American trypanosomiasis,commonly known as Chagas disease,is caused by the flagellate protozoan parasite Trypanosoma cruzi.An estimated eight million people infected with T.cruzi currently reside in the endemic region...American trypanosomiasis,commonly known as Chagas disease,is caused by the flagellate protozoan parasite Trypanosoma cruzi.An estimated eight million people infected with T.cruzi currently reside in the endemic regions of Latin America.However,as the disease has now been imported into many non-endemic countries outside of Latin America,it has become a global health issue.We reviewed the transmission patterns and current status of disease spread pertaining to American trypanosomiasis at the global level,as well as recent advances in research.Based on an analysis of the gaps in American trypanosomiasis control,we put forward future research priorities that must be implemented to stop the global spread of the disease.展开更多
Background:Two health concerns primarily related to triatomine bugs are transmission of Trypanosoma cruzi through infective feces,and allergic reactions induced by triatomine bites.In the Southwestern United States,re...Background:Two health concerns primarily related to triatomine bugs are transmission of Trypanosoma cruzi through infective feces,and allergic reactions induced by triatomine bites.In the Southwestern United States,reduviid bugs bites commonly cause insect allergy.In South China,four cases of anaphylactic shock have been reported after this bite exposure.To further classify the species of these bugs and confirm the sensitization of the triatomine saliva,we caught triatomine bugs from the region where the bites occurred and performed phylogenetic and immunohistochemical(IHC)analysis.Methods:Triatomine bugs were collected in Donghai Island of Zhanjiang City in South China.The genomic DNA was extracted from three legs of the bugs.The fragments of mitochondrial 16S rRNA,cytochrome c oxidase subunit I(COI)gene and nuclear ribosomal 18S and 28S rRNA genes were obtained by PCR and sequenced.A phylogenetic tree was constructed based on the sequence of 16S rRNA gene using a maximum likelihood method with MEGA 7.0 software.Trypanosomal specific fragments and vertebrate COI genes were amplified from the fecal DNA to detect the infection of trypanosomes and analyze the blood feeding patterns,respectively.Paraffin-embedded sections were then prepared from adult triatomines and sent for IHC staining.Results:We collected two adult triatomine bugs in Donghai Island.Morphological and molecular analyses indicated that the triatomines were Triatoma rubrofasciata.No fragments of T.cruzi or other trypanosomes were detected from the fecal DNA.Mitochondrial gene segments of Homo sapiens and Mus musculus were successfully amplified.The allergens which induced specific IgE antibodies in human serum were localized in the triatomine saliva by IHC assay.Conclusions:The two triatomine bugs from Donghai Island were T.rubrofasciata.They had bitten humans and mice.Their saliva should contain the allergens related to the allergic symptoms and even anaphylactic shock of exposed residents.Great consideration should be given to this triatomine bugs展开更多
Trypanosoma cruzi is the etiologic agent of Chagas disease.This flagellated protozoan is transmitted to humans as well as different species of domestic and wild animals via vectors from the Reduviidae family(known as&...Trypanosoma cruzi is the etiologic agent of Chagas disease.This flagellated protozoan is transmitted to humans as well as different species of domestic and wild animals via vectors from the Reduviidae family(known as"kissing bugs").Despite the fact that hundreds of species of wild mammals are part of the reservoir system,the morphologi-cal changes and clinical manifestations resulting from the pathogenesis of the infection have been largely neglected.The aim of this review is to systematically compile the available information regarding clinicopathological altera-tions in wild mammals due to natural infection by T.cruzi.Information was obtained from six online bibliographic data search platforms,resulting in the identification of 29 publications that met the inclusion criteria.Mortality was the most common clinical manifestation,cardiac damage was the main finding at necropsy,and lymphoplas-macytic inflammation was the most frequent microscopic injury.Thus,regardless of its role as a reservoir,T.cruzi has the potential to affect the health status of wild mammals,a situation that highlights the need for further research to analyze,measure,and compare its effects at both the individual and population levels.展开更多
Trypanosoma cruzi(T. cruzi), the etiological agent of Chagas disease, affects nearly 18 million people in Latin America and 90 million are at risk of infection. The parasite presents two stages of medical importance i...Trypanosoma cruzi(T. cruzi), the etiological agent of Chagas disease, affects nearly 18 million people in Latin America and 90 million are at risk of infection. The parasite presents two stages of medical importance in the host, the amastigote, intracellular replicating form, and the extracellular trypomastigote, the infective form. Thus infection by T. cruzi induces a complex immune response that involves effectors and regulatory mechanisms. That is why control of the infection requires a strong humoral and cellular immune response; hence, the outcome of host-parasite interaction in the early stages of infection is extremely important. A critical event during this period of the infection is innate immune response, in which the macrophage's role is vital. Thus, after being phagocytized, the parasite is able to develop intracellularly; however, during later periods, these cells induce its elimination by means of toxic metabolites. In turn, as the infection progresses, adaptive immune response mechanisms are triggered through the TH1 and TH2 responses. Finally, T. cruzi, like other protozoa such as Leishmania and Toxoplasma, have numerous evasive mechanisms to the immune response that make it possible to spread around the host. In our Laboratory we have developed a vaccination model in mice with Trypanosoma rangeli, nonpathogenic to humans, which modulates the immune response to infection by T. cruzi, thus protecting them. Vaccinated animals showed an important innate response(modulation of NO and other metabolites, cytokines, activation of macrophages), a strong adaptive cellular response and significant increase in specific antibodies. The modulation caused early elimination of the parasites, low parasitaemia, the absence of histological lesions and high survival rates. Even though progress has been made in the knowledge of some of these mechanisms, new studies must be conducted which could target further prophylactic and therapeutic trials against T. cruzi infection.展开更多
Chagas disease cardiomyopathy(CCC), the main consequence of Trypanosoma cruzi(T.cruzi) infection, is an inflammatory cardiomyopathy that develops in up to 30% of infected individuals. The heart inflammation in CCC pat...Chagas disease cardiomyopathy(CCC), the main consequence of Trypanosoma cruzi(T.cruzi) infection, is an inflammatory cardiomyopathy that develops in up to 30% of infected individuals. The heart inflammation in CCC patients is characterized by a Th1 T cell-rich myocarditis with increased production of interferon(IFN)-γ, produced by the CCC myocardial infiltrate and detected at high levels in the periphery. IFN-γ has a central role in the cardiomyocyte signaling during both acute and chronic phases of T.cruzi infection. In this review, we have chosen to focus in its pleiotropic mode of action during CCC, which may ultimately be the strongest driver towards pathological remodeling and heart failure. We describe here the antiparasitic protective and pathogenic dual role of IFN-γ in Chagas disease.展开更多
Objective:Aqueous extracts of Zapoteca portoricensis are used traditionally as antidiarrhea agent and in the treatment of diverse gastrointestinal disorders here in Nigeria specifically,the southern part.Similarly,the...Objective:Aqueous extracts of Zapoteca portoricensis are used traditionally as antidiarrhea agent and in the treatment of diverse gastrointestinal disorders here in Nigeria specifically,the southern part.Similarly,the aqueous extract of the plant is also used traditionally as anticonvulsant,antispasmodic and in the treatment of tonsillitis.Recently too,the anti-inflammatory and antimicrobial activities of the methanol extracts of the root of Zapoteca portoricensis was reported.In this research,we are set to investigate the trypanocidal activity of Zapoteca portoricensis.Methods:The methanol extract of the root of Zapoteca portoricensis was investigated for both in vitro and in vivo trypanocidal activity following established models.In summary,phytochemical analysis was carried out on both the crude powdered root and on the methanol extract following standard procedures. The oral acute toxicity test(LD<sub>50</sub> ) of the crude methanol extract was determined according to the method described by Lorke（1983）.Albino mice（17g-21g） of either sex were used.The methanol extract was suspended in 3%v/v tween 85 and administered orally at doses of 10 mg/kg,100 mg/kg and 1 000 mg/kg to three groups of mice（n = 3 ）.The animals were observed for 24 hours.Based on the result obtained in this initial test,doses of 4 mg/kg,6 mg/kg,and 8 mg/kg were administered to three different mice.The LD<sub>50</sub> was calculated as the geometric mean of the lowest dose killing a mouse and the highest dose showing no death.The invivo /in-vitro antitrypanosomal evaluations were carried out in experimental animals and tissue cell culture respectively. Results:The result of the in vitro studies shows the inhibitive concentration-50（IC-50） against Trypanosoma brucei rhodesiense（T.b.rhodesiense） to be 0.372 mg/kg,while the control drug melarsoprol was 0.006 mg/kg.On Trypanosoma brucei brucei（T.cruzi）,the IC-50 is 6.42 mg/kg against 0.87 of the reference drug Benznidazole.The cytotoxicity on L-6 cells exhibited an IC-50 展开更多
Understanding the biological parameters of some triatomine subspecies of Meccus phyllosomus （Burmeister） is a crucial first step in estimating the epidemiologie importance of this group. Biological parameters relate...Understanding the biological parameters of some triatomine subspecies of Meccus phyllosomus （Burmeister） is a crucial first step in estimating the epidemiologie importance of this group. Biological parameters related to hatching, lifetime, number of blood meals to molt, percentage of females at the end of the cycle, number of laid eggs, and mortality for each instar of 3 M. phyllosomus subspecies [M. p. mazzottii （Usinger）, M. p. pallidipennis （Stal）, and M. p. phyllosomus] and their laboratory hybrids were evaluated and compared. No significant differences （P 〉 0.05） were found among the experimental hybrids （MaPa, MaPhy, PaPhy） and reciprocal cohorts. In 5 （hatching, number of blood meals to molt, accumulative mortality, percentage of females, and mean number of laid eggs） of the 6 studied parameters （with the exception of development time）, the hybrid cohorts had better fitness results than the parental cohorts involved in each set of crosses. The increase in hybrid fitness found in our study could lead to an increase in the epidemiologic risks caused by transmission of Trypanosoma cruzi to humans.展开更多
Almost 110 years after the first studies by Dr. Carlos Chagas describing an infectious disease that was named for him, Chagas disease remains a neglected illness and a death sentence for infected people in poor countr...Almost 110 years after the first studies by Dr. Carlos Chagas describing an infectious disease that was named for him, Chagas disease remains a neglected illness and a death sentence for infected people in poor countries. This short review highlights the enormous need for new studies aimed at the development of novel and more specific drugs to treat chagasic patients. The primary tool for facing this challenge is deep knowledge about the similarities and differences between the parasite and its human host.展开更多
In Brazil and several other Latin American countries, Chagas' disease still constitutes a serious medical and social problem, and there is a need to develop new, more-potent drugs with fewer side effects to effect...In Brazil and several other Latin American countries, Chagas' disease still constitutes a serious medical and social problem, and there is a need to develop new, more-potent drugs with fewer side effects to effectively treat this disease. We investigated the antitrypanosomal effect of a crude extract, fractions, and a semi-purified subfraction rich in a mix- ture of isomeric labdane sesquiterpenes, obtained from flowers of Anthemis tinctoria, against Trypanosoma cruzi. In epimastigote forms, the aqueous crude extract, dichloromethane fraction, and semi-purified subfraction showed a dose-dependent inhibitory activity, with IC50 of 2.3 μg/ml, 1.8 μg/ml, and 0.2 μg/ml, respectively. In the interaction in- dex, the semi-purified subfraction showed a reduction in both the percentage of infected LLCMK2 cells and the mean number of amastigotes per infected cell. The cytotoxicity evaluation demonstrated that the cytotoxic concentrations of the semi-purified subfraction were higher for LLCMK2 cells than for the protozoans, with a selectivity index of 35.0. Epimastigote forms treated with the semi-purified subfraction showed ultrastructural and morphological alterations such as rounding of the cells and bleb formation in the flagellum and cytoplasmic membrane. These results show that the flowers from A. tinctoria may be a source of new drugs with antiprotozoal activity. However, additional in vitro and in vivo studies are needed to validate the use of A. tinctoria in the treatment of Chagas’ disease.展开更多
American trypanosomiasis is a zoonosis of worldwide medical importance and currently there is no effective treatment in chronic patients, hence the importance of the study of protein function of the parasite with the ...American trypanosomiasis is a zoonosis of worldwide medical importance and currently there is no effective treatment in chronic patients, hence the importance of the study of protein function of the parasite with the objective of finding new drug targets and to know better the biology of the agent causal (Trypano-soma cruzi). T. cruzi is an RNAi-negative parasite, therefore the silencing genes strategies by RNAi is not possible;for that reason, antibodies may be taken as a tool for studying the parasite proteins function by blocking these molecules with specific antibodies. The aim of this work was to establish a methodology for antibody delivery (antibody transfection) into viable parasites. We used anti-cyclin-A antibody (human origin) in western blot assay with epimastigote of T. cruzi proteins and this recognized a ~55 kDa polypeptide. Several methods for antibody transfection (electroporation, saponin permeabilization and a lipid-based formulation) were tested. The first two methods were unsuccessful. In electroporation was impossible to visualize the antibody inside parasites and with saponin permeabilization, antibodies were successfully introduced, but with loss of parasites viability. The lipid-based formulation method forms noncovalent complexes with antibodies. These complexes are internalized by cells and antibodies are released into the cytoplasm. With this method, a successful antibody delivery was achieved. Anti-cyclin antibodies were visualized in the cytoplasm from fixed transfected parasites (immunofluorescence assays). At 24 h post-transfection, parasites maintained their viability (90%) and were able to arrest the cell cycle in G0/G1-phase of cultured epimastigotes (cell population increased in G0/G1-phase from 50.5% to 66.2% and decreased in S-phase from 47.2% to 26%). It was also observed that anti-cyclin-A antibodies inhibit the parasite population doubling (p T. cruzi, with a simple and cheap technique, which will allows carrying out further studies of this protozoan.展开更多
Objective:To investigate the bioecological relationship between Chagas disease peridomestic vectors and reptiles as source of feeding.Methods:In a three-story building,triatomines were captured by direct search and el...Objective:To investigate the bioecological relationship between Chagas disease peridomestic vectors and reptiles as source of feeding.Methods:In a three-story building,triatomines were captured by direct search and electric vacuum cleaner search in and outside the building.Then,age structure of the captured Triatoma maculata(T.maculata) were identified and recorded.Reptiles living in sympatric with the triatomines were also searched.Results:T.maculata were found living sympatric with geckos(Thecadactylus rapicauda) and they bit residents of the apartment building in study.A total of 1 448 individuals of T.maculata were captured within three days,of which 74.2%(1 074 eggs) were eggs,21.5%were nymphs at different stages,and 4.3%were adults.Conclusions:The association of T.maculata and T.rapicauda is an effective strategy of colonizing dwellings located in the vicinity of the habitat where both species are present;and therefore,could have implications of high importance in the intradomiciliary transmission of Chagas disease.展开更多
Objective:To identify whether Canova medication changes TNF-α and IL-10 serum levels in mice infected with Trypanosoma cruzi Y strain.Methods:Animals were divided into five groups:non-treated infected animals(I); ben...Objective:To identify whether Canova medication changes TNF-α and IL-10 serum levels in mice infected with Trypanosoma cruzi Y strain.Methods:Animals were divided into five groups:non-treated infected animals(I); benznidazole-treated infected animals(Bz; 100 mg/kg body weight,single daily dose by gavage); Canova medication(CM) treated infected animals(CM;0.2 mL/animal,single daily dose by gavage); benznidazole- and Canova medication–treated infected animals with the above-mentioned dose(Bz+CM);and non-infected animals(C).TNF-α and IL-10 levels were determined in serum aliquots after 4,7,10,13,and 29 days of infection.An ELISA technique was employed with R&D System Inc.antibody pairs.Results:A high increase in TNF-α and IL-10 levels occurred in the infected and CM-treated groups within the treatment employed on the 10 th day after infection,coupled with a IL-10 decrease on the 13 th day after infection when compared with the other experimental groups.Conclusions:CM may change the balance between plasma cytokine levels(TNF-α and IL-10) in mice infected with Y strain T.cruzi,with important consequences leading towards a more severe infection.展开更多
Substituted 2-benzylidene-1-benzofuran-3-ones are commonly known as aurones. This class of bioactive heterocycles belongs to flavonoid family. The article intends to put forth the rational design and synthesis of a ne...Substituted 2-benzylidene-1-benzofuran-3-ones are commonly known as aurones. This class of bioactive heterocycles belongs to flavonoid family. The article intends to put forth the rational design and synthesis of a new series of aurones using 3’,5’-dibromo-2’,4’-dihydroxychalcones and copper bromide in presence of DMF-water mixture (8:2, v/v) for the first time. Preliminary bioassay shows that most of compounds have good trypanocidal activity against Trypanosoma cruzi at 10 μg/mL. Few compounds are equally potent to the standard drugs Benznidazole and Nifurtimox. The structures of the newly synthesized products 2a-n were established by elemental analysis, FTIR, 1H NMR, 13C NMR and mass spectroscopic studies.展开更多
A series of N1-substituted-3-aryl-4-alkyl-4, 5-dihydro-1H-1-pyrazolethiocarboxamide were prepared from the Mannich bases of aryl ketones in good yields. Some derivatives were found to be active against the cysteine p...A series of N1-substituted-3-aryl-4-alkyl-4, 5-dihydro-1H-1-pyrazolethiocarboxamide were prepared from the Mannich bases of aryl ketones in good yields. Some derivatives were found to be active against the cysteine protease of T.cruzi..展开更多
With the objective to describe the relationship between T. cruzi infection in humans and sinantropic reservoir and vectors in the rural conditions a study was performed in municipalities of the Yucatan state in Mexico...With the objective to describe the relationship between T. cruzi infection in humans and sinantropic reservoir and vectors in the rural conditions a study was performed in municipalities of the Yucatan state in Mexico. Blood samples from humans, dogs and opossum were taken from the households. Vectors were also collected and the infection and infestation indexes were calculated. Serum samples were evaluated by indirect hemagglutination (IH) and indirect immunofluorescence (IFI) to determine IgG antibodies against Trypanosoma cruzi. The polymerase chain reaction (PCR) was also performed in the samples taken from humans and reservoirs. Blood smears were performed in reservoirs. Sampled humans underwent to an electrocardiographic study to identify functional and conduction alterations of the heart. Household building characteristics were noted. A total of 367 blood samples were collected from people. The presence of IgG antibodies was 16.6% and 71.0% at PCR. Electrocardiographic studies revealed that 31% of patients seropositive to T. cruzi have a medical condition. 20.0% of dogs were seropositive and 68.5 positive to PCR. At the direct detection 13.6% resulted positive. In opossum 29.1% were seropositive and 72.9% positive to PCR. A total of 269 triatomineos were captured and 52.7% were infected with T. cruzi. The infection and infestation index were 52.4% and 60.8% respectively. The presence of adult vectors and their nymph’s were more frequently found in households made with wattle roofs (45.2 and 73.9 % respectively) than other kind of building materials. Electrocardiographic abnormalities found in positive persons were: Incomplete right bundle branch block (55%), tachycardia (35%), old myocardial infarction (5%) and incomplete block of the left bundle (5%). This work highlights the importance of comprehensive studies on the transmission of T. cruzi in the Yucatan where the link between human infection in synanthropic reservoirs and vectors is established. This information is important to design programs for t展开更多
Objective:To classify 21 new isolates of Trypanosoma cruai(T.cruzi) according to the Discrete Typing Unit(DTU) which they belong to,as well as tune up a new pair of primers designed to detect the parasite in biologica...Objective:To classify 21 new isolates of Trypanosoma cruai(T.cruzi) according to the Discrete Typing Unit(DTU) which they belong to,as well as tune up a new pair of primers designed to detect the parasite in biological samples.Methods:Strains were isolated,DNA extracted,and classified by using three Polymerase Chain Reactions(PCR).Subsequently this DNA was used along with other isolates of various biological samples,for a new PCR using primers designed.Finally,the amplified fragments were sequenced.Results:It was observed the predominance of DTU i in Colombia,as well as the specificity of our primers for detection of T.cruzi,while no band was obtained when other species were used.Conclusions:This work reveals the genetic variability of 21 new isolates of T.cruzi in Colombia.Our primers confirmed their specificity for detecting the presence of T.cruzi.展开更多
Objective:To evaluate parasitemia by qPCR in patients undergoing etiological treatment and followed in a Brazilian reference center.Methods:Parasite load was quantified by qPCR in 32 participants with chronic Chagas d...Objective:To evaluate parasitemia by qPCR in patients undergoing etiological treatment and followed in a Brazilian reference center.Methods:Parasite load was quantified by qPCR in 32 participants with chronic Chagas disease who were treated with benznidazole.Serological analyses were performed before and after the treatment and parasite loads were compared prior and 12/18 months post the treatment.Results:Thirty-two participants were recruited and treated with benznidazole,and 20 were followed-up.Adverse events(AE)were observed in 22 out of 29 participants that had safety data(76%),and dermatological alterations were the most frequently observed AE.Of the 20 participants analyzed,13 and 7 completed 12 and 18 months follow-up after the treatment,respectively.12 Months after the final treatment,Trypanosoma cruzi was detectable in 3 patients by qPCR;18 months after the final treatment,Trypanosoma cruzi was detectable per qPCR in 4 of the 7 participants.Thus,between 12 and 18 months,7 participants of the 20 initial follow-up cases showed positive qPCR,indicating treatment failures.Conclusions:qPCR can be used as an alternative method for evaluating the effectiveness of the etiological treatment of CD,and can be applied to analyze early therapeutic failures.The study showed that benznidazole therapy had limited effectiveness in treating chronic CD patients,thus emphasizing the importance of conducting continued research for developing more effective therapies and diagnosis for CD.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
Background:Chagas disease is a parasitic disease endemic to Latin America,but it has become a disease of global concern due to migration fows.Asymptomatic carriers may host the parasite for years,without knowing they ...Background:Chagas disease is a parasitic disease endemic to Latin America,but it has become a disease of global concern due to migration fows.Asymptomatic carriers may host the parasite for years,without knowing they are infected.The aim of this study is to assess prevalence of Chagas disease and evaluate the participants’level of knowl‑edge between Latin American migrants attending a community-based screening campaign.Methods:Three community-based campaigns were performed in Alicante(Spain)in 2016,2017 and 2018,including educational chats and blood tests for Trypanosoma cruzi serology.Participants completed a questionnaire assessing knowledge about the mechanisms of transmission,disease presentation,diagnosis,and treatment.People seroposi‑tive for T.cruzi underwent diagnostic confrmation by two diferent tests.Results were analyzed by multivariable logistic regression and expressed as adjusted odds ratios(aORs),adjusting for age,sex,and time in Spain.Results:A total of 596 participants were included in the study;17%were aged under 18 years.Prevalence in adults was 11%[54/496;95%confdence interval(CI):8.3–14.5%]versus 0%among children.All but one case were in Bolivians.Diagnosis was independently associated with having been born in Bolivia(aOR:102,95%CI:13–781)and a primary school-level education(aOR:2.40,95%CI:1.14–5.06).Of 54 people diagnosed with Chagas disease(most of whom were asymptomatic),42(77.7%)returned to the clinic at least once,and 24(44.4%)received treatment.Multivariable analysis showed that coming from Argentina(aOR:13,95%CI:1.61–1188)or Bolivia(aOR:1.90,95%CI:1.19–3.39)and having received information about Chagas disease in Spain(aOR:4.63,95%CI:2.54–8.97)were associ‑ated with a good level of knowledge on the disease.Having primary level studies(aOR:0.59,95%CI:0.34–0.98)and coming from Ecuador(aOR:4.63,95%CI:2.52–847)were independently associated with a lower level of knowledge.Conclusions:Community-based interventions are a good strategy for diagnosing neglected diseases su展开更多
基金This work was supported by the National S&T Major Programme(grant no.2012ZX10004220)Many thanks for Dr.Peiling Yap for her constructive comments on the manuscript.Many thanks also to Mr.Xue Jingbo and Mr.Shen Haimo for their help in drawing the figures.
文摘American trypanosomiasis,commonly known as Chagas disease,is caused by the flagellate protozoan parasite Trypanosoma cruzi.An estimated eight million people infected with T.cruzi currently reside in the endemic regions of Latin America.However,as the disease has now been imported into many non-endemic countries outside of Latin America,it has become a global health issue.We reviewed the transmission patterns and current status of disease spread pertaining to American trypanosomiasis at the global level,as well as recent advances in research.Based on an analysis of the gaps in American trypanosomiasis control,we put forward future research priorities that must be implemented to stop the global spread of the disease.
基金This work was supported by National Key Research and Development Program of China(No.2016YFC1202000,2016YFC1202001,and 2016YFC1200500)Shenzhen San-Ming Project for prevention and research on vector-borne diseases(SZSM201611064).
文摘Background:Two health concerns primarily related to triatomine bugs are transmission of Trypanosoma cruzi through infective feces,and allergic reactions induced by triatomine bites.In the Southwestern United States,reduviid bugs bites commonly cause insect allergy.In South China,four cases of anaphylactic shock have been reported after this bite exposure.To further classify the species of these bugs and confirm the sensitization of the triatomine saliva,we caught triatomine bugs from the region where the bites occurred and performed phylogenetic and immunohistochemical(IHC)analysis.Methods:Triatomine bugs were collected in Donghai Island of Zhanjiang City in South China.The genomic DNA was extracted from three legs of the bugs.The fragments of mitochondrial 16S rRNA,cytochrome c oxidase subunit I(COI)gene and nuclear ribosomal 18S and 28S rRNA genes were obtained by PCR and sequenced.A phylogenetic tree was constructed based on the sequence of 16S rRNA gene using a maximum likelihood method with MEGA 7.0 software.Trypanosomal specific fragments and vertebrate COI genes were amplified from the fecal DNA to detect the infection of trypanosomes and analyze the blood feeding patterns,respectively.Paraffin-embedded sections were then prepared from adult triatomines and sent for IHC staining.Results:We collected two adult triatomine bugs in Donghai Island.Morphological and molecular analyses indicated that the triatomines were Triatoma rubrofasciata.No fragments of T.cruzi or other trypanosomes were detected from the fecal DNA.Mitochondrial gene segments of Homo sapiens and Mus musculus were successfully amplified.The allergens which induced specific IgE antibodies in human serum were localized in the triatomine saliva by IHC assay.Conclusions:The two triatomine bugs from Donghai Island were T.rubrofasciata.They had bitten humans and mice.Their saliva should contain the allergens related to the allergic symptoms and even anaphylactic shock of exposed residents.Great consideration should be given to this triatomine bugs
文摘Trypanosoma cruzi is the etiologic agent of Chagas disease.This flagellated protozoan is transmitted to humans as well as different species of domestic and wild animals via vectors from the Reduviidae family(known as"kissing bugs").Despite the fact that hundreds of species of wild mammals are part of the reservoir system,the morphologi-cal changes and clinical manifestations resulting from the pathogenesis of the infection have been largely neglected.The aim of this review is to systematically compile the available information regarding clinicopathological altera-tions in wild mammals due to natural infection by T.cruzi.Information was obtained from six online bibliographic data search platforms,resulting in the identification of 29 publications that met the inclusion criteria.Mortality was the most common clinical manifestation,cardiac damage was the main finding at necropsy,and lymphoplas-macytic inflammation was the most frequent microscopic injury.Thus,regardless of its role as a reservoir,T.cruzi has the potential to affect the health status of wild mammals,a situation that highlights the need for further research to analyze,measure,and compare its effects at both the individual and population levels.
文摘Trypanosoma cruzi(T. cruzi), the etiological agent of Chagas disease, affects nearly 18 million people in Latin America and 90 million are at risk of infection. The parasite presents two stages of medical importance in the host, the amastigote, intracellular replicating form, and the extracellular trypomastigote, the infective form. Thus infection by T. cruzi induces a complex immune response that involves effectors and regulatory mechanisms. That is why control of the infection requires a strong humoral and cellular immune response; hence, the outcome of host-parasite interaction in the early stages of infection is extremely important. A critical event during this period of the infection is innate immune response, in which the macrophage's role is vital. Thus, after being phagocytized, the parasite is able to develop intracellularly; however, during later periods, these cells induce its elimination by means of toxic metabolites. In turn, as the infection progresses, adaptive immune response mechanisms are triggered through the TH1 and TH2 responses. Finally, T. cruzi, like other protozoa such as Leishmania and Toxoplasma, have numerous evasive mechanisms to the immune response that make it possible to spread around the host. In our Laboratory we have developed a vaccination model in mice with Trypanosoma rangeli, nonpathogenic to humans, which modulates the immune response to infection by T. cruzi, thus protecting them. Vaccinated animals showed an important innate response(modulation of NO and other metabolites, cytokines, activation of macrophages), a strong adaptive cellular response and significant increase in specific antibodies. The modulation caused early elimination of the parasites, low parasitaemia, the absence of histological lesions and high survival rates. Even though progress has been made in the knowledge of some of these mechanisms, new studies must be conducted which could target further prophylactic and therapeutic trials against T. cruzi infection.
基金financial assistance from CNPq (Brazilian National Research Council)FAPESP (S o Paulo State Research Funding Agency-Brazil) and Institut National de la Santé et de la Recherche Médicale (INSERM)+4 种基金the Aix-Marseille University (Direction des Relations Internationales)USP-COFECUB programthe ARCUS Ⅱ PACA Brésil programfunded either by the French ANR (Br-FrCHAGAS) and the Brazilian FAPESP agenciessupported by the French consulate in Brazil and the University of S o Paulo
文摘Chagas disease cardiomyopathy(CCC), the main consequence of Trypanosoma cruzi(T.cruzi) infection, is an inflammatory cardiomyopathy that develops in up to 30% of infected individuals. The heart inflammation in CCC patients is characterized by a Th1 T cell-rich myocarditis with increased production of interferon(IFN)-γ, produced by the CCC myocardial infiltrate and detected at high levels in the periphery. IFN-γ has a central role in the cardiomyocyte signaling during both acute and chronic phases of T.cruzi infection. In this review, we have chosen to focus in its pleiotropic mode of action during CCC, which may ultimately be the strongest driver towards pathological remodeling and heart failure. We describe here the antiparasitic protective and pathogenic dual role of IFN-γ in Chagas disease.
文摘Objective:Aqueous extracts of Zapoteca portoricensis are used traditionally as antidiarrhea agent and in the treatment of diverse gastrointestinal disorders here in Nigeria specifically,the southern part.Similarly,the aqueous extract of the plant is also used traditionally as anticonvulsant,antispasmodic and in the treatment of tonsillitis.Recently too,the anti-inflammatory and antimicrobial activities of the methanol extracts of the root of Zapoteca portoricensis was reported.In this research,we are set to investigate the trypanocidal activity of Zapoteca portoricensis.Methods:The methanol extract of the root of Zapoteca portoricensis was investigated for both in vitro and in vivo trypanocidal activity following established models.In summary,phytochemical analysis was carried out on both the crude powdered root and on the methanol extract following standard procedures. The oral acute toxicity test(LD<sub>50</sub> ) of the crude methanol extract was determined according to the method described by Lorke（1983）.Albino mice（17g-21g） of either sex were used.The methanol extract was suspended in 3%v/v tween 85 and administered orally at doses of 10 mg/kg,100 mg/kg and 1 000 mg/kg to three groups of mice（n = 3 ）.The animals were observed for 24 hours.Based on the result obtained in this initial test,doses of 4 mg/kg,6 mg/kg,and 8 mg/kg were administered to three different mice.The LD<sub>50</sub> was calculated as the geometric mean of the lowest dose killing a mouse and the highest dose showing no death.The invivo /in-vitro antitrypanosomal evaluations were carried out in experimental animals and tissue cell culture respectively. Results:The result of the in vitro studies shows the inhibitive concentration-50（IC-50） against Trypanosoma brucei rhodesiense（T.b.rhodesiense） to be 0.372 mg/kg,while the control drug melarsoprol was 0.006 mg/kg.On Trypanosoma brucei brucei（T.cruzi）,the IC-50 is 6.42 mg/kg against 0.87 of the reference drug Benznidazole.The cytotoxicity on L-6 cells exhibited an IC-50
文摘Understanding the biological parameters of some triatomine subspecies of Meccus phyllosomus （Burmeister） is a crucial first step in estimating the epidemiologie importance of this group. Biological parameters related to hatching, lifetime, number of blood meals to molt, percentage of females at the end of the cycle, number of laid eggs, and mortality for each instar of 3 M. phyllosomus subspecies [M. p. mazzottii （Usinger）, M. p. pallidipennis （Stal）, and M. p. phyllosomus] and their laboratory hybrids were evaluated and compared. No significant differences （P 〉 0.05） were found among the experimental hybrids （MaPa, MaPhy, PaPhy） and reciprocal cohorts. In 5 （hatching, number of blood meals to molt, accumulative mortality, percentage of females, and mean number of laid eggs） of the 6 studied parameters （with the exception of development time）, the hybrid cohorts had better fitness results than the parental cohorts involved in each set of crosses. The increase in hybrid fitness found in our study could lead to an increase in the epidemiologic risks caused by transmission of Trypanosoma cruzi to humans.
文摘Almost 110 years after the first studies by Dr. Carlos Chagas describing an infectious disease that was named for him, Chagas disease remains a neglected illness and a death sentence for infected people in poor countries. This short review highlights the enormous need for new studies aimed at the development of novel and more specific drugs to treat chagasic patients. The primary tool for facing this challenge is deep knowledge about the similarities and differences between the parasite and its human host.
文摘In Brazil and several other Latin American countries, Chagas' disease still constitutes a serious medical and social problem, and there is a need to develop new, more-potent drugs with fewer side effects to effectively treat this disease. We investigated the antitrypanosomal effect of a crude extract, fractions, and a semi-purified subfraction rich in a mix- ture of isomeric labdane sesquiterpenes, obtained from flowers of Anthemis tinctoria, against Trypanosoma cruzi. In epimastigote forms, the aqueous crude extract, dichloromethane fraction, and semi-purified subfraction showed a dose-dependent inhibitory activity, with IC50 of 2.3 μg/ml, 1.8 μg/ml, and 0.2 μg/ml, respectively. In the interaction in- dex, the semi-purified subfraction showed a reduction in both the percentage of infected LLCMK2 cells and the mean number of amastigotes per infected cell. The cytotoxicity evaluation demonstrated that the cytotoxic concentrations of the semi-purified subfraction were higher for LLCMK2 cells than for the protozoans, with a selectivity index of 35.0. Epimastigote forms treated with the semi-purified subfraction showed ultrastructural and morphological alterations such as rounding of the cells and bleb formation in the flagellum and cytoplasmic membrane. These results show that the flowers from A. tinctoria may be a source of new drugs with antiprotozoal activity. However, additional in vitro and in vivo studies are needed to validate the use of A. tinctoria in the treatment of Chagas’ disease.
文摘American trypanosomiasis is a zoonosis of worldwide medical importance and currently there is no effective treatment in chronic patients, hence the importance of the study of protein function of the parasite with the objective of finding new drug targets and to know better the biology of the agent causal (Trypano-soma cruzi). T. cruzi is an RNAi-negative parasite, therefore the silencing genes strategies by RNAi is not possible;for that reason, antibodies may be taken as a tool for studying the parasite proteins function by blocking these molecules with specific antibodies. The aim of this work was to establish a methodology for antibody delivery (antibody transfection) into viable parasites. We used anti-cyclin-A antibody (human origin) in western blot assay with epimastigote of T. cruzi proteins and this recognized a ~55 kDa polypeptide. Several methods for antibody transfection (electroporation, saponin permeabilization and a lipid-based formulation) were tested. The first two methods were unsuccessful. In electroporation was impossible to visualize the antibody inside parasites and with saponin permeabilization, antibodies were successfully introduced, but with loss of parasites viability. The lipid-based formulation method forms noncovalent complexes with antibodies. These complexes are internalized by cells and antibodies are released into the cytoplasm. With this method, a successful antibody delivery was achieved. Anti-cyclin antibodies were visualized in the cytoplasm from fixed transfected parasites (immunofluorescence assays). At 24 h post-transfection, parasites maintained their viability (90%) and were able to arrest the cell cycle in G0/G1-phase of cultured epimastigotes (cell population increased in G0/G1-phase from 50.5% to 66.2% and decreased in S-phase from 47.2% to 26%). It was also observed that anti-cyclin-A antibodies inhibit the parasite population doubling (p T. cruzi, with a simple and cheap technique, which will allows carrying out further studies of this protozoan.
基金Supported by Proyecto Control de Vectores IMT-UCV
文摘Objective:To investigate the bioecological relationship between Chagas disease peridomestic vectors and reptiles as source of feeding.Methods:In a three-story building,triatomines were captured by direct search and electric vacuum cleaner search in and outside the building.Then,age structure of the captured Triatoma maculata(T.maculata) were identified and recorded.Reptiles living in sympatric with the triatomines were also searched.Results:T.maculata were found living sympatric with geckos(Thecadactylus rapicauda) and they bit residents of the apartment building in study.A total of 1 448 individuals of T.maculata were captured within three days,of which 74.2%(1 074 eggs) were eggs,21.5%were nymphs at different stages,and 4.3%were adults.Conclusions:The association of T.maculata and T.rapicauda is an effective strategy of colonizing dwellings located in the vicinity of the habitat where both species are present;and therefore,could have implications of high importance in the intradomiciliary transmission of Chagas disease.
文摘Objective:To identify whether Canova medication changes TNF-α and IL-10 serum levels in mice infected with Trypanosoma cruzi Y strain.Methods:Animals were divided into five groups:non-treated infected animals(I); benznidazole-treated infected animals(Bz; 100 mg/kg body weight,single daily dose by gavage); Canova medication(CM) treated infected animals(CM;0.2 mL/animal,single daily dose by gavage); benznidazole- and Canova medication–treated infected animals with the above-mentioned dose(Bz+CM);and non-infected animals(C).TNF-α and IL-10 levels were determined in serum aliquots after 4,7,10,13,and 29 days of infection.An ELISA technique was employed with R&D System Inc.antibody pairs.Results:A high increase in TNF-α and IL-10 levels occurred in the infected and CM-treated groups within the treatment employed on the 10 th day after infection,coupled with a IL-10 decrease on the 13 th day after infection when compared with the other experimental groups.Conclusions:CM may change the balance between plasma cytokine levels(TNF-α and IL-10) in mice infected with Y strain T.cruzi,with important consequences leading towards a more severe infection.
文摘Substituted 2-benzylidene-1-benzofuran-3-ones are commonly known as aurones. This class of bioactive heterocycles belongs to flavonoid family. The article intends to put forth the rational design and synthesis of a new series of aurones using 3’,5’-dibromo-2’,4’-dihydroxychalcones and copper bromide in presence of DMF-water mixture (8:2, v/v) for the first time. Preliminary bioassay shows that most of compounds have good trypanocidal activity against Trypanosoma cruzi at 10 μg/mL. Few compounds are equally potent to the standard drugs Benznidazole and Nifurtimox. The structures of the newly synthesized products 2a-n were established by elemental analysis, FTIR, 1H NMR, 13C NMR and mass spectroscopic studies.
文摘A series of N1-substituted-3-aryl-4-alkyl-4, 5-dihydro-1H-1-pyrazolethiocarboxamide were prepared from the Mannich bases of aryl ketones in good yields. Some derivatives were found to be active against the cysteine protease of T.cruzi..
文摘With the objective to describe the relationship between T. cruzi infection in humans and sinantropic reservoir and vectors in the rural conditions a study was performed in municipalities of the Yucatan state in Mexico. Blood samples from humans, dogs and opossum were taken from the households. Vectors were also collected and the infection and infestation indexes were calculated. Serum samples were evaluated by indirect hemagglutination (IH) and indirect immunofluorescence (IFI) to determine IgG antibodies against Trypanosoma cruzi. The polymerase chain reaction (PCR) was also performed in the samples taken from humans and reservoirs. Blood smears were performed in reservoirs. Sampled humans underwent to an electrocardiographic study to identify functional and conduction alterations of the heart. Household building characteristics were noted. A total of 367 blood samples were collected from people. The presence of IgG antibodies was 16.6% and 71.0% at PCR. Electrocardiographic studies revealed that 31% of patients seropositive to T. cruzi have a medical condition. 20.0% of dogs were seropositive and 68.5 positive to PCR. At the direct detection 13.6% resulted positive. In opossum 29.1% were seropositive and 72.9% positive to PCR. A total of 269 triatomineos were captured and 52.7% were infected with T. cruzi. The infection and infestation index were 52.4% and 60.8% respectively. The presence of adult vectors and their nymph’s were more frequently found in households made with wattle roofs (45.2 and 73.9 % respectively) than other kind of building materials. Electrocardiographic abnormalities found in positive persons were: Incomplete right bundle branch block (55%), tachycardia (35%), old myocardial infarction (5%) and incomplete block of the left bundle (5%). This work highlights the importance of comprehensive studies on the transmission of T. cruzi in the Yucatan where the link between human infection in synanthropic reservoirs and vectors is established. This information is important to design programs for t
基金funded by a FPU a grant from the Ministry of Education of Spain
文摘Objective:To classify 21 new isolates of Trypanosoma cruai(T.cruzi) according to the Discrete Typing Unit(DTU) which they belong to,as well as tune up a new pair of primers designed to detect the parasite in biological samples.Methods:Strains were isolated,DNA extracted,and classified by using three Polymerase Chain Reactions(PCR).Subsequently this DNA was used along with other isolates of various biological samples,for a new PCR using primers designed.Finally,the amplified fragments were sequenced.Results:It was observed the predominance of DTU i in Colombia,as well as the specificity of our primers for detection of T.cruzi,while no band was obtained when other species were used.Conclusions:This work reveals the genetic variability of 21 new isolates of T.cruzi in Colombia.Our primers confirmed their specificity for detecting the presence of T.cruzi.
基金Fundação de AmparoàPesquisa do Estado de São Paulo-FAPESP.Process number 2016/08737-0TBSP received a Ph.D.scholarship from the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior(CAPES,Finance code 001).
文摘Objective:To evaluate parasitemia by qPCR in patients undergoing etiological treatment and followed in a Brazilian reference center.Methods:Parasite load was quantified by qPCR in 32 participants with chronic Chagas disease who were treated with benznidazole.Serological analyses were performed before and after the treatment and parasite loads were compared prior and 12/18 months post the treatment.Results:Thirty-two participants were recruited and treated with benznidazole,and 20 were followed-up.Adverse events(AE)were observed in 22 out of 29 participants that had safety data(76%),and dermatological alterations were the most frequently observed AE.Of the 20 participants analyzed,13 and 7 completed 12 and 18 months follow-up after the treatment,respectively.12 Months after the final treatment,Trypanosoma cruzi was detectable in 3 patients by qPCR;18 months after the final treatment,Trypanosoma cruzi was detectable per qPCR in 4 of the 7 participants.Thus,between 12 and 18 months,7 participants of the 20 initial follow-up cases showed positive qPCR,indicating treatment failures.Conclusions:qPCR can be used as an alternative method for evaluating the effectiveness of the etiological treatment of CD,and can be applied to analyze early therapeutic failures.The study showed that benznidazole therapy had limited effectiveness in treating chronic CD patients,thus emphasizing the importance of conducting continued research for developing more effective therapies and diagnosis for CD.
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.
基金partially supported by the third call for research grants(J-M.R.R.)from the Institute of Health and Biomedical Research of Alicante(ISABIAL)/FISABIO Foundation(Ⅲ convocatoria de ayudas a proyectos de investigación del Instituto de Investigación Sanitaria y Biomédica de Alicante(ISABIAL)–Fundación FISABIO)(UGP-16-158)by the collaborative agreement between ISABIAL/Fundación FISABIO and Fundación Mundo Sano-Spain,in accordance with the Sponsorship Law.
文摘Background:Chagas disease is a parasitic disease endemic to Latin America,but it has become a disease of global concern due to migration fows.Asymptomatic carriers may host the parasite for years,without knowing they are infected.The aim of this study is to assess prevalence of Chagas disease and evaluate the participants’level of knowl‑edge between Latin American migrants attending a community-based screening campaign.Methods:Three community-based campaigns were performed in Alicante(Spain)in 2016,2017 and 2018,including educational chats and blood tests for Trypanosoma cruzi serology.Participants completed a questionnaire assessing knowledge about the mechanisms of transmission,disease presentation,diagnosis,and treatment.People seroposi‑tive for T.cruzi underwent diagnostic confrmation by two diferent tests.Results were analyzed by multivariable logistic regression and expressed as adjusted odds ratios(aORs),adjusting for age,sex,and time in Spain.Results:A total of 596 participants were included in the study;17%were aged under 18 years.Prevalence in adults was 11%[54/496;95%confdence interval(CI):8.3–14.5%]versus 0%among children.All but one case were in Bolivians.Diagnosis was independently associated with having been born in Bolivia(aOR:102,95%CI:13–781)and a primary school-level education(aOR:2.40,95%CI:1.14–5.06).Of 54 people diagnosed with Chagas disease(most of whom were asymptomatic),42(77.7%)returned to the clinic at least once,and 24(44.4%)received treatment.Multivariable analysis showed that coming from Argentina(aOR:13,95%CI:1.61–1188)or Bolivia(aOR:1.90,95%CI:1.19–3.39)and having received information about Chagas disease in Spain(aOR:4.63,95%CI:2.54–8.97)were associ‑ated with a good level of knowledge on the disease.Having primary level studies(aOR:0.59,95%CI:0.34–0.98)and coming from Ecuador(aOR:4.63,95%CI:2.52–847)were independently associated with a lower level of knowledge.Conclusions:Community-based interventions are a good strategy for diagnosing neglected diseases su
