Ageing with Trypanosoma cruzi infection in a community where the transmission has been interrupted: the Bambuí Health and Ageing Study (BHAS)

MFF Lima e Costaa,b, SM Barretoa,b, HL Guerraa, JOA Firmoa, E Uchoaa,b and PG Vidigala,b

a Oswaldo Cruz Foundation René Rachou Research Center, Brazil.
b Federal University of Minas Gerais Medical School, Brazil.

Reprint requests to: Prof. Maria Fernanda F Lima e Costa, Centro de Pesquisas René Rachou, Av. Augusto de Lima 1714, 30.190.002, Belo Horizonte, Minas Gerais, Brazil.


    Abstract
 Top
 Abstract
 Introduction
 Material and Methods
 Results
 Discussion
 References
 
Background The prevalence of Chagas' disease is decreasing in Brazil. Due to cohort effect, the disease might remain a public health problem for some time among older individuals. The present burden of Trypanosoma cruzi infection for the elderly living in areas where the transmission has been interrupted has not been studied.

Methods The prevalence of T. cruzi infection and its association with indicators of health status and health services use were assessed among the elderly living in one of the oldest endemic areas in Brazil (Bambuí, MG). Seropositivity was determined by blood tests (IHA and ELISA) performed in 85.6% of all residents aged 60+ (1496/1742) and in 83.1% of sampled residents aged 5–59 years (1212/1458).

Results Seropositivity showed a cohort effect, with no cases below 20 years and high prevalence among those aged 60+ years (37.7%). After adjustment for confounders, seropositivity was associated with self-rated health reasonable (OR = 1.43; 95% CI : 1.03–1.98) and bad/very bad (OR = 1.89; 95% CI : 1.30–2.75), staying in bed in past 2 weeks (OR = 1.88; 95% CI : 1.21–2.92), hospitalization in past 12 months (OR = 1.41; 95% CI : 1.05–1.89) and use of 5+ prescribed medications in past 3 months (OR = 1.75; 95% CI : 1.15–2.59).

Implications Our results are an example of how survival of individuals with past exposure to infectious disease may lead to a different picture of ageing in the developing world. Policy makers need to consider the extra burden imposed by increasing rates of non-infectious disease among the elderly (as observed in Brazil) including the consequences of T. cruzi infection in areas where the infection was widespread in the past.

Keywords Elderly, Chagas' disease, Trypanosoma cruzi, Bambuí, Brazil, BHAS

Accepted 6 December 2000


    Introduction
 Top
 Abstract
 Introduction
 Material and Methods
 Results
 Discussion
 References
 
Chagas' disease is a chronic disease caused by the parasite Trypanosoma cruzi, which is transmitted by a triatomine bug and also by blood transfusion and transplacentally. The infection may cause an acute self-limited disease, which evolves to a symptomless period. Several years after infection about 30% of individuals present clinical evidence of heart disease, and around 8% develop megavisceras.1 It is estimated that 16–18 million people are currently infected in South and Central America.2 Infection is thought to be lifelong though detection of parasitaemia during the chronic phase is very difficult.3 Thus, its diagnosis is based mainly on the detection of serum antibodies to T. cruzi using serological tests.4 The effect of treatment during the chronic phase is controversial. Early clinical trials did not show any effect of treatment in preventing the development of chronic Chagas' disease in adults. More recent findings suggest that treatment may be effective in producing negative seroconversion of specific antibodies in schoolchildren treated during the first year of infection.1

The Chagas' Disease Control Programme in Brazil is based on control of the triatomine bug. This programme began on a national scale in the mid-1970s and mortality and hospitalizations due to Chagas' disease have been declining since then.5 In addition, in some endemic areas infection by T cruzi in children has been reduced or has even disappeared, which is regarded as an indication of a control programme's effectiveness.68 These factors, among others, lead the WHO to predict that the interruption of Chagas' disease transmission might be achieved in Brazil by 2003.9

When transmission of the infection is reduced or interrupted we expect to observe a cohort effect, with higher prevalence of T. cruzi infection among older individuals. Consequently, in areas where the programme has been successful, the disease might remain a public health problem for some time, and for a longer time among the elderly. There has been little investigation of the present burden of T. cruzi infection for the elderly population living in these areas.

We studied one of the oldest endemic areas for Chagas' disease in Brazil to address this question.10 The municipality of Bambuí was a pioneer in the control of the disease in Brazil. The first experiments for the extermination of triatomine bugs were performed in the municipality in the mid-1940s and established the basis for control of the disease.11,12 The control programme in Bambuí can be summarized in three phases: the first comprised routine spraying of poor dwellings (1945–1948 and 1950);13 the second consisted of extensive spraying of rural and urban dwellings (1956–1958 and 1969–1970) and in 1964 selective spraying in the rural area;14,15 and the last phase was initiated in 1974 and involved continuous surveillance in both rural and urban areas, including periodic examinations of houses to detect residual foci of domestic vector and spraying of infested dwellings.15 There is strong evidence of the effectiveness of this programme including: (1) a great reduction in the density of triatomine bugs and household infection indexes; (2) a decrease in the number of acute cases of Chagas' disease; (3) a decline in the prevalence of T. cruzi infection among children (<14 years) in the rural area; and (4) a lowering in the prevalence of infection among health service users aged 15–30 years with a cohort effect.15

We present here the prevalence of T. cruzi infection in the town of Bambuí 50 years after the beginning of the control programme. The consequences of T. cruzi infection were assessed for elderly participants in the baseline of the Bambuí Health and Ageing Study (BHAS), which is a population-based cohort study of elderly living in the town.10 We investigated differences among seropositive and seronegative individuals in relation to selected indicators of health status and use of health services, considering several potential confounding factors in the analysis.


    Material and Methods
 Top
 Abstract
 Introduction
 Material and Methods
 Results
 Discussion
 References
 
Study area
The municipality comprises 20 573 inhabitants, 73% of those living in the urban area (Bambuí town). Life expectancy in the community was 70.2 years and 75% of deaths were of people aged 50+ years in 1990–1991.10 The main causes of death for the population in this municipality in 1996 were stroke (ICD-10: 160-169), Chagas' disease (ICD-10: B57), ischaemic heart disease (ICD-10: I20–I25), and pulmonary chronic obstructive disease (ICD-10: J43, J44) (death rates = 110.0, 61.4, 42.5 and 18.9 per 100 000, respectively).16

Study population
A complete census was carried out in Bambuí town in November and December 1996 to identify elderly (aged 60+) participants for the baseline of the BHA cohort study. All residents aged 60+ years were selected for interview, physical measurements and blood tests.10

A cross-sectional study of younger individuals was also carried out to compare the characteristics of the elderly measured in the baseline survey with those observed in younger residents. The census for identification of younger participants was carried out between October and November 1994. A non-replaceable simple probabilistic sample of those aged 5–59 (1458/12 429) was selected for a short interview, physical examination and blood tests in this study. Assumptions for the sample size calculations were: prevalence of the characteristic = 0.50, type I error = 0.05, precision = 0.03 and losses = 0.20.

Data collection, physical measurements and blood tests
The baseline interview consisted of questions on: (1) sociodemographic characteristics (age, gender, place of birth, marital status, number of years of schooling, monthly family income); (2) history of medical diagnosis (A doctor has ever said you had: Chagas' disease, coronary heart disease—angina pectoris or myocardial infarction, or any other chronic condition); (3) selected indicators of social support (satisfaction with social network, satisfaction with free-time arrangements, presence of an informal caregiver); (4) lifestyle (frequency of alcohol consumption in any amount in past 12 months, current smoking status); (5) selected health status and use of health services indicators (self-rated health in past 6 months, being unable to perform routine activities because of a health problem in past 2 weeks, staying in bed in past 2 weeks, visits to doctor in past 12 months, hospitalizations in past 12 months, use of prescribed and non-prescribed medications in past 3 months). Further details are described elsewhere.10

Neither interviewer nor interviewee knew the results of any examination or blood test results at the time of the interview. A proxy respondent was used when a respondent was unable to participate because of cognitive deficit or for some other health-related reason.17 Proxy respondents were not asked questions requiring personal judgement, such as psychosocial well-being, self-rated health and previous knowledge about T. cruzi infection. Ten per cent of participants were selected for re-interview.10

Blood pressure measurements were obtained 30 or more minutes after last caffeine intake or cigarette smoked. Three measures were taken after 5 minutes of initial rest with 2-minute intervals between them.18 Blood pressure was considered as the arithmetic mean of the second and third measurements. The nutritional indicator used was body mass index (weight/height squared). All measurements were performed in our outpatient clinic in Bambuí by trained health technicians, using standard equipment (sphygmomanometer: Tyco's 5097–30, USA; stethoscope: Littman's Cardiology II, USA; anthropometric measurement: CMS Weighing Equipment Ltd, UK).

Serum samples were investigated for anti-T. cruzi antibodies by indirect haemagglutination (IHA) and enzyme-linked immunobsorbent assays (ELISA) (Biolab and Abbott Laboratories, Brazil, respectively). Seropositivity was defined when the serum samples showed positive results in the two serological tests performed.19 Blood tests also included biochemical analysis for total cholesterol, low density lipoprotein (LDL) cholesterol and blood glucose, using an automated analyser (Eclipse Vitablab, Merck, Netherlands).10

Interviews, physical measurements, blood sample collection and serological tests were performed between October 1996 and August 1997. A free and signed informed consent was obtained from all participants.10

Data analysis
The Kappa statistic was used to assess the reliability of the two serological tests. Crude analysis of factors associated with seropositivity for T. cruzi was based on the Wilcoxon rank test (for medians), and on Pearson {chi}2 or {chi}2 test for linear trend (for proportions).20 Multivariate logistic regression21 was used to assess the independent association between seropositivity or previous knowledge of infection and each of the seven variables regarded as measures of the burden of infection in this study. Multivariate logistic models included all variables associated with seropositivity beyond the 0.20 significance level in the univariate analysis.22 Age, gender and need of a proxy respondent were included in the logistic model independently of the significance level. When two variables were highly associated, such as years of schooling and monthly family income, as well as diastolic and systolic blood pressure, only the one strongly related with seropositivity was included in the models. The analysis was carried out using the Stata statistical software.23


    Results
 Top
 Abstract
 Introduction
 Material and Methods
 Results
 Discussion
 References
 
Of 1742 residents aged 60+, 1496 (85.9%) participated in this study. Among 1458 residents aged 5–59 years, 1212 (83.1%) participated. Fifteen participants were classified as borderline for T. cruzi infection (only one out of two serological tests was positive) and excluded from the analysis. The agreement between the two serological tests used was very high (Kappa statistic = 0.983).

The overall seropositivity for T. cruzi was 22.8% (617/2711). Prevalence of the infection was high among older participants (316/564 = 35.9%, 185/280 = 39.8% and 62/90 = 40.8% among those aged 60–69, 70–79 and 80+ years, respectively). For younger individuals the corresponding results were: 0/438 = 0.0% (95% CI : 0.0–1.1); 3/216 = 1.4% (95% CI : 0.4–4.3); 2/227 = 0.9% (95% CI : 0.2–3.5); 12/184 = 6.5% (95% CI : 3.6–11.4) and 37/147 = 25.2% (95% CI : 18.6–33.1) for those aged <20, 20–29, 30–39, 40–49 and 50–59 years, respectively. Among males, the highest level was found for those aged 70–79 years (33.3%) and among females for those aged 80+ (47.8%) (Figure 1Go).



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Figure 1 Prevalence of Trypanosoma cruzi infection according to age and gender

 
Table 1Go shows the distribution of socio-demographic characteristics of the elderly, according to seropositivity for T. cruzi. Seropositivity was significantly associated with age, gender, marital status, years of schooling and monthly family income.


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Table 1 Distribution of socio-demographic characteristics among older adults, according to seropositivity for Trypanosoma cruzi (Bambuí, Brazil)
 
Median systolic and diastolic blood pressure, and median body mass index were significantly smaller among seropositive cases in comparison with seronegative cases. History of any other chronic condition was less frequent among seropositive individuals. No significant differences between seropositive and seronegative cases were found for history of coronary heart disease, median total cholesterol, LDL cholesterol or blood glucose (Table 2Go).


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Table 2 Distribution of history of selected non-infectious chronic diseases and other chronic conditions among older adults, according to seropositivity for Trypanosoma cruzi (Bambuí, Brazil)
 
There was no significant difference between seroposive and seronegative individuals with regard to satisfaction with social network (P = 0.524), satisfaction with free-time arrangements (P = 0.573), existence of an informal caregiver (P = 0.413), current smoking status (P = 0.356), frequency of alcoholic consumption in past 12 months (P = 0.362) and necessity of a proxy respondent during the interview (P = 0.126).

The association of selected indicators of health status and use of health services with seropositivity for T. cruzi is presented in Table 3Go. After adjustment for potential counfounders, self-rated health in past 6 months, staying in bed in past 2 weeks, higher number of prescribed medications in past 3 months and hospitalization in past 12 months were found to be associated with seropositivity for T. cruzi.


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Table 3 Association of selected indicators of health status and use of health services among older adults, according to seropositivity for Trypanosoma cruzi (Bambuí, Brazil)
 
At the time of the interview, 61.5% (324/527) of positive cases knew about their infection status and 96.7% (859/888) of negative cases reported themselves as being uninfected. Table 4Go shows the variables significantly associated with previous knowledge of T. cruzi infection among seropositive individuals. Report of previous knowledge of infection was strongly associated with: worse self-rated health in past 6 months, use of higher number of prescribed medications in past 3 months, and greater number of visits to the doctor in past 12 months. Being unable to perform routine activities because of health problem in past 2 weeks (P = 0.060), staying in bed in past 2 weeks (P = 0.133), number of non-prescribed medications in past 3 months (P = 0.686), and hospitalization in past 12 months (P = 0.056) were not significantly associated with reported previous knowledge of the infection.


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Table 4 Selected indicators of health status, use of health services among older adults significantly associated with previous knowledge of Trypanosoma cruzi infection among seropositive individuals (Bambuí, Brazil)
 

    Discussion
 Top
 Abstract
 Introduction
 Material and Methods
 Results
 Discussion
 References
 
Our results show that the elderly had the highest seropositivity for T. cruzi in the study community with a cohort effect. There were no positive cases among those below 20 years of age (born after 1977), suggesting that the interruption of T. cruzi transmission occurred around 20 years ago.

Prevalence of T. cruzi seropositivity was higher among elderly women in comparison with men. Seroprevalence was reasonably similar between younger males and females. Higher prevalence of infection among women aged 60+ years could be explained by their higher exposure to infection in the past, by differences in survival or by a combination of these factors. The survival hypothesis is coherent with previous reports of higher mortality24 and higher prevalence25 or incidence3,26 of cardiac involvement among males in comparison with females infected by T. cruzi.

The indicators of the burden of the infection in this study comprised: inability to perform routine activities due to health problems, staying in bed, use of medications, visits to doctors, hospitalizations and self-rated health. The latter was considered as an indicator of the burden of infection because it has been found to be a consistent predictor of mortality among older adults across countries and cultures.2730 Adjusting variables included socio-demographic characteristics, history of selected diseases and presence of other health-related conditions (emphasizing cardiovascular diseases and associated risk factors, which are major causes of death in Bambuí and among Brazilian elderly),16,31 as well as social support indicators (which have been found to be associated with higher mortality among the elderly).32,33

We found an important burden from infection by T. cruzi for the elderly living in the study community. Of the indicators examined, perceived health as bad or very bad, staying in bed and use of prescribed medications appear to be the factors most strongly associated with T. cruzi seropositivity. An increased odds ratio for hospitalization was also found.

A high prevalence of cardiac involvement is expected among seropositive individuals,3,24,34 and so the burden of T. cruzi infection for the elderly could be partially explained by cardiac involvement and/or other symptoms associated with Chagas' disease. It is also possible that reported previous knowledge of T. cruzi seropositivity alone intensifies the burden of the infection. In our study, among positive cases, worse perception of health, higher number of visits to a doctor and higher number of prescribed medications were strongly associated with previous knowledge of T. cruzi infection. The magnitude of these associations was even stronger than that found when comparing seropositive with seronegative individuals. However, we cannot be sure whether the strong association found between these indicators and knowledge of the disease is due to Chagas' disease associated symptoms (once it is expected that those with symptoms are also more likely to know about their infection status), the effect of knowledge of infection per se or a combination of these factors. Further investigation is required to disentangle the effects of symptoms associated with Chagas' disease and reported previous knowledge of infection on health perception, visits to the doctor and medication use by the seropositive elderly.

Regarding methodological aspects, several steps were followed to minimize bias in this study: collecting information double-blind, assessing the reliability of data gathered, standardizing procedures and instruments, training of field-work and laboratory teams, and inclusion in data analysis of several potential confounding variables. Nevertheless, one cannot be sure that the control for confounders was complete. Regarding internal validity, the elderly participants in the study were similar to the total Bambuí's town population aged 60+ in relation to age, gender, marital status, monthly family income and years of schooling. Similar figures were found for the younger participants.10 The sensitivity and specificity of the serological tests used in this study varies from 82–100% to 83–100%,4 respectively, and so it is possible that some individuals may have been misclassified in relation to infection status. Since this misclassification is non-differential, it would reduce the magnitude of the associations found. In addition, because this is a cross-sectional study, our data are restricted to surviving cases living in the community. Assuming that mortality of infected individuals was higher and tended to occur earlier than that of non-infected individuals,3,20,21,34 our results underestimate the lifetime burden of infection in this community, i.e. the generation to which they belong has experienced worse consequences of infection than that observed among the surviving elderly.

In summary, our results show a cohort effect of T. cruzi seropositivity in the study community, with no cases below 20 years of age and highest prevalence among elderly individuals. An important burden associated with T. cruzi infection among the elderly was found regarding four indicators of worse health status and higher use of health services. To our knowledge, the evaluation of the long-lasting effect of past exposure to T. cruzi infection in relation to the above-mentioned indicators has never been investigated. Our results are an example of how survival of individuals with past exposure to infectious disease may lead to a different picture of ageing in the developing world. Policy makers need to consider the extra burden imposed by the increasing rates of non-infectious disease (as observed in Brazil and in Bambuí)16 as a result of the enduring consequences of T. cruzi infection when planning health actions in areas where the risk of infection was widespread in the past.


KEY MESSAGES

  • The elderly had the highest seropositivity for Trypanosoma cruzi in the study community with a cohort effect.
  • There were no positive cases among those below 20 years of age (born after 1977), suggesting that the interruption of T. cruzi infection occurred around 20 years ago.
  • An important burden associated with T. cruzi infection among the elderly was found regarding four indicators of worse health status and higher use of health services after adjustment for confounders.
  • The results of this study are an example of how survival of individuals with past exposure to infectious diseases may lead to a different picture of ageing in the developing world.

 


    Acknowledgments
 
This study was supported by the Financiadora de Estudos e Projetos (FINEP), Brazil. Maria FF Lima e Costa, SM Barreto and E Uchoa, are fellows of the Brazilian Research Council (CNPq). This study could not be carried out without the co-operation of the Bambuí population.


    References
 Top
 Abstract
 Introduction
 Material and Methods
 Results
 Discussion
 References
 
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