Tetanus Antitoxin Research Articles

CURRENT CONCEPTS IN THE MANAGEMENT OF TETANUS

The study focuses on the problem of severe tetanus cases, which continue to be reported worldwide. The population of countries with low vaccination rates, including Ukraine, is particularly at risk. Despite the increase in the level of DPT vaccination in our country among adults and children, it remains insufficient, which leads to the registration of new cases of tetanus. The aim of the study was to analyze the main directions in the treatment of tetanus. The authors searched for information in electronic databases such as MEDLINE/Pub Med and Google Scholar for the last 20 years. The search was performed on such terms as tetanus, treatment, benzodiazepines, tetanus immunoglobulin (medical topics). The main components of modern treatment are analyzed in the paper, which include removal of the pathogen by careful surgical treatment of wounds, rational antibiotic therapy. Drugs of choice for the eradication of vegetative forms of the pathogen are benzylpenicillin and metronidazole, but can also be used antibacterial drugs of other groups (macrolides, tetracyclines, cephalosporins). Specific immunotherapy with tetanus immunoglobulin can neutralize the toxin that freely circulates in the blood. Those who do not have vaccination data are also indicated for the introduction of tetanus toxoid. Intrathecal administration of anti-tetanus immunoglobulin remains a debatable issue. In the treatment of convulsions, drugs of the benzodiazepine group are preferred. Infusions of high doses of magnesium, dexmetomedin, baclofen, propofol or their combination can also be used. In the case of severe muscular rigidity, muscle relaxants of nondepolarizing action are used. If the spasms are prolonged, botulinum toxin A may be recommended as an injection into peripheral muscles. B-blockers (esmolol), dexmetomedin, clonidine are used to overcome autonomic dysfunction of the nervous system. Supportive therapy is important. It is aimed at providing the patient with complete nutrition. Adequate ventilation with early tracheostomy helps to avoid complications of prolonged intubation. The above methods can significantly reduce mortality from tetanus from 100% (in the absence of treatment) to 10%–20%. Keywords: tetanus, management, benzodiazepines, magnesium sulfate, tetanus immunoglobin, tracheostomy.

Scald burns in a 7-h old neonate: A consequence of traditional hot water bath

Burn injuries are rare in the neonatal period. Most of the cases reported in the literature are iatrogenic. We report the case of a 7-h old female neonate who presented with domestic accidental scald burns involving 18% of the total body surface area. She sustained the burns during a traditional bath with hot water. She was resuscitated with intravenous fluid, and urine output was monitored. She was nursed under a radiant heater and was given analgesics and tetanus antitoxin. She had wound sepsis from Pseudomonas species which was successfully treated with intravenous antibiotic (ceftazidime). She also had anemia which was corrected with packed red blood cell transfusion. Wound dressing was done with antibiotic-impregnated gauze until the wounds were satisfactorily healed. She was discharged from the hospital on the 29th-day postburn.

Seroprevalence of <i>Clostridium tetani</i> in Donkeys in Kaduna State, Nigeria

Tetanus is an acute non-contagious and infectious disease caused by Clostridium tetani exotoxins that affect many animal species and humans. It is associated with high mortality rate, ranging from 58% to 80% in Equidae. This study investigated the seroprevalence of C. tetani antibodies in donkeys in Kaduna State. A total of 384 donkeys were sampled from the study area, 5 ml of blood was collected aseptically from the jugular vein and sera was harvested and tested for tetanus using ELISA kits. A seroprevalence of C. tetani of 295/384 (76.8%) was recorded. Male donkeys had a higher sero-prevalence (89.9%) than female (64.1%), young donkeys had 78.5% compared to 75.7% for adults; donkeys with wounds had a seroprevalence of 92.1% while those without wounds (42.4%). Donkeys from free range had a higher seroprevalence of 88.0%. Donkeys with BCS of 1 and 2 had 87.8% being the highest value, based on breeds, the Fari and Idabari had the higher seroprevalence (85.7% and 87.2% respectively), It was concluded that the donkeys in the Northern Kaduna had a high seroprevalence to C. tetani and also sex, age, breeds and presence of wounds were the main risk factors to C. tetani infection in donkeys and it was recommended that the use of donkeys in production of tetanus antitoxins and toxoid should be investigated.

Impact of Anti-CD19 CAR-T Axicabtagene Ciloleucel on Vaccine Titers of DTaP and MMR

Background: Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of relapsed/refractory B-cell lymphoid malignancies. Axicabtagene ciloleucel (axi-cel), an anti-CD19 CAR-T not only targets the malignant B-cell, but can potentially also target and eliminate normal B-cells. This can interfere with the normal B-cell repertoire, compromising host humoral immunity such as decreased titers of common vaccines (DTaP, MMR). To assess if this was a clinically significant problem, we evaluated all recipients of axi-cel at our center between 6/2018 through 7/2019. Patients and methods: For patients who received commercial axi-cel, humoral immunity was evaluated both quantitatively [absolute lymphocyte count (ALC)] as well as qualitatively by serology titers [IgG antibodies (Abs)] for diphtheria, tetanus, pertussis, measles, mumps, and rubella, and total Immunoglobulin G (IgG) levels. Data was collected within 30 days prior to CAR-T infusion, then at day +30 and between days +60 and +100 after CAR-T infusion. Results: We identified 10 patients (males = 5, 50%), with a median age of 49.9 years (range 30-65) who received commercial axi-cel during the study period. Patient characteristics and indications for CAR-T therapy are shown in Table 1; the cohort represented a heavily pre-treated aggressive B-cell lymphoma patient population. Baseline information on antibody (Ab) titers was available in 8 patients. At baseline, all patients had positive tetanus IgG Abs (≥0.01 IU/mL), 7 had positive diphtheria IgG Abs (≥0.01 IU/mL), 6 had positive measles IgG Abs (≥ 1.1 AI), 5 had positive rubella IgG Abs (≥ 1.0 AI), 3 had positive mumps IgG Abs (≥ 1.1 AI). None of the patients had a positive pertussis IgG Abs (≥100 IU/mL). At follow-up, all patients with positive Ab at baseline maintained titers in the positive range at day +30 and between days +60 and +100 (Figure 1). None of the patients demonstrated a clinically meaningful decrease in Abs titers, despite a drop in ALC and IgG levels (table 2). Conclusions: Albeit a small sample size, IgG Ab titers for diphtheria, tetanus, measles, mumps, and rubella did not appear to be affected by axi-cel at a short interval follow-up after infusion (up to day +100). We plan to extend this analysis in a larger cohort with a longer-term prospective follow-up to validate our findings, especially in light of dropping absolute lymphocyte counts and IgG levels. Disclosures Ailawadhi: Celgene: Consultancy; Amgen: Consultancy, Research Funding; Cellectar: Research Funding; Janssen: Consultancy, Research Funding; Takeda: Consultancy; Pharmacyclics: Research Funding. Foran:Agios: Honoraria, Research Funding. Tun:Celgene: Research Funding; Curis: Research Funding; TG Therapeutics: Research Funding; Mundi-pharma: Research Funding; DTRM Biopharma: Research Funding; BMS: Research Funding. Chanan-Khan:Pharmacyclics: Research Funding; Merck: Research Funding; Jansen: Research Funding; Mayo Clinic: Employment; Ascentage: Research Funding; Millennium: Research Funding; AbbVie: Research Funding; Xencor: Research Funding. Kharfan-Dabaja:Daiichi Sankyo: Consultancy; Pharmacyclics: Consultancy.

Contribution of Fc fragment of monoclonal antibodies to tetanus toxin neutralization.

Monoclonal antibodies (MAbs) against neurotoxin of Clostridium tetani are considered as a novel source of immunoglobulins for passive immunotherapy of tetanus. Toxin neutralization is classically attributed to the Fab and F(ab')2 fragments of antibodies. Herein, we generated Fab and F(ab')2 fragments of three toxin neutralizing mouse MAbs and compared their neutralizing activities to those of their intact molecules. Fab and F (ab')2 fragments of the antibodies were generated by papain and pepsin digestions, respectively, and their toxin neutralizing activities were compared with those of the intact antibodies in an in vivo toxin neutralization assay. While low doses of the intact MAbs were able to fully protect the mice against tetanus toxin, none of the mice which received Fab or F(ab')2 fragments survived until day 14, even at the highest administered dose. All mice receiving human polyclonal anti-tetanus immunoglobulin or their fragments were fully protected. Reduction in toxin neutralization activities of Fab and F(ab')2 fragments of our MAbs seems to be influenced by their Fc regions. Steric hindrance of the Fc region on the receptor-binding site of the toxin may explain the stronger neutralization of the toxin by the intact MAbs in comparison to their fragments.

Human Immunodeficiency Virus Exposure but Not Early Cytomegalovirus Infection Is Associated With Increased Hospitalization and Decreased Memory T-Cell Responses to Tetanus Vaccine.

Human immunodeficiency virus (HIV)-exposed, uninfected (HEU) infants experience high rates of infectious morbidity. We hypothesized that early cytomegalovirus (CMV) infection was associated with increased hospitalization rates and decreased vaccine responses in HEU compared with HIV-unexposed (HUU) infants. Among infants enrolled in the Tshipidi study in Botswana, we determined CMV infection status by 6 months of age and compared hospitalization rates and responses to tetanus and Bacille Calmette-Guérin vaccines among HEU and HUU vaccinees. Fifteen of 226 (6.6%) HEU infants and 17 (19.3%) of 88 HUU infants were CMV-infected by 6 months. The HEU infants were approximately 3 times as likely to be hospitalized compared with HUU infants (P = .02). The HEU peripheral blood cells produced less interleukin (IL)-2 (P = .004), but similar amounts of interferon-γ, after stimulation with tetanus toxoid. Antitetanus immunoglobulin G titers were similar between groups. Cellular responses to purified protein derivative stimulation did not differ between groups. Maternal receipt of 3-drug antiretroviral therapy compared with zidovudine was associated with increased IL-2 expression after tetanus toxoid stimulation. The infants' CMV infection status was not associated with clinical or vaccine response outcomes. We observed that increased rates of hospitalization and decreased memory T-cell responses to tetanus vaccine were associated with HIV exposure and incomplete treatment of maternal HIV infection, but not early CMV infection.

Sergey Petrovich FEDOROV - founder of the largest Russian surgical school, "father of Russian urology» (to the 150th of birthday)

Sergey Petrovich Fedorov was born in Moscow in 1869. In 1886 he graduated with honors from the gymnasium, and in 1891 - the medical faculty of Moscow University. In 1892, he was the first in Russia to manufacture and put into practice cholera and tetanus antitoxins, in 1893 - tetanus toxoid serum. In 1895, he defended his doctoral dissertation and was appointed as an assistant, and in 1896 - as a privat-docent of the faculty surgical clinic of Moscow University. In 1899 S.P. For the first time, Fedorov performed a single-step trans-vesicular prostatectomy, in 1901 a laparotomy for purulent peritonitis, in 1902 a gastrectomy with resection of the esophagus, resection of the colon. From 1903 to 1936, Sergei Petrovich headed the department of the hospital surgical clinic of the Military Medical Academy. In 1907, on his initiative, the Russian Urological Society was organized in Russia, the chairman of which he was elected (now bearing his name), the Urological Institute was established at the Military Medical Academy. In 1909 S.P. For the first time in the world, Fedorov performed the operation under intravenous hedonal anesthesia, which was the beginning of the widespread use of inhalation anesthesia. In 1909 he was awarded the title of honorary life-surgeon, and at the end of 1912 he was confirmed as a life-surgeon of the imperial family, which he combined with work in the Military Medical Academy. At this time, he wrote "Atlas of Cystoscopy and Rectoscopy" (1911), the monograph "Gallstones and surgery of the biliary tract" (1918). May 2, 1920 S.P. Fedorov was detained and put in prison. September 9, 1920, he was sentenced to a suspended five-year prison term. September 14, 1921 S.P. Fedorov was arrested again and at the end of November under escort sent to Moscow for a free settlement. In 1921 S.P. Fedorov took part in the creation of the first Soviet surgical journal "New Surgical Archive". From 1926 to 1933, he headed the Institute of Surgical Neuropathology (now the Leningrad Research Neurosurgical Institute named after A.L. Polenov, M3 of the RSFSR). S.P. Fedorov proposed new methods and modifications of operations on the nervous system, kidneys, intestines, biliary tract, new tools for their implementation. Under his leadership, the development of blood transfusion problems began for the first time in the USSR. He created the largest surgical school (N.N. Elansky, I.S. Kolesnikov, P.A. Kupriyanov, V.N. Shamov, etc.). In 1928, S. P. Fedorov was awarded the title of Honored Scientist of the RSFSR. In 1933, he was the first of the surgeons to be awarded the Order of Lenin.Died S.P. Fedorov in Leningrad in 1936 and was buried at the Communist site (now the Cossack cemetery) of the Alexander Nevsky Monastery. He has published over 120 scientific papers, including 11 manuals and monographs. Memorial plaque in memory of SP Fedorov installed on the building of the Faculty Surgery Clinic of the Military Medical Academy. CM. Kirov.

Insufficient knowledge and inappropriate practices of emergency doctors towards tetanus prevention in trauma patients: a pilot survey

ABSTRACTChina has a shocking number of tetanus cases in the world, but little research has investigated doctors’ knowledge of and practices in tetanus prophylaxis, especially tetanus vaccination. To this end, we conducted a pilot study on 197 emergency doctors using a mixed method of web-based (163; 82.8%) and paper-based (34; 17.2%) surveys. There was no difference between the two groups except for the percentage of doctors receiving a tetanus booster in the past 10 years and the responses to question 11. Surprisingly, only 28.9% of doctors had received formal training on tetanus immunization and only 21.3% had themselves received a tetanus vaccine booster in the past 10 years. Furthermore, only 14.2% of the respondents confirmed the availability of the tetanus vaccine in their respective institutions. Finally, the correct rates and Tetanus-immune-globulin (TIG)-only option rates for questions 11–15 were unsatisfactory. Our results showed that most emergency doctors’ knowledge and practices strayed from the recommendations of Advisory Committee on Immunization Practices (ACIP): 1) TIG alone for most trauma patients instead of vaccine was an overused treatment approach. 2) Most of the emergency doctors lacked formal training on and knowledge of tetanus vaccination. 3) Even the emergency doctors themselves were not properly vaccinated. 4) The tetanus vaccine was only available in a small number of the respondents’ institutions. The findings of this study suggest an urgent need to improve this dire situation.

Tetanus antitoxin potency assessment by surface plasmon resonance and ToBI test

Potency testing of tetanus antitoxin must be performed in vivo, in a very painful, stressful and prone to high variability assay. It is, therefore, mandatory to find alternatives to this kind of potency assessment. Immunochemical tests as ELISA or ToBI test are already available but usually results in a poor correlation to the in vivo protection. Considering research and development of mono and oligoclonal antibodies against tetanus and the improvement of equine polyclonal antitoxin production and control, we developed an alternative instrumental test for tetanus antitoxin by using surface plasmon resonance. Tetanus antitoxin from hyperimmune equine sera (16 batches) were tested and the results indicated excellent concordance and correlation to the in vivo test (Lin's ρ = 0.9). This innovative approach should now be improved in order to extend it to oligoclonal and monoclonal human antibodies aiming to replace mice for the potency assessment of tetanus antitoxin especially during research and development steps.

Erişkinlerde Tetanoz Antikor Düzeylerinin Araştırılması

Aim: Tetanus is an acute and lethal disease caused by exotoxins named tetanospasmin produced by Clostridium tetani. Despite being vaccine-preventable, tetanus is still a toxic-infectious disease with high mortality. In this cross-sectional study, it is aimed to determine levels of tetanus anti-toxin IgG and factors affecting it in adults in the region.Material and Methods: This cross-sectional study was conducted with patients applied to the blood sampling laboratory unit of Düzce University Hospital. Tetanus anti-toxin IgG Enzyme-Linked Immuno Sorbent Assay kits (Catalog number: EI 2060-9601 G, Euroimmun, Germany) were used for detection of tetanus antibodies. Those with tetanus anti-toxin IgG >0.1 IU/ml were considered immunized. Socio-demographic information of participants were collected using a questionnaire during blood collection.Results: Sufficient tetanus antibody was detected in 140 (39.3%) of 356 patients. Protective antibody ratios were found as 49 (70.0%) in 30-40 age group, 39 (54.9%) in 41-50 age group, 22 (31.0%) in 51-60 age group, 16 (22.2%) in 61-70 age group and 14 (19.4%) in >71 age group. Tetanus immunity ratios were significantly reduced with aging (p<0.001). Protective antibodies were found to be higher in the groups who had more education and who were vaccinated in adult ages for any reason than in the other groups (both p<0.001).Conclusion: It was thought that the childhood immunity should be reinforced with the booster doses during adulthood by routine tetanus immunization program. In addition, the high level of tetanus immunity in those with high educational level has shown the importance of education.

Generalised tetanus in a cat

This case report describes the presentation of a cat with generalised tetanus, which is uncommon in this species. The onset of clinical signs with focal limb rigidity occurred one week...

Clinical features and outcomes of tetanus: a retrospective study.

Background: Tetanus is a serious disease resulting in muscle spasm, and even death.Methods: A retrospective, single-center study was conducted by analyzing demographic and clinical parameters.Results: The study included 12 males (70.6%) and 5 females (29.4%). The mean age of the patients was 56.71±9.05 years. Patient occupations included farming (47.0%), retired (23.5), homebound (23.5), and workers (6.0%). The causes of patient injuries were as follows: metal injury (52.9%), deep injury (29.4%), electrical injury (5.9%), maxillofacial region and knee injury (5.9%), and skin ulceration (5.9%). The disease duration ranged from 3 to 36 days, and the mean incubation period was 12.65±10.17 days. Four patients had co-morbidities. The infected patients were given tetanus antitoxin (TAT) and antibiotics treatment. One patient was given continuous renal replacement therapy (CRRT) and only one patient died.Conclusions: In our department, although tetanus is a serious disease, with effective treatment, patients have reasonable cure and low death rates.

The Immunogenicity of the C Fragment of Tetanus Neurotoxin in Production of Tetanus Antitoxin.

The demand of tetanus antitoxin (TAT) as tetanus treatment in developing and underdeveloped countries is still great since it is relatively easy to achieve and affordable. However, there are still issues in the preparation of highly effective TAT with tetanus toxoid (TT) as the immunogen. The tetanus toxin native C-fragment (TeNT-Hc) retains many properties and it is a very promising candidate for the development of tetanus human vaccine. In this study, we tested the immunogenicity of TeNT-Hc in the preparation of tetanus antibodies, by TeNT-Hc alone or in different combinations with TT. The antibody titers and components in horse serum or plasma in different groups were analyzed and compared with those immunized by the conventional TT and it showed comparability with the results of traditional methods. The plasma efficacy and in vivo tetanus toxin neutralization were also tested. After two stages of immunizations, the average potency in plasma of all groups reached more than 1,000 IU / mL except that in group 4. In group 5, the first two basic immunizations with TT and the subsequent immunizations with TeNT-Hc, it showed slightly higher antibody titers and potency. This study demonstrated that TeNT-Hc is a safe, effective, and yet easy-to-produce low-cost immunogen and suitable for TT replacement in tetanus antitoxin production.

Viral testing of 18 consecutive cases of equine serum hepatitis: A prospective study (2014-2018).

BackgroundThree flaviviruses (equine pegivirus [EPgV]; Theiler's disease–associated virus [TDAV]; non‐primate hepacivirus [NPHV]) and equine parvovirus (EqPV‐H) are present in equine blood products; the TDAV, NPHV, and EqPV‐H have been suggested as potential causes of serum hepatitis.ObjectiveTo determine the prevalence of these viruses in horses with equine serum hepatitis.AnimalsEighteen horses diagnosed with serum hepatitis, enrolled from US referral hospitals.MethodsIn the prospective case study, liver, serum, or both samples were tested for EPgV, TDAV, NPHV, and EqPV‐H by PCR.ResultsBoth liver tissue and serum were tested for 6 cases, serum only for 8 cases, and liver only for 4 cases. Twelve horses received tetanus antitoxin (TAT) 4‐12.7 weeks (median = 8 weeks), 3 horses received commercial equine plasma 6‐8.6 weeks, and 3 horses received allogenic stem cells 6.4‐7.6 weeks before the onset of hepatic failure. All samples were TDAV negative. Two of 14 serum samples were NPHV‐positive. Six of 14 serum samples were EPgV‐positive. All liver samples were NPHV‐negative and EPgV‐negative. EqPV‐H was detected in the serum (N = 8), liver (N = 4), or both samples (N = 6) of all 18 cases. The TAT of the same lot number was available for virologic testing in 10 of 12 TAT‐associated cases, and all 10 samples were EqPV‐H positive.Conclusions and Clinical ImportanceWe demonstrated EqPV‐H in 18 consecutive cases of serum hepatitis. EPgV, TDAV, and NPHV were not consistently present. This information should encourage blood product manufacturers to test for EqPV‐H and eliminate EqPV‐H–infected horses from their donor herds.

Intravenous magnesium sulphate infusion as first-line therapy in the control of spasms and muscular rigidity in childhood tetanus

ABSTRACTBackground: Reports suggest that, in tetanus, magnesium sulphate (MgSO4) alone may control muscle spasms, thereby avoiding sedation and mechanical ventilation.Aim: To study the efficacy and safety of intravenous MgSO4 in controlling spasms and rigidity in children with tetanus.Methods: All children with tetanus consecutively admitted over a 2-year period in a tertiary-care teaching hospital were recruited. In addition to human tetanus immunoglobulin and parenteral metronidazole, patients received MgSO4 100 mg/kg intravenously followed by infusion at 40 mg/kg/hr. The infusion rate was increased by 5 mg/kg/hr every 6 h until cessation of spasms or abolition of the patellar tendon reflex. Efficacy was determined by control of spasms. Time to commencement of feeds, frequency of autonomic instability, the need for ventilatory support, duration of hospitalisation and mortality were also recorded.Results: Twenty-seven children with tetanus aged between 18 months and 10 years were recruited. A contaminated wound was the most common portal of entry of tetanus spores. The incidences of severity were: grade I, 3; grade II, 7; grades IIIa and b, 17. Rigidity and spasms were controlled by magnesium therapy alone in 14 patients. Additional sedation was required for 13 patients (grade II, 1; grade III, 12). Feeding could be commenced early in five patients. Mechanical ventilation was required in eight patients. The mean (SD) duration of hospitalisation was 26.5 (12.0) days. Five patients died (18.5%). Asymptomatic hypocalcaemia was a universal finding and was treated with calcium supplements.Conclusion: MgSO4 alone is effective in mild-to-moderate tetanus but not when it is severe.

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.

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

Theiler's disease associated with administration of tetanus antitoxin contaminated with nonprimate (equine) hepacivirus and equine parvovirus‐hepatitis virus

SummaryAn 11‐year‐old Trakehner gelding was presented for evaluation of lethargy, decreased appetite, mild icterus, and elevated hepatic enzyme activities. Physical examination, serum chemistry results, and liver biopsy histopathologic findings were supportive of Theiler's disease. Polymerase chain reaction (PCR) testing results of serum and liver tissue were positive for nonprimate (equine) hepacivirus (NPHV) and a novel equine parvovirus‐hepatitis virus (EqPV‐H). PCR testing of the lot of tetanus antitoxin administered to the gelding 3 months previously also yielded positive results for NPHV and EqPV‐H. Treatment included supportive care and clinical signs resolved within 1 week, although hepatic enzyme activities remained elevated for several months. The horse successfully returned to work as a hunter/jumper for about 1 year until it developed a forelimb lameness and progressive atrophy of shoulder musculature (sweeney), prompting a decision for euthanasia 20 months after initial evaluation. Serial PCR testing of serum revealed persistent infection with both NPHV and EqPV‐H and necropsy examination revealed chronic active hepatitis, mild liver atrophy, and positive PCR results for NPHV and EqPV‐H in liver tissue. This case highlights the possible risk of administering potentially contaminated biologics of equine origin and the importance of screening for recently identified hepatic viruses in donors from which blood products are prepared.

A Report of Five Child Tetanus Cases

AbstractWe present five cases of generalized tetanus in children 5 to 13 years old, who were admitted to the intensive care unit of Ternopil Regional Children's Hospital (Western Ukraine) during the past 6 years (2012–2017). In our study, four children were unvaccinated and one received the full series of vaccinations. Proper vaccination in cases of infected wound may not prevent the development of the disease but improves the prognosis for recovery. Treatment of tetanus in Ukraine requires standardization of treatment protocols according to the World Health Organization recommendations, including making human tetanus immune globulin available, as specified by evidence-based medicine. Vaccines availability and education of physicians and parents about the benefits of immunization should be priority national health measures to prevent tetanus.

Development and application of passive immunizing agents against tetanus: a literature review

Immunoprophylaxis against tetanus is divided into passive and active immunization.Passive immunizing agents include tetanus antitoxin and human tetanus immunoglobulin.Tetanus antitoxin played an important role in early tetanus immunoprophylaxis.However, some safety problems do exist as it contains allogeneic serum and because of that, it has been gradually replaced by human tetanus immunoglobulin.Misapplication of passive immune agents has resulted in a waste of medical resources and revealed potential medical risks.Standardized and rational application of active immunizing agents (tetanus toxoid) with reduced usage of passive immunizing agents is the most effective measure to prevent Clostridium tetani infection. Key words: Tetanus; Immunoprophylaxis; Passive immunity; Active immunity