Wolbachia bacteria seem to have evolved as essential endosymbionts of their filarial nematode hos... more Wolbachia bacteria seem to have evolved as essential endosymbionts of their filarial nematode hosts. Studies in mice have suggested that these bacteria are associated with systemic inflammatory reactions to filarial chemotherapy. We took blood samples from 15 Indonesian patients before and after treatment with diethylcarbamazine for Brugia malayi infection, and recorded the severity of any post-treatment inflammatory reactions. Blood from all three patients with severe adverse reactions and from one of six with moderate reactions was positive for Wolbachia DNA 4-48 h after diethylcarbamazine treatment. We suggest that these severe inflammatory reactions are associated with the release of endosymbionts into the blood after treatment for filariasis.
To assess whether antifilarial IgG4 can be used to study various epidemiological facets of filari... more To assess whether antifilarial IgG4 can be used to study various epidemiological facets of filarial infections, we studied this isotype in 238 individuals resident in areas endemic for brugian filariasis, focusing on the differences between men and women. In the study area, the prevalence of microfilariae was 6.7% and the prevalence of antifilarial IgG4 was 49.2%. All microfilariae carriers were positive for antifilarial IgG4, whereas a proportion of the endemic normals (94/208) and clephantiasis patients (7/14) had IgG4 antibodies to filarial antigens. Data were analysed as a function of gender in distinct clinical groups and stratified for age. The prevalence of microfilariae was higher in males in all age groups, as reflected in significantly higher antifilarial IgG4 antibody levels compared to females. The prevalence of IgG4 increased to reach a plateau at the age of 30 years in both males and females. These results indicate that antifilarial IgG4 antibodies can reflect the differences in the extent of infection in males and females as measured by microfilarial counts, and that this parameter can be used for epidemiological assessments of filarial infection.
Search by Subject Search using Medical Subject Headings (< b> MeSH&... more Search by Subject Search using Medical Subject Headings (< b> MeSH</b>), a controlled vocabulary for indexing life sciences content.< br/> Note that some records do not have MeSH. These include Patents and the latest PubMed and PubMed Central records.
International Archives of Allergy and Immunology, 2001
Allergic diseases seem less prevalent in communities in less developed parts of the world, where ... more Allergic diseases seem less prevalent in communities in less developed parts of the world, where parasite infections are highly prevalent. Altogether not much is known about the association between chronic infections with tissue and blood-dwelling parasites and atopy. In an area in Gabon endemic for blood and tissue parasites, 520 schoolchildren were parasitologically examined and skin prick-tested for a set of common environmental aeroallergens. Levels of allergen-specific IgE and polyclonal IgE were measured. In schoolchildren schistosome and filarial infections increased with age, whereas malaria was more prevalent in younger children. In contrast to allergen sensitization that increased with age, skin test reactivity tended to decline. The number of children with mite-specific IgE antibodies (47%) by far exceeded the number responding to skin prick testing (11%). Mite sensitization was found to be the highest in children infected with schistosomes and/or filariae whereas skin test reactivity was lowest. The multiple logistic regression showed that the risk of a positive skin test was 8-fold higher with increasing levels of mite-specific IgE but was reduced by 72% when infected with blood stage helminths. Chronic blood and tissue parasite infections that are often capable of modulating immune responses in the host are negatively associated with skin test reactivity in a sensitized population.
In an attempt to overcome T cell unresponsiveness to filarial antigens, 65 individuals belonging ... more In an attempt to overcome T cell unresponsiveness to filarial antigens, 65 individuals belonging to the three clinical groups of elephantiasis patients, microfilaraemics, and asymptomatic amicrofilaraemics who exhibited unresponsiveness to Brugia malayi adult worm antigen (BmA) were studied. Peripheral blood mononuclear cells were co-cultured with antigen and one of the following reagents that have been reported to be effective in reconstituting T cell proliferation: interleukin-2 (IL-2), interleukin-7 (IL-7), anti-interleukin-4, anti-interleukin-10, anti-CD2, anti-CD27, anti-CD28, indomethacin, phorbol myristate acetate (PMA), or calcium ionophore (A23I87). We were able to overcome antigen-specific unresponsiveness in only a minority of the individuals studied. Co-culture with IL-2, IL-7, indomethacin and PMA were the only conditions which resulted in enhanced proliferation to BmA in these individuals. In general, unresponsiveness in elephantiasis patients was easier to reverse than in other clinical groups: in 50% of elephantiasis patients, in 12.5% of microfilaraemics and in 20% of asymptomatic amicrofilaraemics. The results indicate that more than one distinct immunological mechanism may account for the antigen-specific unresponsiveness in individuals exposed to and infected with brugian filariasis.
Summary: Helminths are multicellular pathogens which infect vast numbers of human and animal host... more Summary: Helminths are multicellular pathogens which infect vast numbers of human and animal hosts, causing widspread chronic disease and morbidity, Vaccination against these parasites requires more than identification of effective target antigens, because without understanding the immunology of the host–parasite relationship, ineffective immune mechanisms may he invoked, and there is a danger of amplifying immuno-pathogenic responses. The fundamental features of the immune response to helminths are therefore summarised in the context of vaccines to helminths parasites. The contention between type-1 and type-2 responses is a central issue in helminth infections, which bias the immune system strongly to the type-2 pathway. Evidence from both human and experimental animal infections indicates that both lineages contribute to immunity in differing circumstances, and that a balanced, response leads to the most favourable outcome. A diversity of immune mechanisms can be brought to bear on various helminth species, ranging from antibody-independent macrophages, antibody-dependent granulocyte killing, and non-lymphoid actions, particularly in the gut. This diversity is highlighted by analysis of rodent infections, particularly in comparisons of cytokine-depleted and gene-targeted animals. This knowledge of protective mechanisms needs to he combined with a careful choice of parasite antigens for vaccines. Many existing candidates have been selected with host antibodies, rather than T-cell responses, and include a preponderance of highly conserved proteins with similarities to mammalian or invertebrate antigens. Advantage has yet to he taken of parasite genome projects, or of directed searches for novel, parasite-specific antigens and targets expressed only by infective stages and not mature forms which may generate immunopathology. With advances under way in parasite genomics and new vaccine delivery systems offering more rapid assessment and development, there are now excellent opportunities for new antihelminth vaccines.
To assess the immunological changes occurring during filarial infection with or without elephanti... more To assess the immunological changes occurring during filarial infection with or without elephantiasis, 145 patients in different clinical groups from an endemic area in Indonesia were compared with respect to plasma levels of both soluble CD25 (sCD25) and sCD27; interleukin-4 (IL-4) and interferon-γ release by peripheral blood mononuclear cells was also measured in a smaller subset of individuals. Levels of sCD27 were significantly elevated in elephantiasis and microfilaremic patients compared with endemic normals (p < 0.002), whereas sCD25 levels remained low in microfilaremics and was only slightly elevated in elephantiasis patients compared with endemic normals (p <0.02). As activated T cell populations release both sCD27 and sCD25, these findings imply that there is filarial-driven activation of a Tcell subset that releases sCD27 rather than sCD25. The expansion of a particular Tcell population by filarial parasites is further suggested by the enhancement in both IL-4-producing and CD4+CD27−T cells in PBMC from elephantiasis and microfilaremic patients compared with endemic normals. More detailed characterization and comparison of CD27− lymphocytes from these individuals may identify mechanisms involved in the pathogenesis of lymphatic filariasis.
Wolbachia bacteria seem to have evolved as essential endosymbionts of their filarial nematode hos... more Wolbachia bacteria seem to have evolved as essential endosymbionts of their filarial nematode hosts. Studies in mice have suggested that these bacteria are associated with systemic inflammatory reactions to filarial chemotherapy. We took blood samples from 15 Indonesian patients before and after treatment with diethylcarbamazine for Brugia malayi infection, and recorded the severity of any post-treatment inflammatory reactions. Blood from all three patients with severe adverse reactions and from one of six with moderate reactions was positive for Wolbachia DNA 4-48 h after diethylcarbamazine treatment. We suggest that these severe inflammatory reactions are associated with the release of endosymbionts into the blood after treatment for filariasis.
To assess whether antifilarial IgG4 can be used to study various epidemiological facets of filari... more To assess whether antifilarial IgG4 can be used to study various epidemiological facets of filarial infections, we studied this isotype in 238 individuals resident in areas endemic for brugian filariasis, focusing on the differences between men and women. In the study area, the prevalence of microfilariae was 6.7% and the prevalence of antifilarial IgG4 was 49.2%. All microfilariae carriers were positive for antifilarial IgG4, whereas a proportion of the endemic normals (94/208) and clephantiasis patients (7/14) had IgG4 antibodies to filarial antigens. Data were analysed as a function of gender in distinct clinical groups and stratified for age. The prevalence of microfilariae was higher in males in all age groups, as reflected in significantly higher antifilarial IgG4 antibody levels compared to females. The prevalence of IgG4 increased to reach a plateau at the age of 30 years in both males and females. These results indicate that antifilarial IgG4 antibodies can reflect the differences in the extent of infection in males and females as measured by microfilarial counts, and that this parameter can be used for epidemiological assessments of filarial infection.
Search by Subject Search using Medical Subject Headings (&amp;lt; b&amp;gt; MeSH&amp;... more Search by Subject Search using Medical Subject Headings (&amp;lt; b&amp;gt; MeSH&amp;lt;/b&amp;gt;), a controlled vocabulary for indexing life sciences content.&amp;lt; br/&amp;gt; Note that some records do not have MeSH. These include Patents and the latest PubMed and PubMed Central records.
International Archives of Allergy and Immunology, 2001
Allergic diseases seem less prevalent in communities in less developed parts of the world, where ... more Allergic diseases seem less prevalent in communities in less developed parts of the world, where parasite infections are highly prevalent. Altogether not much is known about the association between chronic infections with tissue and blood-dwelling parasites and atopy. In an area in Gabon endemic for blood and tissue parasites, 520 schoolchildren were parasitologically examined and skin prick-tested for a set of common environmental aeroallergens. Levels of allergen-specific IgE and polyclonal IgE were measured. In schoolchildren schistosome and filarial infections increased with age, whereas malaria was more prevalent in younger children. In contrast to allergen sensitization that increased with age, skin test reactivity tended to decline. The number of children with mite-specific IgE antibodies (47%) by far exceeded the number responding to skin prick testing (11%). Mite sensitization was found to be the highest in children infected with schistosomes and/or filariae whereas skin test reactivity was lowest. The multiple logistic regression showed that the risk of a positive skin test was 8-fold higher with increasing levels of mite-specific IgE but was reduced by 72% when infected with blood stage helminths. Chronic blood and tissue parasite infections that are often capable of modulating immune responses in the host are negatively associated with skin test reactivity in a sensitized population.
In an attempt to overcome T cell unresponsiveness to filarial antigens, 65 individuals belonging ... more In an attempt to overcome T cell unresponsiveness to filarial antigens, 65 individuals belonging to the three clinical groups of elephantiasis patients, microfilaraemics, and asymptomatic amicrofilaraemics who exhibited unresponsiveness to Brugia malayi adult worm antigen (BmA) were studied. Peripheral blood mononuclear cells were co-cultured with antigen and one of the following reagents that have been reported to be effective in reconstituting T cell proliferation: interleukin-2 (IL-2), interleukin-7 (IL-7), anti-interleukin-4, anti-interleukin-10, anti-CD2, anti-CD27, anti-CD28, indomethacin, phorbol myristate acetate (PMA), or calcium ionophore (A23I87). We were able to overcome antigen-specific unresponsiveness in only a minority of the individuals studied. Co-culture with IL-2, IL-7, indomethacin and PMA were the only conditions which resulted in enhanced proliferation to BmA in these individuals. In general, unresponsiveness in elephantiasis patients was easier to reverse than in other clinical groups: in 50% of elephantiasis patients, in 12.5% of microfilaraemics and in 20% of asymptomatic amicrofilaraemics. The results indicate that more than one distinct immunological mechanism may account for the antigen-specific unresponsiveness in individuals exposed to and infected with brugian filariasis.
Summary: Helminths are multicellular pathogens which infect vast numbers of human and animal host... more Summary: Helminths are multicellular pathogens which infect vast numbers of human and animal hosts, causing widspread chronic disease and morbidity, Vaccination against these parasites requires more than identification of effective target antigens, because without understanding the immunology of the host–parasite relationship, ineffective immune mechanisms may he invoked, and there is a danger of amplifying immuno-pathogenic responses. The fundamental features of the immune response to helminths are therefore summarised in the context of vaccines to helminths parasites. The contention between type-1 and type-2 responses is a central issue in helminth infections, which bias the immune system strongly to the type-2 pathway. Evidence from both human and experimental animal infections indicates that both lineages contribute to immunity in differing circumstances, and that a balanced, response leads to the most favourable outcome. A diversity of immune mechanisms can be brought to bear on various helminth species, ranging from antibody-independent macrophages, antibody-dependent granulocyte killing, and non-lymphoid actions, particularly in the gut. This diversity is highlighted by analysis of rodent infections, particularly in comparisons of cytokine-depleted and gene-targeted animals. This knowledge of protective mechanisms needs to he combined with a careful choice of parasite antigens for vaccines. Many existing candidates have been selected with host antibodies, rather than T-cell responses, and include a preponderance of highly conserved proteins with similarities to mammalian or invertebrate antigens. Advantage has yet to he taken of parasite genome projects, or of directed searches for novel, parasite-specific antigens and targets expressed only by infective stages and not mature forms which may generate immunopathology. With advances under way in parasite genomics and new vaccine delivery systems offering more rapid assessment and development, there are now excellent opportunities for new antihelminth vaccines.
To assess the immunological changes occurring during filarial infection with or without elephanti... more To assess the immunological changes occurring during filarial infection with or without elephantiasis, 145 patients in different clinical groups from an endemic area in Indonesia were compared with respect to plasma levels of both soluble CD25 (sCD25) and sCD27; interleukin-4 (IL-4) and interferon-γ release by peripheral blood mononuclear cells was also measured in a smaller subset of individuals. Levels of sCD27 were significantly elevated in elephantiasis and microfilaremic patients compared with endemic normals (p < 0.002), whereas sCD25 levels remained low in microfilaremics and was only slightly elevated in elephantiasis patients compared with endemic normals (p <0.02). As activated T cell populations release both sCD27 and sCD25, these findings imply that there is filarial-driven activation of a Tcell subset that releases sCD27 rather than sCD25. The expansion of a particular Tcell population by filarial parasites is further suggested by the enhancement in both IL-4-producing and CD4+CD27−T cells in PBMC from elephantiasis and microfilaremic patients compared with endemic normals. More detailed characterization and comparison of CD27− lymphocytes from these individuals may identify mechanisms involved in the pathogenesis of lymphatic filariasis.
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