Intrigue sur le paludisme insulaire de Madagascar

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Intrigue sur le paludisme insulaire de Madagascar - Conférence du 7e édition du Cours international « Atelier Paludisme » - RANDRIANARIVELOJOSIA Milijaona - Madagascar - milijaon@pasteur.mg

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Intrigue sur le paludisme insulaire de Madagascar

  1. 1. Intrigue sur le paludisme insulaire de Madagascar Milijaona Randrianarivelojosia, PhD, HDR 7ème édition du cours international “Atelier Paludisme” 16 Mars 2009 – Institut Pasteur de Madagascar
  2. 2. History of malaria in Madagascar linked to the origin of Malagasy peopleP aludism e à M adagascar Source : Atlas nautique portugais (Atlas Miller) de Lopo Homem (1519)
  3. 3. Malagasy people: Afro-Asian features mainlyP aludism e à M adagascar
  4. 4. History of malaria in Madagascar linked to the origin of Malagasy people Origin of the human populationP aludism e à M adagascar in the south-western part of the Indian Ocean On the basis of - laguage - agricultural practice - archeological data - genetic study - traditional habit Source : Biodiversité du paludisme dans le monde
  5. 5. Paludisme Maladie parasitaire, curable mais mortelle, due à Plasmodium spP aludism e à M adagascar Groupes vulnérables au paludisme : femmes enceintes et enfants de moins de 5 ans (~35% des cas de paludisme présumé à Madagascar selon le rapport officiel du Ministère de la Santé et du Planning Familial) Murphy SC & Breman JG: Gaps in the childhood malaria burden in Africa: cerebral malaria, neurological sequelae, anemia, respiratory distress, hypoglycemia, and complications of pregnancy. Am J Trop Med Hyg 2001, 64(1-2 Suppl):57-67.
  6. 6. Paludisme : problème de santé dans le mondeP aludism e à M adagascar World Malaria Report 2008, WHO/HTM/GMP/2008.1
  7. 7. Malaria, among major communicable diseases in MadagascarP aludism e à M adagascar
  8. 8. Madagascar in few words Geological diversityP aludism e à M adagascar Climate determined by geographic variables of latitude and altitude with a contrast between • eastern and central regions (humid climate) • versus western and southern regions (dry climate)
  9. 9. Madagascar in few words 587,000 km2 111 districtsP aludism e à M adagascar 18 ethnical groups Afro-asian One language (with dialects) ~19 millions inhabitants 2 millions of presumed malaria cases/year TB, AIDS, leprosy, … 1 physician per 6,000 inhabitants GNP per capita : less than 300 USD … a lovely country
  10. 10. Malaria risk, vector, parasite species and transmissionP aludism e à M adagascar P . falciparum P . vivax P . m alariae P . ovale
  11. 11. Malaria history in the island of Madagascar: myth, legend and reality Oral tradition prior to the European arrivalP aludism e à M adagascar “Hazo (trees) and tazo (fever) are the protection of the kingdom. Do not open the road” said the queen of the central highland. “Man is the one who survives tazo (fever) in the costal areas” Madagascar: known as cemetery for Europeans fever as killer in the cost areas as in XVI century fever as killer during the French military campaign in 1895
  12. 12. 1878 : first malaria outbreak on the central highlandP aludism e à M adagascar Events: • extension of irrigated rice field • introduction of immigrant manpower from mainland Africa to build churches above all Plasmodium falciparum probably !! Anopheles funestus ++
  13. 13. 1895 : Second malaria outbreak on the central highland EventsP aludism e à M adagascar construction of railway, and population migration due to the colonial war Plasmodium falciparum probably Anopheles funestus ++ Repost: use of quinine for cure and prevention mainly among French people, and extended to local population step by step later on
  14. 14. Evolution of Malagasy population between 1900 and 2005 (X1000)P aludism e à M adagascar DDT and Chloroquine massive use Gastineau B., Rakotoson L. (2005). Evolution de la population à Madagascar. Travaux et Documents, n°5, Programme 4D, Institut Catholique de Madagascar et IRD, 14p., Antananarivo.
  15. 15. 1980s : last malaria outbreak in MadagascarP aludism e à M adagascar (Africa Malaria Report, WHO, 2003)
  16. 16. P aludism e à M adagascar Little is known on malaria in Madagascar Example : malaria burden
  17. 17. P aludism e à M adagascar
  18. 18. What were mapped ?P aludism e à M adagascar http://www.pasteur.mg/AtlasPalu/index.html
  19. 19. Malaria burden in MadagascarP aludism e à M adagascar Presumed malaria cases per consultant 20 – 30% 30 – 40% >40% Data from the official report at the Ministry of Health as in 1999 – 2000
  20. 20. Malaria burden in MadagascarP aludism e à M adagascar Lack of malaria How high is malaria prevalence diagnosis tool is a in Madagascar ? big issue
  21. 21. Malaria burden in Madagascar: unclear Area Region Type of Month Year Age Examined MalariaP aludism e à M adagascar locality Group positive Brickaville E coast Rural 9-11 2006 <15 321 4 (1.2%) Antananarivo IP highland Urban 1-12 2004 All 1456 21 (1.4%) Antananarivo CS highland Urban 7 2003 All 739 11 (1.5%) Antananarivo CS highland Urban 2 2003 All 771 15 (1.9%) Antananarivo IP highland Urban 1-12 2003 All 1754 39 (2.2%) Andapa E coast Rural 9-11 2006 <15 304 21 (6.9%) Mahajanga W coast All 9-11 2003 All 107 19 (17.8%)
  22. 22. Malaria burden in Madagascar: unclearP aludism e à M adagascar Area Region Type of Month Year Age Examined Malaria locality Group positive Ambohibary foothill Rural 3-6 2005 <5 60 24 (40%) Tsiroanomandidy foothill All 3-7 2006 All 1656 731 (44.1%) Lakato foothill Rural 3-6 2005 <5 147 70 (47.6%) Ambodifotatra E. coast Rural 3-5 2004 <5 164 90 (54.9%)
  23. 23. Surveillance clinique des fièvres àP aludism e à M adagascar Madagascar, 2007-2008 Paludisme confirmé Suspicion d’arboviroses Syndrome grippal Autres mars2007 à avril2008
  24. 24. P aludism e à M adagascar Paludisme confirmé Suspicion d’arboviroses Syndrome grippal Mars à Avril 2007 Autres Mars à Avril 2008
  25. 25. P aludism e à M adagascar Malaria control in Madagascar today
  26. 26. Malaria in the south-western part of the Indian Ocean (described since ~1500) Today situation (2009)P aludism e à M adagascar Endemic malaria Comoros Union Mayotte (France) Madagascar Almost eradicated Maurice Eradication done La Reunion (France) Absence of local anopheles Seychelles
  27. 27. What are used for malaria control in the south- western part of the Indian Ocean ? Drugs Bed nets Diagnosis (treatment) (ITN) (biological) Madagascar +++ +++ +/- Comoros Union +++ +++ ++ Mayotte +++ +++ +++ Maurice +++ ! +++ La Reunion +++ ! +++
  28. 28. Malaria cases in the south-western part of the Indian Ocean (source : OMS)P aludism e à M adagascar Year 1995 1999 2003 La Reunion Imported cases 132 153 163 Local transmission - - - Maurice Imported cases 46 73 40 Local transmission - - - (biologically diagnosed cases of malaria)
  29. 29. Key for malaria control in MadagascarP aludism e à M adagascar Environment Malaria Parasite Vector endemicity Autochthonous or imported Nets (ITN) Indoor spraying Drugs (CT) Diagnosis Human
  30. 30. Politique nationale de traitement antipaludique à Madagascar • Accès palustre simpleP aludism e à M adagascar Dans le passé Chloroquine en 1ère ligne (1945 – 2005) Sulfadoxine-pyrimethamine en 2nde ligne Depuis Décembre 2005 Artesunate + amodiaquine en 1ère ligne Artemether + luméfantrine en 2nde ligne • Accès palustre grave : Quinine • TPI (femmes enceintes) : sulfadoxine-pyrimethamine
  31. 31. Traitement de 3 jours par ASAQ Co-blister AS+AQ Combinaison fixe ASAQ Artesunate-amodiaquine Artesunate-amodiaquineP aludism e à M adagascar AS: 50 mg; AQ 153 mg Infants (4.5-8 kg) AS: 25 mg AQ: 67.5 mg Young Children (8-17 kg) AS: 50 mg AQ: 135 mg Children (17-35 kg) AS: 100 mg AQ: 270 mg Adults (≥36 kg) AS: 100 mg AQ: 270 mg
  32. 32. Recommendations versus reality introduction of ACT in MadagascarP aludism e à M adagascar ACT efficacy confirmed Questions: Availability of ACT ? Funding for ACT : for how long ? artemisinin
  33. 33. Recommendation versus reality: therapeutic itinerary in Madagascar Weakness of the health systemP aludism e à M adagascar Long distance between villages and health facilities Lack of health personnel Local population leans sometimes on traditional medicine usage and drugs sold at groceries within the village
  34. 34. Recommendations versus reality: therapeutic error Fever is not malaria (it may be dueP aludism e à M adagascar to viruses, bacterial infection, …) Self medication Usage of « traditional remedies » while their efficacies are not demonstrated Therapeutic anarchy (such as systematic quinine use at the health centre and some hospital) (?)
  35. 35. P aludism e à M adagascar Susceptibility of P. falciparum to drugs in Madagascar today
  36. 36. Surveillance of antimalarial drug resistance (RER created in 1999)P aludism e à M adagascar Randrianarivelojosia et al., Parassitologia 2002, 44: 141-147
  37. 37. Surveillance of antimalarial drug resistance ChemosusceptibilityP aludism e à M adagascar of parasites in vitro Blood In vitro tests samples Genotyping of genetic resistance markers In vivo test (WHO protocols)
  38. 38. Sainte Marie island, in the eastern coast of Madagascar Ambatouro Sainte Marie Toamasina Antananarivo Loukintsy Sahasifotra Maromandia Ambodifotatra Ambodiforaha Ambodivoampeno Vohilava
  39. 39. Chloroquine efficacy to treat falciparum malaria in Sainte Marie (Madagascar)P aludism e à M adagascar Therapeutic responses in children <5 years ETF LCF LPF ACPR Total CQ (25 mg/kg) 1 (2%) 3 (5%) 17 (30%) 36 (63%) 57 CQ prepackaged 0 2 (8%) 4 (16%) 19 (76%) 25 Total 1 (1%) 5 (6%) 21 (26%) 55 (67%) 82 OMS protocol, 14 day follow up, March-June 2004
  40. 40. Chloroquine efficacy to treat falciparum malaria in Sainte Marie (Madagascar) 55.000 50.000 45.000Parasites/µl blood 40.000 35.000 30.000 RCPA (n = 35) EPT (n = 17) 25.000 ECT (n = 3) 20.000 14 day follow-up 15.000 10.000 5.000 0 J0 J3 J7 J14 Day of follow-up CQ 25 mg/kg
  41. 41. Study in the eastern foothill area: SaharevoP aludism e à M adagascar
  42. 42. Variation of the Anopheles density in SaharevoP aludism e à M adagascar Anopheles density 1 2 3 4 5 6 7 8 9 10 11 12 Months (1996 – 2000)
  43. 43. Malaria incidence in Saharevo (%) 0.5P aludism e à M adagascar 0.4 0.3 0.2 0.1 0 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 1999 2000 2001 Months
  44. 44. Malaria infection in Saharevo 6%P aludism e à M adagascar 30% clone no.:1 clone no.:2 clone no.:3 64% (Courtesy of Razaiarimanga)
  45. 45. Chloroquine efficacy in children with P . falciparum malaria in Saharevo in 2004 (14 day follow-up) Age (year)P aludism e à M adagascar Therapeutic responses <5 5-15 Total Early Treatment Failure 0 0 0 Late Clinical Failure 5 1 6 (13.3%) Late Parasitological Failure 3 5 8 (17.8%) Accurate Parasitological 11 20 31 (68.9%) and Clinical Response Total 19 26 45 OMS protocol, 14 day follow up, 2004 But no pfcrt K76T mutant Plasm odium falciparum
  46. 46. Efficacy of monotherapy amodiaquine or SP in Saharevo (Madagascar) in children <10 yearsP aludism e à M adagascar Therapeutic responses Drug ACPR ETF LCF LPF Total Amodiaquine 68 0 0 0 68 (100%) SP 92 0 0 0 92 (100%) WHO protocol, 14 day follow-up, in 2005
  47. 47. First evidence of pfcrt Comoros mutant P . falciparum in Madagascar Sambava AntsohihyP aludism e à M adagascar Andapa Mahajanga Ste Marie mutant pfcrt detected Tsiroanomandidy Saharevo Antananarivo No mutant pfcrt detected yet Where is IPM Randrianarivelojosia M et al. Trans R Soc Trop Med Hyg. 2006 Madagascar
  48. 48. First evidence of pfcrt mutant P . falciparum in Madagascar 183 isolates of P. falciparumP aludism e à M adagascar (PCR/RFLP) Absence of pfcrt K76T Presence of pfcrt K76T mutation: 177 mutation : 6 (Analysis of the pfcrt gene segment, spanning codons 72-76) (n = 12) Haplotypes Haplotype CVMNK CVIET (n = 4) CVIDT (n = 2) Randrianarivelojosia M et al. Trans R Soc Trop Med Hyg. 2006
  49. 49. Massive uses of chloroquine in Madagascar ?P aludism e à M adagascar Since 1945 : chloroquine, first line drug to treat malaria 1952 – 1971 : chemoprophylaxis (children at the Red Cross Centers and at the primary schools) 1971 – 1975/78 : irregular chemoprophylaxis (MOH) 1985 – 1988 : in-home treatment of fever to control the malaria outbreak (CQ dispatched by 37,480 dispensers throughout the country)
  50. 50. Massive uses of chloroquine in Madagascar todayP aludism e à M adagascar Marketing social (0.025 USD) Free of charge The current massive distribution of chloroquine for in-home management of fever in children will promote the dissemination of these mutant, chloroquine-resistant parasites.
  51. 51. Etude clinique phase III avec la combinaison fixeartésunate + amodiaquine en 2006 à Madagascar• 179 patients inclus (dont 58 enfants < 5 ans)• Aucun patient perdu de vue• Un seul patient s’est retiré de l’étude• Les patients ne se présentant le jour prévu de la visite étaient immédiatement contactésAucun événement indésirable grave
  52. 52. Résultats des examens parasitologiques à J3 à MadagascarP aludism e à M adagascar Sans Coarsucam-1 Coarsucam-2 Coartem Total parasites OUI 59 59 60 178 (100.0%) (100.0%) (100.0%) (100.0%) NON 0 0 0 0 Absent 0 1 0 1
  53. 53. Efficacité thérapeutique de Coarsucam® à J28 à Madagascar après la correction par PCR (PP population)P aludism e à M adagascar Réponses Coarsucam-1 Coarsucam-2 Coartem Total thérapeutiques N=59 N=58 N=60 N=177 ECP 0 0 0 0 ECT 0 0 1 (1.7%) 1 (0.6%) EPT 1 (1.7%) 0 0 1 (0.6%) 58 58 59 175 RCPA (98.3%) (100.0%) (98.3%) (98.9%)
  54. 54. Avis personnel : artésunate + amodiaquine pour Madagascar Co-blister AS+AQ Combinaison fixe ASAQ Artesunate-amodiaquine Artesunate-amodiaquineP aludism e à M adagascar AS: 50 mg; AQ 153 mg Infants (4.5-8 kg) AS: 25 mg AQ: 67.5 mg Young Children (8-17 kg) AS: 50 mg AQ: 135 mg Children (17-35 kg) AS: 100 mg AQ: 270 mg Adults (≥36 kg) AS: 100 mg AQ: 270 mg
  55. 55. P aludism e à M adagascar What is malaria for the population ? And how to deal and live with ?
  56. 56. Nouvelle vision à Madagascar : « Elimination du paludisme »P aludism e à M adagascar Missions : Moustiquaire imprégnée d’insecticide Aspersion intra-domiciliaire d’insecticide Artesunate + amodiaquine TPI par SP (femmes enceintes) PECADOM …
  57. 57. Plan stratégique de lutte antipaludique à Madagascar de 2008 – 2012P aludism e à M adagascar
  58. 58. Malaria known as well known by MalagasyP aludism e à M adagascar (page 73) Tazo (fever, chill, headache, fatigue …) is not only malaria
  59. 59. Recommendations versus reality introduction of ACT in Madagascar First line treatment:P aludism e à M adagascar Artesunate + amodiaquine (Dec 2005) ACT efficacy confirmed Questions : artemisinin Are they used ? Are they accepted ?
  60. 60. Results from Manja, south-western regionP aludism e à M adagascar Remote area 13,430 km² 62,606 inhabitants Manja 6 communes Moderate to high malaria transmission 150 mothers/caregivers interviewed April 2006 (courtesy of Ralemary)
  61. 61. Child caregiver’s knowledge on malaria in Manja Clinical signs of malaria Fever 147 (98%)P aludism e à M adagascar Chill 78 (52%) Loss of appetite 19 (13%) Muscle pain 4 (2%) Malaria treatment for children Chloroquine 136 (91%) Paracetamol 135 (90%) Aspirin 63 (42%) Cotrim 52 (35%) Tetracycline 35 (23%) PaluStop (prepacked chloroquine) 26 (17%) Ody Tazomoka (prepacked chloroquine) 27 (18%) Plante 3 (2%) Source : Nicolas Ralemary, IMATEP 2006
  62. 62. Enquête CAP chez les femmes enceintes vues N en CPN à Antananarivo en 2007P aludism e à M adagascar a : CSB2 Isotry Central b : CSB2 Tsaralalàna (CSMI) c : CSB2 Ambohipo d : CSB2 Andoharanofotsy Source : Jemima RAVELONARIVO. Femmes enceintes face au paludisme : connaissances et pratiques. Thèse de Médecine. 20 Décembre 2007
  63. 63. Évaluation de l’état de connaissances des femmes enceintes à Antananarivo (N = 404)P aludism e à M adagascar  Association de la fièvre au diagnostic du paludisme CSB2 d’Ambohipo : 69,6% CSB2 d’Andoharanofotsy : 56,2% CSB2 d’Isotry Central : 45,8% CSB2 de Tsaralalàna : 68,7% Total : 57,9% (IC95% : 52,9 – 62,8%)
  64. 64. Attitudes et pratiques des femmes enceintes à Antananarivo  Médicaments les plus utilisés pour traiter leP aludism e à M adagascar paludisme avec ou sans prescription médicale : - Antipaludiques Chloroquine 76,9% (IC95% : 72,5 – 80,9%) Quinine injectable 25,7% (IC95% : 21,6 – 30,3%) - Antipyrétiques : Paracetamol 60,6% - Antibiotiques : Cotrimoxazole 10,6% - Médecine traditionnelle : 2,9%
  65. 65. Attitudes et pratiques des femmes enceintes à Antananarivo  Médicaments les plus utilisés pour traiter leP aludism e à M adagascar paludisme avec ou sans prescription médicale : - Antipaludiques Chloroquine 76,9% (IC95% : 72,5 – 80,9%) ACT = 0% Quinine injectable 25,7% (IC95% : 21,6 – 30,3%) - Antipyrétiques : Paracetamol 60,6% - Antibiotiques : Cotrimoxazole 10,6% - Médecine traditionnelle : 2,9%
  66. 66. Etude de la prescription d’antipaludiques à Moramanga (marge est) en 2008 Médicaments antipaludiques prescrits : quinine (49,4%), artéméther-P aludism e à M adagascar luméfantrine (21,5%), sulfadoxine-pyriméthamine (12,7%), artésunate- amodiaquine (11,4%), chloroquine (5,1%) Prescripteurs Prescripteurs p privés (%) publics (%) ACT 18 (50) 7 (17,9) < 10-3 Quinine 8 (22,2) 29 (74,4) Chloroquine ou SP 10 (27,8) 3 (7,8) Total 36 (100) 39 (100) 66
  67. 67. P aludism e à M adagascar View point : Is malaria elimination doable in Madagascar ?
  68. 68. Sainte Marie island, in the eastern coast of Madagascar AmbatouroP aludism e à M adagascar Sainte Marie Toamasina Antananarivo Loukintsy Sahasifotra Maromandia Ambodifotatra Ambodiforaha Ambodivoampeno Vohilava
  69. 69. Health project support for the district of Ste Marie to combat malaria, worm, filariasisP aludism e à M adagascar French Malagasy WHO Governement Government (MoH) office in Madagascar
  70. 70. Health project support for the district of Ste Marie to combat malaria, worm, filariasis Since 2006P aludism e à M adagascar Malaria diagnosis by RDT and use of ACT at the health facilities IPT by SP in pregnant women ITN for malaria prevention (almost one net per inhabitant) Passive and active detection of malaria + Mass drug administration of anti-helminth Treatment of acute and chronic filariasis Coordinated actions (with extra manpower for the project)
  71. 71. Résultats de lutte antipaludique mitigés à Ste Marie en 2009 Moustiquaires distribuées > nombre de populationP aludism e à M adagascar Prévalence du paludisme chez les écoliers Mars – Mai 2004 = ~50% Janvier – Février 2009 = ~23% Moustiquaire pour la pêche, clôture de pépinière, …
  72. 72. P aludism e à M adagascar Concluding remarks
  73. 73. Paludisme dans le monde (1900 – 2002)P aludism e à M adagascar
  74. 74. Malaria in the future in MadagascarP aludism e à M adagascar Unpredictable ! "Our current events will someday become ancient history indispensable to those who are our successors."
  75. 75. Main problem in Madagascar: poverty and corruptionP aludism e à M adagascar
  76. 76. P aludism e à M adagascar To combat malaria and infectious diseases related to poverty in general Research has the first words Intervention has the last words
  77. 77. People naturally live with malaria in Madagascar PreventionP aludism e à M adagascar Traditional method: burn aromatic plant Modern method: bed nets, drugs, repellent, indoor spraying of insecticide, modern house Treatment Traditional medicine: plants, exorcism, prayers Modern drug in : self medication at home, recommended in-home management of fever, mass treatment, health facilities, intermittent preventive treatments, …
  78. 78. Concluding remarks on combat against parasitesP aludism e à M adagascar The revised policy recommendations: - Shift from chloroquine to ACT as first line treatment (artesunate + amodiaquine) - Use of SP for IPT in pregnant women Genotyping of pfcrt, pfdhfr, pfdhps, and of any “meaningful” resistance markers is a useful tool for drug resistance surveillance in Madagascar
  79. 79. Concluding remarks on combat against parasitesP aludism e à M adagascar The pfcrt K76T mutation which is critical for resistance to chloroquine was detected in few samples within the mutant haplotypes CVIET and CVIDT In this context, the genotyping of pfcrt remains a useful tool for chloroquine resistance surveillance as the prevalence of pfcrt mutations is far from saturation in Madagascar
  80. 80. Ma conviction :P aludism e à M adagascar « Améliorer le contrôle du paludisme entraînera une amélioration du contrôle des autres maladies dont les premiers symptômes se traduisent par de la fièvre »
  81. 81. Will chloroquine withdrawal be enough to bring backP aludism e à M adagascar chloroquine-sensitive P. falciparum in Madagascar ? cf. Malawi experiences; and the malaria transmission levels in Madagascar How to maintain the use of ACT? (funding issue; distribution matter; ) How to bring ACT to the communities? How to assess properly malaria burden?
  82. 82. In which way the ACTs use will affect the Plasm odiumP aludism e à M adagascar sp population structures and the malaria transmission in Madagascar ? cf. the malaria transmission levels in Madagascar Madagascar an island can house the first trial at large scale to “eliminate malaria” by use of combined therapy (ACT or non-ACT) and insecticide cf. the successful malaria control in Madagascar by use of CQ and DDT in the 1950s
  83. 83. P aludism e à M adagascar
  84. 84. Acknowledgements Villagers and patients IP Madagascar PNLP, Comoros from different study sites Lucie Raharimalala Union Laurence RandrianasoloP aludism e à M adagascar Rahamatou Silai SLP Madagascar Arthur Randriamantena Said Ahmed Bedja Louise H. Ranaivo Arsène Ratsimbasoa Ahmed Ouledi Josée Sahondra-Harisoa Léon Rabarijaona … Désiré Rakotoson Ronan Jambou Oversea collaborations Andrianirina Raveloson Frédéric Ariey Frédéric Ariey Arthur Rakotonjanabelo Marie Ange Rason Odile Puijalon Virginio Pietra … David Fidock … Christophe Rogier Peripheral health facilities … Financial supports Ministry of Health and Family Planning, Madagascar French Government World Bank (Cresan-2) FSP/RAI Raf 6025, IAEA Pal+, France WHO Académies des Sciences, France European Union Institut Pasteur
  85. 85. Intrigue sur le paludisme insulaire de Madagascar Milijaona Randrianarivelojosia, PhD, HDR 7ème édition du cours international “Atelier Paludisme” 16 Mars 2009 – Institut Pasteur de Madagascar

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