[Improving immunization strategy and promoting the development of tetanus prevention and control in China].

Neonatal tetanus has been basically eliminated in China, but the incidence of non-neonatal tetanus is still high. Tetanus after trauma is the main type of non-neonatal tetanus. The correct application of tetanus toxoid containing vaccine (TTCV) has been neglected in the prevention of tetanus after trauma in China. On May 9, 2019, National Advisory Committee of Experts on Immunization Planning (NIAC) reviewed and approved the first guidelines for the use of TTCV and passive immune preparation after trauma, which clarified the basic process of treatment of tetanus after trauma, as well as the pointer to the use of TTCV and passive immune preparation after trauma. The main measure to prevent tetanus after trauma is to use TTCV for active immunization, and to use passive immune preparation for those without TTCV immune history. Through the construction of the top-down control and prevention system of tetanus, the change of the concept of tetanus immunoprophylaxis of medical staff is promoted. Active immunization is the main measure, but passive immunization is an added measure for the prevention of tetanus after trauma, which is of great significance to reverse the mistake of prevention of tetanus in China.

Post-neonatal Tetanus in a PICU of a Developing Economy: Intensive Care Needs, Outcome and Predictors of Mortality.

Objectives: To evaluate pediatric intensive care unit (PICU) needs, outcome and predictors of mortality in post-neonatal tetanus. Materials and methods: Review of 30 consecutive post-neonatal tetanus cases aged 1 months to 12 years admitted to a PICU in north India over a period of 10 years (January 2006 to December 2015). Results: Chronic suppurative otitis media was the commonest portal of entry. All received tetanus toxoid, human tetanus immunoglobulin (HTIG) and appropriate antibiotics; 7 (23.3%) received intrathecal HTIG. Common complications were respiratory failure, rhabdomyolysis, autonomic dysfunction, acute kidney injury and healthcare-associated infections. PICU needs were as follows: ventilation; benzodiazepine, morphine and magnesium sulfate infusion; neuromuscular blockers, inotropes, tracheostomy and renal replacement therapy. Mortality rate was 40%; severity Grade IIIb, autonomic dysfunction, use of vasoactive drugs and those who did not receive intrathecal HTIG were significantly associated with mortality. Conclusion: Post-neonatal tetanus is associated with high mortality, and PICU needs include management of spasms, autonomic dysfunction and complications and cardiorespiratory support.

Comparative tetanus antibody response of Nigerian children to diphtheria-pertussis-tetanus and pentavalent vaccines.

BACKGROUND: In Nigeria and many parts of the world, the pentavalent vaccine is replacing the diphtheria-pertussis-tetanus (DPT) vaccine in tetanus prevention. AIMS AND OBJECTIVES: The aim of this study was to compare the anti-tetanus immunoglobulin G (IgG) response of children who received DPT with those who received the pentavalent vaccine. SUBJECTS AND METHODS: A cross-sectional survey of anti-tetanus IgG levels in children aged 6 months to 5 years who received DPT and in children who received the pentavalent vaccine. IgG antibody levels were determined using enzyme-linked immunosorbent assay. The protective level was set at ≥0.1 IU/ml. RESULTS: One hundred and twenty-two out of 130 children (93.9%) who had received DPT had protective levels of anti-tetanus IgG compared to 278 out of 288 children (96.5%) who had received the pentavalent vaccine. The difference was not statistically significant (P = 0.21). The median IgG antibody level in those who received DPT was 1.1 IU/ml (interquartile range (IQR) 0.4-1.8) compared with 0.6 IU/ml (IQR 0.4-1.4) in those who received pentavalent vaccine (P = 0.006), with age being the only predictor of variability in the multivariate analysis. CONCLUSION/RECOMMENDATION: DPT and pentavalent vaccines are equally effective in inducing protective levels of anti-tetanus IgG in children. Vaccination with the pentavalent vaccine, which is the current policy in Nigeria and many other parts of the world, should continue.

[Chinese expert consensus on tetanus immunization].

Tetanus is an acute specific infection caused by obligate anaerobes, which is still a serious public health problem. Tetanus bacterium is an obligate anaerobic bacterium, widely distributed in nature, which can exist in dust, soil, human or animal excrement. The bacteria invade the body primarily through the skin or mucosal wounds, and most commonly in trauma and burn patients, unclean newborns, and unsafe surgical instruments. Exotoxin produced by tetanus bacteria can cause temporary changes in the central nervous system, manifested as systemic skeletal muscle persistence and paroxysmal spasm, severe cases of laryngospasm, asphyxia, lung infections and organ failure, which is a very serious and potentially fatal disease. This article is an expert consensus on the tetanus immunologic defense, aiming to aid the clinical decision making after open injury. According to epidemiological investigation of tetanus, types of injured population, wound exposure and misunderstandings of immunologic defense, the key measures to prevent tetanus are good wound management and immunization. This statement describes a preventive framework of tetanus immunization, including the tetanus immunization programs of infants, pregnant women, potentially high-risk population, immunodeficiency patients and children born to HIV-infected mothers. This consensus only provides academic guidance, the treatment of the patient must be based on the prevailing medical conditions.

A Rare Case of Localized Tetanus.

Tetanus is a severe and potentially fatal infection caused by the bacterium Clostridium tetani. Presentations of tetanus include generalized tetanus, neonatal tetanus, cephalic tetanus, and localized tetanus, the latter two being much rarer. We present case of a 55-year-old male farmer, presented with an injury to the left toe. A surgical wound exploration and washout with administration of human tetanus immunoglobulin and tetanus toxoid were given as treatment with antibiotic support. This case report points out the importance of the early recognition of a rare form of this fatal infectious disease, which may present with prodromal symptoms before the generalized form shows its clinical effects. Successful management includes prompt diagnosis, neutralization of circulating toxin and elimination of C. tetani infection, control of spasms, maintenance of the airway, and management of respiratory failure and autonomic dysfunction.

Craniocervical Tetanus: A Practical Consideration During Work-up of Acute-Onset Trismus.

This clinical record revisits the classical and pathognomonic features of craniocervical tetanus in a 65-year-old farmer who presented with acute-onset trismus, multiple cranial nerve pareses (III, IX, and X), risus sardonicus, and spasm of the head-neck musculature. This paper explores the relevant literature and presents a brief pictorial analysis of the global epidemiologic data. With most countries successfully adopting the maternal and neonatal tetanus elimination (MNTE) program, the incidence and mortality of tetanus across age groups have sharply reduced in high-income and most middle-income nations. In adults, tetanus is now encountered in specialized situations like waning immunity and incomplete vaccination, in the resource-poor and low-income nations, in countries achieving MNTE recently, and as cluster cases in the aftermath of natural disasters involving human settlements. Therefore, present-day practicing otolaryngologists and residents who have limited exposure to the tell-tale clinical features of craniocervical tetanus should consider it during work-up of acute-onset trismus in adults in susceptible situations and with a conducive background. The clinical spectrum of craniocervical tetanus as depicted in this report, including the demonstration of the pathognomonic positive spatula test, provides valuable learning points for otolaryngologists in this regard.

Collaborative study for the establishment of Ph. Eur. Biological Reference Preparation for Human tetanus immunoglobulin batch 2.

This publication describes the outcome of a project to develop a replacement European Pharmacopoeia (Ph. Eur.) Biological Reference Preparation (BRP) for Human tetanus immunoglobulin (TIg) as well as for the World Health Organization (WHO) International Standard (IS) for Tetanus Immunoglobulin, Human. Bulk TIg was kindly provided by a European manufacturer and was used to prepare the candidate standard. The candidate standard was freeze-dried and calibrated in an international collaborative study jointly co-ordinated by the Medicines & Healthcare products Regulatory Agency (MHRA) and the European Directorate for the Quality of Medicines & HealthCare (EDQM, Council of Europe). The results of this study show that there was good agreement between laboratories for the potency estimates obtained for the candidate standard relative to the current WHO IS/Ph. Eur. BRP. The study also demonstrated that the candidate standard is suitable for use in Ph. Eur. assays for potency testing of TIg products and there was good agreement in the potency estimates obtained using the different assay methods included in the study. Accelerated degradation studies performed at the MHRA over a period of 4 years suggest that the freeze-dried candidate standard will be very stable. The candidate standard was established as Ph. Eur. BRP for Human tetanus immunoglobulin, batch 2 with an assigned potency of 45 IU/ampoule. The same preparation was also adopted by the WHO Expert Committee on Biological Standardization (ECBS) to serve as the WHO 2nd IS for Tetanus Immunoglobulin, Human (13/240).

Collaborative study for the establishment of Ph. Eur. Biological Reference Preparation for Human tetanus immunoglobulin batch 2.

This publication describes the outcome of a project to develop a replacement European Pharmacopoeia (Ph. Eur.) Biological Reference Preparation (BRP) for Human tetanus immunoglobulin (TIg) as well as for the World Health Organization (WHO) International Standard (IS) for Tetanus Immunoglobulin, Human. Bulk TIg was kindly provided by a European manufacturer and was used to prepare the candidate standard. The candidate standard was freeze-dried and calibrated in an international collaborative study jointly co-ordinated by the Medicines & Healthcare products Regulatory Agency (MHRA) and the European Directorate for the Quality of Medicines & HealthCare (EDQM, Council of Europe). The results of this study show that there was good agreement between laboratories for the potency estimates obtained for the candidate standard relative to the current WHO IS/Ph. Eur. BRP. The study also demonstrated that the candidate standard is suitable for use in Ph. Eur. assays for potency testing of TIg products and there was good agreement in the potency estimates obtained using the different assay methods included in the study. Accelerated degradation studies performed at the MHRA over a period of 4 years suggest that the freeze-dried candidate standard will be very stable. The candidate standard was established as Ph. Eur. BRP for Human tetanus immunoglobulin, batch 2 with an assigned potency of 45 IU/ampoule. The same preparation was also adopted by the WHO Expert Committee on Biological Standardization (ECBS) to serve as the WHO 2nd IS for Tetanus Immunoglobulin, Human (13/240).

Tetanus Vaccination 2020 and Collateral Protections against Pertussis and Diphtheria.

Tetanus is a life-threatening but vaccine-preventable disease caused by the toxin of the bacterium Clostridium tetani and is characterized by muscle spasms and autonomic nervous system dysfunction. It is prevented through vaccination with tetanus toxoid, but because the causative agent is widespread in the environment, eradication is impossible. Therefore, efforts to reduce incidence are aimed at reaching elimination, rather than eradication. This article reviews the pathogenesis, clinical manifestation and treatment of tetanus, and summarizes all recommendations from CDC's Advisory Committee on Immunization Practices (ACIP) regarding prevention and control of tetanus in the United States.

Neonatal tetanus in St. Mary's Hospital Lacor: A case report.

Umbilical stump sepsis in a nonpassively immunized neonate poses a high risk to neonatal tetanus. Management of neonatal tetanus is still a great challenge in resource-limited settings where some health facilities lack tetanus toxoid containing vaccines, ventilator support, and inaccessibility of tetanus immunoglobulin.

The Life-Threatening Risk of a Dirty Wound: A Lesson From the Past.

Tetanus is a severe and potentially life-threatening infection caused by the bacterium Clostridium Tetani. It is a gram-negative anaerobe, often found in soil in spore form and in the gastrointestinal tract of humans and animals. It produces a potent neurotoxin called tetanospasmin. The presence of this toxin on the affected wound contributes to its pathogenesis. In developed countries such as the United Kingdom, tetanus poses a diagnostic challenge as cases are becoming scarce and, therefore, difficult to diagnose in an acute setting following the national immunisation programme in 1961. The prognosis of an acute tetanus can be derived from several risk-stratifying scoring systems such as the Tetanus Severity Score (TSS), with any score above 8 representing a 53% case-fatality rate. Prompt clinical diagnosis, immediate delivery of treatment and strict adherence to the national vaccination programme are paramount to suppress the incidence and the fatality rate from tetanus.

Intrathecal Immunoglobulin for treatment of adult patients with tetanus: A randomized controlled 2x2 factorial trial.

Despite long-standing availability of an effective vaccine, tetanus remains a significant problem in many countries. Outcome depends on access to mechanical ventilation and intensive care facilities and in settings where these are limited, mortality remains high. Administration of tetanus antitoxin by the intramuscular route is recommended treatment for tetanus, but as the tetanus toxin acts within the central nervous system, it has been suggested that intrathecal administration of antitoxin may be beneficial. Previous studies have indicated benefit, but with the exception of one small trial no blinded studies have been performed. The objective of this study is to establish whether the addition of intrathecal tetanus antitoxin reduces the need for mechanical ventilation in patients with tetanus. Secondary objectives: to determine whether the addition of intrathecal tetanus antitoxin reduces autonomic nervous system dysfunction and length of hospital/ intensive care unit stay; whether the addition of intrathecal tetanus antitoxin in the treatment of tetanus is safe and cost-effective; to provide data to inform recommendation of human rather than equine antitoxin. This study will enroll adult patients (≥16 years old) with tetanus admitted to the Hospital for Tropical Diseases, Ho Chi Minh City. The study is a 2x2 factorial blinded randomized controlled trial. Eligible patients will be randomized in a 1:1:1:1 manner to the four treatment arms (intrathecal treatment and human intramuscular treatment, intrathecal treatment and equine intramuscular treatment, sham procedure and human intramuscular treatment, sham procedure and equine intramuscular treatment). Primary outcome measure will be requirement for mechanical ventilation. Secondary outcome measures: duration of hospital/ intensive care unit stay, duration of mechanical ventilation, in-hospital and 240-day mortality and disability, new antibiotic prescription, incidence of ventilator associated pneumonia and autonomic nervous system dysfunction, total dose of benzodiazepines and pipecuronium, and incidence of adverse events. Trial registration: ClinicalTrials.gov NCT02999815 Registration date: 21 December 2016.

Functional and proteomic comparison of different techniques to produce equine anti-tetanus immunoglobulin F(ab')2 fragments.

Tetanus is still a major cause of human deaths in several developing countries. In particular, the neonatal form remains a significant public health problem. According to the World Health Organization, administration of tetanus toxoid is recommended for neonatal tetanus patients. Furthermore, tetanus antitoxin or anti-tetanus immunoglobulin (Ig) are used for mild case or intensive care. This paper discusses a novel purification technique for improving equine anti-tetanus Ig production. First, equine plasma dealt with two steps salting out with ammonium sulfate; second, ultrafiltration concentration liquid purified by one successive protein G based affinity chromatography steps; finally, the purified F(ab')2 fragments was characterized using biochemical and proteomic methods and shown to be pure and homogeneous. Compared with the original technique product, specific activity increased by 80% (about 90,000 IU/g) and recovery of F(ab')2 is approximately equal 75%. Furthermore, Proteomic profiling of total technique process is demonstrated by nano-HPLC-MS and bioinformatics analysis. New technique to produce equine anti-tetanus immunoglobulin F(ab')2 fragments from crude plasma in high quality and yield. And it also could be used for industrial amplification.