Effect of vaccine program on IgG antibody titers for measles,rubella, varicella,and mumps in young adults in Japan: Survey between 2018 and 2021

IntroductionImproved routine immunizations in Japan have led to a reduction in vaccine-preventable diseases. Due to changes in the vaccination program, current young adults received their second vaccination for measles and rubella at different times depending on their birth year, and most of them have not been vaccinated against varicella and mumps. This study investigated the effect of vaccine programs on the immunity of people in Japan.MethodsImmunoglobulin G antibody (IgG) titers against four viruses were determined by enzyme immunoassay in 795 students at a medical university. Titers for measles and rubella were compared according to the students’ birth dates (Group 1: April 2, 1990–April 1, 2000; Group 2: April 2, 2000–).ResultsThe titers of students that satisfied the standard IgG values against measles, rubella, varicella, and mumps were 24.3%, 56.9%, 87.4%, and 47.2%, respectively. Measles and rubella titers were lower in group 2 (estimated mean period from last vaccination, 7.0 years) than group 1 (13.5 years) (p = 0.023 measles, p = 0.037 rubella), indicating attenuation of titers over time. Varicella and mumps antibody prevalence indicated that these infections were endemic, whereas rates of negative titers were higher than those for measles and rubella.ConclusionsIgG titers against viruses were affected by vaccination programs. Declining titers after vaccination should be monitored when the diseases are almost eliminated and boosting is absent. Antibody testing is meaningful for recommending vaccinations and for surveillance of waning immunity. Continuous improvements of vaccination program should be considered to prevent and eliminate diseases.     

Susceptibility of medical students to vaccine-preventable viral diseases: a serological study

As a measure for the prevention and control of nosocomial infections in medical school students, we examined the students titers of antibodies to measles, rubella, varicella, and mumps viruses to determine whether vaccination was required. We also analyzed and discussed correlations among antibody titers to the viruses. Subjects were 363 Juntendo University students, ranging from freshmen to seniors. EIA was used to measure IgG antibody titers. Eight subjects (2.2%) had negative titers for measles, 36 (9.9%) for rubella, 8 (2.2%) for varicella, and 10 (2.7%) for mumps. Seronegative subjects were vaccinated against each virus and high seroconversion rates were obtained: 100% for measles and rubella, 67% for varicella, and 89% for mumps. In addition, we used Pearsons test to search for correlations among the antibody titers for each virus. A weak correlation was observed among antibody titers for measles, rubella, and mumps but not for varicella. These results suggest that MMR vaccine might be effective in people with low levels of antibody to measles, rubella, and mumps.     

Self-reported histories of disease and vaccination against measles,mumps, rubella and varicella in health care personnel in Japan

Health care personnel are required to be immune against vaccine-preventable diseases, such as measles, mumps, rubella, and varicella. The aim of this study is to evaluate the accuracy of self-reported histories of disease and vaccination against measles, mumps, rubella, and varicella in order to determine the immune status of health care personnel. A self-reported questionnaire of history of previous disease and vaccination against these diseases was administered to a total of 910 health care personnel in Shimane university hospital in Japan, whose results were compared with serological evidences. There were numerous subjects who did not remember a history of disease (greater than 33% each) and of vaccination (greater than 58% each). Self-reported history of disease and vaccination had high positive predictive value against either disease for testing positive for antiviral antibodies. However, a considerable number of false-negative subjects could be found; 88.9% of subjects for measles, 89.3% for mumps, 62.2% for rubella and 96.3% for varicella in the population who had neither a self-reported history of disease nor a vaccination against each disease. In addition, regardless of the disease in question, a negative predictive value in self-reported history of disease and vaccination was remarkably low. These results suggest that self-reported history of disease and vaccination was not predictive to determine the accurate immune status of health care personnel against measles, mumps, rubella, and varicella. A seroprevalence survey, followed by an adequate immunization program for susceptible subjects, is crucial to prevent and control infection in hospital settings.     

Heparin‐induced thrombocytopenia: towards standardization of platelet factor 4/heparin antigen tests

Summary. Background: Laboratory confirmation of heparin‐induced thrombocytopenia (HIT) is based on detection of heparin‐dependent platelet‐activating antibodies. Platelet factor 4 (PF4)/heparin enzyme‐immunoassays (EIA) are a widely available surrogate for platelet‐activating antibodies. Objective: Defining the optical density (OD) reactivity profiles of a PF4/heparin EIA in reference subject and patient populations and the correlation of the EIA results (expressed in OD units) with the prevalence of platelet‐activating antibodies. Patients/methods: Using quantile regression we determined the 97.5th percentile of PF4/heparin‐immunoglobulin G (IgG) EIA reactivities in non‐heparin‐treated individuals [blood donors (n = 935)] and patients before heparin therapy (n = 1207). In patients with suspected HIT, we compared the correlation of EIA‐IgG reactivities (Greifswald laboratory; n = 2821) and the heparin‐induced platelet activation assay (HIPA) with the correlation of reactivities of another EIA‐IgG (McMaster laboratory; n = 1956) with the serotonin‐release assay (SRA). Results: PF4/heparin‐IgG EIA OD reactivities had a lower OD 97.5th percentile in blood donors compared with patient groups before heparin treatment (P < 0.001). The percentage of sera testing positive in the functional assays strongly correlated with PF4/heparin‐IgG EIA OD reactivities in both laboratories with very similar results (correlation coefficient > 0.9) when normalized OD ranges (maximum OD divided by 10) were used instead of absolute OD values. Conclusions: Results of PF4/heparin‐IgG EIA should not be reported as only positive or negative as there is no single acceptable cut‐off value. Instead, reporting PF4/heparin‐IgG EIA OD results in ranges allows for risk‐stratified prediction for presence of platelet‐activating antibodies. Use of normalized OD ranges permits a standardized approach for inter‐laboratory comparisons.     

浙江省金华市人群麻疹、腮腺炎、水痘、乙型病毒性肝炎和甲型病毒性肝炎抗体水平监测分析

目的 了解浙江省金华市健康人群麻疹、腮腺炎、水痘、乙型病毒性肝炎（乙肝）和甲型病毒性肝炎（甲肝）的抗体水平情况,为制订和完善免疫策略提供科学依据。方法 采用酶联免疫吸附试验（enzyme-linked immunosorbent assay,ELISA）检测麻疹IgG、腮腺炎IgG、水痘IgG、乙肝表面抗体（HBsAb）和甲肝IgG。结果 共检测1170份血清标本,麻疹、腮腺炎、水痘IgG阳性率分别为89.40%、80.34%和71.37%,HBsAb阳性率为78.29%,甲肝IgG阳性率为55.21%。结论 金华市健康人群麻疹、腮腺炎具有较高的免疫水平,乙肝、水痘和甲肝免疫水平较低,应重点关注水痘、甲肝疫情,同时进一步做好免疫预防接种工作,提高人群免疫覆盖水平。     

2020年辽宁省不同年龄组健康人群麻疹、风疹、流行性腮腺炎抗体血清学分析

目的 了解辽宁省扩大免疫规划实施10年后不同年龄组健康人群麻疹、风疹及流行性腮腺炎IgG抗体水平,为及时发现免疫薄弱人群,采取针对性免疫措施提供依据。方法 采用单纯随机抽样方法采集辽宁省3个地市6个县（区）共计498名健康人群血标本,使用酶联免疫吸附试验检测血清中麻疹、风疹及流行性腮腺炎IgG抗体,分析抗体阳性率和几何平均浓度（GMC）。结果 本次监测麻疹抗体阳性率为94.78%,GMC为851.10 m IU/m L;风疹抗体阳性率为87.15%,GMC为40.90 IU/m L;流行性腮腺炎抗体阳性率为90.16%,GMC为330.93 U/mL。不同地区麻疹、风疹及流行性腮腺炎IgG抗体阳性率和GMC水平差异均有统计学意义（P<0.01）;不同年龄组麻疹GMC水平、风疹及流行性腮腺炎IgG抗体阳性率和GMC水平差异有统计学意义（P<0.01）,但麻疹IgG抗体阳性率差异无统计学意义（P>0.05）;不同性别间麻疹、风疹及流行性腮腺炎IgG抗体阳性率和GMC水平差异无统计学意义（P>0.05）。结论 辽宁省麻疹和流行性腮腺炎IgG抗体水平较高,风疹IgG抗体...     

Simultaneous and rapid detection method for measles and rubella using single-tube multiplex real-time quantitative RT-PCR

Patients with measles or rubella infections manifest acute onset fever accompanying systemic exanthema, which are clinically difficult to be distinguish. Rapid diagnosis and differentiation of such epidemic viral diseases is essential to prevent outbreaks. We developed a single-tube multiplex real-time PCR assay for these indistinguishable viruses. We used previously-reported primer settings, with a slight modification of reporter dye, and applied to multiplex Taqman real-time PCR by cobas z480 (Roche Molecular Systems, Inc.). Consequently, the assay could detect 10 copies/10 μl of measles and rubella with coefficient of variations of 11.2% and 21.8%, respectively. Strengths of our methodology include simplicity of operation, short measurement time (2 h), uses of internal control (confirming a run of PCR), and quantitative measurement with high sensitivity. Both measles and rubella currently cause social outbreaks in Japan. We hope that our single-tube multiplex assay contributes to an early diagnosis, leading to an appropriate infection control measure and prevention of epidemics.     

Evaluation of a rapid enzyme immunoassay system for serologic diagnosis of Mycoplasma pneumoniae infection

A 5-min qualitative membrane enzyme-linked immunoassay (EIA) from Remel (Mycoplasma pneumoniae immunoglobulin G (IgG)/IgM Antibody Test System) was evaluated for its ability to detect IgG and IgG at levels indicating active or recent infection. Specimens from 131 patients were evaluated using an immunofluorescent antibody assay (IFA) to determine IgG and IgM titers and the membrane EIA. An enzymelinked immunosorbent assay (ELISA) performed by a reference laboratory was used for discrepancy resolution. There were 34 IgM positive specimens (titer ⩾ 1:16), 19 IgG positive specimens (titer ⩾ 1:64), and 78 negative specimens. Compared with IFA and/or ELISA, the membrane EIA was 97% sensitive for the detection of IgM and 79% sensitive for the detection of IgG. Of the 78 specimens called negative, 17 specimens had IgG titers (⩽1:32) or an ELISA result indicating prior exposure, and the membrane EIA called seven of 17 (41%) positive. For the detection of both IgG and IgM, the membrane EIA had a sensitivity of 91 %, specificity of 91%, and positive and negative predictive values of 87 and 93%, respectively. The Remel membrane EIA is a rapid and reliable assay for the diagnosis of active or recent M. pneumoniae respiratory tract infections.     

The estimated burden of 15 vaccine-preventable diseases from 2008 to 2020 in Japan: A transition by the COVID-19 pandemic

BackgroundEvaluating the national burdens across multiple vaccine-preventable diseases (VPDs) can be informative to identify the areas for improvements in the national immunization program.MethodsThe annual burden of diseases from 2008 to 2020 in Japan were calculated with the incidence- and pathogen-based approach for the 15 VPDs (hepatitis B virus infection, human papillomavirus (HPV), influenza, invasive pneumococcal disease, invasive Haemophilus influenzae type b (Hib) disease, invasive meningococcal disease, Japanese encephalitis, measles, mumps, pertussis, rotavirus, rubella, tetanus, tuberculosis and varicella), using disability-adjusted life year (DALY).ResultsThe average annual burden between 2008 and 2020 is the highest in influenza (114,129 DALY/year), followed by HPV infection, hepatitis B virus infection, tuberculosis and mumps (109,782, 69,883, 23,855 and 5693 DALY/year). In the pre-COVID-19 period (2008–2019), the decreasing trend of burden was observed in hepatitis B virus infection, invasive pneumococcal disease, invasive Hib disease, tuberculosis and varicella. HPV infection is the only VPD which had more than 100,000 DALY/year for all years during the study period. In 2020, the estimated annual burdens are decreased in influenza (71%), invasive pneumococcal disease (51%), invasive Hib diseases (54%), invasive meningococcal disease (64%), measles (98%), mumps (47%) pertussis (83%), rotavirus infection (95%), rubella (94%) and varicella (35%) compared with those in 2019.ConclusionsThe study demonstrated decreasing trends of burdens for some VPDs, while a persistently high burden has been observed for other VPDs, including HPV infection. The COVID-19 pandemic has caused dramatic reductions in the burdens of many VPDs in 2020.     

Performance of Directigen flu A+B enzyme immunoassay and direct fluorescent assay for detection of influenza infection during the 2004–2005 season

Early diagnosis of influenza infection is needed to optimize the benefit of prescribing antiviral drugs. However, the accuracy of rapid tests is highly variable. This study evaluated the performance of Directigen flu A+B enzyme immunoassay (EIA) and direct fluorescent assay (DFA) during the 2004–2005 influenza season. Participants with medically attended acute respiratory illness were identified through an active surveillance. Consenting patients (n = 818) were enrolled and cultured for influenza. Physicians ordered a rapid antigen test (EIA or DFA) according to their clinical judgment. Physicians ordered rapid tests with EIA (n = 109), DFA (n = 86), or both (n = 9) in 204 patients with acute respiratory illness who were also cultured for influenza. The EIA detected 18 of 43 influenza infections (sensitivity, 42%; 95% confidence interval [CI], 28–57%), whereas DFA detected 26 of 38 influenza infections (sensitivity, 68%; 95% CI, 53–81%). Compared with culture, specificity of both EIA and DFA was 96%. During the 2004–2005 influenza season, both the EIA and DFA had low sensitivity and failed to detect influenza in many patients.     

江苏省赣榆县1～9岁儿童脊髓灰质炎、麻疹、风疹、流行性乙型脑炎抗体水平调查

目的 了解江苏省赣榆县1～9岁儿童脊髓灰质炎、麻疹、风疹和流行性乙型脑炎4种传染病特异性IgG抗体水平,为免疫规划工作提供参考数据. 方法 采用整群抽样的方法,共采集1～9 岁儿童手指血样39 363份,分离血清;采用酶联免疫吸附试验进行4 种病毒特异性IgG抗体水平检测,并进行统计分析. 结果 脊髓灰质炎病毒、麻疹病毒、风疹病毒和流行性乙型脑炎病毒IgG 抗体阳性率分别为97.5%、96.3%、 97.9%和95.9%.阳性率与调查对象的年龄、性别之间差异无统计学意义. 结论 赣榆县1～9岁4类传染病特异性IgG抗体均维持在较高水平,对控制传染病的暴发和流行起到了较好的免疫屏障作用.     

麻疹-腮腺炎-风疹-水痘四联疫苗免疫原性和安全性的系统评价

目的评价麻疹-腮腺炎-风疹-水痘四联疫苗的免疫效果和安全性。方法采用Cochrane系统评价的方法,电子检索1990年到2010年4月期间PubMed、BIOSIS Previews、CDSR、Cochrane Library、CBM、CNKI、VIP等,辅以手工检索及追查已纳入文献的参考文献。纳入比较麻疹-腮腺炎-风疹-水痘四联疫苗（MMRV）与麻疹-腮腺炎-风疹三联疫苗和水痘疫苗（MMR＋V）分别接种的随机对照试验（RCT）。由两名研究者独立筛选文献、评价质量、提取数据并交叉核对。对符合纳入标准的研究采用RevMan 4.2.10进行Meta分析。结果共纳入5个RCT,其中B级2个,C级3个。Meta分析结果显示,MMRV组和MMR＋V组的安全性指标比较：①接种部位疼痛发生率差异无统计学意义[RR=0.94,95%CI（0.83,1.05）,P=0.28];②接种部位红肿发生率差异无统计学意义[RR=1.08,95%CI（0.90,1.29）,P=0.40];③接种部位硬结发生率差异无统计学意义[RR=1.16,95%CI（0.95,1.43）,P=0.14];④接种后发热率差异有统计学意义[RR=1.20,95%CI（1.12,1.29）,P〈0.000 01];⑤接种后全身皮疹发生率差异无统计学意义[RR=1.18,95%CI（1.00,1.41）,P=0.05];两组免疫原性指标比较：①接种后血清麻疹抗体阳转率差异无统计学意义[RR=1.00,95%CI（0.99,1.01）,P=0.80];②血清腮腺炎抗体阳转率差异无统计学意义[RR=0.99,95%CI（0.50,1.01）,P=0.11];③血清风疹抗体阳转率差异无统计学意义[RR=1.00,95%CI（0.99,1.01）,P=0.68];④血清水痘抗体阳转率差异无统计学意义[RR=1.00,95%CI（0.99,1.01）,P=0.58]。结论与MMR＋V分开接种相比,MMRV四联疫苗具有同等的免疫效果,在免疫安全性方面,除接种后发热率稍高外,其他局部和全身反应性良好。鉴于MMRV四联疫苗在免疫效果和安全性方面的良好表现以及它在减少接种次数方面的作用,认为MMRV四联疫苗可以作为儿童预防接种的候选疫苗进行接种。后续工作中需加强对疫苗新组分引起发热机制的研究。鉴于纳入研究的整体质量不高且数量有限,本系统评价中的部分证据引用需谨慎,建议在今后的研究中扩大样本量、完善试验设计、增加分析指标,以提高研究质量和论证强度。     

北京市昌平区6岁儿童加强接种前后麻疹、流行性腮腺炎和风疹抗体水平监测分析

目的 分析北京市昌平区6岁儿童加强接种疫苗前后麻疹、流行性腮腺炎和风疹抗体水平变化,为控制相应传染病,完善相关免疫策略提供依据。方法 采用分层随机抽样法,将昌平区20个镇街分成3个等级镇街,每级镇街随机抽取2个镇街,共6个镇街作为监测现场。每个镇街随机选取6岁儿童作为免疫水平监测对象,依据知情同意的原则,共入组308名儿童,各采集静脉血3 ml,用ELISA试剂盒定量检测麻疹、腮腺炎和风疹IgG抗体水平,在接种麻疹、腮腺炎、风疹疫苗（麻腮风疫苗,MMR）后35~42 d,共采集274名儿童静脉血各3 ml,分析接种MMR前后麻疹、腮腺炎和风疹IgG抗体阳性率及抗体水平变化。结果 加强MMR接种前,麻疹、腮腺炎和风疹抗体阳性率分别为94.16%、87.99%和72.40%,加强接种后三者抗体阳性率均为100.00%。麻疹、腮腺炎和风疹抗体几何平均浓度（GMC）加强接种前分别为999 mIU/ml、469 U/ml和44 IU/ml,接种后分别为1 700 mIU/ml、2 293 U/ml和107 IU/ml。加强接种前后三者抗体阳性率和GMC均升高,差异均有统计学意义（阳性率比较2=16.524、35.150和88.549,P=0.001;GMC比较t=-7.425、-10.001和-16.913,P=0.001）。结论 MMR加强接种前抗体阳性率下降,风疹和腮腺炎抗体阳性率较低,接种后风疹和腮腺炎抗体阳性率上升明显,昌平区6岁儿童麻腮风疫苗加强免疫效果良好,应继续保持较高的疫苗接种率。     

Development of a highly sensitive sandwich enzyme immunoassay for human ferritin using affinity-purified anti-ferritin labelled with β-d-galactosidase from Escherichia coli

A highly sensitive sandwich enzyme immunoassay of human ferritin was developed. Polystyrene balls were coated with rabbit anti-human ferritin IgG by physical adsorption, and rabbit anti-human ferritin Fab' was purified by affinity chromatography and labelled with β-d-galactosidase from Escherichia coli. Using the antiferritin-coated polystyrene balls and labelled anti-ferritin, the sensitivity obtained was 23 fg (0.05 amol) of ferritin per tube. The range of serum ferritin levels that could be determined using 0.1 μ1 of serum was 0.23–4500 ng/ml, and even 2.3 pg/ml was measurable by using 10 μl of serum. The coefficients of within-assay (n = 25) and between-assay (n = 10) variations were 5.9–8.8%. The regression equation and coefficient of correlation to a radioimmunoassay were Y(RIA) = 0.92X(EIA) + 3.0 and 0.99 (n = 78), respectively. The corresponding sandwich radioimmunoassay was less sensitive, partly because the specific radioactivity of ¹²⁵I-labelled anti-ferritin IgG used was not sufficiently high.     

A sensitive and specific sandwich enzyme immunoassay for human thyroid-stimulating hormone

A sensitive and specific sandwich enzyme immunoassay (EIA) for human thyroid-stimulating hormone (hTSH) has been developed. hTSH is incubated with anti-hTSH IgG-coated polystyrene balls, and after washing they are further incubated with anti-hTSH Fab'-β-d-galactosidase conjugate. The β-d-galactosidase activity bound to the polystyrene balls is proportional to the amount of hTSH to be assayed. Polystyrene balls are coated with rabbit anti-hTSH IgG which had been affinity-purified and treated with human chorionic gonadotropin-Sepharose 4B to remove antibodies cross-reacting with structurally related hormones. Rabbit anti-hTSH Fab', which had been affinity-purified was conjugated with β-d-galactosidase from Escherichia coli using N,N′-o-phenylenedimaleimide.In the specific sandwich enzyme immunoassay developed, 1 nU (1 × 10^?9 U) of hTSH per tube can be measured and the sensitivity for serum hTSH level is 0.1 μU/ml when 10 μl of serum is used. No significant interference was observed in the presence of 1.3 mU hLH/tube, 0.5 mU hFSH/tube or 0.5 U hCG/tube. Recoveries of hTSH added to human sera were 95.3–104% with a standard deviation of 12.0–14.9%. The coefficients of within-assay and between-assay variations were 6.0–7.5% and 4.9–8.7%, respectively. The regression equation and coefficient for correlation to radioimmunoassay (RIA) were y (RIA) = 0.95x (EIA) + 3.2 and 0.97, respectively.Serum levels of hTSH in normal male and female adults were 2.4 ± 1.0 (SD) (n = 41) and 2.9 ± 1.3 (n = 46) μU/ml, respectively; those in hyperthyroidism and hypothyroidism were 0.28 ± 0.06 (n = 20) and 49.6 ± 24.7 (n = 22) μU/ml, respectively; and those in pregnant and postmenopausal women were 2.5 ± 1.2 (n = 7) and 2.7 ± 1.0 (n = 35) μU/ml, respectively, indicating that high serum levels of hCG or hLH and hFSH under these conditions did not significantly interfere with the present assay of hTSH at normal levels.     

六安市2009～2011年麻疹风疹疑似病例检测结果分析

目的评价2009～2011年六安市麻疹/风疹实验室网络在加速麻疹和风疹控制中的作用。方法采用酶联免疫吸附试验,对麻疹、风疹疑似病例的血清标本进行特异性抗体检测。结果 2009～2011年共收集484例麻疹、风疹疑似病例的血清标本,检测结果证实麻疹IgM抗体阳性率为31.82%(154/484),风疹IgM抗体阳性率17.15%(83/484);麻疹、风疹病例中小于1岁年龄组人群阳性分别为4.55%和0;1～4岁为53.90%和4.82%;5～15岁为10.39%和61.45%;大于15岁为31.17%和33.73%。结论麻疹、风疹的免疫预防工作,在提高免疫接种质量的同时应高度重视人群的免疫状况监测。     

YEAST PANEL multiplex PCR for identification of clinically important yeast species: stepwise diagnostic strategy,useful for developing countries

Identification of opportunistic yeasts in developing countries is mainly performed by phenotypic assays, which are time-consuming and prone to errors. Wrong species identification may result in suboptimal treatment and inaccurate epidemiological data. To improve rapidity and accuracy of species identification, a diagnostic strategy using a stepwise “YEAST PANEL multiplex PCR assays” targeting 21 clinically important yeast species of Candida, Trichosporon, Rhodotorula, Cryptococcus, and Geotrichum was designed. Four hundred CBS reference strains were used for optimization and specificity testing. Eight hundred clinical species were prepared in blinded sets for multiplex polymerase chain reaction (PCR) and matrix-assisted laser desorption time of flight mass spectrophotometry (MALDI-TOF MS) investigation. Results obtained from YEAST PANEL multiplex PCR assay were 100% consistent with those of MALDI-TOF MS. Utilization of pure colony testing showed distinct amplicons for each species, thus eliminating the need for DNA extraction. The targeted yeast species of this assay are responsible for 95% of the yeast infections. In conclusion, due to the high accuracy and coverage of a broad range of yeasts, this assay could be useful for identification in routine laboratories and epidemiological studies.     

Heparin-induced thrombocytopenia: a prospective study on the incidence, platelet-activating capacity and clinical significance of antiplatelet factor 4/heparin antibodies of the IgG, IgM, and IgA classes

INTRODUCTION: Platelet-activating antiplatelet factor 4/heparin (anti-PF4/heparin) antibodies are the major cause of heparin-induced thrombocytopenia (HIT). However, the relative utility of functional (platelet activation) vs. antigen [enzyme-immunoassay (EIA)] assays, and the significance of assay discrepancies remain unresolved. METHODS: Consecutive patient sera (n = 1650) referred for diagnostic HIT testing were screened prospectively by both the heparin-induced platelet activation (HIPA) test and anti-PF4/heparin EIA - including individual classes (IgG, IgA, IgM) - with clinical correlations studied. Platelet microparticle and annexin-V-binding properties of the sera were also investigated. RESULTS: Only 205 (12.4%) sera tested positive in either the HIPA and/or EIA: 95 (46.3%) were positive in both, 109 (53.1%) were only EIA-positive, and, notably, only one serum was HIPA-positive/EIA-negative. Of 185 EIA-positive sera, only 17.6% had detectable IgM and/or IgA without detectable IgG. Among sera positive for EIA IgG, optical density values were higher when the sera were HIPA-positive (1.117 vs. 0.768; P < 0.0001), with widely overlapping values. Two HIPA-positive but EIA-IgG-negative sera became HIPA-negative following IgG depletion, suggesting platelet-activating antibodies against non-PF4-dependent antigens. Clinical correlations showed that HIPA-negative/EIA-positive patients did not develop thrombosis and had reasons other than HIT to explain thrombocytopenia. IgM/A antibodies did not increase microparticle penetration, but increased annexin-V binding. CONCLUSIONS: The anti-PF4/heparin EIA has high ( approximately 99%) sensitivity for HIT. However, only about half of EIA-positive patients are likely to have HIT. Anti-PF4/heparin antibodies of IgM/A class and non-PF4-dependent antigens have only a minor role in HIT.     

10-Year survey on serum antibody positivity rates and titers for measles and rubella in healthcare workers; an observational study at a Japanese university hospital

BackgroundWe evaluated the effect of the two-dose vaccination strategy, which has been a widely adopted as childhood routine schedule worldwide to acquire herd immunity, on healthcare workers (HCWs) in Japan.MethodsBetween 2010 and 2019, antibody titers for measles and rubella were measured annually among newly employed HCWs at Osaka University Hospital, Japan, using Enzygnost® assays (Siemens Healthcare Diagnostics Co. Ltd., Marburg, Germany). The data were categorized by age to compare the antibody positivity rates and antibody titers among no-vaccine, single-dose, and two-dose groups.ResultsOver the 10-year period, the annual antibody positivity rates for measles and rubella were 84.0%–95.3% and 90.0%–94.5%, respectively, without any particular trend. The antibody titers for measles (median [interquartile range]: 8.4 [3.9, 20] vs. 6.1 [3.5, 12]) and rubella (11 [5.5, 20] vs. 6 [3.7, 11]) were statistically lower (p < 0.001) in the two-dose generation than in the single-dose generation.DiscussionA shift from single-dose to two-dose vaccination did not yield an increase in antibody positivity rates for both measles and rubella among HCWs. Notably, antibody titers were significantly lower in the two-dose generation.ConclusionDespite several limitations, our data suggests a paradoxical vulnerability in young HCWs who received the two-dose vaccination in a view of sero-positivity rates.