Development of Diagnostics for Chagas Disease: Where Should We Put Our Limited Resources?
Ontology highlight
ABSTRACT:
SUBMITTER: Picado A
PROVIDER: S-EPMC5221646 | biostudies-literature | 2017 Jan
REPOSITORIES: biostudies-literature
Publications
Development of Diagnostics for Chagas Disease: Where Should We Put Our Limited Resources?
Picado Albert A Angheben Andrea A Marchiol Andrea A Alarcón de Noya Belkisyolé B Flevaud Laurence L Pinazo Maria Jesus MJ Gállego Montserrat M Meymandi Sheba S Moriana Silvia S
PLoS neglected tropical diseases 20170105 1
Similar Datasets
Project description:Globally, more than six million people are infected with Trypanosoma cruzi, the causative protozoan parasite of the vector-borne Chagas disease (CD). We conducted a cross-sectional ethnopharmacological field study in Bolivia among different ethnic groups where CD is hyperendemic. A total of 775 extracts of botanical drugs used in Bolivia in the context of CD and botanical drugs from unrelated indications from the Mediterranean De Materia Medica compiled by Dioscorides two thousand years ago were profiled in a multidimensional assay uncovering different antichagasic natural product classes. Intriguingly, the phylobioactive anthraquinone hotspot matched the antichagasic activity of Senna chloroclada, the taxon with the strongest ethnomedical consensus for treating CD among the Izoceño-Guaraní. Testing common 9,10-anthracenedione derivatives in T. cruzi cellular infection assays demarcates hydroxyanthraquinone as a potential antichagasic lead scaffold. Our study systematically uncovers in vitro antichagasic phylogenetic hotspots in the plant kingdom as a potential resource for drug discovery based on ethnopharmacological hypotheses.
| S-EPMC8040286 | biostudies-literature
Project description:Health system responses to the emergence of non-communicable diseases (NCDs) in many Southeast Asian nations, Cambodia included, have been insufficient. Little is known about how people suffering from such conditions behave in constrained contexts. We examined the experience of patients with NCDs as they seek care for their conditions and manage them.In-depth interviews with 28 purposively selected patients with hypertension and/or diabetes using an interview guide to capture the trajectory followed by interviewees from the development and recognition of symptoms to adherence to treatment. A general outline of major topics to be discussed was used instead of a predetermined list of specific questions.All interviewees had experienced symptoms for a substantial period of time, sometimes many years, before being diagnosed. Initial treatment focused on symptoms instead of underlying conditions, often at considerable financial cost. Following diagnosis, many struggled to take medicines daily for their condition and adhering to the required behaviour changes. Many resorted to complementary medicine. Lack of financial resources was a common reason to discontinue treatment. Many reported loss of income and assets such as livestock and productive land and increasingly relied on others.In order to assist people with NCDs in Cambodia, there is a need for a multipronged approach focusing on communities and healthcare providers. Information campaigns could focus on the timely recognition by communities of symptoms indicative of the conditions, together with instigating demand for routine screening at qualified health providers. Peer support is considerable, and locally adjusted approaches based on this principle should be considered.
| S-EPMC5717921 | biostudies-other
Project description:IntroductionPathogenesis of Chagas disease (CD) caused by the protozoan parasite Trypanosoma cruzi (T. cruzi) involves chronic oxidative and inflammatory stress. In this review, we discuss the research efforts in therapeutic vaccine development to date and the potential challenges imposed by oxidative stress in achieving an efficient therapeutic vaccine against CD.Areas coveredThis review covers the immune and nonimmune mechanisms of reactive oxygen species production and immune response patterns during T. cruzi infection in CD. A discussion on immunotherapy development efforts, the efficacy of antigen-based immune therapies against T. cruzi, and the role of antioxidants as adjuvants is discussed to provide promising insights to developing future treatment strategies against CD.Expert opinionAdministration of therapeutic vaccines can be a good option to confront persistent parasitemia in CD by achieving a rapid, short-lived stimulation of type 1 cell-mediated immunity. At the same time, adjunct therapies could play a critical role in the preservation of mitochondrial metabolism and cardiac muscle contractility in CD. We propose combined therapy with antigen-based vaccine and small molecules to control the pathological oxidative insult would be effective in the conservation of cardiac structure and function in CD.
| S-EPMC8671175 | biostudies-literature
Project description:Chagas disease is a zoonosis caused by the protozoan parasite Trypanosoma cruzi. Transmission cycles are maintained by haematophagous triatomine bug vectors that carry infective T. cruzi in their faeces. Most human infections are acquired by contamination of mucosal membranes with triatomine faeces after being bitten, however, T. cruzi can be transmitted by several other routes. Oral transmission is an increasingly important aspect of Chagas disease epidemiology, typically involving food or drink products contaminated with triatomines. This has recently caused numerous outbreaks and been linked to unusually severe acute infections. The long-term impact of oral transmission on infection dynamics and disease pathogenesis is unclear. We used highly sensitive bioluminescence imaging and quantitative histopathology to study orally transmitted T. cruzi infections in mice. Both metacyclic and bloodform trypomastigotes were infectious via the oral cavity, but only metacyclics led to established infections by intra-gastric gavage. Mice displayed only mild acute symptoms but later developed significantly increased myocardial collagen content (p = 0.017), indicative of fibrosis. Gastrointestinal tissues and skin were the principal chronic infection reservoirs. Chronic phase parasite load profiles, tissue distribution and myocardial fibrosis severity were comparable to needle-injected controls. Thus, the oral route neither exacerbates nor ameliorates experimental Chagas disease.
| S-EPMC6062536 | biostudies-literature
Project description:Chagas disease is the clinical condition triggered by infection with the protozoan Trypanosoma cruzi. The infection is transmitted by triatomine insects while blood feeding on a human host. Field studies predict that one third of an estimated 18 million T cruzi-infected humans in Latin America will die of Chagas disease. Acute infections are usually asymptomatic, but the ensuing chronic T cruzi infections have been associated with high ratios of morbidity and mortality: Chagas heart disease leads to unexpected death in 37.5% of patients, 58% develop heart failure and die and megacolon or megaoesophagus has been associated with death in 4.5%. The pathogenesis of Chagas disease appears to be related to a parasite-induced mutation of the vertebrate genome. Currently, treatment is unsatisfactory.
| S-EPMC2653922 | biostudies-literature
Project description:In ribosome biogenesis, a large fraction of ribosomes is used for producing ribosomal proteins. Here, we deal with the question what fraction of ribosomes should be allocated for synthesis of ribosomal proteins to optimize the cellular economy for growth. We define the "r-fraction" as the fraction of mRNA of the ribosomal protein genes out of the total mRNA and simulated how the amount of the total protein is affected by the r-fraction. Then, we empirically measured the amount of protein and RNA in fission yeast cells cultured at a high or low nitrogen source. In the cells cultured at a low nitrogen source, the r-fraction decreased from 0.46 to 0.42 with a 40% reduction of rRNA, but the reduction of the total protein was smaller at 30%. These results indicate that the r-fraction is internally controlled to optimize the efficiency of protein synthesis at a limited cellular cost.
2015-10-22 | GSE68173 | GEO
Project description:BackgroundHuman resources are a key determinant for the quality of healthcare and health outcomes. Several human resource management approaches or practices have been proposed and implemented to better understand and address health workers' challenges with mixed results particularly in low- and middle-income countries (LMICs). The aim of this framework synthesis was to review the human resources frameworks commonly available to address human resources for health issues in LMIC.MethodsWe searched studies in Medline, Embase, CAB Global Health, CINAHL (EBSCO) and WHO global Index Medicus up to 2021. We included studies that provided frameworks to tackle human resources for health issues, especially for LMICs. We synthesised the findings using a framework and thematic synthesis methods.ResultsThe search identified 8574 studies, out of which 17 were included in our analysis. The common elements of different frameworks are (in descending order of frequency): (1) functional roles of health workers; (2) health workforce performance outcomes; (3) human resource management practises and levers; (4) health system outcomes; (5) contextual/cross-cutting issues; (6) population health outcomes and (7) the humanness of health workers. All frameworks directly or indirectly considered themes around the functional roles of health workers and on the outcomes of health workforce activities, while themes concerning the humanness of health workers were least represented. We propose a synthesised Human-Centred Health Workforce Framework.ConclusionsSeveral frameworks exist providing different recurring thematic areas for addressing human resources for health issues in LMIC. Frameworks have predominantly functional or instrumental dimensions and much less consideration of the humanness of health workers. The paradigms used in policy making, development and funding may compromise the effectiveness of strategies to address human resources challenges in LMIC. We propose a comprehensive human resources for health framework to address these pitfalls.
| S-EPMC11429363 | biostudies-literature
Project description:Obtaining continuing education can be difficult in countries with limited resources. Members of the Pediatric Orthopaedic Society of North America (POSNA) have developed a program for providing outreach continuing education courses in pediatric orthopaedics. POSNA members provide their own transportation to the host country, while the orthopaedic physicians along with the educational institutions in the host country in turn provide the support needed to carry out the courses. They also provide lodging, meals, and local transportation. Since its inception in 1998, 30 courses have been conducted in 19 countries with limited resources. The program has expanded to develop a partnership with the European Pediatric Orthopaedic Society. The protocol for organizing the courses is discussed.
| S-EPMC2584285 | biostudies-other
Project description:Ingroup favoritism and fairness are two potentially competing motives guiding intergroup behaviors in human. Here, we investigate if and how limited resources can modulate the way these two motives affect individuals' decisions in intergroup situation. In the present study, participants (N = 58) were asked to accept or reject three types of resource allocation proposals generated by a computer: the ingroup advantageous condition, outgroup advantageous condition, and neutral condition. In general, participants were more willing to accept the proposals in the ingroup advantageous condition than the outgroup advantageous or the neutral conditions, and also in the moderate inequality than the extreme inequality condition. This may indicate that people sought a careful balance between ingroup favoritism and fairness, although we also found marked individual differences in their preferences for ingroup favoritism or fairness. Importantly, as predicted, participants were more likely to show ingroup favoritism only when limited resources affect the well-being of ingroup members. The present study provides novel insights into the situational and personality factors affecting human intergroup behaviors, shedding light on motives underlying intergroup conflicts prevalent in human societies.
| S-EPMC8927613 | biostudies-literature
Project description:The last three years have been spent combating COVID-19, and governments have been seeking optimal solutions to minimize the negative impacts on societies. Although two types of testing have been performed for this-follow-up testing for those who had close contact with infected individuals and mass-testing of those with symptoms-the allocation of resources has been controversial. Mathematical models such as the susceptible, infectious, exposed, recovered, and dead (SEIRD) model have been developed to predict the spread of infection. However, these models do not consider the effects of testing characteristics and resource limitations. To determine the optimal testing strategy, we developed a testing-SEIRD model that depends on testing characteristics and limited resources. In this model, people who test positive are admitted to the hospital based on capacity and medical resources. Using this model, we examined the infection spread depending on the ratio of follow-up and mass-testing. The simulations demonstrated that the infection dynamics exhibit an all-or-none response as infection expands or extinguishes. Optimal and worst follow-up and mass-testing combinations were determined depending on the total resources and cost ratio of the two types of testing. Furthermore, we demonstrated that the cumulative deaths varied significantly by hundreds to thousands of times depending on the testing strategy, which is encouraging for policymakers. Therefore, our model might provide guidelines for testing strategies in the cases of recently emerging infectious diseases.
| S-EPMC9956024 | biostudies-literature