat antral circular smooth muscle contractile responses to the cholinomimetic agent,bethanechol and the subtypes of muscarinic receptors mediating the cholinergic contraction. METHODS:Circular smooth muscle strips from the antrum of Sprague-Dawley rats were mounted in muscle baths in Krebs buffer.Isometric tension was recorded.Cumulative concentration-response curves were obtained for(+)-cis- dioxolane(cD),a nonspecific muscarinic agonist,at 10^(-8)- 10^(-4)mol/L,in the presence of tetrodotoxin(TTX,10^(-7)mol/L). Results were normalized to cross sectional area.A repeat concentration-response curve was obtained after incubation of the muscle for 90 min with antagonists for M1(pirenzepine), M2(methoctramine)and M3(darifenadn)muscarinic receptor subtypes.The sensitivity to PTX was tested by the ip injection of 100 mg/kg of PTX 5 d before the experiment.The antral circular smooth muscles were removed from PTX-treated and non-treated rats as strips and dispersed smooth muscle cells to identify whether PTX-linked pathway mediated the contractility to bethanechol. RESULTS:A dose-dependent contractile response observed with bethanechol,was not affected by TTx.The pretreatment of rats with pertussis toxin decreased the contraction induced by bethanechol.Lack of calcium as well as the presence of the L-type calcium channel blocker,nifedipine,also inhibited the cholinergic contraction,with a reduction in response from 2.5±0.4 g/mm^2 to 1.2±0.4 g/mm^2(P<0.05).The dose- response curves were shifted to the right by muscarinic antagonists in the following order of affinity:darifenacin (M_3)>methocramine(M_2)>pirenzepine(M_1). CONCLUSION:The muscarinic receptors-dependent contraction of rat antral circular smooth muscles was linked to the signal transduction pathway(s)involving pertussis-toxin sensitive GTP-binding proteins and to extracellular calcium via L-type voltage gated calcium channels.The presence of the residual contractile response after the treatment with nifedipine,suggests that an additional pathway could mediate the cholinergic contraction.The involvement of more than one muscarinic receptor(functionally predominant type 3 over type 2)also suggests more than one pathway mediating the cholinergic contraction in rat antrum.

Human μ-opioid receptor overexpressed in Sf9 insect cells functionally coupled to endogenous G_(i/o) proteins

Human μ-opioid receptor （HμOR） with a tag of six consecutive histidines at its carboxyl terminus had been expressed in recombinant baculovirus infected Sf9 insect cells.The maximal binding capacity for the [3H] diprenorphine and [3H]ohmefentanyl （Ohm） were 9.1± 0.7 and 6.52±0.23 nmol/g protein, respectively. The [3H] diprenorphine or [3H] Ohm binding to the receptor expressed in Sf9 cells was strongly inhibited by μ-selective agonists [D-Ala2], N-methylPhe4, glyol5]enkephalin （DAGO）, Ohm, and morphine, but neither by δ nor by K selective agonist. Na+ （100 mM） and GTP （50 μM） could reduce HμOR agonists etorphine and Ohm affinity binding to the overexpressed HμOR. μ-selective agonists DAGO and Ohm effectively stimulated [35S]GTPγS binding (EC50 = 2.7nM and 6.9 nM) and inhibited forskolin- stimulated cAMP accumulation (IC50 = 0.9 nM and 0.3 nM). The agonist-dependent effects could be blocked by opioid antagonist naloxone or by pretreatment of cells with pertussis toxin （PTX）. These results demonstrated that HμOR overexpressed in Sf9 insect cells functionally coupled to endogenous Gi/o proteins.

High IFN-α expression is associated with the induction of experimental autoimmune uveitis (EAU) in Fischer 344 rat

Th1-response plays a crucial role in determining pathogenesis of organ-specific autoimmune diseases. It is believed that both IL-12 and INF-alpha are initiators to regulate Th1-response. In our experimental autoimmune uveitis (EAU) model, both Lewis and Fischer 344 rats share the same MHC class II molecules, while Lewis rat is EAU susceptible and Fischer 344 rat is EAU resistant. However, under the same condition of immunization, if pertussis toxin (PTX) was injected intraperitoneally as an additional adjuvant, Fischer 344 rat can develop EAU. In this study we investigate which mechanisms are involved in the induction of EAU in CFA+R16+PTX-treated (CRP-treated) Fischer 344 rats. In vivo and in vitro data demonstrated that Th1-cytokine, IFN-gamma mRNA expression was significantly increased in disease target tissue-eyes and in draining lymph node cells of CRP-treated Fischer 344 rat. When IL-12 and IFN-alpha mRNA expression were compared in the experimental groups, only IFN-alpha mRNA expression was associated with EAU development. To distinguish the sources of IFN-alpha producing cells, it was observed that IFN-alpha expression was mainly produced by macrophages. It was further confirmed that normal macrophage from Fischer 344 rat was able to produce significant IFN-alpha in the presence of PTX. The data strongly suggested that IFN-alpha might be involved in initiating Th1-cell differentiation and in turn contribute to the induction of EAU. High IFN-alpha expression induced by PTX may represent a novel pathway to initiate Th1 response in Fischer 344 rat.

Vaccinations against respiratory infections in Arabian Gulf countries: Barriers and motivators

AIM To study the uptake, barriers and motivators of influen-za, pneumococcal, meningococcal and pertussis vaccines among members of public in Arabian Gulf countries.METHODS A cross-sectional survey among the Gulf Cooperation Council(GCC) countries' residents. Data collected electronically through a smartphone app. The survey variables aimed to investigate the respondents' awareness about vaccines against influenza, pneumococcal, meningococcal and pertussis infections. Collected data concerning the respondents' socio-demographic characteristics, their perception toward vaccine uptake and the factors that motivate or demotivate them from taking influenza vaccine. The data were analysed statistically using the SPSS v.23.0. Differences in the characteristics of users from different countries were quantified through bivariate analysis. Other important variables and controlling factors were studied using logistic regression. RESULTS A total of 1812 respondents participated in the study. Their mean age was 27 years, 82% were male and 24% had ≥ 1 chronic diseases. The overall uptake of influenza vaccine was 17%(21% among "at risk" people) and ranged from 15% in Saudi Arabia to 24% in Qatar. Doctor's advice(23%) and a perception of having low body immunity(21%) were the main cited reasons for being vaccinated, whereas unawareness about the vaccine(43%) was the main barrier. The overall uptake of pneumococcal vaccine in the preceding three years was 22%(25% among "at risk" individuals) and ranged from 0% in Bahrain to 79% in Kuwait. The overall uptake of pertussis vaccine was 16%(31% among "vulnerable" people), and ranged from 7% in Saudi Arabia to 75% in Oman. The overall uptake of meningococcal vaccine was 20%(29% among the "at risk" people) and ranged from 3% in Oman to 50% in Bahrain.CONCLUSION The vaccination uptake across GCC countries is suboptimal and varies widely across the countries. Further research is needed to unearth the reasons and formulate action plan.

diabetes mellitus

950257 Report of a case of glucagonoma misdiag-nosed as“eczema”and“hepatic angioma”for three yearsand review of literature.DAI Weixin(戴为信),et al.PUMC Hosp,Beijing,100730.Chin J Intern Med 1995;34(3):190-192.Glucagonoma is a rare pancreatic tumor,necrolyticmigratory erythema is its distinctive feature and it isoften associated with diabetes mellitus,weight loss.anemia,hypoaminoacidemia,glossitis and stomatitis.

23.PREVENTION

920405 Immunization of hepatitis Bvaccineintegrated with EPI schedule in children.

Analysis of prevailing pertussis strains from different regions in China after the application of acellular vaccines

To the Editor:With the extensive uptake of pertussis vaccine,morbidity and mortality related to pertussis have decreased significantly.The application of acellular vaccines(ACVs)occurred later in China than in developed countries;correspondingly,the pertussis resurgence in China also began later.The latest global genotype dynamic prediction model cannot explain the B.pertussis genotype change trend in China.[1]Chinese B.pertussis strains gradually formed their own unique developmental branches.[2]Here,a phylogenetic tree of prevailing B.pertussis strains from three different regions of China was visualized by EvolView(http://www.evolgenius.info/evolview.html).A total of 199 isolated B.pertussis strains were used for the phylogenetic analysis.The B.para-pertussis strain isolated from Tianjin was used as the out-group,and Chinese strain(CS),which is widely used as a vaccine strain for ACV production in China,was used as the reference strain.In particular,we analyzed the multilocus sequence typing(MLST)and macrolide-resistance-conferring gene mutations.

Biosynthesis and transfer of 2‑acetamido‑4‑methylamino‑l‑fucose to the core‑lipid A in Bordetella pertussis

The trisaccharide unit in lipopolysaccharide of Bordetella pertussis is important for immune recognition,but how the rare sugar 2-acetamido-4-methylamino-fucose in the trisaccharide unit is synthesized and transferred to the core of lipopolysaccharide in B.pertussis remains unclear.In this study,we demonstrated that the genes bplF,bplG,bplL and bplI are involved in the synthesis and transfer of 2-acetamido-4-methylamino-fucose to the core of lipopolysaccharide in B.pertussis.These genes were overexpressed with various combination in a recombinant E.coli strain which can synthesize B.pertussis corelipid A.Lipopolysaccharides were isolated from these strains and analyzed by using SDS-PAGE,ion chromatography and NMR.Based on these analyses,the mechanism of biosynthesis and transfer of 2-acetamido-4-methylamino-l-fucose to the core-lipid A in B.pertussis is proposed.