Department of Population Health Sciences

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Risk Factors of Porcine Cysticercosis in the Eastern Cape Province, South Africa
Krecek, Rosina Claudia; Mohammed, Hamish; Michael, Lynne Margaret; Schantz, Peter Mullineaux; Ntanjana, Lulama; Morey, Liesl; Werre, Stephen R.; Willingham, Arve Lee, III (PLOS, 2012-05-24)
There is a high prevalence of Taenia solium taeniosis/cysticercosis in humans and pigs in the Eastern Cape Province (ECP) of South Africa. The objective of this study was to identify risk factors of porcine cysticercosis in select districts of the ECP. Data were collected in 2003 by interviewing 217 pig producers from the area. Blood samples were collected from 261 of their pigs, which were tested using two enzyme-linked immunosorbent assays (ELISA) for the presence of antibodies to cysticercosis. Frequencies of both owner- and pig-level characteristics were determined. For pig-level analysis, all bivariable and multivariable associations were determined using the surveylogistic procedure of the SAS/STAT® software to accommodate for the intraclass correlation that exists for clusters of pigs within one owner and for clusters of owners within a district. All tests for significance were performed at the α = 0.05 level, and adjusted odds ratios (aOR) and 95% confidence intervals (CI) were determined. Among the respondents, 48% of their households lacked a latrine, 98% slaughtered pigs at home, and 99% indicated that meat inspection services were not available. On bivariable analysis, there was a significant association between porcine infection and district (p = 0.003), breed (p = 0.041) and the absence of a latrine (p = 0.006). On multivariable analysis, the absence of a latrine was the only variable significantly associated with porcine infection (aOR = 1.89; 95% CI = 1.07, 3.35) (p = 0.028). The increased odds of porcine infection with households lacking a latrine contributes to our understanding of the transmission of this parasite in the ECP. Determining and addressing the risk factors for T. solium infection can potentially lower the very high prevalence in humans and pigs in this endemic area.
Rethinking health systems strengthening: key systems thinking tools and strategies for transformational change
Swanson, R. Chad; Cattaneo, Aadriano; Bradley, Elizabeth; Chunharas, Somsak; Atun, Rifat; Abbas, Kaja M.; Katsaliaki, Korina; Mustafee, Navonil; Mason Meier, Benjamin; Best, Allan (Oxford University Press, 2012-10-01)
While reaching consensus on future plans to address current global health challenges is far from easy, there is broad agreement that reductionist approaches that suggest a limited set of targeted interventions to improve health around the world are inadequate. We argue that a comprehensive systems perspective should guide health practice, education, research and policy. We propose key ‘systems thinking’ tools and strategies that have the potential for transformational change in health systems. Three overarching themes span these tools and strategies: collaboration across disciplines, sectors and organizations; ongoing, iterative learning; and transformational leadership. The proposed tools and strategies in this paper can be applied, in varying degrees, to every organization within health systems, from families and communities to national ministries of health. While our categorization is necessarily incomplete, this initial effort will provide a valuable contribution to the health systems strengthening debate, as the need for a more systemic, rigorous perspective in health has never been greater.
LAT Region Factors Mediating Differential Neuronal Tropism of HSV-1 and HSV-2 Do Not Act in Trans
Bertke, Andrea S.; Apakupakul, K.; Ma, AyeAye; Imai, Y.; Gussow, A. M.; Wang, K.; Cohen, J. I.; Bloom, D. C.; Margolis, Todd P. (PLOS, 2012-12-31)
After HSV infection, some trigeminal ganglion neurons support productive cycle gene expression, while in other neurons the virus establishes a latent infection. We previously demonstrated that HSV-1 and HSV-2 preferentially establish latent infection in A5+ and KH10+ sensory neurons, respectively, and that exchanging the latency-associated transcript (LAT) between HSV-1 and HSV-2 also exchanges the neuronal preference. Since many viral genes besides the LAT are functionally interchangeable between HSV-1 and HSV-2, we co-infected HSV-1 and HSV-2, both in vivo and in vitro, to determine if trans-acting viral factors regulate whether HSV infection follows a productive or latent pattern of gene expression in sensory neurons. The pattern of HSV-1 and HSV-2 latent infection in trigeminal neurons was no different following co-infection than with either virus alone, consistent with the hypothesis that a trans-acting viral factor is not responsible for the different patterns of latent infection of HSV-1 and HSV-2 in A5+ and KH10+ neurons. Since exchanging the LAT regions between the viruses also exchanges neuronal preferences, we infected transgenic mice that constitutively express 2.8 kb of the LAT region with the heterologous viral serotype. Endogenous expression of LAT did not alter the pattern of latent infection after inoculation with the heterologous serotype virus, demonstrating that the LAT region does not act in trans to direct preferential establishment of latency of HSV-1 and HSV-2. Using HSV1-RFP and HSV2-GFP in adult trigeminal ganglion neurons in vitro, we determined that HSV-1 and HSV-2 do not exert trans-acting effects during acute infection to regulate neuron specificity. Although some neurons were productively infected with both HSV-1 and HSV-2, no A5+ or KH10+ neurons were productively infected with both viruses. Thus, trans-acting viral factors do not regulate preferential permissiveness of A5+ and KH10+ neurons for productive HSV infection and preferential establishment of latent infection.
Different mechanisms regulate productive herpes simplex virus 1 (HSV-1) and HSV-2 infections in adult trigeminal neurons
Bertke, Andrea S.; Ma, AyeAye; Margolis, Mathew S.; Margolis, Todd P. (2013-03-20)
Herpes simplex virus 1 (HSV-1) and HSV-2 establish latency in different neuronal subtypes (A5+ and KH10+) in murine trigeminal ganglia, results which correlate with restricted productive infection in these neurons in vitro. HSV-2 latency-associated transcript (LAT) contains a cis-acting regulatory element near the transcription start site that promotes productive infection in A5+ neurons and a second element in exon 1 that inhibits productive infection in KH10+ neurons. HSV-1 contains no such regulatory sequences, demonstrating different mechanisms for regulating productive HSV infection in neurons.
Editorial Comment: Cost-Effectiveness Analysis for Prioritization of Limited Public Health Resources - Tuberculosis Interventions in Texas
Abbas, Kaja M. (2014)
Public health departments have limited evidence to understand and analyze the costs and benefits of different health programs, including tuberculosis control and prevention programs. The study by Miller et. al addresses this challenge to estimate costs and benefits of tuberculosis prevention programs in Texas and identify cost-effective diagnostic and treatment combinations, thereby improving the evidence-based decision making power of the public health departments.
Epidemiological Modeling of Bovine Brucellosis in India
Kang, Gloria J.; Gunaseelan, L.; Abbas, Kaja M. (IEEE, 2014-01-01)
Spatial Big Data Analytics of Influenza Epidemic in Vellore, India
Lopez, Daphne; Gunasekaran, M.; Murugan, B. Senthil; Kaur, Harpreet; Abbas, Kaja M. (IEEE, 2014-01-01)
The study objective is to develop a big spatial data model to predict the epidemiological impact of influenza in Vellore, India. Large repositories of geospatial and health data provide vital statistics on surveillance and epidemiological metrics, and valuable insight into the spatiotemporal determinants of disease and health. The integration of these big data sources and analytics to assess risk factors and geospatial vulnerability can assist to develop effective prevention and control strategies for influenza epidemics and optimize allocation of limited public health resources. We used the spatial epidemiology data of the HIN1 epidemic collected at the National Informatics Center during 2009-2010 in Vellore. We developed an ecological niche model based on geographically weighted regression for predicting influenza epidemics in Vellore, India during 2013-2014. Data on rainfall, temperature, wind speed, humidity and population are included in the geographically weighted regression analysis. We inferred positive correlations for H1N1 influenza prevalence with rainfall and wind speed, and negative correlations for H1N1 influenza prevalence with temperature and humidity. We evaluated the results of the geographically weighted regression model in predicting the spatial distribution of the influenza epidemic during 2013-2014.
A Mathematical Model of Skeletal Muscle Disease and Immune Response in the mdx Mouse
Jarrah, Abdul Salam; Castiglione, Filippo; Evans, Nicholas P.; Grange, Robert W.; Laubenbacher, Reinhard C. (Hindawi, 2014-06-11)
Duchenne muscular dystrophy (DMD) is a genetic disease that results in the death of affected boys by early adulthood. The genetic defect responsible for DMD has been known for over 25 years, yet at present there is neither cure nor effective treatment for DMD. During early disease onset, the mdx mouse has been validated as an animal model for DMD and use of this model has led to valuable but incomplete insights into the disease process. For example, immune cells are thought to be responsible for a significant portion of muscle cell death in the mdx mouse; however, the role and time course of the immune response in the dystrophic process have not been well described. In this paper we constructed a simple mathematical model to investigate the role of the immune response in muscle degeneration and subsequent regeneration in the mdx mouse model of Duchenne muscular dystrophy. Our model suggests that the immune response contributes substantially to the muscle degeneration and regeneration processes. Furthermore, the analysis of the model predicts that the immune system response oscillates throughout the life of the mice, and the damaged fibers are never completely cleared.
Lost in translation: Delivering culturally and linguistically appropriate interventions to Hispanic populations
Valenzuela, Ivette (2015)
Hispanics became the United States' largest minority in 2012. Lack of culturally and linguistically appropriate interventions in the Hispanic population at the health-care and community levels increases the risk of negative health outcomes, such as obesity and type 2 diabetes. Delivering nutrition education can modify cultural traditions associated with food and decrease diseases associated with food habits. Barriers faced by many Hispanics include, but are not limited to, limited English proficiency and/or immigration status. Developing interventions to improve Hispanics' health outcomes requires understanding of Hispanics' cultural values and diversity. Active recruitment and training of Hispanics into food system fields is crucial to developing and implementing culturally sensitive and language-oriented intervention.
A rapid and high content assay that measures cyto-ID-stained autophagic compartments and estimates autophagy flux with potential clinical applications
Guo, Sujuan; Liang, Yanping; Murphy, Susan F.; Huang, Angela; Shen, Haihong; Kelly, Deborah F.; Sobrado, Pablo; Sheng, Zhi (Taylor & Francis, 2015-03-01)
The lack of a rapid and quantitative autophagy assay has substantially hindered the development and implementation of autophagy-targeting therapies for a variety of human diseases. To address this critical issue, we developed a novel autophagy assay using the newly developed Cyto-ID fluorescence dye. We first verified that the Cyto-ID dye specifically labels autophagic compartments with minimal staining of lysosomes and endosomes. We then developed a new Cyto-ID fluorescence spectrophotometric assay that makes it possible to estimate autophagy flux based on measurements of the Cyto-ID-stained autophagic compartments. By comparing to traditional autophagy approaches, we found that this assay yielded a more sensitive, yet less variable, quantification of the stained autophagic compartments and the estimate of autophagy flux. Furthermore, we tested the potential application of this autophagy assay in high throughput research by integrating it into an RNA interference (RNAi) screen and a small molecule screen. The RNAi screen revealed WNK2 and MAP3K6 as autophagy-modulating genes, both of which inhibited the MTOR pathway. Similarly, the small molecule screen identified sanguinarine and actinomycin D as potent autophagy inducers in leukemic cells. Moreover, we successfully detected autophagy responses to kinase inhibitors and chloroquine in normal or leukemic mice using this assay. Collectively, this new Cyto-ID fluorescence spectrophotometric assay provides a rapid, reliable quantification of autophagic compartments and estimation of autophagy flux with potential applications in developing autophagy-related therapies and as a test to monitor autophagy responses in patients being treated with autophagy-modulating drugs.
Herpes Simplex Virus 1 Reactivates from Autonomic Ciliary Ganglia Independently from Sensory Trigeminal Ganglia To Cause Recurrent Ocular Disease
Lee, Sungseok; Ives, Angela M.; Bertke, Andrea S. (American Society for Microbiology, 2015-08-01)
Herpes simplex virus 1 (HSV-1) and HSV-2 establish latency in sensory and autonomic neurons after ocular or genital infection, but their recurrence patterns differ. HSV-1 reactivates from latency to cause recurrent orofacial disease, and while HSV-1 also causes genital lesions, HSV-2 recurs more efficiently in the genital region and rarely causes ocular disease. The mechanisms regulating these anatomical preferences are unclear. To determine whether differences in latent infection and reactivation in autonomic ganglia contribute to differences in HSV-1 and HSV-2 anatomical preferences for recurrent disease, we compared HSV-1 and HSV-2 clinical disease, acute and latent viral loads, and viral gene expression in sensory trigeminal and autonomic superior cervical and ciliary ganglia in a guinea pig ocular infection model. HSV-2 produced more severe acute disease, correlating with higher viral DNA loads in sensory and autonomic ganglia, as well as higher levels of thymidine kinase expression, a marker of productive infection, in autonomic ganglia. HSV-1 reactivated in ciliary ganglia, independently from trigeminal ganglia, to cause more frequent recurrent symptoms, while HSV-2 replicated simultaneously in autonomic and sensory ganglia to cause more persistent disease. While both HSV-1 and HSV-2 expressed the latency-associated transcript (LAT) in the trigeminal and superior cervical ganglia, only HSV-1 expressed LAT in ciliary ganglia, suggesting that HSV-2 is not reactivation competent or does not fully establish latency in ciliary ganglia. Thus, differences in replication and viral gene expression in autonomic ganglia may contribute to differences in HSV-1 and HSV-2 acute and recurrent clinical disease.
The Burden of Livestock Parasites on the Poor
Rist, Cassidy; Garchitorena, Andres; Ngonghala, Calistus N.; Gillespie, Thomas R.; Bonds, Matthew H. (2015-11)
Modeling the burden of poultry disease on the rural poor in Madagascar
Rist, Cassidy; Ngonghala, Calistus N.; Garchitorena, Andres; Brook, Cara E.; Ramananjato, Ranto; Miller, Ann C.; Randrianarivelojosia, Milijaona; Wright, Patricia C.; Gillespie, Thomas R.; Bonds, Matthew H. (2015-12)
Livestock represent a fundamental economic and nutritional resource for many households in the developing world; however, a high burden of infectious disease limits their production potential. Here we present an ecological framework for estimating the burden of poultry disease based on coupled models of infectious disease and economics. The framework is novel, as it values humans and livestock as co-contributors to householdwellbeing, incorporating feedbacks between poultry production and human capital in disease burden estimates.Weparameterize this coupled ecological–economic model with household-level data to provide an estimate of the overall burden of poultry disease for the Ifanadiana District inMadagascar,where over 72% of households rely on poultry for economic and food security. Our models indicate that households may lose 10–25% of their monthly income under current disease conditions. Results suggest that advancements in poultry health may serve to support income generation through improvements in both human and animal health.
Environmental Predictors of US County Mortality Patterns on a National Basis
Chan, Melissa P. L.; Weinhold, Robert S.; Thomas, Reuben; Gohlke, Julia M.; Portier, Christopher J. (PLOS, 2015-12-02)
A growing body of evidence has found that mortality rates are positively correlated with social inequalities, air pollution, elevated ambient temperature, availability of medical care and other factors. This study develops a model to predict the mortality rates for different diseases by county across the US. The model is applied to predict changes in mortality caused by changing environmental factors. A total of 3,110 counties in the US, excluding Alaska and Hawaii, were studied. A subset of 519 counties from the 3,110 counties was chosen by using systematic random sampling and these samples were used to validate the model. Step-wise and linear regression analyses were used to estimate the ability of environmental pollutants, socio-economic factors and other factors to explain variations in county-specific mortality rates for cardiovascular diseases, cancers, chronic obstructive pulmonary disease (COPD), all causes combined and lifespan across five population density groups. The estimated models fit adequately for all mortality outcomes for all population density groups and, adequately predicted risks for the 519 validation counties. This study suggests that, at local county levels, average ozone (0.07 ppm) is the most important environmental predictor of mortality. The analysis also illustrates the complex inter-relationships of multiple factors that influence mortality and lifespan, and suggests the need for a better understanding of the pathways through which these factors, mortality, and lifespan are related at the community level.
Feasibility for Measuring Transverse Area Ratios and Asymmetry of Lumbosacral Region Paraspinal Muscles in Working Dogs Using Computed Tomography
Cain, Bethany; Jones, Jeryl C.; Holaskova, Ida; Freeman, Larry E.; Pierce, Bess J. (Frontiers, 2016)
Objectives: Describe computed tomographic (CT) anatomy of canine lumbosacral (LS) paraspinal muscles, a method for measuring paraspinal muscle transverse area ratios and asymmetry using CT, and application of this method in a small sample of working dogs with versus without LS pain. Methods: Published anatomy references and atlases were reviewed and discrepancies were resolved by examination of anatomic specimens and multiplanar reformatted images to describe transverse CT anatomy of LS region paraspinal muscles. Sixteen Belgian malinois military working dogs were retrospectively recruited and assigned to LS pain positive versus negative groups based on medical record entries. A single observer unaware of dog group measured CT transverse areas of paraspinal muscles and adjacent vertebral bodies, in triplicate, for L5-S1 vertebral locations. A statistician compared muscle transverse area ratios and asymmetry at each vertebral location between groups. Results: The relative coefficient of variation for triplicate CT area measurements averaged 2.15% (N = 16). Multifidus lumborum (L6-7), psoas/iliopsoas (L5-6, L6-7), and sacrocaudalis dorsalis lateralis (L6-7, L7-S1) transverse area ratios were significantly smaller in dogs with LS pain (n = 11) versus without LS pain (n = 5) (p <= 0.05). Muscle asymmetry values were not significantly greater in dogs with versus without LS pain. Clinical relevance: Computed tomographic morphometry of LS region paraspinal muscles is a feasible objective method for use in future evidence-based research studies in working dogs. Potential future research applications include determining whether decreased paraspinal muscle area ratios and/or increased paraspinal muscle asymmetry could be used as markers for preclinical LS pain in stoic dogs or risk factors for other injuries in high performance canine athletes, or determining whether core muscle strengthening exercise prescriptions for dogs with LS pain have an effect on paraspinal muscle area ratios and asymmetry.
A Sustainable Engineering Solution for Paediatric Dehydration in Low-Resource Clinical Environments
Taylor, Ashley R.; Turovskiy, Jeffrey; Drew, Benjamin; Muelenaer, Andre A.; Redican, Kerry J.; Kochersberger, Kevin B.; Bickford, Lissett R. (Engineers Without Borders Australia, 2016)
Engineering efforts in low resource environments pose a unique set of challenges, requiring an in-depth understanding of local needs, comprehensive mapping of community resources, and extensive collaboration with local expertise. The importance of these principles is demonstrated in this paper by detailing the novel design and field demonstration of an affordable, locally manufactured intravenous fluid regulation device. Collaboration with clinical personnel in Uganda and Malawi guided device design. In-country physicians emphasised the need to regulate volume of intravenous (IV) fluid delivered to a paediatric patient without use of electricity. The proposed device regulates IV fluid delivery within ±20 mL of total prescribed dosage, providing a method of reducing fatalities caused by over-hydration in low resource environments; the feasibility of building the device from local resources was demonstrated by a field research team in Malawi. The device was successfully constructed entirely from local resources for a total cost of $46.21 (USD). Additionally, the device was demonstrated in rural clinics where 89 % of surveyed clinical staff reported that they would use the device to regulate IV fluid delivery. This paper emphasises the importance of collaborating with communities for community-based engineering solutions. Mapping community assets and collaborating with local expertise are crucial to success of engineering efforts. Long-term, community-based efforts are likely to sustainably improve health outcomes and strengthen economies of communities worldwide.
Increasing HIV-1 pretreatment drug resistance among antiretroviral-naive adults initiating treatment between 2006 and 2014 in Nairobi, Kenya
Chung, Michael H.; Silverman, Rachel A.; Beck, Ingrid A.; Yatich, Nelly; Dross, Sandra; McKernan-Mullin, Jennifer; Bii, Stephen; Tapia, Kenneth; Stern, Joshua A.; Chohan, Bhavna; Sakr, Samah R.; Kiarie, James N.; Frenkel, Lisa M. (Lippincott Williams & Wilkins, 2016-06-19)
Antiretroviral-naïve adults initiating antiretroviral therapy in Nairobi, Kenya were tested for HIV-1 drug resistance at codons K103N, Y181C, G190A, M184V, and K65R using an oligonucleotide ligation assay. Prevalence of pretreatment drug resistance increased from 3.89% in 2006 to 10.93% in 2014 (P < 0.001), and 95% of those with resistance had at least one nonnucleoside reverse transcriptase inhibitor mutation. Resistance to tenofovir (K65R) was found in 2014 but not in 2006.
Mechanisms of Communicating Health Information Through Facebook: Implications for Consumer Health Information Technology Design
Menefee, Hannah K.; Thompson, Morgan J.; Guterbock, Thomas M.; Williams, Ishan C.; Valdez, Rupa S. (2016-08)
Background: Consumer health information technology (IT) solutions are designed to support patient health management and have the ability to facilitate patients' health information communication with their social networks. However, there is a need for consumer health IT solutions to align with patients' health management preferences for increased adoption of the technology. It may be possible to gain an understanding of patients' needs for consumer health IT supporting their health information communication with social networks by explicating how they have adopted and adapted social networking sites, such as Facebook, for this purpose. Objective: Our aim was to characterize patients' use of all communication mechanisms within Facebook for health information communication to provide insight into how consumer health IT solutions may be better designed to meet patients' communication needs and preferences. Methods: This study analyzed data about Facebook communication mechanisms use from a larger, three-phase, sequential, mixed-methods study. We report here on the results of the study's first phase: qualitative interviews (N=25). Participants were over 18, used Facebook, were residents or citizens of the United States, spoke English, and had a diagnosis consistent with type 2 diabetes. Participants were recruited through Facebook groups and pages. Participant interviews were conducted via Skype or telephone between July and September 2014. Data analysis was grounded in qualitative content analysis and the initial coding framework was informed by the findings of a previous study. Results: Participants' rationales for the use or disuse of a particular Facebook mechanism to communicate health information reflected six broad themes: (1) characteristics and circumstances of the person, (2) characteristics and circumstances of the relationship, (3) structure and composition of the social network, (4) content of the information, (5) communication purpose, and (6) attributes of the technology. Conclusions: The results of this study showed that participants consider multiple factors when choosing a Facebook mechanism for health information communication. Factors included what information they intended to share, what they were trying to accomplish, attributes of technology, and attributes and communication practices of their social networks. There is a need for consumer health IT that allows for a range of choices to suit the intersectionality of participants' rationales. Technology that better meets patients' needs may lead to better self-management of health conditions, and therefore, improve overall health outcomes.
Clinical Response, Outbreak Investigation and Epidemiology of the Fungal Meningitis Epidemic in the United States: Systematic Review
Abbas, Kaja M.; Dorratoltaj, Nargesalsadat; O'Dell, Margaret L.; Bordwine, Paige; Kerkering, Thomas M.; Redican, Kerry J. (2016-10-01)
We conducted a systematic review of the 2012-2013 multistate fungal meningitis epidemic in the United States from the perspectives of clinical response, outbreak investigation, and epidemiology. Articles focused on clinical response, outbreak investigation, and epidemiology were included, whereas articles focused on compounding pharmacies, legislation and litigation, diagnostics, microbiology, and pathogenesis were excluded. We reviewed 19 articles by use of the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) framework. The source of the fungal meningitis outbreak was traced to the New England Compounding Center in Massachusetts, where injectable methylprednisolone acetate products were contaminated with the predominant pathogen, Exserohilum rostratum. As of October 23, 2013, the final case count stood at 751 patients and 64 deaths, and no additional cases are anticipated. The multisectoral public health response to the fungal meningitis epidemic from the hospitals, clinics, pharmacies, and the public health system at the local, state, and federal levels led to an efficient epidemiological investigation to trace the outbreak source and rapid implementation of multiple response plans. This systematic review reaffirms the effective execution of a multisectoral public health response and efficient delivery of the core functions of public health assessment, policy development, and service assurances to improve population health.
Navigable rivers facilitated the spread and recurrence of plague in pre-industrial Europe
Yue, Ricci P. H.; Lee, Harry F.; Wu, Connor Y. H. (Springer Nature, 2016-10-10)
Infectious diseases have become a rising challenge to mankind in a globalizing world. Yet, little is known about the inland transmission of infectious diseases in history. In this study, we based on the spatiotemporal information of 5559 plague (Yersinia pestis) outbreaks in Europe and its neighboring regions in AD1347-1760 to statistically examine the connection between navigable rivers and plague outbreak. Our results showed that 95.5% of plague happened within 10 km proximity of navigable rivers. Besides, the count of plague outbreak was positively correlated with the width of river and negatively correlated with the distance between city and river. This association remained robust in different regression model specifications. An increase of 100 m in the width of river and a shortening of 1 km distance between city and river resulted in 9 and 0.96 more plague outbreaks in our study period, respectively. Such relationship shows a declining trend over our study period due to the expansion of city and technological advancement in overland transportation. This study elucidates the key role of navigable river in the dissemination of plague in historical Europe.

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