A model of development of acquired immunity to malaria in humans living under endemic conditions.

Malaria remains a significant global health problem. Most morbidity and mortality in an endemic setting is in children less than 5 years old, and increasing resistance to infection and disease with age is thought to reflect a slow, gradual acquisition of protective immunity. It is not clear if the semi-immune status of adults, in which parasites are present at below clinical threshold, is the result of cumulative exposure to Plasmodium falciparum or reflects an underlying difference between adult and infant immunity. Immuno-epidemiological studies of people living in malaria-endemic areas have not produced consistent examples of surrogate markers of protection. This gulf in our understanding of immunity to malaria may be addressed by novel application of an established murine model of immune regulation of blood stage infection. This exploits two examples of loss of immunity, selective immunosuppression in pregnancy, and waning of maternally transferred protection in neonates, to distinguish the immunological determinants involved in the radical transition between susceptible and resistant immune status. It is suggested that application of this unique model should significantly advance knowledge of how acquired immunity to malaria develops and is highly relevant to the pathogenesis of malaria in human pregnancy and the design of antimalarial vaccines for use in children.

[1]  B. Luft,et al.  Effect of pregnancy on augmentation of natural killer cell activity by Corynebacterium parvum and Toxoplasma gondii. , 1984, Journal of immunology.

[2]  C. Newbold,et al.  Relationships between sequestration, antigenic variation and chronic parasitism in Plasmodium chabaudi chabaudi– a rodent malaria model , 1990, Parasite immunology.

[3]  A. Taylor-Robinson.  Immunoregulation of malarial infection: balancing the vices and virtues. , 1998, International journal for parasitology.

[4]  Purnomo,et al.  Age-specific prevalence of Plasmodium falciparum among six populations with limited histories of exposure to endemic malaria. , 1993, The American journal of tropical medicine and hygiene.

[5]  A. Taylor-Robinson,et al.  Functional characterization of protective CD4+ T-cell clones reactive to the murine malaria parasite Plasmodium chabaudi. , 1992, Immunology.

[6]  V. Thomas,et al.  A case of congenital malaria in Malaysia with IgM malaria antibodies. , 1980, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[7]  Patrick E. Duffy,et al.  Adherence of Plasmodium falciparum to Chondroitin Sulfate A in the Human Placenta , 1996, Science.

[8]  C. Chizzolini,et al.  Isotypic analysis, antigen specificity, and inhibitory function of maternally transmitted Plasmodium falciparum-specific antibodies in Gabonese newborns. , 1991, The American journal of tropical medicine and hygiene.

[9]  A. Taylor-Robinson,et al.  Protective CD4+ T‐cell lines raised against Plasmodium chabaudi show characteristics of either Th1 or Th2 cells , 1993, Parasite immunology.

[10]  L. Bruce-Chwatt.  Malaria in African infants and children in Southern Nigeria. , 1952, Annals of tropical medicine and parasitology.

[11]  T. Mosmann,et al.  The expanding universe of T-cell subsets: Th1, Th2 and more. , 1996, Immunology today.

[12]  W. Eling,et al.  Depressed malarial immunity in pregnant mice , 1980, Infection and immunity.

[13]  A. Taylor-Robinson,et al.  A dichotomous role for nitric oxide in protection against blood stage malaria infection. , 1999, Immunology letters.

[14]  J. Langhorne,et al.  Frequencies of CD4+ T cells reactive with Plasmodium chabaudi chabaudi: distinct response kinetics for cells with Th1 and Th2 characteristics during infection. , 1989, International immunology.

[15]  M. Hommel,et al.  Antigenic variation in malaria parasites. , 1985, Immunology today.

[16]  W. Eling,et al.  Pregnancy-induced recrudescences strengthen malarial immunity in mice infected with Plasmodium berghei , 1985, Parasitology.

[17]  S. Romagnani.  The Th1-Th2 paradigm in disease , 1996 .

[18]  P. Perlmann,et al.  T-cell control of immunity to the asexual blood stages of the malaria parasite. , 1994, Critical reviews in immunology.

[19]  R. Turner,et al.  QUININE AND SEVERE FALCIPARUM MALARIA IN LATE PREGNANCY , 1985, The Lancet.

[20]  May Ho,et al.  Bruce-Chwatt's essential malariology (3rd Edn.) , 1994 .

[21]  B. Greenwood,et al.  Association between immune recognition of the malaria vaccine candidate antigen Pf155/RESA and resistance to clinical disease: a prospective study in a malaria-endemic region of west Africa. , 1991, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[22]  R. Raghupathy.  Th1-type immunity is incompatible with successful pregnancy. , 1997, Immunology today.

[23]  B. Brabin,et al.  Consequences of maternal anaemia on outcome of pregnancy in a malaria endemic area in Papua New Guinea. , 1990, Annals of tropical medicine and parasitology.

[24]  W. Wernsdorfer,et al.  Malaria: Principles and Practice of Malariology , 1989 .

[25]  Chris Newbold,et al.  Relation between severe malaria morbidity in children and level of Plasmodium falciparum transmission in Africa , 1997, The Lancet.

[26]  R. Coffman,et al.  TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. , 1989, Annual review of immunology.

[27]  G. Pollock.  Anaemia and Pregnancy , 1937 .

[28]  A. Holder,et al.  Clinical immunity to Plasmodium falciparum malaria is associated with serum antibodies to the 19-kDa C-terminal fragment of the merozoite surface antigen, PfMSP-1. , 1996, The Journal of infectious diseases.

[29]  B. Greenwood,et al.  Suppression of cell-mediated immune responses to malaria antigens in pregnant Gambian women. , 1989, The American journal of tropical medicine and hygiene.

[30]  B. Brabin.  An analysis of malaria in pregnancy in Africa. , 1983, Bulletin of the World Health Organization.

[31]  T. Mosmann,et al.  Bidirectional cytokine interactions in the maternal-fetal relationship: is successful pregnancy a TH2 phenomenon? , 1993, Immunology today.

[32]  T. Godal,et al.  Malaria vaccine development: current status. , 1998, Parasitology today.

[33]  Purnomo,et al.  Age-dependent acquired protection against Plasmodium falciparum in people having two years exposure to hyperendemic malaria. , 1991, The American journal of tropical medicine and hygiene.

[34]  J. Langhorne.  The immune response to the blood stages of Plasmodium in animal models. , 1994, Immunology letters.

[35]  B. Greenwood,et al.  Relationships between maternal malaria and malarial immune responses in mothers and neonates , 1995, Parasite immunology.

[36]  J. Baird.  Age-dependent characteristics of protection v. susceptibility to Plasmodium falciparum. , 1998, Annals of tropical medicine and parasitology.

[37]  T. Mosmann,et al.  Synthesis of T helper 2-type cytokines at the maternal-fetal interface. , 1993, Journal of immunology.

[38]  C. Menéndez.  Malaria during pregnancy: a priority area of malaria research and control. , 1995, Parasitology today.

[39]  J. Baird.  Host age as a determinant of naturally acquired immunity to Plasmodium falciparum. , 1995, Parasitology today.

[40]  J. Langhorne,et al.  Differential T cell responses to Plasmodium chabaudi chabaudi in peripheral blood and spleens of C57BL/6 mice during infection. , 1991, Journal of immunology.

[41]  H. Gilles,et al.  Malaria, anaemia and pregnancy. , 1969, Annals of tropical medicine and parasitology.

[42]  W. Wernsdorfer,et al.  Major animal models in malaria research: rodent. , 1988 .

[43]  A. Taylor-Robinson,et al.  Kinetics of nitric oxide production during infection and reinfection of mice with Plasmodium chabaudi , 1996, Parasite immunology.

[44]  A. Holder,et al.  Naturally acquired cellular and humoral immune responses to the major merozoite surface antigen (Pf MSP1) of Plasmodium falciparum are associated with reduced malaria morbidity , 1992, Parasite immunology.

[45]  J. Hustin,et al.  Anatomical Studies of the Utero-Placental Vascularization in the First Trimester of Pregnancy , 1988 .

[46]  I. McGregor.  Epidemiology, malaria and pregnancy. , 1984, The American journal of tropical medicine and hygiene.

[47]  R. Hayes,et al.  Antibodies to blood stage antigens of Plasmodium falciparum in rural Gambians and their relation to protection against infection. , 1989, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[48]  T. Mosmann,et al.  Pregnancy impairs resistance of C57BL/6 mice to Leishmania major infection and causes decreased antigen-specific IFN-gamma response and increased production of T helper 2 cytokines. , 1996, Journal of immunology.

[49]  Irwin W. Sherman,et al.  Malaria : parasite biology, pathogenesis, and protection , 1998 .

[50]  R. Desowitz.  Prenatal immune priming in malaria: antigen-specific blastogenesis of cord blood lymphocytes from neonates born in a setting of holoendemic malaria. , 1988, Annals of tropical medicine and parasitology.

[51]  P. Ringwald,et al.  MALARIA CELLULAR IMMUNE RESPONSES IN NEONATES FROM CAMEROON , 1996, Parasite immunology.

[52]  L. Guilbert.  There is a bias against type 1 (inflammatory) cytokine expression and function in pregnancy. , 1996, Journal of reproductive immunology.

[53]  S. Ibhanesebhor.  Clinical characteristics of neonatal malaria. , 1995, Journal of tropical pediatrics.

[54]  M. Tam,et al.  Differential induction of helper T cell subsets during blood‐stage Plasmodium chabaudi AS infection in resistant and susceptible mice , 1993, Clinical and experimental immunology.

[55]  C. Long,et al.  Immunity to blood stages of malaria. , 1993, Current opinion in immunology.

[56]  N. C. Smith,et al.  An immunological hypothesis to explain the enhanced susceptibility to malaria during pregnancy. , 1996, Parasitology today.

[57]  C. Menéndez,et al.  Suppressed peripheral and placental blood lymphoproliferative responses in first pregnancies: relevance to malaria. , 1993, The American journal of tropical medicine and hygiene.

[58]  R. Steketee,et al.  Malaria infection in pregnant women in Zaire: the effects and the potential for intervention. , 1988, Annals of tropical medicine and parasitology.

[59]  C. Chougnet,et al.  Malaria and pregnancy in Cameroonian primigravidae: humoral and cellular immune responses to Plasmodium falciparum blood-stage antigens. , 1995, American Journal of Tropical Medicine and Hygiene.

[60]  A. Taylor-Robinson.  Regulation of immunity to malaria: valuable lessons learned from murine models. , 1995, Parasitology today.

[61]  S. Moncada,et al.  The role of TH1 and TH2 cells in a rodent malaria infection. , 1993, Science.

[62]  P. Balmer,et al.  Antigenic variation during malaria infection—the contribution from the murine parasite Plasmodium chabaudi , 1997, Parasite immunology.

[63]  A. Taylor-Robinson,et al.  T cells in immunity to Plasmodium chabaudi chabaudi: operation and regulation of different pathways of protection. , 1994, Research in immunology.

[64]  S. Kano,et al.  The effects of pyronaridine on the morphology of Plasmodium falciparum in Aotus trivirgatus. , 1996, The American journal of tropical medicine and hygiene.

[65]  R. Snow,et al.  Malaria is an important cause of anaemia in primigravidae: evidence from a district hospital in coastal Kenya. , 1996, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[66]  R. Maizels,et al.  Th1-Th2: reliable paradigm or dangerous dogma? , 1997, Immunology today.

[67]  A. Taylor-Robinson,et al.  A role for cytokines in potentiation of malaria vaccines through immunological modulation of blood stage infection , 1999, Immunological reviews.