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

  1. Max T Eyre  Is a corresponding author
  2. Fábio N Souza
  3. Ticiana SA Carvalho-Pereira
  4. Nivison Nery
  5. Daiana de Oliveira
  6. Jaqueline S Cruz
  7. Gielson A Sacramento
  8. Hussein Khalil
  9. Elsio A Wunder
  10. Kathryn P Hacker
  11. José E Hagan
  12. James E Childs
  13. Mitermayer G Reis
  14. Mike Begon
  15. Peter J Diggle
  16. Albert I Ko
  17. Emanuele Giorgi
  18. Federico Costa
  1. Centre for Health Informatics, Computing, and Statistics, Lancaster University Medical School, United Kingdom
  2. Liverpool School of Tropical Medicine, United Kingdom
  3. Institute of Collective Health, Federal University of Bahia, Brazil
  4. Swedish University of Agricultural Sciences, Sweden
  5. Oswaldo Cruz Foundation, Brazilian Ministry of Health, Brazil
  6. Department of Epidemiology of Microbial Diseases, Yale School of Public Health, United States
  7. University of Pennsylvania, United States
  8. World Health Organization (WHO) Regional Office for Europe, Denmark
  9. Department of Evolution, Ecology and Behaviour, University of Liverpool, United Kingdom
9 figures, 8 tables and 2 additional files

Figures

Study site and timeline.

(A) Map of the three valleys within the study site in Pau da Lima, with household locations for the serosurveys marked as orange circles. Locations sampled in the the rat ecology study are shown for …

Directed acyclic graph (DAG) of the rattiness-infection model framework.

R(x) is the value of a spatially continuous stochastic rattiness process at location x. The outcome variables Yk:k=1,,5 are the set of five rat abundance indices that provide information about R(x): traps (k=1)…

The study participant flow chart in line with the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) statement (http://www.strobestatement.org).
Household infection and elevation maps.

(A) Map of participant household locations with the number of leptospiral infections in each household marked (grey circle - no infections; orange square - 1 infection; red diamond - 2 infections; …

Predicted relationship between rattiness and infection risk from the multivariable mixed effects logistic regression demonstrating evidence of an interaction with relative elevation category (low, medium and high).

Shown on the log-odds scale with shaded areas corresponding to 95% confidence intervals.

Joint rattiness-infection model predictions.

(A) Mean predicted rattiness; (B) Mean predicted leptospiral infection risk for 30-year-old male participants with a household per capita income of USD$1 /day who never/rarely have contact with …

Appendix 1—figure 1
Generalized Additive Model (GAM) partial dependence plots for the unstructured random variation in rattiness,,U^i plotted against the continuous explanatory variables considered in the analysis (shaded areas correspond to 95% confidence intervals).

(A) elevation relative to the bottom of valley, (B) distance to large refuse piles, (C) impervious land cover in 20 m radius buffer around sampling point. are estimated using a non-spatial model …

Appendix 1—figure 2
Generalized Additive Model (GAM) partial dependence plots for human infection risk plotted against the continuous explanatory variables considered in this analysis (shaded areas correspond to 95% confidence intervals).

(A) age, (B) household per capita income (in USD), (C) years of education, (D) household elevation relative to the bottom of valley, (E) impervious land cover in 20 m radius buffer around household.

Appendix 7—figure 1
Residual diagnostic plots showing randomised quantile residuals plotted against: (A) fitted values; (B–H) variables in the model.

Tables

Table 1
Multivariable linear regression analysis of predictors for rattiness (note that rattiness is a unit-variance random variable when interpreting the magnitude of effect estimates).
VariableEstimate (95% CI) *
Relative elevation (per 1 m increase)
0–8 m0.04 (0.00, 0.07)
8–22 m–0.04 (-0.09, 0.01)
>22 m0.06 (0.00, 0.10)
Distance to large refuse piles (per 10 m increase)
0–50 m–0.07 (-0.13,–0.01)
>50 m0.02 (-0.05, 0.09)
Impervious land cover (per 10% increase)–0.05 (-0.08,–0.01)
  1. *

    CI, Confidence interval.

  2. The effects of relative elevation and distance to refuse are modelled as broken linear models with transitions at 8m and 22m, and 50m, respectively. This was informed by the relationship described by Generalized Additive Modelling in Appendix 1—figure 1.

Table 2
Univariable mixed effects logistic regression analysis of human risk factors for leptospiral infection.
VariableOR (95% CI)*aOR (95% CI)*
Demographic and social status
Age (per year)
 0–30 years old1.08 (1.03, 1.13)1.09 (1.04, 1.15)
 >30 years old1.02 (0.96, 1.09)1.02 (0.95, 1.08)
Male gender2.22 (1.31, 3.85)2.78 (1.56, 4.96)
Daily per capita household income (US$/day)1.01 (0.89, 1.11)0.92 (0.80, 1.05)
Valley
 1REFREF
 23.35 (1.33, 10.37)3.52 (1.23, 10.05)
 32.39 (0.93, 7.38)2.53 (0.88, 7.27)
Adult illiteracy1.34 (0.61, 2.79)0.66 (0.29, 1.49)
Education (per year of education)
 0–5 years1.05 (0.85, 1.32)1.14 (0.91, 1.44)
 >5 years0.96 (0.73, 1.27)0.96 (0.75, 1.26)
Household environment
Impervious land cover (per 10% increase)0.87 (0.76, 0.99)0.82 (0.71, 0.95)
Relative elevation (per 1 m increase)
 0–20 m0.94 (0.89, 0.99)0.93 (0.88, 0.99)
 >20 m1.12 (0.98, 1.29)1.12 (0.97, 1.29)
Relative elevation category
 Low (0–6.7 m)REFREF
 Medium (6.7–15.6 m)0.72 (0.37, 1.39)0.72 (0.36, 1.44)
 High (>15.6 m)0.58 (0.27, 1.20)0.51 (0.23, 1.11)
Open sewer within 10 m1.60 (0.85, 3.17)1.69 (0.85, 3.37)
Unprotected from open sewer1.00 (0.55, 1.79)1.11 (0.61, 2.03)
Live on hillside0.99 (0.52, 1.86)0.89 (0.46, 1.71)
Occupational exposures
Work in construction §1.36 (0.51, 3.21)0.62 (0.23, 1.67)
Work as travelling salesperson §4.81 (1.12, 18.78)2.97 (0.71, 12.40)
Work in refuse collection §2.95 (1.04, 7.89)1.57 (0.56, 4.42)
Work involves contact with floodwater §0.89 (0.04, 5.61)0.52 (0.05, 4.96)
Work involves contact with sewer water §3.61 (0.45, 20.38)1.92 (0.29, 12.80)
Behavioural exposures
Contact with floodwater in last 6 months
 Never/rarelyREFREF
 Sometimes0.61 (0.27, 1.25)0.66 (0.30, 1.47)
 Frequently2.14 (0.91, 4.94)2.84 (1.18, 6.86)
Contact with sewer water in last 6 months
 Never/rarelyREFREF
 Sometimes0.55 (0.19, 1.31)0.67 (0.25, 1.78)
 Frequently1.42 (0.51, 3.50)1.63 (0.61, 4.41)
  1. *

    OR, Odds ratio; aOR, Adjusted odds ratio; CI, Confidence interval; REF, Reference level.

  2. The effect of age, education and relative elevation are modelled as broken linear models with transitions at 30 years old, 5 years of education and an elevation of 20m. This was informed by the relationship described by Generalized Additive Modelling (Appendix 1—figure 2).

  3. Relative elevation category consists of three discrete groups representing three regions with different floodingrisk profiles.

  4. §

    Binary variable with reference category of ‘no occupational exposure’.

Table 3
Parameter estimates for the full joint rattiness-infection model.
ParameterEstimate (95% CI)
Human infection risk factorsOR
Age (per year)
 0–30 years old1.09 (1.04, 1.19)
 >30 years old1.02 (0.92, 1.09)
Male gender2.69 (1.58, 5.89)
Daily per capita household income (US$/day)0.93 (0.74, 1.05)
Valley
 1REF
 22.91 (1.03, 20.82)
 32.28 (0.86, 14.00)
Relative elevation category
 Low (0–6.7 m)REF
 Medium (6.7–15.6 m)0.77 (0.31, 1.66)
 High (>15.6 m)0.67 (0.11, 1.64)
Work as travelling salesperson3.16 (0.38, 20.57)
Contact with floodwater in last 6 months
 Never/rarelyREF
 Sometimes0.62 (0.18, 1.39)
 Frequently2.47 (0.67, 7.41)
Rattiness (per unit rattiness)
ξlow1.14 (1.05, 1.53)
ξmed1.25 (1.08, 1.74)
ξhigh3.27 (1.68, 19.07)
σ2(variance of household-level random effect)1.36 (0.23, 5.35)
Rattiness variables
Relative elevation (per 1 m increase)2
 0–8 m0.05 (-0.01, 0.13)
 8–22 m–0.06 (-0.16, 0.02)
 >22 m0.05 (-0.03, 0.14)
Distance to large refuse piles (per 10 m increase)3
 0–50 m–0.10 (-0.21, 0.02)
 >50 m0.03 (-0.11, 0.17)
Impervious land cover (per 10% increase)–0.07 (-0.14,–0.01)
Rattiness parameters
αtraps–2.94 (-3.27,–2.65)
αplates–2.06 (-2.50,–1.74)
αburrows–1.41 (-1.67,–1.16)
αfaeces–2.82 (-3.83,–2.32)
αtrails–2.22 (-2.96,–1.76)
σtraps0.72 (0.45, 0.97)
σplates2.37 (2.05, 2.68)
σburrows1.28 (1.08, 1.45)
σfaeces2.36 (1.80, 3.34)
σtrails2.43 (1.85, 3.12)
ψ0.67 (0.29, 1.00)
ϕ9.23 (3.21, 18.24)
Appendix 2—table 1
AIC fit of the five highest ranked multivariable rattiness models (’+’ indicates that a variable was selected in the model).
ModelDist. refuse (0–50)Dist. refuse (>50)Land coverElevation (0–8 m)Elevation (8–22 m)Elevation (>22 m)df*AICc *
M1++++++81476.48
M2++++61479.31
M3+++++71481.01
M4+++++71481.99
M5+++++71482.97
  1. *

    df, degrees of freedom; AICc, corrected Akaike Information Criterion.

Appendix 2—table 2
AIC fit of the five highest ranked multivariable human infection models (’+’ indicates that a variable was selected in the model).
ModelAge (0–30)Age (>30)SexValleyFloodwaterIncomeLand coverSalespersonElevation levelRattinessRatt:Elevdf*AICc *
M1++++++++++16523.14
M2+++++++++15523.52
M3+++++++++++17523.72
M4++++++++++16524.11
M5+++++++++14525.04
M*++++++++13532.13
  1. *

    df, degrees of freedom; AICc, corrected Akaike Information Criterion

  2. Model M* was ranked outside of the top 5 models but is included here for reference to demonstrate the improvement in model fit when rattiness is included.

Appendix 3—table 1
Multivariable mixed effects logistic regression analysis of risk factors for leptospiral infection in community members.

Note: there was missing information for the contact with floodwater question for two individuals and consequently only 1399 participants from 668 households were included in this analysis.

VariableOR (95% CI)
Demographic and social status
Age (per year)*
 0–30 years old1.10 (1.04, 1.16)
 >30 years old1.02 (0.96, 1.09)
Male gender2.90 (1.59, 5.28)
Daily per capita household income (US$/day)0.93 (0.81, 1.06)
Valley
 1REF
 23.91 (1.33, 11.68)
 32.26 (0.74, 6.93)
Household environment
Relative elevation level
 High (>15.6 m)REF
 Medium (6.7–15.6 m)0.71 (0.30, 1.70)
 Low (0–6.7 m)1.08 (0.44, 2.62)
Occupational exposures
Work as travelling salesperson 3.38 (0.77, 14.87)
Behavioural exposures
Contact with floodwater in last 6 months
 Never/rarelyREF
 Sometimes0.64 (0.28, 1.43)
 Frequently2.48 (1.02, 6.02)
Rattiness
Rattiness at high elevation level (per unit rattiness)6.92 (1.88, 25.47)
Elevation level: Low × rattiness0.10 (0.02, 0.62)
Elevation level: Medium × rattiness0.15 (0.02, 0.91)
σ2 (variance of household random effect)1.78
  1. *

    The effect of age is modelled as a broken linear model with a transition at 30 years old, as informed by the relationship described by Generalized Additive Modelling (Appendix 1—figure 2).

  2. Binary variable with reference category of ‘no occupational exposure’.

Appendix 5—table 1
Summary of demographic, socioeconomic and environmental risk factors.
VariableNo. or Median (% or IQR) *
Demographic and social status
Age (years)27 (15–41)
Male gender597 (42.6%)
Daily per capita household income (US$/day)1.6 (0.8–2.8)
 Valley 1259 (18.5%)
 Valley 2557 (39.8%)
 Valley 3585 (41.8%)
 Literacy1125 (80.3%)
Education (years)6 (4-9)
Household environment
Impervious land cover (%)49.6 (35.1–70.6)
Relative elevation (metres)11.0 (5.9–16.3)
Elevation level
 Low (0–6.7 m)474 (33.8%)
 Medium (6.7–15.6 m)524 (37.4%)
 High (>15.6 m)403 (28.8%)
Open sewer within 10 m926 (66.1%)
Unprotected from open sewer666 (47.6%)
Live on hillside453 (32.4%)
Occupational exposures
Work in construction105 (7.5%)
Work as travelling salesperson24 (1.7%)
Work in refuse collection61 (4.4%)
Work involves contact with mud27 (1.9%)
Work involves contact with floodwater23 (1.6%)
Work involves contact with sewer water16 (1.1%)
Behavioural exposures
Contact with floodwater in last 6 months
 Never/rarely986 (70.5%)
 Sometimes299 (21.4%)
 Frequently114 (8.1%)
Contact with sewer water in last 6 months
 Never/rarely1120 (80.2%)
 Sometimes180 (12.9%)
 Frequently97 (6.9%)
  1. *

    No., number; IQR, interquartile range; Percentages are calculated without missing values. All variables had ≤ 5 missing values.

Appendix 6—table 1
Trap disturbance sensitivity analysis: non-spatial rattiness model parameter estimates and between-imputation standard errors.
ParameterEstimateSEimp
αtraps–2.82740.0128
αplates–1.90580.0004
αburrows–1.37940.0008
αfaeces–2.86170.0027
αtrails–2.15380.0023
σtraps0.70100.0120
σplates2.40160.0004
σburrows1.38200.0008
σfaeces2.67040.0031
σtrails2.64310.0036
Relative elevation (per 1 m increase)2
 0–8 m0.05250.0001
 8–22 m–0.05830.0001
 >22 m0.11120.0002
Distance to large refuse piles (per 10 m increase)3
 0–50 m–0.10900.0002
 >50 m0.04050.0001
Impervious land cover (per 10% increase)–0.05920.0001

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