The most interesting finding in our data was consistent blunting of cardiovascular autonomic responses in T. cruzi
-infected children compared with their matched controls. Ours are the first such data for children with chronic T. cruzi
infection, but similar findings have been reported in infected adults.13–15,31
Because the absolute differences in performance on the autonomic tests between groups were small and all children were well, we cannot interpret the clinical significance of this finding. Pathological studies of Chagas disease show marked parasympathetic denervation, both in human autopsy specimens and animal models.32
The neuronal damage is thought to occur during the acute phase of the infection and is presumed to be permanent.12
The occurrence of autonomic dysfunction in children as well as adults is consistent with this hypothesis. What is less clear is how autonomic dysfunction relates to the pathogenesis of Chagas cardiomyopathy.12,19
Some investigators postulate that these are independent phenomena.17
Because this study was not longitudinal in design and none of our subjects had any evidence of clinically significant cardiac dysfunction, we could not draw any conclusions about the relationship between autonomic abnormalities and the development of Chagas cardiomyopathy. Although we found no association between autonomic test results and EKG findings, we found few EKG abnormalities and may have lacked the statistical power to detect such an association.
In contrast to earlier studies showing a substantial prevalence of conduction system disease in infected children in highly affected areas,8,9
we found no significant difference in the prevalence of EKG abnormalities between seropositive and seronegative children. Indeed, we found a low frequency of the conduction system abnormalities (right bundle branch block and left anterior hemiblock) and ventricular arrhythmias typical of Chagas disease in our case children. This finding may reflect lower intensity of parasite exposure, lower parasite burdens, and/or strain differences in Arequipa compared with other study sites. The lower infection prevalence in Arequipa suggests a lower force of infection compared with study sites in Brazil, Argentina, or Bolivia,33–36
whereas the relatively flat age prevalence curve supports the hypothesis that the parasite was only introduced into the periurban communities of Arequipa in the early 1990s.26
Investigators have shown that repeated infection increases cardiac pathology in animal models37,38
and have suggested that vector control, by decreasing reinfection rates, may be responsible for the milder disease now seen in formerly endemic communities.39
Similarly, the children in our study may have had few repeated infections after their initial exposure. Another hypothesis, not mutually exclusive, is that the T. cruzi
strain in Arequipa is less virulent than strains found in other parts of South America. Our previous work shows that the immunological responses to whole epimastigote lysate and recombinant antigens are substantially lower than in specimens from Bolivia.40
The risk factors that we identified for urban transmission of Chagas disease were quite similar to those found in rural epidemiological studies.20,22,41
Not surprisingly, household members' reports of triatomine infestation as well as traces of triatomine exuvia or feces in the child's room were very strong predictors of infection. However, household infestation rates based on bugs collected by the Ministry of Health spray teams were not strongly associated with the child's risk of infection. Heavy infestation was associated with increased risk in studies in Argentina, and vector density was shown previously to be an independent risk factor for infection in children in Guadalupe (one community within the current study area).25,41
Reports from families and the presence of triatomine exuviae and feces may preferentially indicate heavier infestations, which more strongly elevate the risk of T. cruzi
infection. Other risk factors for T. cruzi
infection in the child included the reported presence of Chagas disease in a relative or household member, a factor that could reflect both shared exposures and the possible role of the infected household member as a reservoir of the parasite.
In studies from Argentina, the presence of dogs was strongly associated with infection risk.20–24
In our data, the presence of a dog per se did not significantly increase risk of infection; the majority of households owned dogs. However, allowing an animal to sleep in the child's bedroom was associated with significantly increased T. cruzi
risk; this factor was associated with increased bedroom vector infestation in our earlier analysis.25
Building materials, in particular those used in the child's room, also altered the risk of T. cruzi
. In Arequipa, most shantytown homes are built of basalt stones, brick, or sillar that are either stacked or held together with cement and corrugated metal or brick roofs. Cracks in the walls and unmortared bricks increased risk, whereas plastering the walls and ceiling with stucco was protective, presumably by decreasing triatomine hiding places and eliminating crevices protected from insecticide application.25,42
Our study had a number of limitations. Risk factor studies for T. cruzi suffer unavoidably from the chronic character of this infection: the factors measured now may not indicate the situation 5 or 10 years ago when children were initially infected. The youngest study children were not always able to perform some of the autonomic tests, particularly, deep breathing and Valsalva maneuver, exactly to directions; the Valsalva maneuver might also have been better standardized if a pressure gauge mouthpiece had been available. Most tests were done in the afternoon after school, but a proportion was performed in the morning, introducing the possibility of diurnal variation and differences in food and caffeine intake, which may have affected hemodynamic measures and autonomic responsiveness. Furthermore, there are few data describing autonomic function in healthy children, and normal limits have never been defined; our study may be the largest pediatric group with autonomic testing reported to date. Finally, our data are cross-sectional and therefore, cannot address the question of the prognostic value of autonomic dysfunction to predict the development of cardiomyopathy.
Our risk factor data highlight the importance of household insecticide application programs to interrupt domestic vector-borne transmission of T. cruzi
. Long-term success will require surveillance for and effective responses to reinfestation.43
Meanwhile, advice to keep animals from sleeping in bedrooms and appropriate location-specific housing improvements may help to decrease infestation and infection risk. Targeted screening strategies may improve the efficiency of programs to detect infected children and facilitate early treatment.27
Antitrypanosomal drug treatment is indicated for all T. cruzi
infected individuals younger than 18 years, with a recent trend to treat adults as well,44,45
introducing important ethical considerations when considering the possibility of longitudinal cohort studies to investigate the prognostic value of autonomic dysfunction to predict development or progression of cardiomyopathy.