4.1. Case analysis
In this study, the total number of non-neonatal tetanus cases in the past 20 years is 6084, plus there are 9 out of 34 provincial administrative regions in China in which the number of tetanus was unclear, besides the cases are limited to 1~5 hospitals in these provinces, so the actual patients may be more. Although in 2012, China was validated as having eliminated maternal and neonatal tetanus15, the control situation of non-neonatal tetanus in China is dire in this study, and more attention should be paid to reducing the morbidity of it. According to the survey, the percentage of males (66.67%) was greater than females (33.33%), similar to the studies of S Anuradha, Sam Olum, and Surabhi GS16–18, but it is less than the study of Ananda19. The higher prevalence in males may be related to the fact that males are often engaged in heavy and outdoor work, such as agricultural or technical work, which has a higher likelihood of injury. While the lower incidence in females may be associated with the factor that females are usually engaged in light physical labor and had immunizations during pregnancy20. Patient occupation is a significant risk factor for tetanus. The proportion of farmers was as high as 83.56 %, and the proportion of people living in rural areas was as high as 88.62% in the study, which is greater than other research; Zhee Fan reported 47.0%10, Dr. K.V.L. Sudha Rani reported 28.65%21 , but is similar to AHM FEROZ reported 72.5%22. The results showed that the leading group of people suffering from tetanus are low-income people, especially farmers and workers from rural areas; the reasons probably are that they are more likely to be exposed to the causal organism, short of necessary labor protection in agricultural production and work site activities, sufficient awareness of tetanus, and formal treatment of wounds after injury, which increase the risk of tetanus infection23,24. In this study, most tetanus cases were among young and middle-aged people; the overall average age was 46.69 years, average age greater than 40 years accounted for 83.42%, the mean age of the 40~60 years population accounted for the highest percentage (80.03%). Compared to developed countries, the patients from China are younger; S. Tosun reported that most tetanus cases were during the advanced ages25, 62% were patients aged 65 years in a report Australia3, and around 80% of the patients were 60 years of age in Japan26. However, the mean age of the patients is similar in Africa, the mean age was 33.0 years in a report in Nigeria27, and Amanuel Amare reported the mean age was 33.8 years in Ethiopia28. The leading reasons are that the level of tetanus antibodies and protection rate of people over 40 years are shallow in China29–31, and young people lack effective immunization programs and appropriate treatment of injuries in developing country21.
4.2. Analysis of circumstances of the injury
In this study, the causes of injury were mainly some common factors in life, such as stabs by nail and wood, cuts by knife and glass, firecracker explosions, and animal bites, etc32–36, injury by metal and wood accounted for the highest percentage (54.52%). The others included road traffic accidents, burns, fissures of the foot, fall injury, intravenous drug taking, and post-surgical wounds33,37,38. The injury causes resembled other research, for example, these reports from Southern India 39, Northwestern Tanzania23, Ethiopia28, and Turkey25. There were also cases of atypical injuries such as abrasions40, sole abrasions41, stomatitis34, otitis media 42, and paronychia43, so it can be known that there is a possibility of tetanus as long as an open wound in the skin or mucous membrane, coupled with the presence of pollution, hypoxia and moisture environment. In the study, 90.82% of Tetanus attacks were due to infection of the extremities, especially the lower extremity (54.35%), which is much higher than reported in Nigeria (lower limbs (39.24%) and the upper limbs 18.99%))44, similar to a report that the injuries were on the lower limbs patients(48.75%), the injuries were described on the upper limbs (36.25%)45, differs from a report from India that upper limb wounds were the most common(51.6%). Followed by wounds on the lower limb (38.3%)16. 87.74% of patients in this study did not deal with their wounds 24h after injury, and 9.30% of patients treated their wounds by their native methods, for instance, using a Band-aid to stanch after alcohol briefly46, self-binding with Chinese herbal medicine24,33, which can lead to incomplete disinfection and even create a polluted and oxygen-deprived environment, furthermore, 96.66% of patients did not inject TAT or TIG47,48, resulting in significantly increase in the risk of infection. It is similar to some research in Bangladesh45 and India16,21. It is evident that injury site, wound management 24h after injury, and causes of Injury are significantly associated with patients' occupations and place of residence. Factors of injury are common in agricultural work and industrial labor daily, so the affected population is mainly farmers, workers, and people in rural areas. The principal causes are insufficient knowledge of tetanus, poor hygiene attitudes and conditions, and little hospitalization consciousness. Besides, they suffered minor injuries, so they didn’t take it seriously or did not. Therefore, it is unlikely that many people will go to the hospital and be injected with tetanus immunoglobulin or tetanus antitoxin. It is one of the leading causes of why non-neonatal tetanus frequently occurs in developing countries, including China.
4.3. Analysis of toxin neutralization
Although some studies have shown that TAT has a high probability of allergy (5%~30%), and the chance of allergy after desensitization remains 14.1%49, some countries have banned TAT as a passive immunization agent against tetanus50, and the incidence of TIG allergy is only 0.2%51, which has the advantages of safety, easy clinical operation, low incidence of allergic reactions, strong neutralizing effect of toxins, and longer protective and preventive effect than TAT52. However, in this study, most hospitals, including tertiary hospitals, preferred tetanus antitoxin to strengthen passive immunity53–55, and some hospitals continued to use TAT after desensitization after positive skin tests55–57, due to the disadvantages of TIG, such as high price, few sources, complex preparation, and insufficient supply.
4.4. Analysis of Therapies of sedation and spasmolysis
Tetanus spasm is the most potent toxin, causing muscle tonicity, spasm, and autonomic instability58. In severe cases, continuous spasms of respiratory muscles lead to asphyxia and respiratory arrest59,60, so controlling muscle spasms and sedation is one of the keys to treatment. However, excessive sedation and muscle relaxation may prolong the duration of tracheal intubation and mechanical ventilation and increase the risk of ventilator-associated pneumonia, tracheal stenosis, complicated deconditioning, and acute respiratory distress syndrome61; besides, the use of continuous drugs is associated with several adverse effects, these effects are usually caused by prolonged immobility and may result in muscle atrophy, eye injuries, nerve injuries due to compression and deep vein thrombosis62. Thus, moderate analgesia, analgesia, and muscle relaxation therapy were required. In this study, the treatment regimens of analgesic, sedative, and muscle relaxation varied among different hospitals, such as using diazepam or midazolam alone, diazepam combined with phenobarbital/ hibernation mixture /midazolam in dual therapy, propofol combined with magnesium sulfate/midazolam, and even triple therapy in severe tetanus63–66. The varying treatment regimens may be related to the variable severity of the patient's condition, individual differences in patient sensitivity to drugs, and the lack of relevant guidelines in China. The guidelines for managing accidental tetanus in adult patients can be referred to as the drugs of choice to provide sedation, spasm control, and muscle relaxation in tetanus patients are benzodiazepines with opioids. For complete spasm control, a combination of diazepam and vecuronium was necessary62. The combined application of Chinese and western medicine may be a new direction with value to explore. In a report, the combined application of Chinese and western medicine has a better effect on the control of tetanus convulsion and spasm than western medicine alone; it can reduce the dosage of western medicine, prolong the interval of administration, shorten the course of treatment, and strengthen the effect of sedation, spasmodic relief, and calm down, and play the role of Chinese and western medicine treatment complement each other67.
4.5 Analysis of tracheotomy and outcomes
Due to persistent muscle spasm tetanus, tetanus, especially severe tetanus, is easily complicated by respiratory failure and airway management difficulties, so early tracheal intubation or tracheotomy to strengthen tracheal management is the key to saving the patient 68. In this study, the leading causes of death were the abandonment of treatment by family members due to critical condition, asphyxia, and respiratory failure, in which asphyxia and respiratory failure accounted for 45.78%, so early implementation of tracheotomy is the top priority for critical tetanus patients, it differs from a report that shock/multiple organ failure is the leading cause of death (72.9%)69. In this study, the mortality of tetanus in the normal group was 11.21%, and the tracheotomy rate reached 58.42%; the tracheotomy rate and mortality were similar to that of Japan 26, and it is lower than a report from Brazil ( 44.5%)70, tracheostomy rate is much greater than Ethiopia (10.5%), of which the mean case-fatality increased from 21 % to 51% from 1996 to 200971. The low mortality in China may be related to the significant development of intensive care medicine technology and equipment, which could meet the intensive care needs of tetanus patients. Because fully configured ICUs and ventilator supportive care are not readily available in these developing countries, even when such resources are available, they may not be utilized when patients cannot afford their cost. The mortality rate associated with tetanus remains high26.