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Background: The factors involved in the progression from Plasmodium falciparum infection to severe malaria (SM) are still incompletely understood. Altered antibody and cellular immunity against P. falciparum might contribute to increase the risk of developing SM.

Methods: To identify immune responses associated with SM, a sex- and age-matched case-control study was carried out in 134 Mozambican children with SM (cerebral malaria, severe anaemia, acidosis and/or respiratory distress, prostration, hypoglycaemia, multiple seizures) or uncomplicated malaria (UM). IgG and IgM against P. falciparum lysate, merozoite antigens (MSP-119, AMA-1 and EBA-175), a Duffy binding like (DBL)-α rosetting domain and antigens on the surface of infected erythrocytes were measured by ELISA or flow cytometry. Plasma concentrations of IL-12p70, IL-2, IFN-γ, IL-4, IL-5, IL-10, IL-8, IL-6, IL-1β, TNF, TNF-β and TGF-β1 were measured using fluorescent bead immunoassays. Data was analysed using McNemar's and Signtest.

Results: Compared to UM, matched children with SM had reduced levels of IgG against DBLα (P < 0.001), IgM against MSP-119 (P = 0.050) and AMA-1 (P = 0.047), TGF-β1 (P < 0.001) and IL-12 (P = 0.039). In addition, levels of IgG against P. falciparum lysate and IL-6 concentrations were increased (P = 0.004 and P = 0.047, respectively). Anti-DBLα IgG was the only antibody response associated to reduced parasite densities in a multivariate regression model (P = 0.026).

Conclusions: The lower levels of antibodies found in children with SM compared to children with UM were not attributable to lower exposure to P. falciparum in the SM group. IgM against P. falciparum and specific IgG against a rosetting PfEMP1 domain may play a role in the control of SM, whereas an imbalanced pro-inflammatory cytokine response may exacerbate the severity of infection. A high overlap in symptoms together with a limited sample size of different SM clinical groups reduced the power to identify immunological correlates for particular forms of SM.

Titel:	Low antibodies against Plasmodium falciparum and imbalanced pro-inflammatory cytokines are associated with severe malaria in Mozambican children: a case-control study.
Autor/in / Beteiligte Person:	Rovira-Vallbona, E ; Moncunill, G ; Bassat, Q ; Aguilar, R ; Machevo, S ; Puyol, L ; Quintó, L ; Menéndez, C ; Chitnis, CE ; Alonso, PL ; Dobaño, C ; Mayor, A
Link:	Volltext (PDF) View record at Springer (Volltext)
Zeitschrift:	Malaria journal, Jg. 11 (2012-05-30), S. 181
Veröffentlichung:	London : BioMed Central, [2002-, 2012
Medientyp:	academicJournal
ISSN:	1475-2875 (electronic)
DOI:	10.1186/1475-2875-11-181
Schlagwort:	Antigens, Protozoan immunology Case-Control Studies Child, Preschool Enzyme-Linked Immunosorbent Assay Flow Cytometry Humans Immunoglobulin G blood Immunoglobulin M blood Infant Male Mozambique Antibodies, Protozoan blood Cytokines blood Malaria, Falciparum immunology Malaria, Falciparum pathology Plasmodium falciparum immunology
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [Malar J] 2012 May 30; Vol. 11, pp. 181. <i>Date of Electronic Publication: </i>2012 May 30. MeSH Terms: Antibodies, Protozoan / blood ; Cytokines / blood ; Malaria, Falciparum / immunology ; Malaria, Falciparum / pathology ; Plasmodium falciparum / *immunology ; Antigens, Protozoan / immunology ; Case-Control Studies ; Child, Preschool ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Humans ; Immunoglobulin G / blood ; Immunoglobulin M / blood ; Infant ; Male ; Mozambique References: Mol Biochem Parasitol. 2001 Dec;118(2):247-51. (PMID: 11738714) ; Nat Med. 1997 Jan;3(1):80-3. (PMID: 8986746) ; Afr Health Sci. 2009 Jun;9(2):66-74. (PMID: 19652739) ; Parasite Immunol. 2011 Feb;33(2):124-31. (PMID: 21226725) ; PLoS Med. 2009 Jul;6(7):e1000116. (PMID: 19636353) ; J Infect Dis. 2006 Nov 15;194(10):1438-46. (PMID: 17054074) ; J Exp Med. 1998 Jul 6;188(1):39-48. (PMID: 9653082) ; Proc Natl Acad Sci U S A. 1994 Aug 16;91(17):8097-101. (PMID: 8058763) ; Am J Trop Med Hyg. 2002 Dec;67(6):597-603. (PMID: 12518849) ; Infect Immun. 2004 Oct;72(10):5630-7. (PMID: 15385460) ; PLoS One. 2011 Apr 29;6(4):e19422. (PMID: 21559373) ; Nat Rev Immunol. 2004 Jul;4(7):553-64. (PMID: 15229474) ; Mol Biochem Parasitol. 2002 Aug 7;123(1):23-33. (PMID: 12165386) ; Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10700-2. (PMID: 7938013) ; Vaccine. 2009 Jan 1;27(1):62-71. (PMID: 18977268) ; J Immunol. 2009 Aug 1;183(3):2176-82. (PMID: 19592645) ; J Infect Dis. 2011 Jul 1;204(1):27-35. (PMID: 21628655) ; PLoS One. 2011 Apr 13;6(4):e18185. (PMID: 21533209) ; Am J Trop Med Hyg. 2000 May;62(5):566-72. (PMID: 11289665) ; Nat Immunol. 2011 Dec 11;13(2):188-95. (PMID: 22157630) ; J Infect Dis. 2008 Mar 1;197(5):766-74. (PMID: 18260767) ; Am J Trop Med Hyg. 1995 Nov;53(5):532-8. (PMID: 7485713) ; Clin Exp Immunol. 1992 Aug;89(2):296-300. (PMID: 1638773) ; Immunology. 1990 Jul;70(3):315-20. (PMID: 2379940) ; Nature. 1997 Jul 17;388(6639):292-5. (PMID: 9230440) ; PLoS One. 2012;7(1):e31011. (PMID: 22295123) ; Stat Med. 1999 Dec 30;18(24):3453-62. (PMID: 10611618) ; Malar J. 2008 Aug 16;7:155. (PMID: 18706102) ; J Clin Microbiol. 1993 Mar;31(3):636-41. (PMID: 8458956) ; Trans R Soc Trop Med Hyg. 2003 Nov-Dec;97(6):661-6. (PMID: 16117958) ; Malar J. 2008 Feb 26;7:37. (PMID: 18302771) ; J Infect Dis. 2000 Sep;182(3):988-92. (PMID: 10950804) ; EMBO Rep. 2005 Aug;6(8):775-81. (PMID: 16025132) ; N Engl J Med. 1989 Jun 15;320(24):1586-91. (PMID: 2657427) ; J Infect Dis. 1991 Jul;164(1):163-9. (PMID: 1711552) ; Infect Immun. 2006 Sep;74(9):5249-60. (PMID: 16926419) ; Bioprocess Biosyst Eng. 2010 Aug;33(6):719-30. (PMID: 19921275) ; Clin Microbiol Rev. 2009 Jan;22(1):13-36, Table of Contents. (PMID: 19136431) ; J Clin Microbiol. 1990 Feb;28(2):265-8. (PMID: 2179259) ; Trends Parasitol. 2004 Dec;20(12):597-603. (PMID: 15522670) ; Lancet. 1990 Dec 15;336(8729):1457-60. (PMID: 1979090) ; Parasite Immunol. 2005 May;27(5):171-80. (PMID: 15987340) ; Infect Immun. 2008 May;76(5):1837-47. (PMID: 18299339) ; J Infect Dis. 1995 Sep;172(3):838-44. (PMID: 7658079) ; Malar J. 2008 Jul 29;7:142. (PMID: 18664257) ; Southeast Asian J Trop Med Public Health. 1985 Jun;16(2):307-13. (PMID: 3906923) ; Blood. 1994 Dec 1;84(11):3909-14. (PMID: 7949147) ; Nature. 2002 Feb 7;415(6872):673-9. (PMID: 11832955) ; Nature. 1961 Nov 25;192:733-7. (PMID: 13880318) ; Infect Immun. 2009 Sep;77(9):3857-63. (PMID: 19546191) ; J Infect Dis. 2004 Feb 1;189(3):540-51. (PMID: 14745713) ; Infect Immun. 2000 Jul;68(7):3909-15. (PMID: 10858202) ; Lancet Infect Dis. 2011 Jul;11(7):541-56. (PMID: 21700241) ; Lancet. 2004 Oct 16-22;364(9443):1411-20. (PMID: 15488216) ; Infect Immun. 2002 Aug;70(8):4471-6. (PMID: 12117958) ; Am J Trop Med Hyg. 2006 Feb;74(2):191-7. (PMID: 16474069) ; J Immunol. 2009 Sep 1;183(5):3356-63. (PMID: 19675168) ; Infect Immun. 2011 Apr;79(4):1654-9. (PMID: 21300778) ; Malar J. 2011 Sep 19;10:271. (PMID: 21929748) ; Nat Immunol. 2011 Mar;12(3):189-94. (PMID: 21321588) ; Trans R Soc Trop Med Hyg. 1999 Jul-Aug;93(4):369-74. (PMID: 10674079) ; Acta Trop. 2004 Apr;90(2):131-40. (PMID: 15177139) Substance Nomenclature: 0 (Antibodies, Protozoan) ; 0 (Antigens, Protozoan) ; 0 (Cytokines) ; 0 (Immunoglobulin G) ; 0 (Immunoglobulin M) Entry Date(s): Date Created: 20120601 Date Completed: 20130130 Latest Revision: 20211021 Update Code: 20231215 PubMed Central ID: PMC3464173

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Low antibodies against Plasmodium falciparum and imbalanced pro-inflammatory cytokines are associated with severe malaria in Mozambican children: a case-control study.