Clinical outcomes and healthcare costs of inpatients with tetanus in Korea, 2011-2019.

BACKGROUND: Tetanus is a rare, vaccine-preventable but extremely serious disease. We investigated the recent trend of the clinical outcomes and medical costs for inpatients with tetanus in South Korea over 10 years. METHODS: We conducted a retrospective review to determine the clinical factors and medical costs associated with tetanus at two national university hospitals in South Korea between January 2011 and October 2019. RESULTS: Forty-nine patients were admitted for tetanus (mean age, 67.0 years [range, 53.0-80.0 years]; 32 women [57.1%]). All the patients had generalized tetanus, and 5 (10.2%) died during hospitalization. The median duration from symptom onset to hospital admission was 4 days. Trismus (85.7%) was the most common symptom, and the median hospital stay was 39 days. Thirty-two patients (65.3%) required mechanical ventilation, and 20 (40.8%) developed aspiration pneumonia. The median total healthcare cost per patient was US $18,011. After discharge, 35 patients (71.4%) recovered sufficiently to walk without disability. CONCLUSIONS: Tetanus requires long hospital stays and high medical expenditures in South Korea; however, the vaccination completion rate is low. Medical staff should therefore promote medical advice and policies on the management of tetanus to the general South Korean population.

Incremental costs of treating tetanus with intrathecal antitetanus immunoglobulin.

OBJECTIVE: To estimate the incremental cost of delivering intrathecal tetanus immunoglobulin compared to an intramuscular option. METHODS: To compare the two interventions, costs were estimated using standard cost methodology. Cost categories were personnel, overhead, consumables, antibiotics to treat infection, gases for respiratory assistance and immunoglobulin. Tetanus patients, aged 12 years or older, who were part of a randomised controlled clinical trial conducted in a referral hospital in Recife, Brazil, were allocated to two groups: a control group (58) and a study group (62). Patients allocated to the control group received 3000 international units (IU) of human immunoglobulin, with preservative, intramuscularly. The study group received the same quantity of immunoglobulin also intramuscularly plus an intrathecal dose of 1000 IU of a human immunoglobulin, free of preservatives, to prevent irritation of the meninges and avoid the need for corticosteroids. Thus, the difference between the two groups was the exclusive use of intrathecal immunoglobulin. The outcome measurements were clinical progression, hospital stay, respiratory assistance and respiratory infection. RESULTS: Delivering intrathecal immunoglobulin to patients saved a total of US$ 60 389, in a 10-day intensive care treatment, by preventing a worsening of their tetanus severity (e.g. from Grade I to Grades II, III, IV). Substantial cost saving was also observed in terms of hospital stay (US$ 173 104). CONCLUSIONS: Intrathecal treatment of tetanus is cost saving. This intervention deserves consideration by doctors and decision-makers as a mean of saving resources while maintaining high-quality health outcomes.

[Epidemiological and economic impact of tetanus vaccination in Colombian adults]. / Impacto epidemiológico y económico de la vacunación contra el tétanos en adultos de Colombia.

OBJECTIVE: Assess the potential epidemiological and economic impact of vaccinating the over-15 Colombian population against tetanus with a booster dose every 10 years. METHODS: A cost-effectiveness analysis of tetanus vaccination with a booster dose every 10 years was conducted in Colombia and compared with the current strategy (2, 4, 6, 18, and 60 months). Estimates of the burden of disease were based on three official data sources. A Markov model from the perspective of the third party payer was developed. The time horizon was the lifetime of a person. Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: In Colombia, 30 to 48 cases of tetanus resulting in 9.6 to 10.1 deaths are reported each year. Although booster vaccination for the entire population was cost-effective (the cost per disability-adjusted life year [DALY] avoided was US$ 11,314 in the entire population), gender-based differentiation of the results showed that it would not be cost-effective in women (cost per DALY avoided was US$ 4,903 in men and US$ 22,332 in women). CONCLUSIONS: This is the first study that evaluates the cost-effectiveness of a tetanus vaccine booster dose every 10 years in a developing country. Use of this measure would be cost-effective in Colombia, especially for men. As a result of the gender-based differences in the results, any decision about its use in women of childbearing age should take current vaccination into account.

An investment case for maternal and neonatal tetanus elimination.

INTRODUCTION: Globally, 13 countries have yet to eliminate maternal and neonatal tetanus. While efforts have improved access to tetanus toxoid containing vaccines (TTCVs) and increased clean delivery practices, reaching elimination targets (<1 case of neonatal tetanus per 1000 live births per district per year) may require significant resources to reach the remaining high risk and hard-to-reach districts. METHODS: We estimated the cost to achieve maternal and neonatal tetanus elimination (MNTE) in three years in the remaining 13 countries: Afghanistan, Angola, Central African Republic, Democratic Republic of the Congo, Guinea, Mali, Nigeria, Pakistan, Papua New Guinea, Somalia, South Sudan, Sudan, and Yemen. Costs were estimated for: (1) vaccination campaigns using standard TTCVs and TT-Uniject™ targeting women of reproductive age in high risk areas, (2) additional vaccinations delivered to pregnant women at antenatal care (ANC) clinics, (3) clean delivery and umbilical cord care promotion, (4) neonatal tetanus surveillance strengthening, and (5) validation activities. We forecasted the averted mortality to assess the cost-effectiveness of achieving MNTE. RESULTS: It will cost an estimated US$197.7 million to realize MNTE over three years. These costs include $161.4 million for vaccination campaigns, $6.1 million for routine vaccination during ANC, $23.3 million for promotion of clean delivery practices, $4 million for surveillance, and $3 million for validation of MNTE. Achieving MNTE will avert approximately 70,000 neonatal deaths over ten years of vaccine protection, resulting in approximately 4.4 million life years gained. It will cost $2,900 per death averted and $45 per life year gained. CONCLUSION: Maternal and neonatal tetanus can be eliminated with significant financial investment, high prioritization, and strong political will. While substantial costs must be incurred to reach hard-to-reach populations, MNTE should be accomplished as a matter of health equity, and will significantly contribute to reaching the United Nations' Sustainable Development Goals.

Economic impact of implementing decennial tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccination in adults in the United States.

BACKGROUND: In the United States, persons ≥11 years are recommended to receive one dose of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine, followed by decennial tetanus- and diphtheria-toxoid (Td) boosters. Many providers use Tdap instead of Td. We evaluated epidemiologic and economic impacts of replacing Td boosters with Tdap. METHODS: We used a static cohort model to examine replacing Td with Tdap over the lifetime of 4,386,854 adults ≥21 years. Because pertussis is underdiagnosed and true incidence is unknown, we varied incidence from 2.5 cases/100,000 person-years to 500 cases/100,000 person-years. We calculated vaccine and medical costs from claims data. We estimated cost per case prevented and per quality-adjusted life year (QALY) saved; sensitivity analyses were conducted on vaccine effectiveness (VE), protection duration, vaccine cost, disease duration, hospitalization rates, productivity loss and missed work. We did not include programmatic advantages resulting from use of a single tetanus-toxoid containing vaccine. RESULTS: At lowest incidence estimates, administering Tdap resulted in high costs per averted case ($111,540) and QALY saved ($8,972,848). As incidence increased, cases averted increased and cost per QALY saved decreased rapidly. With incidence estimates of 250 cases/100,000 person-years, cost per averted case and QALY saved were $984 and $81,678 respectively; at 500 cases/100,000 person-years, these values were $427 and $35,474. In multivariate sensitivity analyses, assuming 250 cases/100,000 person-years, estimated cost per QALY saved ranged from $971 (most favorable) to $217,370 (least favorable). CONCLUSIONS: Our findings suggest that replacing Td with Tdap for the decennial booster would result in high cost per QALY saved based on reported cases. However, programmatic considerations were not accounted for, and if pertussis incidence, which is incompletely measured, is assumed to be higher than reported through national surveillance, substituting Tdap for Td may lead to moderate decreases in pertussis cases and cost per QALY.

Pediatric Tetanus in Central Pennsylvania.

Approximately 20% of the nationally reported tetanus infections in children aged 0 to 14 years that occurred in the United States between 2005 and 2015 were treated at Penn State Children's Hospital. With an electronic medical record search, we identified 5 cases of pediatric tetanus; 100% of these cases occurred in unimmunized children. Their median length of stay was 10 days, and the costs were significant.

Evaluating scenarios of locations and capacities for vaccine storage in Nigeria.

Many developing countries still face the prevalence of preventable childhood diseases because their vaccine supply chain systems are inadequate by design or structure to meet the needs of their populations. Currently, Nigeria is evaluating options in the redesign of the country's vaccine supply chain. Using Nigeria as a case study, the objective is to evaluate different regional supply chain scenarios to identify the cost minimizing optimal hub locations and storage capacities for doses of different vaccines to achieve a 100% fill rate. First, we employ a shortest-path optimization routine to determine hub locations. Second, we develop a total cost minimizing routine based on stochastic optimization to determine the optimal capacities at the hubs. This model uses vaccine supply data between 2011 and 2014 provided by Nigeria's National Primary Health Care Development Agency (NPHCDA) on Tuberculosis, Polio, Yellow Fever, Tetanus Toxoid, and Hepatitis B. We find that a two-regional system with no central hub (NC2) cut costs by 23% to achieve a 100% fill rate when compared to optimizing the existing chain of six regions with a central hub (EC6). While the government's leading redesign alternative - no central three-hub system (Gov NC3) - reduces costs by 21% compared with the current EC6, it is more expensive than our NC2 system by 3%. In terms of capacity increases, optimizing the current system requires 42% more capacity than our NC2 system. Although the proposed Gov NC3 system requires the least increase in storage capacity, it requires the most distance to achieve a 100% coverage and about 15% more than our NC2. Overall, we find that improving the current system with a central hub and all its variants, even with optimal regional hub locations, require more storage capacities and are costlier than systems without a central hub. While this analysis prescribes the no central hub with two regions (NC2) as the least cost scenario, it is imperative to note that other configurations have benefits and comparative tradeoffs. Our approach and results offer some guidance for future vaccine supply chain redesigns in countries with similar layouts to Nigeria's.

The economic value of increasing geospatial access to tetanus toxoid immunization in Mozambique.

BACKGROUND: With tetanus being a leading cause of maternal and neonatal morbidity and mortality in low and middle income countries, ensuring that pregnant women have geographic access to tetanus toxoid (TT) immunization can be important. However, immunization locations in many systems may not be placed to optimize access across the population. Issues of access must be addressed for vaccines such as TT to reach their full potential. METHODS: To assess how TT immunization locations meet population demand in Mozambique, our team developed and utilized SIGMA (Strategic Integrated Geo-temporal Mapping Application) to quantify how many pregnant women are reachable by existing TT immunization locations, how many cannot access these locations, and the potential costs and disease burden of not covering geographically harder-to-reach populations. Sensitivity analyses covered a range of catchment area sizes to include realistic travel distances and to determine the area some locations would need to cover in order for the existing system to reach at least 99% of the target population. RESULTS: For 99% of the population to reach health centers, people would be required to travel up to 35km. Limiting this distance to 15km would result in 5450 (3033-7108) annual cases of neonatal tetanus that could be prevented by TT, 144,240 (79,878-192,866) DALYs, and $110,691,979 ($56,180,326-$159,516,629) in treatment costs and productivity losses. A catchment area radius of 5km would lead to 17,841 (9929-23,271) annual cases of neonatal tetanus that could be prevented by TT, resulting in 472,234 (261,517-631,432) DALYs and $362,399,320 ($183,931,229-$522,248,480) in treatment costs and productivity losses. CONCLUSION: TT immunization locations are not geographically accessible by a significant proportion of pregnant women, resulting in substantial healthcare and productivity costs that could potentially be averted by adding or reconfiguring TT immunization locations. The resulting cost savings of covering these harder to reach populations could help pay for establishing additional immunization locations.

[Management and new current French recommendations for tetanus care]. / Actualités et nouvelles recommandations françaises dans la prise en charge du tétanos.

Tetanus is an acute severe disease induced by an exotoxin, often lethal. All cases occur in untreated or inadequately vaccinated patients and mainly in elderly patients who accumulate many risk factors. The current management of wounds faced difficulties in the assessment of immunization status and wound risks status. Indeed, all injuries can potentially lead to tetanus. Minor risks and chronic wounds are mainly found as tetanus cause. Vaccination remains the key element in reducing the morbidity and mortality associated with tetanus. It is estimated that the vaccine's coverage is fairly good, but decreases with age. To improve tetanus prevention, new vaccine recommendations have been established which recommend vaccine's injections at fixed age, but their impact seems to be limited especially in the elderly. The immunochromatographic tests have demonstrated cost-effectiveness in the Emergency department settings. They are currently not available outside hospital while general practionners also face a significant risk. Effectiveness of these tests should be studied in outpatients population including cost-effectiveness.

Tetanus--Kansas, 1993.

In 1993, two tetanus cases were reported to the Kansas Department of Health and Environment--the first cases reported in the state since 1987. This report summarizes the findings of the case investigations.

[Health and economic benefits of mandatory regular vaccination in the Slovak Republic. III. Diphtheria, tetanus and pertussis] . / Zdravotná a ekonomická návratnost' povinného pravidelného ockovania v Slovenskej republike. III. Záskrt, tetanus a cierny kasel.

The authors tried to evaluate the cost-effectiveness and cost-benefit of regular vaccination of children against diphtheria, tetanus and pertussis in Slovakia. On the basis of model costs of treatment of these diseases before and after vaccination in 1996, the total saved expenditure (102.6 million Sk) and cost-effectiveness (31,619 Sk) were calculated, as well as the cost-benefit.

Impacto epidemiológico y económico de la vacunación contra el tétanos en adultos de Colombia / Epidemiological and economic impact of tetanus vaccination in Colombian adults

OBJETIVO: Evaluar el potencial impacto epidemiológico y económico de la vacunación antitetánica en la población colombiana mayor de 15 años de edad, con dosis de refuerzo cada 10 años. MÉTODOS: Se realizó un análisis de costo-efectividad de la vacunación con refuerzo cada 10 años contra el tétanos en Colombia, comparándola con la actual estrategia (2, 4, 6, 18 y 60 meses). La carga de enfermedad se estimó con base en tres fuentes oficiales de datos. Se realizó un modelo de Markov desde la perspectiva del tercer pagador. El horizonte temporal fue el tiempo de vida de una persona. Se realizaron análisis de sensibilidad determinístico y probabilístico. RESULTADOS: En Colombia se notifican anualmente entre 30 y 48 casos de tétanos que ocasionan entre 9,6 y 10,1 muertes. Si bien la vacunación con refuerzo resultó costo-efectiva para toda la población (el costo por año de vida ajustado por discapacidad [AVAD] evitado fue de US$ 11 314 en toda la población), al discriminar los resultados por género no sería costoefectiva en las mujeres (el costo por AVAD evitado en hombres fue de US$ 4 903, y en mujeres de US$ 22 332). CONCLUSIONES: Este es el primer estudio que evalúa la costo- efectividad de una dosis de refuerzo cada 10 años de la vacuna contra el tétanos en un país en desarrollo. La aplicación de esta medida sería costo-efectiva en Colombia, especialmente para los hombres. Las diferencias en los resultados por género obliga a que cualquier decisión de implementación deba tener en cuenta la vacunación actual en mujeres en edad fértil.

OBJECTIVE: Assess the potential epidemiological and economic impact of vaccinating the over-15 Colombian population against tetanus with a booster dose every 10 years. METHODS: A cost-effectiveness analysis of tetanus vaccination with a booster dose every 10 years was conducted in Colombia and compared with the current strategy (2, 4, 6, 18, and 60 months). Estimates of the burden of disease were based on three official data sources. A Markov model from the perspective of the third party payer was developed. The time horizon was the lifetime of a person. Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: In Colombia, 30 to 48 cases of tetanus resulting in 9.6 to 10.1 deaths are reported each year. Although booster vaccination for the entire population was cost-effective (the cost per disability-adjusted life year [DALY] avoided was US$ 11,314 in the entire population), gender-based differentiation of the results showed that it would not be cost-effective in women (cost per DALY avoided was US$ 4,903 in men and US$ 22,332 in women). CONCLUSIONS: This is the first study that evaluates the cost-effectiveness of a tetanus vaccine booster dose every 10 years in a developing country. Use of this measure would be cost-effective in Colombia, especially for men. As a result of the gender-based differences in the results, any decision about its use in women of childbearing age should take current vaccination into account.

Cost-effectiveness of primary tetanus vaccination among elderly Canadians.

Although tetanus is now rare, vaccination is currently recommended for the entire population. Most elderly North Americans have never received tetanus vaccination. We evaluated the expected cost-effectiveness of using mailed reminders from family physicians to increase primary tetanus vaccination coverage among elderly Canadians. We estimated that over 10 years the program would prevent five cases of tetanus and one death from tetanus, resulting in a gain of 13 life-years. There would be 16,700 adverse reactions to tetanus toxoid, 17% in people already immune to tetanus. The net cost of the program (in 1984 Canadian dollars) would be $1.9 million per case of tetanus prevented, $7.1 million per death prevented and $810,000 per life-year gained. These high cost-effectiveness ratios are largely attributable to the very low risk of tetanus, even among nonimmune elderly people. Tetanus toxoid and physicians' services for vaccination would account for 86% of the program costs. Because the mailed reminders would be responsible for only 13% of the program costs, other possible programs to increase primary tetanus vaccination coverage could not be expected to have substantially lower cost-effectiveness ratios. We conclude that efforts to increase primary tetanus vaccination coverage among elderly Canadians would be a questionable use of health care resources.

Should adult tetanus immunization be given as a single vaccination at age 65? A cost-effectiveness analysis.

OBJECTIVE: To compare three vaccination strategies for the prevention of adult tetanus. Each strategy includes childhood primary immunization and wound prophylaxis, and one of the following: 1) the currently recommended booster every ten years; 2) a single booster at 65 years of age; or 3) no intervention after age 6 except for wound prophylaxis. METHODS: Cost-effectiveness analysis was used to compare the three different strategies. A Markov model, cycled annually from age 5 through age 85, was applied to each strategy to predict the incidence and costs of tetanus for the U.S. adult population. RESULTS: The three strategies have very similar effects on life expectancy but different costs. Expressed incremental to no intervention after childhood primary immunization, the decennial booster strategy is least cost-effective, with a discounted incremental cost-effectiveness ratio of $143,138 per year of life saved compared with $4,527 for the single-booster strategy. Sensitivity analysis demonstrates that the decennial strategy is more effective but more costly over a wide range of model assumptions. CONCLUSIONS: The current policy of recommending tetanus booster vaccinations every ten years is effective but much more costly than a more easily implemented policy that also provides considerable protection against tetanus. The authors recommend forsaking decennial boosters in favor of a policy of including a single booster at age 65 along with other recommended health maintenance maneuvers reserved for that age.

Unfinished business: adult immunization against tetanus.

Where effective child immunization schemes have been established virtually all cases of tetanus occur in persons aged over 50 years. Adult immunization programmes should be introduced in order to protect this age group against the disease.

Benefits of immunization versus risk factors in tetanus.

The risk of tetanus is universal, but it depends on numerous factors (socio-economic, environmental and biological) which combine to determine the force of infection. Tetanus is a murderous and costly disease. Its morbidity has greatly regressed in industrialized countries (less than 1 case per 100,000, involving mainly aged persons). On the contrary, developing countries are still severely affected (10 to 50 cases per 100,000, involving mainly neonates and children). Tetanus vaccine is one of the most effective, best tolerated and least expensive vaccines. Vaccination is the main weapon for starting disease control in developing countries, and the only way of eradicating tetanus in developed countries. Whatever the socio-economic level may be, some evaluations show that immunization cost is approximately equal to avoided treatment and seroprevention expenditures. The essential benefit of vaccination is the prevention of death, suffering and disability.

[Tetanus in the Murcia region: the clinico-epidemiological characteristics of 150 cases]. / Tétanos en la Región de Murcia: características clínico-epidemiológicas de 150 casos.

150 tetanus cases registered on the region of Murcia have been retrospectively analyzed, they have been collected from the patients admitted at a Intensive Care Unit during a period of 18 years; the clinical together with the epidemiological features, as well as their variations, have been studied through out the years. The impact of a vaccination program in adults which was performed in our region during 1981 has been also evaluated in relationship with the incidence of disease and the economical cost of it. Incidence remained homogeneous until 1982, from that date on a sudden decrease on the number of cases was observed, related with the vaccination program [Period previous to the vaccination program: mean 10 cases/year, versus 5 cases/year since it was started (p < 0.001)]. Regarding the epidemiological characteristics, it is remarkable the shift of the disease toward a more advanced age of onset together with a predominance on females beginning in 1978, but without reaching statically significance. More frequent route of infection is nowadays the intramuscular suppurative injection. Besides this fact the severity of the cases have been increasing (from 59% to 71%, p < 0.005), which has determined that the global mortality of the disease remains almost the same (38%). Mortality has no relationship with age, but is related with being a female (p < 0.05), with intramuscular injection as route of infection (p < 0.025), with the clinical stage (p < 0.001) and with a short incubation period (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Tetanus in a central Italian region: scope for more effective prevention among unvaccinated agricultural workers.

In 1997, Italy had the highest number of tetanus cases in the European Union; cases in the Marches region were more numerous than in France or Germany. In a retrospective study of the patients infected in Marches in 1996-1999, subjects or relatives were interviewed to ascertain disease severity, infection mode, occupation and immunization state at the time of infection. There were 32 cases, 29 (90.6%) females and three (9.4%) males, mean age 74.65 years (SD 9.06). The raw annual incidence was 5.6 per million and raw annual mortality 0.5 (n = 3). Twenty-seven patients (84.4%) were agricultural workers and five (15.6%) housewives; 25 (78.2%) had never been vaccinated, two (6.2%) had been immunized several years earlier and five (15.6%) had received only the first dose of vaccine at least 15 years earlier. In Italy, tetanus vaccination is compulsory for agricultural workers. Occupational health physicians should monitor workers' tetanus immunization state during their periodic surveillance visits.