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


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


Two Two types of HIVtypes of HIV

HIV-1

Global spread

HIV-2

West Africa


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


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


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


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?


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


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


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



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?


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


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 ?


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


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


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


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


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


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


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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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


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 ?

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Animal origin agents that have emerged into « high public health impact » zoonoses HIV… · UMR...

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