Introduction

Tetanus is a severe infectious disease that occurs world wide, as its causal agent, Clostridium tetani, is ubiquitous in the environment. Tetanus spores are introduced into the body through a wound contaminated with soil, street dust, or animal or human faeces. Spores can also enter via lacerations, burns or minor scratches (1); injection drug use is also known to be a risk factor, and occasionally, tetanus follows surgical procedures (2).

Tetanus remains an important public health problem in developing countries, but cases also occur, although rarely, in developed countries (3-6). Over the last 50 years, large-scale use of tetanus vaccination and improved wound care have changed the epidemiology of tetanus in industrialised countries: neonatal cases have disappeared and a huge reduction in the incidence of the disease in the other age groups has been observed (3). The estimated incidence of tetanus in the United States and the WHO European Region in the 1990s was of 0.15 and 0.8 per million inhabitants respectively (3,6).

In Italy, tetanus vaccination has been mandatory since 1938 for military personnel, since 1963 for all children, for high-risk workers and athletes, and since 1968 the childhood immunisation was brought forward to the age of 1 year (7). The current vaccination schedule for primary immunisation consists of three doses in the first year of life followed by a booster dose at 5-6 years of age. Administration of additional booster doses is recommended for every subsequent ten years according to the WHO recommendations (8). The vaccination coverage for infant primary vaccination is 95% (9); data on vaccination coverage among adolescents and adults are not routinely collected and coverage is suspected to be low. Vaccination is also recommended as post-exposure prophylaxis, together with simultaneous immunoglobulin administration, for individuals with unknown vaccination history or with history of previous vaccination more than 10 years previously (10).

In the time period 1955–63, prior to the introduction of routine childhood vaccination for tetanus, tetanus incidence in Italy was estimated at 1.4/100 000. By the late 1960s it started decreasing, reaching an incidence rate of 0.2/100 000 in the 1990s (5,7).

During the evaluation of the reporting system of tetanus cases in Italy, and in order to describe the current epidemiology of tetanus in Italy, a review of available national routine data over approximately 30 years, from 1971 to 2000, was conducted. Available data on tetanus cases for the years 1971 to 2000, and on tetanus deaths for the years 1971 to 1997, were also analysed in detail.

Methods

Source of information on cases

In Italy, tetanus has been a statutory reportable disease since 1955 (11). Diagnosis is based on clinical grounds (e.g. acute onset of hypertonia, and/or painful muscular contractions and generalised muscle spasms after excluding all other possible causes), and does not require specific laboratory or bacteriological confirmation. The diagnosing physician is requested to report the case immediately (within 12 hours) to the local health unit which has to notify the competent regional health authority (RHA). The RHA in turn notifies the Ministry of health (MoH), the National institute of public health (ISS) and the National institute of statistics (ISTAT) (12). Historical data sets are kept, as for all notifiable diseases, by the ISTAT.

The present analysis was based on computerised records of individual notifications of cases provided by ISTAT for the years 1976-96, by the Ministry of Health for the years 1997-98 and on the individual notification forms available at ISS for the years 1999-2000. In the national databases at ISTAT and MoH only information on the date of notification, place and date of onset of symptoms, age and sex was available.

Source of information on deaths

In Italy, mortality data are available from the ISTAT national database, and available for the years 1971–97. Data on tetanus deaths were collected with the international classification of disease code ICD 9 code 037.

Data analysis

The numbers of cases and deaths reported per year were considered. Case fatality ratios were calculated for the period 1971-1997 by decade of notification (i.e., 1971-80, 1981-90, and 1991-97), and by age group.

National incidence rates of tetanus cases were computed by decade of notification (i.e., 1971-80, 1981-90, and 1991-2000), and age group (i.e., 0-14, 15-24, 25-64, and >64 years). ISTAT Italian population census data for 1971, 1981 and 1991 were used as denominators. Gender and age-specific rates were also computed by geographical area (Northern, Central, and Southern Italy) and decade of notification. Direct standardisation was applied, using the 1971, 1981, and 1991 national population census data as the standard population.

For the tetanus cases occurring in 1998-2000, the distribution by exposure, type, and site of injury, location where injury occurred and vaccination status was also calculated from individual notification forms with available information.

Analysis was performed using Epi-Info version 6.04 (13).

Results

Three hundred and seventy five tetanus cases were reported in 1971, then a continuous decrease was observed until 1991 when a historical minimum of 65 cases was recorded. A slight increase in the number of cases was observed afterwards, with an average number of 102 cases per year over the years 1992-2000 (figure 1).

Over the whole 30 year period observed, the highest incidence rates were observed during the summer, with an average of 37% of the cases occurring between June and August (data not shown). The annual number of tetanus deaths decreased steadily over the time, from a mean of 171 in the 1970s to a mean of 38 for the years 1991 to 1997.

Case-fatality ratio decreased from 68% in the period 1971-1980 to 39% in 1991-1997. For all the time intervals considered, the case fatality ratio increased with age, and in 1991–1997 no deaths were reported in the 0-24 years age group but the case-fatality ratio was 43% in individuals >64 years of age (table 1).

Table 1. Tetanus case fatality rate by age-group and by decade, Italy, 1971-1997

At the national level, the tetanus incidence rate per 100 000 population decreased from a mean value of 0.5/100 000 in the 1970s, to 0.3/100 000 in the 1980s, and to 0.2/100 000 in the 1990s. The decrease in incidence by decade was observed in all areas of the country, ranging from 0.63 to 0.18/100 000 in Northern Italy, from 0.60 to 0.24 in Central Italy, and from 0.36 to 0.11/100 000 in Southern Italy (figure 2).

In all periods considered, a varied pattern of incidence by geographical area was visible, with a higher incidence in northern and central Italy compared with southern Italy. Incidence in Northern and Central Italy was 1.66 and 1.75 times higher than the incidence in southern Italy in the 1970s, and 1.63 and 2.18 times higher in the 1990s.

A reduction in the incidence rate over time was observed in all age groups, and especially for those aged 15-24 years, for whom a 95% decrease was observed between the 1970s and the 1990s (139 cases in the 1970s, 13 cases in the 1990s). In contrast, the lowest decrease in incidence was observed in individuals aged over 64 years, which represents a 52% reduction from the 1970s to the 1990s (930 cases in the 1970s vs 778 cases in the 1990s) (figure 3).

The incidence rate of tetanus in the age group over 64 decreased from 1.71 in the 1970s to 0.81 in the 1990s. Over the whole period considered, the majority of cases reported in the younger age group (i.e. < 25 years of age) occurred among men, while the proportion of women was higher from 25 years of age onwards (table 2).

Table 2. Number of tetanus cases and incidence rate per 100 000 population by age-group, gender and decade, Italy, 1971-2000

During the years 1998-2000, 292 cases were reported and analysed according to exposure and vaccination status. Exposure was indicated on the case report forms in 125/292 (43%) cases. Of these 125 cases, an injury had occurred in 121 cases (97%), and four (3%) had a history of intravenous drug use.

When considering only cases associated with injuries, the place where injury occurred was reported in 35 of 112 cases (31%), the type and site of injury were reported in 94 of 112 cases (84%), and in 92 of 112 cases (82%), respectively. Most of the injuries associated with infection occurred outdoors (agricultural field: 55%), were described as lacerations /bruises (55%) and affected the lower limbs (68%) (table 3). The median incubation period was 10 days.

Table 3. Distribution of tetanus cases by place, type and site of injury, Italy, 1998-2000

The vaccination status was reported in 181 of 292 cases (62%). Among the 181 cases with known vaccination status, 163 (90%) were unvaccinated, and 18 were reported to have received at least one vaccine dose. All these 18 individuals were over 24 years old. The number of doses given was known for 13 of the 18 vaccinated people. Two patients had received at least three doses: one was a 72 years old woman who had received four doses with the last dose received seven years before the onset of symptoms, and the second case was a 32 year old man who had received five doses with the last dose given 18 years before the onset of symptoms. Two patients were given two doses, and nine were given one dose only. Seven out of 11 of these patients were vaccinated 30 days prior to date of notification, probably as a post-exposure prophylaxis.

Discussion

Routine vaccination against tetanus was introduced in Italy for all new-borns in 1968, and in the 1970s, the incidence showed a 2.8-fold decrease compared to the pre-vaccination period, the mean being 0.5 cases/100 000. During the following 20 years of observation, we observed a further 2.5 fold decrease, and in the 1990s the estimated incidence was of 0.2/100 000. However, in the 1990s a plateau became apparent, and no further reduction in incidence was observed over the years 1991-2000, with approximately 100 cases reported each year. To date, this is the highest reported number of cases in any European Union country. For example, in the 1990s, both France and the United Kingdom, which have approximately the same population than Italy, reported a mean of 40 and 12 cases per year, corresponding to an incidence of 0.07 and 0.01 per 100 000 (5). In addition, the tetanus incidence observed in Italy in the 1990s is 2.5 to 13.3 times higher than the average reported in the United States and the WHO European Region, reaching 0.02 and 0.08 cases per 100 000 respectively (3, 6).

Our study was based on information recorded on statutory notifications, therefore it suffered from limitations of routinely passive surveillance data. In particular, the sensitivity of the surveillance system and the quality of the data collected should be considered in interpreting the results. A difference in the sensitivity by geographical area could explain the higher incidence of tetanus and case-fatality ratio observed in northern and central Italy compared to southern Italy. Since northern and central Italy have higher routine vaccination coverage than the rest of the country, it is unlikely that the higher incidence of tetanus in these areas could be related to a higher proportion of susceptible individuals. In contrast, the higher degree of underreporting in southern Italy is well known and documented for other preventable diseases, such as measles and pertussis (14,15). Despite the fact that underreporting is probably lower for tetanus than for other milder diseases, a previous study highlighted that in most of the southern regions tetanus case-fatality ratio in the 1990s was exceeding 100%. As in our study, case-fatality ratio was computed using two independent sources of information on cases and deaths, a ratio exceeding 100% indicates a poorer reporting of cases compared to deaths (6). Differences in the sensitivity of the surveillance system should also be considered in interpreting the decrease in the tetanus case fatality ratio observed from the 1970’s to the 1990’s. This decrease was actually probably related to improved treatment of injuries, but could also be explained by an increase in case reporting, at least in northern and central Italy.

Regarding the quality of data, we observed a high ratio of missing information for somes variables. For example, between 1998-2000, data on the vaccination status were available for 63% of the cases, and data on the acquisition mode of the infection for 43% of cases. Relatively minor injuries may cause tetanus disease and go unrecognised or unreported. However, this high ratio of missing information is another evidence of the need to improve the reporting system. Despite the incompleteness of reporting, Italy shows the highest incidence in Europe, and since Clostridium tetani is widely present in the environment, the number of cases and the age distribution reflect an incomplete vaccination coverage (16).

As in other western countries, tetanus in Italy is mainly a disease of unvaccinated adults, particularly the elderly (3,17). The incidence peak in the summer season, and the fact most tetanus cases were associated with injuries occurring in an outdoor setting indicate that gardening or farm work are the main risk factors for acquiring tetanus, as documented in other studies (16,18). Tetanus vaccination coverage in childhood is high (9), but individuals born before 1968 (when universal childhood vaccination was introduced) may never have been vaccinated. Booster doses are recommended every ten years in adults in order to maintain adequate immunity levels, but no records of the uptake of booster doses are available and it is suspected to be low. Of the 975 cases notified during the years 1991-2000, 98% occurred in adults older than 24 years of age, and 73% in individuals older than 64 years. In our study, 90% of cases with known vaccination status reported between 1998 and 2000 occurred in unvaccinated individuals. More precise data on vaccination history of cases and on the vaccinations administered to adults would provide some evidence about the need of repeating booster administration every 10 years. The epidemiological picture obtained in Italy clearly demonstrates the need to improve primary vaccination coverage among unvaccinated adults.

Elderly women are most affected, and elderly women >64 years represented the majority of cases reported in the 1990s (i.e. 53%). Women of this age are less likely to have received vaccination as they were born prior to the introduction of routine childhood vaccination, and had fewer opportunities to receive vaccine compared to men of the same age group who were vaccinated because of professional or military duties (compulsory in Italy for all men).

Population based serological surveys carried out in various parts of Italy in the 1980s indicate that people aged >50 years are more likely than younger people to lack protective levels of tetanus antibodies and that women are less protected than men (7, 19, 20). In particular, it is estimated that between 21 to 55% of women aged 61-70 years of age are susceptible to tetanus, and that this proportion reaches 75-90% in women over aged > 69 years of age. Vaccination campaigns therefore need to be conducted to target this group.

In contrast to the gender distribution observed in older age groups, in the younger age groups (<25 years old), there was a higher incidence among males. Since no differences in childhood vaccination coverage among sex are observed, this may be due to an increased risk of injuries in young men compared to women of the same age-group. This hypothesis is supported also by the higher incidence of road accidents in males aged less than 25 years old compared to women (21). This may be due to differences in behaviour, such as different use of crash helmets and safety belts (21).

Tetanus is the only vaccine preventable disease that is infectious but not contagious. It is non-transmissible from person to person, so vaccination strategies cannot take advantage of the herd immunity effect. As the post-exposure prophylaxis administered in hospitals may be inappropriate (19,20,22), and not efficacious in preventing the clinical disease, the priority in Italy should be reminding adults about the recommended booster doses and actively offering the vaccination to women older than 65 year of age.