The Veterinary Journal 222 (2017) 29–35

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The Veterinary Journal

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Hotspots of canine leptospirosis in the United States of America

Allison M. White a, Carlos Zambrana-Torrelio a,*, Toph Allen a, Melinda K. Rostal a,
Andrea K. Wright b, Eileen C. Ball b, Peter Daszak a, William B. Karesh a
a
EcoHealth Alliance, 460 West 34th Street, 17th Floor, New York, NY 10001, USA
b Zoetis, 100 Campus Drive, Florham Park, NJ 07932, USA

A R T I C L E I N F O A B S T R A C T

Article history: Leptospirosis is a widespread zoonotic disease that causes hepatic and renal disease in dogs and human
Accepted 28 February 2017 beings. The incidence of leptospirosis in dogs in the USA appears to be increasing. This study used 14
years of canine leptospirosis testing data across 3109 counties in the USA to analyze environmental and
Keywords: socio-economic correlates with rates of infection and to produce a map of locations of increased risk for
Canine canine leptospirosis. Boosted regression trees were used to identify the probability of a dog testing pos-
Leptospirosis
itive for leptospirosis based on microscopic agglutination test (MAT) results, and environmental and socio-
Zoonosis
economic data. The Midwest, East and Southwest were more likely to yield positive tests for leptospirosis,
Risk
Topography although specific counties in Appalachia had some of the highest predicted probabilities. Location (sub-
Climate urban areas or areas with deciduous forest) and climate (precipitation and temperature) were predictors
for positive MAT results for leptospirosis, although the precise direction and strength of the effects was
difficult to interpret. Wide geographic variation in predicted risk was identified. This risk mapping ap-
proach may provide opportunities for improved diagnosis, control and prevention of leptospirosis in dogs.
© 2017 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Introduction positive microscopic agglutination test (MAT) results increased

Leptospirosis is a common and widespread zoonotic disease, with
reservoirs in domestic and wild animals (Waitkins, 1985; Bharti et al.,
2003; Nelson and Couto, 2003; Heymann, 2008; Costa et al., 2015).
The disease is caused by spirochaetal bacteria belonging to the genus
Leptospira, which infect a range of mammals, including humans, live-
stock (e.g. cattle pigs and goats) and companion animals (e.g. dogs
and horses) (Nelson and Couto, 2003; Heymann, 2008)1. Infection
is typically transmitted through direct contact of oral or nasal
mucosa, or broken skin, with contaminated urine or water, and dogs
are at risk of infection from drinking contaminated water (Nelson
and Couto, 2003; Heymann, 2008). Leptospirosis can cause severe
clinical disease in dogs, including acute hepatic and/or renal failure.
It can also produce a chronic carrier status, presenting as idio-
pathic polyuria/polydipsia, which may not be preceded by severe
hepatic or renal disease (Ward, 2002b; Nelson and Couto, 2003).
Canine leptospirosis has been reported in the USA for more than
100 years (Bolin, 1996) and the prevalence of leptospirosis is reported
to be increasing; the rate increased by 1.2 cases/100,000 dogs/year
from 1983 to 1998 (Ward et al., 2002). The national proportion of
* Corresponding author.
E-mail address: zambrana@ecohealthalliance.org (C. Zambrana-Torrelio).
1
See: CDC, 2014. Leptospirosis. https://www.cdc.gov/leptospirosis/ (accessed 10
May 2016).
from 8.7% to 12% from 2002 to 2004 (Glickman et al., 2006; Moore
et al., 2006). Clusters of cases of canine leptospirosis have been
detected in Texas, California and the upper Midwest, suggesting that,
whilst leptospirosis is ubiquitous across the USA, some areas are
disproportionately affected (Ward, 2002a; Gautam et al., 2010;
Hennebelle et al., 2013).
Environmental and socio-economic factors are thought to explain
the distribution and transmission of leptospirosis (Gubler et al., 2001;
Sehgal, 2006; Reis et al., 2008). Flooding has been linked to out-
breaks of leptospirosis (Reis et al., 2008). The risk of leptospirosis
is also related to land cover (e.g. evergreen forests, percentage of
wetlands and public open spaces) and proximity to forests
(Tangkanakul et al., 2000; Ward et al., 2004; Ahern et al., 2005;
Ghneim et al., 2007; Alton et al., 2009; Raghavan et al., 2011, 2012a,
2012b, 2013). To date, there has been no systematic analysis of the
distribution of leptospirosis in the USA and risk factors associated
with the occurrence of the disease.
In the current study, we used novel statistical approaches to
analyze large sets of leptospirosis test data. We tested for the
correlation of positive results with a wide range of hypothesized
drivers and used the results to identify ‘hotspots’ of leptospirosis
(areas of relative higher probability for leptospirosis cases) and
the factors that are likely associated with them. Based on the
ecology and epidemiology of leptospirosis, we hypothesized that
abiotic factors, such as precipitation and temperature, as well as
anthropic activities, measured as change in land use cover, can be

http://dx.doi.org/10.1016/j.tvjl.2017.02.009
1090-0233/© 2017 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/
4.0/).
30 A.M. White et al. / The Veterinary Journal 222 (2017) 29–35

used to detect areas of higher prevalence (i.e. hotspots) of canine using R (Jorge et al., 2015) and the R program dismo (R package, version 1.0–12).
leptospirosis in the USA. The predicted probability per county was mapped using ArcGIS version 10.2
(Environmental Systems Research Institute).

Materials and methods

Results
Literature review
Literature review
Literature related to the prevalence of canine leptospirosis and associated factors
was reviewed to identify variables for selection and to assist model building. PubMed
and ISI Web of Knowledge data bases were searched for the terms ‘(leptospirosis Five hundred articles were identified in the initial search, 474
OR Leptospira) AND (dog OR dogs OR canine OR Canis familiaris)’. Articles used were of which were excluded on the basis of geography and relevance
limited to those published from 2000 onwards that were published in English, French (e.g. randomized control trials, vaccine studies, laboratory diag-
or Spanish that focused on North America (Canada, USA and Mexico); most data were
nostic development, case studies and studies examining acute renal
from post-2000, although some publications included earlier data, extending as far
back as 1970. failure). We identified 26 peer reviewed publications with de-
tailed testing data (see Appendix: Supplementary material). The
Data sources and explanatory variables sample size in these articles ranged from 32 (Martin et al., 2014)
to over 1 million dogs (Ward et al., 2002). We identified a range of
We obtained serological canine leptospirosis MAT results in the USA through
climatic, land-cover and socio-economic factors associated with
an agreement with IDEXX Laboratories. A total of 87,355 tests were available in the
proprietary database; however, vaccine history and whether samples were submit- canine leptospirosis (Tangkanakul et al., 2000; Ward et al., 2004;
ted for paired MATs were unknown. All MAT results for tests conducted from 2000 Ahern et al., 2005; Ghneim et al., 2007; Alton et al., 2009; Raghavan
to 2014 at IDEXX Laboratories were included. The sensitivity of MAT has been es- et al., 2011, 2012a, 2012b, 2013) and included these variables in the
timated to be 50–67% at 1:400 dilution and 22–67% at 1:800 dilution, while the
model when data was available (Table S1; see Appendix: Supple-
specificity ranges from 69–93% at 1:400 dilution and 69–100% for 1:800 dilution
in dogs with confirmed leptospirosis, and dogs with clinical and laboratory indica-
mentary material).
tors for leptospirosis, but where ultimately leptospirosis was ruled out (Miller et al.,
2008). MATs performed at the same laboratories on samples from specific patho- Descriptive statistics
gen free dogs were 100% specific at both 1:400 and 1:800 dilutions (Miller et al.,
2008). Although the sensitivity and specificity of both titers were similar, a cut-off
of ≥1:800 dilution was selected for this study to limit the effect of unknown vacci- A total of 12,317/87,355 (14.1%) MAT tests performed by IDEXX
nation status; this was also the cut-off value used by IDEXX for diagnostic purposes. in the USA from 2000 to 2014 were positive for leptospirosis. At
All serovars were included in our analysis without distinction. All data was anonymized least one MAT result was available for 1260/3109 (40.5%) counties
and geo-referenced at USA zip code level.
in the contiguous USA (Fig. 1) from which 746/1260 (59.2%) coun-
To control the effect of dog population size on the number of samples submit-
ted for testing, we estimated the dog population at county level. We weighted total
ties had one or more positive tests. The number of samples submitted
state level dog population data (American Veterinary Medical Association, 2012) by for MAT from a county ranged from 1 to 3761 (mean 62) and the
county level human population data2, assuming the proportion of dog owners is maximum number of positive tests in one county was 670 (Cook
uniform within a state’s counties. County, Illinois).
Variables for the spatial analyses were compiled in four main categories:
(1) climate; (2) land cover type; (3) ecology; and (4) socio-economic status. Results
from the literature review were used to provide information for selection of vari- Modeling
ables. Climatic variables included precipitation and temperature across the USA over
a 30 year period (1981–2010) (Hijmans et al., 2005)3. Land cover type and percent- Values from predictive modeling were interpreted as the prob-
age cover were collected from the 2011 National Land Cover Database (Jin et al., 2013).
The mean number of rodent species per county distributed across the USA was
ability that a diagnostic test in a given county would be positive;
used as an ecological indicator of host diversity under the assumption that higher for example, a probability of 0.14 indicates that there is a 14%
diversity increases the likelihood of transmission of leptospirosis, in the absence of chance that any given MAT will be positive. The Midwest, East
viable data on the number of rodents in a region (which is also likely to fluctuate and Southwest were more likely to yield positive tests for lepto-
widely over time).
spirosis, although specific counties in Appalachia had some of the
Median household income and percentage of residents with a Bachelor’s degree
or higher were used as socio-economic variables4. All variables were aggregated highest predicted probabilities (Table 1). The highest predicted
at county level using US Census 2010 county boundaries5. Since the number of re- probability observed was 0.37 in Webster County, West Virginia,
quested tests varied highly among counties, we determined the percentage of positive whilst the lowest was 0.02 in Harney County, Oregon. The overall
tests by county and used this proportion for all our analyses. median predicted probability was 0.12. Eighty-four (2.7%) coun-
ties had predicted probabilities >0.2. The final model fitted 1200
Modeling
trees; the cross-validation accuracy was 0.58, which is better than
Predictive models were constructed using boosted regression trees (BRTs) random chance, but closer to random chance than perfect accura-
(Leathwick et al., 2006) with internal cross-validation, previously used to model species cy. Hotspot maps of the relative risk of leptospirosis were produced
distributions (Leathwick et al., 2006; De’ath, 2007; Pittman et al., 2009) and disease from the BRT model for MAT results (Figs. 2 and 3). These show
ranges (Hay et al., 2013). Boosted regression trees fit an ensemble of regression trees
to data in a stepwise fashion, up-weighting poorly predicted data points at each step
and monitoring predictive accuracy to prevent over-fitting. Compared to tradition-
al statistical techniques, they predict patterns in complex data sets accurately and Table 1
are robust for use on data sets with many interacting variables or non-linear rela- Counties with the highest predicted probabilities for canine leptospirosis in the USA.
tionships; no P values, regression coefficients or confidence intervals are reported
(Cutler et al., 2007; Elith et al., 2008). Rank County State Predicted Dogs expected to
The BRT used 31 county level variables for climate and precipitation, dog own- probability test positive
ership, landscape composition and rodent diversity. Data analysis was performed 1 Webster County West Virginia 0.370 1/2.7
2 Marion County Indiana 0.34 1/2.9
3 Harrisonburg City Virginia 0.33 1/3.0
2 See: US Census Bureau, 2010. 2010 American Community Survey 1-Year Estimates, 4 Staunton City Virginia 0.33 1/3.0
5 Waynesboro City Virginia 0.31 1/3.2
Washington, DC. https://factfinder.census.gov (accessed 10 May 2016).
3 6 Adair County Kentucky 0.31 1/3.2
See: PRISM Climate Group. http://prism.oregonstate.edu (accessed 10 May 2016).
4 See: US Census Bureau, 2010. 2010 American Community Survey 1-Year Estimates, 7 Covington City Virginia 0.30 1/3.3
8 Curry County Oregon 0.30 1/3.3
Washington, DC. https://factfinder.census.gov (accessed 10 May 2016).
5 9 Nicholas County West Virginia 0.30 1/3.3
See: US Census Bureau, 2014. 2014 TIGER/Line Shapefiles. https://www
10 Bedford City Virginia 0.29 1/3.4
.census.gov/geo/maps-data/data/tiger-line.html (accessed 10 May 2016).
 A.M. White et al. / The Veterinary Journal 222 (2017) 29–35 31

Fig. 1. Percent of microscopic agglutination tests (MAT) results positive by county in the USA in 2000–2014. Darker colors indicate a greater proportion of positive tests.
Counties with no data indicate that no MATs were submitted to the reference laboratory during the study period.

Fig. 2. Predicted probability of a positive microscopic agglutination test (MAT) result for canine leptospirosis in the continental USA. Predicted probabilities range from
0.023 to 0.371, indicating that approximately 1/3 dogs tested is expected to be positive for leptospirosis. Scale is green to red where green indicates lower probability and
red indicates higher probability.
32 A.M. White et al. / The Veterinary Journal 222 (2017) 29–35

Fig. 3. Insets from Figs. 1 and 2, showing the counties for Maine (above) and Idaho (below). The left side shows the percent of positive microscopic agglutination test (MAT)
results and the right side shows the predicted probability of a positive MAT result.

the probability by county that a given test will be positive for Discussion
leptospirosis. Since the BRT model analyses complex interactions
and non-linear relationships, the directionality and precise rela- This analysis has produced the first comprehensive predictive
tionship between any individual variable and the outcome is too risk map for canine leptospirosis in the contiguous USA and statistical
idiosyncratic and context dependent to be meaningful on its own;
for example, there appears to be a slightly decreased probability
Table 2
of a positive test at higher ranges of precipitation in the coldest Relative influence of the five most important variables on the boosted regression
quarter of the year, conditional on other variables, and there appears tree model.
to be a modest increase as the proportion of a county covered by
Variable Group Percentage relative
low intensity developed land approaches 0.3. Instead, the overall influence a
predictions of a model for a county should be considered. Vari-
Deciduous forest Land cover 10.9
ables important to the model’s overall output included precipitation, Precipitation (coldest quarter mean) Bioclimate 9.0
temperature, deciduous forested land, and low density developed Scrubland and shrub land Land cover 6.30
land (e.g. residential areas with houses built on large lots or areas Developed (low intensity) Land cover 5.7
with 20–49% of surface areas covered with impervious material) Temperature (mean) Bioclimate 5.0

(Table 2). a Greater relative influence indicates greater contribution to model results.
 A.M. White et al. / The Veterinary Journal 222 (2017) 29–35
support for some previously hypothesized risk factors. The varia-
tion in canine leptospirosis risk in specific counties and regions of
the USA appears to be mainly influenced by environmental and land
use factors. Our model suggests that landscape and environmen-
tal factors, specifically low density developed land (e.g. residential
areas with houses built on large lots or areas with 20–49% of surface
areas covered with impervious material), deciduous forested land,
precipitation and temperature, are useful in predicting MAT test
results. However, as stated above, the model’s predictions for in-
dividual variables are too idiosyncratic and context dependent to
be broadly applicable or simply summarized.
Whilst boosted regression trees allow for the building of complex
models with multiple variables, one of the major drawbacks of this
approach is that the individual effects of any one specific variable
are not easily interpretable. Given the complexity of our model and
the number of variables included (e.g. multiple land cover vari-
ables), we could identify important variables, but could not describe
the precise relationship between one variable and the risk of lep-
tospirosis. Despite the complexity, the analysis allowed us to indicate
how much influence a particular variable might have on the model
prediction (Table 2).
The mechanistic relationship between different vegetation types
and the risk of leptospirosis is unclear and may be a reflection that
rural regions provide more opportunity for rodent reservoirs to trans-
mit leptospirosis to dogs. Deciduous forest cover, which contributed
most to the predictive power of the model, has not been proposed
previously as a risk factor for canine leptospirosis. It is likely that
deciduous forest is a proxy for other conditions favorable for lep-
tospirosis transmission, such as specific precipitation regimes, higher
rodent density and specific dog behavior.
One drawback of our model is that it does not account for flood-
ing; therefore, it is possible that variables representing precipitation
could explain some of the leptospirosis risk attributed to flooding
in the literature (Ahern et al., 2005; Raghavan et al., 2012a). Our
finding of the risk for leptospirosis in spacious residential areas
(lower density developed land) aligns with the findings of previ-
ous studies (Ward et al., 2004; Ghneim et al., 2007; Raghavan et al.,
2011), whilst only one study has cited rural areas as a risk for lep-
tospirosis (Alton et al., 2009). Lower density developed land provides
a combination of impervious surfaces that can concentrate rain water
run-off and acts as a good habitat for reservoir animals, such as
rodents and raccoons, hence simulating the effects of ‘flooding’
without requiring a specific level of annual rainfall.
Many of the counties with the highest overall predicted risk
are in Appalachia (i.e. West Virginia, Eastern Kentucky and Western
Virginia). The Appalachian Mountains receive high annual
precipitation6 and contain predominantly deciduous forests. Clus-
ters of leptospirosis cases have been identified in Illinois and
Michigan in other studies (Ward, 2002a; Gautam et al., 2010) and
coincide with the results of our modeling. Significant spatial clus-
ters were observed throughout the USA, including in Texas, California,
the greater Chicago area and some regions of the upper Midwest
(Ward, 2002a; Gautam et al., 2010; Hennebelle et al., 2013). This
increased risk may be explained by the proximity to the Great Lakes
and the moderately high annual precipitation in these areas.
In addition, we identified several counties in Kansas and
Nebraska at higher risk for leptospirosis, despite the absence of
available testing data for many counties in those states. The pres-
ence of leptospirosis in these states is supported by the literature.
Raghavan et al. (2011) Raghavan et al., (2012a), Raghavan et al.,
(2012b) examined specific risk factors (hydrologic, environmental
6 See: PRISM Climate Group. http://prism.oregonstate.edu (accessed 10 May 2016).
33
and socio-economic factors) for canine leptospirosis in Kansas and
Nebraska. In the study of Harkin et al. (2003), 41/500 (8.2%) dogs
were shedding leptospires.
Our analytical approach has some important limitations. Firstly,
due to a lack of available testing data, some areas of the contiguous
USA (i.e. the upper Midwest and parts of the Southeast) were poorly
represented in our testing data. Whilst the use of predictive methods
allows us to make predictions even when data are lacking, the in-
clusion of data from these areas would increase predictive accuracy.
Additional analyses using testing data from these areas would provide
a means to refine and externally validate our results.
Secondly, we used a titer threshold ≥1:800 to select positive tests
for our model. This cut-off threshold is expected to identify more
exposures, whilst minimizing the risk of including positive titers
due to vaccination. When vaccinated dogs were monitored for 1 year
post-vaccination, some dogs developed titers ≥1:800 by weeks 7–15,
whereas by weeks 29–52 none of the dogs had titers ≥1:400 and
only a small percentage had titers ≥1:100 (Martin et al., 2014). Our
literature review indicated that MAT titer thresholds for consider-
ing a test to be positive ranged from ≥1:100 to ≥1:3,200. The 2010
American College of Veterinary Internal Medicine (ACVIM) Small
Animal Consensus Statement on Leptospirosis (Sykes et al., 2011)
states that there is a lack of consensus as to which titer level should
be used to determine that a test is negative for leptospirosis and
also that single positive titers must be considered with clinical signs
and a paired titer, since even a titer ≥1:800 does not confirm a di-
agnosis of leptospirosis. We followed the recommendation of the
diagnostic laboratory (positive titer ≥1:800), which fits with our
desire to exclude animals vaccinated within the past year and to
have enough confidence in the likelihood of exposure to proceed
with the epidemiological analysis.
Given the relatively low vaccination rates for canine leptospi-
rosis in the USA (<4% of dogs in 2011) (American Veterinary Medical
Association, 2012), we do not expect this to have a major impact
on the results (Klaasen et al., 2003). Although vaccine history and
whether samples were submitted for paired MATs were unknown,
given the overall size of the data set, this was considered unlikely
to have an impact on results.
Data were aggregated at county level due to data availability and
to estimate leptospirosis risk in an easily interpretable manner to
aid veterinarians in describing risks to owners. County lines are often
arbitrary and may have changed during the course of our study. Using
an arbitrary unit of area (county) may have augmented some of the
observed effects. This would be likely to have the greatest impact
in the Western USA, where the counties are large.
Our analysis provided some counterintuitive results. Several coun-
ties with high-predicted values were found in areas where clusters
of leptospirosis had not previously been identified. In some of these
counties, the available data did not have a high proportion of pos-
itive tests, indicating differences between the predicted values and
existing leptospirosis clusters (Figs. 2 and 3) (Gautam et al., 2010;
Hennebelle et al., 2013). Counties with low risk sometimes adjoin
counties at high risk; for example, in Virginia, small counties with
high risk are sometimes entirely surrounded by larger counties with
lower risk. This may be due to smaller counties being population
centers or due to artifacts in the data. These specific counties should
be examined further to determine whether the low level of re-
ported leptospirosis is due to lack of data, lack of testing or better
vaccination coverage.
Areas identified by our model as higher risk areas differed from
the overall distribution of proportion of available positive tests
throughout the USA (Figs. 1 and 2), indicating that this method
provides utility compared to analyzing historical testing data alone.
Identifying the county level risk for leptospirosis can contribute to
determining where to implement prevention and control mea-
sures, testing and vaccination.
34 A.M. White et al. / The Veterinary Journal 222 (2017) 29–35
Leptospirosis is a disease of increasing concern for both people
and dogs. Identified canine leptospirosis incidences in the USA have
ranged from 0.04% in a study of hospital prevalence from 1970–
1998 across the USA, to as high as 29% in a study examining tests
submitted to the veterinary diagnostic lab in Illinois from 1996 to
2001. This variation makes it important to identify risk areas for
this disease (Ward et al., 2002; Boutilier et al., 2003). The US Centers
for Disease Control and Prevention recently reinstated leptospiro-
sis in human beings as a nationally notifiable disease; in 2014, there
were 21 human cases of leptospirosis (Centers for Disease Control,
2015). Dogs play an important role as potential indicators of areas
with high endemicity for leptospirosis and, although infrequent, zoo-
notic transmission of leptospirosis from dogs to human beings can
occur. Thus, recognizing and preventing canine leptospirosis has im-
plications for human health as well as dogs.
Conclusions
Our model can be used to characterize the risk of canine lepto-
spirosis across the USA and can be applied to improve delivery of
veterinary services, including diagnostics and vaccination, and to
identify areas for increased research and surveillance efforts. Canine
leptospirosis remains an important disease, widely distributed in
the USA, with varying levels of disease risk. Recognizing and iden-
tifying the areas most at risk will help to provide improved veterinary
care and control of this disease.
Conflict of interest statement
Funds for this project were provided by Zoetis, which currently
markets a vaccine against canine leptospirosis. Andrea Wright and
Eileen Ball are employees of Zoetis. None of the other authors of
this paper have a financial or personal relationship with other people
or organizations that could inappropriately influence or bias the
content of the paper.
Acknowledgements
Funding for this project was provided by Zoetis. The authors
would like to thank IDEXX Laboratories for providing the data for
this project.
Appendix: Supplementary material
Supplementary data to this article can be found online at
doi:10.1016/j.tvjl.2017.02.009.
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