Traditional malaria control is in a crisis on account of chemo-resistance of Plasmodium falciparu... more Traditional malaria control is in a crisis on account of chemo-resistance of Plasmodium falciparum and insecticide-resistance of the malaria mosquito. New ways to control malaria have been opened by the possibility of producing a vaccine. Several malaria proteins (e.g. CSP, gp195, Pf155/RESA, GLURP) have been sequenced and it has been shown that most of the proteins have repetitive units. Analyses of T- and B-cell epitopes show that T-cell epitopes are mainly localized to the non-conserved parts of the antigens. Repeated malaria infections, therefore, may be seen as a number of primary infections, which partly explains the very slow development of immunity to the parasite. The initial three vaccination experiments in humans did not succeed in inducing a complete protection of the individual but it showed that partial immunization is possible.
To evaluate the protective efficacy of a DNA vaccine encoding Toxoplasma gondii rhoptry protein 5... more To evaluate the protective efficacy of a DNA vaccine encoding Toxoplasma gondii rhoptry protein 5 (ROP5) and GRA15 antigens. We constructed eukaryotic plasmids expressing pVAX-ROP5 and pVAX-GRA15, and measured the immune responses to these DNA vaccines. Kunming mice immunized with pVAX-ROP5 or pVAX-GRA15 showed significantly increased serum IgG2a titers; Th1 responses association with the production of IFN-γ, IL-2, IL12 p40 and IL-12 p70; cell-mediated cytotoxic activity with increased frequencies of IFN-γ secreting CD8(+) T cells (CD8(+) IFN-γ+ T cells), as well as prolonged survival time (19.4 ± 4.9 days for ROP5; 17.8 ± 3.8 days for GRA15) and brain cyst reduction (57.4% for ROP5; 65.9% for GRA15) compared to control mice. Co-administration with pVAX-ROP5 and pVAX-GRA15 boosted the cellular and humoral immune responses, and significantly increased cyst reduction (79%) and prolonged the survival of immunized mice (22.7 ± 7.2 days). Co-immunization of pVAX-ROP5 and pVAX-GRA15 incre...
International Journal of Infectious Diseases, 2015
Tuberculosis (TB) today remains a global emergency affecting 9.0 million people globally. The Afr... more Tuberculosis (TB) today remains a global emergency affecting 9.0 million people globally. The African Region bears the highest global TB/HIV burden and over 50% of TB cases in SSA are co-infected with HIV. An estimated 1.5 million died from the TB globally in 2013. A large majority of the 360,000 HIV-positive TB cases who died were from sub-Saharan Africa. Research and development is an important pillar of the WHO post-2015 global TB strategy. Advances in development of diagnostics, drugs, host-directed therapies, and vaccines will require evaluation under field conditions through multi-centre clinical trials at different geographical locations. Thus it is critically important that these evaluations are fully supported by all African governments and the capacity, trained staff and infrastructure required to perform the research and evaluations is built and made available. This viewpoint article reviews the opportunities provided by recently launched second programme (2015-2024) of the European & Developing Countries Clinical Trials Partnership (EDCTP2) for tackling the TB epidemic in Africa through its magnanimous portfolio. The unique opportunities provided by EDCTP2 for leadership of scientific research in TB and other diseases fully devolving to Africa are also covered.
Toxoplasma gondii can infect all warm-blooded animals including humans. Infection with T. gondii ... more Toxoplasma gondii can infect all warm-blooded animals including humans. Infection with T. gondii is probably the leading cause of posterior uveitis in humans and the most comment route of transmission is raw and undercooked meat from infected animals. T. gondii calcium-dependent protein kinase 1 (TgCDPK1) plays a critical role in direct parasite motility, host-cell invasion, and egress. We constructed a DNA vaccine expressing TgCDPK1 inserted into eukaryotic expression vector pVAX I and evaluated the immune protection induced by pVAX-CDPK1 in Kunming mice. Mice immunized with pVAX-CDPK1 intramuscularly and/or with a plasmid encoding IL-15 and IL-21 (pVAX-IL-21-IL-15). The immune responses were analyzed including lymphoproliferative assay, cytokine, antibody measurements, lymphocyte surface markers by flow cytometry and protective efficacy were measured as survival and cysts numbers after challenge 1 to 2 months post vaccination. Immunization with pVAX-CDPK1 or pVAX-IL-21-IL-15 alone...
When antimicrobials are used empirically, pathogen MICs equal to clinical breakpoints or epidemio... more When antimicrobials are used empirically, pathogen MICs equal to clinical breakpoints or epidemiological cutoff values must be considered. This is to ensure that the most resistant pathogen subpopulation is appropriately targeted to prevent emergence of resistance. Accordingly, we determined the pharmacokinetic (PK) profile of moxifloxacin at 400 mg/day in 18 patients treated empirically for community-acquired pneumonia. We developed a population pharmacokinetic model to assess the potential efficacy of moxifloxacin and to simulate the maximal MICs for which recommended pharmacokinetic-pharmacodynamic (PK-PD) estimates are obtained. Moxifloxacin plasma concentrations were determined the day after therapy initiation using ultra-high-performance liquid chromatography. Peak drug concentrations (Cmax) and area under the free drug concentration-time curve from 0 to 24 h (fAUC0-24) values predicted for each patient were evaluated against epidemiological cutoff MIC values for Streptococcus pneumoniae, Haemophilus influenzae, and Legionella pneumophila. PK-PD targets adopted were a Cmax/MIC of ≥12.2 for all pathogens, an fAUC0-24/MIC of >34 for S. pneumoniae, and an fAUC0-24/MIC of >75 for H. influenzae and L. pneumophila. Individual predicted estimates for Cmax/MIC and fAUC0-24/MIC as well as simulated maximal MICs resulting in target attainment for oral and intravenous administration of the drug were suitable for S. pneumoniae and H. influenzae but not for L. pneumophila. These results indicate that caution must be taken when moxifloxacin is used as monotherapy to treat community-acquired pneumonia caused by L. pneumophila. In conclusion, this report reveals key information relevant to the empirical treatment of community-acquired pneumonia while highlighting the robust and flexible nature of this population pharmacokinetic model to predict therapeutic success. (Clinical Trials Registration no. NCT01983839.).
Aging of the human body affects the immune system by a decline in the ability to raise a response... more Aging of the human body affects the immune system by a decline in the ability to raise a response to challenges such as microbial infections or vaccinations. In the very elderly, the decline in such functions appears to relate to a reduced expression of certain co-stimulatory molecules expressed by T lymphocytes. More recently, attention has been drawn to the adhesion molecule CD62L, where differences in expression and function of this molecule between younger and older individuals are suspected to be a part of immunosenescence in the elderly.
Toxoplasma gondii infection is a serious health problem of humans and animals worldwide. T. gondi... more Toxoplasma gondii infection is a serious health problem of humans and animals worldwide. T. gondii eukaryotic initiation factor-2α (TgIF2α) plays a crucial role in parasite viability and is an important virulence factor of T. gondii. To evaluate the vaccine potential of TgIF2α, we constructed a novel eukaryotic plasmid pVAX-IF2α expressing TgIF2α from the RH strain and validated expression and immunogenicity in vitro in the Marc145 cell expression system by indirect immunofluorescence (IFA). Administration of pVAX-IF2α intramuscularly induced specific humoral immune responses including high levels of specific TgIF2α IgG antibody and a mixed IgG1/IgG2a response with a predominance of IgG2a production. The cellular immune response was elicited, showing significant production of IFN-γ and IL-2 associated with Th1 type response, and thus strong cell-mediated cytotoxic activity with increased frequencies of IFN-γ parameters analyzed in both CD4(+) and CD8(+) T cell compartments (CD4(+) IFN-γ(+) T cells and CD8(+) IFN-γ(+) T cells). Immunization resulted in partial protection against acute and chronic toxoplamosis in outbred Kunming mice, demonstrated by a significantly prolonged survival time (15.9±4.6 days) after challenge with the virulent RH strain and significant reduction in brain cysts (44.1%) against chronic infection with PRU cyst in contrast to control mice. Our data suggested that pVAX-IF2α could be used as a DNA vaccine candidate against both acute and chronic T. gondii infection by the activation of effective humoral and cellular immune responses.
Vaccine-induced protection against toxoplasmosis is correlated with cellular immune responses to ... more Vaccine-induced protection against toxoplasmosis is correlated with cellular immune responses to Toxoplasma gondii, both in animals and man. The goal of the current study was to evaluate whether the combination of a recombinant protein and a plasmid DNA vaccine could offer an advantage over the protein mixture, and protect outbred mice against infection with T. gondii. To this purpose, the chimeric protein rEC2, encoding antigenic fragments of surface-associated proteins MIC2, MIC3 and SAG1, was combined with pGRA7 plasmid DNA or rGRA7 protein. High levels of antibodies were elicited by both vaccine formulations. The protein-DNA vaccine elicited a polarized Th1/Th2 immune response, characterized by IFN-gamma and IL-10, and afforded low protection (24%) against brain cyst formation. In contrast, the protein-protein vaccine elicited a Th1-focused immune response, characterized by IFN-gamma and IL-2 production, conferring a strong protection (79%) against brain cyst formation in chronic toxoplasmosis. We show here that GERBU adjuvanted protein vaccines confer better protection against toxoplasmosis than the protein-DNA heterologous vaccine.
The synergistic protective efficacy of murine interleukin 21 (mIL-21) and mIL-15 administrated wi... more The synergistic protective efficacy of murine interleukin 21 (mIL-21) and mIL-15 administrated with DNA vaccine against acute and chronic Toxoplasma gondii infection in mice was investigated using T. gondii MIC8 (TgMIC8) as a model. We cloned mIL-21 and mIL-15 from splenic tissues of Kunming mice, and constructed eukaryotic plasmid pVAX/mIL-15, pVAX/mIL-21, and pVAX/mIL-21/mIL-15, respectively. After immunizing with pVAX/TgMIC8 in the presence or absence of these cytokines, immune responses were analyzed using lymphoproliferative assay, cytokine and serum antibody measurements, flow cytometric surface markers on lymphocytes and protection against acute and chronic T. gondii infection. Mice receiving pVAX/TgMIC8 alone developed a strong humoral responses and Th1 type cellular immune responses, and showed an increase of CD4+ and CD8+ T cells compared with all the controls. Adding pVAX/mIL-21 to pVAX/TgMIC8 compared to pVAX/TgMIC8 resulted in only a slight increase in humoral and cellular immune responses, and this immune response was lower than that induced by the pVAX/mIL-15 combined with pVAX/TgMIC8. Co-administration of pVAX/mIL-21/mIL-15 combined with pVAX/TgMIC8 elicited the strongest humoral and cellular immune responses among all the groups, leading to significantly increased survival time against acute infection and the significant reduction of tissue cysts, compared to all the controls. Synergy of mIL-21 and mIL-15 can facilitate specific humoral as well as cellular immune responses elicited by DNA vaccine against acute and chronic T. gondii infection in mice.
To evaluate an immunofluorescence antibody test (IFAT) for diagnosis of schistosomiasis in nonimm... more To evaluate an immunofluorescence antibody test (IFAT) for diagnosis of schistosomiasis in nonimmune travellers and immigrants from endemic areas. 65 patients (48 Danes and 17 immigrants) with schistosomiasis were included. The diagnosis of schistosomiasis was based on the presence of schistosome eggs in faeces, urine, sperm, rectal or bladder biopsies and/or the presence of specific antibodies determined by the serological immunofluorescence antibody test (IFAT). Egg excretion was detected using conventional methods and the IFAT performed on whole S. mansoni schistosomula worms, harvested after 8 weeks from mice. Two patterns of immunofluorescence were observed: Fluorescence in the gut of the schistosome called 'Gut Associated Antigen, GAA', and fluorescence of the surface of the schistosomula called 'Membrane Bound Antigen, MBA'. Eggs were found in 44% of the Danish patients and in 76% of immigrants. The diagnosis was based on a positive IFAT in 48% of the patients. In patients from nonendemic areas, the finding of antibodies against GAA was diagnostic while optimal sensitivity in the immigrants was reached by measuring antibodies against both GAA and MBA. In patients from nonendemic areas GAA is a sensitive marker of acute infection with schistosomiasis. In patients from endemic areas the demonstration of both GAA and MBA is necessary to properly identify long-lasting, nonacute infections. Egg-detection and/or measurement of CAA and CCA remain the methods of choice to monitor treatment as the immunofluorescence assay may remain positive for several years after treatment.
The first 2 cases of infection with Enterocytozoon bieneusi in Denmark and Scandinavia are report... more The first 2 cases of infection with Enterocytozoon bieneusi in Denmark and Scandinavia are reported. Both patients were women and to the best of our knowledge this is the first report of E. bieneusi in female AIDS patients. Both had late stage AIDS, and both had complained of intermittent diarrhoea for more than 1 year. At the time microsporidiosis was diagnosed, no other pathogens causing diarrhoea were found. Immunodeficient patients with chronic unexplained diarrhoea should be investigated for intestinal microsporidiosis, especially as treatment is now available.
Egg detection is the gold standard in diagnosing and controlling treatment in schistosomiasis, bu... more Egg detection is the gold standard in diagnosing and controlling treatment in schistosomiasis, but sensitivity is poor in lightly infected individuals, whereas Schistosoma-specific antibodies are more sensitive. The purpose of the study was to evaluate use of Gut Associated Antigen (GAA) and Membrane Bound Antigen (MBA) assays in assessment of treatment efficacy and number of treated non-immune individuals with signs of treatment failure. In a retrospective study, residents in Denmark diagnosed with positive Schistosoma antibodies in the period 1987 - 2004 were offered follow-up including analyses for GAA, MBA, IgE and eosinophil count. Among 98 patients with positive antibody at time of diagnosis, 73 were examined for eggs and 27% had detectable eggs. 15% still had detectable living eggs after 1 course of treatment. At follow-up it was demonstrated that antibodies continued to increase for up to 6 months after treatment and average duration of positive GAA antibody was approximately 10 y. The study confirms that the GAA- and MBA-IFAT are not suitable in monitoring results of therapy. Treatment failure in 15% of non-immune patients indicates that studies are needed to define the correct dose of praziquantel in those individuals or to evaluate if resistance to praziquantel is a growing problem.
Candida albicans endocarditis involves infrequently the tricuspid valve and involvement of the pu... more Candida albicans endocarditis involves infrequently the tricuspid valve and involvement of the pulmonic valve is rare. We report our experience with an immunosuppressed liver-transplanted female who developed both tricuspid and pulmonic valve endocarditis, review the literature and discuss the importance of effective antimycotic therapy combined with surgical replacement of the affected valve.
Traditional malaria control is in a crisis on account of chemo-resistance of Plasmodium falciparu... more Traditional malaria control is in a crisis on account of chemo-resistance of Plasmodium falciparum and insecticide-resistance of the malaria mosquito. New ways to control malaria have been opened by the possibility of producing a vaccine. Several malaria proteins (e.g. CSP, gp195, Pf155/RESA, GLURP) have been sequenced and it has been shown that most of the proteins have repetitive units. Analyses of T- and B-cell epitopes show that T-cell epitopes are mainly localized to the non-conserved parts of the antigens. Repeated malaria infections, therefore, may be seen as a number of primary infections, which partly explains the very slow development of immunity to the parasite. The initial three vaccination experiments in humans did not succeed in inducing a complete protection of the individual but it showed that partial immunization is possible.
To evaluate the protective efficacy of a DNA vaccine encoding Toxoplasma gondii rhoptry protein 5... more To evaluate the protective efficacy of a DNA vaccine encoding Toxoplasma gondii rhoptry protein 5 (ROP5) and GRA15 antigens. We constructed eukaryotic plasmids expressing pVAX-ROP5 and pVAX-GRA15, and measured the immune responses to these DNA vaccines. Kunming mice immunized with pVAX-ROP5 or pVAX-GRA15 showed significantly increased serum IgG2a titers; Th1 responses association with the production of IFN-γ, IL-2, IL12 p40 and IL-12 p70; cell-mediated cytotoxic activity with increased frequencies of IFN-γ secreting CD8(+) T cells (CD8(+) IFN-γ+ T cells), as well as prolonged survival time (19.4 ± 4.9 days for ROP5; 17.8 ± 3.8 days for GRA15) and brain cyst reduction (57.4% for ROP5; 65.9% for GRA15) compared to control mice. Co-administration with pVAX-ROP5 and pVAX-GRA15 boosted the cellular and humoral immune responses, and significantly increased cyst reduction (79%) and prolonged the survival of immunized mice (22.7 ± 7.2 days). Co-immunization of pVAX-ROP5 and pVAX-GRA15 incre...
International Journal of Infectious Diseases, 2015
Tuberculosis (TB) today remains a global emergency affecting 9.0 million people globally. The Afr... more Tuberculosis (TB) today remains a global emergency affecting 9.0 million people globally. The African Region bears the highest global TB/HIV burden and over 50% of TB cases in SSA are co-infected with HIV. An estimated 1.5 million died from the TB globally in 2013. A large majority of the 360,000 HIV-positive TB cases who died were from sub-Saharan Africa. Research and development is an important pillar of the WHO post-2015 global TB strategy. Advances in development of diagnostics, drugs, host-directed therapies, and vaccines will require evaluation under field conditions through multi-centre clinical trials at different geographical locations. Thus it is critically important that these evaluations are fully supported by all African governments and the capacity, trained staff and infrastructure required to perform the research and evaluations is built and made available. This viewpoint article reviews the opportunities provided by recently launched second programme (2015-2024) of the European & Developing Countries Clinical Trials Partnership (EDCTP2) for tackling the TB epidemic in Africa through its magnanimous portfolio. The unique opportunities provided by EDCTP2 for leadership of scientific research in TB and other diseases fully devolving to Africa are also covered.
Toxoplasma gondii can infect all warm-blooded animals including humans. Infection with T. gondii ... more Toxoplasma gondii can infect all warm-blooded animals including humans. Infection with T. gondii is probably the leading cause of posterior uveitis in humans and the most comment route of transmission is raw and undercooked meat from infected animals. T. gondii calcium-dependent protein kinase 1 (TgCDPK1) plays a critical role in direct parasite motility, host-cell invasion, and egress. We constructed a DNA vaccine expressing TgCDPK1 inserted into eukaryotic expression vector pVAX I and evaluated the immune protection induced by pVAX-CDPK1 in Kunming mice. Mice immunized with pVAX-CDPK1 intramuscularly and/or with a plasmid encoding IL-15 and IL-21 (pVAX-IL-21-IL-15). The immune responses were analyzed including lymphoproliferative assay, cytokine, antibody measurements, lymphocyte surface markers by flow cytometry and protective efficacy were measured as survival and cysts numbers after challenge 1 to 2 months post vaccination. Immunization with pVAX-CDPK1 or pVAX-IL-21-IL-15 alone...
When antimicrobials are used empirically, pathogen MICs equal to clinical breakpoints or epidemio... more When antimicrobials are used empirically, pathogen MICs equal to clinical breakpoints or epidemiological cutoff values must be considered. This is to ensure that the most resistant pathogen subpopulation is appropriately targeted to prevent emergence of resistance. Accordingly, we determined the pharmacokinetic (PK) profile of moxifloxacin at 400 mg/day in 18 patients treated empirically for community-acquired pneumonia. We developed a population pharmacokinetic model to assess the potential efficacy of moxifloxacin and to simulate the maximal MICs for which recommended pharmacokinetic-pharmacodynamic (PK-PD) estimates are obtained. Moxifloxacin plasma concentrations were determined the day after therapy initiation using ultra-high-performance liquid chromatography. Peak drug concentrations (Cmax) and area under the free drug concentration-time curve from 0 to 24 h (fAUC0-24) values predicted for each patient were evaluated against epidemiological cutoff MIC values for Streptococcus pneumoniae, Haemophilus influenzae, and Legionella pneumophila. PK-PD targets adopted were a Cmax/MIC of ≥12.2 for all pathogens, an fAUC0-24/MIC of >34 for S. pneumoniae, and an fAUC0-24/MIC of >75 for H. influenzae and L. pneumophila. Individual predicted estimates for Cmax/MIC and fAUC0-24/MIC as well as simulated maximal MICs resulting in target attainment for oral and intravenous administration of the drug were suitable for S. pneumoniae and H. influenzae but not for L. pneumophila. These results indicate that caution must be taken when moxifloxacin is used as monotherapy to treat community-acquired pneumonia caused by L. pneumophila. In conclusion, this report reveals key information relevant to the empirical treatment of community-acquired pneumonia while highlighting the robust and flexible nature of this population pharmacokinetic model to predict therapeutic success. (Clinical Trials Registration no. NCT01983839.).
Aging of the human body affects the immune system by a decline in the ability to raise a response... more Aging of the human body affects the immune system by a decline in the ability to raise a response to challenges such as microbial infections or vaccinations. In the very elderly, the decline in such functions appears to relate to a reduced expression of certain co-stimulatory molecules expressed by T lymphocytes. More recently, attention has been drawn to the adhesion molecule CD62L, where differences in expression and function of this molecule between younger and older individuals are suspected to be a part of immunosenescence in the elderly.
Toxoplasma gondii infection is a serious health problem of humans and animals worldwide. T. gondi... more Toxoplasma gondii infection is a serious health problem of humans and animals worldwide. T. gondii eukaryotic initiation factor-2α (TgIF2α) plays a crucial role in parasite viability and is an important virulence factor of T. gondii. To evaluate the vaccine potential of TgIF2α, we constructed a novel eukaryotic plasmid pVAX-IF2α expressing TgIF2α from the RH strain and validated expression and immunogenicity in vitro in the Marc145 cell expression system by indirect immunofluorescence (IFA). Administration of pVAX-IF2α intramuscularly induced specific humoral immune responses including high levels of specific TgIF2α IgG antibody and a mixed IgG1/IgG2a response with a predominance of IgG2a production. The cellular immune response was elicited, showing significant production of IFN-γ and IL-2 associated with Th1 type response, and thus strong cell-mediated cytotoxic activity with increased frequencies of IFN-γ parameters analyzed in both CD4(+) and CD8(+) T cell compartments (CD4(+) IFN-γ(+) T cells and CD8(+) IFN-γ(+) T cells). Immunization resulted in partial protection against acute and chronic toxoplamosis in outbred Kunming mice, demonstrated by a significantly prolonged survival time (15.9±4.6 days) after challenge with the virulent RH strain and significant reduction in brain cysts (44.1%) against chronic infection with PRU cyst in contrast to control mice. Our data suggested that pVAX-IF2α could be used as a DNA vaccine candidate against both acute and chronic T. gondii infection by the activation of effective humoral and cellular immune responses.
Vaccine-induced protection against toxoplasmosis is correlated with cellular immune responses to ... more Vaccine-induced protection against toxoplasmosis is correlated with cellular immune responses to Toxoplasma gondii, both in animals and man. The goal of the current study was to evaluate whether the combination of a recombinant protein and a plasmid DNA vaccine could offer an advantage over the protein mixture, and protect outbred mice against infection with T. gondii. To this purpose, the chimeric protein rEC2, encoding antigenic fragments of surface-associated proteins MIC2, MIC3 and SAG1, was combined with pGRA7 plasmid DNA or rGRA7 protein. High levels of antibodies were elicited by both vaccine formulations. The protein-DNA vaccine elicited a polarized Th1/Th2 immune response, characterized by IFN-gamma and IL-10, and afforded low protection (24%) against brain cyst formation. In contrast, the protein-protein vaccine elicited a Th1-focused immune response, characterized by IFN-gamma and IL-2 production, conferring a strong protection (79%) against brain cyst formation in chronic toxoplasmosis. We show here that GERBU adjuvanted protein vaccines confer better protection against toxoplasmosis than the protein-DNA heterologous vaccine.
The synergistic protective efficacy of murine interleukin 21 (mIL-21) and mIL-15 administrated wi... more The synergistic protective efficacy of murine interleukin 21 (mIL-21) and mIL-15 administrated with DNA vaccine against acute and chronic Toxoplasma gondii infection in mice was investigated using T. gondii MIC8 (TgMIC8) as a model. We cloned mIL-21 and mIL-15 from splenic tissues of Kunming mice, and constructed eukaryotic plasmid pVAX/mIL-15, pVAX/mIL-21, and pVAX/mIL-21/mIL-15, respectively. After immunizing with pVAX/TgMIC8 in the presence or absence of these cytokines, immune responses were analyzed using lymphoproliferative assay, cytokine and serum antibody measurements, flow cytometric surface markers on lymphocytes and protection against acute and chronic T. gondii infection. Mice receiving pVAX/TgMIC8 alone developed a strong humoral responses and Th1 type cellular immune responses, and showed an increase of CD4+ and CD8+ T cells compared with all the controls. Adding pVAX/mIL-21 to pVAX/TgMIC8 compared to pVAX/TgMIC8 resulted in only a slight increase in humoral and cellular immune responses, and this immune response was lower than that induced by the pVAX/mIL-15 combined with pVAX/TgMIC8. Co-administration of pVAX/mIL-21/mIL-15 combined with pVAX/TgMIC8 elicited the strongest humoral and cellular immune responses among all the groups, leading to significantly increased survival time against acute infection and the significant reduction of tissue cysts, compared to all the controls. Synergy of mIL-21 and mIL-15 can facilitate specific humoral as well as cellular immune responses elicited by DNA vaccine against acute and chronic T. gondii infection in mice.
To evaluate an immunofluorescence antibody test (IFAT) for diagnosis of schistosomiasis in nonimm... more To evaluate an immunofluorescence antibody test (IFAT) for diagnosis of schistosomiasis in nonimmune travellers and immigrants from endemic areas. 65 patients (48 Danes and 17 immigrants) with schistosomiasis were included. The diagnosis of schistosomiasis was based on the presence of schistosome eggs in faeces, urine, sperm, rectal or bladder biopsies and/or the presence of specific antibodies determined by the serological immunofluorescence antibody test (IFAT). Egg excretion was detected using conventional methods and the IFAT performed on whole S. mansoni schistosomula worms, harvested after 8 weeks from mice. Two patterns of immunofluorescence were observed: Fluorescence in the gut of the schistosome called 'Gut Associated Antigen, GAA', and fluorescence of the surface of the schistosomula called 'Membrane Bound Antigen, MBA'. Eggs were found in 44% of the Danish patients and in 76% of immigrants. The diagnosis was based on a positive IFAT in 48% of the patients. In patients from nonendemic areas, the finding of antibodies against GAA was diagnostic while optimal sensitivity in the immigrants was reached by measuring antibodies against both GAA and MBA. In patients from nonendemic areas GAA is a sensitive marker of acute infection with schistosomiasis. In patients from endemic areas the demonstration of both GAA and MBA is necessary to properly identify long-lasting, nonacute infections. Egg-detection and/or measurement of CAA and CCA remain the methods of choice to monitor treatment as the immunofluorescence assay may remain positive for several years after treatment.
The first 2 cases of infection with Enterocytozoon bieneusi in Denmark and Scandinavia are report... more The first 2 cases of infection with Enterocytozoon bieneusi in Denmark and Scandinavia are reported. Both patients were women and to the best of our knowledge this is the first report of E. bieneusi in female AIDS patients. Both had late stage AIDS, and both had complained of intermittent diarrhoea for more than 1 year. At the time microsporidiosis was diagnosed, no other pathogens causing diarrhoea were found. Immunodeficient patients with chronic unexplained diarrhoea should be investigated for intestinal microsporidiosis, especially as treatment is now available.
Egg detection is the gold standard in diagnosing and controlling treatment in schistosomiasis, bu... more Egg detection is the gold standard in diagnosing and controlling treatment in schistosomiasis, but sensitivity is poor in lightly infected individuals, whereas Schistosoma-specific antibodies are more sensitive. The purpose of the study was to evaluate use of Gut Associated Antigen (GAA) and Membrane Bound Antigen (MBA) assays in assessment of treatment efficacy and number of treated non-immune individuals with signs of treatment failure. In a retrospective study, residents in Denmark diagnosed with positive Schistosoma antibodies in the period 1987 - 2004 were offered follow-up including analyses for GAA, MBA, IgE and eosinophil count. Among 98 patients with positive antibody at time of diagnosis, 73 were examined for eggs and 27% had detectable eggs. 15% still had detectable living eggs after 1 course of treatment. At follow-up it was demonstrated that antibodies continued to increase for up to 6 months after treatment and average duration of positive GAA antibody was approximately 10 y. The study confirms that the GAA- and MBA-IFAT are not suitable in monitoring results of therapy. Treatment failure in 15% of non-immune patients indicates that studies are needed to define the correct dose of praziquantel in those individuals or to evaluate if resistance to praziquantel is a growing problem.
Candida albicans endocarditis involves infrequently the tricuspid valve and involvement of the pu... more Candida albicans endocarditis involves infrequently the tricuspid valve and involvement of the pulmonic valve is rare. We report our experience with an immunosuppressed liver-transplanted female who developed both tricuspid and pulmonic valve endocarditis, review the literature and discuss the importance of effective antimycotic therapy combined with surgical replacement of the affected valve.
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Papers by Eskild Petersen