EcoEpidemeiologia das Leishmanioses e

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XIV Congresso de Sociedade Brasileira de Medicina
Tropical
Recife11th March 2009
Eco-Epidemeiologia das Leishmanioses e
Prioridades de Pesquisa
Jeffrey Shaw São Paulo University Biomedical
Sciences Institute jeffreyj_at_usp.br
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LeishmaniasisGlobally an enormous problem

• A Leishmania specie occurs in different
  environments and eco-epidemiological studies need
  to be performed in each of them.

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Endemic regions of Leishmania (Viannia)
braziliensis in Pará State
Serra das Carajás Vector Psychodopygus
wellcomei Diapause in dry season no transmission
Paragominas Vector - Psychodopygus complexus No
diapause transmission continuous
Parasite populations genetically distinct
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Endemic L. (V.) braziliensis regions of north
east Brazil
Lu. intermedia
Ponte do Gravatá, Jequitinhonha river valley,
Minas Gerais
Lu.whtmani
Amaraji, Pernambuco State Três Braços, Bahia
State
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Vector presence then Disease

• Implications The principal factor controlling
  the distribution of the disease is the vector.
• Exceptions Mechanical transmission Within or
  Outside the vectors range.
• An example VL in Spanish drug users

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Transmission within an endemic area
Hot Spot
Micro Habitat
Specific ecological Niche
Endemic area
Increasing density of Vector
Improving conditions for transmission
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Eco-Epidemiogical Research Priorities
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Accurate ID
Vector Biology
Disease Epidemiology
Which one?
Accurate Parasite ID
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Periods of preferential actions based on
variations of sand fly numbers
Detection of Infected Reservoirs
Detection of Infected Vectors
Action against vector
Action against Vector Reservoir
Numbers of females
Reservoir reproductive cycle?
Time
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Multilocus genotypes (MLG) of Leishmania
(Leishmania) infantum stocks from dogs and sand
flies of the Priorat region of Spain.

MLG No. 2 4 5 8 9 10
11 12 13 14 15 16 17 Dog stocks (42) 2
2 3 3 5 20 4 3 0 0 0 0
0 Sand fly stocks (15) 0 0 1 1 2 0
2 0 1 1 3 2 2
Red figures Difference statistically significant
(plt0.05)
Priorat
Source Montoya et al. 2007
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Relationship of genetic population structure to
type of reservoir
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Leishmania (Viannia) shawi
Reservoirs Large Arboreal Mammals
The vector
Lutzomyia whitmani
Coatis
Sloths (Preguiça-real)
Chiropetes satanus (Saki, cuxiú-preto)
Cebus apella (Capuchin monkey macaco-prego)
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UPGMA phenogram of Leishmania (Viannia) shawi
AN Ananindeua Municipality BN Benevides,
Belém Municipality CJ Serra das Carajás,
Parauapebas Municipality MD Monte Dourado,
Almerim Municipality PG Paragominas
Municipality.
RAPD using the M13-40 oligonucleotide
Source Ishikawa et al. 2002
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Leishmania (Viannia) braziliensis populations
CJ Serra das Carajás, Parauapebas Municipality
Pará State, Brazil PG Paragominas
Municipality, Pará State Brazil R Paraná
State, Brazil PU Amazonian Peru.
Source Ishikawa et al. 2002
RAPD using the M13-40 oligonucleotide
Jeffrey Shaw ICB, USP
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L (V.) braziliensis
?
Anthroponotic cycle
Sylvatic zoonosis
Sylvatic enzootic
Domestic zoonosis
Domestic enzootic
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Evidence of VL enzootic in the absence of canine
VL
Infections in foxes captured in area Endemic and
Non-Endemic for canine visceral leishmaniasis,
Pará State, Brazil

• No.
  Exam ve
• ENDEMIC AREA
• Salvaterra, Marajó 37
  48.6
• Camara, Marajó 26
  42.5
• NON-ENDEMIC AREA
• EMBRAPA, Belém 23 13.0
• Diagnosed serologically - Parasites
  isolated but not from all animals

Jeffrey Shaw ICB, USP
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Further Evidence of a VL enzootic in the
absence of canine VL

• Serological records of infections in wild rodents
• The next step -
• Isolate the Parasite

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South American VLAn alternative Sylvatic life
cycle
Zoonotic cycle
Vector Lu.longipalpis Other species??
? Anthroponotic cycle
Sylvatic Enzootic cycle
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The importance of water saturation levels in soil

• Linked too larval development and possibly choice
  of oviposition sites by the female

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Effect of ground water on Bichromomyia
flaviscutellata in two different ecological niches
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• Terra firme forest
• 1 meter

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Artificially increased ground water

• So ecotopes with higher ground water levels
  represent high risk areas for amazonensis

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Vector Reservoir Adaption
After a number of years Bi.flaviscutellata
and Le. amazonensis infected Proechimys were
found. This explains the increase of amazonensis
in older settled regions of eastern Amazonia
Source Ready et al 1983
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Ny whitmani in deforested Atlantic Rain Forest,
Pernambuco State
Sugar cane
2.3 in forest remnants
98.74 sand fly fauna are Ny. whitmani
2.2 in houses
95.5 in stables
Source Sinval Brandão et al 2003
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Presence of Ny. whitmani in different ecotopes
in the Mato Grosso
Source Galati et al 1996
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Lutzomyia whitmani populations in Brazil based on
cytochrome B haplotypes
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Visceral leishmaniasis - The urbanization of
Lutzomyia longipalpis Brazil

• More than 13 major cities are now facing
  VL control problems
• Studying the biolggy the vector will help to
  understand why this is happening
• .

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Ecological Changes Lu. longipalpis

• Different scenarios
• Expansion of populations that are present in an
  area
• Expansion into an area where the fly had
  apparently been absent
• Both can be related to environmental changes
  linked to climatic variation and mans activities
  

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Forest Houses Lu.longipalpis in the Brazilian
Savanna

• Dry Season
• Wet Season

Forest
House in Savanna
House
longipalpis
Other spp.
Savanna
Dry Season Wet Season
End of wet season 1 0 218
longipalpis 289
89 3 Other spp.
Source Lainson et al 1989 Salvaterra, Marajõ
Isalnd Brazil
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VL advances into Brazils capital
VL Endemic Since the 1990s
Lago Norte
2008 Dogs
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Ecological changes caused by urban development in
Brasília
Cerrado
Lutzomyia longipalpis absent
Lutzomyia longipalpis Present Food domestic
animals Humidity
Gallery forest
Before After
Lutzomyia longipalpis?
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Lu.longipalpis invasion of São Paulo
1st human case 1998 - fatal
Canine VL
By 2005 38 municipalaties ve for Lu.longipalpis
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The dangers of generalizations

• There are more sand flies in the rainy season
• True or False?

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Seasonal variation 25,428 female sand flies
captured in 1999 in Cacaulândia, Rondônia, Brazil
Precipitation 2000 1984
OK its True
Number of females
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BUT Lu. longipalpis was absent in the wet season
present in the Spring when the temperature and
rains are increasing
Precipitation 2000 1984
Nos. L.longipalpis
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Lu. longipalpis in Belo Horizonte peaks in the
Summer just after max temp and rain
Summer
Source Rezende et al 2006
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The longipalpis complexWhat are the Biological
significances of genetic differences?
Pheromones types
(S)-9-methylgermacrene-B
3-methyl-?-himachalene
cembreno, um diterpeno monocíclico
Canções de acasalamento dos machos
Fontes Ward et al Peixoto et al
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Priorities all linked

• Accurate Molecular definitions of parasite
  populations.
• Identification of reservoirs, study their
  reproductive cycles and show their infectiousness
  to vectors.
• Identify vectors and study their biology (feeding
  habits, ecological preferences, seasonal
  fluctuations).
• Association of biological differences of vectors
  to molecular markers.

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• When the evidence changes
• I change my opinion
• What do you do?
• Lord Keynes British economist