Tetanus Cases in Mogadishu-Somalia: A Tragic Disease Despite the Existence of a Century-Old Safe and Efficient Tetanus Vaccine

Introduction

The neurotoxin generated by Clostridium tetani (C. tetani), which is present in soil, dust, or animal feces, causes tetanus, an infection marked by generalized hypertonia that presents as excruciating jaw and neck muscle spasms.^1–3 Tetanospasmin and tetanolysin, secreted by C. tetani, cause agonist and antagonist muscles to contract, resulting in hypertonia, which manifests as the recognizable “tetanic spasm”. Tetanospasmin specifically impacts the motor plate of the nerve and muscle, resulting in a clinical condition that includes rigidity, muscle spasms, and autonomic instability.⁴ Tetanolysin complicates matters by causing tissue damage, while hypertonia can result in death from asphyxia, heart failure, or pulmonary problems.⁵ The severity of symptoms varies depending on the distance of the infected focus from the central nervous system. Once the neurotoxin reaches the brainstem, usually within two weeks of symptom onset, it causes autonomic dysfunction. This dysfunction can lead to catastrophic rhythm abnormalities due to the loss of autonomous control, especially in individuals with fluctuating blood pressure and heart rate. Studies have revealed that 10% of infected patients die from their illness, and symptoms might linger for weeks or months. In developing countries, the mortality rate is estimated to rise from 20% to 45%, depending on access to early therapy and intensive care.⁶ According to the Centers for Disease Control and Prevention (CDC), nearly 100% of tetanus patients die in nations without access to critical care.⁷ Long-term mental problems and motor impairment are frequently seen in survivors.⁴

C. tetani, the gram-positive, spore-forming, obligatory anaerobic bacillus, is more commonly found in hot, humid areas with rich soil containing organic content.^8,9 Tetanus spores can endure for extended periods due to their hardiness.¹⁰ Tetanus is frequently linked to trauma,¹¹ and although C. tetani can enter the human body by skin ruptures, tears, and punctures, it can also be spread by insect bites or syringe inoculation.^8,12 A wound, often small and unnoticed, like a tiny tear from metal or wood splinters or thorns, is the most frequent source of infection. Individuals most at-risk include those who have not received vaccinations, those who use intravenous drugs, and those with weakened immune systems are among the groups most at risk of infection among individuals who have this wound. Dog bites, open fractures, injections, and dental diseases are other known sources of infection.^8,9,12 The most evident fact is that vaccine deficiency is the primary cause of tetanus. Individuals who are not vaccinated, just partially immunized, or completely immunized but lack a sufficient booster dosage are often at risk of contracting tetanus.¹⁰

Tetanus remains 135 times more common in low-income countries than in wealthy ones, despite recent reductions in tetanus fatality rates linked to vigorous immunization programs, according to the World Health Organization (WHO). Maternal and neonatal tetanus poses a risk to 75 million mothers and infants globally, according to CDC data. The Global Burden of Disease research projected more than 73,000 cases of tetanus in 2019. A modeling study indicates that between January and December 2020, an estimated 30 million children failed to receive all three necessary doses of the tetanus-containing vaccine. Despite efforts, tetanus immunization is still not consistently and preventively delivered in several countries.⁴ In the last twenty years, the implementation of supplementary immunization activities (SIAs) has allowed WHO to determine that tetanus has vanished as a public health issue in nearly fifty countries; however, data indicates that tetanus remains a public health concern in 12 countries.¹³ Despite evidence that vaccination programs are being started in these 12 nations, Somalia does not appear to have been included in the programs for the Implementation of SIAs.¹⁴

The Global Peace Index indicates that Somalia remains one of the areas with high conflict risks, even with a post-terrorism order recently established in East Africa.¹⁵ The inability to implement vaccination programs may be the main cause of public health issues exacerbated by the hazards of war, terrorism, and conflict. Despite the efforts and assistance of the WHO and other international organizations, tetanus remains an acute disease with major complications that can result in death. Our study sought to assess tetanus patients who applied to the emergency service in Somalia, a country with persistent civil war, extreme poverty, and limited access to public health, social security, and hospital services.

Materials and Methods

Study Design

This study is a retrospective review of the database of tetanus patients who were admitted between January 1, 2022, and November 1, 2023 to Mogadishu Somali Turkey Recep Tayyip Erdoğan Training and Research Hospital, which is under the mentorship of Turkey in Somalia. Permission from the Mogadishu Somalia Turkey Recep Tayyip Erdoğan Training and Research Hospital Scientific Research Ethics Committee (08.11.2023-MSTH/16085-881) and hospital administration was acquired prior to the study’s commencement. Furthermore, the “Ethical Principles of the World Medical Association Declaration of Helsinki” were taken into consideration when conducting the research. Since the study was retrospective in nature, patient consent was not obtained.

Place of Study

The study was conducted at the Mogadishu Somali Turkey Recep Tayyip Erdoğan Training and Research Hospital, established by Turkey as part of humanitarian aid efforts in Mogadishu, the capital of Somalia. This hospital employs medical professionals from Somalia and Turkey, including doctors, nurses, and other healthcare workers. It serves all indigenous people in Somalia; most of whom reside in Mogadishu. As one of the largest and most comprehensive training hospitals in sub-Saharan Africa (SSA), it is a reference center for critical care, operating rooms, and various medical services. The hospital’s infectious diseases clinic receives patients from the emergency room, nearby regional clinics, other local medical facilities, and other hospital departments, treating a large number of patients, particularly those with infectious illnesses.

Patient Selection

Study participants comprised all patients, regardless of age, who were diagnosed with tetanus and admitted to the hospital emergency room, clinic, or intensive care unit (ICU). Excluded from the study group were patients who were admitted to the infectious diseases clinic and transferred to another facility within 24 hours, patients who died there, patients who were brought to the emergency room in cardiopulmonary arrest, and patients whose clinical records could not be accessed.

Acquisition of Data

Using research forms, information about the hospitalized patients’ demographics, potential sources of infection exposure, and requirement for ICU admission were noted. Demographic information and anamnesis details are initially entered into the files for every patient at the infection clinic. Information and prognostic data are documented on the patient follow-up forms subsequent to the examination and testing. The attending clinician creates the diagnostic data for the patients. In this context, in addition to vital follow-ups and prognoses for the patient, the data recorded in the case report forms are as follows: the site and region of the disease in terms of tetanus, the severity of tetanus, the duration of hospitalization, whether or not he stayed in the ICU, the duration of the stay in the ICU, if any, the time he received hospital treatment, service period, clinical classification, clinical symptoms, autonomic nerve dysfunction, tetanus vaccination history, whether there are tetanus complications, if so, which complications, mortality, treatment of the patient, duration of treatments, blood culture, iv antibiotic use, antibiotic name, antibiotic duration, comorbidity and routine blood hemogram and biochemical parameters.

Statistics

Statistical analyzes of the study were conducted using Statistical Package for Social Sciences version 25.0 software for Windows (IBM SPSS Statistics for Windows, Version 25.0. Armonk, NY: IBM Corp., United States of America [USA]). The assumption of normality for quantitative variables was tested with Kolmogorov–Smirnov and Shapiro–Wilk tests. For univariate analyzes of the variables included in the study, Chi-Square, Fisher Exact test and Mann Whitney U-tests were used, depending on the variable type and whether the assumptions were met.

Results

Retrospective scanning, recording, and analysis were done on the 196 cases of tetanus that were diagnosed and monitored between research period. The ages of the patients ranged from 7 days to 71 years, with an average of 10 years old. The patient population consisted of 63 (32.1%) females and 133 (67.9%) males. Of the patients, 144 (73.5%) reported being unemployed. Acute injury accounted for 53.1% of cases of tetanus, followed by medical interventions (11.2%) and traditional treatments (9.7%). The most common body parts into which the agent penetrated were the arms (26.9%), face (21.7%), and legs (28.8%). 161 people (82.1%) were hospitalized for tetanus diagnosis and treatment, and their average length of stay was 11 days (minimum-maximum: 1–38 days). 61 patients (31.1%) were followed in ICU and their average stay in ICU was 12 days (min-max: 1–32 days). Clinic durations ranged from 1 to 34 days, with an average of 9 days.

The symptoms, complications, and supportive care administered are listed in Table 1.

Table 1 Symptoms of the Cases, Developing Complications and Supportive Treatments Administered

According to the severity of the illness, we separated the cases into four groups: 38 mild cases (19.4%), 65 moderate cases (33.2%), 47 severe cases (24.0%), and 46 very severe cases (23.5%). Upon doing a clinical classification of the patients, we identified 130 cases of generalized tetanus (70.4%), 43 cases of localized tetanus (21.9%), 14 cases of newborn tetanus (7.1%), and 1 case of cephalic tetanus (0.5%).

The types and rates of antibiotics given to patients during their course of therapy and follow-up are displayed in Table 2.

Table 2 Antibiotic Treatments Administered to Cases

Questioning the patients about their immunization history revealed that 168 (85.7%) had never received a tetanus vaccination, 6 (3.1%) had received a partial vaccination, and 3 (1.5%) had received a full vaccination. Regarding 19 people (9.7%), there was ambiguity about their vaccination history. In all, 84 individuals (42.9%) had tetanus-related complications. Using the disease severity as a guide, we divided the cases into two categories: mild-moderate and severe-very severe. At least two body locations were injured in 16 patients (8.2%). In terms of clinical tetanus, 15 of these individuals (93.8%) belong into the severe category (p<0.001). According to our analysis, road accidents accounted for 50.0% (n:8) of the causes of multiple extremities injuries. The leg was the most often observed anatomical location (81.3%, n:13) in individuals with multiple extremity injuries. Table 3 presents a comparison of blood culture characteristics, job, gender, entry site, entry site counts and etiology based on the severity of the disease.

Table 3 Characteristics of Gender, Job, Etiology, Site of Entry, Site of Entry Counts and Blood Culture According to Severity of the Disease

Of the patients that were monitored for tetanus, 28 (14.3%) passed away. 168 patients (85.7%) underwent “Tetanus vaccine (T.vaccine) + Human Tetanus Immunoglobulin (HTIG) + Antibiotics + Supportive” treatment. Table 4 enumerates hospitalization, ICU stay, clinical categorization, autonomic nerve dysfunction, history of vaccinations, complications, mortality, and therapies in accordance with disease severity.

Table 4 Characteristics of Hospitalization, ICU Stay, Clinical Classification, Autonomic Nervous Dysfunction, Vaccination History, Complication, Mortality and Treatment According to Severity of the Disease

In 79 (40.3%) of the patients, the blood culture was positive. A total of 180 cases (91.8%) received intravenous antibiotics. In total, 14.3% of the patients had diabetes mellitus in 11 patients (5.6%), hypertension in 9 patients (4.6%), chronic renal failure in 2 patients (1.0%), chronic cardiac disease in 4 patients (2.0%), neurological disorders in 7 patients (3.6%), and other chronic comorbid illnesses in 4 patients (2.0%).

Table 5 presents the length of hospital stay, length of treatment, and features of laboratory results categorized by disease severity.

Table 5 Characteristics of Hospitalization Duration, Treatment Duration and Laboratory Findings According to Severity of the Disease

Discussion

Tetanus remains a major public health concern, causing fatalities in low- and middle-income countries (LMIC) despite the availability of an inexpensive, safe, and highly effective vaccine against the tetanus disease.¹⁶ Thus, raising the level of vaccination against tetanus in adults who have experienced trauma or whose vaccination history is unclear is essential to reducing the number of tetanus cases.^5,17 For lifelong protection against tetanus, the CDC recommends receiving a booster shot every ten years.¹⁸ It is well acknowledged that a booster dosage may be necessary due to waning immunity, as evidenced by the fact that most of the 35–70 tetanus cases recorded annually in the USA occur among the elderly population.¹⁹

In Mogadishu, the capital of Somalia, where bombings and terrorism are persistent problems, our hospital admits a significant number of trauma patients, a major risk factor for tetanus. Unfortunately, low vaccination rates are caused by several factors, including living in rural regions, poverty, lack of knowledge, cultural and religious beliefs promoting anti-vaccine sentiments, and general ignorance. WHO data indicate that terrorism forced almost 2.6 million people to relocate within Somalia, a nation with a high proportion of poverty. Increased migration has made access to even very basic health care, including vaccinations, more challenging.²⁰ The main reasons for the high incidence of tetanus in underdeveloped nations are inadequate wound care and immunization programs.²¹

We categorized the cases into two groups (Group 1: mild-moderate cases, Group 2: severe-very severe cases) based on the severity of the condition. There was no statistically significant difference between the groups regarding age, gender, and profession (p>0.05). However, severe rates of both neonatal and generalized tetanus were higher in the severe group (<0.001). Out of the patients in our study, 147 (75.1%) had a history of trauma or injury that could have caused tetanus (medical intervention, dirty delivery, and unknown groups were excluded). A statistically significant difference was found between the groups regarding the tetanus entry site. Patients with a history of dirty delivery, road accidents, electric shock, or gunshot were considerably more likely to be in the severe tetanus category (p: <0.001), while medical interventions and acute injuries were more common in mild cases. Differences were also noted regarding the point of entry. Arm injuries were more common in the mild group, while unidentified tetanus entry sites were mostly in the severe group (p:0.027). Fifteen of the sixteen patients with injuries to at least two body parts belonged to the severe tetanus category (93.8%, p<0.001). The most common anatomical location for multiple extremity injuries in 13 individuals (81.3%) was the leg, and traffic accidents accounted for 50% of the cases. In addition, The male-to-female ratio was 2.11 and ages ranging from 7 days to 71 years.

According to a Far Eastern research, 26% of tetanus cases had no identified source.²² Some previous studies have shown that uncertainty in the entrance site is important.^5,23 A lengthy incubation period may potentially impact the detection of the entrance site, as may a weakness in the history or physical examination of patients in whom a definite entry site is not found. Additionally, the wound might be chronic (lasting a long time) or minor enough to be ignored. In 6.1% of the study participants, the entrance point was not identifiable.

Neonatal tetanus, linked to unhygienic deliveries, is prevalent in developing nations due to unsanitary living conditions, inadequate prenatal care, and low vaccination rates among pregnant women.² Noteworthy, 14 cases of newborn tetanus in our study were associated with rural women treated conventionally in non-hospital settings with a history of contaminated births.

Male gender has been linked to an increased risk of tetanus-related illness and death due to occupational exposure and the lower rates of immunization among males. Routine immunization of pregnant women may explain the high frequency in men.^11,24,25 In line with previous research, we also found a higher case rate (67.9%) in males.

Tetanus symptoms appear days or weeks after a wound, with an incubation period of one to three weeks. Symptoms include excruciating muscular spasms, trismus, dysphagia, opisthotonus, and abnormalities of the autonomic nervous system (hypo/hypertension, brady/tachycardia, or other arrhythmias). A complete recovery might take months, and muscle spasms could last up to four weeks.²⁶ In Tanzania, Melkert et al’s²⁷ study reported that 95.7% of the patients had trismus, 89.3% had neck stiffness, 73% had general body muscular spasms, and 38.9% had dysphagia. In the Fan et al’s²⁸ study, dysphagia was shown to be the symptom for which patients sought medical attention the most frequently, despite trismus being the initial symptom in virtually all of the patients. The study findings indicated that trismus (100.0%), neck/muscle stiffness (92.9%), fever (79.1%), and dysphagia (67.3%) were the most frequently occurring symptoms.

Holistic treatments in tetanus patients include wound dressing/debridement, isolation in a quiet/dark room, passive immunization (anti-toxin immunoglobulin), antibiotics (metronidazole, penicillin), medications to control muscle spasms (magnesium, baclofen), adequate fluid/nutritional supplements, and airway/respiratory support.^5,29,30 Tetanus toxin is neutralized by an antitoxin, a therapeutic intervention that needs to be given early and in the right dosages. High death rates are linked to low or incorrect dosages. Human-derived antitoxin, due to its longer half-life and lower side effect profile, should be used extensively.³¹ Numerous studies have also highlighted the efficacy of penicillin and metronidazole, which are advised as initial antibiotic regimens.^29,30

Key treatment objectives also include reducing convulsions, muscle spasms, and autonomic nervous system symptoms. Benzodiazepines are the most recommended drugs for these outcomes. As an option for managing abnormalities of the autonomic nervous system, clonidine, opioid analgesics, and epidural blocking medications have been found helpful.³² According to recent statistics, tracheotomy is a better respiratory support option than endotracheal intubation as it can reduce the incidence of tracheal stenosis during long-term follow-up.³³

Treating tetanus requires nutritional assistance, but the present evidence on the ideal calorie intake for critically sick individuals is still inadequate. The higher metabolic rate brought on by sympathetic activity, convulsions, malnourishment from trismus, the inability to open their mouth fully, and dysphagia can all be considered reasons why patients require extra energy.³⁴

A study conducted in Korea between 2011 and 2019 on tetanus cases found an average patient age of 67 with women constituting 57.1% of cases. All patients had generalized tetanus; 85.7% of patients had trismus as the most common symptom; the average length of hospitalization was 39 days; 65.3% of the patients were monitored with mechanical ventilation; 20 patients (40.8%) had aspiration pneumonia; 5 patients (10.2%) passed away; and 35 patients (71.4%) were discharged with no further complications.²³

In our study, metronidazole was the most often chosen antibiotic (78.6%). The severe group took antibiotics for a longer period of time (mean: 14 days, p<0.001). Diazepam (80.1%) and baclofen (68.4%) were the most often chosen medicines as supportive treatment (in terms of convulsions, muscle spasms, and autonomic nervous system symptoms). In the severe group, all patients were treated with “T. vaccine + HTIG + Antibiotics + Supportive” treatment (p<0.001). The majority of patients who had complications belonged to the severe category (p<0.001), as did all patients who experienced autonomic nerve dysfunction (p<0.001). Aspiration pneumonia/urinary system infection accounted for 33.2% of all associated complications.

The research findings indicate that the patients in the severe group had considerably longer hospital stays (mean: 15 days, p<0.001) and ICU stays (mean: 12 days, p<0.001) compared to the mild group. The severe group also had a higher blood culture positive rate (p<0.001). There were differences between the two groups when analyzed in terms of laboratory parameters, with the exception of hemoglobin, hematocrit, and platelet values. These differences included total bilirubin (p:0.005), CRP (p<0.001), WBC (p<0.001), glucose (p:0.015), urea (p:0.001), creatinine (p:0.001), AST (p:0.042), and ALT (p: 0.014). These differences are expected due to more complications, antibiotic use, and extended hospital and ICU stays in the severe group.

The mortality rate of a severe case of tetanus left untreated is nearly 100%. With appropriate treatment, this rate decreases significantly. In 2015, there were 56,743 tetanus-related deaths globally, with a fatality rate of less than 5% in affluent nations. South Asia and SSA accounted for 79% of these fatalities.^1,2,5 A recent study of several SSA nations reported that the mortality rates in Nigeria, Uganda, Tanzania, and Cameroon were 64%, 47%, 43.1%, and 48.5%, respectively.³⁵ Based on data, the countries with the highest number of instances of newborn tetanus fatalities per 100,000 people include Kenya, South Sudan, Somalia, and Afghanistan.² Critical care services are often unavailable in LMIC, where severe respiratory failure is the primary cause of death in tetanus patients.³⁶ Of the patients who had a follow-up tetanus diagnosis, 14.3% died; all of them were in the severe category (p<0.001). This rate is highly successful compared to SSA standards and is comparable to death rates in two developed nations like USA (13.2%) and Italy (16.5%).^37,38

Regular childhood vaccinations improve children’s health and development and boost the nation’s economy by lowering mortality rates. The 2030 Immunization Agenda and Global Vaccine Action Plan, endorsed by the World Health Assembly in 2020, focus on universal vaccination.^39,40 Importantly, tetanus immunity cannot develop naturally; therefore, children should develop sufficient immunity against tetanus and maintain high antibody levels throughout life with booster shots every ten years.⁴¹ Disruptions to regular immunization schedules brought on by the COVID-19 pandemic may revive some illnesses in the future.⁴² In underdeveloped nations, the tetanus vaccine presents challenges due to a lack of healthcare workers, financial constraints, and transportation issues affecting rural areas.⁴³

Nine individuals (8.7%) who were fully or partially vaccinated belonged to the mild-moderate category and in contrast, a larger percentage of unvaccinated individuals or those whose status was unknown made up the severe group (p = 0.011).

Limitations

The primary drawback of our study is the lack of data in SSA nations, where tetanus fatalities are highest. Studies conducted in these nations will clarify the existing ambiguity around vaccination, illness incidence, and mortality.

Conclusion

We examined 196 patients who were followed up in our hospital in a period of approximately 2 years and unfortunately we lost 28 of these patients. During this period, we do not have information about how many tetanus patients could not apply to the hospital or applied to other hospitals in Somalia, one of the SSA countries. Vaccination against tetanus in LMIC, especially among children, is crucial due to the vaccine’s affordability and high efficacy. Immunization programs should be continually refined and improved. Local health experts must persistently educate, inform, and encourage the public about the importance of vaccination, combating anti-vaccination sentiments that pose a significant threat comparable to the lack of access to vaccines. Without these efforts, diseases like tetanus-which are nearly eradicated in wealthy nations-will continue to be a severe issue in developing nations.

The tetanus toxin is particularly lethal, causing severe muscle spasms, autonomic dysfunction, and potentially fatal complications. Ensuring widespread vaccination is vital to prevent the catastrophic impacts of tetanus toxin. It is a matter of civilization and equity that we do not allow individuals in the 21st century to die from tetanus when we have had a safe and effective tetanus vaccine for 100 years.

To the best of our knowledge, this is the largest case series conducted in Somalia, and it will provide valuable insights and guidance for future research. This study, which included patients of all ages, aimed to generate data that will aid in developing new strategies and providing recommendations the severity and mortality associated with tetanus.