Medicine › Epidemiology

Trypanosoma species research and implications

Works Count: 61878

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This cluster of papers covers a wide range of topics related to Chagas disease, including the epidemiology, genomics, treatment, and control strategies. It discusses the causative agent Trypanosoma cruzi, the impact of Chagas disease in Latin America and non-endemic countries, as well as the challenges of drug resistance and the development of new therapies. Additionally, it explores the clinical aspects such as cardiomyopathy and provides insights into the molecular mechanisms underlying the disease.

Keywords

Trypanosoma cruzi; Chagas Disease; African Trypanosomiasis; Glycosylphosphatidylinositol; Chemotherapy; Epidemiology; Genome Sequence; Vector Control; Cardiomyopathy; Drug Resistance

Control of Chagas Disease

2006-01-01

Yoichi YAMAGATA , Jun Nakagawa

Revision of the Triatominae (Hemiptera, Reduviidae), and their significance as vectors of Chagas' disease.

1979-01-01

Herman Lent , Pedro W. Wygodzinsky

Biochemistry of the glycosyl-phosphatidylinositol membrane protein anchors

1987-05-15

M G Low

Research Article| May 15 1987 Biochemistry of the glycosyl-phosphatidylinositol membrane protein anchors M G Low M G Low 1Oklahoma Medical Research Foundation, Oklahoma City 73104. Search for other works by … Research Article| May 15 1987 Biochemistry of the glycosyl-phosphatidylinositol membrane protein anchors M G Low M G Low 1Oklahoma Medical Research Foundation, Oklahoma City 73104. Search for other works by this author on: This Site PubMed Google Scholar Biochem J (1987) 244 (1): 1–13. https://doi.org/10.1042/bj2440001 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share MailTo Twitter LinkedIn Cite Icon Cite Get Permissions Citation M G Low; Biochemistry of the glycosyl-phosphatidylinositol membrane protein anchors. Biochem J 15 May 1987; 244 (1): 1–13. doi: https://doi.org/10.1042/bj2440001 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Journal Search Advanced Search This content is only available as a PDF. © 1987 London: The Biochemical Society1987 Article PDF first page preview Close Modal You do not currently have access to this content.

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The structure, biosynthesis and functions of glycosylphosphatidylinositol anchors, and the contributions of trypanosome research

1999-09-01

Michael A. J. Ferguson

The discovery of glycosylphosphatidylinositol (GPI) membrane anchors has had a significant impact on several areas of eukaryote cell biology. Studies of the African trypanosome, which expresses a dense surface coat … The discovery of glycosylphosphatidylinositol (GPI) membrane anchors has had a significant impact on several areas of eukaryote cell biology. Studies of the African trypanosome, which expresses a dense surface coat of GPI-anchored variant surface glycoprotein, have played important roles in establishing the general structure of GPI membrane anchors and in delineating the pathway of GPI biosynthesis. The major cell-surface molecules of related parasites are also rich in GPI-anchored glycoproteins and/or GPI-related glycophospholipids, and differences in substrate specificity between enzymes of trypanosomal and mammalian GPI biosynthesis may have potential for the development of anti-parasite therapies. Apart from providing stable membrane anchorage, GPI anchors have been implicated in the sequestration of GPI-anchored proteins into specialised membrane microdomains, known as lipid rafts, and in signal transduction events.

The structure, biosynthesis and function of glycosylated phosphatidylinositols in the parasitic protozoa and higher eukaryotes

1993-09-01

Malcolm J. McConville , Michael A. J. Ferguson

Research Article| September 01 1993 The structure, biosynthesis and function of glycosylated phosphatidylinositols in the parasitic protozoa and higher eukaryotes M J McConville; M J McConville 1Department of Biochemistry, University … Research Article| September 01 1993 The structure, biosynthesis and function of glycosylated phosphatidylinositols in the parasitic protozoa and higher eukaryotes M J McConville; M J McConville 1Department of Biochemistry, University of Dundee, Dundee DD1 4HN, U.K. Search for other works by this author on: This Site PubMed Google Scholar M A J Ferguson M A J Ferguson 1Department of Biochemistry, University of Dundee, Dundee DD1 4HN, U.K. Search for other works by this author on: This Site PubMed Google Scholar Biochem J (1993) 294 (2): 305–324. https://doi.org/10.1042/bj2940305 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation M J McConville, M A J Ferguson; The structure, biosynthesis and function of glycosylated phosphatidylinositols in the parasitic protozoa and higher eukaryotes. Biochem J 1 September 1993; 294 (2): 305–324. doi: https://doi.org/10.1042/bj2940305 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Journal Search Advanced Search This content is only available as a PDF. © 1993 The Biochemical Society, London1993 Article PDF first page preview Close Modal You do not currently have access to this content.

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The Alamar Blue® assay to determine drug sensitivity of African trypanosomes (T.b. rhodesiense and T.b. gambiense) in vitro

1997-11-01

Barbara Räz , M Iten , Yvonne Grether-Bühler +2 more

Trypanosoma brucei: A rapid “matching” method for estimating the host's parasitemia

1976-12-01

W.J. Herbert , W. H. R. Lumsden

Glycosyl-Phosphatidylinositol Moiety That Anchors <i>Trypanosoma brucei</i> Variant Surface Glycoprotein to the Membrane

1988-02-12

Michael A. J. Ferguson , Steve W. Homans , Raymond A. Dwek +1 more

Two forms of protein-membrane anchor have been described for the externally disposed glycoproteins of eukaryotic plasma membranes; namely, the hydrophobic transmembrane polypeptide and the complex glycosylphosphatidylinositol (G-PI) moiety. The chemical … Two forms of protein-membrane anchor have been described for the externally disposed glycoproteins of eukaryotic plasma membranes; namely, the hydrophobic transmembrane polypeptide and the complex glycosylphosphatidylinositol (G-PI) moiety. The chemical structures of the major species of G-PI anchors found on a single variant surface glycoprotein (VSG) of the parasitic protozoan Trypanosoma brucei were determined by a combination of nuclear magnetic resonance spectroscopy, mass spectrometry, chemical modification, and exoglycosidase digestions. The G-PI anchor was found to be heterogeneous with respect to monosaccharide sequence, and several novel glycosidic linkages were present. The results are pertinent to the mechanism of the biosynthesis of G-PI anchors.

Chagas disease: A Latin American health problem becoming a world health problem

2009-11-21

Gabriel A. Schmuñis , Zaida E. Yadón

Chagas disease in Spain, the United States and other non-endemic countries

2009-07-30

Joaquím Gascón , Caryn Bern , María‐Jesús Pinazo

Isolation of salivarian trypanosomes from man and other mammals using DEAE-cellulose

1970-12-01

Sheila M. Lanham , D.G. Godfrey

Major transcript of the frameshifted coxll gene from trypanosome mitochondria contains four nucleotides that are not encoded in the DNA

1986-09-01

Rob Benne , J. van den Burg , Just P. J. Brakenhoff +3 more

Evaluation and Treatment of Chagas Disease in the United States

2007-11-13

Caryn Bern , Susan P. Montgomery , Barbara L. Herwaldt +7 more

Because of population migration from endemic areas and newly instituted blood bank screening, US clinicians are likely to see an increasing number of patients with suspected or confirmed chronic Trypanosoma … Because of population migration from endemic areas and newly instituted blood bank screening, US clinicians are likely to see an increasing number of patients with suspected or confirmed chronic Trypanosoma cruzi infection (Chagas disease).To examine the evidence base and provide practical recommendations for evaluation, counseling, and etiologic treatment of patients with chronic T cruzi infection. Evidence Acquisition Literature review conducted based on a systematic MEDLINE search for all available years through 2007; review of additional articles, reports, and book chapters; and input from experts in the field.The patient newly diagnosed with Chagas disease should undergo a medical history, physical examination, and resting 12-lead electrocardiogram (ECG) with a 30-second lead II rhythm strip. If this evaluation is normal, no further testing is indicated; history, physical examination, and ECG should be repeated annually. If findings suggest Chagas heart disease, a comprehensive cardiac evaluation, including 24-hour ambulatory ECG monitoring, echocardiography, and exercise testing, is recommended. If gastrointestinal tract symptoms are present, barium contrast studies should be performed. Antitrypanosomal treatment is recommended for all cases of acute and congenital Chagas disease, reactivated infection, and chronic T cruzi infection in individuals 18 years or younger. In adults aged 19 to 50 years without advanced heart disease, etiologic treatment may slow development and progression of cardiomyopathy and should generally be offered; treatment is considered optional for those older than 50 years. Individualized treatment decisions for adults should balance the potential benefit, prolonged course, and frequent adverse effects of the drugs. Strong consideration should be given to treatment of previously untreated patients with human immunodeficiency virus infection or those expecting to undergo organ transplantation.Chagas disease presents an increasing challenge for clinicians in the United States. Despite gaps in the evidence base, current knowledge is sufficient to make practical recommendations to guide appropriate evaluation, management, and etiologic treatment of Chagas disease.

The future of Chagas disease control

2006-10-18

C.J. Schofield , J Jannin , Roberto Salvatella

Localization of nine glycolytic enzymes in a microbody‐like organelle in <i>Trypanosoma brucei</i>: The glycosome

1977-08-15

Fred R. Opperdoes , Piet Borst

Clinical and epidemiological aspects of Chagas disease

2001-09-01

Áluízio Prata

The revised Trypanosoma cruzi subspecific nomenclature: Rationale, epidemiological relevance and research applications

2011-12-27

Bianca Zingales , Michael A. Miles , David A. Campbell +7 more

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The impact of Chagas disease control in Latin America: a review

2002-07-01

JCP Dias , AC Silveira , CJ Schofield

Discovered in 1909, Chagas disease was progressively shown to be widespread throughout Latin America, affecting millions of rural people with a high impact on morbidity and mortality. With no vaccine … Discovered in 1909, Chagas disease was progressively shown to be widespread throughout Latin America, affecting millions of rural people with a high impact on morbidity and mortality. With no vaccine or specific treatment available for large-scale public health interventions, the main control strategy relies on prevention of transmission, principally by eliminating the domestic insect vectors and control of transmission by blood transfusion. Vector control activities began in the 1940s, initially by means of housing improvement and then through insecticide spraying following successful field trials in Brazil (Bambui Research Centre), with similar results soon reproduced in São Paulo, Argentina, Venezuela and Chile. But national control programmes only began to be implemented after the 1970s, when technical questions were overcome and the scientific demonstration of the high social impact of Chagas disease was used to encourage political determination in favour of national campaigns (mainly in Brazil). Similarly, large-scale screening of infected blood donors in Latin America only began in the 1980s following the emergence of AIDS. By the end of the last century it became clear that continuous control in contiguous endemic areas could lead to the elimination of the most highly domestic vector populations - especially Triatoma infestans and Rhodnius prolixus - as well as substantial reductions of other widespread species such as T. brasiliensis, T. sordida, and T. dimidiata, leading in turn to interruption of disease transmission to rural people. The social impact of Chagas disease control can now be readily demonstrated by the disappearance of acute cases and of new infections in younger age groups, as well as progressive reductions of mortality and morbidity rates in controlled areas. In economic terms, the cost-benefit relationship between intervention (insecticide spraying, serology in blood banks) and the reduction of Chagas disease (in terms of medical and social care and improved productivity) is highly positive. Effective control of Chagas disease is now seen as an attainable goal that depends primarily on maintaining political will, so that the major constraints involve problems associated with the decentralisation of public health services and the progressive political disinterest in Chagas disease. Counterbalancing this are the political and technical cooperation strategies such as the "Southern Cone Initiative" launched in 1991. This international approach, coordinated by PAHO, has been highly successful, already reaching elimination of Chagas disease transmission in Uruguay, Chile, and large parts of Brazil and Argentina. The Southern Cone Initiative also helped to stimulate control campaigns in other countries of the region (Paraguay, Bolivia, Peru) which have also reached tangible regional successes. This model of international activity has been shown to be feasible and effective, with similar initiatives developed since 1997 in the Andean Region and in Central America. At present, Mexico and the Amazon Region remain as the next major challenges. With consolidation of operational programmes in all endemic countries, the future focus will be on epidemiological surveillance and care of those people already infected. In political terms, the control of Chagas disease in Latin America can be considered, so far, as a victory for international scientific cooperation, but will require continuing political commitment for sustained success.

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Biology of Trypanosoma Cruzi

1973-10-01

Z. Brener

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Chagas disease: a new worldwide challenge

2010-06-01

José Rodrigues Coura , Pedro Albajar-Viñas

Development and Validation of a Risk Score for Predicting Death in Chagas' Heart Disease

2006-08-23

Anis Rassi , William C. Little , Sérgio Salles Xavier +6 more

Chagas' disease is an important health problem in Latin America, and cardiac involvement is associated with substantial morbidity and mortality. We developed a model to predict the risk of death … Chagas' disease is an important health problem in Latin America, and cardiac involvement is associated with substantial morbidity and mortality. We developed a model to predict the risk of death in patients with Chagas' heart disease.

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DNA markers define two major phylogenetic lineages of Trypanosoma cruzi

1996-12-20

Ricardo Peres do Souto

An improved parasitological technique for the diagnosis of African trypanosomiasis

1977-01-01

Max Murray , P.K. Murray , W. I. M. McIntyre

Journal Article An improved parasitological technique for the diagnosis of African trypanosomiasis Get access Max Murray, Max Murray International Laboratory for Research on Animal Diseases, Nairobi, Kenya Search for other … Journal Article An improved parasitological technique for the diagnosis of African trypanosomiasis Get access Max Murray, Max Murray International Laboratory for Research on Animal Diseases, Nairobi, Kenya Search for other works by this author on: Oxford Academic PubMed Google Scholar P. K. Murray, P. K. Murray Glasgow University Veterinary School Search for other works by this author on: Oxford Academic PubMed Google Scholar W. I. M. McIntyre W. I. M. McIntyre Glasgow University Veterinary School Search for other works by this author on: Oxford Academic PubMed Google Scholar Transactions of The Royal Society of Tropical Medicine and Hygiene, Volume 71, Issue 4, 1977, Pages 325–326, https://doi.org/10.1016/0035-9203(77)90110-9 Published: 01 January 1977 Article history Published: 01 January 1977 Accepted: 09 February 1977

The Genome of the African Trypanosome <i>Trypanosoma brucei</i>

2005-07-14

Matthew Berriman , Elodie Ghedin , Christiane Hertz‐Fowler +7 more

African trypanosomes cause human sleeping sickness and livestock trypanosomiasis in sub-Saharan Africa. We present the sequence and analysis of the 11 megabase-sized chromosomes of Trypanosoma brucei. The 26-megabase genome contains … African trypanosomes cause human sleeping sickness and livestock trypanosomiasis in sub-Saharan Africa. We present the sequence and analysis of the 11 megabase-sized chromosomes of Trypanosoma brucei. The 26-megabase genome contains 9068 predicted genes, including approximately 900 pseudogenes and approximately 1700 T. brucei-specific genes. Large subtelomeric arrays contain an archive of 806 variant surface glycoprotein (VSG) genes used by the parasite to evade the mammalian immune system. Most VSG genes are pseudogenes, which may be used to generate expressed mosaic genes by ectopic recombination. Comparisons of the cytoskeleton and endocytic trafficking systems with those of humans and other eukaryotic organisms reveal major differences. A comparison of metabolic pathways encoded by the genomes of T. brucei, T. cruzi, and Leishmania major reveals the least overall metabolic capability in T. brucei and the greatest in L. major. Horizontal transfer of genes of bacterial origin has contributed to some of the metabolic differences in these parasites, and a number of novel potential drug targets have been identified.

Comparative Genomics of Trypanosomatid Parasitic Protozoa

2005-07-14

Najib M. El-Sayed , Peter J. Myler , Gaëlle Blandin +7 more

A comparison of gene content and genome architecture of Trypanosoma brucei, Trypanosoma cruzi , and Leishmania major , three related pathogens with different life cycles and disease pathology, revealed a … A comparison of gene content and genome architecture of Trypanosoma brucei, Trypanosoma cruzi , and Leishmania major , three related pathogens with different life cycles and disease pathology, revealed a conserved core proteome of about 6200 genes in large syntenic polycistronic gene clusters. Many species-specific genes, especially large surface antigen families, occur at nonsyntenic chromosome-internal and subtelomeric regions. Retroelements, structural RNAs, and gene family expansion are often associated with syntenic discontinuities that—along with gene divergence, acquisition and loss, and rearrangement within the syntenic regions—have shaped the genomes of each parasite. Contrary to recent reports, our analyses reveal no evidence that these species are descended from an ancestor that contained a photosynthetic endosymbiont.

A tightly regulated inducible expression system for conditional gene knock-outs and dominant-negative genetics in Trypanosoma brucei

1999-03-01

Elizabeth Wirtz , Simone Leal , Claudia M. Ochatt +1 more

Which neuropsychiatric and behavioural features distinguish frontal and temporal variants of frontotemporal dementia from Alzheimer's disease?

2000-08-01

Sasha Bozeat

<h3>OBJECTIVES</h3> To investigate the prevalence of changes in mood, personality, and behaviour in frontotemporal dementia (FTD) and Alzheimer9s disease (AD) and hence, which features reliably distinguish between them. To establish … <h3>OBJECTIVES</h3> To investigate the prevalence of changes in mood, personality, and behaviour in frontotemporal dementia (FTD) and Alzheimer9s disease (AD) and hence, which features reliably distinguish between them. To establish whether the frontal and temporal variants of FTD are characterised by different behavioural changes. <h3>METHODS</h3> A questionnaire was designed to assess a wide range of neuropsychiatric changes; it incorporated features reported in previous studies of FTD and components of the neuropsychiatric inventory.<sup>1</sup> This was completed by 37 carers of patients with Alzheimer9s disease (AD) and 33 patients with frontotemporal dementia (FTD), comprising 20 with temporal variant FTD (tv FTD) or semantic dementia and 13 with frontal variant FTD (fv FTD). An exploratory principal components factor analysis and discriminant function analysis was applied. <h3>RESULTS</h3> Factor analysis showed four robust and meaningful symptom clusters: factor 1—stereotypic and eating behaviour; factor 2—executive dysfunction and self care; factor 3—mood changes; factor 4—loss of social awareness. Only stereotypic and altered eating behaviour and loss of social awareness reliably differentiated AD from FTD with no effect of disease severity. By contrast, executive dysfunction, poor self care, and restlessness showed a significant effect of disease severity only, with the more impaired patients scoring more highly. Changes in mood were found to be equally prevalent in the three patient groups. Analysis of individual symptoms showed increased rates of mental rigidity and depression in the patients with semantic dementia compared with those with fv FTD. Conversely, the latter group showed greater disinhibition. Discriminant function analysis correctly classified 71.4% overall and 86.5% of the patients with AD. <h3>CONCLUSIONS</h3> This questionnaire disclosed striking differences between patients with FTD and AD, but only stereotypic behaviour, changes in eating preference, disinhibition, and features of poor social awareness reliably separated the groups. The patients with fv FTD and semantic dementia were behaviourally very similar, reflecting the involvement of a common network, the ventral frontal lobe, temporal pole, and amygdala. Dysexecutive symptoms and poor self care were found to be affected by the severity of the disease, reflecting perhaps spread to dorsolateral prefrontal areas relatively late in the course of both FTD and AD. This questionnaire may be of value in the diagnosis and the monitoring of therapies.

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Randomized Trial of Posaconazole and Benznidazole for Chronic Chagas' Disease

2014-05-14

Israel Molina , Jordi Gómez i Prat , Fernando Salvador +7 more

Current therapeutic options for Chagas' disease are limited to benznidazole and nifurtimox, which have been associated with low cure rates in the chronic stage of the disease and which have … Current therapeutic options for Chagas' disease are limited to benznidazole and nifurtimox, which have been associated with low cure rates in the chronic stage of the disease and which have considerable toxicity. Posaconazole has shown trypanocidal activity in murine models.We performed a prospective, randomized clinical trial to assess the efficacy and safety of posaconazole as compared with the efficacy and safety of benznidazole in adults with chronic Trypanosoma cruzi infection. We randomly assigned patients to receive posaconazole at a dose of 400 mg twice daily (high-dose posaconazole), posaconazole at a dose of 100 mg twice daily (low-dose posaconazole), or benznidazole at a dose of 150 mg twice daily; all the study drugs were administered for 60 days. We assessed antiparasitic activity by testing for the presence of T. cruzi DNA, using real-time polymerase-chain-reaction (rt-PCR) assays, during the treatment period and 10 months after the end of treatment. Posaconazole absorption was assessed on day 14.The intention-to-treat population included 78 patients. During the treatment period, all the patients tested negative for T. cruzi DNA on rt-PCR assay beyond day 14, except for 2 patients in the low-dose posaconazole group who tested positive on day 60. During the follow-up period, in the intention-to-treat analysis, 92% of the patients receiving low-dose posaconazole and 81% receiving high-dose posaconazole, as compared with 38% receiving benznidazole, tested positive for T. cruzi DNA on rt-PCR assay (P<0.01 for the comparison of the benznidazole group with either posaconazole group); in the per-protocol analysis, 90% of the patients receiving low-dose posaconazole and 80% of those receiving high-dose posaconazole, as compared with 6% receiving benznidazole, tested positive on rt-PCR assay (P<0.001 for the comparison of the benznidazole group with either posaconazole group). In the benznidazole group, treatment was discontinued in 5 patients because of severe cutaneous reactions; in the posaconazole groups, 4 patients had aminotransferase levels that were more than 3 times the upper limit of the normal range, but there were no discontinuations of treatment.Posaconazole showed antitrypanosomal activity in patients with chronic Chagas' disease. However, significantly more patients in the posaconazole groups than in the benznidazole group had treatment failure during follow-up. (Funded by the Ministry of Health, Spain; CHAGASAZOL ClinicalTrials.gov number, NCT01162967.).

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TriTrypDB: a functional genomic resource for the Trypanosomatidae

2009-10-20

Martin Aslett , Cristina Aurrecoechea , Matthew Berriman +7 more

TriTrypDB (http://tritrypdb.org) is an integrated database providing access to genome-scale datasets for kinetoplastid parasites, and supporting a variety of complex queries driven by research and development needs. TriTrypDB is a … TriTrypDB (http://tritrypdb.org) is an integrated database providing access to genome-scale datasets for kinetoplastid parasites, and supporting a variety of complex queries driven by research and development needs. TriTrypDB is a collaborative project, utilizing the GUS/WDK computational infrastructure developed by the Eukaryotic Pathogen Bioinformatics Resource Center (EuPathDB.org) to integrate genome annotation and analyses from GeneDB and elsewhere with a wide variety of functional genomics datasets made available by members of the global research community, often pre-publication. Currently, TriTrypDB integrates datasets from Leishmania braziliensis, L. infantum, L. major, L. tarentolae, Trypanosoma brucei and T. cruzi. Users may examine individual genes or chromosomal spans in their genomic context, including syntenic alignments with other kinetoplastid organisms. Data within TriTrypDB can be interrogated utilizing a sophisticated search strategy system that enables a user to construct complex queries combining multiple data types. All search strategies are stored, allowing future access and integrated searches. 'User Comments' may be added to any gene page, enhancing available annotation; such comments become immediately searchable via the text search, and are forwarded to curators for incorporation into the reference annotation when appropriate.

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Global economic burden of Chagas disease: a computational simulation model

2013-02-08

Bruce Y. Lee , Kristina M. Bacon , María Elena Bottazzi +1 more

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Trypanosoma cruzi and Chagas' Disease in the United States

2011-10-01

Caryn Bern , Sonia A. Kjos , Michael J. Yabsley +1 more

SUMMARY Chagas' disease is caused by the protozoan parasite Trypanosoma cruzi and causes potentially life-threatening disease of the heart and gastrointestinal tract. The southern half of the United States contains … SUMMARY Chagas' disease is caused by the protozoan parasite Trypanosoma cruzi and causes potentially life-threatening disease of the heart and gastrointestinal tract. The southern half of the United States contains enzootic cycles of T. cruzi , involving 11 recognized triatomine vector species. The greatest vector diversity and density occur in the western United States, where woodrats are the most common reservoir; other rodents, raccoons, skunks, and coyotes are also infected with T. cruzi. In the eastern United States, the prevalence of T. cruzi is highest in raccoons, opossums, armadillos, and skunks. A total of 7 autochthonous vector-borne human infections have been reported in Texas, California, Tennessee, and Louisiana; many others are thought to go unrecognized. Nevertheless, most T. cruzi -infected individuals in the United States are immigrants from areas of endemicity in Latin America. Seven transfusion-associated and 6 organ donor-derived T. cruzi infections have been documented in the United States and Canada. As improved control of vector- and blood-borne T. cruzi transmission decreases the burden in countries where the disease is historically endemic and imported Chagas' disease is increasingly recognized outside Latin America, the United States can play an important role in addressing the altered epidemiology of Chagas' disease in the 21st century.

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Identification, purification and properties of clone-specific glycoprotein antigens constituting the surface coat of<i>Trypanosoma brucei</i>

1975-12-01

George Cross

Soluble glycoproteins have been purified from a series of clones of Trypanosoma brucei 427. Each clone yielded a characteristic predominant glycoprotein which induced clone-specific immunity to trypanosome infection in mice. … Soluble glycoproteins have been purified from a series of clones of Trypanosoma brucei 427. Each clone yielded a characteristic predominant glycoprotein which induced clone-specific immunity to trypanosome infection in mice. These glycoproteins were shown by specific labelling and enzyme digestion of cells to be the major components of the trypanosome surface coat. Each glycoprotein consisted of a single polypeptide chain having an apparent molecular weight of 65 000 (as measured by SDS-polyacrylamide gel electrophoresis) and containing around 600 amino acid and 20 monosaccharide residues. Preliminary structural studies indicated large changes in amino acid sequence dispersed over a considerable length of the polypeptide chain. Proteolytic activity was demonstrated in semi-purified trypanosome extracts, providing one reason for the heterogeneity sometimes observed in surface glycoprotein antigen preparations.

An Estimate of the Burden of Chagas Disease in the United States

2009-07-29

Caryn Bern , Susan P. Montgomery

Chagas disease causes the highest burden of any parasitic disease in the Western hemisphere. By applying published seroprevalence figures to immigrant populations, we estimate that 300,167 individuals with Trypanosoma cruzi … Chagas disease causes the highest burden of any parasitic disease in the Western hemisphere. By applying published seroprevalence figures to immigrant populations, we estimate that 300,167 individuals with Trypanosoma cruzi infection live in the United States, with 30,000-45,000 cardiomyopathy cases and 63-315 congenital infections annually. T. cruzi causes a substantial disease burden in the United States.

Human African trypanosomiasis

2009-10-15

Reto Brun , Johannes Blum , François Chappuis +1 more

The Genome Sequence of <i>Trypanosoma cruzi</i> , Etiologic Agent of Chagas Disease

2005-07-14

Najib M. El-Sayed , Peter J. Myler , Daniella Castanheira Bartholomeu +7 more

Whole-genome sequencing of the protozoan pathogen Trypanosoma cruzi revealed that the diploid genome contains a predicted 22,570 proteins encoded by genes, of which 12,570 represent allelic pairs. Over 50% of … Whole-genome sequencing of the protozoan pathogen Trypanosoma cruzi revealed that the diploid genome contains a predicted 22,570 proteins encoded by genes, of which 12,570 represent allelic pairs. Over 50% of the genome consists of repeated sequences, such as retrotransposons and genes for large families of surface molecules, which include trans-sialidases, mucins, gp63s, and a large novel family (>1300 copies) of mucin-associated surface protein (MASP) genes. Analyses of the T. cruzi, T. brucei , and Leishmania major (Tritryp) genomes imply differences from other eukaryotes in DNA repair and initiation of replication and reflect their unusual mitochondrial DNA. Although the Tritryp lack several classes of signaling molecules, their kinomes contain a large and diverse set of protein kinases and phosphatases; their size and diversity imply previously unknown interactions and regulatory processes, which may be targets for intervention.

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Continuous Cultivation of Trypanosoma brucei Blood Stream Forms in a Medium Containing a Low Concentration of Serum Protein without Feeder Cell Layers

1989-12-01

H. Hirumi , K. Hirumi

Blood stream forms (BSF) of Trypanosoma brucei brucei GUT at 3.1 were propagated in vitro in the absence of feeder layer cells at 37 C, using a modified Iscove's medium … Blood stream forms (BSF) of Trypanosoma brucei brucei GUT at 3.1 were propagated in vitro in the absence of feeder layer cells at 37 C, using a modified Iscove's medium (HMI-18). The medium was supplemented with 0.05 mM bathocuproine sulfonate, 1.5 mM L-cysteine, 1 mM hypoxanthine, 0.2 mM 2-mercaptoethanol, 1 mM sodium pyruvate. 0.16 mM thymidine, and 20% (v/v) Serum Plus (SP) (Hazleton Biologics, Lenexa, Kansas). The latter contained a low level of serum proteins (13 micrograms/ml). Each primary culture was initiated by placing 3.5-4 x 10(6) BSFs isolated from infected mice in a flask containing 5 ml of the medium (HMI-9) supplemented with 10% fetal bovine serum (FBS) and 10% SP. The cultures were maintained by replacing the medium every 24 hr for 5-7 days. During this period, many BSFs died. However, from day 4 onward, long slender BSFs increased in number. On days 5-7, trypanosome suspensions were pooled and cell debris was removed by means of diethylaminoethyl cellulose (DE52) column chromatography. Blood stream forms then were collected by centrifugation, resuspended in fresh medium at 7-9 x 10(5)/ml, and transferred to new flasks. Subcultures were maintained by readjusting the BSF density to 7-9 x 10(5)/ml every 24 hr. Concentrations of FBS were reduced gradually at 5-7-day intervals by alternating the amounts of FBS and SP in HMI-9 with 5% FBS and 15% SP, with 2% FBS and 18% SP, and finally with 20% SP (HMI-18). By this method, 2-3 x 10(6) VSFs/ml were obtained consistently every 24 hr. for more than 80 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Activation of Toll-Like Receptor-2 by Glycosylphosphatidylinositol Anchors from a Protozoan Parasite

2001-07-01

Marco Antônio Campos , Igor C. Almeida , Osamu Takeuchi +7 more

Abstract Glycosylphosphatidylinositol (GPI) anchors and glycoinositolphospholipids (GIPLs) from parasitic protozoa have been shown to exert a wide variety of effects on cells of the host innate immune system. However, the … Abstract Glycosylphosphatidylinositol (GPI) anchors and glycoinositolphospholipids (GIPLs) from parasitic protozoa have been shown to exert a wide variety of effects on cells of the host innate immune system. However, the receptor(s) that are triggered by these protozoan glycolipids has not been identified. Here we present evidence that Trypanosoma cruzi-derived GPI anchors and GIPLs trigger CD25 expression on Chinese hamster ovary-K1 cells transfected with CD14 and Toll-like receptor-2 (TLR-2), but not wild-type (TLR-2-deficient) Chinese hamster ovary cells. The protozoan-derived GPI anchors and GIPLs containing alkylacylglycerol and saturated fatty acid chains or ceramide were found to be active in a concentration range of 100 nM to 1 μM. More importantly, the GPI anchors purified from T. cruzi trypomastigotes, which contain a longer glycan core and unsaturated fatty acids in the sn-2 position of the alkylacylglycerolipid component, triggered TLR-2 at subnanomolar concentrations. We performed experiments with macrophages from TLR-2 knockout and TLR-4 knockout mice, and found that TLR-2 expression appears to be essential for induction of IL-12, TNF-α, and NO by GPI anchors derived from T. cruzi trypomastigotes. Thus, highly purified GPI anchors from T. cruzi parasites are potent activators of TLR-2 from both mouse and human origin. The activation of TLR-2 may initiate host innate defense mechanisms and inflammatory response during protozoan infection, and may provide new strategies for immune intervention during protozoan infections.

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Pathogenesis of Chronic Chagas Heart Disease

2007-03-05

José Antônio Marin‐Neto , Edécio Cunha‐Neto , Benedito Carlos Maciel +1 more

Background— Chagas disease remains a significant public health issue and a major cause of morbidity and mortality in Latin America. Despite nearly 1 century of research, the pathogenesis of chronic … Background— Chagas disease remains a significant public health issue and a major cause of morbidity and mortality in Latin America. Despite nearly 1 century of research, the pathogenesis of chronic Chagas cardiomyopathy is incompletely understood, the most intriguing challenge of which is the complex host-parasite interaction. Methods and Results— A systematic review of the literature found in MEDLINE, EMBASE, BIREME, LILACS, and SCIELO was performed to search for relevant references on pathogenesis and pathophysiology of Chagas disease. Evidence from studies in animal models and in anima nobile points to 4 main pathogenetic mechanisms to explain the development of chronic Chagas heart disease: autonomic nervous system derangements, microvascular disturbances, parasite-dependent myocardial aggression, and immune-mediated myocardial injury. Despite its prominent peculiarities, the role of autonomic derangements and microcirculatory disturbances is probably ancillary among causes of chronic myocardial damage. The pathogenesis of chronic Chagas heart disease is dependent on a low-grade but incessant systemic infection with documented immune-adverse reaction. Parasite persistence and immunological mechanisms are inextricably related in the myocardial aggression in the chronic phase of Chagas heart disease. Conclusions— Most clinical studies have been performed in very small number of patients. Future research should explore the clinical potential implications and therapeutic opportunities of these 2 fundamental underlying pathogenetic mechanisms.

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A new consensus for Trypanosoma cruzi intraspecific nomenclature: second revision meeting recommends TcI to TcVI

2009-11-01

Bianca Zingales , Andrade Sg , Marcelo R. S. Briones +7 more

In an effort to unify the nomenclature of Trypanosoma cruzi, the causative agent of Chagas disease, an updated system was agreed upon at the Second Satellite Meeting.A consensus was reached … In an effort to unify the nomenclature of Trypanosoma cruzi, the causative agent of Chagas disease, an updated system was agreed upon at the Second Satellite Meeting.A consensus was reached that T. cruzi strains should be referred to by six discrete typing units (T.cruzi I-VI).The goal of a unified nomenclature is to improve communication within the scientific community involved in T. cruzi research.The justification and implications will be presented in a subsequent detailed report.

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Definition of individual components within the cytoskeleton of <i>Trypanosoma brucei</i> by a library of monoclonal antibodies

1989-07-01

Angela Woods , Trevor Sherwin , Rosemary Sasse +3 more

ABSTRACT The detergent-insoluble T. brucei cytoskeleton consists of several morphologically distinct regions and organelles, many of which are detectable only by electron microscopy. We have produced a set of monoclonal … ABSTRACT The detergent-insoluble T. brucei cytoskeleton consists of several morphologically distinct regions and organelles, many of which are detectable only by electron microscopy. We have produced a set of monoclonal antibodies that define each structural component of this highly ordered cytoskeleton. The monoclonal antibodies were selected by cloning of hybridomas produced from mice injected with complex mixtures of proteins of either the cytoskeleton itself or salt extracts thereof. Four antibodies define particular tubulin isotypes and locate the microtubules of the axoneme and sub-pellicular array; two antibodies recognize the flagellum attachment zone; one recognizes the paraflagellar rod and another the basal bodies. Finally, one antibody defines a detergent-insoluble component of the nucleus. The antigens detected by each monoclonal antibody have been analysed by immunofluorescence microscopy, immunogold electron microscopy and Western blotting.

Therapeutic activity and criterion of cure on mice experimentally infected with Trypanosoma cruzi.

1962-11-01

Z Brener

DEVELOPMENTAL CYCLES AND BIOLOGY OF PATHOGENIC TRYPANOSOMES

1985-01-01

Keith Vickerman

Journal Article DEVELOPMENTAL CYCLES AND BIOLOGY OF PATHOGENIC TRYPANOSOMES Get access Keith Vickerman Keith Vickerman Department of Zoology, University of Glasgow Search for other works by this author on: Oxford … Journal Article DEVELOPMENTAL CYCLES AND BIOLOGY OF PATHOGENIC TRYPANOSOMES Get access Keith Vickerman Keith Vickerman Department of Zoology, University of Glasgow Search for other works by this author on: Oxford Academic PubMed Google Scholar British Medical Bulletin, Volume 41, Issue 2, 1985, Pages 105–114, https://doi.org/10.1093/oxfordjournals.bmb.a072036 Published: 01 June 1985

Randomized Trial of Benznidazole for Chronic Chagas’ Cardiomyopathy

2015-09-01

Carlos A. Morillo , José Antônio Marin‐Neto , Álvaro Avezum +7 more

We conducted a prospective, multicenter, randomized study involving 2854 patients with Chagas' cardiomyopathy who received benznidazole or placebo for up to 80 days and were followed for a mean of … We conducted a prospective, multicenter, randomized study involving 2854 patients with Chagas' cardiomyopathy who received benznidazole or placebo for up to 80 days and were followed for a mean of 5.4 years. The primary outcome in the time-to-event analysis was the first event of any of the components of the composite outcome of death, resuscitated cardiac arrest, sustained ventricular tachycardia, insertion of a pacemaker or implantable cardioverter–defibrillator, cardiac transplantation, new heart failure, stroke, or other thromboembolic event.

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Manson's Tropical Diseases.

1973-08-01

This book continues to be one of the most outstanding in the world on the subject of tropical disease. It is a complete single volume concerned with tropical medicine, but, … This book continues to be one of the most outstanding in the world on the subject of tropical disease. It is a complete single volume concerned with tropical medicine, but, like all single volumes, it is not truly encyclopedic. This thirteenth edition has been brought up to date to include the new antibiotic drugs and the experiences obtained during World War II. This book is highly recommended to students of tropical medicine, especially those interested in the British points of view.

Chagas disease

2010-04-01

Anis Rassi , José Antônio Marin‐Neto

Chagas disease

2017-07-01

José A. Pérez‐Molina , Israel Molina

The trypanosomiases

2003-11-01

Michael P. Barrett , Richard Burchmore , August Stich +4 more

Chagas’ Disease

2015-07-29

Caryn Bern

The infection of millions of people with the protozoan parasite Trypanosoma cruzi is a public health concern. Treatments for Chagas' disease remain marginally effective. Cardiac and gastrointestinal complications dominate the … The infection of millions of people with the protozoan parasite Trypanosoma cruzi is a public health concern. Treatments for Chagas' disease remain marginally effective. Cardiac and gastrointestinal complications dominate the clinical picture.

Chagas disease in Latin America: an epidemiological update based on 2010 estimates.

2015-02-06

Cultivation and in vitro cloning or procyclic culture forms of Trypanosoma brucei in a semi-defined medium. Short communication.

1979-09-01

R. Brun , Schönenberger

Application of the Strategic “Démarche” to the Clinical Research Laboratory on Chagas Disease at the Evandro Chagas National Institute of Infectious Diseases, Fiocruz

2025-06-24

Alejandro Marcel Hasslocher‐Moreno , Elizabeth Artmann | Revista de Gestão Social e Ambiental

Objective: To assess the relevance of applying the Strategic Démarche in the Strategic planning process of the Clinical Research Laboratory on Chagas Disease (Lapclin-Chagas) at INI/Fiocruz. Theoretical Framework: Grounded in … Objective: To assess the relevance of applying the Strategic Démarche in the Strategic planning process of the Clinical Research Laboratory on Chagas Disease (Lapclin-Chagas) at INI/Fiocruz. Theoretical Framework: Grounded in the concept of Strategic Démarche as an adaptive, iterative, and participatory approach, initially developed in hospital settings and here applied to a hybrid institution integrating care, research, and education. Method: The Strategic Démarche steps were applied: situational diagnosis, Strategic segmentation, value and competitive position analysis, portfolio construction, action plan development, and monitoring indicators. Results and Discussion: Four key segments were identified: Cardiology, Diagnosis, Gastroenterology, and Etiological Treatment. The Cardiology and Diagnosis segments showed high value and competitiveness, while Gastroenterology had a higher Strategic risk. Specific actions were proposed for each segment based on the appropriation of Key Success Factors (KSFs). Research Implications: The experience enhances the evaluative culture and supports Strategic management in institutions addressing neglected diseases. Originality/Value: This is an unprecedented application of the Strategic Démarche in a national reference laboratory for Chagas disease, showcasing its adaptability to complex organizational contexts that integrate care, research, and teaching.

Detection of antibodies against the African parasite Trypanosoma brucei using synthetic glycosylphosphatidylinositol oligosaccharide fragments

2025-06-24

Maurice Michel , Benoı̂t Stijlemans , Monika Garg +3 more | Glycoconjugate Journal

Community-based surveillance of Chagas Disease: Characterization and use of triatomine information posts (TIPs) in a high-risk area for triatomine reinfestation in Latin America

2025-06-23

Valéria Carla Faria Amaral , Millena Vieira Simões de Freitas , Gustavo Libério de Paulo +5 more | PLoS neglected tropical diseases

In Brazil, vector surveillance with public participation is a prioritized action in the primary prevention of Chagas Disease (CD). It is anchored in the implementation of Triatomine Information Posts (TIPs), … In Brazil, vector surveillance with public participation is a prioritized action in the primary prevention of Chagas Disease (CD). It is anchored in the implementation of Triatomine Information Posts (TIPs), spaces recognized by health surveillance for receiving insects suspected of being triatomines. For the first time in the scientific literature, a study is dedicated to characterizing PITs operationally, structurally, and functionally, as well as understanding the factors that hinder their sustainability. The study was conducted in one of the most vulnerable regions for CD in the Americas. Using mixed approaches applied to health, an electronic form was sent to the municipal coordinators of endemic diseases to characterize the implementation, operational status, and description of TIPs. Data from an information system were accessed to analyze their productivity. Lastly, five focus groups were conducted to capture the perception of the endemic disease coordinators regarding TIPs. 100% of the municipalities did not maintain documentary records of the use and productivity of TIPs, 40% of municipalities had never implemented a TIP; of those implemented, more than 30% were deactivated, with a significant portion located in rural areas. TIPs located in areas shared with Primary Health Care facilities showed lower deactivation rates. Key factors hindering the functioning and sustainability of TIPs included the population's lack of awareness about them, the need for increased publicity of these locations, a shortage of qualified professionals, TIP distribution in hard-to-access areas, and the absence of feedback on insect examinations to residents. A scenario of heterogeneous distribution was revealed in the implementation/functioning of TIPs, as well as low public engagement and usage. There is an urgent need for health systems to be organized to regulate surveillance with public participation and to conduct awareness campaigns aimed at preventing future household reinfestations by triatomines and the resurgence of CD transmission in endemic areas.

Evolutionary analysis of the Leishmania major orthologues for the newly identified cyclic AMP response proteins

2025-06-23

S. Bhadra , Chandan Das , Sriparna Bawali +1 more | Archives of Microbiology

Prevalence Study on Feline Trypanosomiasis in and Around Hyderabad, India

2025-06-23

K Dhileep , K Padmaja , K. V. Lakshmi | Archives of Current Research International

Aim:To determine the prevalence of Trypanosomiasis in cats in and around Hyderabad, and to study the associated clinical signs and therapeutic management. Study Design: The study involved cats presented to … Aim:To determine the prevalence of Trypanosomiasis in cats in and around Hyderabad, and to study the associated clinical signs and therapeutic management. Study Design: The study involved cats presented to the Veterinary Clinical Complex (VCC), College of Veterinary Science, Rajendra Nagar, Hyderabad, as well as those referred from local dispensaries with clinical signs suggestive of Trypanosomiasis, such as fever and unilateral or bilateral corneal opacity. Data were analyzed based on breed, age, and gender. Place and Duration of Study: The study was conducted at the VCC, College of Veterinary Science, Rajendra Nagar, Hyderabad, from September 2024 to March 2025. Methodology: Suspected cases were screened for Trypanosomiasis using wet blood film examination, Giemsa stained blood smears along with hematological and biochemical analyses. The data obtained was subjected to statistical analysis. Results: Out of 1002 cats examined, 16 (1.6%) were diagnosed with Trypanosomiasis. The majority of affected cats were Domestic Short Hair (DSH) breed (62.5%), and young males (less than 1 year of age) were predominantly affected. The most common clinical signs included corneal opacity (87.5%), fever (81.25%), lymphadenopathy (75%), Inappetence (56.25%), pale mucous membranes (50%), turbidity in the anterior chamber (43.75%) and dehydration (31.25%). Microscopic examination of wet blood films revealed motile, spindle-shaped trypomastigote forms of Trypanosoma spp., which were also confirmed in Giemsa-stained blood smears. Hematological and biochemical findings included anemia, eosinophilia, and hypoglycemia. Treatment and Outcome: Affected cats were treated with Diminazene aceturate at a dosage of 3.5 mg/kg body weight for five consecutive days, along with supportive symptomatic therapy. All treated cats showed complete clinical recovery following the full course of treatment. Conclusion: Trypanosoma spp were detected in some cats presented at VCC College of Veterinary Science, Rajendranagar, Hyderabad.In cats, unlike in dogs, Diminazene aceturate must be administered for five consecutive days to achieve complete recovery. Interruption of the treatment regimen may lead to relapse.

Changing malaria epidemiology in a small island developing state and the implications for global health

2025-06-23

Shalini Pooransingh , Nyeil Ali , Naresh Nandram +3 more | Tropical Doctor

Case Report of Chronic Asymptomatic Chagas Disease: "The Importance of Epidemiological Laboratory Surveillance" at the Institute of Security and Social Services of Workers of the State of Mexico

2025-06-21

Marietta Vázquez | International Journal of Medical Science and Clinical Research Studies

Chagas disease, also known as American trypanosomiasis, is a neglected parasitic infection caused by Trypanosoma cruzi, primarily transmitted through hematophagous triatomine insects. Endemic across Latin America, the disease poses a … Chagas disease, also known as American trypanosomiasis, is a neglected parasitic infection caused by Trypanosoma cruzi, primarily transmitted through hematophagous triatomine insects. Endemic across Latin America, the disease poses a significant public health challenge, especially in impoverished rural and peri-urban areas. Its complex transmission cycle involves wild, domestic, and peridomestic reservoirs, with the vector playing a central role. Although most infections remain asymptomatic during the chronic phase, the disease can lead to severe cardiac and gastrointestinal complications. Diagnosis relies on serological, parasitological, and clinical evaluations, while treatment options are limited to the acute phase with antiparasitic drugs that have notable side effects. Epidemiological surveillance shows underdiagnosis, emphasizing the need for early detection and integrated control strategies. This review highlights the disease's epidemiology, transmission dynamics, clinical manifestations, diagnostic approaches, and current control measures, with a case illustration from Mexico demonstrating the importance of vigilant detection and management efforts to prevent progression and transmission.

Towards elimination: Challenges in community participation to a gHAT ‘screen and treat’ strategy using the new oral drug acoziborole in the Democratic Republic of the Congo

2025-06-20

Catiane Vander Kelen , Alain Mpanya , Ruth Nzuzi +4 more | PLoS neglected tropical diseases

Until recently, treatment options for gambiense human African trypanosomiasis (gHAT) have been limited and toxic, negatively impacting community participation to screening and treatment. A new, non-toxic, single-dose oral drug has … Until recently, treatment options for gambiense human African trypanosomiasis (gHAT) have been limited and toxic, negatively impacting community participation to screening and treatment. A new, non-toxic, single-dose oral drug has shown efficacy in a Phase III trial and is being tested in a trial called ‘STROGHAT’, which aims to demonstrate cessation of HAT transmission using a ‘screen and treat’ strategy. This study aims to explore community perceptions about current and future screening and treatment strategies and identify what could act as barriers to participation in order to prevent them. We conducted 8 focus group discussions and 18 semi-structured interviews with communities, community leaders and mobile unit managers in 4 selected villages out of 74 endemic villages included in the STROGHAT study. Our results highlight four main potential barriers: the rarity of cases has led to gHAT being perceived as a disease that no longer exists and participation to screening as a waste of time. Lack of awareness of new treatment and screening procedures perpetuates fears and misconceptions about treatment toxicity, lumbar puncture and mandatory hospitalisation. The introduction of a single-dose oral drug to be administered on the spot raised the issue of side effect monitoring and care. Finally, the lack of sensitivity to community cultural norms in the organisation of screening discourages people from participating. Those barriers are important to anticipate and include in elimination strategy. Also a monitor perception about acoziborole screen and treat during all the process through other social science based research is to foreseen.

CD4+TH17 cells play a critical role in conferring resistance to Trypanosoma cruzi infection while also demonstrating potential in mitigating the development of severe cardiac complications

2025-06-20

Mariana C. Duarte , Gildo Pedro Ribeiro , Ana Maria Ravena Severino Carvalho +7 more | Life Sciences

TRATAMENTO DA DOENÇA DE CHAGAS: DESAFIOS NA FASE CRÔNICA E PERSPECTIVAS TERAPÊUTICAS FUTURAS

2025-06-20

Elionay Pereira de Oliveira Torres , Maysa Lorrane Medeiros de Araújo , Jorge da Silva Vieira Júnior +4 more | Revista fisio&terapia.

New Histone H4 variant and H2B variant Exhibits Distinct Genomic Locations, Chromatin Affinities, and Dynamics Throughout Life Cycle and Cell Cycle of Trypanosoma cruzi

2025-06-20

Juliana Nunes Rosón , Mariana Loterio Silva , Herbert G. S. Silva +7 more | bioRxiv (Cold Spring Harbor Laboratory)

Histone variants play crucial roles in chromatin organization and transcriptional regulation in eukaryotes. Trypanosomatids display histone variants for all histones, although a functional homolog of H4.V had not yet been … Histone variants play crucial roles in chromatin organization and transcriptional regulation in eukaryotes. Trypanosomatids display histone variants for all histones, although a functional homolog of H4.V had not yet been described in Trypanosoma cruzi. In this study, we identified a putative H4 variant in T. cruzi that is encoded by a single-copy gene located outside of the typical tandem arrays of canonical histones. Functional characterization using ChIP-seq assays revealed that H4.V is located at telomeric regions, demarcates convergent strand-switch regions (cSSRs), and determines new transcription termination sites at codirectional PTUs interrupted by tDNA loci. Throughout the cell cycle, H4.V transcript levels remain stable, while protein abundance increases in G2/M and decreases during cytokinesis, as shown by immunofluorescence and image flow cytometry. In contrast, H2B.V transcripts peak at S-phase, but protein abundance accumulates progressively. H4.V is more abundant in the nuclei of metacyclic trypomastigotes but barely detectable in amastigotes and bloodstream trypomastigotes. In contrast, H2B.V shows a punctate nuclear pattern and is present in all life stages, withthe highest levels also observed in metacyclics. During metacyclogenesis, both variants show a progressive increase in expression, particularly H4.V, suggesting a role in parasite differentiation in the insect vector. Ultimately, salt extraction experiments demonstrated differing chromatin binding affinities across life stages for both variants, with H4.V displaying a more permanent chromatin association than H2B.V, indicating that H4.V may be associated with a more compact chromatin state. Our data reveal H4.V as a novel histone variant in T. cruzi, characterized by unique genomic localization, expression profiles, and chromatin-binding dynamics in contrast to H2B.V, underscoring its potential function as an epigenetic marker in transcriptional regulation and adaptation to diverse host environments.

Effect of diminazene aceturate and in combination with Aloe vera on parasitaemia, serum chemistry, physiological and haematological parameters of West African dwarf goats infected with Trypanosoma congolense

2025-06-19

Ridwan Bolaji Yusuf , Abdulhakeem Binhambali , Suleiman Garba Salihu +2 more | The Journal of Basic and Applied Zoology

Abstract Background Tsetse-transmitted trypanosomiasis severely hampers livestock productivity in Africa, imposing significant economic and health challenges. Traditional trypanocidal treatments are limited by toxicity and emerging drug resistance. Recent interest has … Abstract Background Tsetse-transmitted trypanosomiasis severely hampers livestock productivity in Africa, imposing significant economic and health challenges. Traditional trypanocidal treatments are limited by toxicity and emerging drug resistance. Recent interest has focused on use of ethnoveterinary medicines like Aloe vera (AV) which are known for their medicinal and potential antitrypanosomal properties. This study was designed to evaluate the combined effects of diminazene aceturate (DA) and Aloe vera gel (AVG) on parasitemia, serum chemistry, physiological parameters, and hematological profiles in West African Dwarf Goats (WADG) infected with Trypanosoma congolense . Results Sixteen adult goats were randomly allocated into four groups (A–D) of four animals each. Groups B, C, and D were infected intraperitoneally with 3.0 × 10 6 /mL trypanosomes, while Group A served as the uninfected control. Two weeks post-infection, Group C received 3.5 mg/kg DA alone, and Group D received 3.5 mg/kg DA in combination with 1.2 ml/kg AVG; Group B remained untreated. Treatment was successful in both Groups C and D, but Group D demonstrated a significantly greater improvement in hematological parameters, with higher packed cell volume (PCV), red blood cell (RBC) count, and hemoglobin (Hb) levels compared to Group C. In contrast, untreated goats in Group B exhibited significantly elevated parasitemia, fever, tachypnea, tachycardia, and reductions in key haematological and serum chemistry values. Conclusion The combination of Aloe vera gel with diminazene aceturate not only enhances haematological recovery but also achieves earlier zero parasitemia compared to diminazene aceturate alone. These findings support the potential of integrating Aloe vera as an adjunct therapy in the management of trypanosomiasis in livestock.

TrypPROTACs Unlocking New Therapeutic Strategies for Chagas Disease

2025-06-19

Ana Luísa Rodriguez Gini , Pamela Souza Tada da Cunha , Emílio Emílio João +4 more | Pharmaceuticals

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), continues to pose significant public health challenges due to the toxicity, poor tolerability, and limited efficacy of current treatments. … Chagas disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), continues to pose significant public health challenges due to the toxicity, poor tolerability, and limited efficacy of current treatments. Targeted protein degradation (TPD) using proteolysis-targeting chimeras (PROTACs) represents a novel therapeutic avenue by leveraging the ubiquitin-proteasome system to selectively degrade essential parasite proteins. This review introduces the conceptual framework of "TrypPROTACs" as a prospective strategy for T. cruzi, integrating a comprehensive analysis of druggable targets across critical biological pathways, including ergosterol biosynthesis, redox metabolism, glycolysis, nucleotide synthesis, protein kinases, molecular chaperones such as heat shock protein 90 (Hsp90), and epigenetic regulators such as T. cruzi bromodomain factor 3 (TcBDF3). It is important to note that no TrypPROTAC compound has yet been synthesized or experimentally validated in T. cruzi; the approach discussed herein remains theoretical and forward-looking. Representative inhibitors for each target class are compiled, highlighting potency, selectivity, and structural features relevant to ligand design. We also examine the parasite's ubiquitination machinery and compare it to the human system to identify putative E3 ubiquitin ligases. Key aspects of linker engineering and ternary complex stabilization are discussed, alongside potential validation techniques such as the cellular thermal shift assay (CETSA) and bioluminescence resonance energy transfer (NanoBRET). Collectively, these insights outline a roadmap for the rational design of TrypPROTACs and support the feasibility of expanding targeted protein degradation strategies to neglected tropical diseases.

Bioactivity profiles of progressively ring‐fluorinated cyclohexyl motifs in the WKYMVm peptide as formylpeptide FPR2 agonists and in keto‐piperazines as anti‐trypanosome agents.

2025-06-18

David O’Hagan , Mengfan He , Christina MacGregor Thomson +4 more | ChemBioChem

A series of all‐cis ring fluorinated cyclohexylalanines with progressively increasing levels of vicinal fluorines, as well as 4‐fluorophenylalanine and pentafluoroarylphenylalanine were introduced into the WKYMVm peptide in place of its … A series of all‐cis ring fluorinated cyclohexylalanines with progressively increasing levels of vicinal fluorines, as well as 4‐fluorophenylalanine and pentafluoroarylphenylalanine were introduced into the WKYMVm peptide in place of its tyrosine residue, for assays against the G‐protein coupled formylpeptide receptor, FPR2. Selected all‐cis ring cyclohexylalanines of this class were also incorporated into a keto‐piperazine molecular scaffold to generate sp3 rich derivatives for assays against the parasite Trypanosoma. brucei. For these cyclohexylalanine analogues bioactivity trends correlated progressively with the levels of fluorination in each of the case studies. Notably, the all‐cis pentafluorocyclohexylalanine analogue of the W‐peptide was least active perhaps correlating with the well‐known polarity of this ‘Janus face’ cyclohexane. Although the trend was also apparent in the anti‐trypanosomal assays of the keto‐piperazine derivatives, it was less so and some compounds were more active than the previously reported phenylalanine derived analogue.

Changes in biodiversity drive trypanosome infections of wildlife in Panama

2025-06-18

Magdalena Meyer , Georg Joachim Eibner , Alexander Christoph Heni +2 more | One Health

Association of antibody and T cell receptor repertoires in Trypanosoma cruzi infected rhesus macaques and host response to infection

2025-06-18

Rachel M Clear , Weihong Tu , Kelly Goff +3 more | Journal of Biomedical Science

Abstract Background Chagas disease, caused by Trypanosoma cruzi parasites, leads to chronic cardiac disease in 20–40% of infected patients, while the majority remain asymptomatic. The mechanisms and drivers of pathogenesis … Abstract Background Chagas disease, caused by Trypanosoma cruzi parasites, leads to chronic cardiac disease in 20–40% of infected patients, while the majority remain asymptomatic. The mechanisms and drivers of pathogenesis are still poorly understood, limiting treatment options. We tested for differences in immunoglobulin (Ig) and T cell receptor (TCR) repertoires and their association with T. cruzi parasite diversity (i.e. the cruziome) and host responses in naturally infected rhesus macaques. Methods Ig and TCR complementarity-determination region (CDR)3 sequences were identified from RNA-sequencing data from peripheric blood mononuclear cells of T. cruzi infected rhesus macaques and analyzed for composition and diversity. Results T. cruzi chronic infection was associated with a broader Ig clonotype repertoire, while TCR repertoire presented limited clonal expansion. There was a high individual diversity as most of these repertoires were private, although a few public clonotypes were detected. Remarkably, limited differences in Ig and TCR repertoires were found in association with the cruziome of infected macaques, even though parasite diversity seemed to play an important in shaping the immune response. Conclusion Chronic T. cruzi infection is associated with strong alterations in Ig and TCR repertoires in rhesus macaques, but these repertoires are minimally affected by parasite diversity and host responses to infection. A better understanding of these processes could help develop new immunotherapies against T. cruzi infection.

Mass spectrometry-based discovery and diagnostic validation of T. cruzi antigens in the urine of congenitally infected Chagas Disease patients

2025-06-16

Kathryn Cassels , Raghad Almofeez , Jessica Roman +7 more | PLoS neglected tropical diseases

Background Caused by the parasite Trypanosoma cruzi , Chagas disease affects an estimated 7 million people globally. Diagnosis of Chagas disease in infants is urgently needed, as early detection allows … Background Caused by the parasite Trypanosoma cruzi , Chagas disease affects an estimated 7 million people globally. Diagnosis of Chagas disease in infants is urgently needed, as early detection allows for more effective treatment and reduced mortality. However, current diagnostics are inappropriate for effective detection in infants due to differences in the mechanism of disease in infants and the infant immune system, as well as lack of diagnostic sensitivity and loss to follow up. Studying peripheral biomarkers in urine can leverage physiological concentration in the bladder to increase yield of proteins secreted by pathogen, infected cells, or antigen processed by immune cells residing in different body sites. Principal findings We analyzed the urine of a cohort of infants who were congenitally infected with Chagas disease, using a method including affinity enrichment, mass spectrometry, and bioinformatics analysis to characterize the T. cruzi secreted peptidome. We identified 198 peptides specific for T. cruzi and analyzed them in light of their potential for diagnostic utility. Our protocol revealed that peptides of the hyper-mutating mucin-associated surface protein and trans-sialidase protein families could be identified in patient urine and can serve as diagnostic markers of disease. We developed antibodies against conserved regions of each protein and validated that these antibodies could be used to differentiate the urine of Chagas disease patients (N = 16 cases) from healthy controls (N = 19). By utilizing affinity enrichment sample preprocessing and anti-trans-sialidase and anti-MASP antibodies in tandem, we differentiated cases from controls with 87.5% sensitivity and 94.7% specificity. Conclusions/Significance Our work suggests that it is possible to detect Trypanosoma cruzi infection directly from a noninvasively collected fluid such as urine. A direct test in urine with this success rate would be well suited for rapid diagnosis in low-resource areas. Further studies to validate this approach are warranted.

Reversal of ATP synthase is a key attribute for cellular differentiation of the Trypanosoma brucei insect forms

2025-06-16

Michaela Kunzová , Eva Doleželová , Martin Moos +2 more | bioRxiv (Cold Spring Harbor Laboratory)

The mitochondrial FoF1-ATP synthase is a reversible nanomachine responsible for generating the majority of cellular ATP by oxidative phosphorylation. In various pathological contexts associated with mitochondrial dysfunction, this enzyme can … The mitochondrial FoF1-ATP synthase is a reversible nanomachine responsible for generating the majority of cellular ATP by oxidative phosphorylation. In various pathological contexts associated with mitochondrial dysfunction, this enzyme can reverse its function to maintain essential mitochondrial membrane potential at the expense of ATP. This reversal is regulated by the conserved protein Inhibitory Factor 1 (IF1). Here, we demonstrate that ATP synthase reversal also occurs under physiological conditions during the cellular differentiation of the unicellular parasite Trypanosoma brucei, which transitions between insect and mammalian hosts. Differentiation of the insect forms is marked by upregulation of alternative oxidase (AOX) along with decreased expression of trypanosomal IF1 (TbIF1), collectively creating a metabolic environment conducive to ATP synthase reversal. We show that this reversal is key for proper parasite differentiation: parasites lacking TbIF1 efficiently transitioned into the mammalian-infective form. In these TbIF1 knockout parasites, ATP synthase reversal was associated with an increased ADP/ATP ratio, activation of AMP-activated protein kinase, enhanced cellular respiration driven by elevated proline metabolism, and increased mitochondrial and cellular reactive oxygen species (ROS), known signaling molecules. Conversely, parasites with inducible TbIF1 overexpression failed to reverse ATP synthase activity, showed no AMPK activation or ROS elevation, and remained locked in the initial insect stage. Our findings highlight the critical role of TbIF1 downregulation in enabling life cycle progression and underscore the unique function of the ATP synthase/IF1 axis in cellular signaling.

Stumpy forms are the predominant transmissible forms of Trypanosoma brucei

2025-06-16

Jean Marc Tsagmo Ngoune , Parul Sharma , Aline Crouzols +2 more | eLife

Schuster et al . demonstrated that bloodstream slender forms of African trypanosomes are readily transmissible to young tsetse flies where they can complete their complex life cycle (Schuster et al., … Schuster et al . demonstrated that bloodstream slender forms of African trypanosomes are readily transmissible to young tsetse flies where they can complete their complex life cycle (Schuster et al., 2021). In their experimental conditions, a single slender parasite was sufficient for productive infection. Here, we compared the infectivity of slender and stumpy bloodstream forms in adult flies with a mature immune system, and without using any chemical compounds that would alter the insect immune response and/or promote the infection. After ingestion of slender forms, infected flies were observed only in 1 out of 24 batches of non-immunocompetent teneral flies and with a high number of parasites. In contrast, infected flies were detected in 75% (18/24) of the batches infected with stumpy parasites, and as few as 10 stumpy parasites produced mature infections in immune adult flies. We discuss that, although Schuster et al. have demonstrated the intrinsic capacity of slender form trypanosomes to infect young and naive tsetse flies, highlighting the remarkable plasticity and adaptability of these protists, this phenomenon is unlikely to significantly contribute to the epidemiology of African trypanosomiases. According to both experimental and field observations, stumpy forms appear to be the most adapted forms for African trypanosome transmission from the mammalian host to the tsetse fly vector in natural conditions.

<i>PIGO</i> Gene Variants: New Insights Into Prenatal Diagnosis

2025-06-13

A. Zambiasi , Jacqueline Aziza , Nicolas Chassaing +4 more | Prenatal Diagnosis

Comparative analysis of the mobilome yields new insights into its diversity, dynamics and evolution in parasites of the Trypanosomatidae family

2025-06-13

Percy Omar Tullume-Vergara , Adriana Ludwig , Vyacheslav Yurchenko +6 more | Parasitology

Abstract Transposable elements (TEs) have the ability to move and amplify inside the host genome, making them a pivotal source of genome plasticity. Presently, only 4 TE clades (all classified … Abstract Transposable elements (TEs) have the ability to move and amplify inside the host genome, making them a pivotal source of genome plasticity. Presently, only 4 TE clades (all classified as Class I retrotransposons) have been identified in trypanosomatids. We predicted repeat content and manually curated TEs across the genomes of 57 trypanosomatids, shedding light on their proportions, diversity and dynamics. Our analysis yielded 214 TE consensus sequence models across the dataset, with abundance ranging from 0.1% to 7.2%. We found evidence of recent transposon activity in most species, with notable bursts in the Vickermania, Lafontella, Porcisia and Angomonas spp., along with Leishmania (Mundinia) chancei, L. (M.) orientalis and L. (M.) procaviensis . We confirmed that the 4 TE clades have colonized virtually all lineages of trypanosomatids, potentially playing a role in shaping their genome architecture. The effort of this work culminated in the establishment of the Trypanosomatid TE Database 1.0, a resource designed to standardize the TE annotation process that can serve as a foundation for future studies on trypanosomatid TEs.

Entomological and parasitological current situation of African animal trypanosomosis in the Cascades Region, Burkina Faso

2025-06-11

Soumaïla Pagabeleguem , Lassané Percoma , Sié Hermann Pooda +6 more | International Journal of Biological and Chemical Sciences

In Sub-Saharan countries infested with tsetse flies, African Animal Trypanosomosis is considered as the primary pathological constraint in bovine farming. This study aimed to assess the epidemiological risk of trypanosomosis … In Sub-Saharan countries infested with tsetse flies, African Animal Trypanosomosis is considered as the primary pathological constraint in bovine farming. This study aimed to assess the epidemiological risk of trypanosomosis in four departments of the Special Economic Zone in Burkina Faso, namely Loumana, Niankorodougou, Ouéléni and Niangoloko. The study carried out from December 2022 to February 2023 and combined parasitological and entomological investigations. For the parasitological survey, 704 cows were sampled, and examination using the Buffy-Coat method. For the entomological component, in each village, two tsetse prospection sites were selected and at each site, two biconical traps were set for 72 hours. The parasitological analysis revealed 49 positive cases, resulting in a prevalence of 6.68% (CI: 4.83 - 8.52%). Analysis by department showed the highest prevalence in Loumana (11.60%), which was significantly different from the other three departments (p < 0.03), (Niangoloko (2.58%), Ouéléni (3.23%) and Niankorodougou (6.25%). Two species of trypanosomes were responsible for the infections, Trypanosoma (T.) congolense and T. vivax, with T. congolense being the predominant species (6.68%). A total of 135 tsetse flies were captured, with an overall apparent density of 0.79 flies per trap per day. Glossina palpalis gambiense was the only species encountered. Mechanical vectors were also captured at a low density, with 0.32 flies per trap per day. This study indicates that while the landscape fragmentation is associated with a reduction in tsetse fly species diversity, the trypanosomiasis risk remains significant, as evidenced by the high prevalence in animals.