The Puerto Rico Alzheimer Disease Initiative (PRADI): A Multisource Ascertainment Approach.

INTRODUCTION: Puerto Ricans, the second largest Latino group in the continental US, are underrepresented in genomic studies of Alzheimer disease (AD). To increase representation of this group in genomic studies of AD, we developed a multisource ascertainment approach to enroll AD patients, and their family members living in Puerto Rico (PR) as part of the Alzheimer's Disease Sequencing Project (ADSP), an international effort to advance broader personalized/precision medicine initiatives for AD across all populations. METHODS: The Puerto Rico Alzheimer Disease Initiative (PRADI) multisource ascertainment approach was developed to recruit and enroll Puerto Rican adults aged 50 years and older for a genetic research study of AD, including individuals with cognitive decline (AD, mild cognitive impairment), their similarly, aged family members, and cognitively healthy unrelated individuals age 50 and up. Emphasizing identification and relationship building with key stakeholders, we conducted ascertainment across the island. In addition to reporting on PRADI ascertainment, we detail admixture analysis for our cohort by region, group differences in age of onset, cognitive level by region, and ascertainment source. RESULTS: We report on 674 individuals who met standard eligibility criteria [282 AD-affected participants (42% of the sample), 115 individuals with mild cognitive impairment (MCI) (17% of the sample), and 277 cognitively healthy individuals (41% of the sample)]. There are 43 possible multiplex families (10 families with 4 or more AD-affected members and 3 families with 3 AD-affected members). Most individuals in our cohort were ascertained from the Metro, Bayamón, and Caguas health regions. Across health regions, we found differences in ancestral backgrounds, and select clinical traits. DISCUSSION: The multisource ascertainment approach used in the PRADI study highlights the importance of enlisting a broad range of community resources and providers. Preliminary results provide important information about our cohort that will be useful as we move forward with ascertainment. We expect that results from the PRADI study will lead to a better understanding of genetic risk for AD among this population.

Ancestral origin of ApoE ε4 Alzheimer disease risk in Puerto Rican and African American populations.

The ApoE ε4 allele is the most significant genetic risk factor for late-onset Alzheimer disease. The risk conferred by ε4, however, differs across populations, with populations of African ancestry showing lower ε4 risk compared to those of European or Asian ancestry. The cause of this heterogeneity in risk effect is currently unknown; it may be due to environmental or cultural factors correlated with ancestry, or it may be due to genetic variation local to the ApoE region that differs among populations. Exploring these hypotheses may lead to novel, population-specific therapeutics and risk predictions. To test these hypotheses, we analyzed ApoE genotypes and genome-wide array data in individuals from African American and Puerto Rican populations. A total of 1,766 African American and 220 Puerto Rican individuals with late-onset Alzheimer disease, and 3,730 African American and 169 Puerto Rican cognitively healthy individuals (> 65 years) participated in the study. We first assessed average ancestry across the genome ("global" ancestry) and then tested it for interaction with ApoE genotypes. Next, we assessed the ancestral background of ApoE alleles ("local" ancestry) and tested if ancestry local to ApoE influenced Alzheimer disease risk while controlling for global ancestry. Measures of global ancestry showed no interaction with ApoE risk (Puerto Rican: p-value = 0.49; African American: p-value = 0.65). Conversely, ancestry local to the ApoE region showed an interaction with the ApoE ε4 allele in both populations (Puerto Rican: p-value = 0.019; African American: p-value = 0.005). ApoE ε4 alleles on an African background conferred a lower risk than those with a European ancestral background, regardless of population (Puerto Rican: OR = 1.26 on African background, OR = 4.49 on European; African American: OR = 2.34 on African background, OR = 3.05 on European background). Factors contributing to the lower risk effect in the ApoE gene ε4 allele are likely due to ancestry-specific genetic factors near ApoE rather than non-genetic ethnic, cultural, and environmental factors.

Measuring User Compliance and Cost Effectiveness of Safe Drinking Water Programs: A Cluster-Randomized Study of Household Ultraviolet Disinfection in Rural Mexico.

Low adoption and compliance levels for household water treatment and safe storage (HWTS) technologies have made it challenging for these systems to achieve measurable health benefits in the developing world. User compliance remains an inconsistently defined and poorly understood feature of HWTS programs. In this article, we develop a comprehensive approach to understanding HWTS compliance. First, our Safe Drinking Water Compliance Framework disaggregates and measures the components of compliance from initial adoption of the HWTS to exclusive consumption of treated water. We apply this framework to an ultraviolet (UV)-based safe water system in a cluster-randomized controlled trial in rural Mexico. Second, we evaluate a no-frills (or "Basic") variant of the program as well as an improved (or "Enhanced") variant, to test if subtle changes in the user interface of HWTS programs could improve compliance. Finally, we perform a full-cost analysis of both variants to assess their cost effectiveness (CE) in achieving compliance. We define "compliance" strictly as the habit of consuming safe water. We find that compliance was significantly higher in the groups where the UV program variants were rolled out than in the control groups. The Enhanced variant performed better immediately postintervention than the Basic, but compliance (and thus CE) degraded with time such that no effective difference remained between the two versions of the program.

Water quality effects of intermittent water supply in Arraiján, Panama.

Intermittent drinking water supply is common in low- and middle-income countries throughout the world and can cause water quality to degrade in the distribution system. In this study, we characterized water quality in one study zone with continuous supply and three zones with intermittent supply in the drinking water distribution network in Arraiján, Panama. Low or zero pressures occurred in all zones, and negative pressures occurred in the continuous zone and two of the intermittent zones. Despite hydraulic conditions that created risks for backflow and contaminant intrusion, only four of 423 (0.9%) grab samples collected at random times were positive for total coliform bacteria and only one was positive for E. coli. Only nine of 496 (1.8%) samples had turbidity >1.0 NTU and all samples had ≥0.2 mg/L free chlorine residual. In contrast, water quality was often degraded during the first-flush period (when supply first returned after an outage). Still, routine and first-flush water quality under intermittent supply was much better in Arraiján than that reported in a previous study conducted in India. Better water quality in Arraiján could be due to better water quality leaving the treatment plant, shorter supply outages, higher supply pressures, a more consistent and higher chlorine residual, and fewer contaminant sources near pipes. The results illustrate that intermittent supply and its effects on water quality can vary greatly between and within distribution networks. The study also demonstrated that monitoring techniques designed specifically for intermittent supply, such as continuous pressure monitoring and sampling the first flush, can detect water quality threats and degradation that would not likely be detected with conventional monitoring.

Field efficacy evaluation and post-treatment contamination risk assessment of an ultraviolet disinfection and safe storage system.

Inconsistent use of household water treatment and safe storage (HWTS) systems reduces their potential health benefits. Ultraviolet (UV) disinfection is more convenient than some existing HWTS systems, but it does not provide post-treatment residual disinfectant, which could leave drinking water vulnerable to recontamination. In this paper, using as-treated analyses, we report on the field efficacy of a UV disinfection system at improving household drinking water quality in rural Mexico. We further assess the risk of post-treatment contamination from the UV system, and develop a process-based model to better understand household risk factors for recontamination. This study was part of a larger cluster-randomized stepped wedge trial, and the results complement previously published population-level results of the intervention on diarrheal prevalence and water quality. Based on the presence of Escherichia coli (proportion of households with ≥ 1 E. coli/100 mL), we estimated a risk difference of -28.0% (95% confidence interval (CI): -33.9%, -22.1%) when comparing intervention to control households; -38.6% (CI: -48.9%, -28.2%) when comparing post- and pre-intervention results; and -37.1% (CI: -45.2%, -28.9%) when comparing UV disinfected water to alternatives within the household. We found substantial increases in post-treatment E. coli contamination when comparing samples from the UV system effluent (5.0%) to samples taken from the storage container (21.1%) and drinking glasses (26.0%). We found that improved household infrastructure, additional extractions from the storage container, additional time from when the storage container was filled, and increased experience of the UV system operator were associated with reductions in post-treatment contamination. Our results suggest that the UV system is efficacious at improving household water quality when used as intended. Promoting safe storage habits is essential for an effective UV system dissemination. The drinking glass appears to represent a small but significant source of recontamination that is likely to impact all HWTS systems.

A stepped wedge, cluster-randomized trial of a household UV-disinfection and safe storage drinking water intervention in rural Baja California Sur, Mexico.

In collaboration with a local non-profit organization, this study evaluated the expansion of a program that promoted and installed Mesita Azul, an ultraviolet-disinfection system designed to treat household drinking water in rural Mexico. We conducted a 15-month, cluster-randomized stepped wedge trial by randomizing the order in which 24 communities (444 households) received the intervention. We measured primary outcomes (water contamination and diarrhea) during seven household visits. The intervention increased the percentage of households with access to treated and safely stored drinking water (23-62%), and reduced the percentage of households with Escherichia coli contaminated drinking water (risk difference (RD): -19% [95% CI: -27%, -14%]). No significant reduction in diarrhea was observed (RD: -0.1% [95% CI: -1.1%, 0.9%]). We conclude that household water quality improvements measured in this study justify future promotion of the Mesita Azul, and that future studies to measure its health impact would be valuable if conducted in populations with higher diarrhea prevalence.

Comparison of enterovirus and adenovirus concentration and enumeration methods in seawater from Southern California, USA and Baja Malibu, Mexico.

Despite being important etiological agents of waterborne illness, the sources, transport and decay of human viruses in recreational waters are not well understood. This study examines enterovirus and adenovirus concentrations in coastal water samples collected from four beaches impacted by microbial pollution: (1) Malibu Lagoon, Malibu; (2) Tijuana River, Imperial Beach; (3) Baja Malibu, Baja California; and (4) Punta Bandera, Baja California. Water samples were concentrated using a flocculation-based skim milk method and dead-end membrane filtration (MF). Viruses were enumerated using cell culture infectivity assays and reverse transcription quantitative polymerase chain reaction (RT-QPCR). Across concentration and quantification methods, enteroviruses were detected more often than adenoviruses. For both viruses, MF followed by (RT)QPCR yielded higher concentrations than skim milk flocculation followed by (RT)QPCR or cell culture assays. Samples concentrated by skim milk flocculation and enumerated by (RT)QPCR agreed more closely with concentrations enumerated by cell culture assays than MF followed by (RT)QPCR. The detection of viruses by MF and (RT)QPCR was positively correlated with the presence of infectious viruses. Further research is needed to determine if detection of viruses by rapid methods such as (RT)QPCR can be a useful water quality monitoring tool to assess health risks in recreational waters.

Rethinking indicators of microbial drinking water quality for health studies in tropical developing countries: case study in northern coastal Ecuador.

To address the problem of the health impacts of unsafe drinking water, methods are needed to assess microbiologic contamination in water. However, indicators of water quality have provided mixed results. We evaluate five assays (three for Escherichia coli and one each for enterococci and somatic coliphage) of microbial contamination in villages in rural Ecuador that rely mostly on untreated drinking water. Only membrane filtration for E. coli using mI agar detected a significant association with household diarrheal disease outcome (odds ratio = 1.29, 95% confidence interval = 1.02-1.65 in household containers and odds ratio = 1.18, 95% confidence interval = 1.02-1.37) in source samples. Our analysis and other published research points to the need for further consideration of study design factors, such as sample size and variability in measurements, when using indicator organisms, especially when relating water quality exposure to health outcomes. Although indicator organisms are used extensively in health studies, we argue that their use requires a full understanding of their purposes and limitations.

Drivers of water quality variability in northern coastal Ecuador.

Microbiological safety of water is commonly measured using indicator organisms, but the spatiotemporal variability of these indicators can make interpretation of data difficult. Here, we systematically explore the variability in Escherichia coil concentrations in surface source and household drinking water in a rural Ecuadorian village over one year. We observed more variability in water quality on an hourly basis (up to 2.4 log difference) than on a daily (2.2 log difference) or weekly basis (up to 1.8 log difference). E. coli counts were higher in the wet season than in the dry season for source (0.42 log difference, p < 0.0001) and household (0.11 log difference, p = 0.077) samples. In the wet season, a 1 cm increase in weekly rainfall was associated with a 3% decrease (p = 0.006) in E. coli counts in source samples and a 6% decrease (p = 0.012) in household samples. Each additional person in the river when source samples were collected was associated with a 4% increase (p = 0.026) in E. coil counts in the wet season. Factors affecting household water quality included rainfall, water source, and covering the container. The variability can be understood as a combination of environmental (e.g., seasonal and soil processes) and other drivers (e.g., human river use, water practices, and sanitation), each working at different time scales.

Following the water: a controlled study of drinking water storage in northern coastal Ecuador.

BACKGROUND: To design the most appropriate interventions to improve water quality and supply, information is needed to assess water contamination in a variety of community settings, including those that rely primarily on unimproved surface sources of drinking water. OBJECTIVES: We explored the role of initial source water conditions as well as household factors in determining household water quality, and how levels of contamination of drinking water change over time, in a rural setting in northern coastal Ecuador. METHODS: We sampled source waters concurrently with water collection by household members and followed this water over time, comparing Escherichia coli and enterococci concentrations in water stored in households with water stored under controlled conditions. RESULTS: We observed significant natural attenuation of indicator organisms in control containers and significant, although less pronounced, reductions of indicators between the source of drinking water and its point of use through the third day of sampling. These reductions were followed by recontamination in approximately half of the households. CONCLUSIONS: Water quality improved after water was transferred from the source to household storage containers, but then declined because of recontamination in the home. Our experimental design allowed us to observe these dynamics by controlling for initial source water quality and following changes in water quality over time. These data, because of our controlled experimental design, may explain why recontamination has been reported in the literature as less prominent in areas or households with highly contaminated source waters. Our results also suggest that efforts to improve source water quality and sanitation remain important.

Sludge accumulation, characteristics, and pathogen inactivation in four primary waste stabilization ponds in central Mexico.

To support the development of safe and feasible sludge management strategies, the accumulation rates of sludge and its characteristics were studied in four primary wastewater stabilization ponds (WSPs) in central Mexico (three facultative and one anaerobic). The accumulation rates and distribution of sludge were determined by measuring the thickness of the sludge layer at 8-40 locations throughout each pond. The average, per capita sludge accumulation rates ranged from 0.021 to 0.036m(3)/person/yr. In the anaerobic pond the sludge distribution was uniform throughout the pond, whereas in the three facultative ponds most of the sludge accumulated directly in front of the inlet. To measure the horizontal and vertical variation in the sludge characteristics, sludge cores were collected from 3 to 7 locations in three of the ponds. Each core was divided into 4 sub-samples in which various physical, chemical, and microbiological parameters were measured. In addition, the inactivation of several pathogen indicator organisms was studied in a batch of sludge for 7 months. Based on the microbiological results, it is concluded that reasonable estimates of the inactivation of fecal coliform bacteria, fecal enterococci, F+ coliphage, somatic coliphage, and Ascaris eggs in WSP sludge in central Mexico can be made using first-order rate constants of 0.1, 0.1, 0.01, 0.001, and 0.001d(-1), respectively. From the observed changes in the concentrations of total solids and the volatile to fixed solids ratio, empirical equations were developed to describe anaerobic degradation and compression, which are the two most important processes affecting the volume of sludge after its deposition.