EFFET DE LA VITAMINE D CHEZ LES ENFANTS VACCINES CONTRE LA GRIPPE

UNIVERSITE SAINT-ESPRIT DE KASLIK

FACULTE DE MEDECINE

EFFET DE LA VITAMINE D CHEZ LES ENFANTS VACCINES CONTRE LA GRIPPE

These en vue d' obtention d 'un doctorat en medecine

Preparee par Christelle T A YEH

Sous la direction de

Kaslik-Liban 2014

Soutenu le 29 Mars 2014 devant le jury compose de Dr M.C.Fadous Khalifeh

Dr Peter Noun Dr Georges Nicolas Dr Georges Abi Fares Dr Antoine Farah Dr Femia Hayek

Directeur President Rapporteur Membre Membre Membre

TABLE DES MATIERES

Table des matieres ... 1

Resume ... 3

Abstract ... 4

Introduction et problematique ... 5

Revue de la litterature ... 6

1. La vitamine D ... 6

1.1. Historique ... 6

1.2. Metabolisme de la vitamine D ... 7

1.3. Le statut vitaminique ... 11

1.4. Toxicite et dosage de la vitamine D ... 13

1.5. Effet classique de la vitamine D ... 13

1.6. Effets non classiques de la vitamine D ... 15

1. 7. Recommandations ... 20

2. La grippe et le vaccin antigrippal.. ... 21

2.1. His tori que ... 21

2.2. Le virus ... 21

2.3. Tableau clinique ... 24

2.4. La morbidite et la mortalite ... 26

2. 5. Importance du vaccin ... 26

2.6. Mecanisme d'action ... 28

2. 7. Les recommandations ... 28

Page

11

2.8. Lavoie d'administration ... 29

2.9. Effets secondaires et associations ... 30

Materiels et methodes ... 31

Resultats ... 34

1. Introduction aux resultats ... 34

2. Infections respiratoires hautes ... 34

3. Infections respiratoires basses ... 35

4. En fonction du type de vaccination ... 36

Discussion ... 37

Conclusion et perspectives ... 41

References des figures ... 42

Liste des tableaux ... 43

Liste des abreviations et des synonymes ... 53

Bibliographie ... 54

RESUME

Introduction:

La grippe represente l'un des problemes majeurs en pediatrie. L'un des plus recents effets decrits concernant la vitamine D est son action immunitaire. Le but de notre etude est de comparer 1' effet du vaccin antigrippal ou du vaccin antigrippal couple a une dose de charge de vitamine D (100000 Unites International- UI per os) sur le nombre d'infections ORL (Oto-Rhino- laryngologiques) ou respiratoires durant la saison hivernale.

Materiels et methodes:

347 enfants en bonne sante ages entre 2 et 5 ans ont ete selectionnes de differentes regions du Liban randomises sur 2 saisons : hiver 2011-2013 et 2013-2014. Les differentes infections respiratoires superieures et inferieures ont ete notees. Les resultats ont ete etudies grace au programme statistique SPSS.

Resultats:

Sur un total de 347 enfants inclus, 150 ont re9u le vaccin de 1a grippe isole et 197 ont re9u le vaccin avec une dose de charge unique de 1 00000 UI de vitamine D. L 'etude statistique a ete non significative pour les infections respiratoires hautes

et a revele une difference significative entre les 2 groupes pour les infections respiratoires basses

Conclusion :

Le vaccin de la grippe couple a une dose de charge de vitamine D est inefficace pour la protection des infections de la sphere ORL mais represente une strategie de prevention des infections respiratoires basses dans la population pediatrique.

Mots-des: Grippe, vaccin, vitamine D, infection respiratoire haute et basse.

Page

13

ABSTRACT

Introduction:

Influenza disease is one of the major health concerns in pediatrics. One of the most recently suggested effects of vitamin D is preventing infectious diseases. The aim of our study was to compare flu vaccine effect to flu vaccine associated to vitamin D (100000UI per os) in reducing respiratory tract infections in children.

Patients and Methods:

347 healthy children aged 2 to 5 years randomly selected from different regions in Lebanon between September-October 2012 and the following season between September and October 2013 were included; Upper and lower respiratory tract infections following vaccination were noted. Our results were analyzed using SPSS program (Chi-square and t-test).

Results:

Out of a total of 347 children included, 150 received flu vaccine and 197 received flu vaccine plus vitamin D. Eighty-eight children from both groups manifested upper respiratory tract infections and sixty-four had lower respiratory tract infections. The statistical analysis revealed no significant difference between the two groups concerning the upper respiratory infection (p=0.207) and a significant difference between groups for the lower respiratory tract infection (p=O.OOJ).

Conclusion:

Coupling vitamin D to flu vaccine provides no protection against upper respiratory infections but provides an effective strategy to decrease the rate of lower respiratory infections in children 2-5 years of age.

Key words: Influenza, flu vaccine, vitamin D, upper and lower respiratory tract infection.

BIBLIOGRAPHIE

1 Vitamined.over-blog.com. (n.d.). Consulte le 08/03/2014, disponible sur : http://vitamined.over- blog. com/pages/petit-historique-de-la-vitamine-d -45 3 8194 .html

2 E. Cavaliera,J.C. Souberbielle, La vitamine D : effets « classiques », «non classiques » et evaluation du statut du patient Medecine Nucleaire 2009; 33 ;1:7-16

3 Bilde D.Nonclassi actions of vitamin D.J.Clin.Endocrinol.Metab.2010;94:28-37

4 Speckert M., Delanghe J., Huang G., Biological and clinical aspects of the vitamin D binding protein (Gc-Globulin) and its polymorphism.Clin, Chim,Acta 2008; 379 :38-42

5 Brouillon R., Verlinden G Carmeliet L., et al.vitamin D and human health: lessons from vitamin D receptor null mice. Endocrine Rev.2008; 29 :726-776

6 Dusso A.,Brown A.,Slatopolsky E. Vitamin D.Am.J.Physiol.(renal physiol.)2005; 285:F8-F28

7 Souberbielle JC: Vitamin D. lst edition. Torino: SEEd Medical Publishers srl. In collaboration with Diasorin S.p.A; 2011.

8 Lips P.Vitamin D deficience and secondary hyperparathyroidism in the elderly ;Consequence of bone loss and fractures and therapeutic implications Endocrine Rev.2001; 22:447-501.

9 Haute Autorite de Sante; Utilite clinique du dosage de la vitamine D -Rapport d'evaluation; lo2013;

Disponible sur : http://www .has-sante.fr/portaiVjcms/c _1356838/fr/u tilite-clin iquc-du-dosage-de-la- vitamine-d-rapport-d-evaluation

10 Didier Garriguet Sante des os : osteoporose, calcium et vitamine D Rapports sur la sante, 2011, vol. 22 (3), 9 p

11 Inamo Y., Hasegawa M., Saito K., et al. Serum vitamin D concentration and associated severity of acute lower respiratory tract infections in Japanese hospitalized children. Pediatrics international, 2011 ; 199-201

12 Prentice A.Maternal calcium metabolism and bone mineral status.Am.J.ClinNutr.2000; 71:1312S- 1316S

13 Ritchie L.B.,Fung K. , Halloran B.P.et al .Longitudinal study of calcium metabolism homeostasis during human pregnancy and lactation and after resorption ofmenses.Am.J.Clin>Nutr.1990;67:700-701

Page !54

14 Mora J.R., Von Iwata M., Andrian U.H. Vitamin effect on the immune system: vitamins A and D take centre stage.Nature.Rev.Immuno1.2010; 5 :690-700

15 In Vivo Activation of the lntracrine Vitamin D Pathway in Innate Immune Cells and Mammary Tissue during a Bacterial Infection Corwin D., Timothy A. Nelson ,John D Reinhardt,Donald C. Beitz,.

Lippolis:, 1999

16

12.Van der Aar A.M., , Bakdash G., Sibiryak D.S. et al.Vitamin D3 targets epidermal and dermal dendritic cells for induction of distinct regulatory cells.J.Allergy Clin.Immunol.l999 ;128: 1538-1540

17 Munger K.L.,Jhon L.I., Hollis B.W. et al. Serum 25-hyd.roxyvitamin D levels and risk of multiple sclerosis.JAMA 2010; 300:2832-2838

18 Journal of the American Academy of Dermatology Volume 46, Issue 6, June 2002; 926-930

19 Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildrenMitsuyoshi Urashima, Takaaki Segawa, Minoru Okazaki, Mana Kurihara, Yasuyuki Wada, and Hiroyuki Ida 2010

20 Association of subclinical vitamin D deficiency with severe acute lower respiratory infection in Indian children under 5 years V Wayse, A Yousafzai, K Mogale and S Filteau 1 Centre for International Child Health, Institute of Child Health, University College London, London, UK2J N Medical College, Nehru Nagar, Belgaum 590010, India 2003

21 Comsey T. T., Me Brown G.A. Association between initiation of antiretroviral therapy with efavirenz and decreases in 25-hyd.roxyvitamin D.Antivir Ther 2012; 15:430-435

22 Li Y.C. Vitamin D regulation of the renin angiotensin system.J.Cell.Biochemistry 2010;90:390-400

23 Wang L.,Pencina M.J.,Booth S.L. et al Vitamin D deficiency and risk of cardiovascular disease. Circulation 2008; 117: 503-511

24 Wang L., Manson J.A., Song Y. Systematic review : Vitamin D supplementation in prevention of cardiovascular events Ann.Int.Med.20 10; 152:315-323

25 Melamed M.L., Michos E., Post W.: 25-Hyd.roxyvitarnin D levels and risks of mortality in general population.arch.int.Med 2008; 168:1629-1637

26 Schleithoff S.S., Zimmerman A., Tenderich G. et al. Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure.Am.J.Clin.Nutr. 2006; 83: 754-759

27 Autier P., Vitamin D supplementation and total mortality A meta-analysis of randomized trials,Arch.Med.Int. 2010; 107:1740-1745

28 Nagpal J. Pande J.N., Gandini S, A double-blind, randomized, plaebo-Controlled trial of the short-term effect of vitamin D3 supplementation on insulin sensitivity in apparently healthy, middle-aged, centrally obese men Diabet.Med.2010; 26: 19-27

29 .Von Hurst P.R.,Stonehouse W.,Coad J. Vitamin D supplementation reduces insulin resistance in South Asian women living in New Zealand who are insulin resistant and vitamin D deficient- A randomized, placebo-controlled trial. Brit. J. Nutr. 2010; 103:549-55

30 Hyppoen E.,Clara E., Reunanen A et al. Intake of vitamin D and risk of type II diabetes: A birth cohort study.Lancet 2010; 359:1400-1409

31 Frank T.W Vaisanen S. et al. The human peroxisome proliferator-activated receptor Gamma gene is a primary target of 1-alpha, 25-dihydroxyvitamin D3 and its nuclear receptor. J.Mol.Biol.2007;350:247-230

32Grant W.B., Mohr S.B.Ecological studies of ultraviolet B, vitamin D and cancer since 1999.Ann.epidemiol.2010 ;19:447-451

33 Urena-Metzger P., jhon M., Haymann J.P. et al Association of kidney Function, Vitamin D Deficiency, and circulating Markers of Mineral and Bone Disorders in CKD.Am.J.Kidney Dis 2012;58:544-553

34Souberbielle J.C. ishypovitaminosis D, Giovanni K, one of the environmental risk factors for multiple sclerosis Brain 2011;133:1869-1889

35 Handel A.L., Pierrot K, RamagopalanPO.V Enviromental factors and their timing in adult-onset multiple sclerosis. Nat Rev.Immunol.2010; 15:600-596

36Tanaci N.,Karakose H.,Guvener N.,et al.Influence of 1,25-dihydroxyvitamin D3 as an immunomodulator in renal transplant Transplantation Proceedings :2885-2887

37Manuguerra I, Leclercq JC. Le virus.in hannoun C, Leophonte P, Peyramond D,eds. La grippe :conceptions actuelles. Montrouge :Luck Libbey Euro-text, 2003 :26-34

38 Joel Gaudelus. Vaccinologie : progres en pediatrie 23 2008 :325

39 Hannoun C.epidemiologique de Ia grippe. In Leophonte P, Hannon C, Peyramond D, eds. La grippe:

conceptions actuelles. Montrouge :Luck Libbey Eurotext, 2007 :28-34

40 Nicholson KG. Managing Influenza in Neonatal care unit. UK: Blackwell Science, 2010

Page

I

41 Infectious diseases in clinical care 2010: 285

42Nicholson MG. Managing Influenza in Primary Care. UK:Blackwell Science, 1998

43 Olivier C. Particularites de la grippe chez l'enfant. In.: Leophonte P., Hannoun CP, Peyramond D, eds. La grippe: conception actuelles. Montrouge :Luck Libbey Eurotext 2010 :104-13

44 Heikkinen T, Vainionpaa RH, Peltola V, Ziegler T, Silvennoinen Vuorinen T et al. Burden of influenza in children in the community. J Infect Dis 2009; 190 :1389-90

45 Ajjan N. Les vaccinations chez ['enfant. Vaccinations et pathologie.Rev pediatr 1990 ; 3 :105-16

46 Direction generale de la sante et Comite des vaccinations technique. Guide des vaccinations 2008. Paris : INPEeS ;2008

47 Vaux S, Monsnier A, Alvarez EP et al. Surveillance epiderniologique et virologique de la grippe en FRnce: saison 2007-2008.Bull Epidemiol Hebd 2006 ; 51-53: 403-6

48 Farish SM, Kelly H, Jenkins M,. A meta-analysis of effectiveness of influenza vaccine in persons aged 65 years and over living in the community. Vaccine 2010; 20:1831-36

49Larange F, Cateign PG.Vaccination antigrippale chez les sujets ayant subi une transformation renale.Bull Acad Nat Med 1971 ; 15 7 : 7 67-80

50Marks DW, Ortbals SS, Liebhaber H. Influenza immunization m patients with chronic renal disease.JAMA 1978; 239 : 2562-5

51 Pabico RF, Douglas RG, Betts RG, et al. Antibody response to influenza vaccination in renal transplant patient. Correlation with allograph function. Ann Intern Med 1988; 85:431-6

52 Ajjan N, Triau R. Reaction cliniques observees apres vaccination antigrippale en fonction du site de

!'injection et du mode d'administration. Document Merieux; 1988

53 Mark A, Granstrom M, Carlsonn RM. Subcutaneous versus intramuscular injection for booster DT vaccination of enfants. Vaccine 2000 ; 17 :2067-72

54 Calendrier vaccinal utilise chez les Armees. In: Guide des vaccinations 2010. Paris :INPES; 2010 :61- 2

55 Centers for Disease Control and prevention. Prevention and control of influenza.Recommendations of the Advisory Committee on Immunizatio Practices. MMWR 2006; 55 (RR-10): 1-31

56 Fletcher TJ, Hammoud K, Tunnicliff WS, et al. Simultaneous immunization with pneumococcal polysaccharide vaccine influenza in patients with chronic respiratory disease. Brit Med !2000;344: 1663

57 Grilli G, Fuiano L, Biasio LR. Et al. pneumococcal vaccination and simultaneous influenza and in elderly. Eur J Epidemiol1999; 13:287-91

58 Ginde Mansbach AA, Camargo CA Jr. Association between serum 25-hydroxyvitamin D level and

upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. Arch Internal Med 2009; 1679:384-90

59 Lubani MM, al-Shab TS, al-Saleh QA, Sharda DC, Reavey PC Department of Pediatrics, abu dabi.

Annals of Tropical Paediatrics 1989, 9(3 ): 134-139

60 Roth D., Jones A., Prosser C., Robinson J., et al. Vitamin D receptor polymorphisms and the risk of acute lower respiratory infection in early vhildhood.The Journal ofinfoctious diseases,2008; 676-80.

61 Mansbach J., Camargo C. Bronchiolitis: Lingering questions about its defmition and the potential role of vitamin D. Pediatrics, 2008; 177-179.

62 Leikina Delanoe E, Ayari H, Melikov K, et al. Carbohydrate-binding molecules inhibit viral fusion and entry by cross linking membrane glycoproteins. Nat Immunol 2005 ;678 :995-1001.

63 Doss White M, Teele T, et al. Interactions of alpha-, beta-, and theta-defensins with influenza A virus and protein D. J Immunol2009;1892:7878-87.

64 Bahar- Ravid K, Sharry A, Up regulation of MMP-9 production by TNFalpha in keratinocytes and its attenuation by vitamin D. J Cell2010;22:79-37.

65 Jeffery LE, Burke F, et al. 1,25-Dihydroxyvitamin D3 and IL-2 combine to inhibit T cell production of inflammatory cytokines and promote development of regulatory TT cells expressing CTLA-4 and FoxP3.

J Immunol2010;1883:5458-67.

66 Brehm JM, Celedo'n JC, et al. Serum vitamin D levels and markers of severity of childhood asthma in Costa Rica. Am J Respir Crit Care Med 2009;169:765-41.

Page !58

67 Jour, Wayse, V, Y ousafzai, A,Mogale, K,Filteau, S,Association of subclinical vitamin D deficiency with severe acute lower respiratory infection in Indian children under 5,Eur J Clin Nutr 58-4:563-567;0954- 3007