Rotavirus Transmission in Rural, Coastal Ecuador

Rotavirus is a major cause of under-five mortality, particularly in the developing world, yet how it is transmitted is not well understood. How and why rotavirus spreads through populations is a critical concern for both preventing disease and reducing the burden. In this dissertation, I consider how rotavirus spreads through a region by focusing on two important processes: human travel and hydrological transport. I also examine how the introduction of the rotavirus vaccine in a remote region of Ecuador has changed rotavirus transmission, affecting both direct and indirect pathways. I use a combination of regression analysis and simulation modeling to address these questions. In chapter 2, I consider the effect of human travel on rotavirus transmission. To do so, I use longitudinal data from 15 villages in rural, coastal Ecuador to identify important determinants of travel patterns and the extent to which these variables are stable over time. I then incorporate these predictors into a regional transmission model to assess how demographic heterogeneity in travel impacts regional risk of rotavirus and the implications of this heterogeneity for disease interventions. In chapter 3, I investigate the conditions in which rotavirus can be transmitted through water sources and how this pathway depends on both temperature and local hydrologic conditions. I use previously published empirical studies of temperature and rotavirus persistence in water sources to conduct a meta-analysis relating temperature to rotavirus decay in water sources. Then, I combine the resulting temperature-decay function with data on hydrological characteristics of our Ecuador study site to build a transmission model that accounts for both direct transmission and water-mediated transmission. Using this model, I assess the importance of waterborne transmission to amplification of rotavirus infection within communities and spread of rotavirus through hydrological transport within a watershed. In chapter 4, I consider how the Rotarix vaccine has changed rotavirus transmission patterns in our study region. I combine data on rotavirus vaccination from local health posts with 10 years of data from a population based case control study and 18 months of diarrheal disease surveillance to estimate: (1) the direct effect of vaccination on the rate all-cause diarrhea, (2) the overall effect of vaccination on rotavirus infection and all-cause diarrhea both by age group and at a population level, and (3) the fraction of cases attributable to rotavirus in our study region.PHDEpidemiological ScienceUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/144196/1/amullis_1.pd

Fomite-mediated transmission as a sufficient pathway: a comparative analysis across three viral pathogens

Abstract Background Fomite mediated transmission can be an important pathway causing significant disease transmission in number of settings such as schools, daycare centers, and long-term care facilities. The importance of these pathways relative to other transmission pathways such as direct person-person or airborne will depend on the characteristics of the particular pathogen and the venue in which transmission occurs. Here we analyze fomite mediated transmission through a comparative analysis across multiple pathogens and venues. Methods We developed and analyzed a compartmental model that explicitly accounts for fomite transmission by including pathogen transfer between hands and surfaces. We consider two sub-types of fomite-mediated transmission: direct fomite (e.g., shedding onto fomites) and hand-fomite (e.g., shedding onto hands and then contacting fomites). We use this model to examine three pathogens with distinct environmental characteristics (influenza, rhinovirus, and norovirus) in four venue types. To parameterize the model for each pathogen we conducted a thorough literature search. Results Based on parameter estimates from the literature the reproductive number ( R 0 $\mathcal {R}_{0}$ ) for the fomite route for rhinovirus and norovirus is greater than 1 in nearly all venues considered, suggesting that this route can sustain transmission. For influenza, on the other hand, R 0 $\mathcal {R}_{0}$ for the fomite route is smaller suggesting many conditions in which the pathway may not sustain transmission. Additionally, the direct fomite route is more relevant than the hand-fomite route for influenza and rhinovirus, compared to norovirus. The relative importance of the hand-fomite vs. direct fomite route for norovirus is strongly dependent on the fraction of pathogens initially shed to hands. Sensitivity analysis stresses the need for accurate measurements of environmental inactivation rates, transfer efficiencies, and pathogen shedding. Conclusions Fomite-mediated transmission is an important pathway for the three pathogens examined. The effectiveness of environmental interventions differs significantly both by pathogen and venue. While fomite-based interventions may be able to lower R 0 $\mathcal {R}_{0}$ for fomites below 1 and interrupt transmission, rhinovirus and norovirus are so infectious ( R 0 > > 1 $\mathcal {R}_{0}>>1$ ) that single environmental interventions are unlikely to interrupt fomite transmission for these pathogens.https://deepblue.lib.umich.edu/bitstream/2027.42/146145/1/12879_2018_Article_3425.pd

Risk for Fomite-Mediated Transmission of SARS-CoV-2 in Child Daycares, Schools, Nursing Homes, and Offices.

Severe acute respiratory syndrome coronavirus 2 can persist on surfaces, suggesting possible surface-mediated transmission of this pathogen. We found that fomites might be a substantial source of transmission risk, particularly in schools and child daycares. Combining surface cleaning and decontamination with mask wearing can help mitigate this risk

Lives saved with vaccination for 10 pathogens across 112 countries in a pre-COVID-19 world.

BackgroundVaccination is one of the most effective public health interventions. We investigate the impact of vaccination activities for Haemophilus influenzae type b, hepatitis B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, rotavirus, rubella, Streptococcus pneumoniae, and yellow fever over the years 2000-2030 across 112 countries.MethodsTwenty-one mathematical models estimated disease burden using standardised demographic and immunisation data. Impact was attributed to the year of vaccination through vaccine-activity-stratified impact ratios.ResultsWe estimate 97 (95%CrI[80, 120]) million deaths would be averted due to vaccination activities over 2000-2030, with 50 (95%CrI[41, 62]) million deaths averted by activities between 2000 and 2019. For children under-5 born between 2000 and 2030, we estimate 52 (95%CrI[41, 69]) million more deaths would occur over their lifetimes without vaccination against these diseases.ConclusionsThis study represents the largest assessment of vaccine impact before COVID-19-related disruptions and provides motivation for sustaining and improving global vaccination coverage in the future.FundingVIMC is jointly funded by Gavi, the Vaccine Alliance, and the Bill and Melinda Gates Foundation (BMGF) (BMGF grant number: OPP1157270 / INV-009125). Funding from Gavi is channelled via VIMC to the Consortium's modelling groups (VIMC-funded institutions represented in this paper: Imperial College London, London School of Hygiene and Tropical Medicine, Oxford University Clinical Research Unit, Public Health England, Johns Hopkins University, The Pennsylvania State University, Center for Disease Analysis Foundation, Kaiser Permanente Washington, University of Cambridge, University of Notre Dame, Harvard University, Conservatoire National des Arts et Métiers, Emory University, National University of Singapore). Funding from BMGF was used for salaries of the Consortium secretariat (authors represented here: TBH, MJ, XL, SE-L, JT, KW, NMF, KAMG); and channelled via VIMC for travel and subsistence costs of all Consortium members (all authors). We also acknowledge funding from the UK Medical Research Council and Department for International Development, which supported aspects of VIMC's work (MRC grant number: MR/R015600/1).JHH acknowledges funding from National Science Foundation Graduate Research Fellowship; Richard and Peggy Notebaert Premier Fellowship from the University of Notre Dame. BAL acknowledges funding from NIH/NIGMS (grant number R01 GM124280) and NIH/NIAID (grant number R01 AI112970). The Lives Saved Tool (LiST) receives funding support from the Bill and Melinda Gates Foundation.This paper was compiled by all coauthors, including two coauthors from Gavi. Other funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication

Disparities in healthcare access experienced by Hispanic chronic kidney disease patients: a cross-sectional analysis

Abstract Background Chronic kidney disease (CKD) is a public health concern, and the disease disproportionately affects Hispanics. Improved healthcare access for Hispanic CKD patients can reduce the disease burden. This study assesses the healthcare access disparities experienced by Hispanic CKD patients compared to Whites. Methods We analyzed three National Health and Nutrition Examination Survey (NHANES) datasets for 2013–2014, 2015–2016, and 2017–2018. The primary predictor variable was race, and the outcome variable was three domains of healthcare access: insurance status, having any routine place for healthcare, and having any health visits in the past year. Chi-square tests and unadjusted and adjusted multivariate logistic regressions were conducted. The models were adjusted for age, education, income, and CKD stages and were weighted to account for the sampling strategy. Results The sample size was 1864 CKD patients from three two-year cycles of NHANES datasets (2013–2014, 2015–2016, and 2017–2018). The final adjusted model found that Hispanic CKD patients were more likely to be uninsured (OR: 2.52, CI 1.66–3.83) and have no routine place for healthcare (OR: 1.68, CI 1.03–2.75) than White CKD patients, but did not have differences in healthcare visits in the past year. Conclusions Hispanic CKD patients have limited healthcare access compared to White populations showing existing care access disparities experienced by them. Improved programs and policies are required to enhance kidney health among Hispanics and promote equity in CKD

Understanding the Impact of Rainfall on Diarrhea: Testing the Concentration-Dilution Hypothesis Using a Systematic Review and Meta-Analysis.

BackgroundProjected increases in extreme weather may change relationships between rain-related climate exposures and diarrheal disease. Whether rainfall increases or decreases diarrhea rates is unclear based on prior literature. The concentration-dilution hypothesis suggests that these conflicting results are explained by the background level of rain: Rainfall following dry periods can flush pathogens into surface water, increasing diarrhea incidence, whereas rainfall following wet periods can dilute pathogen concentrations in surface water, thereby decreasing diarrhea incidence.ObjectivesIn this analysis, we explored the extent to which the concentration-dilution hypothesis is supported by published literature.MethodsTo this end, we conducted a systematic search for articles assessing the relationship between rain, extreme rain, flood, drought, and season (rainy vs. dry) and diarrheal illness.ResultsA total of 111 articles met our inclusion criteria. Overall, the literature largely supports the concentration-dilution hypothesis. In particular, extreme rain was associated with increased diarrhea when it followed a dry period [incidence rate ratio (IRR)=1.26; 95% confidence interval (CI): 1.05, 1.51], with a tendency toward an inverse association for extreme rain following wet periods, albeit nonsignificant, with one of four relevant studies showing a significant inverse association (IRR=0.911; 95% CI: 0.771, 1.08). Incidences of bacterial and parasitic diarrhea were more common during rainy seasons, providing pathogen-specific support for a concentration mechanism, but rotavirus diarrhea showed the opposite association. Information on timing of cases within the rainy season (e.g., early vs. late) was lacking, limiting further analysis. We did not find a linear association between nonextreme rain exposures and diarrheal disease, but several studies found a nonlinear association with low and high rain both being associated with diarrhea.DiscussionOur meta-analysis suggests that the effect of rainfall depends on the antecedent conditions. Future studies should use standard, clearly defined exposure variables to strengthen understanding of the relationship between rainfall and diarrheal illness. https://doi.org/10.1289/EHP6181

Understanding the Impact of Rainfall on Diarrhea: Testing the Concentration-Dilution Hypothesis Using a Systematic Review and Meta-Analysis.

BackgroundProjected increases in extreme weather may change relationships between rain-related climate exposures and diarrheal disease. Whether rainfall increases or decreases diarrhea rates is unclear based on prior literature. The concentration-dilution hypothesis suggests that these conflicting results are explained by the background level of rain: Rainfall following dry periods can flush pathogens into surface water, increasing diarrhea incidence, whereas rainfall following wet periods can dilute pathogen concentrations in surface water, thereby decreasing diarrhea incidence.ObjectivesIn this analysis, we explored the extent to which the concentration-dilution hypothesis is supported by published literature.MethodsTo this end, we conducted a systematic search for articles assessing the relationship between rain, extreme rain, flood, drought, and season (rainy vs. dry) and diarrheal illness.ResultsA total of 111 articles met our inclusion criteria. Overall, the literature largely supports the concentration-dilution hypothesis. In particular, extreme rain was associated with increased diarrhea when it followed a dry period [incidence rate ratio (IRR)=1.26; 95% confidence interval (CI): 1.05, 1.51], with a tendency toward an inverse association for extreme rain following wet periods, albeit nonsignificant, with one of four relevant studies showing a significant inverse association (IRR=0.911; 95% CI: 0.771, 1.08). Incidences of bacterial and parasitic diarrhea were more common during rainy seasons, providing pathogen-specific support for a concentration mechanism, but rotavirus diarrhea showed the opposite association. Information on timing of cases within the rainy season (e.g., early vs. late) was lacking, limiting further analysis. We did not find a linear association between nonextreme rain exposures and diarrheal disease, but several studies found a nonlinear association with low and high rain both being associated with diarrhea.DiscussionOur meta-analysis suggests that the effect of rainfall depends on the antecedent conditions. Future studies should use standard, clearly defined exposure variables to strengthen understanding of the relationship between rainfall and diarrheal illness. https://doi.org/10.1289/EHP6181

Modeling environmentally mediated rotavirus transmission: The role of temperature and hydrologic factors.

Rotavirus is considered a directly transmitted disease due to its high infectivity. Environmental pathways have, therefore, largely been ignored. Rotavirus, however, persists in water sources, and both its surface water concentrations and infection incidence vary with temperature. Here, we examine the potential for waterborne rotavirus transmission. We use a mechanistic model that incorporates both direct and waterborne transmission pathways, coupled with a hydrological model, and we simulate rotavirus transmission between two communities with interconnected water sources. To parameterize temperature dependency, we estimated temperature-dependent decay rates in water through a meta-analysis. Our meta-analysis suggests that rotavirus decay rates are positively associated with temperature (n = 39, P [Formula: see text] 0.001). This association is stronger at higher temperatures (over 20 °C), consistent with tropical climate conditions. Our model analysis demonstrates that water could disseminate rotavirus between the two communities for all modeled temperatures. While direct transmission was important for disease amplification within communities, waterborne transmission could also amplify transmission. In standing-water systems, the modeled increase in decay led to decreased disease, with every 1 °C increase in temperature leading to up to a 2.4% decrease in incidence. These effect sizes are consistent with prior meta-analyses, suggesting that environmental transmission through water sources may partially explain the observed associations between temperature and rotavirus incidence. Waterborne rotavirus transmission is likely most important in cooler seasons and in communities that use slow-moving or stagnant water sources. Even when indirect transmission through water cannot sustain outbreaks, it can seed outbreaks that are maintained by high direct transmission rates