leptospirosis and environment - leg-ufprleg.ufpr.br/lib/exe/fetch.php/pessoais:marilia:lepto... ·...
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Leptospirosis and Leptospirosis and
EnvironmentEnvironment
Marilia S Carvalhoá
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SummarySummary
What is Leptospirosis and which are the main questionsData sets: cases and climateModelling:
basic modelclimatic covariates: threshold and lags
Problems and doubts...
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LeptospirosisLeptospirosis
Bacterial zoonosis (Leptospira sp)
Transmitted to humans through contact with urine from infected animals (rats in urban setting)
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Disease Disease cyclecycle
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LeptospirosisLeptospirosis
Incubation period: 5 to 25 daysClinical manifestations:
self-limiting fever, with headache and muscle pain – easily taken for a bad cold or dengue fever life-threatening disease – kidney failure, pulmonary haemorrhage, Weil's syndrome
Early treatment! Dialysis mainly
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EpidemiologyEpidemiology
Globally spread, affecting people on all continents.
Different epidemiological patterns:
Sporadic disease, related with specific occupational exposures and recreational activities
Slums and flooding in urban areas
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In BrazilIn Brazil
10,000 reported cases per year in the major cities
Under-registration
10-15% mortality when diagnosed; more due to late treatment
Main suspected factors: poor sanitation, slum housing and flooding
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Favela in SalvadorFavela in Salvador
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Favela in SalvadorFavela in Salvador
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General questionsGeneral questions
People living in slums – seroprevalence study estimates 23% at 50y, so what determines severe cases?
different virulence according to the bacteria strain inoculant dose – related to behaviour (higher male prevalence – cleaning sewers) and environmentprevious immunity – how is it acquired? (a vaccine is on its way)
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Leptospirosis & ClimateLeptospirosis & Climate
Does rainfall rainfall really cause epidemics of severe leptospirosis? Why?
Reasoning: the rain clean up the rats holes, bringing to the soil surface leptospiraIs it a linear relationship?
When to give an alarm to decrease fatalities – thresholdthreshold
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QuestionsQuestions
Other environment factors: humidity humidity & temperature& temperature
Time delayTime delay
duration of incubation period – related to inoculant dosis
duration of the Leptospira on the soil – related with temperature and moisture on the soil
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DataData
Salvador surveillance system
Cases: weekly aggregated
Climate covariates:
Mean weekly temperature (°C)
Mean weekly relative humidity (%)
Weekly accumulated rainfall (mm)
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0
10
20
30
0
100
200
300
75
80
85
90
Mar/96 Mar/97 Mar/98 Mar/99 Mar/00 Mar/01 Mar/02 Mar/03 Mar/04
26
28
30
32
Accumulated rainfall (mm)
Number of cases
Mean relative humidity (%)
Mean temperature (°C)
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The basic modelThe basic model
(temporal random effect, accounting for overdispersion)
Y t ~Poissont
lnt=tt
t=2t−1−t−2t
t~N 0,2
(2nd order random walk prior)
where:
Fitted in BayesX (www.stat.uni-muenchen.de/~bayesx/bayesx.html)
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0
10
20
30
1
0
1Random Walk
Number of cases
Mar/96 Mar/97 Mar/98 Mar/99 Mar/00 Mar/01 Mar/02 Mar/03 Mar/04
Seasonality
Downward general trend?
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Including climate covsIncluding climate covs
Which are the important temporal lags? Is the corresponding effect linear?
ln t=tt∑k=05
k xt−k
k
x t−5 , .... , xt
is a nonparametric spline
measures humidity OR temperature OR rainfall
k lags, from the same week up to the 5th previous one
k=0
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Lags and LinearityLags and Linearity
75 80 85 90
1.00.50.00.51.0
Lag 0
75 80 85 90 75 80 85 90 75 80 85 90 75 80 85 90 75 80 85 90
26 28 30 32
2
1
0
1
2
26 28 30 32 26 28 30 32 26 28 30 32 26 28 30 32 26 28 30 32
0 50 100150
2.01.51.00.50.0
0 50 100150 0 50 100150 0 50 100150 0 50 100150 0 50 100150
Relative humidity (%)
Temperature (°C)
Rainfall (mm)
Lag 1 Lag 2 Lag 3 Lag 4 Lag 5
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Rain > 5mmRain > 5mm
Comparison of DIC of models with different thresholds
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Rain > 5mmRain > 5mm
Chosen based on.... civil defence information as well
0 1 2 3 4 5 6
0.5
0.0
0.5
Number of Days > 5mm rainfall
0 1 2 3 4 5 6 0 1 2 3 4 5 6 0 1 2 3 4 5 6 0 1 2 3 4 5 6 0 1 2 3 4 5 6
Lag 0 Lag 1 Lag 2 Lag 3 Lag 4 Lag 5
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Complete modelComplete model
ln t =0tt
H1Humid 1H2Humid 2
T1Temp1T2Temp2
R1Rain1R2Rain2R3Rain3R4 Rain4
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Variables Relative riskexp(β)
2.5% quantile 97.5% quantile
Mean relative humidity, week(t-1) 1,045834 1,024385 1,067776Mean relative humidity, week(t-2) 1,055043 1,032454 1,078136Mean temperature, week(t-1) 0,945387 0,873472 1,020173Mean temperature, week(t-2) 1,055784 0,976662 1,139499Num. days rain > 5mm, week(t-1) 1,150296 1,093561 1,210880Num. days rain > 5mm, week(t-2) 1,117894 1,059795 1,175944Num. days rain > 5mm, week(t-3) 1,067789 1,027711 1,109781Num. days rain > 5mm, week(t-4) 1,063815 1,023835 1,106515
EffectsEffects
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0.5
0.0
0.5
1.0
Mar/96 Mar/97 Mar/98 Mar/99 Mar/00 Mar/01 Mar/02 Mar/03 Mar/04
0
5
10
15
20
25
30
35
Mar/96 Mar/97 Mar/98 Mar/99 Mar/00 Mar/01 Mar/02 Mar/03 Mar/04
PredictedObserved
Number of cases/week
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ConclusionsConclusions
Leptospirosis depends upon:
rainfall (up to 4 weeks previously),
humidity (up to 2 weeks previously),
not temperature.
Alert to public health and guidelines to emergency doctors
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Downward trend?Downward trend?
climate related – el niño phenomena?structural changes in favelas – no! sanitation – Blue Bahia (World Bank project) was entirely devoted to touristic areas
0.5
0.0
0.5
1.0
Mar/96 Mar/97 Mar/98 Mar/99 Mar/00 Mar/01 Mar/02 Mar/03 Mar/04
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Statistical problemsStatistical problems
Better models to discover the rainfall threshold?
How to analyse the lagged effect?
Colinearity!Polynomial distributed lag models (package pdl in R)
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Future researchFuture research
Space-time analysis – data is now localised in small area, in a GIS, with level curves (1m) and socio-economic covariatesThe Natural history of severe leptospirosis project (NIH grant) – a longitudinal study going on in Pau-da-Lima favela, already in its 3rd visitVaccine – phase 1
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AcknowledgementsAcknowledgements
This analysis was mostly done by RA Claudio Bustamante Pereira de Sá,
who died of aneurism last year