1 First Nations and Inuit Health Branch, Health Canada, Ottawa, Canada
2 London School of Hygiene and Tropical Medicine, London, UK
Correspondence: Michael Clark, Tuberculosis Program Officer, Directorate of Primary Health Care and Public Health, First Nations and Inuit Health Branch, Health Canada, PL 1920D, Tunney's Pasture, Ottawa, Ontario, K1A 0L3, Canada. E-mail: Michael_Clark{at}hc-sc.gc.ca
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Abstract |
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Methods The trend in the annual risk of infection (ARI) since 1926 was estimated using tuberculous meningitis mortality statistics and skin testing data. Risks of progression from infection to disease were estimated by fitting model predictions of disease incidence to TB notifications, using maximum likelihood methods. Infectious TB notifications were matched with ARI estimates to obtain the number of transmissions per infectious case over time.
Results We estimate that the ARI decreased from more than 10% during the prechemotherapy era to less than 0.1% by 2000. The risks of primary, reactivation, and exogenous re-infection disease among adults aged 2544 years were 22%, 0.1%, and 6%, respectively. The number of transmissions per infectious case decreased from 16 to 2 from the early 1970s to the late 1990s.
Conclusions This study shows that the risk of infection among British Columbia First Nations people is decreasing, while the relative contribution of reactivation to disease incidence is increasing. Once infected, First Nations people may have a higher risk of developing disease than other populations.
Accepted 3 July 2003
Tuberculosis (TB) is still a major public health problem in Canadian First Nations communities. During the 1990s, notification rates in the First Nations, on-reserve population were 810 times higher than the overall Canadian rates.1 A high prevalence of latent tuberculous infection, and socioeconomic factors such as overcrowded housing and substance abuse, are known contributors to this disproportionate burden.2,3 During the period 19971999, the age-adjusted TB notification rate among First Nations people living on reserves in British Columbia was 32 per 100 000.3 In urban areas such as Vancouver, the risk of TB may be elevated among First Nations people due to human immunodeficiency virus (HIV)/AIDS, injection drug use, and homelessness.4
The Indian Act of 1867 defined a reserve as, ...any tract or tracts set apart by treaty or otherwise for the use and benefit of or granted to a particular band of Indians....5 In 2000, it was estimated that 110 529 First Nations people lived in British Columbia, and 51% of these people lived on reserves.6 The objective of this study was to examine the epidemiology of tuberculous infection and disease in the First Nations population of British Columbia over time, using available data. We attempt to estimate the following: the annual risk of infection (ARI) between 1926 and 2000; the age-specific prevalence of infection between 1972 and 2000; the risk of progression to disease from primary infection, latent infection (endogenous disease), and exogenous re-infection; and the number of new infections per infectious disease case between 1972 and 2000.
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Methods |
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Estimating the ARI during the prechemotherapy era
Given the absence of reliable tuberculin data for the prechemotherapy era, we used tuberculous meningitis mortality data among First Nations children aged 04 years to estimate ARI values during this period. We assumed that 1% of those infected develop meningitis and subsequently die, as estimated elsewhere.710 These data are available from Statistics Canada since 1926. Use of streptomycin for TB treatment in Canada began in 1947,11 and thus mortality rates from meningitis after this year can no longer be assumed to reflect morbidity. Mass vaccination of newborns with bacille Calmette-Guérin (BCG) was not commenced in any Canadian province until after 1948.12 Therefore, effects of BCG on TB meningitis during the period before 1947 were assumed to be negligible.
Estimating the ARI after 1947
School screening data from 1991 to 2000 were supplied by the British Columbia Centre for Disease Control (BC CDC). This screening programme is supported by Health Canada as part of the National Tuberculosis Elimination Strategy implemented in First Nations, on-reserve communities. The data included the number of grade six children who were screened with a tuberculin skin test, and the number of these with a positive skin test, by year (Table 1). Since grade six children are generally aged from exactly 11 years to the end of 12 years (12 years and 11 months), we assume the prevalence of positive tests in these cohorts approximates the prevalence at age 12 years. Children were excluded from the data if they met any of the following criteria: the BC CDC had a record in their BCG registry for the child prior to the date of skin testing; the child had a BCG scar; or the parent or guardian reported the child had received BCG prior to the test. The criterion for a positive test was 10 mm induration to 5 TU (0.1 ml of tuberculin) of purified protein derivative (PPD). These data were used to estimate ARI values between 1979 (the year of birth for the earliest cohort represented in the data set) and 2000 (the last year of screening used in the analysis). We first assessed the nature of the trend in the ARI by calculating the average ARI experienced in each year of life of a cohort tested at time t using the formula:13
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For simplicity, the ARI between 1947 and 1979 was assumed to decline at a constant rate.7,18 To assess the validity of this assumption, and the estimated trend between 1979 and 2000, we compared estimates of the expected prevalence of infection in 1992 and 1999 against the proportion of individuals aged 014, 1524, and 2544 years found to be tuberculin positive in cross-sectional surveys during the periods 19911993 and 19982000, respectively.
Estimating the risk of progression to TB disease
Reported TB case tallies for the British Columbia First Nations population from 1972 to 2000 for the 014, 1524, 2534, and 3544 year age groups were provided by the Population and Public Health Branch of Health Canada. Owing to the high variance of reported TB cases from year to year among 024 year olds, and the possible impact of neonatal BCG vaccination on disease incidence in this age group, data from the 014 and 1524 age groups were excluded from the analyses. These data include First Nations TB cases diagnosed on and off reserve, as case report forms did not include this distinction prior to 1990. Between 1990 and 2000, the TB notification rate among First Nations people living on and off reserve (39 per 100 000) was only slightly higher than the on-reserve notification rate of 36 per 100 000.
Disease cases included in the model were new TB cases (pulmonary and extrapulmonary), diagnosed with bacteriological proof and/or clinical symptoms consistent with TB. Relapsed cases (those cases with recurrent active disease after a known period of inactivity) were excluded from the model. Estimates of the risk of disease were derived using methods similar to those of Sutherland et al. applied to the Dutch population,19 namely by fitting predictions of the number of cases expected in different age groups over time, expressed in terms of the risks of disease, to these data. Given small differences between the notification rates among males and females, the data were not stratified by sex. The method assumes that individuals develop disease either soon after primary infection (primary disease) or many years thereafter through endogenous reactivation, or after exogenous re-infection. Endogenous disease refers to reactivation of a longstanding latent infection among those infected individuals who did not develop primary disease. Exogenous disease refers to the development of disease soon after an individual with longstanding latent infection is re-infected with a new strain of M. tuberculosis. The number of TB disease cases in each age group at time t D(a,t) is given by the sum of the number of individuals experiencing primary disease P(a,t), disease through endogenous reactivation En(a,t), and exogenous disease Ex(a,t), as follows:
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The numbers of individuals in age group A at time t (where A spans the ages aj, aj+1) were calculated using estimates of the ARI at different times t (ARI(t)) and estimates of the prevalence of infection among individuals of age a at time t, as follows:
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The risks of developing primary, endogenous, and exogenous disease were estimated using maximum likelihood methods, by minimizing the following Poisson log-likelihood chi-square deviance function:
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Estimating the number of new infections per infectious case
Three-year, moving rates of reported infectious TB were calculated from 19721974 to 19982000. Those cases considered infectious were respiratory cases in which M. tuberculosis was isolated from a sputum sample using smear microscopy and/or culture. This definition includes smear-negative respiratory cases with a positive sputum culture, due to a recent report showing that 17% of transmissions in San Francisco were attributed to such cases.22 The number of new infections per infectious case over time was calculated using the ratio between the ARI and the incidence of infectious TB cases.
Population data sources
Population estimates from the 1931, 1941, and 1951 censuses were used to calculate mortality rates from tuberculous meningitis during the pre-chemotherapy era. Population data between 1972 and 2000, by one-year age group, were obtained from the Department of Indian and Northern Affairs Canada.
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Results |
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According to best-fitting estimates (Figure 1), the ARI was 0.031% (95% CI: 0.023, 0.040) in the year 2000. The estimated annual rate of decline from 1979 to 2000 was 13.8% (95% CI: 11.5, 15.9). The estimated ARI since 1926 is presented in Figure 2. The assumed constant rate of decline between 1947 and 1979 was 9.1%.
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Discussion |
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Estimates of the ARI during the prechemotherapy era have been calculated using a ratio between mortality rates from tuberculous meningitis among 04 year olds and the ARI, which was derived from European studies.710 It is possible that the risk of TB disease among First Nations children was higher than in European populations, which would inflate our ARI estimates. In this context, it is worth noting that the average ARI estimates among two cohorts of First Nations children skin tested during the prechemotherapy era were 12% and 20%,25 which is consistent with the range of ARI values found in our study (621%). One would expect very high ARI values during the 1930s and 1940s, as death rates among British Columbia First Nations ranged between 581.5 and 1026.9 per 100 000.26 In the modern era, it is important to recognize the possible impact of BCG use on our interpretation of screening data. Some children with unrecognized BCG vaccination may have been included in the data set. The effects of this should be minimal, given the observation that BCG given in the first year of life rarely affects skin testing results beyond the age of 10 years.27,28 More importantly, the use of BCG may be more common in communities where TB incidence is higher. Another limitation in the school screening data was that the exact age of grade sixes screened was not reported. It is possible a small proportion of children in a given year are aged as low as 10 years, or as high as 14.
Despite the limitations described above, two findings indicate that the results of this study are plausible. First, the estimated annual rate of decline in ARI between 1979 and 2000 (13.8% p.a.) is identical to that observed in the Dutch population between 1940 and 1970.19 Predictions of infection prevalence among people aged 024 years in 1992 and 1999 are very similar to the proportion of individuals found to be tuberculin positive in these years (Figure 3), indicating that ARI estimates for the last three decades are in a plausible range. Our finding that predictions of infection prevalence for individuals aged over 25 years did not agree with survey results may be related to waning tuberculin sensitivity among adults who were infected during periods when the risk of infection was higher.29 In contrast with the analyses of Sutherland and colleagues, which included only pulmonary TB cases,19 our analyses considered all new pulmonary and extrapulmonary cases. The above study also included a wider age group (1569 years) of male Europeans. However, it is striking that their estimates for risk of primary and exogenous disease fall within the 95% CI of our estimates for people aged 2544 years. Both of the studies estimate an approximate risk of disease following primary infection of 22%.
It is often assumed that the risk of TB following infection is 5% within 2 years, with a 10% lifetime risk of developing disease,30 which is inconsistent with the findings of this and other studies.19,31 An increased risk of disease in young adults has implications for decisions on treatment of infection, particularly in light of the high incidence of infectious TB in this age group,1 and the possibility of secondary benefits due to reduced transmission. Treatment of infection in adults is controversial, due to poor adherence32 and the increased risk of adverse reactions such as isoniazid (INH) hepatitis.33
It is interesting that our estimate of the risk of developing disease through reactivation is about threefold greater than that estimated in other populations (0.1% p.a. as compared with 0.03% p.a. for The Netherlands and the UK19,31). This may be attributable to several factors including differences in immunosuppression, occurring as a result of poor nutrition and other socioeconomic influences. It is possible that First Nations people experience an elevated risk due to late exposure to European strains of bacilli, and resulting lower levels of innate immunity.12 A recent study showed that several First Nations TB cases had a gene deletion that may have predisposed them to developing active disease.34 The model predicts an increasing contribution of endogenous reactivation to total disease burden over time. The high prevalence of latent infection in many First Nations communities,1 coupled with an increased risk of disease, may result in cases of reactivation disease for many years to come.
These analyses show that the relative contribution of re-infection to disease incidence has decreased markedly over time in the 2544 age group. Re-infection may still play a significant role in older age groups, in which a higher prevalence of latent infection can be expected. In a recent review of DNA fingerprinting data from Vancouver, no cases of re-infection by a different strain of M. tuberculosis were found among individuals with recurrent disease.35 Different results were found in a South African study, in which a high proportion relapsed cases had been re-infected.36
The occurrence of outbreaks and paediatric disease indicates that M. tuberculosis transmission continues in some First Nations communities.1 Rapid progression to disease was reported during a 1992 outbreak among immunocompetent members of a British Columbia First Nations community, in which 13 of 21 TB cases had a conversion of their skin test result during the investigation.37 Despite these observations, we have estimated that the number of transmissions per infectious case is decreasing over time. This may be due in part to earlier case finding and treatment: Wang et al. reported that TB notification rates among British Columbia First Nations people declined more rapidly than those among non-First Nations people between 1992 and 1996, possibly due to greater use of directly observed therapy.38 In many industrialized countries decreasing TB incidence has led to the decentralization of responsibility and funding for TB programmes. This type of reform is often associated with the occurrence of microepidemics, in which a single source case infects a large number of young, previously uninfected contacts.39 Given the possibility of increased susceptibility to TB disease among First Nations people, and the occurrence of large outbreaks in First Nations communities, TB programme erosion must be prevented despite the decreasing risk of infection shown in this study.
KEY MESSAGES
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References |
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