Skin Cancer Risk Is Increased by Somatic Mutations Detected Noninvasively in Healthy-Appearing Sun-Exposed Skin.

Skin cancer risk is increased by exposure to ultraviolet radiation (UVR). Because UVR exposure accumulates over time and lighter skin is more susceptible to UVR, age and skin tone are risk factors for skin cancer. However, measurements of somatic mutations in healthy-appearing skin have not been used to calculate skin cancer risk. In this study, we developed a noninvasive test that quantifies somatic mutations in healthy-appearing sun-exposed skin and applied it to a 1038-subject cohort. Somatic mutations were combined with other known skin cancer risk factors to train a model to calculate risk. The final model (DNA-Skin Cancer Assessment of Risk) was trained to predict personal history of skin cancer from age, family history, skin tone, and mutation count. The addition of mutation count significantly improved model performance (OR = 1.3, 95% confidence interval = 1.14-1.48; P = 5.3 × 10-6) and made a more significant contribution than skin tone. Calculations of skin cancer risk matched the known United States population prevalence, indicating that DNA-Skin Cancer Assessment of Risk was well-calibrated. In conclusion, somatic mutations in healthy-appearing sun-exposed skin increase skin cancer risk, and mutations capture risk information that is not accounted for by other risk factors. Clinical utility is supported by the noninvasive nature of skin sample collection through adhesive patches.

Bartonella in Norway rats (Rattus norvegicus) from the urban slum environment in Brazil.

Bartonella are rodent-borne bacteria that cause varied human etiologies. Studies on synanthropic rodents are rare, causing gaps in epidemiological knowledge. We tested bloodclot samples from 79 rats from an urban slum in Salvador, Brazil through PCR targeting gltA gene. Nine samples (11.4%) were positive: six had 100% identity with Bartonella sp. isolate JF429580 and 99.5% with B. queenslandensis strain AUST/NH8; three were 100% identical to isolate JF429532 and 99.7% to B. tribocorum. This is the second report on urban rat Bartonella indicating bacterial circulation at detectable rates. Its presence in rats from vulnerable human settlements demands public health attention.

Extracorporeal membrane oxygenators with light-diffusing fibers for treatment of carbon monoxide poisoning: Experiments, mathematical modeling, and performance assessment with unit cells.

BACKGROUND AND OBJECTIVES: Approximately 50,000 emergency department visits per year due to carbon monoxide (CO) poisoning occur in the United States alone. Tissue hypoxia can occur at very low CO concentration exposures because CO binds with a 250-fold higher affinity than oxygen to hemoglobin. The most effective therapy is 100% hyperbaric oxygen (HBO) respiration. However, there are only a limited number of cases with ready accessibility to the specialized HBO chambers. In previous studies, we developed an extracorporeal veno-venous membrane oxygenator that facilitates exposure of blood to an external visible light source to photo-dissociate carboxyhemoglobin (COHb) and significantly increase CO removal from CO-poisoned blood (photo-extracorporeal veno-venous membrane oxygenator [p-ECMO]). One objective of this study was to describe in vitro experiments with different laser wavelength sources to compare CO elimination rates in a small unit-cell ECMO device integrated with a light-diffusing optical fiber. A second objective was to develop a mathematical model that predicts CO elimination rates in the unit-cell p-ECMO  device design upon which larger devices can be based. STUDY DESIGN/MATERIAL AND METHODS: Two small unit-cell p-ECMO devices consisted of a plastic capillary with a length and inside diameter of 10 cm and 1.15 mm, respectively. Either five (4-1 device) or seven (6-1 device) gas exchange tubes were placed in the plastic capillary and a light-diffusing fiber was inserted into one of the gas exchange tubes. Light from lasers emitting either 635 nm or 465 nm wavelengths was coupled into the light-diffusing fiber as oxygen flowed through the gas exchange membranes. To assess the ability of the device to remove CO from blood in vitro, the percent COHb reduction in a single pass through the device was assessed with and without light. The Navier Stokes equations, Carreau-Yesuda model, Boltzman equation for light distribution, and hemoglobin kinetic rate equations, including photo-dissociation, were combined in a mathematical model to predict COHb elimination in the experiments. RESULTS: For the unit-cell devices, the COHb removal rate increases with increased 635 nm laser power, increased blood time in the device, and greater gas exchange membrane surface-to-blood volume ratio. The 6-1 device COHb half-life versus that of the 4-1 device with 4 W at 635 nm light was 1.5 min versus 4.25 min, respectively. At 1 W laser power, 635 nm and 465 nm exhibited similar CO removal rates. The COHb half-life times of the 6-1 device were 1.25, 2.67, and 8.5 min at 635 nm (4 W), 465 nm (1 W), and 100% oxygen only, respectively. The mathematical model predicted the experimental results. An analysis of the in vivo COHb half-life of oxygen respiration therapy versus an adjunct therapy with a p-ECMO device and oxygen respiration shows a reduction from 90 min to as low as 10 min, depending on the device design. CONCLUSION: In this study, we experimentally studied and developed a mathematical model of a small unit-cell ECMO device integrated with a light-diffusing fiber illuminated with laser light. The unit-cell device forms the basis for a larger device and, in an adjunct therapy with oxygen respiration, has the potential to remove COHb at much higher rates than oxygen therapy alone. The mathematical model can be used to optimize the design in practical implementations to quickly and efficiently remove CO from CO-poisoned blood.

Linking rattiness, geography and environmental degradation to spillover Leptospira infections in marginalised urban settings: An eco-epidemiological community-based cohort study in Brazil.

Background: Zoonotic spillover from animal reservoirs is responsible for a significant global public health burden, but the processes that promote spillover events are poorly understood in complex urban settings. Endemic transmission of Leptospira, the agent of leptospirosis, in marginalised urban communities occurs through human exposure to an environment contaminated by bacteria shed in the urine of the rat reservoir. However, it is unclear to what extent transmission is driven by variation in the distribution of rats or by the dispersal of bacteria in rainwater runoff and overflow from open sewer systems. Methods: We conducted an eco-epidemiological study in a high-risk community in Salvador, Brazil, by prospectively following a cohort of 1401 residents to ascertain serological evidence for leptospiral infections. A concurrent rat ecology study was used to collect information on the fine-scale spatial distribution of 'rattiness', our proxy for rat abundance and exposure of interest. We developed and applied a novel geostatistical framework for joint spatial modelling of multiple indices of disease reservoir abundance and human infection risk. Results: The estimated infection rate was 51.4 (95%CI 40.4, 64.2) infections per 1000 follow-up events. Infection risk increased with age until 30 years of age and was associated with male gender. Rattiness was positively associated with infection risk for residents across the entire study area, but this effect was stronger in higher elevation areas (OR 3.27 95% CI 1.68, 19.07) than in lower elevation areas (OR 1.14 95% CI 1.05, 1.53). Conclusions: These findings suggest that, while frequent flooding events may disperse bacteria in regions of low elevation, environmental risk in higher elevation areas is more localised and directly driven by the distribution of local rat populations. The modelling framework developed may have broad applications in delineating complex animal-environment-human interactions during zoonotic spillover and identifying opportunities for public health intervention. Funding: This work was supported by the Oswaldo Cruz Foundation and Secretariat of Health Surveillance, Brazilian Ministry of Health, the National Institutes of Health of the United States (grant numbers F31 AI114245, R01 AI052473, U01 AI088752, R01 TW009504 and R25 TW009338); the Wellcome Trust (102330/Z/13/Z), and by the Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB/JCB0020/2016). MTE was supported by a Medical Research UK doctorate studentship. FBS participated in this study under a FAPESB doctorate scholarship.

Evaluation of the impact of chemical control on the ecology of Rattus norvegicus of an urban community in Salvador, Brazil.

BACKGROUND: The presence of synanthropic rodents, such as Rattus norvegicus, in urban environments generates high costs of prophylaxis and control, in large part due to the environmental transmission of the pathogenic spirochete Leptospira interrogans, which causes leptospirosis. In Salvador, Brazil, The Center for Control of Zoonosis (CCZ) is responsible for planning and implementing Rodent Control Programs (RCP) which are based on chemical rodenticide. However, these strategies have not been standardized for use in developing countries. AIM: This study aimed to identify the effect of a chemical control campaign on the demographic variables of urban R. norvegicus, analyzing relative abundance, sex structure, body mass, and age of the population, as well as the characterization of spatial distribution among households, rodent capture campaigns and interventions. METHODS: This study was carried out during 2015 in three valleys of an urban poor community in Salvador. Individuals of R. norvegicus were systematically captured before (Pre-intervention) and three months (1st post-intervention) and six months (2nd post-intervention) after a chemical control intervention conducted by the CCZ in two valleys of the study area while the third valley was not included in the intervention campaign and was used as a non-intervention reference. We used analysis of variance to determine if intervention affected demographic variables and chi-square to compare proportions of infested households (Rodent infestation index-PII). RESULTS: During the chemical intervention, 939 households were visited. In the pre-intervention campaign, an effort of 310 trap nights resulted in 43 rodents captured, and in the 1st and 2nd, post-intervention campaigns resulted in 47 rodents captured over 312 trap nights and 36 rodents captured over 324 traps-nights, respectively. The rodent infestation index (PII) points did not show a reduction between the period before the intervention and the two periods after the chemical intervention (70%, 72%, and 65%, respectively). Regarding relative abundances, there was no difference between valleys and period before and two periods after chemical intervention (trap success valley 1: 0,18; 0,19; 0,18 / Valley 3 0,15; 0,17; 0,13/ P>0,05). Other demographic results showed that there was no difference in demographic characteristics of the rodent population before and after the intervention, as well as there being no influence of the application of rodenticide on the areas of concentration of capture of rodents between the campaigns. CONCLUSION: Our study indicates that the chemical control was not effective in controlling the population of R. norvegicus and provides evidence of the need for re-evaluation of rodent control practices in urban poor community settings.

Population dynamics of synanthropic rodents after a chemical and infrastructural intervention in an urban low-income community.

Synanthropic rodents are ubiquitous in low-income communities and pose risks for human health, as they are generally resistant to control programs. However, few or no studies have evaluated the long-term effect of chemical and infrastructural interventions on rodent population dynamics, especially in urban low-income communities, or evaluated the potential recovery of their population following interventions. We conducted a longitudinal study in a low-income community in the city of Salvador (BA, Brazil) to characterize the effect of interventions (chemical and infrastructural) on the dynamics of rodent population, and documented the post-intervention recovery of their population. We evaluated the degree of rodent infestation in 117 households/sampling points over three years (2014-2017), using tracking plates, a proxy for rodent abundance/activity. We reported a significant lower rodent activity/abundance after the chemical and infrastructural interventions (Z = -4.691 (p < 0.001)), with track plate positivity decreasing to 28% from 70% after and before interventions respectively. Therefore, the combination of chemical and infrastructural interventions significantly decreased the degree of rodent infestation in the study area. In addition, no rodent population rebound was recorded until almost a year post-intervention, and the post-intervention infestation level did not attain the pre-intervention level all through the study. Moreover, among pre-treatment conditions, access to sewer rather than the availability of food was the variable most closely associated with household rodent infestation. Our study indicates that Integrated Pest Management (IPM)-approaches are more effective in reducing rodent infestation than the use of a single method. Our findings will be useful in providing guidance for long-term rodent control programs, especially in urban low-income communities.

Genetic Evidence for a Potential Environmental Pathway to Spillover Infection of Rat-Borne Leptospirosis.

In this study, we genotyped samples from environmental reservoirs (surface water and soil), colonized rat specimens, and cases of human severe leptospirosis from an endemic urban slum in Brazil, to determine the molecular epidemiology of pathogenic Leptospira and identify pathways of leptospirosis infection. We identified a well-established population of Leptospira interrogans serovar Copenhageni common to human leptospirosis cases, and animal and environmental reservoirs. This finding provides genetic evidence for a potential environmental spillover pathway for rat-borne leptospirosis through the environment in this urban community and highlights the importance of environmental and social interventions to reduce spillover infections.

Amplification of pathogenic Leptospira infection with greater abundance and co-occurrence of rodent hosts across a counter-urbanizing landscape.

Land use change can elevate disease risk by creating conditions beneficial to species that carry zoonotic pathogens. Observations of concordant global trends in increased pathogen prevalence or disease incidence and landscape change have generated concerns that urbanization could increase transmission risk of some pathogens. Yet host-pathogen relationships underlying transmission risk have not been well characterized within cities, even where contact between humans and species capable of transmitting pathogens of concern occurs. We addressed this deficit by testing the hypothesis that areas in cities experiencing greater population loss and infrastructure decline (i.e., counter-urbanization) can support a greater diversity of host species and a larger and more diverse pool of pathogens. We did so by characterizing pathogenic Leptospira infection relative to rodent host richness and abundance across a mosaic of abandonment in post-Katrina New Orleans (Louisiana, USA). We found that Leptospira infection loads were highest in areas that harboured increased rodent species richness (which ranged from one to four rodent species detected). Areas with greater host co-occurrence also harboured a greater abundance of hosts, including the host species most likely to carry high infection loads, indicating that Leptospira infection can be amplified by increases in overall and relative host abundance. Evidence of shared infection among rodent host species indicates that cross-species transmission of Leptospira probably increases infection at sites with greater host richness. Additionally, evidence that rodent co-occurrence and abundance and Leptospira infection load parallel abandonment suggests that counter-urbanization can elevate zoonotic disease risk within cities, particularly in underserved communities that are burdened with disproportionate concentrations of derelict properties.

Effects of Accounting for Interval-Censored Antibody Titer Decay on Seroincidence in a Longitudinal Cohort Study of Leptospirosis.

Accurate measurements of seroincidence are critical for infections undercounted by reported cases, such as influenza, arboviral diseases, and leptospirosis. However, conventional methods of interpreting paired serological samples do not account for antibody titer decay, resulting in underestimated seroincidence rates. To improve interpretation of paired sera, we modeled exponential decay of interval-censored microscopic agglutination test titers using a historical data set of leptospirosis cases traced to a point source exposure in Italy in 1984. We then applied that decay rate to a longitudinal cohort study conducted in a high-transmission setting in Salvador, Brazil (2013-2015). We estimated a decay constant of 0.926 (95% confidence interval: 0.918, 0.934) titer dilutions per month. Accounting for decay in the cohort increased the mean infection rate to 1.21 times the conventionally defined rate over 6-month intervals (range, 1.10-1.36) and 1.82 times that rate over 12-month intervals (range, 1.65-2.07). Improved estimates of infection in longitudinal data have broad epidemiologic implications, including comparing studies with different sampling intervals, improving sample size estimation, and determining risk factors for infection and the role of acquired immunity. Our method of estimating and accounting for titer decay is generalizable to other infections defined using interval-censored serological assays.

Truth, hope, compassion in a time of corona virus and a presidential election.

Despite signs of public unity in response to the COVID-19 pandemic, the pandemic has also highlighted our divisions, disparities, and racism. The churches can have a voice for greater harmony and community if their public theology flows from their core beliefs and practices and is marked by engagement with truth, and a vision of hope acted out with compassion.

Publisher Correction: Pattern analysis of 532- and 1,064-nm picosecond-domain laser-induced immediate tissue reactions in ex vivo pigmented micropig skin.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Pattern analysis of 532- and 1,064-nm picosecond-domain laser-induced immediate tissue reactions in ex vivo pigmented micropig skin.

Optical pulses from picosecond lasers can be delivered to the skin as single, flat-top beams or fractionated beams using a beam splitter or microlens array (MLA). In this study, picosecond neodymium:yttrium aluminum garnet laser treatment using a single flat-top beam and an MLA-type beam at the wavelengths of 532 nm and 1,064 nm were delivered on ex vivo genotype-regulated, pigmented micropig skin. Skin specimens were obtained immediately after treatment and microscopically analyzed. Single flat-top beam treatment at a wavelength of 532 nm and a fluence of 0.05-J/cm2 reduced melanin pigments in epidermal keratinocytes and melanocytes, compared to untreated controls. Additionally, 0.1 J/cm2- and 1.3 J/cm2-fluenced laser treatment at 532 nm elicited noticeable vacuolation of keratinocytes and melanocytes within all epidermal layers. Single flat-top beam picosecond laser treatment at a wavelength of 1,064 nm and a fluence of 0.18 J/cm2 also reduced melanin pigments in keratinocytes and melanocytes. Treatment at 1,064-nm and fluences of 1.4 J/cm2 and 2.8 J/cm2 generated increasing degrees of vacuolated keratinocytes and melanocytes. Meanwhile, 532- and 1,064-nm MLA-type, picosecond laser treatment elicited fractionated zones of laser-induced micro-vacuolization in the epidermis and dermis. Therein, the sizes and degrees of tissue reactions differed according to wavelength, fluence, and distance between the microlens and skin.

Pattern analysis of 532- and 1064-nm microlens array-type, picosecond-domain laser-induced tissue reactions in ex vivo human skin.

Optical pulses from picosecond lasers can be delivered to the skin using microlens array (MLA) optics or a diffractive beam splitter to generate multiple, focused, high-intensity, micro-injury zones in the epidermis and dermis. The aim of our study was to histopathologically and immunohistochemically evaluate the patterns of 532- and 1064-nm MLA-type, picosecond laser-induced tissue reactions in human skin immediately after treatment. Picosecond neodymium:yttrium-aluminum-garnet (Nd:YAG) laser treatment using an MLA-type beam at the wavelengths of 532 nm and 1064 nm was delivered ex vivo to human skin. Irradiated skin specimens were then microscopically analyzed after hematoxylin and eosin staining and CD31 and Melan-A immunostaining. A single pulse of 532-nm MLA-type, picosecond laser treatment elicited cystic cavitation lesions at sizes of 83.4 ± 16.5 µm × 70.2 ± 17.3 µm (31-mm distance step) and 91.0 ± 44.7 µm × 81.2 ± 36.3 µm (48-mm distance step) in the epidermis and papillary dermis. Meanwhile, a single pulse of 1064-nm laser treatment generated cystic cavitation lesions at sizes of 107.0 ± 18.1 µm × 83.3 ± 37.4 µm (single-pulse mode) and 100.8 ± 40.4 µm × 83.1 ± 29.4 µm (dual-pulse mode) throughout the lower epidermis and upper papillary dermis. Lining epithelial cells in cystic cavitation lesions in the epidermis showed Melan-A-positive immunoreactivity, while cystic cavitation lesions in the dermis exhibited CD31-positive or CD31-negative/Melan-A-negative immunoreactivity. The present data can be used to predict 532- and 1064-nm MLA-type, picosecond-domain laser-induced tissue reactions in human skin.

Fine-scale GPS tracking to quantify human movement patterns and exposure to leptospires in the urban slum environment.

BACKGROUND: Human movement is likely an important risk factor for environmentally-transmitted pathogens. While epidemiologic studies have traditionally focused on household risk factors, individual movement data could provide critical additional information about risk of exposure to such pathogens. We conducted global positioning system (GPS) tracking of urban slum residents to quantify their fine-scale movement patterns and evaluate their exposures to environmental sources of leptospirosis transmission. METHODOLOGY/PRINCIPAL FINDINGS: We recruited participants from an ongoing cohort study in an urban slum in Brazil and tracked them for 24 hours at 30-second intervals. Among 172 subjects asked to participate in this cross-sectional study, 130 agreed to participate and 109 had good quality data and were included in analyses. The majority of recorded locations were near participant residences (87.7% within 50 meters of the house), regardless of age or gender. Similarly, exposure to environmental sources of leptospirosis transmission did not vary by age or gender. However, males, who have higher infection rates, visited a significantly larger area during the 24-hour period than did females (34,549m2 versus 22,733m2, p = 0.005). Four male participants had serologic evidence of Leptospira infection during the study period. These individuals had significantly larger activity spaces than uninfected males (61,310m2 vs 31,575m2, p = 0.006) and elevated exposure to rodent activity (p = 0.046) and trash deposits (p = 0.031). CONCLUSIONS/SIGNIFICANCE: GPS tracking was an effective tool for quantifying individual mobility in the complex urban slum environment and identifying risk exposures associated with that movement. This study suggests that in addition to source reduction, barrier interventions that reduce contact with transmission sources as slum residents move within their communities may be a useful prevention strategy for leptospirosis.

A model for leptospire dynamics and control in the Norway rat (Rattus norvegicus) the reservoir host in urban slum environments.

Leptospirosis is a zoonosis that humans can contract via contact with animal reservoirs directly or with water contaminated with their urine. The primary reservoir of pathogenic leptospires within urban slum environments is the Norway rat (Rattus norvegicus). Motivated by the annual outbreaks of human leptospirosis in slum urban settings, the within population infection dynamics of the Norway rat were investigated in Pau da Lima, an community in Salvador, Brazil. A mechanistic model of the dynamics of leptospire infection was informed by extensive field and laboratory data was developed and explored analytically. To identify the intraspecific transmission route of most importance, a global sensitivity analysis of the basic reproduction number to its components was performed. In addition, different methods of rodent control were investigated by calculating target reproduction numbers. Our results suggest environmental transmission plays an important role in the maintenance of infection in the rodent population. To control numbers of wild Norway rats, combinations of controls are recommended but environmental control should also be investigated to reduce prevalence of infection in rats.

Quantification of pathogenic Leptospira in the soils of a Brazilian urban slum.

BACKGROUND: Leptospirosis is an important zoonotic disease that causes considerable morbidity and mortality globally, primarily in residents of urban slums. While contact with contaminated water plays a critical role in the transmission of leptospirosis, little is known about the distribution and abundance of pathogenic Leptospira spp. in soil and the potential contribution of this source to human infection. METHODS/PRINCIPAL FINDINGS: We collected soil samples (n = 70) from three sites within an urban slum community endemic for leptospirosis in Salvador, Brazil. Using qPCR of Leptospira genes lipl32 and 16S rRNA, we quantified the pathogenic Leptospira load in each soil sample. lipl32 qPCR detected pathogenic Leptospira in 22 (31%) of 70 samples, though the median concentration among positive samples was low (median = 6 GEq/g; range: 4-4.31×102 GEq/g). We also observed heterogeneity in the distribution of pathogenic Leptospira at the fine spatial scale. However, when using 16S rRNA qPCR, we detected a higher proportion of Leptospira-positive samples (86%) and higher bacterial concentrations (median: 4.16×102 GEq/g; range: 4-2.58×104 GEq/g). Sequencing of the qPCR amplicons and qPCR analysis with all type Leptospira species revealed that the 16S rRNA qPCR detected not only pathogenic Leptospira but also intermediate species, although both methods excluded saprophytic Leptospira. No significant associations were identified between the presence of pathogenic Leptospira DNA and environmental characteristics (vegetation, rat activity, distance to an open sewer or a house, or soil clay content), though samples with higher soil moisture content showed higher prevalences. CONCLUSION/SIGNIFICANCE: This is the first study to successfully quantify the burden of pathogenic Leptospira in soil from an endemic region. Our results support the hypothesis that soil may be an under-recognized environmental reservoir contributing to transmission of pathogenic Leptospira in urban slums. Consequently, the role of soil should be considered when planning interventions aimed to reduce the burden of leptospirosis in these communities.

The helminth community of a population of Rattus norvegicus from an urban Brazilian slum and the threat of zoonotic diseases.

Urban slums provide suitable conditions for infestation by rats, which harbour and shed a wide diversity of zoonotic pathogens including helminths. We aimed to identify risk factors associated with the probability and intensity of infection of helminths of the digestive tract in an urban slum population of Rattus norvegicus. Among 299 rats, eleven species/groups of helminths were identified, of which Strongyloides sp., Nippostrongylus brasiliensis and, the human pathogen, Angiostrongylus cantonensis were the most frequent (97, 41 and 39%, respectively). Sex interactions highlighted behavioural differences between males and females, as eg males were more likely to be infected with N. brasiliensis where rat signs were present, and males presented more intense infections of Strongyloides sp. Moreover, rats in poor body condition had higher intensities of N. brasiliensis. We describe a high global richness of parasites in R. norvegicus, including five species known to cause disease in humans. Among these, A. cantonensis was found in high prevalence and it was ubiquitous in the study area - knowledge which is of public health importance. A variety of environmental, demographic and body condition variables were associated with helminth species infection of rats, suggesting a comparable variety of risk factors for humans.

Zoonotic and Vector-Borne Diseases in Urban Slums: Opportunities for Intervention.

Urban slums provide conditions that increase the risk of exposure to vector-borne and zoonotic pathogens. Large interventions, such as social and sanitary changes, are a priority but their implementation is challenging. Integration between the multidisciplinary understanding of pathogens' dynamics and community participatory approaches is a key prevention strategy.

Using fine-scale spatial genetics of Norway rats to improve control efforts and reduce leptospirosis risk in urban slum environments.

The Norway rat (Rattus norvegicus) is a key pest species globally and responsible for seasonal outbreaks of the zoonotic bacterial disease leptospirosis in the tropics. The city of Salvador, Brazil, has seen recent and dramatic increases in human population residing in slums, where conditions foster high rat density and increasing leptospirosis infection rates. Intervention campaigns have been used to drastically reduce rat numbers. In planning these interventions, it is important to define the eradication units - the spatial scale at which rats constitute continuous populations and from where rats are likely recolonizing, post-intervention. To provide this information, we applied spatial genetic analyses to 706 rats collected across Salvador and genotyped at 16 microsatellite loci. We performed spatially explicit analyses and estimated migration levels to identify distinct genetic units and landscape features associated with genetic divergence at different spatial scales, ranging from valleys within a slum community to city-wide analyses. Clear genetic breaks exist between rats not only across Salvador but also between valleys of slums separated by <100 m-well within the dispersal capacity of rats. The genetic data indicate that valleys may be considered separate units and identified high-traffic roads as strong impediments to rat movement. Migration data suggest that most (71-90%) movement is contained within valleys, with no clear source population contributing to migrant rats. We use these data to recommend eradication units and discuss the importance of carrying out individual-based analyses at different spatial scales in urban landscapes.