AGE-DEPENDENT IMPAIRMENT OF IgG RESPONSES TO GLYCOSYLPHOSPHATIDYLINOSITOL WITH EQUAL EXPOSURE TO PLASMODIUM FALCIPARUM AMONG JAVANESE MIGRANTS TO PAPUA, INDONESIA

SARAH N. HUDSON KEENIHAN United States Navy Medical Research Unit 2, Jakarta, Indonesia; Infectious Disease Medical Research Center, Ministry of Health Research and Development, Jakarta, Indonesia; Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania; United States Naval Medical Research Center, Silver Spring, Maryland

Search for other papers by SARAH N. HUDSON KEENIHAN in
Current site
Google Scholar
PubMed
Close
,
SUTANTI RATIWAYANTO United States Navy Medical Research Unit 2, Jakarta, Indonesia; Infectious Disease Medical Research Center, Ministry of Health Research and Development, Jakarta, Indonesia; Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania; United States Naval Medical Research Center, Silver Spring, Maryland

Search for other papers by SUTANTI RATIWAYANTO in
Current site
Google Scholar
PubMed
Close
,
SARASWATI SOEBIANTO United States Navy Medical Research Unit 2, Jakarta, Indonesia; Infectious Disease Medical Research Center, Ministry of Health Research and Development, Jakarta, Indonesia; Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania; United States Naval Medical Research Center, Silver Spring, Maryland

Search for other papers by SARASWATI SOEBIANTO in
Current site
Google Scholar
PubMed
Close
,
KRISIN United States Navy Medical Research Unit 2, Jakarta, Indonesia; Infectious Disease Medical Research Center, Ministry of Health Research and Development, Jakarta, Indonesia; Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania; United States Naval Medical Research Center, Silver Spring, Maryland

Search for other papers by KRISIN in
Current site
Google Scholar
PubMed
Close
,
HARIJANI MARWOTO United States Navy Medical Research Unit 2, Jakarta, Indonesia; Infectious Disease Medical Research Center, Ministry of Health Research and Development, Jakarta, Indonesia; Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania; United States Naval Medical Research Center, Silver Spring, Maryland

Search for other papers by HARIJANI MARWOTO in
Current site
Google Scholar
PubMed
Close
,
GOWDAHALLI KRISHNEGOWDA United States Navy Medical Research Unit 2, Jakarta, Indonesia; Infectious Disease Medical Research Center, Ministry of Health Research and Development, Jakarta, Indonesia; Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania; United States Naval Medical Research Center, Silver Spring, Maryland

Search for other papers by GOWDAHALLI KRISHNEGOWDA in
Current site
Google Scholar
PubMed
Close
,
D. CHANNE GOWDA United States Navy Medical Research Unit 2, Jakarta, Indonesia; Infectious Disease Medical Research Center, Ministry of Health Research and Development, Jakarta, Indonesia; Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania; United States Naval Medical Research Center, Silver Spring, Maryland

Search for other papers by D. CHANNE GOWDA in
Current site
Google Scholar
PubMed
Close
,
MICHAEL J. BANGS United States Navy Medical Research Unit 2, Jakarta, Indonesia; Infectious Disease Medical Research Center, Ministry of Health Research and Development, Jakarta, Indonesia; Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania; United States Naval Medical Research Center, Silver Spring, Maryland

Search for other papers by MICHAEL J. BANGS in
Current site
Google Scholar
PubMed
Close
,
DAVID J. FRYAUFF United States Navy Medical Research Unit 2, Jakarta, Indonesia; Infectious Disease Medical Research Center, Ministry of Health Research and Development, Jakarta, Indonesia; Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania; United States Naval Medical Research Center, Silver Spring, Maryland

Search for other papers by DAVID J. FRYAUFF in
Current site
Google Scholar
PubMed
Close
,
THOMAS L. RICHIE United States Navy Medical Research Unit 2, Jakarta, Indonesia; Infectious Disease Medical Research Center, Ministry of Health Research and Development, Jakarta, Indonesia; Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania; United States Naval Medical Research Center, Silver Spring, Maryland

Search for other papers by THOMAS L. RICHIE in
Current site
Google Scholar
PubMed
Close
,
SANJAI KUMAR United States Navy Medical Research Unit 2, Jakarta, Indonesia; Infectious Disease Medical Research Center, Ministry of Health Research and Development, Jakarta, Indonesia; Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania; United States Naval Medical Research Center, Silver Spring, Maryland

Search for other papers by SANJAI KUMAR in
Current site
Google Scholar
PubMed
Close
, and
J. KEVIN BAIRD United States Navy Medical Research Unit 2, Jakarta, Indonesia; Infectious Disease Medical Research Center, Ministry of Health Research and Development, Jakarta, Indonesia; Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania; United States Naval Medical Research Center, Silver Spring, Maryland

Search for other papers by J. KEVIN BAIRD in
Current site
Google Scholar
PubMed
Close
Restricted access

Immune responses directed at glycosylphosphatidylinositol (GPI) anchors of Plasmodium falciparum may offer protection against symptomatic malaria. To independently explore the effect of age on generation of the anti-GPI IgG response, we measured serum anti-GPI IgGs in a longitudinal cohort of migrant Javanese children (6–12 years old) and adults (≥20 years old) with equivalent numbers of exposures to P. falciparum in Papua, Indonesia. While the peak response in adults was achieved after a single infection, comparable responses in children required ≥3–4 infections. Significantly fewer children (16%) than adults (41%) showed a high (optical density > 0.44) anti-GPI IgG response (odds ratio [OR] = 3.8, 95% confidence interval [CI] = 2.3–6.3, P < 0.0001), and adults were more likely to show a persistently high response (OR = 5.5, 95% CI = 1.0–56.8, P = 0.03). However, the minority of children showing a strong response were significantly less likely to experience symptoms with subsequent parasitemia compared with those with a weak response (OR = 4.0, 95% CI = 1.1–13.8, P = 0.02). This effect was not seen among high- and low-responding adults (OR = 1.2, 95% CI = 0.5–2.8, P = 0.60). Host age, independent of cumulative exposure, apparently represents a key determinant of the quantitative and qualitative nature of the IgG response to P. falciparum GPI.

Author Notes

Reprint requests: Commanding Officer, United States Navy Medical Research Unit 2, American Embassy Jakarta, FPO AP 96520 USA, Attn: Publications Office.
  • 1

    Greenwood B, Mutabingwa T, 2002. Malaria in 2002. Nature 415 :670–672.

  • 2

    Miller LH, Baruch DI, Marsh K, Doumbo OK, 2002. The pathogenic basis of malaria. Nature 415 :673–679.

  • 3

    Richie TL, Saul A, 2002. Progress and challenges for malaria vaccines. Nature 415 :694–701.

  • 4

    Cohen S, McGregor IA, Carrington S, 1961. Gamma globulin and acquired immunity to malaria. Nature 192 :773–777.

  • 5

    Edozien JC, Gilles HM, Udezo IOK, 1962. Adult and cord-blood gamma-globulin and immunity to malaria in Nigerians. Lancet ii :951–955.

  • 6

    McGregor IA, 1964. The passive transfer of human malarial immunity. Am J Trop Med Hyg 13 :237–239.

  • 7

    McGregor IA, Carrington S, Cohen S, 1963. Treatment of east African Plasmodium falciparum malaria with west African human gamma globulin. Trans R Soc Trop Med Hyg 57 :170–175.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Bouharoun-Tayoun H, Attanath P, Sabchareon A, Chongsuphajaisiddhi T, Druilhe P, 1990. Antibodies that protect humans against Plasmodium falciparum blood stages do not on their own inhibit parasite growth and invasion in vitro, but act in cooperation with monocytes. J Exp Med 172 :1633–1641.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Sabchareon A, Burnouf T, Ouattara D, Attanath P, Bouharoun-Tayoun H, Chantavanich P, Foucault C, Chongsuphajaisiddhi T, Druilhe P, 1991. Parasitologic and clinical human response to immunoglobulin administration in falciparum malaria. Am J Trop Med Hyg 45 :297–308.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Ramasamy R, Ramasamy M, Yasawardena S, 2001. Antibodies and Plasmodium falciparum merozoites. Trends Parasitol 17 :194–197.

  • 11

    Gowda DC, Gupta P, Davidson EA, 1997. Glycosylphosphatidylinositol anchors represent the major carbohydrate modification in proteins of intraerythrocytic stage Plasmodium falciparum. J Biol Chem 272 :6428–6439.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Schofield L, Hackett F, 1993. Signal transduction in host cells by a glycosylphosphatidylinositol toxin of malaria parasites. J Exp Med 177 :145–153.

  • 13

    Tachado SD, Gerold P, McConville MJ, Baldwin T, Quilici D, Schwarz RT, Schofield L, 1996. Glycosylphosphatidylinositol toxin of Plasmodium induces nitric oxide synthase expression in macrophages and vascular endothelial cells by a protein tyrosine kinase-dependent and protein kinase C-dependent signaling pathway. J Immunol 156 :1897–1907.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Schofield L, Novakovic S, Gerold P, Schwarz RT, McConville MJ, Tachado SD, 1996. Glycosylphosphatidylinositol toxin of Plasmodium up-regulates intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin expression in vascular endothelial cells and increases leukocyte and parasite cytoadherence via tyrosine kinase-dependent signal transduction. J Immunol 156 :1886–1896.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Schofield L, Vivas L, Hackett F, Gerold P, Schwarz RT, Tachado S, 1993. Neutralizing monoclonal antibodies to glycosylphosphatidylinositol, the dominant TNF-alpha-inducing toxin of Plasmodium falciparum: prospects for the immunotherapy of severe malaria. Ann Trop Med Parasitol 87 :617–626.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Schofield L, Hewitt MC, Evans K, Siomos M, Seeberger PH, 2002. Synthetic GPI as a candidate anti-toxic vaccine in a model of malaria. Nature 418 :785–789.

  • 17

    Naik RS, Branch OH, Woods AS, Vijaykumar M, Perkins DJ, Nahlen BL, Lal AA, Cotter RJ, Costello CE, Ockenhouse CF, Davidson EA, Gowda DC, 2000. Glycosylphosphatidylinositol anchors of Plasmodium falciparum: molecular characterization and naturally elicited antibody response that may provide immunity to malaria pathogenesis. J Exp Med 192 :1563–1576.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Boutlis CS, Gowda DC, Naik RS, Maguire GP, Mgone CS, Bockarie MJ, Lagog M, Ibam E, Lorry K, Anstey NM, 2002. Antibodies to Plasmodium falciparum glycosylphosphatidylinositols: inverse association with tolerance of parasitemia in Papua New Guinean children and adults. Infect Immun 70 :5052–5057.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    De Souza JB, Todd J, Krishegowda G, Gowda DC, Kwiatkowski D, Riley EM, 2002. Prevalence and boosting of antibodies to Plasmodium falciparum glycosylphosphatidylinositols and evaluation of their association with protection from mild and severe clinical malaria. Infect Immun 70 :5045–5051.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Baird JK, 1995. Host age as a determinant of naturally acquired immunity to Plasmodium falciparum. Parasitol Today 11 :105–111.

  • 21

    McGregor IA, 1987. The significance of parasitic infections in terms of clinical disease: a personal view. Parasitology 94 (Suppl): S159–S178.

  • 22

    Baird JK, 1998. Age-dependent characteristics of protection v. susceptibility to Plasmodium falciparum. Ann Trop Med Parasitol 92 :367–390.

  • 23

    Kurtis JD, Mtalib R, Onyango FK, Duffy PE, 2001. Human resistance to Plasmodium falciparum increases during puberty and is predicted by dehydroepiandrosterone sulfate levels. Infect Immun 69 :123–128.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Day KP, Marsh K, 1991. Naturally acquired immunity to Plasmodium falciparum. Immunol Today 12 :A68–A71.

  • 25

    Snow RW, Marsh K, 1998. New insights into the epidemiology of malaria relevant for disease control. Br Med Bull 54 :293–309.

  • 26

    Berhe S, Schofield L, Schwarz RT, Gerold P, 1999. Conservation of structure among glycosylphosphatidylinositol toxins from different geographic isolates of Plasmodium falciparum. Mol Biochem Parasitol 103 :273–278.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27

    Morell A, Skvaril F, Hitzig WH, Barandun S, 1972. IgG subclasses: Development of the serum concentrations in “normal” infants and children. J Pediatr 80 :960–964.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28

    Oxelius V, 1979. IgG subclass levels in infancy and childhood. Acta Paediatr Scand 68 :23–27.

  • 29

    Fulford AJC, Webster M, Ouma JH, Kimani G, Dunne DW, 1998. Puberty and age-related changes in susceptibility to schistosome infection. Parasitol Today 14 :23–26.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30

    Baird JK, Masbar S, Basri H, Tirtokusumo S, Subianto B, Hoffman SL, 1998. Age-dependent susceptibility to severe disease with primary exposure to Plasmodium falciparum. J Infect Dis 178 :592–595.

    • PubMed
    • Search Google Scholar
    • Export Citation
Past two years Past Year Past 30 Days
Abstract Views 800 734 27
Full Text Views 252 5 0
PDF Downloads 40 12 0
 

 

 

 
 
Affiliate Membership Banner
 
 
Research for Health Information Banner
 
 
CLOCKSS
 
 
 
Society Publishers Coalition Banner
Save