Safety and efficacy of Magnesium Sulfate in the management of Tetanus: A systematic review.

Tetanus is a rare life-threatening condition often complicated by repetitive spasms, dysautonomia and neuromuscular respiratory failure contributing to high fatality rates in its severe form. Benzodiazepines used to treat muscle spasms pose a high risk of respiratory failure requiring mechanical ventilation, which is unaffordable and inaccessible for many. Magnesium sulfate, a cheap and widely available medication in all urban and rural health centres of LMICs for the treatment of eclampsia, can be used to control muscle spasms and dysautonomia. We thus conducted a systematic review of evidence to assess the safety and efficacy of magnesium sulfate in the treatment of tetanus. Any study published before April 15, 2021, discussing the efficacy and/or safety of MgSO4 infusion in the treatment of tetanus was systemically reviewed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Our systematic review included data from 13 studies, three were randomised, double-blind and controlled trials. The remaining ten studies were observational; six prospective and four retrospective studies. Our review showed no mortality benefit associated with the use of magnesium sulfate. However, magnesium sulfate was found to be effective in reducing spasms along with diazepam, leading to better control of dysautonomia, reduced need for mechanical ventilation and shorter hospital stay by 3-7 days. The incidence of magnesium toxicity was very low in the studies included.

Prevalence and predictors of taking tetanus toxoid vaccine in pregnancy: a cross-sectional study of 8,722 women in Sierra Leone.

BACKGROUND: Immunization of women during pregnancy to protect them and their infants against tetanus, pertussis and influenza is recommended by the World health Organization (WHO). However, there is limited information about the coverage rate and associated factors in low-income countries. The aim of this study was to measure the prevalence and predictors of taking tetanus toxoid among pregnant women in Sierra Leone. METHODS: This study was based on the fifth round of Multiple Indicator Cluster Survey (MICS 5) conducted in Sierra Leone in 2017. In total 8722 women aged between 15 and 49 years were included in this study. Outcome variable was taking of Tetanus Toxoid vaccination during the last pregnancy. Data were analyzed using cross-tabulation and logistic regression methods. RESULTS: The overall prevalence of receiving TT immunization during women's last pregnancy was 96.3% and that of taking at least two doses was 82.12%. In the regression analysis, women from Mende ethnicity had a 0.48 fold lower chance of being immunized (OR = 0.480, 95% CI = 0.385,0.59768) than those from the other ethnicity. In addition, women who attended at least four ANC visits had higher odds of receiving TT vaccine (OR = 1.919, 95% CI = 1.639,2.245) compared to those who attended less ANC visits. Stratified by areas, this association was observed in both urban (OR = 2.661, 95% CI = 1.924,3.679) and rural areas (OR = 1.716, 95% CI = 1.430,2.059). Attending at least four ANC visits showed a positive association with receiving at least two doses TT (OR = 2.434, 95% CI = 1.711,3.464) in both urban (OR = 2.815, 95% CI = 1.413,5.610) and rural areas (OR = 2.216, 95% CI = 1.463,3.356) as well. CONCLUSION: Higher number of ANC visits, mass media exposure and higher wealth quintile increased the odds of receiving TT immunization. In addition, minimum two doses which were identified to reduce neonatal mortality. Therefore, immunization campaigns targeting improved utilization of healthcare and immunization services by women of childbearing age in Sierra Leone are strongly recommended.

New evidence on the impact of the quality of prenatal care on neonatal and infant mortality in India.

Evidence on the impact of the quality of prenatal care on childhood mortality is limited in developing countries, including India. Therefore, using nationally representative data from the latest round of the National Family Health Survey (2015-16), this study examined the impact of the quality of prenatal care on neonatal and infant mortality in India using a multivariable binary logistic regression model. The effect of the essential components of prenatal care services on neonatal and infant mortality were also investigated. The results indicate that improvement in the quality of prenatal care is associated with a decrease in neonatal (OR: 0.93, 95% CI: 0.91-0.97) and infant (OR: 0.94, 95% CI: 0.92-0.96) mortality in India. Tetanus toxoid vaccination, consumption of iron-folic acid tablets during pregnancy and having been weighed during pregnancy were statistically associated with a lower risk of neonatal and infant mortality. Educating women on pregnancy complications was also associated with a lower risk of neonatal mortality. No effect of blood pressure examination, blood test and examination of the abdomen during pregnancy were found on either of the two indicators of childhood mortality. Although the coverage of prenatal care has increased dramatically in India, the quality of prenatal care is still an area of concern. There is therefore a need to ensure high-quality prenatal care in India.

The Prevalence and Case-Fatality Rates of Post-Neonatal Tetanus in a Population of Hospitalized Nigerian Children: An 8-Year Retrospective Review.

BACKGROUND: Although tetanus is a vaccine-preventable disease, reports indicate that it remains a significant cause of morbidity and mortality in both neonatal and post-neonatal periods especially in most developing countries. AIM: This study aimed to determine the prevalence and case fatality rates of post-neonatal tetanus among children managed at the Federal Medical Centre Asaba, Delta State, Nigeria over 8 years. METHOD: The study was a retrospective review of the records of the children above 1 month of age admitted into Federal Medical Centre, Asaba, with a clinical diagnosis of tetanus from January 2008 to May 2016. Data analysis was conducted on descriptive and inferential statistics using Statistical Package for Social Sciences version 22.0. Mean, standard deviation and other relevant parameters were calculated. Level of significance was set at p < 0.05. RESULTS: During the study period, 32 out of 3693 admitted Paediatric patients had post-neonatal tetanus: giving a prevalence rate of 0.9%. The male : female ratio was 1.9 : 1 and patients' ages ranged from 2 to 15 years with a mean age 8.9 ± 3.1 years. Twenty-nine percent of them had complete immunization during infancy, but none had booster doses. Also, 60.9% of them presented with lower limb injuries as the portal of entry. Over 17.4% of the patients had very severe tetanus. Of the 32 patients studied, 62.5% resided in the neighbouring rural communities, while 50.0% were admitted for ≤10 days. The calculated case fatality rate was 50%. CONCLUSION: The prevalence and case fatality rates of post-neonatal tetanus are still relatively high in this clime. Given the prevalent nature of the disease in children aged 5 years and above, there is a need to include the booster doses of tetanus toxoid in the country's National Programme on Immunization schedule.

Prognostic factors for generalized tetanus in adults: A retrospective study in a Chinese hospital.

BACKGROUND: We evaluated factors associated with mortality in patients with moderate/severe generalized tetanus. METHODS: This retrospective study included patients with moderate/severe generalized tetanus admitted to the Affiliated Hospital of Nantong University (China) between January 2005 and January 2017. Clinical data were extracted from medical records. Patients were divided into two groups based on outcome (survival or death). Factors associated with mortality were analyzed using univariate and multivariate logistic regression. RESULTS: Seventy-five patients were included (57.3% male; age, 57.9 ±â€¯18.4 years; APACHE II score, 10.6 ±â€¯3.4; severe tetanus, 49.3%; mortality, 25.3%). Multivariate analysis identified severe tetanus (odds ratio [OR], 30.364; 95% confidence interval [CI], 2.459-374.896) and APACHE II score (OR, 1.536; 95%CI, 1.051-2.243) as positively associated with mortality, whereas high-calorie nutrition (OR, 0.027; 95%CI, 0.002-0.359) and dexmedetomidine use (OR, 0.035; 95%CI, 0.003-0.467) were negatively associated with mortality (all P < 0.05). CONCLUSION: Tetanus severity and APACHE II score were associated with mortality in patients with generalized tetanus, whereas high-calorie nutrition and dexmedetomidine use reduced the odds of death. High-calorie nutrition and dexmedetomidine administration may improve prognosis in adult patients with moderate/severe generalized tetanus.

Disease burden of varicella versus other vaccine-preventable diseases before introduction of vaccination into the national immunisation programme in the Netherlands.

IntroductionEstimating burden of disease (BoD) is an essential first step in the decision-making process on introducing new vaccines into national immunisation programmes (NIPs). For varicella, a common vaccine-preventable disease, BoD in the Netherlands was unknown.AimTo assess national varicella BoD and compare it to BoD of other vaccine-preventable diseases before their introduction in the NIP.MethodsIn this health estimates reporting study, BoD was expressed in disability-adjusted life years (DALYs) using methodology from the Burden of Communicable Diseases in Europe (BCoDE)-project. As no parameters/disease model for varicella (including herpes zoster) were available in the BCoDE toolkit, incidence, disease progression model and parameters were derived from seroprevalence, healthcare registries and published data. For most other diseases, BoD was estimated with existing BCoDE-parameters, adapted to the Netherlands if needed.ResultsIn 2017, the estimated BoD of varicella in the Netherlands was 1,800 (95% uncertainty interval (UI): 1,800-1,900) DALYs. Herpes zoster mainly contributed to this BoD (1,600 DALYs; 91%), which was generally lower than the BoD of most current NIP diseases in the year before their introduction into the NIP. However, BoD for varicella was higher than for rotavirus gastroenteritis (1,100; 95%UI: 440-2,200 DALYs) and meningococcal B disease (620; 95%UI: 490-770 DALYs), two other potential NIP candidates.ConclusionsWhen considering the introduction of a new vaccine in the NIP, BoD is usually estimated in isolation. The current approach assesses BoD in relation to other vaccine-preventable diseases' BoD, which may help national advisory committees on immunisation and policymakers to set vaccination priorities.

Tetanus in Poland in 2017

INTRODUCTION: In the last decade, the number of tetanus cases in Poland has not exceeded 20 cases. Since 1984, neonatal tetanus has not been reported. OBJECTIVE OF THE WORK: The aim of the study is to present the data of epidemiological surveillance of tetanus in 2017 in a historical perspective, taking into account the role of protective vaccination and a reference to activities for the elimination of neonatal tetanus on a global scale. SUMMARY AND CONCLUSIONS. Tetanus is an infectious disease acquired in the environment and associated with wound pollution. Few cases of illness in Poland are associated with non-compliance with recommendations for booster vaccinations. MATERIAL AND METHODS: The material of the study are individual reports on tetanus sent to the Department of Epidemiology, NIZP-PZH and the bulletin "Infectious diseases and poisoning in Poland in 2017. The historical data is based on earlier Polish and foreign studies. RESULTS: In 2017, 11 cases of tetanus were reported. Four men and seven women got sick. One man died in the age > 69.

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.

Tetanus in Poland in 2016

THE PURPOSE of the STUDY: The purpose of the study was to provide data on tetanus incidence in 2016 in the basic categories of epidemiological surveillance. MATERIAL AND METHODS: The study is based on the individual forms of tetanus cases submitted to the NIZP-PZH Epidemiology Department and the data of the bulletin "Infectious Diseases and Poisoning in Poland in 2016. RESULTS: The number of tetanus cases in 2016 was 12, exactly as it was in the previous year 2015. Among the infected people there were six men and six women. Among the infected people two men and one women died. All the fatalities were in the age groups of 70 and older. SUMMARY AND CONCLUSIONS: The environmental nature of tetanus infections makes the immunity of individual exposed persons the basic preventive tool, which underlines the role of individual vaccinations.

Tetanus in adults: results of the multicenter ID-IRI study.

Tetanus is an acute, severe infection caused by a neurotoxin secreting bacterium. Various prognostic factors affecting mortality in tetanus patients have been described in the literature. In this study, we aimed to analyze the factors affecting mortality in hospitalized tetanus patients in a large case series. This retrospective multicenter study pooled data of tetanus patients from 25 medical centers. The hospitals participating in this study were the collaborating centers of the Infectious Diseases International Research Initiative (ID-IRI). Only adult patients over the age of 15 years with tetanus were included. The diagnosis of tetanus was made by the clinicians at the participant centers. Izmir Bozyaka Education and Research Hospital's Review Board approved the study. Prognostic factors were analyzed by using the multivariate regression analysis method. In this study, 117 adult patients with tetanus were included. Of these, 79 (67.5%) patients survived and 38 (32.5%) patients died. Most of the deaths were observed in patients >60 years of age (60.5%). Generalized type of tetanus, presence of pain at the wound area, presence of generalized spasms, leukocytosis, high alanine aminotransferase (ALT) and C-reactive protein (CRP) values on admission, and the use of equine immunoglobulins in the treatment were found to be statistically associated with mortality (p < 0.05 for all). Here, we describe the prognostic factors for mortality in tetanus. Immunization seems to be the most critical point, considering the advanced age of our patients. A combination of laboratory and clinical parameters indicates mortality. Moreover, human immunoglobulins should be preferred over equine sera to increase survival.

Mortality from tetanus between 1990 and 2015: findings from the global burden of disease study 2015.

BACKGROUND: Although preventable, tetanus still claims tens of thousands of deaths each year. The patterns and distribution of mortality from tetanus have not been well characterized. We identified the global, regional, and national levels and trends of mortality from neonatal and non-neonatal tetanus based on the results from the Global Burden of Disease Study 2015. METHODS: Data from vital registration, verbal autopsy studies and mortality surveillance data covering 12,534 site-years from 1980 to 2014 were used. Mortality from tetanus was estimated using the Cause of Death Ensemble modeling strategy. RESULTS: There were 56,743 (95% uncertainty interval (UI): 48,199 to 80,042) deaths due to tetanus in 2015; 19,937 (UI: 17,021 to 23,467) deaths occurred in neonates; and 36,806 (UI: 29,452 to 61,481) deaths occurred in older children and adults. Of the 19,937 neonatal tetanus deaths, 45% of deaths occurred in South Asia, and 44% in Sub-Saharan Africa. Of the 36,806 deaths after the neonatal period, 47% of deaths occurred in South Asia, 36% in sub-Saharan Africa, and 12% in Southeast Asia. Between 1990 and 2015, the global mortality rate due to neonatal tetanus dropped by 90% and that due to non-neonatal tetanus dropped by 81%. However, tetanus mortality rates were still high in a number of countries in 2015. The highest rates of neonatal tetanus mortality (more than 1,000 deaths per 100,000 population) were observed in Somalia, South Sudan, Afghanistan, and Kenya. The highest rates of mortality from tetanus after the neonatal period (more than 5 deaths per 100,000 population) were observed in Somalia, South Sudan, and Kenya. CONCLUSIONS: Though there have been tremendous strides globally in reducing the burden of tetanus, tens of thousands of unnecessary deaths from tetanus could be prevented each year by an already available inexpensive and effective vaccine. Availability of more high quality data could help narrow the uncertainty of tetanus mortality estimates.

Maternal and neonatal tetanus.

Maternal and neonatal tetanus is still a substantial but preventable cause of mortality in many developing countries. Case fatality from these diseases remains high and treatment is limited by scarcity of resources and effective drug treatments. The Maternal and Neonatal Tetanus Elimination Initiative, launched by WHO and its partners, has made substantial progress in eliminating maternal and neonatal tetanus. Sustained emphasis on improvement of vaccination coverage, birth hygiene, and surveillance, with specific approaches in high-risk areas, has meant that the incidence of the disease continues to fall. Despite this progress, an estimated 58,000 neonates and an unknown number of mothers die every year from tetanus. As of June, 2014, 24 countries are still to eliminate the disease. Maintenance of elimination needs ongoing vaccination programmes and improved public health infrastructure.

Tetanus disease and deaths in men reveal need for vaccination.

With efforts focused on the elimination of maternal and neonatal tetanus, less attention has been given to tetanus incidence and mortality among men. Since 2007 voluntary medical male circumcision has been scaled-up in 14 sub-Saharan African countries as an effective intervention to reduce the risk of human immunodeficiency virus (HIV) acquisition among men. As part of a review of adverse events from these programmes, we identified 13 cases of tetanus from five countries reported to the World Health Organization (WHO) up to March 2016. Eight patients died and only one patient had a known history of tetanus vaccination. Tetanus after voluntary medical male circumcision was rare among more than 11 million procedures conducted. Nevertheless, the cases prompted a review of the evidence on tetanus vaccination coverage and case notifications in sub-Saharan Africa, supplemented by a literature review of non-neonatal tetanus in Africa over the years 2003-2014. The WHO African Region reported the highest number of non-neonatal tetanus cases per million population and lowest historic coverage of tetanus-toxoid-containing vaccine. Coverage of the third dose of diphtheria-tetanus-polio vaccine ranged from 65% to 98% across the 14 countries in 2013. In hospital-based studies, non-neonatal tetanus comprised 0.3-10.7% of admissions, and a median of 71% of patients were men. The identification of tetanus cases following voluntary medical male circumcision highlights a gender gap in tetanus morbidity disproportionately affecting men. Incorporating tetanus vaccination for boys and men into national programmes should be a priority to align with the goal of universal health coverage.

Avec l'orientation des efforts sur l'élimination du tétanos maternel et néonatal, une moindre attention a été portée sur l'incidence et la mortalité du tétanos dans la population masculine. Depuis 2007, la circoncision médicale masculine volontaire s'est intensifiée dans 14 pays d'Afrique subsaharienne, en tant qu'intervention efficace pour réduire le risque d'acquisition du virus de l'immunodéficience humaine (VIH) chez les hommes. Dans le cadre d'une analyse des effets indésirables de ces programmes, nous avons identifié 13 cas de tétanos, dans cinq pays, qui ont été notifiés à l'Organisation mondiale de la Santé (OMS) jusqu'à mars 2016. Huit patients sont décédés et un seul patient avait un antécédent connu de vaccination antitétanique. Sur plus de 11 millions de procédures réalisées, les infections tétaniques suite à une circoncision médicale masculine volontaire ont été rares. Néanmoins, ces cas d'infection nous ont poussés à mener une étude des données disponibles sur la couverture antitétanique et sur la notification des cas en Afrique subsaharienne, complétée par une revue de la littérature sur le tétanos non-néonatal en Afrique sur la période de 2003 à 2014. Sur la période étudiée, les pays répertoriés dans la Région africaine de l'OMS correspondent au plus grand nombre de cas de tétanos non-néonatal pour un million d'habitants et à la plus faible couverture vaccinale par anatoxine tétanique. En 2013, dans les 14 pays considérés, le taux d'administration de la troisième dose du vaccin diphtérie-tétanos-poliomyélite se situait entre 65% et 98%. Selon les études réalisées dans des hôpitaux, le tétanos non néonatal est responsable de 0,3 à 10,7% des admissions, pour lesquelles 71% des patients, en moyenne, sont des hommes. L'identification des cas de tétanos déclarés après une circoncision médicale masculine volontaire a permis de révéler une disparité homme-femme en termes de mortalité, en défaveur des hommes. L'intégration de la vaccination antitétanique des garçons et des hommes dans les programmes nationaux devrait être une priorité pour poursuivre l'objectif de couverture sanitaire universelle.

Dado que se han concentrado los esfuerzos en la eliminación del tétanos materno y neonatal, se ha prestado menos atención a la incidencia y mortalidad del tétanos en los hombres. Desde 2007, ha aumentado la circuncisión médica masculina voluntaria en 14 países subsaharianos, puesto que se trata de una intervención efectiva para reducir el riesgo de contagio del virus de la inmunodeficiencia humana (VIH) en los hombres. Como parte de una revisión de los fenómenos adversos derivados de estos programas, se identificaron 13 casos de tétanos de cinco países notificados a la Organización Mundial de la Salud (OMS) hasta marzo de 2016. Ocho pacientes murieron y solo uno estaba vacunado contra el tétanos. Tras practicar la circuncisión médica masculina voluntaria, el tétanos era poco frecuente entre más de 11 millones de intervenciones realizadas. No obstante, los casos dieron lugar a una revisión de la prueba de la cobertura de vacunas contra el tétanos y las notificaciones de los casos en el África subsahariana, junto con una revisión documental del tétanos no neonatal en África durante los años 2003 a 2014. La OMS de la región africana informó del mayor número de casos de tétanos no neonatal por cada millón de habitantes y de la menor cobertura de la vacuna con toxoide tetánico de la historia. En 2013, la cobertura de la tercera dosis de la vacuna de la difteria, tétanos, polio abarcó de un 65% a un 98% en los 14 países. En estudios centrados en los hospitales, el tétanos no neonatal abarcó entre un 0,3% y un 10,7% de admisiones, y una media de 71% de los pacientes eran hombres. La identificación de los casos de tétanos tras la circuncisión médica masculina voluntaria destaca una diferencia desproporcionada entre hombres y mujeres en cuanto a la morbilidad por tétanos, en detrimento de los hombres. La incorporación de vacunas contra el tétanos para niños y hombres en programas nacionales debería ser prioritaria para ajustarse al objetivo de cobertura sanitaria universal.

[EPIDEMIOLOGICAL CHARACTERISTICS OF TETANUS IN THE REPUBLIC OF CROATIA]. / EPIDEMIOLOSKE KARAKTERISTIKE TETANUSA U HRVATSKOJ.

The aim of the study was to determine the epidemiological characteristics of tetanus in Croatia and to determine changes in the age and sex structure, morbidity and mortality after the introduction of mandatory immunization and after the introduction of additional immunization for persons aged ≥ 60. The retrospective study was undertaken and the data on the number of patients and deaths from tetanus in the period 1946­2014 in Croatia were analyzed. The data considering age, gender and geographical location of disease occurrence were also analyzed. The study confirmed the reduction of morbidity, mortality and fatality rate from tetanus after the introduction of mandatory immunization. In the last twenty years the average morbidity rate was 1.68/1 000 000 population. A higher incidence of tetanus was observed in female patients. During the last ten years all patients were in the age group of 60 and above. The distribution of patients according to the geographical location showed a higher incidence of tetanus in continental Croatia (26/31; 84%) than in coastal area. The less reported number occurred during the winter months. This preventive measure is very effective and economically justified.

Vaccines for women for preventing neonatal tetanus.

BACKGROUND: Tetanus is an acute, often fatal, disease caused by an exotoxin produced by Clostridium tetani. It occurs in newborn infants born to mothers who do not have sufficient circulating antibodies to protect the infant passively, by transplacental transfer. Prevention may be possible by the vaccination of pregnant or non-pregnant women, or both, with tetanus toxoid, and the provision of clean delivery services. Tetanus toxoid consists of a formaldehyde-treated toxin that stimulates the production of antitoxin. OBJECTIVES: To assess the effectiveness of tetanus toxoid, administered to women of reproductive age or pregnant women, to prevent cases of, and deaths from, neonatal tetanus. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 January 2015), CENTRAL (The Cochrane Library 2015, Issue 1), PubMed (1966 to 28 January 2015), EMBASE (1974 to 28 January 2015) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised or quasi-randomised trials evaluating the effects of tetanus toxoid in pregnant women or women of reproductive age on numbers of neonatal tetanus cases and deaths. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. MAIN RESULTS: Two effectiveness trials (9823 infants) and one safety trial (48 mothers) were included. The main outcomes were measured on infants born to a subset of those randomised women who became pregnant during the course of the studies. For our primary outcomes, there was no high-quality evidence according to GRADE assessments.One study (1182 infants) assessed the effectiveness of tetanus toxoid in comparison with influenza vaccine in preventing neonatal tetanus deaths. A single dose did not provide significant protection against neonatal tetanus deaths, (risk ratio (RR) 0.57, 95% confidence interval (CI) 0.26 to 1.24; 494 infants; GRADE: low-quality evidence). However, a two- or three-dose course did provide protection against neonatal deaths, (RR 0.02, 95% CI 0.00 to 0.30; 688 infants; GRADE: moderate-quality evidence). Administration of a two- or three-dose course resulted in significant protection when all causes of death are considered as an outcome (RR 0.31, 95% CI 0.17 to 0.55; 688 infants; GRADE: moderate-quality evidence). No effect was detected on causes of death other than tetanus. Cases of neonatal tetanus after at least one dose of tetanus toxoid were reduced in the tetanus toxoid group, (RR 0.20, 95% CI 0.10 to 0.40; 1182 infants; GRADE: moderate-quality evidence).Another study, involving 8641 children, assessed the effectiveness of tetanus-diphtheria toxoid in comparison with cholera toxoid in preventing neonatal mortality after one or two doses. Neonatal mortality was reduced in the tetanus-diphtheria toxoid group (RR 0.68, 95% CI 0.56 to 0.82). In preventing deaths at four to 14 days, neonatal mortality was reduced again in the tetanus-diphtheria toxoid group (RR 0.38, 95% CI 0.27 to 0.55). The quality of evidence as assessed using GRADE was found to be low.The third small trial assessed that pain at injection site was reported more frequently among pregnant women who received tetanus diphtheria acellular pertussis than placebo (RR 5.68, 95% CI 1.54 to 20.94; GRADE: moderate-quality evidence). AUTHORS' CONCLUSIONS: Available evidence supports the implementation of immunisation practices on women of reproductive age or pregnant women in communities with similar, or higher, levels of risk of neonatal tetanus, to the two study sites.

Vaccines for women to prevent neonatal tetanus.

BACKGROUND: Tetanus is an acute, often fatal, disease caused by an exotoxin produced by Clostridium tetani. It occurs in newborn infants born to mothers who do not have sufficient circulating antibodies to protect the infant passively, by transplacental transfer. Prevention may be possible by the vaccination of pregnant or non-pregnant women, or both, with tetanus toxoid, and the provision of clean delivery services. Tetanus toxoid consists of a formaldehyde-treated toxin which stimulates the production of antitoxin. OBJECTIVES: To assess the effectiveness of tetanus toxoid, administered to women of childbearing age or pregnant women, to prevent cases of, and deaths from, neonatal tetanus. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 October 2012), The Cochrane Library (2012, Issue 10), PubMed (1966 to 31 October 2012), EMBASE (1974 to 31 October 2012). We also used the results from handsearching and consultations with manufacturers and authors. SELECTION CRITERIA: Randomised or quasi-randomised trials evaluating the effects of tetanus toxoid in pregnant women or women of childbearing age on numbers of neonatal tetanus cases and deaths. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed trials for inclusion and trial quality, and extracted data. MAIN RESULTS: Two trials (10,560 infants) were included. It should be noted that these trials are very old,1966 and 1980 respectively, and one trial randomised exclusively non-pregnant women. The main outcomes were measured on infants born to a subset of those randomised women who became pregnant during the course of the studies. One study (1919 infants) assessed the effectiveness of tetanus toxoid in comparison with influenza vaccine in preventing neonatal tetanus deaths. After a single dose, the risk ratio (RR) was 0.57 (95% confidence interval (CI) 0.26 to 1.24), and the vaccine effectiveness was 43%. With a two- or three-dose course, the RR was 0.02 (95% CI 0.00 to 0.30); vaccine effectiveness was 98%. No effect was detected on causes of death other than tetanus. The RR of cases of neonatal tetanus after at least one dose of tetanus toxoid was 0.20 (95% CI 0.10 to 0.40); vaccine effectiveness was 80%. Another study, involving 8641 children, assessed the effectiveness of tetanus-diptheria toxoid in comparison with cholera toxoid in preventing neonatal mortality after one or two doses. The RR was 0.68 (95% CI 0.56 to 0.82); vaccine effectiveness was 32%. In preventing deaths at four to 14 days, the RR was 0.38 (95% CI 0.27 to 0.55), and vaccine effectiveness 62% (95% CI 45% to 73%). AUTHORS' CONCLUSIONS: Available evidence supports the implementation of immunisation practices on women of childbearing age or pregnant women in communities with similar, or higher, levels of risk of neonatal tetanus, to the two study sites. More information is needed on possible interference of vaccination by malaria chemoprophylaxis on the roles of malnutrition and vitamin A deficiency, and on the quality of tetanus toxoid production and storage.

Vitamin C for preventing and treating tetanus.

BACKGROUND: Tetanus is a severe disease that can be prevented by vaccination. In developing countries vaccination coverage is not always high. Cases still occur also in developed countries, particularly in elderly people owing to their reduced immuno protection. There are about 1 million tetanus cases per year globally. In animal studies, vitamin C has protected against various infections and bacterial toxins. In a study with rats, vitamin C protected against the purified tetanus toxin. OBJECTIVES: To assess the prophylactic and therapeutic effect of vitamin C on tetanus. SEARCH METHODS: In May 2013 we searched the Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations ); and Ovid EMBASE for this third update. SELECTION CRITERIA: Controlled trials of vitamin C as a prevention or treatment for tetanus, whether or not these were placebo controlled, in any language, published or unpublished. Two review authors independently made inclusion decisions. DATA COLLECTION AND ANALYSIS: Both review authors independently extracted data from trial reports and assessed methodological quality. Since one of the cells in a 2 × 2 table had no events, we calculated the odds ratio (OR) and its 95% confidence interval (CI) for case fatality rate by using the Peto-method. Another of the 2 × 2 tables had no empty cells and the inverse-variance method was used to calculate its risk ratio (RR) estimate and 95% CI. We also used the Fisher's exact test to calculate the exact 95% CI for the OR of the 2 × 2 table with the empty cell. MAIN RESULTS: One single trial was eligible for inclusion. This non-randomised, unblinded, controlled trial undertaken in Bangladesh involved 117 tetanus patients. Vitamin C at a dosage of 1 g/day was administered intravenously alongside conventional treatment. At recruitment, the participants were stratified into two age groups and the results were reported by age. There was a significant difference in the vitamin C effect between the two age groups (P = 0.01). In the tetanus patients aged 1 to 12 years (n = 62), vitamin C treatment was associated with a 100% reduction in case fatality rate (95% CI from -100% to -94%). In patients aged 13 to 30 years (n = 55), vitamin C treatment was associated with a 45% reduction in case fatality rate (95% CI from -69% to -5%). AUTHORS' CONCLUSIONS: A single, non-randomised, poorly reported trial of vitamin C as a treatment for tetanus suggests a considerable reduction in mortality. However, concerns about trial quality mean that this result must be interpreted with caution and vitamin C cannot be recommended as a treatment for tetanus on the basis of this evidence. New trials should be carried out to examine the effect of vitamin C on tetanus treatment.

Interventions to reduce neonatal mortality from neonatal tetanus in low and middle income countries--a systematic review.

BACKGROUND: In 1988, WHO estimated around 787,000 newborns deaths due to neonatal tetanus. Despite few success stories majority of the Low and Middle Income Countries (LMICs) are still struggling to reduce neonatal mortality due to neonatal tetanus. We conducted a systematic review to understand the interventions that have had a substantial effect on reducing neonatal mortality rate due to neonatal tetanus in LMICs and come up with feasible recommendations for decreasing neonatal tetanus in the Pakistani setting. METHODS: We systemically reviewed the published literature (Pubmed and Pubget databases) to identify appropriate interventions for reducing tetanus related neonatal mortality. A total of 26 out of 30 studies were shortlisted for preliminary screening after removing overlapping information. Key words used were "neonatal tetanus, neonatal mortality, tetanus toxoid women". Of these twenty-six studies, 20 were excluded. The pre-defined exclusion criteria was (i) strategies and interventions to reduce mortality among neonates not described (ii) no abstract/author (4 studies) (iii) not freely accessible online (1 study) (iv) conducted in high income countries (2 studies) and (v) not directly related to neonatal tetanus mortality and tetanus toxoid immunization (5). Finally six studies which met the eligibility criteria were entered in the pre-designed data extraction form and five were selected for commentary as they were directly linked with neonatal tetanus reduction. RESULTS: Interventions that were identified to reduce neonatal mortality in LMICs were: a) vaccination of women of child bearing age (married and unmarried both) with tetanus toxoid b) community based interventions i.e. tetanus toxoid immunization for all mothers; clean and skilled care at delivery; newborn resuscitation; exclusive breastfeeding; umbilical cord care and management of infections in newborns c) supplementary immunization (in addition to regular EPI program) d) safer delivery practices. CONCLUSION: The key intervention to reduce neonatal mortality from neonatal tetanus was found to be vaccination of pregnant women with tetanus toxoid. In the resource poor countries like Pakistan, this single intervention coupled with regular effective antenatal checkups, clean delivery practices and compliance with the "high- risk" approach can be effective in reducing neonatal tetanus.

Tetanus as cause of mass die-off of captive Japanese macaques, Japan, 2008.

In 2008 in Japan, 15/60 captive Japanese macaques died. Clostridium tetani was isolated from 1 monkey, and 11 had tetanus-specific symptoms. We conclude the outbreak resulted from severe environmental C. tetani contamination. Similar outbreaks could be prevented by vaccinating all monkeys, disinfecting housing areas/play equipment, replacing highly C. tetani-contaminated soil, and conducting epidemiologic surveys.