A 6-year Prospective, Observational, Multi-Center Post-Marketing Surveillance of the Safety of Tetanus Toxoid, Reduced Diphtheria Toxoid, and Acellular Pertussis (Tdap) Vaccine in Korea

BACKGROUND: Incidence of whooping cough is increasing in Korea. Since 2011, occurrence among adolescents and adults has risen putting vulnerable neonates at risk. National immunization guidelines now include Tdap (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis) vaccination during pregnancy and as a cocooning strategy (i.e., vaccinating adults and adolescents in contact with neonates). This study assessed post-marketing Tdap (Boostrix®, GSK, Belgium) vaccine safety in subjects ≥ 10 years. METHODS: This open, non-comparative multi-center study was conducted over six years at 10 hospitals in Korea. Subjects received Tdap in normal clinical practice according to local prescribing information. All adverse events (AEs) were recorded, classified as expected or unexpected, and severity and relationship to Tdap were assessed. RESULTS: The analysis included 672 Korean subjects (mean age, 44 years; range, 11–81), 451 were women and 211 were pregnant. Ninety subjects experienced 124 AEs (incidence 13.39%) of which six were serious AEs (SAEs) assessed as not related to vaccination, and 51 were non-SAEs related to vaccination (mostly administration site reactions). Overall 65/124 AEs were unexpected; the most common were 14 constipation, 5 dyspepsia, 4 common cold and 4 premature labor cases. One case of common cold was assessed as possibly related to vaccination. Pregnancy outcome was ‘live infant, no apparent congenital anomaly’ in 195 subjects (92.42%) or ‘lost to follow-up’ in 16 subjects. CONCLUSION: Tdap administration to Korean subjects ≥ 10 years, including pregnant women, for the prevention of diphtheria, tetanus and pertussis was shown to have a well-tolerated safety profile. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01929291

Knowledge, Attitude and Practice on Maternal Immunization with Tetanus Toxoid, Reduced Diphtheria Toxoid, and Aellular Pertussis (Tdap) among Pregnant Women

PURPOSE: Despite effectiveness and safety of maternal tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccination, Tdap vaccination coverage during pregnancy remains quite low. We assessed the knowledge, attitude and practice on maternal Tdap vaccination among pregnant women. METHODS: This study was a cross-sectional survey of pregnant women who visited tertiary obstetrics and gynecologic units in Seoul and Gyeonggi province of Korea. Individual questionnaires were administered to assess knowledge, attitude and practice on maternal immunization with Tdap. RESULTS: The questionnaires were completed by 184 pregnant women; 158 (86%) had not received information from doctors about pertussis and Tdap, and 166 (90%) did not know the need for Tdap vaccination. Only 7% of pregnant women unlikely to receive Tdap vaccine during current pregnancy answered 3 or more of the 5 knowledge-based questions correctly. By logistic regression analysis, recommendation by doctor (adjusted odd ratio [OR], 236.2; 95% confidence interval [CI], 12.6–4,432), belief that the vaccine is effective (adjusted OR, 40.21; 95% CI, 2.35–687.7), and belief that the vaccine is safe (adjusted OR, 19.83; 95% CI, 1.54–255.9) were significantly important factors to respondents’ intention to be vaccinated. CONCLUSIONS: Most pregnant women seem to be neither recommended nor adequately informed about Tdap vaccination. Information given by health care professionals is very important to increase Tdap coverage among pregnant women.

Evaluation of Potency on Diphtheria and Tetanus Toxoid for Adult Vaccines by In Vivo Toxin Neutralization Assay Using National Reference Standards

OBJECTIVES: Vaccinations against diphtheria and tetanus are essential in providing immunity against these bacterial infections. The potency of diphtheria and tetanus toxoid vaccines can be measured using the in vivo toxin neutralization assay. The limit of potency of this assay was determined only for children. Therefore, we assessed the potency of adult vaccines using this assay to identify the feasibility of limit for adult vaccines. METHODS: Fifteen lots of tetanus-reduced diphtheria and tetanus-diphtheria-acellular pertussis vaccines were used. In vivo toxin neutralization and lethal challenge assays were conducted on each vaccine to calculate the potencies of the toxoids. National reference standards for toxins and antitoxins were used for in vivo toxin neutralization assay. RESULTS: All 15 lots satisfied the limits of potency for lethal challenge assay. The potency of diphtheria and tetanus toxoids exceeded 1 and 8 units/mL, respectively, for in vivo toxin neutralization assay. CONCLUSION: Although additional studies are required for new assays and limits, the current level of potency for adult vaccines as determined by in vivo toxin neutralization assay, was demonstrated in this study. Such efforts to improve assays are expected to promote the development of diphtheria and tetanus vaccines for adults and to contribute to vaccine self-sufficiency.

Determinación rápida de la identidad del polisacárido de Salmonella Typhi y toxoide diftérico en vacunas conjugadas / Rapid determination of the identity of Salmonella Typhi polysaccharide and diphtheria toxoid in conjugate vaccines

El polisacárido Vi (PsVi) de Salmonella Typhi es un antígeno T-independiente y ha demostrado ser protector en adultos jóvenes. Sin embargo, para aumentar la respuesta de anticuerpos y conferir propiedades T-dependientes al polisacárido, se ha conjugado a proteínas. Dentro de los controles exigidos por los organismos regulatorios para estas vacunas está la identidad antigénica de sus componentes y para eso se recomiendan el uso de técnicas de Resonancia Magnética Nuclear o técnicas serológicas. El objetivo del presente trabajo, fue establecer las condiciones óptimas de trabajo de un Dot Blot que permitiera determinar, rápidamente, la identidad de los antígenos en vacunas conjugadas contra S. Typhi. Para ello, se estudiaron los tiempos de incubación, las concentraciones óptimas de anticuerpo monoclonal (AcM) y del ingrediente farmacéutico activo (IFA), así como los volúmenes de aplicación óptimos para las IFAs y formulaciones vacunales, tanto para el PsVi como para el toxoide diftérico (TD). Los resultados mostraron que para la determinación de la identidad antigénica fueron suficientes 5 µL de muestras de los conjugados monovalentes en una dilución de 1/10 (vol/vol) e igual volumen para las formulaciones vacunales. Quedó demostrado que la concentración de 2,5 µg/mL para el AcM contra el PsVi y a 2 µg/mL para el AcM contra TD fueron suficientes para la determinación; mientras que los tiempos de incubación fueron ajustados a 15 min con incubación a 37 ºC. Como conclusión del trabajo se puede decir que quedaron establecidas las condiciones óptimas de trabajo para la determinación rápida de la identidad antigénica del PsVi y del TD presentes en IFA y formulaciones vacunales conjugadas(AU)

Vi polysaccharide from Salmonella Typhi is a T-independent antigen that has proven to be protective in young adults. However, it has been conjugated to proteins in order to confer T-dependent properties to the polysaccharide, and improving the antibody response. The regulatory agencies require knowing the identity of antigens included in vaccines. The Nuclear Magnetic Resonance spectroscopy and serological techniques are recommended. The aim of this work was to establish the optimal working conditions of a Dot Blot that would allow to determine quickly the identity of the antigens in conjugate vaccines against S. Typhi. The incubation times, optimum concentrations of monoclonal antibodies (MAb) and active pharmaceutical ingredient (API), as well as optimum application volumes for APIs and vaccine formulations were studied for both, PsVi and diphtheria toxoid (DT). It was proven that 5 µL of samples of the monovalent conjugates were sufficient at a dilution of 1/10 (vol/vol) and an equal volume for the vaccine formulations. It was demonstrated that the concentration of 2.5 µg/mL for the MAb against PsVi and 2 µg/mL for the MAb against DT were suitable. The incubation times were adjusted to 15 min with incubation at 37 ºC. It was established a simple and rapid method for the specific identification of PsVi and DT present in API and conjugate vaccines(AU)

A Bordetella pertussis proteoliposome induces protection in mice without affecting the immunogenicity of diphtheria and tetanus toxoids in a trivalent formulation

In this study, a formulation of Bordetella pertussis proteoliposome (PLBp), diphtheria, and tetanus toxoids and alum (DT-PLBp) was evaluated as a trivalent vaccine candidate in BALB/c mice. Vaccine-induced protection was estimated using the intranasal challenge for pertussis and enzyme-linked immunosorbent assay fvto assess serological responses for diphtheria or tetanus. Both, diphtheria-tetanus-whole cell pertussis (DTP) and diphtheria-tetanus vaccines (DT) were used as controls. Animals immunized with DT-PLBp, PLBp alone, and DTP showed total reduction of CFU in lungs 7 days after intranasal challenge. Likewise, formulations DT-PLBp, DTP, and DT elicited antibody levels ≥2 IU/mL against tetanus and diphtheria, considered protective when neutralization tests are used. Overall, results showed that combination of PLBp with tetanus and diphtheria toxoids did not affect the immunogenicity of each antigen alone.

Short-term and long-term antibody response by mice after immunization against Neisseria meningitidis B or diphtheria toxoid

Serogroup B Neisseria meningitidis (MenB) is a major cause of invasive disease in early childhood worldwide. The only MenB vaccine available in Brazil was produced in Cuba and has shown unsatisfactory efficacy when used to immunize millions of children in Brazil. In the present study, we compared the specific functional antibody responses evoked by the Cuban MenB vaccine with a standard vaccine against diphtheria (DTP: diphtheria, tetanus, pertussis) after primary immunization and boosting of mice. The peak of bactericidal and opsonic antibody titers to MenB and of neutralizing antibodies to diphtheria toxoid (DT) was reached after triple immunization with the MenB vaccine or DTP vaccine, respectively. However, 4 months after immunization, protective DT antibody levels were present in all DTP-vaccinated mice but in only 20% of the mice immunized against MenB. After 6 months of primary immunization, about 70% of animals still had protective neutralizing DT antibodies, but none had significant bactericidal antibodies to MenB. The booster doses of DTP or MenB vaccines produced a significant antibody recall response, suggesting that both vaccines were able to generate and maintain memory B cells during the period studied (6 months post-triple immunization). Therefore, due to the short duration of serological memory induced by the MenB vaccine (VA-MENGOC-BC® vaccine), its use should be restricted to outbreaks of meningococcal disease.

A Study on the Discourse and Reality of Abortion in Korea: 1920s~1930s / 의사학

This paper tried to collect, classify and analyse the discourse about abortion in 1920~1930. In Korea, modern medical abortion operation started in 1920~30s. At that time abortion was prohibited by the Japanese Government-General of Korea, because the Japanese Government-General of Korea needed large population which was used for labor and exploitation. Hence, the Empire of Japan de-penalized Japanese criminal law related to birth control but Korean law was not revised between 1910~1945. Nevertheless, there were quite a few women who wanted abortion when they had children born in sin or they were too poor to raise their children, so they had abortion secretly. At that time the women generally had abortion through toxic drugs or foods and violence (dropping from a high place or beating their stomach). But high class women did it by medical operation. In 1920s, there was few Korean (modern) medical doctors who could operate for abortion, instead Japanese immigrant medical doctors did it--as the newspaper of that time showed(there were many pieces of news that Japanese doctor who helped abortion was arrested by the police). As time went by Korean doctors got their say about the technique and various knowledge of abortion in newspapers, magazines, and academic Journals; this was especially the case starting in 1930. It is worth noting that they were sometimes arrested for illegal abortion operations. Furthermore, from the late 1920s the insist that abortion should be permitted for women and poor people, appeared. This insist was affected by Japan, the Soviet Union and other countries which was generous with abortion.

Diphtheria Antibodies and T lymphocyte Counts in Patients Infected with HIV-1

We assessed the IgG levels anti-diphtheria (D-Ab) and T cell counts (CD4+ and CD8+) in HIV-1 infected subjects undergoing or not highly active antiretroviral therapy (HAART). Approximately 70% of all HIV-1 patients were unprotected against diphtheria. There were no differences in D-Ab according to CD4 counts. Untreated patients had higher D-Ab (geometric mean of 0.62 IU/ml) than HAART-patients (geometric mean of 0.39 IU/ml). The data indicated the necessity of keeping all HIV-1 patients up-to-date with their vaccination.

The contraindication of comedication drugs and drug utilization review

A drug interaction can be defined as an interaction between a drug and other drugs that prevent the drug from performing as expected. These processes may include alterations in the pharmacokinetics of the drug, such as modulations in the absorption, distribution, metabolism, and elimination (ADME) of a drug. Alternatively, drug interactions may be the result of the pharmacodynamic characteristics of the drug: the concomitant medication of a receptor antagonist and an agonist for the same receptor. The following interaction may increase or decrease the effectiveness of the drugs or the adverse drug reactions of the drugs. The possibilities of drug interactions should increase as the number of drugs being taken increases in patients. Therefore, patients taking several drugs simultaneously are at the greatest risk for interactions. Drug interactions can contribute to the increasing cost of healthcare because of the costs of medical care that are required to treat problems caused by changes in effectiveness or adverse drug reactions. The drug utilization review (DUR) system has been defined as a structured, ongoing initiative that interprets patterns of drug usage in relation to predetermined criteria and attempts to prevent or minimize inappropriate prescribing. The primary objectives of DUR are to improve the quality of health care for healthcare members and to assist in containing health care costs. In order to achieve these goals, prescription claims must be reviewed both prospectively and retrospectively. The DUR system supplies information to prohibit co-dispensing of contraindicated drugs which increases the risk of drug interactions properly to all the healthcare professionals participating in the care of the patients. In this article, we suggest the importance of DUR in relation to the contraindication of co-medication drugs.

The Influence of Postoperative Lesion-Down Head Position on the Recurrence Rate in Chronic Subdural Hematoma after Burr-Hole Surgery / 대한신경손상학회지

OBJECTIVE: Chronic subdural hematoma is a common disorder observed in neurosurgical care and the recurrence rate is relatively high. In this report, we evaluated the relationship between the recurrence rate of chronic subdural hematoma and the postoperative head position of the patient. METHODS: We conducted a retrospective study of 72 patients with unilateral chronic subdural hematoma treated by burr hole surgery with closed system drainage from October 2009 to May 2011. In group A, there was no restriction in head position for days keeping the catheter. In group B, the patients were placed with the lesion side of the head downward after the operation. We analyzed the recurrence rate, amount of postoperative drainage and changes in computed tomography finding of group A and B. RESULTS: Group A and group B consisted of 36 cases, respectively. The mean amount of total postoperative drainage was 248.8+/-127.2 mL in group A and 176.3+/-98.9 mL in group B (p=0.01). The improvement rates of midline shifting before and after surgery showed 60.5+/-25.6% in group A and 73.4+/-26.3% in group B (p=0.039). The total recurrence rate in group A was 11.1% and 5.6% in group B. CONCLUSION: By facing the lesion downward after surgical treatment, chronic subdural hematoma is thought to help reexpand the brain and to prohibit cerebrospinal fluid from flowing into subdural space and to decrease the recurrence rate better than having a free position.

Postoperative Systemic Dissemination of Injected Elemental Mercury

There were only a few reports of mercury on pulmonary artery. However, there is no data on surgery related mercury dissemination. The objective of the present article is to describe one case of postoperative injected mercury dissemination. A 19-year-old man presented severe neck pain including meningeal irritation sign and abdominal pain after injection of mercury for the purpose of suicide. Radiologic study showed injected mercury in the neck involving high cervical epidural space and subcutaneous layer of abdomen. Partial hemilaminectomy and open mercury evacuation of spinal canal was performed. For the removal of abdominal subcutaneous mercury, C-arm guided needle aspiration was done. After surgery, radiologic study showed disseminated mercury in the lung, heart, skull base and low spinal canal. Neck pain and abdominal pain were improved after surgery. During 1 month after surgery, there was no symptom of mercury intoxication except increased mercury concentration of urine, blood and hair. We assumed the bone work during surgery might have caused mercury dissemination. Therefore, we recommend minimal invasive surgical technique for removal of injected mercury. If open exposures are needed, cautious surgical technique to prohibit mercury dissemination is necessary and normal barrier should be protected to prevent the migration of mercury.

Atualidades na técnicas de aplicação das vacinas / Updates to application techniques of vaccines

Este artigo apresenta, detalhadamente, as atualidades relacionadas a programas de vacinação humana e o mais recente calendário de vacinas disponível nos serviços públicos de imunização

Effect of Hyperkalemia and Hemolysis Caused by Hyperacute Rejection on Cardiac Function in Pig to Human Ex Vivo Xenogeneic Cardiac Perfusion Model

BACKGROUND AND OBJECTIVES: Hyperacute rejection (HAR) is a major obstacle to successful xenotransplantation of vascularized organs. This study was conducted to observe the effect of hemolysis of perfused human whole blood on pig heart function, and determine the major risk factors for preservation of xenoperfused cardiac function using ex-vivo pig to human xenogeneic cardiac perfusion model. MATERIALS AND METHODS: Harvested pig hearts were perfused with normal human whole blood (group 1), two different types of pre-treated human whole blood (group 2: immunoglobulins were depleted by plasmapheresis, group 3: pre-treated with plasmapheresis, GAS914, cobra venom factor (CVF) and steroid), and normal porcine whole blood as control (group 4) for 3 hours. RESULTS: Duration of heart beat was significantly prolonged in group 2 and group 3. Histological examination showed widespread HAR features but was gradually delayed in groups 2 and 3 compared to group 1. The absolute levels of serum creatine kinase-MB and Troponin I increased gradually, and was lower in group 3. Serum hemoglobin levels were rapidly increased in groups 3 and 4, compared to group 1. Extracellular potassium level increased sharply from the beginning of blood perfusion in groups 1, 2 and 3, compared to group 4. CONCLUSION: Pretreatment of human whole blood, including immunoglobulin depletion, CVF and steroid reduced and delayed the destruction of pig myocardium by HAR. However, the increased extracellular potassium levels in groups 1, 2 and 3 reflected that these treatments could not prohibit myocardial injury by HAR.

Atualidades na técnicas de aplicação das vacinas

Este artigo apresenta, detalhadamente, as atualidades relacionadas a programas de vacinação humana e o mais recente calendário de vacinas disponível nos serviços públicos de imunização

Diphtheria in Afghanistan

The Disease Early Warning System in Afghanistan has recently detected a suspected case of Diphtheria in the regional hospital of Herat province on 22 June 2010. The suspected case is a 20 years old, married woman who resides in Herat City. She has been treated with Diphtheria Antitoxin and Antibiotic [Penicillin] and she is currently recovering. No other cases have been detected so far,. The close contacts of this suspected case has been put under observation and have received single prophylactic dose of Benzathin Penicillin. Throat swab has been collected and sent to the Central Public Health Laboratory for laboratory confirmation

Prevention of Biofilm Infections

Biofilms are well-organized, complex microbial communities that are often highly resistant to antimicrobial agents and host defenses. Biofilms are often formed on the surfaces of surgical implants and indwelling catheters. Being extremely resistant to removal, biofilms, once formed, cause numerous complications and often result in persistent infections that require long-term hospitalization for treatment. Until now, preventive measures employing prophylactic antimicrobials that prohibit or restrict biofilm formation have been the only feasible, effective options available, with the constant concomitant threat of antimicrobial resistance. However, the development of chemical agents that specifically act upon the virulence of biofilms, rather than destroying the microorganisms or suppressing their growth, is a promising new approach. Such agents are highly desirable in that they might allow clinicians to prevent the development of antimicrobial resistance. Effective suppression of biofilm formation would dramatically change the way to treat infectious disease. In this literature review, the types of infections associated with biofilms and relevant therapeutic options that have been approved, in use, or under development to treat biofilm infections are discussed, along with novel approaches to biofilm control that may be applicable to the development of future anti-biofilm agents.

A diphtheria outbreak in Buri Ram, Thailand.

In May 1996 there was an outbreak of diphtheria in Buri Ram, Thailand which infected 31 patients, 8 males and 23 females. The mean age of the patients was 8 +/- 5 years. Seventy-four percent had a history of childhood vaccinations. Common signs and symptoms included fever (100%) which was low grade in 61%, sore throat (90%), upper airway obstruction (3%), and hoarseness (10%). Pseudomembranes (seen in 100%) were located on the tonsils (71%), pharynx (22%), larynx (9.6%), and uvula (6%). The mean duration of symptoms prior to admission was 2 days with a range of 1 to 5 days. Complications included upper airway obstruction (10%) and cardiac complications (10%). There were no neurological complication or deaths. There were negative associations between cardiac complications, severity of disease and previous diphtheria vaccination. The ages varied from children to adults. Early recognition and prompt treatment decreased complications and mortality in this group of patients when compared with Chiang Mai and Queen Sirikit National Institute of Child Health (QSNICH) studies.

First detection of Corynebacterium ulcerans producing a diphtheria-like toxin in a case of human with pulmonary infection in the Rio de Janeiro metropolitan area, Brazil

The frequency and severity of human infections associated with Corynebacterium ulcerans appear to be increasing in different countries. Here, we describe the first C. ulcerans strain producing a diphtheria-like toxin isolated from an elderly woman with a fatal pulmonary infection and a history of leg skin ulcers in the Rio de Janeiro metropolitan area.