المؤلفون: D. G. Ponomarenko, M. V. Kostyuchenko, E. L. Rakitina, O. V. Logvinenko, A. A. Khachaturova, D. E. Lukashevich, S. A. Kurcheva, D. V. Rusanova, A. N. Kulichenko

المصدر: Медицинская иммунология, Vol 26, Iss 1, Pp 211-220 (2024)

مصطلحات موضوعية: brucellosis, vaccination, protective immunity, antigen reactivity of t lymphocytes, antigenic stimulation coefficient, infection index, Immunologic diseases. Allergy, RC581-607

الوصف: The results of study relationship between antigen reactivity of T-lymphocyte population under ex vivo conditions and the intensity of protective post-vaccination immunity to causative agent of brucellosis are presented. Тaking into account the peculiarities of immunopathogenesis brucellosis and prevailing role of adaptive T-cell immunity to protect against the causative agent of infection, possibility predictive evaluation of protective immunity against brucellosis using CAST-tests is considered as the most important aspect of brucellosis problems. There is an obvious need for an ex vivo correlation analysis of the activity of antigen stimulation of T cells and the intensity of protective immunity formed after vaccination. A close direct proportional relationship was established between the number of live microbial cells Brucella abortus 19BA vaccine strain administered and increase in ex vivo CD3-cell activation. A close correlation was revealed between ex vivo value of antigen-induced stimulation CD3-lymphocytes and level of post-vaccination immunological protection against brucellosis infection. It has been shown that in biomodels vaccinated against brucellosis with a T-lymphocyte stimulation coefficient of 50% or more (according to intensity of antigen-induced ex vivo expression CD25), 100% protection from the development of brucellosis infection after infection with Brucella melitensis at a dose of 1 × 103 live microbial cells are provided. At the same time, there was a lack of a close correlation between an increase in the dose of brucella vaccine strain administered to biomodels and a change in geometric mean antibody titer, presence of a weakly pronounced relationship between level of agglutinins and immunological protection of biomodels from development brucellosis infection and indicators bacterial contamination body.Based on results of study, it was demonstrated that it is possible to quantify the formation and protective activity of T-cell immunity to causative agent of brucellosis based on analysis of level antigen reactivity of CD3-lymphocytes ex vivo. The data obtained and described methodological approach can be used as a predictive criterion in assessing protective level of cellular immunity to causative agent of brucellosis in vaccinated or recovering patients, as well as in order to analyze effectiveness of specific prophylaxis brucellosis and study immunogenicity and protective properties candidate for brucellosis vWe present the results of studies related to antigen reactivity of T lymphocyte population under ex vivo conditions and the intensity of protective post-vaccination immunity to causative agent of brucellosis. Due to peculiarities of immunopathogenesis in brucellosis infection and prevailing role of adaptive T cell immunity for protection against the causative agent of infection, a predictive evaluation of protective immunity against brucellosis using CAST-tests is considered the most important issue in the field. There is an obvious need for ex vivo analysis of correlations between the activity of antigen stimulation of T cells, and the intensity of protective immunity raised after vaccination. A close direct relationship was established between the number of live microbial cells of Brucella abortus 19BA vaccine strain administered, and increase in ex vivo CD3 cell activation. A close correlation (r = -0.841 ÷ -0.966, R2 = 0.708 ÷ 0.969) was revealed between ex vivo values of antigeninduced stimulation of CD3 lymphocytes, and the levels of post-vaccination immunological protection against brucellosis infection. We have shown that, in biomodels vaccinated against brucellosis with a T lymphocyte stimulation coefficient of 50% or more (according to intensity of antigen-induced ex vivo CD25 expression), 100% protection against brucellosis infection was achieved after contamination with Brucella melitensis at a dose of 1×103 live microbial cells. At the same time, a lack of a close correlation was noted between an increased dose of Brucella vaccine strain administered to biomodels, and a change in geometric mean of antibody titer (R2 = 0.357÷0.404), along with a weak relationship between the levels of agglutinins and immunological protection of biomodels from developing brucellosis infection and indices of in vivo bacterial contamination.These results suggest an opportunity to quantify development and protective activity of T cell immunity to the causal agent of brucellosis based ex vivo levels of antigen reactivity of CD3 lymphocytes. A correlation analysis between the state of T cell antigen reactivity and immunological resistance to brucellosis infection indicated a high degree of closeness between these indices. The key influence on activity of protective immunity is exerted by the levels of antigen reactivity of T lymphocytes, whereas the quotient of antigenic stimulation in CD3+CD25+ population may be considered the most informative index of immune protective activity. The data obtained and the described methodology may be used as a predictive criterion in assessing protective level of cellular immunity to causative agent of brucellosis in vaccinated or recovering patients, testing the efficiency of specific prophylaxis in brucellosis and studying immunogenicity and protective properties of candidate vaccines against brucellosis.

وصف الملف: electronic resource

العلاقة: https://www.mimmun.ru/mimmun/article/view/2604Test; https://doaj.org/toc/1563-0625Test; https://doaj.org/toc/2313-741XTest

الوصول الحر: https://doaj.org/article/766323298b5049bfa34fca94f0577f71Test

المؤلفون: D. G. Ponomarenko, M. V. Kostyuchenko, E. L. Rakitina, O. V. Logvinenko, A. A. Khachaturova, D. E. Lukashevich, S. A. Kurcheva, D. V. Rusanova, A. N. Kulichenko, Д. Г. Пономаренко, М. В. Костюченко, Е. Л. Ракитина, О. В. Логвиненко, А. А. Хачатурова, Д. Е. Лукашевич, С. А. Курчева, Д. В. Русанова, А. Н. Куличенко

المصدر: Medical Immunology (Russia); Том 26, № 1 (2024); 211-220 ; Медицинская иммунология; Том 26, № 1 (2024); 211-220 ; 2313-741X ; 1563-0625

مصطلحات موضوعية: индекс инфицированности, vaccination, protective immunity, antigen reactivity of T lymphocytes, antigenic stimulation coefficient, infection index, вакцинация, протективный иммунитет, антигенреактивность Т-лимфоцитов, коэффициент антигенной стимуляции

الوصف: The results of study relationship between antigen reactivity of T-lymphocyte population under ex vivo conditions and the intensity of protective post-vaccination immunity to causative agent of brucellosis are presented. Тaking into account the peculiarities of immunopathogenesis brucellosis and prevailing role of adaptive T-cell immunity to protect against the causative agent of infection, possibility predictive evaluation of protective immunity against brucellosis using CAST-tests is considered as the most important aspect of brucellosis problems. There is an obvious need for an ex vivo correlation analysis of the activity of antigen stimulation of T cells and the intensity of protective immunity formed after vaccination. A close direct proportional relationship was established between the number of live microbial cells Brucella abortus 19BA vaccine strain administered and increase in ex vivo CD3-cell activation. A close correlation was revealed between ex vivo value of antigen-induced stimulation CD3-lymphocytes and level of post-vaccination immunological protection against brucellosis infection. It has been shown that in biomodels vaccinated against brucellosis with a T-lymphocyte stimulation coefficient of 50% or more (according to intensity of antigen-induced ex vivo expression CD25), 100% protection from the development of brucellosis infection after infection with Brucella melitensis at a dose of 1 × 103 live microbial cells are provided. At the same time, there was a lack of a close correlation between an increase in the dose of brucella vaccine strain administered to biomodels and a change in geometric mean antibody titer, presence of a weakly pronounced relationship between level of agglutinins and immunological protection of biomodels from development brucellosis infection and indicators bacterial contamination body.Based on results of study, it was demonstrated that it is possible to quantify the formation and protective activity of T-cell immunity to causative agent of brucellosis based on analysis ...

وصف الملف: application/pdf

العلاقة: https://www.mimmun.ru/mimmun/article/view/2604/1818Test; https://www.mimmun.ru/mimmun/article/downloadSuppFile/2604/10248Test; https://www.mimmun.ru/mimmun/article/downloadSuppFile/2604/10249Test; https://www.mimmun.ru/mimmun/article/downloadSuppFile/2604/10250Test; https://www.mimmun.ru/mimmun/article/downloadSuppFile/2604/10251Test; https://www.mimmun.ru/mimmun/article/downloadSuppFile/2604/10252Test; https://www.mimmun.ru/mimmun/article/downloadSuppFile/2604/10253Test; https://www.mimmun.ru/mimmun/article/downloadSuppFile/2604/10254Test; https://www.mimmun.ru/mimmun/article/downloadSuppFile/2604/10255Test; https://www.mimmun.ru/mimmun/article/downloadSuppFile/2604/10256Test; https://www.mimmun.ru/mimmun/article/downloadSuppFile/2604/10257Test; https://www.mimmun.ru/mimmun/article/downloadSuppFile/2604/10258Test; https://www.mimmun.ru/mimmun/article/downloadSuppFile/2604/10259Test; https://www.mimmun.ru/mimmun/article/downloadSuppFile/2604/10260Test; https://www.mimmun.ru/mimmun/article/downloadSuppFile/2604/10261Test; https://www.mimmun.ru/mimmun/article/downloadSuppFile/2604/10262Test; https://www.mimmun.ru/mimmun/article/downloadSuppFile/2604/10263Test; https://www.mimmun.ru/mimmun/article/downloadSuppFile/2604/10264Test; https://www.mimmun.ru/mimmun/article/downloadSuppFile/2604/10265Test; https://www.mimmun.ru/mimmun/article/downloadSuppFile/2604/10266Test; https://www.mimmun.ru/mimmun/article/downloadSuppFile/2604/10267Test; https://www.mimmun.ru/mimmun/article/downloadSuppFile/2604/10283Test; https://www.mimmun.ru/mimmun/article/downloadSuppFile/2604/10284Test; https://www.mimmun.ru/mimmun/article/downloadSuppFile/2604/10285Test; https://www.mimmun.ru/mimmun/article/downloadSuppFile/2604/10286Test; https://www.mimmun.ru/mimmun/article/downloadSuppFile/2604/12881Test; Бруцеллёз. 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الإتاحة: https://doi.org/10.15789/1563-0625-QAO-2604Test
https://www.mimmun.ru/mimmun/article/view/2604Test

المؤلفون: Tesfaye, Fregenet, Sturegård, Erik, Walles, John, Bekele, Bayissa, Bobosha, Kidist, Björkman, Per, Jansson, Marianne

المصدر: Microbiology spectrum EpiHealth: Epidemiology for Health. 10(5)

مصطلحات موضوعية: HIV-uninfected, interferon-g inducible protein 10, interleukin 2, Mycobacterium tuberculosis antigen reactivity, pregnancy, transforming growth factor-beta1, tuberculosis infection, Medicin och hälsovetenskap, Klinisk medicin, Reproduktionsmedicin och gynekologi, Medical and Health Sciences, Clinical Medicine, Obstetrics, Gynecology and Reproductive Medicine

الوصف: The immune control of tuberculosis (TB) infection could be influenced by pregnancy. To elucidate this, we longitudinally characterized Mycobacterium tuberculosis (Mtb)-specific and nonspecific immune responses in women during pregnancy and postpartum. HIV-uninfected women without past or current active TB, and with blood samples available from the 1st/2nd trimester, 3rd trimester, and 9 months postpartum, were identified at Ethiopian antenatal care clinics. Twenty-two TB1 women and 10 TB2 women, defined according to Mtb-stimulated interferon-g levels ($0.35 and,0.20 IU/mL, respectively, in the Quantiferon-TB Gold-Plus assay), were included in the study. Longitudinal dynamics of six cytokines (IL-1ra, IL-2, IP-10, MCP-2, MCP-3, and TGF-b1) were analyzed in supernatants from Mtb-stimulated and unstimulated whole blood. In TB1 women, Mtb-specific expression of IL-2 and IP-10 was higher at 3rd compared to 1st/2nd trimester (median 139 pg/mL versus 62 pg/mL, P = 0.006; 4,999 pg/mL versus 2,310 pg/mL, P = 0.031, respectively), whereas level of Mtb-triggered TGF-b1 was lower at 3rd compared to 1st/2nd trimester (26.8 ng/mL versus 2.3 ng/mL, P = 0.020). Unstimulated IL-2, IP-10, and MCP-2 levels were increased postpartum, compared with those noted during pregnancy, in TB1 women. Additionally, postpartum levels of proinflammatory cytokines in unstimulated blood were higher in TB1 women, than in TB2 women. None of the women developed active TB during follow-up. Taken together, dynamic changes of Mtb-specific cytokine expression revealed during the 3rd trimester in TB1 women indicate increased Mtb-antigen stimulation at later stages of pregnancy. This could reflect elevated bacterial activity, albeit without transition to active TB, during pregnancy. IMPORTANCE Tuberculosis (TB) is globally one of the most common causes of death, and a quarter of the world's population is estimated to have TB infection. The risk of active TB is increased in connection to pregnancy, a phenomenon that could be due to physiological immune changes. Here, we studied the effect of pregnancy on immune responses triggered in HIV-uninfected women with TB infection, by analyzing blood samples obtained longitudinally during pregnancy and after childbirth. We found that the dynamics of Mtb-specific and nonspecific immune responses changed during pregnancy, especially in later stages of pregnancy, although none of the women followed in this study developed active TB. This suggests that incipient TB, with elevated bacterial activity, occurs during pregnancy, but progression of infection appears to be counteracted by Mtb-specific immune responses. Thus, this study sheds light on immune control of TB during pregnancy, which could be of importance for future intervention strategies.

الوصول الحر: https://lup.lub.lu.se/record/36df593a-8c23-4f4b-aa66-e52f3b21c15cTest
http://dx.doi.org/10.1128/spectrum.01178-22Test

المؤلفون: Tegegn, Fregenet Tesfaye

المصدر: Lund University, Faculty of Medicine Doctoral Dissertation Series. (2022:14)

مصطلحات موضوعية: Interferon-γ, immune mediators, latent tuberculosis infection, Mtb-antigen reactivity, pregnancy, QuantiFERON-TB Gold Plus, Medicin och hälsovetenskap, Klinisk medicin, Infektionsmedicin, Medical and Health Sciences, Clinical Medicine, Infectious Medicine, Medicinska och farmaceutiska grundvetenskaper, Mikrobiologi inom det medicinska området, Basic Medicine, Microbiology in the medical area, Immunologi inom det medicinska området, Immunology in the medical area

الوصف: Pregnancy-induced immune modulation might lead to reactivation of latent tuberculosis infection (LTBI). This thesis explores aspects of immune-based LTBI diagnostics and how pregnancy affects the immune control of Mycobacterium tuberculosis (Mtb) infection. We studied a prospective cohort of women recruited during pregnancy in Ethiopia. LTBI testing was performed by quantification of interferon-γ (IFN-γ) in Mtb-antigen- stimulated whole blood supernatants using the QuantiFERON-TB Gold Plus (QFT) assay.In paper I, we found that 277/829 (33%) of pregnant women had LTBI using the conventional IFN-γ cut-off level (0.35 IU/ml). However, borderline results (0.20-0.70 IU/ml) were common, especially in HIV-positive women. In paper II, we characterized Mtb-antigen cytokine responses for LTBI classification in women with borderline IFN-γ results. A combination of MCP-2, IP-10 and IL-1ra classified 42% of women with borderline IFN-γ as having high likelihood of LTBI. In paper III, we studied longitudinal patterns of Mtb-triggered IFN-γ secretion during pregnancy and post-partum. We observed that Mtb-stimulated IFN-γ response was elevated during the 3rd trimester compared to early pregnancy and post-partum. In paper IV, we investigated longitudinal kinetics of Mtb-specific and -non-specific cytokine responses in women with LTBI. We found elevated expression of Mtb-specific IL-2 and IP-10, and reduced TGF-β1, secretion at the 3rd trimester. Non-specific levels of IL-2, IP-10 and MCP-2 were elevated post-partum in women with LTBI. In conclusion, these findings suggest that cytokines other than IFN-γ, could be used as biomarkers to assess LTBI status of pregnant women. The dynamic immune responses in women with LTBI indicate increased exposure to Mtb at later stages of pregnancy, which in turn suggests that LTBI is transiently reactivated during pregnancy.

وصف الملف: electronic

الوصول الحر: https://lup.lub.lu.se/record/0e84ec20-e647-42cf-a40f-71d92008dfbfTest
https://portal.research.lu.se/files/112692737/Fregenet_Tesfaye_WEBB.pdfTest

المؤلفون: Fregenet Tesfaye, Erik Sturegård, John Walles, Bayissa Bekele, Kidist Bobosha, Per Björkman, Marianne Jansson

المصدر: Microbiology Spectrum, Vol 10, Iss 5 (2022)

مصطلحات موضوعية: tuberculosis infection, pregnancy, Mycobacterium tuberculosis antigen reactivity, HIV-uninfected, interleukin 2, interferon-γ inducible protein 10, Microbiology, QR1-502

الوصف: ABSTRACT The immune control of tuberculosis (TB) infection could be influenced by pregnancy. To elucidate this, we longitudinally characterized Mycobacterium tuberculosis (Mtb)-specific and nonspecific immune responses in women during pregnancy and postpartum. HIV-uninfected women without past or current active TB, and with blood samples available from the 1st/2nd trimester, 3rd trimester, and 9 months postpartum, were identified at Ethiopian antenatal care clinics. Twenty-two TB+ women and 10 TB− women, defined according to Mtb-stimulated interferon-γ levels (≥0.35 and

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2165-0497Test

الوصول الحر: https://doaj.org/article/deb3d51c3cda4650992627a363a80015Test

المؤلفون: Mwesigwa, J, Slater, H, Bradley, J, Saidy, B, Ceesay, F, Whittaker, C, Kandeh, B, Nkwakamna, D, Drakeley, C, Van Geertruyden, J-P, Bousema, T, Achan, J, D'Alessandro, U

المصدر: 13 ; 1

مصطلحات موضوعية: Science & Technology, Life Sciences & Biomedicine, Infectious Diseases, Parasitology, Tropical Medicine, Highly sensitive rapid diagnostic test, Malaria, Mass testing and treatment, Plasmodium falciparum, Transmission areas, PLASMODIUM-FALCIPARUM MALARIA, ANTIGEN REACTIVITY, SOUTHERN ZAMBIA, ELIMINATION, PANMALARIAL, INFECTIONS, IMPACT, VIVAX, HRP2, Adolescent, Adult, Aged, 80 and over, Child, Preschool, Cross-Sectional Studies, Diagnostic Tests, Routine, Female, Gambia

الوصف: Background The Gambia has successfully reduced malaria transmission. The human reservoir of infection could further decrease if malaria-infected individuals could be identified by highly sensitive, field-based, diagnostic tools and then treated. Methods A cross-sectional survey was done at the peak of the 2017 malaria season in 47 Gambian villages. From each village, 100 residents were randomly selected for finger-prick blood samples to detect Plasmodium falciparum infections using highly sensitive rapid diagnostic tests (HS-RDT) and PCR. The sensitivity and specificity of the HS-RDT were estimated (assuming PCR as the gold standard) across varying transmission intensities and in different age groups. A deterministic, age-structured, dynamic model of malaria transmission was used to estimate the impact of mass testing and treatment (MTAT) with HS-RDT in four different scenarios of malaria prevalence by PCR: 5, 15, 30, and 60%, and with seasonal transmission. The impact was compared both to MTAT with conventional RDT and mass drug administration (MDA). Results Malaria prevalence by HS-RDT was 15% (570/3798; 95% CI 13.9–16.1). The HS-RDT sensitivity and specificity were 38.4% (191/497, 95% CI 34.2–42.71) and 88.5% (2922/3301; 95% CI 87.4–89.6), respectively. Sensitivity was the highest (50.9%, 95% CI 43.3–58.5%) in high prevalence villages (20–50% by PCR). The model predicted that in very low transmission areas (≤ 5%), three monthly rounds of MTAT with HS-RDT, starting towards the end of the dry season and testing 65 or 85% of the population for 2 consecutive years, would avert 62 or 78% of malaria cases (over 2 years), respectively. The effect of the intervention would be lower in a moderate transmission setting. In all settings, MDA would be superior to MTAT with HS-RDT which would be superior to MTAT with conventional RDT. Conclusion The HS-RDT’s field sensitivity was modest and varied by transmission intensity. In low to very low transmission areas, three monthly rounds per year of MTAT with HS-RDT at 85% ...

العلاقة: Malaria Journal; http://hdl.handle.net/10044/1/76448Test

الإتاحة: https://doi.org/10.1186/s12936-019-2929-1Test
http://hdl.handle.net/10044/1/76448Test

المؤلفون: Dmitry Grigoryevich Ponomarenko, Marina Vladimirovna Kostyuchenko, Ekaterina Lvovna Rakitina, Olga Vasilievna Logvinenko, Anna Andreevna Khachaturova, Darya Evgenievna Lukashevich, Svetlana Aleksandrovna Kurcheva, Diana Vladimirovna Rusanova, Alexander Nikolaevich Kulichenko

المصدر: Медицинская иммунология, Vol 0, Iss 0 (2019)

مصطلحات موضوعية: brucellosis, vaccination, protective immunity, antigen reactivity of t-lymphocytes, antigenic stimulation coefficient, infection index, Immunologic diseases. Allergy, RC581-607

الوصف: The results of study relationship between antigen reactivity of T-lymphocyte population under ex vivo conditions and the intensity of protective post-vaccination immunity to causative agent of brucellosis are presented. Тaking into account the peculiarities of immunopathogenesis brucellosis and prevailing role of adaptive T-cell immunity to protect against the causative agent of infection, possibility predictive evaluation of protective immunity against brucellosis using CAST-tests is considered as the most important aspect of brucellosis problems. There is an obvious need for an ex vivo correlation analysis of the activity of antigen stimulation of T cells and the intensity of protective immunity formed after vaccination. A close direct proportional relationship was established between the number of live microbial cells Brucella abortus 19BA vaccine strain administered and increase in ex vivo CD3-cell activation. A close correlation was revealed between ex vivo value of antigen-induced stimulation CD3-lymphocytes and level of post-vaccination immunological protection against brucellosis infection. It has been shown that in biomodels vaccinated against brucellosis with a T-lymphocyte stimulation coefficient of 50% or more (according to intensity of antigen-induced ex vivo expression CD25), 100% protection from the development of brucellosis infection after infection with Brucella melitensis at a dose of 1 × 103 live microbial cells are provided. At the same time, there was a lack of a close correlation between an increase in the dose of brucella vaccine strain administered to biomodels and a change in geometric mean antibody titer, presence of a weakly pronounced relationship between level of agglutinins and immunological protection of biomodels from development brucellosis infection and indicators bacterial contamination body.Based on results of study, it was demonstrated that it is possible to quantify the formation and protective activity of T-cell immunity to causative agent of brucellosis based on analysis ...

العلاقة: https://www.mimmun.ru/mimmun/article/view/2604Test; https://doaj.org/toc/1563-0625Test; https://doaj.org/toc/2313-741XTest; https://doaj.org/article/766323298b5049bfa34fca94f0577f71Test

الإتاحة: https://doi.org/10.15789/1563-0625-QAO-2604Test
https://doaj.org/article/766323298b5049bfa34fca94f0577f71Test

المؤلفون: Charlene M.C. Rodrigues, Keith A. Jolley, Ian M. Feavers, Martin C. J. Maiden, J. Claire Cameron, Andrew Smith

المصدر: Journal of Clinical Microbiology

مصطلحات موضوعية: Microbiology (medical), medicine.medical_specialty, meningococcal antigen surface expression (MEASURE) assay, Meningococcal Vaccines, Genomics, Computational biology, Meningococcal vaccine, Neisseria meningitidis, Serogroup B, Neisseria meningitidis, medicine.disease_cause, Meningococcal disease, Genome, Antigen, Meningococcal Deduced Vaccine Antigen Reactivity (MenDeVAR), medicine, Humans, Index case, meningococcal disease, Antigens, Bacterial, business.industry, Public health, public health, meningococcal antigen typing system (MATS), Outbreak, Bacteriology, vaccines, medicine.disease, Meningococcal Infections, whole-genome sequencing, outbreaks, serum bactericidal activity assay, business

الوصف: As microbial genomics makes increasingly important contributions to clinical and public health microbiology, the interpretation of whole-genome sequence data by nonspecialists becomes essential. In the absence of capsule-based vaccines, two protein-based vaccines have been used for the prevention of invasive serogroup B meningococcal disease (IMD) since their licensure in 2013 and 2014. These vaccines have different components and different levels of coverage of meningococcal variants. Hence, decisions regarding which vaccine to use in managing serogroup B IMD outbreaks require information about the index case isolate, including (i) the presence of particular vaccine antigen variants, (ii) the expression of vaccine antigens, and (iii) the likely susceptibility of its antigen variants to antibody-dependent bactericidal killing.
As microbial genomics makes increasingly important contributions to clinical and public health microbiology, the interpretation of whole-genome sequence data by nonspecialists becomes essential. In the absence of capsule-based vaccines, two protein-based vaccines have been used for the prevention of invasive serogroup B meningococcal disease (IMD) since their licensure in 2013 and 2014. These vaccines have different components and different levels of coverage of meningococcal variants. Hence, decisions regarding which vaccine to use in managing serogroup B IMD outbreaks require information about the index case isolate, including (i) the presence of particular vaccine antigen variants, (ii) the expression of vaccine antigens, and (iii) the likely susceptibility of its antigen variants to antibody-dependent bactericidal killing. To obtain this information requires a multitude of laboratory assays, impractical in real-time clinical settings, where the information is most urgently needed. To facilitate assessment for public health and clinical purposes, we synthesized genomic and experimental data from published sources to develop and implement the Meningococcal Deduced Vaccine Antigen Reactivity (MenDeVAR) Index, which is publicly available on PubMLST (https://pubmlst.orgTest). Using whole-genome sequences or individual gene sequences obtained from IMD isolates or clinical specimens, the MenDeVAR Index provides rapid evidence-based information on the presence and possible immunological cross-reactivity of different meningococcal vaccine antigen variants. The MenDeVAR Index enables practitioners who are not genomics specialists to assess the likely reactivity of vaccines for individual cases, outbreak management, or the assessment of public health vaccine programs. The MenDeVAR Index has been developed in consultation with, but independently of, both the 4CMenB (Bexsero; GSK) and rLP2086 (Trumenba; Pfizer, Inc.) vaccine manufacturers.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ce2ea9619ed39f0998f74bfae66e98ccTest
https://doi.org/10.1128/jcm.02161-20Test

المؤلفون: Ballah Kandeh, Charles Whittaker, Jane Achan, Binta Saidy, Teun Bousema, Umberto D'Alessandro, Chris Drakeley, Fatima Ceesay, Julia Mwesigwa, Jean-Pierre Van Geertruyden, Davis Nkwakamna, Hannah C Slater, John S. Bradley

المصدر: Malaria Journal
Malaria journal
Malaria Journal, 18, 1
Malaria Journal, Vol 18, Iss 1, Pp 1-13 (2019)
Malaria Journal, 18

مصطلحات موضوعية: Male, Veterinary medicine, IMPACT, Polymerase Chain Reaction, law.invention, 0302 clinical medicine, law, 1108 Medical Microbiology, Prevalence, 030212 general & internal medicine, Malaria, Falciparum, Child, VIVAX, Aged, 80 and over, Rapid diagnostic test, education.field_of_study, biology, Transmission areas, 1. No poverty, Middle Aged, 3. Good health, Transmission (mechanics), Infectious Diseases, ANTIGEN REACTIVITY, INFECTIONS, Child, Preschool, Female, Gambia, Life Sciences & Biomedicine, Adult, medicine.medical_specialty, lcsh:Arctic medicine. Tropical medicine, Adolescent, lcsh:RC955-962, 030231 tropical medicine, Population, HRP2, Plasmodium falciparum, Sensitivity and Specificity, lcsh:Infectious and parasitic diseases, 1117 Public Health and Health Services, 03 medical and health sciences, Young Adult, All institutes and research themes of the Radboud University Medical Center, Tropical Medicine, parasitic diseases, medicine, Humans, lcsh:RC109-216, Mass drug administration, education, Mass testing and treatment, ELIMINATION, SOUTHERN ZAMBIA, Aged, Science & Technology, business.industry, Highly sensitive rapid diagnostic test, Diagnostic Tests, Routine, Research, Infant, Newborn, Infant, PLASMODIUM-FALCIPARUM MALARIA, Gold standard (test), medicine.disease, biology.organism_classification, Malaria, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Cross-Sectional Studies, Tropical medicine, PANMALARIAL, Parasitology, Human medicine, business

الوصف: Background The Gambia has successfully reduced malaria transmission. The human reservoir of infection could further decrease if malaria-infected individuals could be identified by highly sensitive, field-based, diagnostic tools and then treated. Methods A cross-sectional survey was done at the peak of the 2017 malaria season in 47 Gambian villages. From each village, 100 residents were randomly selected for finger-prick blood samples to detect Plasmodium falciparum infections using highly sensitive rapid diagnostic tests (HS-RDT) and PCR. The sensitivity and specificity of the HS-RDT were estimated (assuming PCR as the gold standard) across varying transmission intensities and in different age groups. A deterministic, age-structured, dynamic model of malaria transmission was used to estimate the impact of mass testing and treatment (MTAT) with HS-RDT in four different scenarios of malaria prevalence by PCR: 5, 15, 30, and 60%, and with seasonal transmission. The impact was compared both to MTAT with conventional RDT and mass drug administration (MDA). Results Malaria prevalence by HS-RDT was 15% (570/3798; 95% CI 13.9–16.1). The HS-RDT sensitivity and specificity were 38.4% (191/497, 95% CI 34.2–42.71) and 88.5% (2922/3301; 95% CI 87.4–89.6), respectively. Sensitivity was the highest (50.9%, 95% CI 43.3–58.5%) in high prevalence villages (20–50% by PCR). The model predicted that in very low transmission areas (≤ 5%), three monthly rounds of MTAT with HS-RDT, starting towards the end of the dry season and testing 65 or 85% of the population for 2 consecutive years, would avert 62 or 78% of malaria cases (over 2 years), respectively. The effect of the intervention would be lower in a moderate transmission setting. In all settings, MDA would be superior to MTAT with HS-RDT which would be superior to MTAT with conventional RDT. Conclusion The HS-RDT’s field sensitivity was modest and varied by transmission intensity. In low to very low transmission areas, three monthly rounds per year of MTAT with HS-RDT at 85% coverage for 2 consecutive years would reduce malaria prevalence to such low levels that additional strategies may achieve elimination. The model prediction would need to be confirmed by cluster-randomized trials.

وصف الملف: pdf; application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1ed5f5cb8e8fe0e9fcf34c3800bb8450Test
http://europepmc.org/articles/PMC6712604Test

المؤلفون: Bachler, Barbara C, Humbert, Michael, Lakhashe, Samir K, Rasmussen, Robert A, Ruprecht, Ruth M

مصطلحات موضوعية: Macaque model, Recombinant protein vaccine, Heterologous R5 SHIV clade C challenge, Complete protection, Subtractive peptide phage display, V3 crown, Boosting of vaccine-induced Ab titers after multiple challenges, Neo-antigen reactivity

الوصف: Background We addressed the question whether live-virus challenges could alter vaccine-induced antibody (Ab) responses in vaccinated rhesus macaques (RMs) that completely resisted repeated exposures to R5-tropic simian-human immunodeficiency viruses encoding heterologous HIV clade C envelopes (SHIV-Cs). Results We examined the Ab responses in aviremic RMs that had been immunized with a multi-component protein vaccine (multimeric HIV-1 gp160, HIV-1 Tat and SIV Gag-Pol particles) and compared anti-Env plasma Ab titers before and after repeated live-virus exposures. Although no viremia was ever detected in these animals, they showed significant increases in anti-gp140 Ab titers after they had encountered live SHIVs. When we investigated the dynamics of anti-Env Ab titers during the immunization and challenge phases further, we detected the expected, vaccine-induced increases of Ab responses about two weeks after the last protein immunization. Remarkably, these titers kept rising during the repeated virus challenges, although no viremia resulted. In contrast, in vaccinated RMs that were not exposed to virus, anti-gp140 Ab titers declined after the peak seen two weeks after the last immunization. These data suggest boosting of pre-existing, vaccine-induced Ab responses as a consequence of repeated live-virus exposures. Next, we screened polyclonal plasma samples from two of the completely protected vaccinees by peptide phage display and designed a strategy that selects for recombinant phages recognized only by Abs present after – but not before – any SHIV challenge. With this “subtractive biopanning” approach, we isolated V3 mimotopes that were only recognized after the animals had been exposed to live virus. By detailed epitope mapping of such anti-V3 Ab responses, we showed that the challenges not only boosted pre-existing binding and neutralizing Ab titers, but also induced Abs targeting neo-antigens presented by the heterologous challenge virus. Conclusions Anti-Env Ab responses induced by recombinant ...

العلاقة: http://www.retrovirology.com/content/10/1/63Test

الإتاحة: http://www.retrovirology.com/content/10/1/63Test