TUBERCULOSIS IN ITALY

Transcription

1 TUBERCULOSIS IN ITALY 1. Cases of TB notiiied in Italy from 1955 to Incidence (Tables ) From 1955 to 1995, the number of cases of TB notified in Italy decreased from 12,247 to 5,225. The crude annual incidence decreased from to 9.12 per 100,000. In 1974, the incidence of TB decreased below 10 per 100,000, and consequently Italy can be considered a country with low prevalence of TB". Nonetheless, this trend differs between pulmonary and extrapulmonary TB (Figure la and lb). The incidence of pulmonary TB markedly decreased in the period , with the rate of decrease differing with the specific period. Between 1955 and 1965, the incidence of pulmonary TB showed an annual decrease of 3.4%. whereas the annual rate of decrease was equal to 7.47% between 1965 and 1975 and to 4.89% between 1975 and By contrast, no marked variations were obsewed in the incidence of extrapulmonary TB, which between 1955 and 1980 oscillated between 0.4 and 0.5 cases per 100,000. Beginning in the early 1980s. the trend for both forms of TB changed. Specifically, the incidence of pulmonary TB no longer continued to decrease, remaining relatively stable, with annual rates at around 6 per That for extrapulmonary TB rapidly increased, reaching more than 2 cases per 100,000 per year, with annual rates of increase of around 8-12%. depending on the specific five-year period considered. The cases of extrapulmonary TB represented 2% of the total of cases notified in 1955, while in 1995 they represented 27% of tbe total of cases. 1.2 Case deiinition according to the European recommendations (Table ) Using the classification adopted in the European recommendations. the number of cases of extrapulmonary TB decreases, whereas there is an increase for pulmonary TB. This is due to the fact that cases of miliary TB are considered both in the group of disseminated and pulmonary TB. In the group of pulmonary TB are also included cases of TB localised in the tracheal-bronchial tree only. 13 Regional trends Crude inciiience rates (Tables ) The incidence of TB varies by geographic region. In 1955 and 1965, well more than half of the cases of TB notified in Italy were from northem regions; the southem regions and the islands of Sardegna and Sicilia reported little more than 10% of the total cases. During these two decades, however, the number of deaths for TB in the southern regions and the islands greatly exceeded the number of notified cases (see the "Lethality" section below). For the following decade no comparison among geographical areas is possible, since there was an abrupt and unexplainable decrease in notifications. In fact, between 1972 and 1981, Centra1 Italy reported a number of cases that was too low to be consistent with reports from previous years: this phenomenon can be almost entirely attributed to the Lazio region and in small part to the Umbria region (Table B). The ISTAT documents for these years repori no problem in the transmission of data from these regions.

2 Table B - Number of TB cases in Central llaly belween 1968 and 1985, by region year Toscana Umbria Marche Lazio Centra1 Italy As observed in the 1950s and 1960s, between 1985 and 1995 the cases notified from Northern Italy represented the greatest proportion of cases at the national leve1 (i.e., 67.9%), though Northern Italy represented only 44.4% of the total Italian population (Table C). The other regions, in particular the South and the Islands, reported a proportion of cases that was lower than the proportion of the population represented by these areas. Table C - Diwibuiion of cumulative TB cases and average popitlation by region, ItarY, Area Average population % TB cases '% North 25,370, Centre 10, , South 13,907, Island 6,622, Total 56,799, , The epidemiological trend of pulmonary and extrapulmonary TB differs by region. The incidence rates for pulmonary TE3 are consistentiy higher for Northern and Central Italy, and these rates have shown a trend of increase in the most recent years; in the South and the Islands, the incidence has remained very low: approximately 2 to 4 cases per

3 100,000 (Figure 2). The incidence of extrapulmonary TB has been increasing since 1988 in Northern Italy and, more recently, in Central Italy, reaching 4 and 2.4 cases per 100,000, respectively. In the southem regions and the islands, no increase has been observed (Figure 3). Slandardised incidence rates (Tables ) The availability of information on individua1 cases notified since 1992 has allowed the standardised rates to be calculated. These rates confirm, for recent years, the North- South gradient (high incidence-low incidence), which had already been highlighted by the crude rates for pulmonary and extrapulmonary TB. L4 Characteristics of individuals with TB Gender (Tables ) Between 1995 and % of thc cases of pulmonary TB were repurted to have been observed among males (range: 62-76%). The incidence rates were also consistently higher among males; the trends were comparable for the two genders (Figure 4). For extrapulmonary TB, males represented 50% of the cases notified between 1955 and 1995 (range: 43-66%). The increase in incidence of extrapulmonary TB is similar for the two genders. Age (Tables ) Between 1955 and 1995, the incidence of pulmonary TB decreased drastically in the age class years (Figure 5). whereas the decrease was more limited in children and adolescents, and in individuals 75 years of age and older. In individuals 75 years of age or older, there has been an increase in the number o cases since An analogous turn around in the trend has also been observed for the age class years, which since 1985 has shown a regular increase in the number of TB cases. In 1990, the curve of incidence rates by age shows two peaks for these two age classes (> 75 years and years) (Figure 6). The incidence of extrapulmonary TB increased considerably for al1 age classes between 1955 and 1995, with particularly high increases obsewed among adults and the elderly (Figures 7 and 8). Between 1992 and 1995, the mean age was 49 years (median age = 50 ycars) for cases of pulmonary TB and 51 years (median age = 53 years) for cases of extrapulmonary TB. Specific grorips Non italian cilizen (Tables ) Between 1992 and 1995, the cases notified as "non-italian citizens" represented overall 10% of the total number of notified cases of TB. This proportion tends to gradually increase (from 8.1% in 1992 to 10.7% in 1995) and is similar for the two forms of TB (pulmonary and extrapulmonary). In the age class years, the percentage of cases of TB represented by foreign citizens is around 20% of notified cases. In 1995, Northern Italy notified 68% of the total number of notified cases among foreigners at the national level, while only 51% of the foreigners residing in Italy live in Northern regions. Nonetheless, the regions of Central Italy notify the highest percentage of cases of TB among non-italian citizens on the total of cases notified. A North-

4 South gradient (from high incidence to low incidence) can be observed in the TB incidente rates for non-italian citizens. Based on the estimates of the number of foreigners residing in Italy, the highest rates are obsewed for persons from Africa (especially Senegal and Somalia), from South America (especially Peru), and Eastern Asia. Persoiis with aids (tables ) Between 1992 and 1995, 1.9% of the total TB cases notified were also notified to the National AIDS Registry as persons with AIDS (PWA). In the age class years. these individuals represent overall5.3% of the TB cases notified (6.1 % in 1995). Of the cases of TB among PWAs notified between 1992 and 1995,97% were from Northern or Central Italy. The number of PWAs, identified by comparing the two surveillance databases. is lower than the number of PWAs notified to the National AIDS Registry as having TB as the first disease indicative of AIDS (Tables ). It thus seems that the PWAs with TB are more frequently notified to the National AIDS Registry. respecting the mandatory notification of AIDS cases, than to both systems. TB is probably considered only as a pathology indicative of AIDS and not as a pathology which in itself is subject to obligatory notification. Moreover, the cases published by the National AIDS Registry represent only a portion of the total number of TB cases obsewed in PWAs, since al1 AIDSrelated conditions, including TB, whose onset occurs after the patient has already been notified as having AIDS, are not normally notified and recorded by the AIDS Registry. The underestimate is still greater for pulmonary TB, which has been included among the pathologies indicative of AIDS only since PWAs and foreigners Persons with AIDS and foreigners represented, in total, 11.3% of TB cases notified at the national level between 1992 and 1995; in the age class years, this proportion increases to 32.5% (34.1% in 1995). This proportion tends to be higher for extrapulmonary TB forms compared to pulmonary forms. When excluding PWAs and foreigners. the peak of incidence obsewed in the age class years tends to disappear almost completely for extrapulmonary TB and a little less for pulmonary TB (figures 9 and 10). 1.5 Extrapulrnonary TB (Tables ) From 1992 to the most frequently reported extrapulmonary site was the peripheral lymph nodes, followed by the genito-urinary apparatus and the pleura. However. there are some differences between males and females in the frequency of extrapulmonary sites: in males, the most frequent site is the pleura. with an incidence twice as high as that among women. In women, the most frequent site of extrapulmonary TB was peripheral lymph nodes, with an incidence approximately twice as high as that among men. From 1992 to 1995, the incidence rate of meningeal TB has remained at 0.9 per 10,000,000 (number of cases of meningeal TB among children aged 0-4 years per lo,m)0,000 genera1 population)l Diagnostie criteria Information on the specificdiagnosticcriteria used for notifyingtb cases hasonly been available since In 4,292 cases (31.1%) of pulmonary TB, the notification form cites a positive culture, whereas in 5,920 cases (42.8%) a positive direct smear of the sputum is reported (Table D). In total, 58.0% of the notified cases of pulmonary TB (8,015) were notified on the basis of at least a positive cultura1 exam andlor a positive direct smear.

5 Table D - Cases of TB in Italy, Disfribrrfion by site and diagnosfic criteria Positive Positive (1) andior (2) Other diagnosis Not Total culture direct smear (clinicalix-ray) known (1) (2) (3) (4) (5) (3+4+5) Pulmonary TB , , ,818 % Extrapulmonary TB , , Noi known Any site ,044 6, ,583 % O Data Iran Lazio region excludcd in 1992 (377 cases) and in 1993 (468 cases) Approximately 32% of the cases were diagnosed exclusively based on clinical andlor radiological criteria. In 10% of the cases, no information was available on the exams carried out for the diagnosis of pulmonary TB. Nonetheless, the accuracy with which the information is collected seems to have improved over the years. In over 60% of the cases reported a culture or at least a positive direct smear and less than 7% of the notifications failed to report any information on the type of diagnosis performed. Between 1992 and 1995, there was a marked decrease in the proportion of missing information on the results of culture and of the direct smear (Table E). Table E - Cases ofpirltnonary TB in ItaIy frotn 1992 to Distribirtion by type of diagnostic criteria and year of nofificatian Culture positive negative not known Direct smear positive negative not known Total cases 3,110 3,159 3,799 3,750 13,818 Data lrom Lazio region excludcd in 1992 (377 cascs) and in 1993 (468 caaes)

6 2. Mortality Between 1955 and 1993, 156,275 deaths due to TB were notified. The crude rate of mortality decreased from 22.5 per 100,000 in 1955 to 0.9 per 100,000 in The standardised rates decreased from 24.0 to 0.7 per 100,000 (Tables ). Between 1955 and 1993, the mean rate of annual decrease was equa1 lo 7.6%. This trend of decrease was similar for pulmonary and extrapulmonary TB (Figure 11) and more accentuated for meningeal forms (9.2%) (Figure 12). Between 1989 and 1993, the mortality rates stabilised at around 0.7 per 100,000 for pulmonary TB and 0.1 per 100,000 for extrapulmonary TB. In the past ten years ( ), the number of deaths due to tubercular meningitis has decreased considerably (less than three deaths every 10,000,000 inhabitants). The number of deaths among children less than 5 years of age is also very low: between 1985 and deaths due to tubercular meningitis were reported in this age class. Males represented 73.3% of total deaths due to TB (range: 66.0%-77.8%). The distribution by gender varies according to the site of disease: males represented 75.6% of the deaths due to pulmonary TB and only 54.6% of those due to extrapulmonary TB. The mean rate of annual decrease of moriality is similar for the two genders. Since 1969, TB moriality, in addition to decreasing regularly, has been concentrated for the most part in older ages (over 55 years): in 1993, 92% of the total deaths due to TB were reported among persons over 55 years of age. In the same year, the year age class represented 8% of deaths, and no deaths due to TB were reported among individuals less than 25 years of age. In recent years, the mortality in the age class years appears to be stable (Tables ). Mortality is consistently higher over time in Northern Italy. The trend of decrease is nonetheless similar in al1 of the geographical areas (North, Centre, South, and the Islands), botb for pulmonary and extrapulmonary TB (Tables ). The case-fatality, calculated on the basis of TB deaths and number oftb notifications in a certain calendar year, represents a very crude estimate of the probability of death among TB cases, fora number of reasons: 1. until only selected pulmonary and extrapulmonary TB cases were subject to mandatory notification, while death for from al1 types of TB has always been mandatory; 2. deaths in a specific calendar year can occur in prevalent TB cases who developed the disease in previous years; 3. the accuracy of this parameter depends on the comparability of the two information systems with respect to the completeness of data. Nevertheless, the comparison of mortality and morbidity data can be useful to evaluate the consistency over time, by geographic area and by persona1 cbaracteristics, of data reported by these two information sources. Table F shows tbe case-fatality for pulmonary TB by calendar year.

7 Table F - Case-fataliry (number of TB deaths/number of TB cmedioo) forpulmonary?'d between 1955 and 1993 Year Case-fatality Year Case-fatality , Between 1955 and 1975, the case-fatality was consistently greater than 50% (in 1961 the number of deaths is even higher than the number of cases); it then begins to decrease, reaching the current 12% (in Europe, WHO reports a case-fatality o 7% in the few countries where data on treatment results are available). It thus seems clear that the high case-fatality observed unti1 the beginning of the 1990s is in part attnbutable to the fact that not al1 the TB cases were subject to mandatory notification, but also, and perhaps mainly, to greater undernotification of TI3 cases in companson to TB deaths. The analysis of case-fatality by age and calendar year points in the same direction (Table G): between 1955 and 1975 for the over 55 years age class, the number of deaths greatly exceeded the number of notified cases, suggesting considerable undemotification.

8 Table C - Case-fatality (niiriiber of Ti3 dealhs/numbrr of TB cases/loo) far pirlmonary TB by age classes and calendar year Age Year The analysis by geographical area and calendar year (Table H) shows that, between 1955 and 1975, the areas in which the undernotification seerns to have been greater were the Southern regions and the Islands: in 1975, considerable undernotification occurred in Central Italy also (this phenornenon has been already pointed out or the Lazio region on the basis of the number of notifications). However, even in recent years, the case-fatality in the Southern Regions and in the Islands continues to be higher than in the North: this may be due to an actual lower risk of death for TB patients in the North orto a greater undernotification of TB cases in the South. Table H - Case-fatality (niin~ber of TB deaths/nnn~ber of TB cases/100) far pirlnlonary TB by geographical area and calendar year Year Geographical area North Centre Souih Islands

9 4. Problems in interpreting the data presented The data provided in this document constitute the only epidemiological information cxisting at the national leve1 over time in Italy. Nonetheless, it is evident that these sources of information have a number of limitations in terms of the quality of data: consequently, caution is required when interpreting the TB trend over time, for different geographical areas or for the main risk groups. Specifically, the major limitations of these data can be summarised as follows: The case definition has been changed several times over the last 40 years. The most substantial change was in 1987, when al1 TB forms were included in the mandatory notiiication system. However, the late 1980s coincides with the end of the trend of decrease. and in some cases the reversal of this trend, in other European countries. Since the changes in the case definition and the changes in the trend of TB overlap, it is difficult to determine to what extent the observed increase reflects a true increase in TB incidence and to what extent it reflects changes in notification criteria. On the basis of these data, it is not possible to estimate the degree of undernotification. However. it is clear that, in certain years, some regions provided data that were not consistent with data from previous years or with evidence obtained from other sources of information. For example: a) in Centra1 Italy, an abrupt and unexplainable decrease in notifications occurred betweqn 1972 and 1981 (Table B); this obsewation was confirmed by the fact that in the same years the number of deaths greatly exceeded the number of notifications (Table H): b) prior to 1975, the number of deaths was higher than the inumber of notifications also in the South and the Islands. These phenomena seem to have been more prevalent in the past than in recent years: in fact, after data are more consistent and no abrupt change in trends has heen observed. Nevertheless, the observed North-South gradient should be interpreted with caution. The comparison between the National AIDS Registry and the TB notification system has highlighted the undernotification of TB in PWAs. In 1995, in fact, the number of PWAs with TB reported as the pathology indicative of AIDS was four times greater than the number of patients identified through the comparison of the two systems. It thus seems that the PWAs with TB are notified as AIDS patients but not as TB cases; this phenomenon can occur when TB develops after the AIDS diagnosis. so that these individuals are not notified either to the AIDS Registry or to the TB notification system. It is clear that the evaluation, on the hasis of these data, of the contribution of PWAs to the epidemiological pattern of TB in Italy should be carried out with great caution. The estimate of the impact of persons who immigrated countnes with a high TB prevalente on the actual epidemiological pattern of TB in Italy is, at best, cmde: a) the variable,l cituenship".. is probably inaccurate, given that fora number of cases "ltaly" was reported, though the names and surnames were clearly not of Italian ongin; b) to estimate TB incidente in persons with "non-ltalian citizenship" the number of immigrants legally residing. according to data provided by ISTAT, were used. This has led to an overestimate of the TB incidence, given that al1 immigrants were included in the numerator and only lega1 residents were included in the denominator. Nonetheless, we chose to use these data, given that the alternative would have been to use data referring to official permits of residence, which would have produced even less accurate rates, since the number of permits of residence is not regularly updated and includes expired permits, several permits for the same individual, and permits for individuals residing only temporanly in Italy.

10 References 1. Dipartimento di Scienze demografiche dell'università degli Studi di Roma "La Sapienza". Ricostruzione della popolazione residente per sesso, età e regione - anni Roma: Università degli Studi la Sapienza, Istituto Nazionale di Statistica. Popolazione e movimento anagrafico dei comuni. Anno Annuario 6. Roma: ISTAT, Istituto Nazionale di Statistica. Popolazione e movimento anagrafico dei comuni. Anno Annuario 7. Roma: ISTAT, Istituto Nazionale di Statistica Annuari di Statistiche Sanitarie ; volumi I-XXVI: anni Statistiche Sanitarie 1986; volume 27: anno Statistiche Sanitarie 1988; volume 28: anno Statistiche Sanitarie 1988; volume 29 tomo 1: anno Statistiche Sanitarie 1989; volume 30 tomo 1: anno Statistiche della Sanità 1990; Annuari 1-3: anni Statistiche della Sanità 1991; Annuario 4: anno Statistiche della Sanità 1992; Annuario 5: anno Statistiche della Sanità 1993; Annuario 6: anno Statistiche della Sanità 1994; Annuario 7: anno Istituto Nazionale di Statistica Annuari di Statistiche Sanitarie ; volumi I-XXVI: anni Statistiche Sanitarie 1986; volume 27: anno Statistiche Sanitarie 1988; volume 28: anno Statistiche Sanitarie 1988; volume 29 tomo 2: anno Statistiche Sanitarie 1989; volume 30 tomo 2: anno Cause di morte 1989; Annuari 1-2: anni Cause di morte 1990; Annuario 3: anno Cause di morte 1991; Annuario 4: anno Cause di morte 1993; Annuario 5: anno Cause di morte 1994; Annuari 6-7: anni Cause di morte 1996: Annuario 8: anno Cause di morte 1996; Anno Ministero della Sanità. Disposizioni sanitarie concernenti le malattie infettive e diffusive. Decreto 23 aprile Gazzetta ufficiale della Repubblica Italiana, , 22/05/ Ministero della Sanità. Revisione dell'elenco di malattie infettive sottoposte a denuncia obbligatoria. Decreto 5 luglio Gazzetta ufficiale della Repubblica Italiana, n.259,29109/ Ministero della Sanità. Malattie infettive e diffusive - Norme generali. Decreto 28 novembre Gazzetta ufficiale della Repubblica Italiana, , 12/12/ Ministero della Sanità. Sistema informativo delle malattie infettive e diffusive. Decreto 15 dicembre Gazzetta ufficiale della Repubblica Italiana, Serie generale n Ministero della Sanità. Circolare Ministeriale D.G.S.I.P. - Div. 11'. N" 400.2/ ,27 marzo Protocollo per la notifica dei casi di tubercolosi.

11 I I. HL Rieder, JM Watson, MC Raviglione et al. Surveillance of tuberculosis in Europe. Eur Respir J 1996; 9: L Clancy, HL Rieder, DA Enarson, S Spinaci. Tuberculosis elirnination in the countnes of Europe and other industrialized countries. Eur Respir J 1991; 4: IUATLD. A Staternent of IUATLD. Criteria for discontinuation of vaccination prograrnmes using Bacille Calmette Guerin (BCG) in countnes with a low prevalence of tuberculosis. Newsletter IUATLD 1994; May: