Immunity to malaria
Abstract
Description
A dissertation submitted in partial fulfillment of the requirements for the award of the degree of Master of Medicine of Makerere University
Section I: literature is reviewed and the pattern of the development of immunity in a population exposed to high malarial endemicity is followed. This is followed by a brief discussion of specific aspects of malarial immunity in an immune population. Section II: two major groups of Ugandan populations were included in the present study. First comprised of pregnant females and their newborns, and second of patients with Tropical Splenomegaly Syndrome. A. Pregnant females and their newborns i. Malarial immunity during pregnancy Increased parasitaemia during pregnancy, in a previously immune female was investigated to elucidate if there was any breakdown in humoral defense. Fifty pregnant females were followed during their pregnancy and were compared with a control group of forty non-pregnant females and seventeen males. Concentrations of serum gamma-globulins and immuno-globulins were found to be normal during pregnancy. The levels of malarial fluorescent antibodies and their distribution in IgG, IgA were also normal during pregnancy. A reciprocal relationship between antibody levels and parasitaemia was established. Thus the results of this study indicated no depression of humoral immunity during pregnancy. Evidence is reviewed to support the possibility of a breakdown in cellular immunity during pregnancy, pregnancy, preventing lysis of ingested malaria parasites by macrophoges, probably as a result of the effect of corticosteroids, which are synthesized in increasing amounts during pregnancy. ii. Intra-uterine infections Intra-uterine infections are known to lead to fetal synthesis of IgM and /or IgA leading to elevated levels of IgM and /or IgA in cord blood sera at birth. In this study, elevated levels of IgM and/or IgA were detected in 18.6% of the cord blood sera tested. Intra-uterine infections play an important role in the etiology of congenital malformations and in postnatal morbidity and mortality. It is suggested that “African macroglobulinaemia” may have its origin in the intra-uterine priming and fetal synthesis of IgM as a result of intra-uterine infections. Defining the population of the newborn likely to have had intra-uterine infection will permit further study of etiological agents and postnatal effects of such infections in Uganda population. An attempt was made to study the possibility of malaria as en etiological agent responsible for intra-uterine infections in these neonates. There was no correlation between levels of malaria antibodies in these samples and elevated levels of immunoglobulins, neither could IgM malaria antibodies be demonstrated in cord blood sera. It was, therefore, concluded that malaria may not be one of the etiological agents responsible for intra-uterine infections in our population in Uganda. iii. Fetal Levels of IgG Placental transfer of maternal IgG was demonstrated, beginning early during intra-uterine life and increasing exponentially to attain maternal levels in the fetus term. iv. Congenital Malaria Must be rare in an immune population as amply recorded in literature and supported in the present study, where none of the 88 neonates had parasites in their peripheral blood smear. v. Malarial placental parasitization and birth-weights Many reports have recorded the effect of malaria placental parasitization on birth-weights. In the present study such a relationship was not obvious. Factors known to affect birth-weights, like sex of the newborn, its birth-rank, nutritional state of the mother and placental sufficiency seem not to have been taken into consideration in older studies. In the present study fetal plasma proteins, especially albumin and gamma-globulins have been demonstrated to be related to maturity at birth. Probably the degree of parasitization, rather than just the presence of parasites in placental smears, together with other placental lesions may be more relevant to placental insufficiency leading to lower birth-weights. vi. Malarial antibodies in cord blood sera Fluorescent antibodies were detected in significant titres in cord blood sera of immune mothers, thus at birth the neonate has a passively acquired immunity against malaria. vii. Malarial antibodies in colostrum Fluorescent antibodies were detected in breast milk of immune mothers, and their neonates may be acquiring further protection against malaria as a result of ingesting these antibodies. B. Tropical Splenomegaly Syndrome (a) From the following two studies it was possible to rule out the possibility of a defect in antibody response to antigenic stimuli, leading to exaggerated IgM synthesis, in TSS patients i. Antibody response to E. coli Vi antigen in TSS patients was normal and resulted in the synthesis of both IgG and IgM antibodies. ii. The distribution of malarial antibodies in IgG, IgA and IgM in TSS patients was normal too. (b) 7S IgM, monomeric units were detected in almost 30% of TSS patients. This may be the effect or the cause of increased synthesis of IgM in TSS patients. Presence of 7S IgM monimeric units in test sera is likely to lead to over-estimation of IgM by radial immunodiffusion technique. (c) Immuno fluorescence study on liver biopsies has demonstrated antibody synthesis by hepatic sinusoidal lymphocytic infiltrates and the possibility that Kupffer cells are engaged in ingesting antigen/antibody complex. (d) Long term malarial prophylaxis has been shown to lead to clinical improvement in TSS patients. In the present study malarial prophylaxis has been shown to reduction in concentrations of IgM though the IgG, IgA and MFAT seem not to be affected during the period of observation.
Section I: literature is reviewed and the pattern of the development of immunity in a population exposed to high malarial endemicity is followed. This is followed by a brief discussion of specific aspects of malarial immunity in an immune population. Section II: two major groups of Ugandan populations were included in the present study. First comprised of pregnant females and their newborns, and second of patients with Tropical Splenomegaly Syndrome. A. Pregnant females and their newborns i. Malarial immunity during pregnancy Increased parasitaemia during pregnancy, in a previously immune female was investigated to elucidate if there was any breakdown in humoral defense. Fifty pregnant females were followed during their pregnancy and were compared with a control group of forty non-pregnant females and seventeen males. Concentrations of serum gamma-globulins and immuno-globulins were found to be normal during pregnancy. The levels of malarial fluorescent antibodies and their distribution in IgG, IgA were also normal during pregnancy. A reciprocal relationship between antibody levels and parasitaemia was established. Thus the results of this study indicated no depression of humoral immunity during pregnancy. Evidence is reviewed to support the possibility of a breakdown in cellular immunity during pregnancy, pregnancy, preventing lysis of ingested malaria parasites by macrophoges, probably as a result of the effect of corticosteroids, which are synthesized in increasing amounts during pregnancy. ii. Intra-uterine infections Intra-uterine infections are known to lead to fetal synthesis of IgM and /or IgA leading to elevated levels of IgM and /or IgA in cord blood sera at birth. In this study, elevated levels of IgM and/or IgA were detected in 18.6% of the cord blood sera tested. Intra-uterine infections play an important role in the etiology of congenital malformations and in postnatal morbidity and mortality. It is suggested that “African macroglobulinaemia” may have its origin in the intra-uterine priming and fetal synthesis of IgM as a result of intra-uterine infections. Defining the population of the newborn likely to have had intra-uterine infection will permit further study of etiological agents and postnatal effects of such infections in Uganda population. An attempt was made to study the possibility of malaria as en etiological agent responsible for intra-uterine infections in these neonates. There was no correlation between levels of malaria antibodies in these samples and elevated levels of immunoglobulins, neither could IgM malaria antibodies be demonstrated in cord blood sera. It was, therefore, concluded that malaria may not be one of the etiological agents responsible for intra-uterine infections in our population in Uganda. iii. Fetal Levels of IgG Placental transfer of maternal IgG was demonstrated, beginning early during intra-uterine life and increasing exponentially to attain maternal levels in the fetus term. iv. Congenital Malaria Must be rare in an immune population as amply recorded in literature and supported in the present study, where none of the 88 neonates had parasites in their peripheral blood smear. v. Malarial placental parasitization and birth-weights Many reports have recorded the effect of malaria placental parasitization on birth-weights. In the present study such a relationship was not obvious. Factors known to affect birth-weights, like sex of the newborn, its birth-rank, nutritional state of the mother and placental sufficiency seem not to have been taken into consideration in older studies. In the present study fetal plasma proteins, especially albumin and gamma-globulins have been demonstrated to be related to maturity at birth. Probably the degree of parasitization, rather than just the presence of parasites in placental smears, together with other placental lesions may be more relevant to placental insufficiency leading to lower birth-weights. vi. Malarial antibodies in cord blood sera Fluorescent antibodies were detected in significant titres in cord blood sera of immune mothers, thus at birth the neonate has a passively acquired immunity against malaria. vii. Malarial antibodies in colostrum Fluorescent antibodies were detected in breast milk of immune mothers, and their neonates may be acquiring further protection against malaria as a result of ingesting these antibodies. B. Tropical Splenomegaly Syndrome (a) From the following two studies it was possible to rule out the possibility of a defect in antibody response to antigenic stimuli, leading to exaggerated IgM synthesis, in TSS patients i. Antibody response to E. coli Vi antigen in TSS patients was normal and resulted in the synthesis of both IgG and IgM antibodies. ii. The distribution of malarial antibodies in IgG, IgA and IgM in TSS patients was normal too. (b) 7S IgM, monomeric units were detected in almost 30% of TSS patients. This may be the effect or the cause of increased synthesis of IgM in TSS patients. Presence of 7S IgM monimeric units in test sera is likely to lead to over-estimation of IgM by radial immunodiffusion technique. (c) Immuno fluorescence study on liver biopsies has demonstrated antibody synthesis by hepatic sinusoidal lymphocytic infiltrates and the possibility that Kupffer cells are engaged in ingesting antigen/antibody complex. (d) Long term malarial prophylaxis has been shown to lead to clinical improvement in TSS patients. In the present study malarial prophylaxis has been shown to reduction in concentrations of IgM though the IgG, IgA and MFAT seem not to be affected during the period of observation.
Keywords
Malaria, Immunity, Uganda