The Zika virus(ZIKV),a member of the Flaviviridae family,attracted worldwide attention for its connection to severe neurological effects,notably microcephaly in newborns,first reported during the 2015 epidemic in Braz...The Zika virus(ZIKV),a member of the Flaviviridae family,attracted worldwide attention for its connection to severe neurological effects,notably microcephaly in newborns,first reported during the 2015 epidemic in Brazil.Yet,its impact goes beyond fetal and neonatal abnormalities,also affecting the central nervous system(CNS)in both children and adults,leading to enduring cognitive and behavioral impairments.展开更多
The Pisolithus tinctorius symbiosis related protein expressed sequence tag (EST PtSRP) was previously identified in the first hours of the interaction between the fungus Pisolithus tinctorius and sweet chestnut Castan...The Pisolithus tinctorius symbiosis related protein expressed sequence tag (EST PtSRP) was previously identified in the first hours of the interaction between the fungus Pisolithus tinctorius and sweet chestnut Castanea sativa, and partially characterized as a fungal marker gene of ectomycorrhizal symbiosis formation. We used the 5’ rapid amplification of cDNA ends (RACE) to obtain the PtSRP mRNA 5’ region, and together with our previously reported 3’ mRNA region, the full mRNA sequence was assembled by use of bioinformatics tools and deposited to GenBank (Accession: GU733439). The full-length mRNA sequence (636 bp) revealed the locations of the 5’ and 3’ untranslated regions (UTRs) and contained the Kozak sequence (ccc aag ATG A) in the 5’ UTR. The in silico translated PtSRP open reading frame (ORF) codes for a 127 amino acid protein and contained four putative post-translational modification sites (two N-glycosylation and two phosphorylation). The protein secondary structure is postulated to be composed of one N-terminal hydrophobic transmembrane alpha helix and at least six hydrophilic beta-strands spread across the protein. Sub-cellular localization prediction suggests that the protein is involved in cellular secretory pathway, supported by the presence of a cleavage site motif close to the membrane anchor. The data presented herein indicate the role of PtSRP as a fungal membrane secreted protein involved in early stages of ectomycorrhizal formation, with application as a possible marker for nascent ectomy-corrhiza fungal development.展开更多
Objective:To evaluate the in vitro anti-Trypanosoma cruzi（T.cruzi） activity of organic extracts prepared from halophyte species collected in the southern coast of Portugal（Algarve）,and chemically characterize the ...Objective:To evaluate the in vitro anti-Trypanosoma cruzi（T.cruzi） activity of organic extracts prepared from halophyte species collected in the southern coast of Portugal（Algarve）,and chemically characterize the most active samples.Methods:Acetone,dichloromethane and methanol extracts were prepared from 31 halophyte species and tested in vitro against trypomastigotes and intracellular amastigotes of the Tulahuen strain of T.cruzi.The most active extract was fractionated by preparative HPLC-DAD,affording 11 fractions.The most selective fraction was fully characterized by 1H-NMR.Results:From 94 samples tested,one was active,namely the root dichloromethane extract of Juncus acutus(IC50 < 20 μg/mL).This extract was fractionated by HPLC,affording 11 fractions,one of them containing only a pure compound（juncunol）,and tested for anti-parasitic activity.Fraction 8(IC50 = 4.1 μg/mL) was the most active,and was further characterized by 1H-NMR.The major compounds were phenanthrenes,9,10-dihydrophenanthrenes and benzocoumarins.Conclusion:Our results suggest that the compounds identified in fraction 8 are likely responsible for the observed anti parasitic activity.Further research is in progress aiming to isolate and identify the specific active molecules.To the best of our knowledge,this is the first report on the in vitro anti T.cruzi activity of halophyte species.展开更多
Various mouse models to study dengue have been described by different authors, some of them using immunodeficient or some using humanized mice. Our group reported previously a deadly murine model, which used the intra...Various mouse models to study dengue have been described by different authors, some of them using immunodeficient or some using humanized mice. Our group reported previously a deadly murine model, which used the intracranial inoculum of highly virulent Dengue virus (DENV) in immune competent mouse. Here we present a model of immune competent mouse (C57BL/6), infected subcutaneously by the same highly virulent DENV (DENV3 genotype I). In this immunocompetent systemic mice model, the cytokine levels and hematological parameters such as total and differential leukocyte and platelets counts, together with weight loss, were considered important monitoring parameters, allowing a better understanding of the systemic human disease. Mice were inoculated subcutaneously and evaluated by the percentage weight variation as well as the clinical signs. Hematological parameters and cytokines levels were measured and viral titration in brain tissue or serum neutralization was performed to confirm mice infection. The subcutaneously DENV inoculated mice showed weight loss after infection, but they did not show any other clinical signs. The leukocytes and platelets decreased after subcutaneous inoculation. The cytokines TNF alpha and IFN gamma increased after infection in mice. The subcutaneous model provided scope for improved understanding of the dengue pathogenesis, as well as possible mechanism for protection to subsequent mouse infected by intracranial route in mice. This model could be used to study the vertebrate immune response and evaluation of drugs or vaccine against dengue virus.展开更多
This study examines the relationship between geomagnetic indices and mortality rates from specific diseases in the Northeast (NE) and Southern (S) regions of Brazil from 1996 to 2020. Solar activity data, including th...This study examines the relationship between geomagnetic indices and mortality rates from specific diseases in the Northeast (NE) and Southern (S) regions of Brazil from 1996 to 2020. Solar activity data, including the Ap and Sudden Ionospheric Disturbance (SID) indices, were sourced from the World Data Center, while mortality data were obtained from the Mortality Information System (SIM-DATASUS). Acute Myocardial Infarction (AMI) emerged as the leading cause of mortality, with average death rates of 60.4, 56.8, and 58.3 deaths per 100,000 inhabitants in Pernambuco (PE), Rio Grande do Sul (RS), and Paraná (PR), respectively. Temporal analysis revealed a consistent upward trend in AMI mortality across most states, except for Santa Catarina (SC). Seasonal patterns identified through Principal Component Analysis (PCA) demonstrated that geomagnetic and climatic indices influenced mortality differently across regions and seasons. The Ap geomagnetic index was strongly correlated with higher AMI mortality rates during summer, while the SID index showed greater relevance during winter. A dipole phenomenon was observed, with AMI deaths increasing alongside geomagnetic activity in the S region but showing an inverse relationship in the NE region. These findings highlight the significant influence of geomagnetic variations on public health, particularly cardiovascular mortality. The study underscores the need for further research into the biological mechanisms underlying these associations and recommends the development of early warning systems and targeted preventive measures to mitigate the potential health impacts of geomagnetic disturbances, especially for vulnerable populations.展开更多
In Brazil,Biomphalaria glabrata,B.tenagophila,and B.straminea are naturally infected by the trematode Schistosoma mansoni,the causative agent of schistosomiasis.Despite decades of governmental efforts through official...In Brazil,Biomphalaria glabrata,B.tenagophila,and B.straminea are naturally infected by the trematode Schistosoma mansoni,the causative agent of schistosomiasis.Despite decades of governmental efforts through official control programs,schistosomiasis remains an important public health problem in the country:thousands of people are infected with the trematode each year and millions live in endemic areas.The World Health Organization recommends using a combination of molluscicide(niclosamide)and mass chemotherapy to control the transmission of schistosomiasis,with this treatment successfully reducing the morbidity of the disease.In the past,niclosamide has been used in official schistosomiasis control programs in Brazil.However,as B.glabrata recolonizes even after molluscicide application,the use of molluscicides has gradually decreased in the country until they were discontinued in 2002,mainly due to the rising global pressure to preserve the environment and the difficulties of obtaining licenses from the Brazilian Ministry of Environment to use toxic substances in aquatic ecosystems.Therefore,the discovery of new molluscicides,which could be more selective to Biomphalaria species and less harmful to the aquatic ecosystem,is necessary.In addition,political efforts to sensitize funders to provide grants for this field of research are required.In this context,this article aims to make a critical analysis of molluscicide application in schistosomiasis control programs in Brazil.展开更多
Background: Leprosy is a chronic infectious disease classified into two subgroups for therapeutic purposes:paucibacillary(PB)and multibacillary(MB),closely related to the host immune responses.In this context it is no...Background: Leprosy is a chronic infectious disease classified into two subgroups for therapeutic purposes:paucibacillary(PB)and multibacillary(MB),closely related to the host immune responses.In this context it is noteworthy looking for immunological biomarkers applicable as complementary diagnostic tools as well as a laboratorial strategy to follow-up leprosy household contacts.Methods:: The cross-sectional study enrolled 49 participants,including 19 patients and 30 healthy controls.Peripheral blood mononuclear cells(PBMC)were isolated and incubated in the presence of Mycobacterium leprae bacilli.The cells were prepared for surface(CD4+and CD8+)and intracytoplasmic cytokine staining(IFN-γ,IL-4 and IL-10).Multiple comparisons amongst groups were carried out by ANOVA,Kruskal–Wallis,Student T or Mann–Whitney test.Comparative analysis of categorical variables was performed by Chi-square.Functional biomarker signature analysis was conducted using the global median values for each biomarker index as the cut-off edge to identify the proportion of subjects with high biomarker levels.Results: The cytokine signature analysis demonstrated that leprosy patients presented a polyfunctional profile of T-cells subsets,with increased frequency of IFN-γ+T-cell subsets along with IL-10+and IL-4+from CD4+T-cells,as compared to health Controls(Venn diagram report).Moreover,statistical analysis was carried out using parametric or non-parametric variance analysis followed by pairwise multiple comparisons,according to the data normality distribution.L(PB)displayed a polyfunctional profile characterized by enhanced percentage of IFN-γ+,IL-10+and IL-4+produced by most T-cell subsets,as compared to L(MB)that presented a more restricted cytokine functional profile mediated by IL-10+and IL-4+T-cells with minor contribution of IFN-γproduced by CD4+T-cells.Noteworthy was that HHC(MB)exhibited enhanced frequency of IFN-γ+T-cells,contrasting with HHC(PB)that presented a cytokine profile limited to IL-10 and IL-4.Conclusions: Our data demonstrated that L(PB)displayed enhanced percentage of IFN-γ+,IL-10+and IL-4+as compared to L(MB)that presented functional profile mediated by IL-10+and IL-4+T-cells and HHC(MB)exhibited enhanced frequency of IFN-γ+T-cells,contrasting with HHC(PB).Together,our findings provide additional immunological features associated with leprosy and household contacts.These data provide evidence that biomarkers of immune response can be useful complementary diagnostic/prognostic tools as well as insights that household contacts should be monitored to access putative subclinical infection.展开更多
Background:Schistosomiasis is a common parasitic disease designated as a neglected tropical disease by the World Health Organization.Schistosomiasis mansoni is a form of the disease that is caused by the digenean trem...Background:Schistosomiasis is a common parasitic disease designated as a neglected tropical disease by the World Health Organization.Schistosomiasis mansoni is a form of the disease that is caused by the digenean trematode Schistosoma mansoni,transmitted through Biomphalaria spp.as an intermediate host.Biomphalaria was introduced to Hong Kong,China in aquatic plants shipments coming from Brazil and the snail rapidly established its habitats in southern China.Earlier studies of Biomphalaria spp.introduced to southern China identified the snails as Biomphalaria straminea,one of the susceptible species implicated in S.mansoni transmission in South America.However,recent molecular investigations also indicated the presence of another South American species,B.kuhniana,which is refractory to infection.As such,it is important to identify accurately the species currently distributed in southern China,especially with emerging reports of active S.mansoni infections in Chinese workers returning from Africa.Methods:We combined morphological and molecular taxonomy tools to precisely identify Biomphalaria spp.distributed in Guangdong Province,southern China.In order to clearly understand the molecular profile of the species,we constructed a phylogeny using mtDNA data(COI and 16S rRNA sequences)from six populations of Biomphalaria spp.from Shenzhen City in Guangdong Province.In addition,we examined the external morphology of the shell and internal anatomy of the reproductive organs.Results:Both morphological and molecular evidences indicated a close affinity between Biomphalaria spp.populations from Guangdong and B.straminea from Brazil.The shell morphology was roughly identical in all the populations collected with rounded whorls on one side and subangulated on the other,a smooth periphery,an egg-shaped aperture bowed to one side,and a deep umbilicus.The shape and number of prostate diverticula(ranged from 11.67 to 17.67)in Guangdong populations supports its close affinity to B.straminea rather than B.kuhniana.Molecular analysis did not conflict with morphological analysis.Little genetic differentiation was observed within Biomphalaria populations collected.Phylogenetic analysis of COI and 16S rRNA haplotypes from snails collected and B.straminea sequences from Brazil and China using Bayesian inference revealed that Guangdong populations were clustered in one clade with B.straminea from Hong Kong of China and B.straminea from Brazil indicating their close affinity to each other.Conclusions:Data obtained in the current study clearly show that the populations of Biomphalaria spp.investigated are B.straminea,and we assume that those snails were either introduced via passive dispersal from Hong Kong of China or as a result of multiple introduction routes from Brazil.展开更多
Background:Chagas disease is endemic in Latin America and still represents an important public health problem in the region.Chronic cardiomyopathy is the most significant chronic form due to its association with morbi...Background:Chagas disease is endemic in Latin America and still represents an important public health problem in the region.Chronic cardiomyopathy is the most significant chronic form due to its association with morbidity and mortality.The last decade has seen increasing evidence that inflammatory cytokines and chemokines are responsible for the generation of inflammatory infiltrate and tissue damage,with chronic chagasic cardiomyopathy patients presenting a pro-inflammatory immune response.Although studies have evaluated the role of chemokines in experimental T.cruzi infection,few have addressed their systemic profile,especially for human infection and in aging populations.The present work aimed to use the data from a large population based study of older adults,conducted in an endemic area for Chagas disease,to examine the association between serum levels of cytokines and chemokines,T.cruzi infection and electrocardiogram(ECG)abnormality.Methods:The present work evaluated serum levels of CCL2,CXCL9,CXCL10,CCL5,CXCL8,IL-1β,IL-6,TNF,IL-12 and IL-10 by Flow Cytometric Bead Array assay(CBA)and the results expressed in pg/ml.The baseline survey started in January 1st 1997,with 1284 participants of an aged population-based cohort.Participants signed an informed consent at baseline and at each subsequent visit and authorized death certificate and medical records verification.Results:Our results demonstrated that Chagas disease patients had higher serum levels of CXCL9,CXCL10 and IL-1βand lower serum levels of CCL5 than non-infected subjects.Moreover,our data demonstrated that CXCL9 and CXCL10 increased in an age-dependent profile in Chagas disease patients.Conclusion:Together,this study provided evidences that serum biomarkers increase along the age continuum and may have potential implications for establishing clinical management protocols and therapeutic intervention in Chagas disease patients.展开更多
Background:Brazil has seen a great decline in malaria and the country is moving towards elimination.However,for eventual elimination,the control program needs efficient tools in order to monitor malaria exposure and t...Background:Brazil has seen a great decline in malaria and the country is moving towards elimination.However,for eventual elimination,the control program needs efficient tools in order to monitor malaria exposure and transmission.In this study,we aimed to evaluate whether seroprevalence to the circumsporozoite protein(CSP)is a good tool for monitoring the exposure to and/or evaluating the burden and distribution of Plasmodium species in the Brazilian Amazon.Methods:Cross-sectional surveys were conducted in a rural area of Porto Velho,Rondônia state.Parasite infection was detected by microscopy and polymerase chain reaction.Antibodies to the sporozoite CSP repeats of Plasmodium vivax,P.falciparum,and P.malariae(PvCS,PfCS,and PmCS)were detected using the enzyme-linked immunosorbent assay technique.Human leukocyte antigen(HLA)-DRB1 and DQB1 genes were typed using Luminex®xMAP®technology.Results:The prevalence of immunoglobulin G against P.vivax CSP peptide(62%)was higher than P.falciparum(49%)and P.malariae(46%)CSP peptide.Most of the studied individuals had antibodies to at least one of the three peptides(72%),34%had antibodies to all three peptides and 28%were non-responders.Although the majority of the population was not infected at the time of the survey,74.3%of parasite-negative individuals had antibodies to at least one of the CSPs.Importantly,among individuals carrying the haplotypes DRB1*04~DQB1*03,there was a significantly higher frequency of PfCS responders,and DRB1*16~DQB1*03 haplotype for PvCS and PfCS responders.In contrast,HLA-DRB1*01 and HLA-DQB1*05 allelic groups were associated with a lack of antibodies to P.vivax and P.falciparum CSP repeats,and the haplotype DRB1*01~DQB1*05 was also associated with non-responders,including non-responders to P.malariae.Conclusions:Our results show that in low transmission settings,naturally acquired antibody responses against the CSP repeats of P.vivax,P.falciparum,and P.malariae in a single cross-sectional study may not represent a valuable marker for monitoring recent malaria exposure,especially in an area with a high prevalence of P.vivax.Furthermore,HLA class II molecules play an important role in antibody response and require further study with a larger sample size.It will be of interest to consider HLA analysis when using serosurveillance to monitor malaria exposure among genetically diverse populations.展开更多
文摘The Zika virus(ZIKV),a member of the Flaviviridae family,attracted worldwide attention for its connection to severe neurological effects,notably microcephaly in newborns,first reported during the 2015 epidemic in Brazil.Yet,its impact goes beyond fetal and neonatal abnormalities,also affecting the central nervous system(CNS)in both children and adults,leading to enduring cognitive and behavioral impairments.
文摘The Pisolithus tinctorius symbiosis related protein expressed sequence tag (EST PtSRP) was previously identified in the first hours of the interaction between the fungus Pisolithus tinctorius and sweet chestnut Castanea sativa, and partially characterized as a fungal marker gene of ectomycorrhizal symbiosis formation. We used the 5’ rapid amplification of cDNA ends (RACE) to obtain the PtSRP mRNA 5’ region, and together with our previously reported 3’ mRNA region, the full mRNA sequence was assembled by use of bioinformatics tools and deposited to GenBank (Accession: GU733439). The full-length mRNA sequence (636 bp) revealed the locations of the 5’ and 3’ untranslated regions (UTRs) and contained the Kozak sequence (ccc aag ATG A) in the 5’ UTR. The in silico translated PtSRP open reading frame (ORF) codes for a 127 amino acid protein and contained four putative post-translational modification sites (two N-glycosylation and two phosphorylation). The protein secondary structure is postulated to be composed of one N-terminal hydrophobic transmembrane alpha helix and at least six hydrophilic beta-strands spread across the protein. Sub-cellular localization prediction suggests that the protein is involved in cellular secretory pathway, supported by the presence of a cleavage site motif close to the membrane anchor. The data presented herein indicate the role of PtSRP as a fungal membrane secreted protein involved in early stages of ectomycorrhizal formation, with application as a possible marker for nascent ectomy-corrhiza fungal development.
基金supported by the Xtreme Bio(PTDC/MAR-EST/4346/2012)Ma Na Cruzi projects(bilateral project,FCT/CAPES 2358,2014/2015)+3 种基金funded by FCT–Foundation for Science and Technology and Portuguese National Budgetit also received national funds through FCT project CCMAR/Multi/04326/2013 and P3DPrograma de Descoberta e Desenvolvimento de Drogas(PROEP/CNPq/FIOCRUZ 401988/2012-0)supported by FCT Investigator Programme(IF/00049/2012)Policarpo Sales by Programa Brasil Sem Miséria/Coordenacao de Aperfeicoamento de Pessoal de Ensino Superior(CAPES)/FIOCRUZ
文摘Objective:To evaluate the in vitro anti-Trypanosoma cruzi（T.cruzi） activity of organic extracts prepared from halophyte species collected in the southern coast of Portugal（Algarve）,and chemically characterize the most active samples.Methods:Acetone,dichloromethane and methanol extracts were prepared from 31 halophyte species and tested in vitro against trypomastigotes and intracellular amastigotes of the Tulahuen strain of T.cruzi.The most active extract was fractionated by preparative HPLC-DAD,affording 11 fractions.The most selective fraction was fully characterized by 1H-NMR.Results:From 94 samples tested,one was active,namely the root dichloromethane extract of Juncus acutus(IC50 < 20 μg/mL).This extract was fractionated by HPLC,affording 11 fractions,one of them containing only a pure compound（juncunol）,and tested for anti-parasitic activity.Fraction 8(IC50 = 4.1 μg/mL) was the most active,and was further characterized by 1H-NMR.The major compounds were phenanthrenes,9,10-dihydrophenanthrenes and benzocoumarins.Conclusion:Our results suggest that the compounds identified in fraction 8 are likely responsible for the observed anti parasitic activity.Further research is in progress aiming to isolate and identify the specific active molecules.To the best of our knowledge,this is the first report on the in vitro anti T.cruzi activity of halophyte species.
文摘Various mouse models to study dengue have been described by different authors, some of them using immunodeficient or some using humanized mice. Our group reported previously a deadly murine model, which used the intracranial inoculum of highly virulent Dengue virus (DENV) in immune competent mouse. Here we present a model of immune competent mouse (C57BL/6), infected subcutaneously by the same highly virulent DENV (DENV3 genotype I). In this immunocompetent systemic mice model, the cytokine levels and hematological parameters such as total and differential leukocyte and platelets counts, together with weight loss, were considered important monitoring parameters, allowing a better understanding of the systemic human disease. Mice were inoculated subcutaneously and evaluated by the percentage weight variation as well as the clinical signs. Hematological parameters and cytokines levels were measured and viral titration in brain tissue or serum neutralization was performed to confirm mice infection. The subcutaneously DENV inoculated mice showed weight loss after infection, but they did not show any other clinical signs. The leukocytes and platelets decreased after subcutaneous inoculation. The cytokines TNF alpha and IFN gamma increased after infection in mice. The subcutaneous model provided scope for improved understanding of the dengue pathogenesis, as well as possible mechanism for protection to subsequent mouse infected by intracranial route in mice. This model could be used to study the vertebrate immune response and evaluation of drugs or vaccine against dengue virus.
文摘This study examines the relationship between geomagnetic indices and mortality rates from specific diseases in the Northeast (NE) and Southern (S) regions of Brazil from 1996 to 2020. Solar activity data, including the Ap and Sudden Ionospheric Disturbance (SID) indices, were sourced from the World Data Center, while mortality data were obtained from the Mortality Information System (SIM-DATASUS). Acute Myocardial Infarction (AMI) emerged as the leading cause of mortality, with average death rates of 60.4, 56.8, and 58.3 deaths per 100,000 inhabitants in Pernambuco (PE), Rio Grande do Sul (RS), and Paraná (PR), respectively. Temporal analysis revealed a consistent upward trend in AMI mortality across most states, except for Santa Catarina (SC). Seasonal patterns identified through Principal Component Analysis (PCA) demonstrated that geomagnetic and climatic indices influenced mortality differently across regions and seasons. The Ap geomagnetic index was strongly correlated with higher AMI mortality rates during summer, while the SID index showed greater relevance during winter. A dipole phenomenon was observed, with AMI deaths increasing alongside geomagnetic activity in the S region but showing an inverse relationship in the NE region. These findings highlight the significant influence of geomagnetic variations on public health, particularly cardiovascular mortality. The study underscores the need for further research into the biological mechanisms underlying these associations and recommends the development of early warning systems and targeted preventive measures to mitigate the potential health impacts of geomagnetic disturbances, especially for vulnerable populations.
文摘In Brazil,Biomphalaria glabrata,B.tenagophila,and B.straminea are naturally infected by the trematode Schistosoma mansoni,the causative agent of schistosomiasis.Despite decades of governmental efforts through official control programs,schistosomiasis remains an important public health problem in the country:thousands of people are infected with the trematode each year and millions live in endemic areas.The World Health Organization recommends using a combination of molluscicide(niclosamide)and mass chemotherapy to control the transmission of schistosomiasis,with this treatment successfully reducing the morbidity of the disease.In the past,niclosamide has been used in official schistosomiasis control programs in Brazil.However,as B.glabrata recolonizes even after molluscicide application,the use of molluscicides has gradually decreased in the country until they were discontinued in 2002,mainly due to the rising global pressure to preserve the environment and the difficulties of obtaining licenses from the Brazilian Ministry of Environment to use toxic substances in aquatic ecosystems.Therefore,the discovery of new molluscicides,which could be more selective to Biomphalaria species and less harmful to the aquatic ecosystem,is necessary.In addition,political efforts to sensitize funders to provide grants for this field of research are required.In this context,this article aims to make a critical analysis of molluscicide application in schistosomiasis control programs in Brazil.
基金This study received financial support from the Conselho de Desenvolvimento Tecnológico e Científico/CNPq/BRAZIL,DECIT 2008,DECIT 2012,FAPEMIG,TC 304/2013/FNS/MS and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior(CAPES).OAMF received PQ fellowships from CNPq.These fundings sources had no role in the design of the study and collection,analysis,implementation,and interpretation of data and in writing the manuscript.
文摘Background: Leprosy is a chronic infectious disease classified into two subgroups for therapeutic purposes:paucibacillary(PB)and multibacillary(MB),closely related to the host immune responses.In this context it is noteworthy looking for immunological biomarkers applicable as complementary diagnostic tools as well as a laboratorial strategy to follow-up leprosy household contacts.Methods:: The cross-sectional study enrolled 49 participants,including 19 patients and 30 healthy controls.Peripheral blood mononuclear cells(PBMC)were isolated and incubated in the presence of Mycobacterium leprae bacilli.The cells were prepared for surface(CD4+and CD8+)and intracytoplasmic cytokine staining(IFN-γ,IL-4 and IL-10).Multiple comparisons amongst groups were carried out by ANOVA,Kruskal–Wallis,Student T or Mann–Whitney test.Comparative analysis of categorical variables was performed by Chi-square.Functional biomarker signature analysis was conducted using the global median values for each biomarker index as the cut-off edge to identify the proportion of subjects with high biomarker levels.Results: The cytokine signature analysis demonstrated that leprosy patients presented a polyfunctional profile of T-cells subsets,with increased frequency of IFN-γ+T-cell subsets along with IL-10+and IL-4+from CD4+T-cells,as compared to health Controls(Venn diagram report).Moreover,statistical analysis was carried out using parametric or non-parametric variance analysis followed by pairwise multiple comparisons,according to the data normality distribution.L(PB)displayed a polyfunctional profile characterized by enhanced percentage of IFN-γ+,IL-10+and IL-4+produced by most T-cell subsets,as compared to L(MB)that presented a more restricted cytokine functional profile mediated by IL-10+and IL-4+T-cells with minor contribution of IFN-γproduced by CD4+T-cells.Noteworthy was that HHC(MB)exhibited enhanced frequency of IFN-γ+T-cells,contrasting with HHC(PB)that presented a cytokine profile limited to IL-10 and IL-4.Conclusions: Our data demonstrated that L(PB)displayed enhanced percentage of IFN-γ+,IL-10+and IL-4+as compared to L(MB)that presented functional profile mediated by IL-10+and IL-4+T-cells and HHC(MB)exhibited enhanced frequency of IFN-γ+T-cells,contrasting with HHC(PB).Together,our findings provide additional immunological features associated with leprosy and household contacts.These data provide evidence that biomarkers of immune response can be useful complementary diagnostic/prognostic tools as well as insights that household contacts should be monitored to access putative subclinical infection.
基金This work was supported by the National Key Research and Development Program of China(No.2016YFC1202001)Research Fund for the Technical Reserves,National Institute of Parasitic Diseases,Chinese CDC(No.CB-1603)+1 种基金Mohamed R.Habib was supported by a Post-doctoral Programme from the Ministry of Science and Technology of China and National Center for International Research on Tropical Diseases(Shanghai,China)Roberta L.Caldeira is supported by a fellowship from Conselho Nacional de Desenvolvimento Científico e Tecnologico/CNPq(No.304121/2014–2).
文摘Background:Schistosomiasis is a common parasitic disease designated as a neglected tropical disease by the World Health Organization.Schistosomiasis mansoni is a form of the disease that is caused by the digenean trematode Schistosoma mansoni,transmitted through Biomphalaria spp.as an intermediate host.Biomphalaria was introduced to Hong Kong,China in aquatic plants shipments coming from Brazil and the snail rapidly established its habitats in southern China.Earlier studies of Biomphalaria spp.introduced to southern China identified the snails as Biomphalaria straminea,one of the susceptible species implicated in S.mansoni transmission in South America.However,recent molecular investigations also indicated the presence of another South American species,B.kuhniana,which is refractory to infection.As such,it is important to identify accurately the species currently distributed in southern China,especially with emerging reports of active S.mansoni infections in Chinese workers returning from Africa.Methods:We combined morphological and molecular taxonomy tools to precisely identify Biomphalaria spp.distributed in Guangdong Province,southern China.In order to clearly understand the molecular profile of the species,we constructed a phylogeny using mtDNA data(COI and 16S rRNA sequences)from six populations of Biomphalaria spp.from Shenzhen City in Guangdong Province.In addition,we examined the external morphology of the shell and internal anatomy of the reproductive organs.Results:Both morphological and molecular evidences indicated a close affinity between Biomphalaria spp.populations from Guangdong and B.straminea from Brazil.The shell morphology was roughly identical in all the populations collected with rounded whorls on one side and subangulated on the other,a smooth periphery,an egg-shaped aperture bowed to one side,and a deep umbilicus.The shape and number of prostate diverticula(ranged from 11.67 to 17.67)in Guangdong populations supports its close affinity to B.straminea rather than B.kuhniana.Molecular analysis did not conflict with morphological analysis.Little genetic differentiation was observed within Biomphalaria populations collected.Phylogenetic analysis of COI and 16S rRNA haplotypes from snails collected and B.straminea sequences from Brazil and China using Bayesian inference revealed that Guangdong populations were clustered in one clade with B.straminea from Hong Kong of China and B.straminea from Brazil indicating their close affinity to each other.Conclusions:Data obtained in the current study clearly show that the populations of Biomphalaria spp.investigated are B.straminea,and we assume that those snails were either introduced via passive dispersal from Hong Kong of China or as a result of multiple introduction routes from Brazil.
文摘Background:Chagas disease is endemic in Latin America and still represents an important public health problem in the region.Chronic cardiomyopathy is the most significant chronic form due to its association with morbidity and mortality.The last decade has seen increasing evidence that inflammatory cytokines and chemokines are responsible for the generation of inflammatory infiltrate and tissue damage,with chronic chagasic cardiomyopathy patients presenting a pro-inflammatory immune response.Although studies have evaluated the role of chemokines in experimental T.cruzi infection,few have addressed their systemic profile,especially for human infection and in aging populations.The present work aimed to use the data from a large population based study of older adults,conducted in an endemic area for Chagas disease,to examine the association between serum levels of cytokines and chemokines,T.cruzi infection and electrocardiogram(ECG)abnormality.Methods:The present work evaluated serum levels of CCL2,CXCL9,CXCL10,CCL5,CXCL8,IL-1β,IL-6,TNF,IL-12 and IL-10 by Flow Cytometric Bead Array assay(CBA)and the results expressed in pg/ml.The baseline survey started in January 1st 1997,with 1284 participants of an aged population-based cohort.Participants signed an informed consent at baseline and at each subsequent visit and authorized death certificate and medical records verification.Results:Our results demonstrated that Chagas disease patients had higher serum levels of CXCL9,CXCL10 and IL-1βand lower serum levels of CCL5 than non-infected subjects.Moreover,our data demonstrated that CXCL9 and CXCL10 increased in an age-dependent profile in Chagas disease patients.Conclusion:Together,this study provided evidences that serum biomarkers increase along the age continuum and may have potential implications for establishing clinical management protocols and therapeutic intervention in Chagas disease patients.
基金This work was supported by grants from PRONEX Rede Malaria,Conselho Nacional de Pesquisa e Tecnologia(CNPq)(5555659/2009-7)Funda cao de AmparoàPesquisa do Rio de Janeiro(E-26/170.003/2010)+2 种基金JO-F is a recipient of research productivity fellowships from the CNPq(307659/2016-0)VAP is the recipient of a CNPq fellowship(142104/2014-0)The funders had no role in the study design,data collection and analysis,decision to publish,or preparation of the paper.
文摘Background:Brazil has seen a great decline in malaria and the country is moving towards elimination.However,for eventual elimination,the control program needs efficient tools in order to monitor malaria exposure and transmission.In this study,we aimed to evaluate whether seroprevalence to the circumsporozoite protein(CSP)is a good tool for monitoring the exposure to and/or evaluating the burden and distribution of Plasmodium species in the Brazilian Amazon.Methods:Cross-sectional surveys were conducted in a rural area of Porto Velho,Rondônia state.Parasite infection was detected by microscopy and polymerase chain reaction.Antibodies to the sporozoite CSP repeats of Plasmodium vivax,P.falciparum,and P.malariae(PvCS,PfCS,and PmCS)were detected using the enzyme-linked immunosorbent assay technique.Human leukocyte antigen(HLA)-DRB1 and DQB1 genes were typed using Luminex®xMAP®technology.Results:The prevalence of immunoglobulin G against P.vivax CSP peptide(62%)was higher than P.falciparum(49%)and P.malariae(46%)CSP peptide.Most of the studied individuals had antibodies to at least one of the three peptides(72%),34%had antibodies to all three peptides and 28%were non-responders.Although the majority of the population was not infected at the time of the survey,74.3%of parasite-negative individuals had antibodies to at least one of the CSPs.Importantly,among individuals carrying the haplotypes DRB1*04~DQB1*03,there was a significantly higher frequency of PfCS responders,and DRB1*16~DQB1*03 haplotype for PvCS and PfCS responders.In contrast,HLA-DRB1*01 and HLA-DQB1*05 allelic groups were associated with a lack of antibodies to P.vivax and P.falciparum CSP repeats,and the haplotype DRB1*01~DQB1*05 was also associated with non-responders,including non-responders to P.malariae.Conclusions:Our results show that in low transmission settings,naturally acquired antibody responses against the CSP repeats of P.vivax,P.falciparum,and P.malariae in a single cross-sectional study may not represent a valuable marker for monitoring recent malaria exposure,especially in an area with a high prevalence of P.vivax.Furthermore,HLA class II molecules play an important role in antibody response and require further study with a larger sample size.It will be of interest to consider HLA analysis when using serosurveillance to monitor malaria exposure among genetically diverse populations.
