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					                  Rodents biodiversity and associated
                     infections in Southeast Asia.

Hugot JP1, Suputtamongkol Y2, Jittapalapong S3, Morand S4, Michaux J5,
Cosson JF5, Dobigny G5, and Herbreteau V6.




1 Origine,   Structure et Evolution de la Biodiversite UMR 5202 du CNRS / USM 601,
55, rue Buffon, 75231 Paris cedex 05; 2 Siriraj Hospital, Bangkok, Thailand; 3
Faculty of Veterinary Medicine, Kasetsart University, Thailand; 4 ISEM, CC064,
Université Montpellier-2, France; 5 CBGP, CS30016, Montferrier-sur-Lez,
France; 6 Institut de Recherche pour le Développement, Paris, France

Email: hugot@cimrs1.mnhn.fr
COMPARED BIODIVERSITY OF HANTAVIRUS ROBOVIROSIS
        IN EUROPE AND SOUTHEAST ASIA

 (Biodiversity of Pathogens and Reservoirs, Modelling and
     Mapping of Risks, Links with Human Geography)


    Franco-Thai Program granted by the French ANR:
                Health and Environment


            Duration: three years (2006-2008)


           Financial support: 240 000,00 euros
 Our partners in Thailand:
 -Dr Siriwan
 Chumphon Hospital, Mahidol University.
 - Dr Niwattayakul Kanigar
 Loei Hospital, Province of Loie.
 - Dr Suputthamongkol Yupin
 Siriraj Hospital, Mahidol University.
 - Dr Suwancharoen Duangjai
 National Institute of Animal Health, Ministry of Agriculture.
 -Dr Jittaparapong Sathaporn, Kasetsart Univ, Dep. Parasitology.
 In Europe:
 - CBGP (Montpellier) 6 scientists involved in the project.
 - University of Lyon-Villeurbane, 2 scientists involved.
 - University of Helsinki 2 scientists involved in the project.
In Cambodia: IP Phnom Penh.
Several roborne infections, which reservoirs are Muridae rodents may
be confused with hantavirosis in South Asia. Investigations are needed
to be able to distinguish the real distribution and impact on human
health of different diseases with similar symptoms. This is the goal of
our current projects in Thailand.

Objective 1. Systematics, population genetics and distribution of
rodent reservoirs; hantavirus diversity; rodent and virus
cophylogeography. Analyze and organization of data about
hemorrhagic diseases coming from the Thai Health Departments.

Objective 2. Mapping distributional data. Characterization of
environmental landscapes. Modeling contamination probability,
within and between potential reservoir species.

Objective 3. Computing epidemiological databases. Crosschecking
field data and GIS data. Definition and standardization of a risk-
scale.
                 Diseases considered

Focus on the 4 main rodent-borne diseases, found in Thailand:

         Leptospirosis (endemic in North-East region),

         Scrub Typhus (endemic in North region),

        Murine Typhus

         Hantavirus related diseases
                  1- Bacterial diseases

Leptospirosis
(Weil’s disease, Haemorrhagic jaundice (Leptospira icterohaemorrhagiae),
canicola fever (Leptospira canicola), dairy worker fever (Leptospira hardjo))


       •Pathogen: Leptospira interrogans (spirochete), more than 200 serovars

       •Vectors and reservoirs: rodents, pigs, dogs, rabbits, reptiles, livestock

       o Transmission: usually transmitted to humans by the urine and entered
              body through small skin lesions
               2- Rickettsial diseases
 Murine typhus (Flea-borne typhus fever, endemic typhus fever, urban
       typhus)
        o Pathogen: Rickettsia mooseri, Rickettsia typhi
        o Vectors: Fleas
        o Reservoirs: Rattus species
        o Transmission: through skin lesions or by bite of fleas


 Scrub typhus (tsutsugamushi disease)
        o Pathogen: Rickettsia tsutsugamushi
         o Vectors: usually larvae (chiggers) of trombiculid mites (genus
         Leptotrombidium) and rodents. Chiggers can be infected by feeding on
infected rodents.
        o Reservoirs: Rattus species
                     3 - Viral diseases
 Hantavirus (Bunyaviridae):
     Haemorrhagic fever with renal syndrome (HFRS), associated with
        Hantaan, Seoul… viruses.
     Hantavirus Pulmonary Syndrome (HPS), associated with Sin Nombre
        Virus (SNV).
        o Vectors, and reservoirs: rodents
        o Transmission: mostly by aerosolization of rodent excreta



 Arenavirus (Arenaviridae)
                                                             LCMV
        o Pathogen: Junin virus, Machupo virus, Lassa virus, LCMV
        o Vectors and reservoirs: rodent species
        o Transmission: by ingestion of contaminated water or food, or by
        aerosolization of rodent excreta
Leptospirosis: an emerging zoonosis
  amplified by seasonal flooding
16000
14000
12000
10000
 8000
 6000
 4000
 2000
        0
            1980   1982   1984   1986   1988   1990   1992   1994   1996   1998   2000   2002


                   Number of Leptospirosis cases in Thailand
            from 1980 to 2002 (Source: Thai Ministry of Public Health)
                        Leptospirosis: an emerging zoonose
                          amplified by seasonal flooding




                                                               Occupational vulnerability: about 75% of
                                                               leptospirosis cases are farmers
Vectors of leptospirosis:
Rice field rodents (Bandicota sp.
And Rattus sp.)



                                     Leptospira interrogans,
                                    transported by water in
                                        the environment

                                                                 Recreational vulnerability affecting a
                                                                 wider range of rural populations
Leptospirosis: an emerging zoonose
  amplified by seasonal flooding




                  Increase of the risk of
              transmission of leptospirosis




       Leptospirosis: Cause-effect framework
Scrub typhus, a re-emerging zoonosis
associated with disturbed forest areas
 4000
 3500
 3000
 2500
 2000
 1500
 1000
   500
         0
               1991   1992   1993   1994   1995   1996   1997   1998   1999   2000


                    Number of Scrub typhus cases in Thailand
             from 1991 to 2000 (Source: Thai Ministry of Public Health)
           Hantavirus and rodents: an
      airbone transmission by aerosolization

- Hantaviruses:
    • Zoonotic viruses
    •(can be transmitted from animals to
    humans),
    • Bunyaviridae family
    •(negative-sensed,    single-stranded
    RNA).




                                             Thin-electron micrograph of Sin Nombre virus

       - transmitted by rodents (rats or mouses)
      Comparative Biodiversity
of rodent host reservoirs of hantavirus
    in Europe and South-East Asia




                        Number of hemorrhagic fever with renal syndrom
                                       cases in Korea
                          NUMBER         %
     Rattus exulans                458       34,2
      Rattus rattu s               279       20,9
    Ban dicota indica              235       17,6
   Rattus norvegicu s               58        4,3
    Maxomys su rifer                44        3,3
 Leopoldamys sabanus                32        2,4
    Ban dicota savilei              27        2,0
      Maxomys sp.                   27        2,0
     Mus cervicolor                 22        1,6
    Rattus bukit bukit              16        1,2
      Niviventer sp.                15        1,1
  Niviventer fulvescens             12        0,9
  Berylmys berdmorei                11        0,8
    Berylmys bowersi                11        0,8
  Rattus ar gentiventer             11        0,8
     Rattus remotus                  9        0,7
       Mus caroli                    5        0,4
  Rattus cr emoriventer              5        0,4
    Rattus koraten sis               5        0,4
Hapalomys longicaudatus              2        0,1
 Leopoldamys edwardsi                2        0,1

        TOTAL                  1286
Sibling species are species which are morphologically similar, and may thus :

               Sibling species may react differently to pathogens,
         and so have different involvement in epidemiological processes




             Species A


        Not a priority for control policies
        Time consuming
        Waste of money
                                                               Species B

                                                       This is the target !!!
Sibling species may :


 lead to deep misunderstanding of species-specific biology and
            geographic distributions

 make pest control policies exceedingly expensive and potentially inaccurate




                                               … like rat species !!!!
Their identification requires the use of alternative and powerful tools such as :

        - karyotypic analyses

        - genetic investigations

        - morphometrics analyses
Objective 1. Systematics, population genetics and distribution of rodent
reservoirs; hantavirus diversity; rodent and virus cophylogeography.
Analyze and organization of data about hemorrhagic diseases coming
from the Thai Health Departments.
                               Large rice-field rats:
                         -Revision of the taxonomy of the Murinae
                         rodents in Thailand, using morphological and
                                Bandicota indica
                         molecular data.
                               Mammae:
                         -Construction of a key of determination.
                               1+2+3
                         -Constitution of a reference collection.
                         -Data collection on ecology and population
                         genetic of these rodents.
                         -Bandicota indica, Rattus rattus, R. norvegicus,
                         R. exulans.
                         -Research and identification of the pathogens.
                                   White ring at the
                         -Rereading statistical data of the archives using
                                   basis, overlapping
                         this new knowledge.
                                   scales
Objective 2. Mapping distributional data. Characterization of
environmental landscapes. Modeling contamination probability,
within and between potential reservoir species.
Objective 3. Computing epidemiological databases. Crosschecking field
data and GIS data. Definition and standardization of a risk-scale.


          Potential presence of rodents




              Identification of the
          parameters describing the
        habitats of rodents



        Spatial
       analysis




  Study of every parameter: physical
  (environment, climate…), human (demographic,
  social…)
RESULTS
RESULTS
RESULTS
RESULTS
RESULTS
RESULTS
RESULTS
       TH O TTAPALAYAM                                                        S H R E W

                            T c h o u p i t o u la s
                                S E O U L

                                              H A N T A A N               C L A D E -1
                                                                         M U R IN A E

                                         DOBRAVA

                                       B A Y O U

                                                                              C L A D E -2
                                                                         S IG M O D O N T IN A E


                                                        A N D E S


                                         P R A I R IE


                                                       T U L A
                                                                             C L A D E -3
3 00
                                                  V l a d iv o s t o k
                                                                           A R V IC O L IN A E




       N E A R C T IC
       P A L E A R C T IC
       N E O T R O P IC A L
                                             HantaAnhui      Niviventer
                                             Soochong1
                                             Amur.AP61
                                             HantaMaaji
                                                                     Hantaan
                                             HT76118         Apodemus
                                             HantaGuizh
                                             Sangassou      Hylomyscus
                                             DobravaRussia
                                             DobravaSlovakia
                                             Saaremaa            Dobrava
             Clade1                          DobravaEstonia
                                             DobravaGreece Apodemus
                                             DobravaBosnia

                                             AJ427513
                                             AJ427512
                                                              Cambodia ??
                                             AJ427511        Rattus rattus
                                             ThaiBi50
                                             AB186420
                                             Thai 1996
                                             ThaiBi1
                                                                 Thailand ??
                                             ThaiBi11        Bandicota indica
                                             ThaiBi35
                                             Seoul.L99
                                             HantaShanx
                                             Sapporo
                                             Tchoupitoulas
                                             AJ427501
                                             AJ427500
                                             AJ427499
                                             AJ427498            Seoul
                                             AJ427507
                                             AJ427506        Rattus spp
                                             AJ427508
                                             AJ427510
                                             AJ427509
Genetic analysis of Thailand hantavirus      AJ427502
                                             SeoulZhejiang
in Bandicota indica trapped in Thailand.     AJ427503
Hugot et al. Virology Journal, 2006: 3, 72   AJ427505
Results in Cytogenetics
                                      Mus sp.




        Leopoldamys
        sabanus




                                                Rattus tanezumi


           Description of several new karyotypes 12 species corresponding to 8 genera

           First identification of a B chromosome within genus Mus

           But generally a very conservative karyotype within Rattus spp. et Mus spp.)

           Evidences of the existence of polymorphism in Bandicota spp.
3 - Parasite diseases Toxoplamosis
                  Species       Nb    %         Positive Prevalence

          Bat                    18       4,5          1         5,6
                  Muridae
          M axomys surifer       28 7,0                2         7,1
          Rattus rattus         158 39,6              10         6,3
          Leopoldamys sabanus    16 4,0                1         6,3
          Bandicota indica       26 6,5                1         3,8
          Rattus exulans         63 15,8               1         1,6
          Rattus norvegicus      38 9,5

                 Sciuridae
          M enetes sp.           52 13,0               3         5,8

                Tupaiidae
          Tupaia glis            24       6,0          1         4,2

          Total                 399   100             19        36,5
 THANKS
   FOR
  YOUR
ATTENTION

				
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