Breyette Lorntz

Magnitude and Impact of Diarrheal Diseases

Among the increasingly unacceptable costs of the diseases of poverty are the largely unmeasured but potentially huge human and economic long-term costs of common tropical infectious diseases, especially those such as repeated dehydrating and malnourishing diarrheal diseases (and enteric infections, even without overt liquid stools) that are so prevalent in the developmentally critical first year or two of early childhood. We review here the high costs of diseases of poverty, increasing diarrhea morbidity (despite decreasing mortality), and new emerging evidence for long-term consequences of early childhood diarrhea on growth and on physical and cognitive development, effects that may translate into costly impairment of human potential and productivity.

Updating the DALYs for diarrhoeal disease

Estimates of global disease burden remain high on the international research and policy agenda as a forum for ranking health priorities. Within this, the quality of life or years lived with varying degrees of disability has been recognized as an important outcome that should be considered alongside estimates of mortality. Recent studies into the long-term consequences of diarrhoeal diseases on physical and mental development suggest that the disability adjusted life year calculations for these conditions could require updating.

Early childhood diarrhea predicts impaired school performance.

Objective: Diarrhea is a leading cause of mortality worldwide; however, its long-term morbidity is poorly understood. Recently, early childhood diarrhea (ECD) has been associated with impaired physical fitness, growth and cognitive function 6 to 9 years later. We studied the effects of ECD on school functioning in a shantytown in northeastern Brazil. Design: We administered 77 educational surveys. Complete diarrhea surveillance (ie, >90%) in the first 2 years of life and demographic and anthropometric information were available for 73 children. Age at starting school was calculated for 62 children, whereas age appropriateness for the current grade (AFG) was calculated for all 73 children who were >6 years old. Stepwise regression was used to examine the independent effect of ECD on school functioning after controlling for socioeconomic factors, maternal education, breast feeding, growth and cognitive functioning. Results: ECD correlated with age at starting school (r = 0.55, P = 0.0005) and remained a significant predictor even after controlling for family demographics, days of breast feeding, early growth and TONI-3 test of nonverbal intelligence. This was true despite significant correlations of ECD with growth shortfalls and impaired cognitive functioning. ECD also correlated with AFG (r = 0.38, P = 0.001). Only TONI-3 test scores explained this association, suggesting that ECD may hinder school performance, but only in part school readiness, by impairing cognitive function as measured by performance on the TONI-3 nonverbal intelligence test. Conclusions: These findings document effects of early childhood diarrhea on later school readiness and performance and hence potential long-term human and economic costs of ECD, which warrant further attention and far greater investment for the control of ECD and its consequences.

APOE4 Protects the Cognitive Development in Children with Heavy Diarrhea Burdens in Northeast Brazil

Polymorphisms in the apolipoprotein E (APOE) have constituted the major rationale to identify potential risk groups for developing late-onset Alzheimers disease and help to predict recovery of cognitive function after brain injury. However, the APOE impact on cognitive development in children living in poor areas of the developing world, where we have discovered profound significant associations of early childhood diarrhea (at 0–2 y) with lasting impairments of growth, cognition, and school performance, is not known. Therefore, we conducted APOE genotyping in 72 Brazilian shantytown children under active surveillance since birth, using purified DNA extracted from buccal cell samples. We found a high frequency of APOE4 alleles (18% versus 9–11% expected) in children with lower diarrhea burdens. When we examined the children who experienced the heavier diarrhea burdens (greater than or equal to the median of seven illnesses in the first 2 y of life), those with APOE4 did significantly better in the coding subtest (p = 0.01) when compared with APOE4-negative children with similar diarrhea burdens. Positive correlations between the APOE4 occurrence and coding scores remained, even after adjusting for family income, maternal education, and breast-feeding. Moreover, the APOE4-positive group, under heavy burdens of diarrhea, had preserved semantic fluency and the mean difference in fluency scores, p = 0.025, a standardized coefficient for disproportional verbal fluency impairment. Our findings show that APOE4 is relatively common in favela children and suggest a protective role of the APOE4 allele in children with a history of heavy burdens of diarrhea in their first 2 y of life.

Limitations in Verbal Fluency Following Heavy Burdens of Early Childhood Diarrhea in Brazilian Shantytown Children

The effects of heavy burdens of diarrhea in the first 2 years of life on specific executive control function like verbal fluency are not well understood. In previous studies, we have shown associations of early childhood diarrhea (ECD) with nonverbal intelligence and school functioning. Therefore, we postulated that ECD might affect early neuropsychological development leading to long-term deficits in normal cognitive development. Based on our extensive 14-year prospective cohort studies of early childhood diarrheal illnesses in a Brazilian shantytown community, we examined ECD correlations between specific impairments of higher mental function and executive skills in shantytown children 5–10 years later (now at 6–12) years of age. Specifically we examined whether heavy diarrheal illnesses correlate with reduced performance on selected tests of executive function. Our study, for the first time, suggests a disproportional impairment in semantic but not phonetic fluency in a subset of children with heavy burdens of diarrhea in their first 2 years of life even when controlling for maternal education, breastfeeding, and child schooling. Similar semantic decrements have been associated with impaired recovery from brain injury. These exploratory studies suggest the importance of verbal fluency tests to assess executive functioning in children challenged by poor nutrition and diarrhea in early life. In addition, our unique findings show the potential influences of early childhood diarrhea on language development that is so critical to productive adulthood and potentially set a foundation for new neuropsychological approaches, which assess early burdens of enteric illnesses on childhood development.