PESTICIDE EXPOSURE AND END-STAGE RENAL DISEASE AMONG PESTICIDE APPLICATORS AND THEIR SPOUSES IN THE AGRICULTURAL HEALTH STUDY

Experimental studies suggest a relationship between pesticide exposure and renal impairment, but epidemiological research on the long-term effects of chronic low-level and acute pesticide exposure on renal disease risk is limited. This study investigated the relationship between end-stage renal disease (ESRD) risk and 1) long-term use of and exposure to specific pesticides; 2) short-term high-level pesticide exposures; and 3) farming and household factors that may increase exposure to pesticides, among male licensed pesticide applicators (N=55,580) and their wives (N=32,099) in the Agricultural Health Study (AHS). AHS participants reported pesticide use and exposure via self-administered questionnaires at enrollment (1993-1997). Associations between ESRD and pesticide exposures were estimated with Cox proportional hazard regression models controlling for age at enrollment, state of enrollment (applicator analyses only), and personal use of any pesticide (wives analyses only). ESRD cases were identified via linkage to the United States Renal Data System (USRDS). Standardized incidence ratios (SIRs) were calculated to compare ESRD incidence rates in the AHS cohort to the general population. We identified 320 and 103 ESRD cases diagnosed between enrollment and 31 December 2011 among pesticide applicators and wives, respectively. Among applicators, ESRD risk was elevated with use of the fungicide metalaxyl, and the herbicides imazethapyr, paraquat, and petroleum oil, with positive exposure-response trends observed for paraquat, pendimethalin, and the insecticide chlordane. Medical visits due to pesticide use were associated with ESRD. Among wives who never applied pesticides, ESRD risk was significantly associated with husbands' ever use of paraquat and butylate, with a positive exposure-response trend observed for husband's cumulative use of these pesticides. Positive associations were observed with private well proximity to pesticide mixing areas, washing pesticide-exposed clothing with the family wash, and spending >10 hours in the sun during the growing season, though estimates were imprecise. ESRD incidence rates were lower among applicators and wives compared to the general population. Our findings support a possible association between ESRD risk and chronic exposure (both direct and indirect) to certain pesticides and suggest that pesticide exposures resulting in medical visits may increase the risk of incident ESRD.Doctor of Philosoph

Experimental Adaptation of a Free-Living Bacterium to the Zebrafish Digestive Tract

Animals have coexisted with an omnipresent and diverse array of bacteria for the entirety of their evolutionary history. As a result, symbioses between animals and bacteria are ubiquitous and can range from mutualism to parasitism. In particular, countless studies have demonstrated the pivotal role that bacteria residing in animal digestive tracts can play in determining animal health and well-being. However, it is still unknown how bacteria evolve the ability colonize animals. Due to the dramatic impacts that animals and bacteria can have on one another’s fitness, it is imperative to understand how symbioses between bacteria and their animal hosts originate. Therefore, to elucidate how bacteria evolve novel associations with vertebrate hosts, I serially passaged six replicate populations of a bacterial species with no prior known host associations (Shewanella oneidensis) through the digestive tracts of a model vertebrate, zebrafish (Danio rerio). After 20 passages through the digestive tracts of groups of larval zebrafish that were derived bacteria free (amounting to approximately 200 bacterial generations), I observed that all six replicate populations evolved to outcompete their unpassaged ancestor in terms of their ability to colonize larval guts. I subsequently sequenced the genomes of four evolved S. oneidensis isolates from each replicate population and found that their competitive advantage stemmed from two distinct classes of mutations that occurred in a mannose sensitive hemagglutinin pilus operon as well as in genes with putative diguanylate cyclase and phosphodiesterase domains. Both types of mutations enhanced bacterial motility, which was associated with increased representation in the aqueous portion of my experimental system and more efficient per capita immigration into zebrafish guts relative to the ancestral S. oneidensis reference strain. These increases in motility, were consistent with the behavior of a closely-related Shewanella species (Shewanella sp. ZOR0012) that has recently been isolated from the zebrafish digestive tract implying that my evolved isolates may be pursuing a similar adaptive trajectory to the one taken by this host-associated species. My results suggest that a non-host-associated microorganism can rapidly improve its ability to colonize hosts, and this study is the first to capture the early adaptive steps necessary to facilitate this transition

Evaluations of Structural Interventions for HIV Prevention: A Review of Approaches and Methods

Structural interventions alter the social, economic, legal, political, and built environments that underlie processes affecting population health. We conducted a systematic review of evaluations of structural interventions for HIV prevention in low- and middle-income countries (LMICs) to better understand methodological and other challenges and identify effective evaluation strategies. We included 27 peer-reviewed articles on interventions related to economic empowerment, education, and substance abuse in LMICs. Twenty-one evaluations included clearly articulated theories of change (TOCs); 14 of these assessed the TOC by measuring intermediary variables in the causal pathway between the intervention and HIV outcomes. Although structural interventions address complex interactions, no evaluation included methods designed to evaluate complex systems. To strengthen evaluations of structural interventions, we recommend clearly articulating a TOC and measuring intermediate variables between the predictor and outcome. We additionally recommend adapting study designs and analytic methods outside traditional epidemiology to better capture complex results, influences external to the intervention, and unintended consequences

Pesticide use and risk of end-stage renal disease among licensed pesticide applicators in the Agricultural Health Study

Experimental studies suggest a relationship between pesticide exposure and renal impairment, but epidemiological evidence is limited. We evaluated the association between exposure to 41 specific pesticides and end-stage renal disease (ESRD) incidence in the Agricultural Health Study (AHS), a prospective cohort study of licensed pesticide applicators in Iowa and North Carolina

Knowledge integration in One Health policy formulation, implementation and evaluation

The One Health concept covers the interrelationship between human, animal and environmental health and requires multistakeholder collaboration across many cultural, disciplinary, institutional and sectoral boundaries. Yet, the implementation of the One Health approach appears hampered by shortcomings in the global framework for health governance. Knowledge integration approaches, at all stages of policy development, could help to address these shortcomings. The identification of key objectives, the resolving of trade-offs and the creation of a common vision and a common direction can be supported by multicriteria analyses. Evidence-based decision-making and transformation of observations into narratives detailing how situations emerge and might unfold in the future can be achieved by systems thinking. Finally, transdisciplinary approaches can be used both to improve the effectiveness of existing systems and to develop novel networks for collective action. To strengthen One Health governance, we propose that knowledge integration becomes a key feature of all stages in the development of related policies. We suggest several ways in which such integration could be promoted

Review: Evidence of Neurological Sequelae in Children With Acquired Zika Virus Infection

Limited information is available on health outcomes related to Zika virus infection acquired during childhood. Zika virus can cause severe central nervous system malformations in congenitally exposed fetuses and neonates. In vitro studies show the capacity of Zika virus to infect neural progenitor cells, induce central and peripheral neuronal cell deaths, and target different brain cells over the course of brain development. Studies of postnatally infected mice and nonhuman primates have detected degradation of neural cells and morphologic brain cell changes consistent with a broad neuroinflammatory response. In addition, case reports of central nervous system disease in adults and in adolescents secondary to Zika virus infection suggest that Zika virus may have a broader impact on neurological health beyond that observed in congenitally exposed newborns. Long-term neurological complications have been observed with other acquired flaviviral infections, with clinical symptoms manifesting for years after primary infection. The extent to which postnatal Zika virus infection in humans negatively affects the central and peripheral nervous systems and causes long-term neurological damage or cognitive effects is currently unknown. To better understand the potential for neurological sequelae associated with acquired Zika virus infection in children, we reviewed the biological, clinical, and epidemiologic literature and summarized the evidence for this link. First, we review biological mechanisms for neurological manifestations of Zika virus infection in experimental studies. Second, we review observational studies of congenital Zika virus infection and case studies and surveillance reports of neurological sequelae of Zika virus infection in adults and in children. Lastly, we discuss the challenges of conducting Zika virus-neurological sequela studies and future directions for pediatric Zika virus research

Implementing early infant diagnosis of HIV infection at the primary care level: experiences and challenges in Malawi

Malawi’s national guidelines recommend that infants exposed to the human immunodeficiency virus (HIV) be tested at 6 weeks of age. Rollout of services for early infant diagnosis has been limited and has resulted in the initiation of antiretroviral therapy (ART) in very few infants

Pesticide exposure and end-stage renal disease risk among wives of pesticide applicators in the Agricultural Health Study

Pesticide exposure has been found to cause renal damage and dysfunction in experimental studies, but epidemiological research on the renal effects of chronic low-level pesticide exposure is limited. We investigated the relationships between end-stage renal disease (ESRD) among wives of licensed pesticide applicators (N = 31,142) in the Agricultural Health Study (AHS) and (1) personal pesticide use, (2) exposure to the husband's pesticide use, and (3) other pesticide-associated farming and household activities

A population-based study of prevalence and risk factors of chronic kidney disease in León, Nicaragua

Abstract Background Recent studies have shown an excess of chronic kidney disease (CKD) among younger adult males in the Pacific coastal region of Nicaragua and suggest a non-conventional CKD etiology in this region. These studies have been conducted in small, non-representative populations. Objectives We conducted a large population-based cross-sectional study to estimate CKD prevalence in León, Nicaragua, and to evaluate the association between previously investigated risk factors and CKD. Methods Estimated glomerular filtration rate, derived using the MDRD equation, was assessed to determine CKD status of 2275 León residents. Multivariable logistic regression was used to estimate adjusted prevalence odds ratios. León CKD prevalence was also standardized to the demographic distributions of the León Health and Demographic Surveillance System and the León 2005 Census. Results CKD prevalence was 9.1%; twice as high for males (13.8%) than females (5.8%). In addition to gender, older age, rural zone, lower education level, and self-reported high blood pressure, more years of agricultural work, lija (unregulated alcohol) consumption, and higher levels of daily water consumption were significantly associated with CKD. Notably, self-reported diabetes was associated with CKD in adjusted models for females but not males. Conclusions Our findings are comparable to those found in regional studies and further support the hypothesis of a Mesoamerican Nephropathy