Animal origin agents that have emerged into « high public health impact » zoonoses HIV… · UMR...
Transcript of Animal origin agents that have emerged into « high public health impact » zoonoses HIV… · UMR...
UMR 145 « VIH/Sida et Maladies associées »
Animal Animal origin origin agentsagents that that have have emerged intoemerged into
«« high high public public health health impactimpact » » zoonoses zoonoses
HIV/SIVHIV/SIV
Second FAO-OIE-WHO Joint scientific consultation
26-29 April 2010, Verona
Martine Peeters
UMR 145, IRD and University of Montpellier 1,
Montpellier, France
UMR 145 « VIH/Sida et Maladies associées »
HIV/AIDS :HIV/AIDS :The most important infectious disease to haveThe most important infectious disease to have
emerged in the past century.emerged in the past century.19841983
2010
?
First cases of unusual immunedeficiency among gay men in USA,
HIV identified as the cause of AIDS
In Africa, a heterosexual AIDS
epidemic is revealed
1985
HIV-2 identified in West Africa
40
30
20
10
0
50
35
25
15
5
45
1980 1985 1990 1995 2000 2005
2009 : 33.2 (30.6 – 36.1) million (1/180) living with HIV/AIDS
25 million deaths
1979-
1981
UMR 145 « VIH/Sida et Maladies associées »
Two Two types of HIVtypes of HIV
HIV-1
Global spread
HIV-2
West Africa
UMR 145 « VIH/Sida et Maladies associées »
Origin of HIVOrigin of HIVCross-species transmission of SIV from non-human primatesCross-species transmission of SIV from non-human primates
HIV-2 from SIVsmm in
sooty mangabeys in
West Africa
HIV-1 from
SIVcpz/SIVgor in
chimpanzees and
gorillas in Central Africa
Phylogenetic relation, viral structure
Geographical coincidence habitat and HIV-1 and HIV-2 epicenters
Contact between primates and humans
UMR 145 « VIH/Sida et Maladies associées »
Cutaneous or mucous membrane exposure
to infected blood or other secretions
- Hunting
- butchering;
injury from butchering
-pets: biting or other injurie,
contact with body fluids?B.Abela-Ridder 2000
B.Abela-Ridder 2000
B.Abela-Ridder 2000
How did SIV cross-species transmission occur?How did SIV cross-species transmission occur?
B.Abela-Ridder 2000
UMR 145 « VIH/Sida et Maladies associées »
How How many cross-species many cross-species transmissions?transmissions?
AE_PA1SIVsmmSL92B
SIVsmmSL92CSIVsmmSL93_119SIVsmmSL93_063
HIV-2SL93FA_RODHIV-2SL93AA_GH1
B_D205B_EHOA
B_UC1HIV-2/G
SIVsmmTAI23SIVsmmTAI31SIVsmmTAI32
D_FO784SIVsmmLIB-1SIVmac251
SIVsmmH4SIVsmmSL93_080SIVstm22579
SIVsmmSL92DSIVsmmCI8
SIVsmmTAI22SIVsmmTAI3
C_22381HIV-2H12034
SIVsmmSL93_134SIVsmmSL92E
SIVsmmSL92F
0.05
HIV-2 group D
HIV-2 group G
HIV-2 group B
HIV-2 group A
HIV-2 group HHIV-2 group C
HIV-2 group F
HIV-2 group E
Epidemic
spread
ANT
TAN3
TAN1
TAN2790971
HIV-1OHIV1-PSIVgor-BQ664
SIVgor-DJ4099
SIVgorCP2117
SIVgor-CP2135#SIVgor-CP2139#SIVgor-CP684#
967923
1000
854
SIVcpz-Gab1SIVcpz-Cam13
SIVcpz-Gab2
SIVcpz-MT145SIVcpz-US
SIVcpz-Cam5
SIVcpz-DP943
SIVcpz-Cam3877SIVcpz-EK505
HIV-1N958
HIV-1MSIVcpz-MB66
SIVcpz-MB897
SIVcpz-MB2340
SIVcpz-LB7
895
714
861
**
*
**
**
*
*
*
*
**
**
SIVcpzPtt
SIVgor
SIVcpzPts
0.05
X
X
X
X
Global epidemic
< 20 in Cameroon
2 Cameroonians
1% of HIV-1 in
Cameroon
Each HIV-1/HIV-2 group represents a zoonotic transmission
8 transmissions for HIV-2 4 transmissions for HIV-1
UMR 145 « VIH/Sida et Maladies associées »
When did these cross-species transmissions occur?When did these cross-species transmissions occur?
HIV-1 O : Norwegian
sailor infected in
Cameroon
1964
1959
1960HIV-1 M
Kinshasa
DRC
HIV-1 M
MRCA: 1921
(1915-1941)
HIV-1 O
MRCA: 1920
(1890-1940)
HIV-2 A and B:
MRCA: 1940-1945
HIV1 (M/O) and HIV-2 started
to diverge in the human
population 1920-1940
1960: Oldest HIV
positive samples in
Africa
Cross-species transmissions occurred before these dates. How many before? After?
HIV-1 N and P
more recent
transmissions?
UMR 145 « VIH/Sida et Maladies associées »
Where Where are are the reservoirs the reservoirs of of the the HIV-1/2 HIV-1/2 ancestorsancestors??
Identify the prevalence and genetic diversity of SIVcpzand SIVsm in wild mangabey and chimpanzee/gorillapopulations?
Primates are highly endangered species,
Large scale studies only possible using non-invasiveapproach
UMR 145 « VIH/Sida et Maladies associées »
Detection Detection of SIV infection in of SIV infection in faecal samplesfaecal samples(B.Hahn, UAB, USA)(B.Hahn, UAB, USA)
Storage: Max 3 weeks in the field at ambiant temp in RNA-later , -80° in the lab
Faecal samples
in RNA-Later
mtDNA:
species/subspecies
Microsatellite analysis:
Enumeration of SIV
positive samples
Antibody detectionafter dialysis
Viral RNA detection: RT-PCR,
Sequence and phylogenetic
analysis
UMR 145 « VIH/Sida et Maladies associées »
96FR12034 HIV-2 H
SIVsmmTaï31
99
99100
100
100
100
98
100
100
100
100
99
SIVsmmTaï37SIVsmmTaï1SIVsmmTaï23
CAM2 60415K
SIVsmmCI2SIVsmmCI8
SIVsmmTaï29SIVsmmTaï32
Abt96 HIV-2 GSIVsmmTaï13
SIVsmmTaï22SIVsmmTaï33
SIVsmmTaï17SIVsmmTaï3
SIVsmmTaï35SIVsmmF098
2238 HIV-2 CEHO
UC1SIVsmmSL93-063
SIVsmmSL93-119SIVsmmSL92B
SIVsmmSL92C
gp41
HIV-2 A
HIV-2 B
Non-invasive
sampling of SIV from
sooty mangabeysSantiago et al. (2005)
Tai Forest, Cote d’Ivoire
Two epidemic groups of HIV-2 (A and B) most closely related to SIVsmm from the Tai Forest,
Eastern Ivory Coast
Where are the reservoirs of HIV-2?Where are the reservoirs of HIV-2?
UMR 145 « VIH/Sida et Maladies associées »
ANT
TAN3
TAN1
TAN2790971
HIV-1O
HIV1-PSIVgor-BQ664
SIVgor-DJ4099
SIVgorCP2117
SIVgor-CP2135#SIVgor-CP2139#SIVgor-CP684#
967923
1000
854
SIVcpz-Gab1SIVcpz-Cam13
SIVcpz-Gab2
SIVcpz-MT145SIVcpz-US
SIVcpz-Cam5
SIVcpz-DP943
SIVcpz-Cam3877SIVcpz-EK505
HIV-1N958
HIV-1M
SIVcpz-MB66
SIVcpz-MB897
SIVcpz-MB2340
SIVcpz-LB7
895
714
861
**
*
**
**
*
*
*
*
**
**
SIVcpzPtt
SIVgor
SIVcpzPts
0.05
X
X
XX
Where are the reservoirs of HIV-1?(Keele et al, 2006; Van Heuverswyn et al, 2006 and 2007, Neel et al 2010, Li et al, 2010)
X
?Gorillas
N>2500
Chimpanzees
N >5000
Chimpanzees from West central Africa are the reservoir for HIV, but also for SIV in gorillas
No SIVcpz infection
UMR 145 « VIH/Sida et Maladies associées »
Cross-species transmissions and emergence of virusesCross-species transmissions and emergence of viruses
• Exposure/contact
frequency of contacts
prevalence in host
transmission mode
• Infection in the new host
• Adaptation and replication in the new host
• Spread from human to human
• From single cross-species transmission to epidemic ?
UMR 145 « VIH/Sida et Maladies associées »
Why Why multiple multiple cross-species cross-species transmissions transmissions with SIVsmmwith SIVsmm
and SIVcpz/gor and SIVcpz/gor in in this this areas?areas?
• Many contacts between primates and humans– mangabeys : 50% of primate bushmeat in West of Ivory
Coast
– Chimpanzees and gorillas :
bushmeat, ….
• High SIV prevalence:– SIVsm: 50% in wild mangabeys
– SIVcpz: 30% in wild chimpanzees infected with M and Nancestors
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What are the potential risks of transmission of What are the potential risks of transmission of SIVs SIVs other thanother than
SIVcpz/SIVgor SIVcpz/SIVgor and and SIVsmm SIVsmm from from NHPs NHPs to humans?to humans?
• Evidence of SIV infection in at least 40African non-human primates (NHP), 32confirmed by sequence
• ongoing exposure to SIVs throughhunting, butchering and handling ofNHPs.
• Cross-species transmission of otherretroviruses has also been documentedamong hunters (Mahieux et al., 1998;Wolfe et al., 2004, Switzer et al, 2010)
• Study more in detail the SIV in
primate bushmeat allows to evaluate
to what extent humans are exposed
to SIV infected primates
S.Loul 2004
HIV-1/ NHIV-1/ M
HIV-1/ O
SIVcpz/SIVgor/
HIV-1 SIVwrc
SIVmus
SIVgsn
SIVmon
SIVery
SIVasc
SIVtal
SIVmnd-2/drl
SIVcol
SIVdeb
SIVsyk
SIVagm
SIVrcm
SIVolc
SIVsmm/HIV-2
SIVdenSIVbkm
SIV lho/sun/mnd-1
UMR 145 « VIH/Sida et Maladies associées »
Extensive Extensive survey survey on on the prevalence the prevalence of of SIVs SIVs in primate in primate bushmeatbushmeat
in in Cameroon Cameroon ((Aghokeng Aghokeng et al, et al, Virology Virology 2006; Aghokeng et al, IGE 2009).2006; Aghokeng et al, IGE 2009).
DBS from fresh hunted or confiscated primates
2586 samples
7 different sites in southern Cameroon
SIV lineage specific Elisas
C.cephus
C.nictitans
C.pogonias
C.agilis
L.albigena
C.guereza
M.ogouensis
C.neglectus
M.sphinx
C.torquatus
C.tantalus
0,00
10
20
30
40
50
60 %
C.c
ephu
sC
.nic
titan
sC
.pog
onia
sC
.agi
lisL.
albi
gena
C.g
uere
zaM
.ogo
uens
isC
.neg
lect
usM
.sph
inx
C.t
orqu
atus
C.t
anta
lus
tota
l
Most frequently hunted species (>90%):
low prevalence or absence of SIV infection
SIV prevalence in bushmeat = 2.93%.
11 species, 3-5 predominate
UMR 145 « VIH/Sida et Maladies associées »
Wild living adult red Wild living adult red colobus colobus represent a substantial represent a substantial SIVwrcSIVwrc
reservoir in Creservoir in Côte dôte d’’Ivoire Ivoire ((Locatelli Locatelli et al, IGE 2008)et al, IGE 2008)
Red colobus,diana monkeys and sooty mangabeys:
most extensively NHP hunted by the human population
SIV infection possibly reaching 50% of the adult red colobus population
living in Tai Forest
BUT NO EVIDENCE YET for transmission of SIV from red colobus to humans!
Two epidemic groups of HIV-2 (A and B) most closely related
to SIVsmm from the Tai Forest
UMR 145 « VIH/Sida et Maladies associées »
1000 Km
12 in West Central Africa
4 in West Africa
2 in Central Africa
4 in East Africa
1 en Afrique
du sud
Limited knowledge Limited knowledge on SIV on SIV diversity and prevalencesdiversity and prevalences
?> 30 species not tested
Most likely sample bias!! Samples
from limited geographic regions
only
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From cross-species transmissions to epidemic?From cross-species transmissions to epidemic?
• Pathogenic potential of the virus
• Host specific differences
• Social, demographic, and environmentalfactors
• Role of iatrogenic factors?
Not all SIVcpz/SIVsmm became epidemic
Combination of several factors
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Ongoing Ongoing risk risk for new for new SIV SIV transmissionstransmissions
Humans continue hunting of primates for bushmeat!!
Other transmission(s) not yet recognized due to long
incubation period?
new SIV variants not detected by actual HIV screening
assays
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UMR 145 « VIH/Sida et Maladies associées »
Increasing demand and trade of bushmeatIncreasing demand and trade of bushmeat
Commercial logging - road constructions into remote
forest areas
Hunters in previously inaccessible forest areas - new
infrastructure to capture and transport bushmeat
High HIV prevalences in rural villages around loggingconcessions.(>20%)
High potential for dissemination of new HIV,recombination between HIV and SIV.
Bushmeat hunting: longstanding common practice of
rural household economies
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Epicenter
HIV-1 M
??
Ancestor
HIV-1 M
Ancestor
HIV-1 N
Ancestor
HIV-1 O et P
??Origin of virus is
different to origin
of epidemic
Only SIVcpz/gor
transmissions in
Cameroon?
First aids cases identified in the US
UMR 145 « VIH/Sida et Maladies associées »
Study whether other cross-transmissions occurredStudy whether other cross-transmissions occurred??
– develop approach for large scale screening with the different SIV antigens?
– continue to identify SIVs ?
– Target population?
• Screen human populations at risk for new SIV infections, hunters?
• In rural areas and around logging concessions wih high hunting
pressure ?
• In urban areas ?