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1.
Rev Soc Bras Med Trop ; 52: e20180541, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31800918

RESUMO

INTRODUCTION: Chagas disease is a major public health problem that is endemic in Brazil and Latin America. This study aimed to determine the socioeconomic, demographic, and clinical characteristics of 171 patients (mean age, 45 years; female, 65%) with Chagas disease at Hospital Universitário de Brasília, Federal District, Brazil. METHODS: We implemented this cross-sectional study using a clinical epidemiological questionnaire, electrocardiography, echocardiography, and quantitative detection of Trypanosoma cruzi DNA in blood using qRT-PCR. RESULTS: Among the patients, 26.3% had a full elementary education, and 13.2% were illiterate. Most (63.6%) were economically classified as class C, and 51.5% were born in Bahia state. A total of 62.0% participants reported previous contact with the triatomine bug. The clinical forms of the disease were indeterminate (69.51%), cardiac (15.24%), digestive (10.37%), and mixed (4.88%). The most common electrocardiographic abnormality was complete right bundle branch block in association with a divisional anterosuperior block. Only 14.6% of the patients complied with benznidazole medication for at least 60 days, and 164 of them were assessed by echocardiography. The parasite load was positive in 56% of the patients. CONCLUSIONS: Chagas disease affected mostly women, with the indeterminate chronic form of the disease.


Assuntos
Doença de Chagas/epidemiologia , Trypanosoma cruzi/genética , Adulto , Idoso , Brasil/epidemiologia , Doença de Chagas/parasitologia , Estudos Transversais , DNA de Protozoário/genética , Ecocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carga Parasitária , Reação em Cadeia da Polimerase em Tempo Real , Fatores Socioeconômicos , Trypanosoma cruzi/isolamento & purificação , Adulto Jovem
2.
Rev Soc Bras Med Trop ; 52: e20190270, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31778401

RESUMO

INTRODUCTION: Trypanosomes can infect humans and animals. This is the first record of the occurrence of Trypanosoma evansi in Rondônia. METHODS: Blood samples were collected from 7 dogs and 22 humans. Furthermore, triatomines and tabanids were collected. RESULTS: It was observed that 42.8% of the dogs tested positive for T. evansi and 14.3% presented mixed infection; 15% of the triatomines tested positive for flagellates identified as T. cruzi TCI (3 specimens), T. cruzi TCI, and T. rangeli (1 specimen), and one with T. cruzi TCV. Two tabanids were infected with T. theileri. CONCLUSIONS: These findings may benefit vector control strategies.


Assuntos
Anticorpos Antiprotozoários/sangue , Doença de Chagas/epidemiologia , Insetos Vetores/parasitologia , Rhodnius/parasitologia , Trypanosoma/isolamento & purificação , Animais , Brasil/epidemiologia , Doença de Chagas/diagnóstico , Doença de Chagas/parasitologia , Cães , Inquéritos Epidemiológicos , Humanos , Trypanosoma/classificação
3.
Biochimie ; 167: 207-216, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31628976

RESUMO

Oligopeptidases B (OPB) belong to the S9 prolyl oligopeptidase family and are expressed in prokaryotes, some eukaryotes and in some higher plants. OPB is not found in any of the mammalian genomes available to date. Evidences indicate that OPB participates in the infections caused by trypanosomatids Trypanosoma cruzi, Leishmania spp. and Trypanosoma brucei spp and therefore it is considered an important virulence factor. Trypanosomatids from the genera Leishmania and Trypanosoma also present other OPB, named OPB2. A more accurate investigation of trypanosomatid OPB sequences brought attention to what could be a third OPB sequence (OPB3). This review aims to discuss biochemical, structural, phylogenetic and functional properties of OPB and its potential as target for the development of drugs against Chagas disease, leishmaniasis and African trypanosomiasis.


Assuntos
Leishmania/enzimologia , Serina Endopeptidases , Trypanosoma brucei brucei/enzimologia , Trypanosoma cruzi/enzimologia , Fatores de Virulência , Animais , Doença de Chagas/parasitologia , Humanos , Leishmaniose/parasitologia , Mamíferos , Proteínas de Protozoários/química , Proteínas de Protozoários/imunologia , Serina Endopeptidases/química , Serina Endopeptidases/classificação , Serina Endopeptidases/imunologia , Tripanossomíase Africana/parasitologia , Fatores de Virulência/química , Fatores de Virulência/classificação , Fatores de Virulência/imunologia
4.
PLoS Negl Trop Dis ; 13(9): e0007447, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31557155

RESUMO

BACKGROUND: Chagas disease (CD) affects over 300,000 people in the United States, but fewer than 1% have been diagnosed and less than 0.3% have received etiological treatment. This is a significant public health concern because untreated CD can produce fatal complications. What factors prevent people with CD from accessing diagnosis and treatment in a nation with one of the world's most advanced healthcare systems? METHODOLOGY/PRINCIPAL FINDINGS: This analysis of barriers to diagnosis and treatment of CD in the US reflects the opinions of the authors more than a comprehensive discussion of all the available evidence. To enrich our description of barriers, we have conducted an exploratory literature review and cited the experience of the main US clinic providing treatment for CD. We list 34 barriers, which we group into four overlapping dimensions: systemic, comprising gaps in the public health system; structural, originating from political and economic inequalities; clinical, including toxicity of medications and diagnostic challenges; and psychosocial, encompassing fears and stigma. CONCLUSIONS: We propose this multidimensional framework both to explain the persistently low numbers of people with CD who are tested and treated and as a potential basis for organizing a public health response, but we encourage others to improve on our approach or develop alternative frameworks. We further argue that expanding access to diagnosis and treatment of CD in the US means asserting the rights of vulnerable populations to obtain timely, quality healthcare.


Assuntos
Doença de Chagas/epidemiologia , Assistência à Saúde , Doença de Chagas/diagnóstico , Doença de Chagas/parasitologia , Doença de Chagas/terapia , Humanos , Saúde Pública , Trypanosoma cruzi/fisiologia , Estados Unidos/epidemiologia
5.
PLoS Negl Trop Dis ; 13(9): e0007226, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31536489

RESUMO

Chagas disease, caused by Trypanosoma cruzi, is a neglected tropical disease that affects 5-6 million people in endemic areas of the Americas. Presently, chemotherapy relies on two compounds that were proposed as trypanocidal drugs four decades ago: nifurtimox and benznidazole. Both drugs are able to eliminate parasitemia and to avoid seroconversion in infected people when used in the acute phase; however, their use in the chronic phase (the time when the majority of cases are diagnosed) is limited due to their serious side effects. Memantine is a glutamate receptor antagonist in the central nervous system of mammals that has been used for the treatment of Alzheimer's disease. Our group previously reported memantine as a trypanocidal drug that is able to induce apoptosis-like death in T. cruzi. In the present work, we further investigated the effects of memantine on the infection of RAW 264.7 macrophages and in vivo (in BALB/c mice). Here, we showed that memantine is able to diminish NO and Ca2+ entry in both LPS-activated and non-activated cells. These results, together with the fact that memantine was also able to reduce the infection of macrophages, led us to propose that this drug is able to activate a pro-oxidant non-NO-dependent cell defense mechanism. Finally, infected mice that were treated with memantine had diminished parasitemia, cardiac parasitic load, and inflammatory infiltrates. In addition, the treated mice had an increased survival rate. Taken together, these results indicate memantine to be a candidate drug for the treatment of Chagas disease.


Assuntos
Doença de Chagas/tratamento farmacológico , Memantina/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Cálcio/metabolismo , Doença de Chagas/parasitologia , Feminino , Coração/parasitologia , Lipopolissacarídeos/farmacologia , Macrófagos/parasitologia , Memantina/administração & dosagem , Camundongos , Camundongos Endogâmicos BALB C , Óxidos de Nitrogênio/metabolismo , Carga Parasitária , Parasitemia , Células RAW 264.7 , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Tripanossomicidas/administração & dosagem
6.
Acta Trop ; 200: 105167, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31513762

RESUMO

It is not currently known which individuals with chronic Chagas disease (ChD) will develop cardiopathy in a determined period and which will be maintained asymptomatic with normal routine laboratory tests all their lives. The parasite burden is a factor that could explain this different evolution. The objective of this study was to quantify Trypanosoma cruzi burden by real-time PCR in blood (qPCR-B) and dejections of triatomines fed by xenodiagnosis (qPCR-XD) in 90 individuals with chronic ChD untreated, classified according to XD results and the presence or absence of cardiopathy. All individuals came from hyperendemic areas of Chile and participated in the study under Informed Consent. The standard qPCR curves for qPCR-B and qPCR-XD were elaborated with a mixture of known concentrations of T. cruzi strains, performing DNA serial dilutions (1/10) with a dynamic range between 105 and 10-1 parasite equivalents/mL. The TaqManⓇ detection system was applied in a Stratagene Mx3000P thermocycler (Agilent Technologies, USA) with cruzi 1 and cruzi 2 satellite primers. 22.2% and 15.6% of cases with cardiopathy or without cardiopathy were XD positive. There was no significant difference between the groups. The positivity of qPCR-B and qPCR-XD in the positive XD group was 82.35% and 100%, respectively, while in the negative XD group was 55.26% and 42.10%, respectively. A superior qPCR value in chronic ChD patients with and without cardiopathy was determined for qPCR in cases with positive XD and positive qPCR-XD. The receiver operating characteristic (ROC) curve analyses show better accuracy for detecting parasite burden (area under the curve, AUC) for qPCR-XD in comparison to qPCR-B. That is to say, major performance in DNA samples obtained of positive XD (gold standard for viable T. cruzi) detected and quantified by qPCR-XD. A high percentage of cases with XD and qPCR-XD positive (80-100%) have result concordant with qPCR-B. In absence of XD, future challenges are especially related to the low parasitic load of chronic ChD patients treated with trypanocidal drugs and post-therapy parasitological evaluations by qPCR-B. Finally, no statistically significant differences were found between presence or absence of cardiopathy and XD, qPCR-B or qPCR-XD.


Assuntos
Doença de Chagas/complicações , Doença de Chagas/parasitologia , Cardiopatias/etiologia , Carga Parasitária , Triatoma/parasitologia , Trypanosoma cruzi/isolamento & purificação , Xenodiagnóstico/métodos , Adulto , Fatores Etários , Idoso , Animais , Doença de Chagas/sangue , Doença de Chagas/epidemiologia , Chile/epidemiologia , Doença Crônica/epidemiologia , Testes Diagnósticos de Rotina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real/métodos , Tripanossomicidas , Trypanosoma cruzi/genética
7.
Parasit Vectors ; 12(1): 424, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31522683

RESUMO

BACKGROUND: Trypanosoma cruzi, the protozoan agent of Chagas disease, is comprised of at least 6 genetic lineages (TcI-TcVI). Their geographical distribution, clinical associations and reservoir hosts are not fully elucidated, as genotyping is hampered due to the difficulty in isolating representative populations of organisms. Lineage-specific serological techniques may address these issues. METHODS: Trypanosoma cruzi lineage-specific serological assays were performed on human, canine, feline and armadillo sera from the Gran Chaco in northern Argentina, a region of ongoing transmission. Synthetic peptides representing lineage-specific epitopes of the trypomastigote small surface antigen (TSSA) were used in ELISA, and the TcII/V/VI shared epitope peptide (TSSApep-II/V/VI) was used in the Chagas Sero K-SeT rapid diagnostic test (RDT). RESULTS: Chagas Sero K-SeT RDT, using Protein G to detect human and canine IgG, was at least as sensitive as TSSApep-II/V/VI ELISA using specific secondary antibodies. For sera from humans TSSApep-II/V/VI seroprevalence by Chagas Sero K-SeT was 273/393 (69.5%), for dogs 48/73 (65.8%) and for armadillos 1/7 (14.3%); by ELISA for cats 5/19 (26.3%). The seroprevalence for humans was similar to that for Bolivian patients, amongst whom we previously observed an association of TSSApep-II/V/VI seropositivity with severity of cardiomyopathy. In humans, prevalence of TSSApep-II/V/VI recognition was associated with locality, and with increasing and decreasing age within the Qom and Creole populations, respectively. For dogs TSSApep-II/V/VI recognition was associated with being born before community-wide insecticide spraying (P = 0.05) and with Qom household (P < 0.001). CONCLUSIONS: We show here that Chagas Sero K-SeT RDT can replace ELISA for TSSApep-II/V/VI serology of humans and dogs; for humans there were statistically significant associations between a positive Chagas Sero K-SeT RDT and being resident in Area IV, and for dogs association with Qom household or with being born before the mass spraying campaign; we also show that with cats the TcII/V/VI epitope can be detected by ELISA. We assessed the lineage distribution in an unprecedented 83% of the human T. cruzi-seropositive population. These results form the basis for more detailed studies, enabling rapid in-the-field surveillance of the distribution and clustering of these lineages among humans and mammalian reservoirs of T. cruzi infection.


Assuntos
Anticorpos Antiprotozoários/sangue , Doença de Chagas/epidemiologia , Doença de Chagas/veterinária , Testes Diagnósticos de Rotina/métodos , Sorogrupo , Testes Sorológicos/métodos , Trypanosoma cruzi/classificação , Animais , Argentina/epidemiologia , Tatus , Gatos , Doença de Chagas/parasitologia , Estudos Transversais , Cães , Ensaio de Imunoadsorção Enzimática/métodos , Humanos , Estudos Soroepidemiológicos , Trypanosoma cruzi/genética , Trypanosoma cruzi/isolamento & purificação
8.
Nat Commun ; 10(1): 3972, 2019 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-31481692

RESUMO

Genetic exchange enables parasites to rapidly transform disease phenotypes and exploit new host populations. Trypanosoma cruzi, the parasitic agent of Chagas disease and a public health concern throughout Latin America, has for decades been presumed to exchange genetic material rarely and without classic meiotic sex. We present compelling evidence from 45 genomes sequenced from southern Ecuador that T. cruzi in fact maintains truly sexual, panmictic groups that can occur alongside others that remain highly clonal after past hybridization events. These groups with divergent reproductive strategies appear genetically isolated despite possible co-occurrence in vectors and hosts. We propose biological explanations for the fine-scale disconnectivity we observe and discuss the epidemiological consequences of flexible reproductive modes. Our study reinvigorates the hunt for the site of genetic exchange in the T. cruzi life cycle, provides tools to define the genetic determinants of parasite virulence, and reforms longstanding theory on clonality in trypanosomatid parasites.


Assuntos
Genoma de Protozoário , Meiose , Trypanosoma cruzi/genética , Animais , Doença de Chagas/parasitologia , Quirópteros/parasitologia , Equador , Variação Genética , Genética Populacional , Recombinação Genética , Reprodução/genética , Roedores/parasitologia , Análise de Sequência de DNA , Triatominae/parasitologia
9.
Exp Parasitol ; 206: 107730, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31494215

RESUMO

Phospholipids are the main component of membranes and are responsible for cell integrity. Alkylphospholipid analogues (APs) were first designed as antitumoral agents and were later tested against different cell types. Trypanosoma cruzi, the Chagas disease etiological agent, is sensitive to APs (edelfosine, miltefosine and ilmofosine) in vitro. We investigated the effect of synthetic ring substituted AP against epimastigotes, amastigotes and trypomastigotes. TCAN26, could inhibit the in vitro growth of epimastigotes and amastigotes with the 50% inhibitory concentrations (IC50) in the nanomolar range. Trypomastigotes lysis was also induced with 24-h treatment and a LC50 of 2.3 µM. Ultrastructural analysis by electron microscopy demonstrated that TCAN26 mainly affected the parasite's membranes leading to mitochondrial and Golgi cisternae swelling, membrane blebs, and autophagic figures in the different parasite developmental stages. While the Golgi of the parasites was significantly affected, the Golgi complex of the host cells remained normal suggesting a specific mechanism of action. In summary, our results suggest that TCAN 26 is a potent and selective inhibitor of T. cruzi growth probably due to disturbances of phospholipid biosynthesis.


Assuntos
Adamantano/farmacologia , Fosforilcolina/análogos & derivados , Fosforilcolina/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Adamantano/química , Animais , Antiprotozoários/química , Antiprotozoários/farmacologia , Autofagia/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Doença de Chagas/tratamento farmacológico , Doença de Chagas/parasitologia , Relação Dose-Resposta a Droga , Citometria de Fluxo , Complexo de Golgi/efeitos dos fármacos , Concentração Inibidora 50 , Dose Letal Mediana , Macrófagos Peritoneais/efeitos dos fármacos , Camundongos , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Microscopia de Fluorescência , Microscopia Imunoeletrônica , Mitocôndrias/efeitos dos fármacos , Fosforilcolina/química , Tripanossomicidas/química , Trypanosoma cruzi/crescimento & desenvolvimento , Trypanosoma cruzi/ultraestrutura
10.
Parasitol Res ; 118(9): 2523-2529, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31385028

RESUMO

Relatively little is known about the fitness effects and life history trade-offs in medically important parasites and their insect vectors. One such case is the triatomine bugs and the parasite Trypanosoma cruzi, the key actors in Chagas disease. Previous studies have revealed some costs but have not simultaneously examined traits related to development, reproduction, and survival or their possible trade-offs. In addition, these studies have not compared the effects of genetically different T. cruzi strains that differ in their weakening effects in their vertebrate hosts. We compared the body size of the bugs after infection, the number of eggs laid, hatching/non-hatching rate, hatching success, survival, and the resulting number of parasites in Meccus (Triatoma) pallidipennis bugs that were experimentally infected with two strains of T. cruzi (Chilpancingo [CH], the most debilitating in vertebrates; and Morelos [MO], the least debilitating) (both belonging to TcI group). Our results showed that infection affects size (MO < CH; MO and CH = control), number of eggs laid (MO and CH < control) hatching/non-hatching rate (MO < control < CH), hatching success (control < MO, CH = control = MO), and survival (Chilpancingo < Morelos < control). In addition, the CH strain produced more parasites than the MO strain. These results suggest that (a) infection costs depend on the parasite's origin, (b) the more debilitating effects of the CH strain are due to its increased proliferation in the host, and (c) differences in pathogenicity among T. cruzi strains can be maintained through their different effects on hosts' life history traits. Probably, the vectorial capacity mediated by a more aggressive strain could be reduced due to its costs on the triatomine, leading to a lower risk of vertebrate and invertebrate infection in natural populations.


Assuntos
Doença de Chagas/parasitologia , Insetos Vetores/parasitologia , Triatoma/crescimento & desenvolvimento , Triatoma/parasitologia , Trypanosoma cruzi/patogenicidade , Animais , Meio Ambiente
11.
Acta Trop ; 199: 105127, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31394076

RESUMO

OBJECTIVES: Congenital Chagas Disease (CCD) has become a global health problem. Early diagnosis and treatment is essential for the cure of the disease. Our aim was to evaluate techniques and samples used for the diagnosis of CCD in order to improve diagnostic strategies. METHODS: A total of 181 children born in Spain from Latin American Chagas-infected mothers were consecutively enrolled and studied by microhematocrit, PCR and serology tests at 0-2, 6 and 9-12 months of age and followed up when it was required. Samples of cord blood and peripheral blood were collected for T. cruzi detection by PCR. Parasite culture was performed in patients with a positive PCR. RESULTS: Of 181 children, 7 children (3.9%) were lost to follow-up. A total of 174 children completed follow-up, 12 were diagnosed with CCD (6.9%) and 162 (93.1%) as uninfected children (negative serology tests at the end of the follow-up). Traditional parasitological diagnosis by microhematocrit had a poor performance (sensitivity was 10%), while PCR in peripheral blood showed high sensitivity (90.9%) and specificity (100%), allowing the early diagnosis of 9 infected children during the first 6-months-old. In the other 3 congenital cases, diagnosis was only possible at 12 months by serological and molecular techniques. However, PCR in cord blood showed low sensitivity (33.3%) and less specificity (96.4%) for the diagnosis. CONCLUSION: PCR in peripheral blood has proven to be the most adequate strategy for the diagnosis of CCD, allowing an early and reliable diagnosis.


Assuntos
Doença de Chagas/diagnóstico , Complicações Parasitárias na Gravidez/diagnóstico , Adolescente , Adulto , Doença de Chagas/congênito , Doença de Chagas/parasitologia , Feminino , Sangue Fetal/parasitologia , Seguimentos , Saúde Global , Hematócrito , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Reação em Cadeia da Polimerase/métodos , Gravidez , Complicações Parasitárias na Gravidez/parasitologia , Sensibilidade e Especificidade , Testes Sorológicos , Espanha , Trypanosoma cruzi/genética , Trypanosoma cruzi/imunologia , Trypanosoma cruzi/isolamento & purificação , Adulto Jovem
12.
Acta Trop ; 199: 105120, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31376368

RESUMO

Chagas disease has become a global health problem due to migration of infected people out of Latin America to non-endemic countries. For more than 40 years, only the nitroimidazole compounds Benznidazole and Nifurtimox, have been used for specific treatment of Trypanosoma cruzi infection with disappointing results, specially due to the long duration of treatment and adverse events in the chronic phase. In the last years, ergosterol inhibitors have been also proposed for specific treatment. Different randomized clinical trials were performed for evaluating their treatment efficacy and safety. One of the greatest concerns in clinical trials is to provide an early surrogate biomarker of response to trypanocidal chemotherapy. Serological response is slow and the classical parasitological tests have poor sensitivity and are time-consuming. Nowadays, PCR is the most helpful tool for assessing treatment response in a short period of time. Different protocols of PCR have been developed, being quantitative real time PCR based on amplification of repetitive satellite or minicircle DNA sequences plus an internal amplification standard, the mostly employed strategies in clinical trials. Standardized protocols and the use of an external quality assessment ensure adequate technical procedures and reliable data. Clinical trials have shown a significant reduction in parasite loads, reaching undetectable DNA levels in bloodstream after specific treatment, however events of treatment failure have also been reported. Treatment failure could be due to inadequate penetrance of the drugs into the affected tissues, to the presence of primary or secondary drug resistance of the infecting strains as well as to the existence of dormant parasite variants reluctant to drug action. The early diagnosis of drug resistance would improve clinical management of Chagas disease patients, allowing dictating alternative therapies with a combination of existing drugs or new anti-T. cruzi agents. The aim of this review was to describe the usefulness of detecting T.cruzi DNA by means of real time PCR assays, as surrogate biomarker in clinical trials for evaluating new drugs for CD or new regimens of available drugs and the possibility to detect treatment failure.


Assuntos
Doença de Chagas/terapia , Ácidos Nucleicos/análise , Reação em Cadeia da Polimerase em Tempo Real , Tripanossomicidas/uso terapêutico , Trypanosoma cruzi/efeitos dos fármacos , Biomarcadores , Doença de Chagas/parasitologia , Doença Crônica , Resistência a Medicamentos/genética , Humanos , Nifurtimox/farmacologia , Nifurtimox/uso terapêutico , Nitroimidazóis/farmacologia , Nitroimidazóis/uso terapêutico , Ácidos Nucleicos/sangue , Carga Parasitária , Falha de Tratamento , Resultado do Tratamento , Tripanossomicidas/farmacologia , Trypanosoma cruzi/genética
13.
Molecules ; 24(15)2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31374887

RESUMO

Dithiocarbamates represent a class of compounds that were evaluated in different biomedical applications because of their chemical versatility. For this reason, several pharmacological activities have already been attributed to these compounds, such as antiparasitic, antiviral, antifungal activities, among others. Therefore, compounds that are based on dithiocarbamates have been evaluated in different in vivo and in vitro models as potential new antimicrobials. Thus, the purpose of this review is to present the possibilities of using dithiocarbamate compounds as potential new antitrypanosomatids-drugs, which could be used for the pharmacological control of Chagas disease, leishmaniasis, and African trypanosomiasis.


Assuntos
Antiparasitários/uso terapêutico , Leishmaniose/tratamento farmacológico , Tiocarbamatos/uso terapêutico , Trypanosoma/efeitos dos fármacos , Animais , Antiparasitários/química , Doença de Chagas/tratamento farmacológico , Doença de Chagas/parasitologia , Humanos , Leishmaniose/parasitologia , Tiocarbamatos/química , Trypanosoma/patogenicidade , Tripanossomíase Africana/tratamento farmacológico , Tripanossomíase Africana/parasitologia
14.
J Vet Diagn Invest ; 31(5): 752-755, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31342874

RESUMO

A 9-y-old, zoo-housed, male red panda (Ailurus fulgens) became progressively lethargic and inappetent over a 1-wk period. Physical examination was unremarkable. A complete blood count showed mild normocytic, normochromic, non-regenerative anemia with the presence of trypomastigote organisms, consistent with a Trypanosoma sp. The organism was confirmed later as Trypanosoma cruzi lineage TcI via PCR and genome sequencing. The panda was initially treated supportively; however, its clinical status within 24 h from presentation deteriorated, and euthanasia was elected. Autopsy showed severe systemic T. cruzi infection with the presence of amastigotes in the heart, brain, peripheral nerves, skeletal muscles, tongue, liver, and testes. We used genome sequencing and serology in identifying the agent.


Assuntos
Ailuridae , Doença de Chagas/veterinária , Trypanosoma cruzi/isolamento & purificação , Animais , Animais de Zoológico , Doença de Chagas/diagnóstico , Doença de Chagas/parasitologia , Kansas , Masculino
15.
Microb Pathog ; 135: 103618, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31310832

RESUMO

P21 is a protein secreted by Trypanosoma cruzi (T. cruzi). Previous studies have shown a spectrum of biological activities performed by P21 such as induction of phagocytosis, leukocyte chemotaxis and inhibition of angiogenesis. However, the activity of P21 in T. cruzi infection remains unknown. Here, we reported the role of P21 in mice harboring late T. cruzi infection. Treatment with recombinant P21 protein (rP21) reduced parasite load and angiogenesis, and induced fibrosis in the cardiac tissue of infected mice. In addition, rP21 reduced the growth of epimastigotes, inhibited intracellular replication of amastigotes and modulated the parasite cell cycle. Our data suggest that P21 controls parasite replication in the host, supporting the survival of both parasite and host.


Assuntos
Doença de Chagas/imunologia , Proteínas de Protozoários/imunologia , Proteínas de Protozoários/metabolismo , Trypanosoma cruzi/imunologia , Trypanosoma cruzi/fisiologia , Animais , Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/imunologia , Ciclo Celular , Doença de Chagas/parasitologia , Doença de Chagas/patologia , Modelos Animais de Doenças , Fibrose , Coração , Interações Hospedeiro-Parasita , Camundongos , Camundongos Endogâmicos BALB C , Carga Parasitária , Proteínas de Protozoários/genética , Proteínas Recombinantes , Trypanosoma cruzi/genética , Trypanosoma cruzi/patogenicidade
16.
Parasitol Res ; 118(9): 2609-2619, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31267245

RESUMO

Trypanosoma cruzi is the etiological agent of Chagas disease. These parasites undergo dramatic morphological and physiological changes during their life cycle. The human-infective metacyclic trypomastigotes differentiate from epimastigotes inside the midgut of the Triatominae insect vector. Our group has shown that the saliva and feces of Rhodnius prolixus contains a lysophospholipid, lysophosphatidylcholine (LPC), which modulates several aspects of T. cruzi infection in macrophages. LPC hydrolysis by a specific lysophospholipase D, autotaxin (ATX), generates lysophosphatidic acid (LPA). These bioactive lysophospholipids are multisignaling molecules and are found in human plasma ingested by the insect during blood feeding. Here, we show the role of LPC and LPA in T. cruzi proliferation and differentiation. Both lysophospholipids are able to induce parasite proliferation. We observed an increase in parasite growth with different fatty acyl chains, such as C18:0, C16:0, or C18:1 LPC. The dynamics of LPC and LPA effect on parasite proliferation was evaluated in vivo through a time- and space-dependent strategy in the vector gut. LPC but not LPA was also able to affect parasite metacyclogenesis. Finally, we determined LPA and LPC distribution in the parasite itself. Such bioactive lipids are associated with reservosomes of T. cruzi. To the best of our knowledge, this is the first study to suggest the role of surrounding bioactive lipids ingested during blood feeding in the control of parasite transmission.


Assuntos
Doença de Chagas/parasitologia , Metabolismo dos Lipídeos , Trypanosoma cruzi/crescimento & desenvolvimento , Trypanosoma cruzi/metabolismo , Animais , Doença de Chagas/transmissão , Humanos , Insetos Vetores/parasitologia , Estágios do Ciclo de Vida , Lipídeos/química , Rhodnius/parasitologia
17.
Rev Soc Bras Med Trop ; 52: e20180505, 2019 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-31271620

RESUMO

INTRODUCTION: The microscopic examination of microhematocrit tubes (mHCT) has been proposed as the gold standard for acute and congenital Chagas disease diagnosis. We compared different mHCT methodologies detecting T. cruzi parasites in the blood. METHODS: The rotating method, water mount, and immersion oil methods were compared for their suitability, sensitivity, and specificity. RESULTS: The rotating method was easier, faster, and more sensitive than the others with 100% specificity. CONCLUSIONS: The rotating method is feasible for laboratory technicians with standard training in microscopic techniques and is recommended for the diagnosis of acute Chagas disease in primary health care facilities.


Assuntos
Tubo Capilar , Centrifugação/métodos , Doença de Chagas/diagnóstico , Hematócrito/métodos , Parasitemia/diagnóstico , Trypanosoma cruzi/isolamento & purificação , Animais , Doença de Chagas/sangue , Doença de Chagas/parasitologia , Serviços de Laboratório Clínico , Humanos , Parasitemia/parasitologia , Sensibilidade e Especificidade
18.
Acta Trop ; 198: 105107, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31351074

RESUMO

Chagas disease is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi. It is a significant public health problem, affecting millions of people worldwide. And although it was described 110 years ago, only two old nitroheterocyclic drugs, benznidazole and nifurtimox, are currently available for the treatment of Chagas disease and both have several limitations. Besides the clear unmet medical need, many challenges preclude the development of new treatments, some of them related to a lack of understanding of the pathophysiology of the disease and parasite-host interactions. New knowledge and tools are becoming available, but the number of new chemical entities progressing through the preclinical pipeline is inadequate. Therefore, it is still uncertain whether safe, effective and accessible new drugs will be available in the near future. The Chagas disease research community must commit to even greater collaboration to ensure that patients eventually benefit from better treatments.


Assuntos
Doença de Chagas/tratamento farmacológico , Descoberta de Drogas , Nifurtimox/uso terapêutico , Nitroimidazóis/uso terapêutico , Tripanossomicidas/uso terapêutico , Doença de Chagas/parasitologia , Humanos , Trypanosoma cruzi/efeitos dos fármacos
19.
Int J Infect Dis ; 87: 100-108, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31357062

RESUMO

OBJECTIVE: Chagas disease affects over six million people, but less than 1% are diagnosed and treated. Complicated diagnostic processes are a major barrier. Colombia's previous diagnostic algorithm, using in-house tests, was difficult to scale up, creating significant access barriers for patients. A new algorithm using commercially manufactured immunoassays would potentially improve access, but these tests' performance in Colombian patients with Chagas disease is not well known. METHODS: We assessed seven commercially available assays. Samples (n=501), 93.8% originating from Colombia, were characterized as positive or negative based on standard procedure at the National Reference Laboratory. Performance characteristics were calculated for individual assays and hypothetical test pairings, then compared to the existing algorithm. RESULTS: Five of seven assays exhibited sensitivity >98% while six showed specificity >97%. A total antigen ELISA paired with a recombinant assay provided similar performance to the current diagnostic process. Six of six assays tested proved capable of detecting different Trypanosoma cruzi genetic lineages. CONCLUSIONS: The study indicated that several commercial assays accurately detect T. cruzi infection in Colombian patients. A simplified testing process with two commercial assays could perform comparably to the previous process, reducing cost and accessibility barriers and facilitating national scale-up.


Assuntos
Doença de Chagas/diagnóstico , Imunoensaio/métodos , Anticorpos Antiprotozoários/sangue , Doença de Chagas/sangue , Doença de Chagas/parasitologia , Colômbia , Humanos , Sensibilidade e Especificidade , Trypanosoma cruzi/genética , Trypanosoma cruzi/fisiologia
20.
Biomed Res Int ; 2019: 8301569, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31355283

RESUMO

Chagas disease is a tropical illness caused by the protozoan Trypanosoma cruzi. The disease affects populations of the Americas and has been spread to other continents due to the migration process. The disease is partially controlled by two drugs, Benznidazole and Nifurtimox. These molecules are active in the acute phase of the infection but are usually ineffective during the symptomatic chronic phase. Several research groups have developed novel candidates to control Chagas disease; however, no novel commercial formulation is available. In this article, we described the anti-T. cruzi effects of phenothiazinium dyes in amastigote and trypomastigote forms of the parasite. Methylene Blue, New Methylene Blue, Toluidine Blue O, and 1,9-Dimethyl Methylene Blue inhibited the parasite proliferation at nanomolar concentrations and also demonstrated low toxicity in host cells. Moreover, combinations of phenothiazinium dyes indicated a synergic pattern against amastigotes compared to the Benznidazole counterparts. Phenothiazinium dyes levels of reactive oxygen species (ROS) and decreased the mitochondrial potential in trypomastigotes, indicating the mechanism of action of the dyes in T. cruzi. Our article offers a basis for future strategies for the control of Chagas disease using low-cost formulations, an important point for endemic underdeveloped regions.


Assuntos
Proliferação de Células/efeitos dos fármacos , Doença de Chagas/tratamento farmacológico , Fenotiazinas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Linhagem Celular , Doença de Chagas/parasitologia , Corantes/farmacologia , Humanos , Azul de Metileno/análogos & derivados , Azul de Metileno/farmacologia , Nifurtimox/farmacologia , Nitroimidazóis/farmacologia , Cloreto de Tolônio/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma cruzi/patogenicidade
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