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1.
Artigo em Inglês | MEDLINE | ID: mdl-38722342

RESUMO

This study aims to evaluate the antitrypanosomiasis activity of a synthetic dichloro-substituted aminochalcone via in vitro assays against infected cell cultures, as well as a theoretical characterization of pharmacokinetics and pharmacodynamics against the protein targets of the evolutionary cycle of T. cruzi. The in vitro evaluation of parasite proliferation inhibition was performed via cytotoxicity analysis on mammalian host cells, effect on epimastigote and trypomastigote forms, and cell death analysis, while computer simulations characterized the electronic structure of (2E)-1-(4-aminophenyl)-3-(2,4-dichlorophenyl)prop-2-en-1-one (DCl), the mechanism of action against the proteins of the evolutionary cycle of T. cruzi: Cruzain, Trypanothione reductase, TcGAPDH, and CYP51 by molecular docking and dynamics and predictive pharmacokinetics by MPO-based ADMET. The in vitro tests showed that the DCl LC50 in order of 178.9 ± 23.9 was similar to the BZN, evidencing the effectiveness of chalcone against Trypomastigotes. Molecular docking and dynamics simulations suggest that DCl acts on the active site of the CYP51 receptor, with hydrogen interactions that showed a high degree of occupation, establishing a stable complex with the target. MPO analysis and ADMET prediction tests suggest that the compound presents an alignment between permeability and hepatic clearance, although it presents low metabolic stability. Chalcone showed stable pharmacodynamics against the CYP51 target, but can form reactive metabolites from N-conjugation and C = C epoxidation, as an indication of controlled oral dose, although the estimated LD50 rate > 500 mg/kg is a indicative of low incidence of lethality by ingestion, constituting a promising therapeutic strategy.

2.
Curr Cardiol Rep ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38656586

RESUMO

PURPOSE OF REVIEW: More than a century since its discovery, the pathogenesis of Chagas heart disease (CHD) remains incompletely understood. The role of derangements in the autonomic control of the heart in triggering malignant arrhythmia before the appearance of contractile ventricular impairment was reviewed. RECENT FINDINGS: Although previous investigations had demonstrated the anatomical and functional consequences of parasympathetic dysautonomia upon the heart rate control, only recently, coronary microvascular disturbances and sympathetic denervation at the ventricular level have been reported in patients and experimental models of CHD, exploring with nuclear medicine methods their impact on the progression of myocardial dysfunction and cardiac arrhythmias. More important than parasympathetic impaired sinus node regulation, recent evidence indicates that myocardial sympathetic denervation associated with coronary microvascular derangements is causally related to myocardial injury and arrhythmia in CHD. Additionally, 123I-MIBG imaging is a promising tool for risk stratification of progression of ventricular dysfunction and sudden death.

3.
Eur J Med Chem ; 271: 116396, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38643671

RESUMO

Neglected tropical diseases (NTDs) comprise diverse infections with more incidence in tropical/sub-tropical areas. In spite of preventive and therapeutic achievements, NTDs are yet serious threats to the public health. Epidemiological reports of world health organization (WHO) indicate that more than 1.5 billion people are afflicted with at least one NTD type. Among NTDs, leishmaniasis, chagas disease (CD) and human African trypanosomiasis (HAT) result in substantial morbidity and death, particularly within impoverished countries. The statistical facts call for robust efforts to manage the NTDs. Currently, most of the anti-NTD drugs are engaged with drug resistance, lack of efficient vaccines, limited spectrum of pharmacological effect and adverse reactions. To circumvent the issue, numerous scientific efforts have been directed to the synthesis and pharmacological development of chemical compounds as anti-infectious agents. A survey of the anti-NTD agents reveals that the majority of them possess privileged nitrogen, sulfur and oxygen-based heterocyclic structures. In this review, recent achievements in anti-infective small molecules against parasitic NTDs are described, particularly from the SAR (Structure activity relationship) perspective. We also explore current advocating strategies to extend the scope of anti-NTD agents.


Assuntos
Doenças Negligenciadas , Doenças Negligenciadas/tratamento farmacológico , Humanos , Relação Estrutura-Atividade , Estrutura Molecular , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia , Animais , Doença de Chagas/tratamento farmacológico , Leishmaniose/tratamento farmacológico , Antiprotozoários/farmacologia , Antiprotozoários/química , Antiprotozoários/síntese química , Testes de Sensibilidade Parasitária , Medicina Tropical
4.
Molecules ; 29(7)2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38611899

RESUMO

2,6-Diaryl-4H-tetrahydro-thiopyran-4-ones and corresponding sulfoxide and sulfone derivatives were designed to lower the major toxicity of their parent anti-kinetoplatidal diarylideneacetones through a prodrug effect. Novel diastereoselective methodologies were developed and generalized from diarylideneacetones and 2,6-diaryl-4H-tetrahydro-thiopyran-4-ones to allow the introduction of a wide substitution profile and to prepare the related S-oxides. The in vitro biological activity and selectivity of diarylideneacetones, 2,6-diaryl-4H-tetrahydro-thiopyran-4-ones, and their S-sulfoxide and sulfone metabolites were evaluated against Trypanosoma brucei brucei, Trypanosoma cruzi, and various Leishmania species in comparison with their cytotoxicity against human fibroblasts hMRC-5. The data revealed that the sulfides, sulfoxides, and sulfones, in which the Michael acceptor sites are temporarily masked, are less toxic against mammal cells while the anti-trypanosomal potency was maintained against T. b. brucei, T. cruzi, L. infantum, and L. donovani, thus confirming the validity of the prodrug strategy. The mechanism of action is proposed to be due to the involvement of diarylideneacetones in cascades of redox reactions involving the trypanothione system. After Michael addition of the dithiol to the double bonds, resulting in an elongated polymer, the latter-upon S-oxidation, followed by syn-eliminations-fragments, under continuous release of reactive oxygen species and sulfenic/sulfonic species, causing the death of the trypanosomal parasites in the micromolar or submicromolar range with high selectivity indexes.


Assuntos
Doença de Chagas , Pró-Fármacos , Piranos , Safrol/análogos & derivados , Compostos de Sulfidrila , Humanos , Animais , Óxidos , Oxirredução , Mamíferos
5.
PLoS Negl Trop Dis ; 18(4): e0012124, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38662649

RESUMO

Chagas disease (CD) is a neglected parasitic zoonotic disease that affects over 6 million people worldwide. We conducted a retrospective study to analyze the spatiotemporal trends and risk factors for hospitalization rates of CD with cardiac and digestive diagnoses in Chile. We used the Mann-Kendall analysis for temporal trends, Global Moran's Index, and Local Indicators of Spatial Association to identify spatial autocorrelation, and regression models to determine the risk factors associated with in-hospital mortality and surgical intervention. Between 2010 and 2020, a total of 654 hospitalizations were reported, corresponding to 527 individuals. The hospitalization rate steadily decreased over the years (t = -0.636; p = 0.009). The Global Moran's I for the study period showed a positive spatial autocorrelation for hospitalization municipality and for residence municipality of CD patients (I = 0.25, p<0.001 and I = 0.45, p<0.001 respectively), indicating a clustering of hospitalizations in northern municipalities. The most frequent diagnosis was a chronic CD with digestive system involvement (55.8%) followed by a chronic CD with heart involvement (44.2%). The highest percentage of hospital discharges was observed among males (56.9%) and in the 60-79 age group (52.7%). In-hospital mortality risk was higher with increasing age (OR = 1.04), and in patients with cardiac involvement (OR = 2.3), whereas factors associated with the risk of undergoing a surgical intervention were sex (OR = 1.6) and diagnosis of CD with digestive involvement (OR = 4.4). The findings of this study indicate that CD is still a significant public health burden in Chile. Efforts should focus on improving access to timely diagnoses and treatment, reducing disease progression and hospitalization burden, and supporting clinicians in preventing complications and deaths.


Assuntos
Doença de Chagas , Mortalidade Hospitalar , Hospitalização , Análise Espaço-Temporal , Humanos , Chile/epidemiologia , Masculino , Feminino , Doença de Chagas/mortalidade , Doença de Chagas/epidemiologia , Hospitalização/estatística & dados numéricos , Fatores de Risco , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Idoso , Doença Crônica , Adulto Jovem , Adolescente , Idoso de 80 Anos ou mais , Criança
6.
Clin Infect Dis ; 78(Supplement_2): S175-S182, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38662705

RESUMO

BACKGROUND: Neglected tropical diseases are responsible for considerable morbidity and mortality in low-income populations. International efforts have reduced their global burden, but transmission is persistent and case-finding-based interventions rarely target asymptomatic individuals. METHODS: We develop a generic mathematical modeling framework for analyzing the dynamics of visceral leishmaniasis in the Indian sub-continent (VL), gambiense sleeping sickness (gHAT), and Chagas disease and use it to assess the possible contribution of asymptomatics who later develop disease (pre-symptomatics) and those who do not (non-symptomatics) to the maintenance of infection. Plausible interventions, including active screening, vector control, and reduced time to detection, are simulated for the three diseases. RESULTS: We found that the high asymptomatic contribution to transmission for Chagas and gHAT and the apparently high basic reproductive number of VL may undermine long-term control. However, the ability to treat some asymptomatics for Chagas and gHAT should make them more controllable, albeit over relatively long time periods due to the slow dynamics of these diseases. For VL, the toxicity of available therapeutics means the asymptomatic population cannot currently be treated, but combining treatment of symptomatics and vector control could yield a quick reduction in transmission. CONCLUSIONS: Despite the uncertainty in natural history, it appears there is already a relatively good toolbox of interventions to eliminate gHAT, and it is likely that Chagas will need improvements to diagnostics and their use to better target pre-symptomatics. The situation for VL is less clear, and model predictions could be improved by additional empirical data. However, interventions may have to improve to successfully eliminate this disease.


Assuntos
Infecções Assintomáticas , Doença de Chagas , Leishmaniose Visceral , Modelos Teóricos , Doenças Negligenciadas , Humanos , Doenças Negligenciadas/prevenção & controle , Doenças Negligenciadas/epidemiologia , Doença de Chagas/transmissão , Doença de Chagas/prevenção & controle , Doença de Chagas/epidemiologia , Doença de Chagas/tratamento farmacológico , Infecções Assintomáticas/epidemiologia , Leishmaniose Visceral/prevenção & controle , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/transmissão , Leishmaniose Visceral/tratamento farmacológico , Tripanossomíase Africana/prevenção & controle , Tripanossomíase Africana/epidemiologia , Tripanossomíase Africana/transmissão , Tripanossomíase Africana/tratamento farmacológico , Índia/epidemiologia , Animais
7.
J Med Entomol ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38564417

RESUMO

Chagas disease is an infectious disease of human and animal health concern, with 6-8 million chronic human infections and over 50,000 deaths throughout the Americas annually. Hematophagous insects of the subfamily Triatominae, also called kissing bugs, vector the protozoan parasite, Trypanosoma cruzi Chagas (Trypanosomatida: Trypanosomatidae), that causes Chagas disease. Despite the large human health burden, Chagas disease is a neglected tropical disease with inadequate funding for research and preventive practices. Given the resource-poor environment of most agencies trying to protect public health, it is critical to consider all control options for reducing vector populations and the risk of human exposure to T. cruzi to identify the most appropriate tools for each context. While numerous triatomine control methods exist, the literature lacks a compilation of the strategies used, a critical examination of their efficiency, and a particular focus on triatomine control in the United States compared to elsewhere in the Americas. Here, we present a review of the literature to assess historical intervention strategies of existing and developing triatomine control methods. For each method, we discuss progress in the field, future research to further advance the method, and limitations. While we found that pyrethroid insecticide is still the most commonly used method of triatomine and Chagas disease control, we suggest that complementing these techniques with alternative control methods in development will help to achieve Chagas disease reduction goals.

8.
Parasitol Int ; 101: 102894, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38604471

RESUMO

Rhodnius species are potential vectors of the etiological agent of Chagas disease (CD), the protozoan Trypanosoma cruzi. CD impacts around seven million people in Latin America, resulting in approximately fourteen thousand deaths per year. Several species of Rhodnius are notable not only for their epidemiological relevance, but also for the challenging distinction between their species. Rhodnius has twenty species, each with its specific epidemiological importance. Rhodnius neglectus and Rhodnius prolixus are found with colonies in domiciliary environments. The observation of eggs in human dwellings signals the colonization process of these insects, increasing the risk of contamination of the population, since correct identification of eggs is necessary to help more effective vector control programs. Here we highlight diagnostic characters of eggs for these three species.

10.
Am J Trop Med Hyg ; 110(4): 663-668, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38452392

RESUMO

Bolivia has one of the highest burdens of Chagas disease in the world. Vertical transmission from mother to infant accounts for a growing number of cases. We performed a systematic review of articles assessing the prevalence of Chagas disease in pregnant women and rates of vertical transmission to infants in Bolivia. Studies were not excluded based on year of publication or language. Random-effects analyses were performed to estimate a pooled prevalence of maternal Chagas disease and pooled vertical transmission rate. Our search yielded 21 articles describing over 400,000 cases of Chagas disease among pregnant women in Bolivia. The reported prevalence of maternal Chagas disease ranged from 17.3% to 64.5%, with a pooled prevalence of 33.0% (95% CI, 27.4-38.7%). The prevalence of maternal Chagas disease trended down over time (P = 0.006), decreasing by approximately 25% to 30% over the last 40 years. Vertical transmission rates ranged from 2.0% to 13% with a pooled average of 6.2% (95% CI, 4.4-7.5%); rates did not significantly change over time. Our study is the first systematic review and meta-analysis of Chagas disease maternal prevalence and vertical transmission in Bolivia. Our findings indicate that maternal Chagas disease has fallen in prevalence but still affects 20% to 30% of pregnant women and poses a considerable risk of vertical transmission. Pregnant women and infants are an important target for public health interventions to limit the mortality and morbidity of Chagas disease and to reduce intergenerational spread.


Assuntos
Doença de Chagas , Trypanosoma cruzi , Lactente , Gravidez , Humanos , Feminino , Prevalência , Bolívia/epidemiologia , Doença de Chagas/epidemiologia , Transmissão Vertical de Doenças Infecciosas , Mães
11.
Artigo em Inglês | MEDLINE | ID: mdl-38545439

RESUMO

Most organisms have developed circadian clocks to adapt to 24-hour cycles in the environment. These clocks have become crucial for modulating and synchronizing complex behavioral and biological processes. A number of parasites seem to have evolved to take advantage of their hosts' circadian rhythms to favor their own infection and survival. Some species, such as Microphallus sp. and Trypanosoma cruzi, can alter the patterns of locomotor behavior of infected intermediate hosts, which can promote transmission to a subsequent primary host. Some fungi of the genera Ophiocordyceps and Entomophthora, as well as hairworms (Nematomorpha), elicit complex behaviors that promote their host's death at a time and place that optimizes continuation of the parasite's life-cycle. At least in some cases, a proposed mechanism might involve a change in the expression of clock-controlled genes. Lastly, some disease-causing protozoan parasites of the genera Trypanosoma, Plasmodium, and Leishmania induce changes in the circadian rhythms of their primary hosts upon infection. Some of these changes may be attributed to circadian alterations resulting from the host's inflammatory response to the infection or other unexplored responses or adaptations to the illness. Thus, a distinction must be made between manipulation of the parasite and response of the host when studying these alterations in the future. Parasitic manipulation of circadian rhythms, which vastly modulates behavior and physiology, is an essential issue that has been relatively understudied. A deeper understanding of this phenomenon could lead to the development of novel therapeutic approaches for the diseases that these parasites convey.

12.
Front Cell Infect Microbiol ; 14: 1297321, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38481660

RESUMO

Chagas' is a neglected disease caused by the eukaryotic kinetoplastid parasite, Trypanosoma cruzi. Currently, approximately 8 million people are infected worldwide, most of whom are in the chronic phase of the disease, which involves cardiac, digestive, or neurologic manifestations. There is an urgent need for a vaccine because treatments are only effective in the initial phase of infection, which is generally underdiagnosed. The selection and combination of antigens, adjuvants, and delivery platforms for vaccine formulations should be designed to trigger mixed humoral and cellular immune responses, considering that T. cruzi has a complex life cycle with both intracellular and bloodstream circulating parasite stages in vertebrate hosts. Here, we report the effectiveness of vaccination with a T. cruzi-specific protein family (TcTASV), employing both recombinant proteins with aluminum hydroxide and a recombinant baculovirus displaying a TcTASV antigen at the capsid. Vaccination stimulated immunological responses by producing lytic antibodies and antigen-specific CD4+ and CD8+ IFNÉ£ secreting lymphocytes. More than 90% of vaccinated animals survived after lethal challenges with T. cruzi, whereas all control mice died before 30 days post-infection. Vaccination also induced a strong decrease in chronic tissue parasitism and generated immunological memory that allowed vaccinated and infected animals to control both the reactivation of the infection after immunosuppression and a second challenge with T. cruzi. Interestingly, inoculation with wild-type baculovirus partially protected the mice against T. cruzi. In brief, we demonstrated for the first time that the combination of the baculovirus platform and the TcTASV family provides effective protection against Trypanosoma cruzi, which is a promising vaccine for Chagas disease.


Assuntos
Doença de Chagas , Parasitos , Vacinas Protozoárias , Trypanosoma cruzi , Vacinas , Humanos , Animais , Camundongos , Baculoviridae/genética , Antígenos de Protozoários/genética , Doença de Chagas/parasitologia , Trypanosoma cruzi/genética , Vacinação , Vacinas Protozoárias/genética
13.
Biomed Pharmacother ; 173: 116307, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38401521

RESUMO

Chagas disease (CHD) is the highest economic burden parasitosis worldwide and the most important cardiac infection, without therapeutic alternatives to halt or reverse its progression. In CHD-experimental models, antioxidant and anti-inflammatory compounds have demonstrated therapeutic potential in cardiac dysfunction. Theobroma cacao polyphenols are potent natural antioxidants with cardioprotective and anti-inflammatory action, which are susceptible to degradation, requiring technological approaches to guarantee their protection, stability, and controlled release. Here, 21 cocoa polyphenol-rich microencapsulates were produced by spray-drying and freeze-drying techniques using two wall materials (maltodextrin and gum arabic). Chemical (total and individual phenolic content and antioxidant activity), structural (morphology), and biological parameters (cytotoxicity, trypanocidal, antioxidant, and immunomodulatory activities) were assessed to determine the most efficient microencapsulation conditions on Trypanosoma cruzi-infected myocardioblast and macrophage cells. Significant antiproliferative properties against infected cells (superior to benznidazole) were found in two microencapsulates which also exhibited cardioprotective properties against oxidative stress, inflammation, and cell death.


Assuntos
Cacau , Trypanosoma cruzi , Humanos , Polifenóis/farmacologia , Polifenóis/química , Antioxidantes/farmacologia , Antioxidantes/química , Cacau/química , Anti-Inflamatórios
14.
Arch Cardiol Mex ; 94(2): 127-132, 2024 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-38377617

RESUMO

OBJECTIVE: Analyze sex hormone's influence during Chagas´ Disease. METHODS: Male and female BALB/c mice were divided into six groups, four experimental (sham, orchiectomized, orchiectomized and supplemented with estradiol, orchiectomized supplemented with testosterone, oophorectomized, oophorectomized and supplemented with estradiol, and oophorectomized and supplemented with testosterone), and two control (healthy and intraperitoneally with T. cruzi strain NINOA infected). Clinical data were recorded daily, parasitemia was evaluated using a Neubauer chamber during the infection, and heart histopathological analysis was performed using the paraffin embedding technique. To analyze parasitemia curves and the area under the parametric curves, two-way ANOVA test was performed to correlate groups´ data. P-values <0.05 were considered statistically significant. RESULTS: Higher mortality rates, cardiomegaly, hepatomegaly, ascites, edema, higher parasitemia levels, more amastigote nests, and more severe inflammatory infiltrate were found in higher testosterone concentration mice, whereas in higher estradiol concentration groups, paresia, prostration, edema, and necrosis were found. CONCLUSIONS: Our results showed that testosterone increased infection severity, whereas estradiol had the opposite effect. This research improves the understanding of sex hormones´infuence upon this infection to contribute with the handling of Chagas´disease.

15.
Nat Commun ; 15(1): 1779, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38413606

RESUMO

Human African trypanosomiasis or sleeping sickness, caused by the protozoan parasite Trypanosoma brucei, is characterized by the manipulation of the host's immune response to ensure parasite invasion and persistence. Uncovering key molecules that support parasite establishment is a prerequisite to interfere with this process. We identified Q586B2 as a T. brucei protein that induces IL-10 in myeloid cells, which promotes parasite infection invasiveness. Q586B2 is expressed during all T. brucei life stages and is conserved in all Trypanosomatidae. Deleting the Q586B2-encoding Tb927.6.4140 gene in T. brucei results in a decreased peak parasitemia and prolonged survival, without affecting parasite fitness in vitro, yet promoting short stumpy differentiation in vivo. Accordingly, neutralization of Q586B2 with newly generated nanobodies could hamper myeloid-derived IL-10 production and reduce parasitemia. In addition, immunization with Q586B2 delays mortality upon a challenge with various trypanosomes, including Trypanosoma cruzi. Collectively, we uncovered a conserved protein playing an important regulatory role in Trypanosomatid infection establishment.


Assuntos
Trypanosoma brucei brucei , Trypanosoma cruzi , Tripanossomíase Africana , Animais , Humanos , Trypanosoma brucei brucei/genética , Interleucina-10/genética , Fatores de Virulência , Parasitemia/parasitologia , Tripanossomíase Africana/parasitologia
16.
Acta Trop ; 252: 107152, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38382592

RESUMO

The control of triatomine vectors depends almost exclusively on conventional insecticides. These compounds can, nevertheless, cause negative effects on environmental and human health as well as induce resistance in triatomines. Therefore, we need to look for more sustainable alternatives. Triatoma pallidipennis is one of the main chagasic vectors in Mexico. We evaluated the insecticidal effectiveness of two oils (neem and cinnamon), and two desiccants (potassium salts of fatty acids and diatomaceous earth), on 3rd instar nymphs of T. pallidipennis. The laboratory test involved direct exposure of the treatments to the insects. We found that diatomaceous earths caused 80 % mortality of nymphs after 30 days. Meanwhile, the cumulative mortality for the other treatments did not exceed 50 %. When applied to inert surfaces, the powder formulation of diatomaceous earth demonstrated greater effectiveness than the aqueous suspension. Thus, diatomaceous earth could be a promising alternative for an environmentally friendly control of triatomines.


Assuntos
Doença de Chagas , Inseticidas , Triatoma , Triatominae , Animais , Humanos , Inseticidas/farmacologia , Terra de Diatomáceas/farmacologia , Insetos Vetores , Ninfa
17.
PLoS Negl Trop Dis ; 18(2): e0011961, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38408095

RESUMO

BACKGROUND: Trypanosoma cruzi and HIV coinfection can evolve with depression of cellular immunity and increased parasitemia. We applied quantitative PCR (qPCR) as a marker for preemptive antiparasitic treatment to avoid fatal Chagas disease reactivation and analyzed the outcome of treated cases. METHODOLOGY: This mixed cross-sectional and longitudinal study included 171 Chagas disease patients, 60 coinfected with HIV. Of these 60 patients, ten showed Chagas disease reactivation, confirmed by parasites identified in the blood, cerebrospinal fluid, or tissues, 12 exhibited high parasitemia without reactivation, and 38 had low parasitemia and no reactivation. RESULTS: We showed, for the first time, the success of the timely introduction of benznidazole in the non-reactivated group with high levels of parasitemia detected by qPCR and the absence of parasites in reactivated cases with at least 58 days of benznidazole. All HIV+ patients with or without reactivation had a 4.0-5.1 higher chance of having parasitemia than HIV seronegative cases. A positive correlation was found between parasites and viral loads. Remarkably, treated T. cruzi/HIV-coinfected patients had 77.3% conversion from positive to negative parasitemia compared to 19.1% of untreated patients. Additionally, untreated patients showed ~13.6 times higher Odds Ratio of having positive parasitemia in the follow-up period compared with treated patients. Treated and untreated patients showed no differences regarding the evolution of Chagas disease. The main factors associated with all-cause mortality were higher parasitemia, lower CD4 counts/µL, higher viral load, and absence of antiretroviral therapy. CONCLUSION: We recommend qPCR prospective monitoring of T. cruzi parasitemia in HIV+ coinfected patients and point out the value of pre-emptive therapy for those with high parasitemia. In parallel, early antiretroviral therapy introduction is advisable, aiming at viral load control, immune response restoration, and increasing survival. We also suggest an early antiparasitic treatment for all coinfected patients, followed by effectiveness analysis alongside antiretroviral therapy.


Assuntos
Doença de Chagas , Coinfecção , Infecções por HIV , Nitroimidazóis , Trypanosoma cruzi , Humanos , Trypanosoma cruzi/genética , Parasitemia/tratamento farmacológico , Parasitemia/parasitologia , Estudos Longitudinais , Estudos Transversais , Estudos Prospectivos , Doença de Chagas/complicações , Doença de Chagas/tratamento farmacológico , Doença de Chagas/parasitologia , Nitroimidazóis/uso terapêutico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Reação em Cadeia da Polimerase , Antiparasitários/uso terapêutico , Coinfecção/parasitologia
18.
J Cardiovasc Electrophysiol ; 35(4): 675-684, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38323491

RESUMO

INTRODUCTION: Despite advancements in implantable cardioverter-defibrillator (ICD) technology, sudden cardiac death (SCD) remains a persistent public health concern. Chagas disease (ChD), prevalent in Brazil, is associated with increased ventricular tachycardia (VT) and ventricular fibrillation (VF) events and SCD compared to other cardiomyopathies. METHODS: This retrospective observational study included patients who received ICDs between October 2007 and December 2018. The study aims to assess whether mortality and VT/VF events decreased in patients who received ICDs during different time periods (2007-2010, 2011-2014, and 2015-2018). Additionally, it seeks to compare the prognosis of ChD patients with non-ChD patients. Time periods were chosen based on the establishment of the Arrhythmia Service in 2011. The primary outcome was overall mortality, assessed across the entire sample and the three periods. Secondary outcomes included VT/VF events and the combined outcome of death or VT/VF. RESULTS: Of the 885 patients included, 31% had ChD. Among them, 28% died, 14% had VT/VF events, and 37% experienced death and/or VT/VF. Analysis revealed that period 3 (2015-2018) was associated with better death-free survival (p = .007). ChD was the only variable associated with a higher rate of VT/VF events (p < .001) and the combined outcome (p = .009). CONCLUSION: Mortality and combined outcome rates decreased gradually for ICD patients during the periods 2011-2014 and 2015-2018 compared to the initial period (2007-2010). ChD was associated with higher VT/VF events in ICD patients, only in the first two periods.


Assuntos
Cardiomiopatias , Desfibriladores Implantáveis , Taquicardia Ventricular , Humanos , Cardiomiopatias/etiologia , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/prevenção & controle , Morte Súbita Cardíaca/etiologia , Desfibriladores Implantáveis/efeitos adversos , América Latina , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/terapia , Taquicardia Ventricular/etiologia , Fibrilação Ventricular/diagnóstico , Fibrilação Ventricular/terapia , Fibrilação Ventricular/etiologia , Estudos Retrospectivos
19.
Parasitol Res ; 123(2): 122, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38311672

RESUMO

Protozoal infections cause significant morbidity and mortality in humans and animals. The use of several antiprotozoal drugs is associated with serious adverse effects and resistance development, and drugs that are more effective are urgently needed. Microorganisms, mammalian cells and fluids, insects, and reptiles are sources of antimicrobial peptides (AMPs) that act against pathogenic microorganisms; these AMPs have been widely studied as a promising alternative therapeutic option to conventional antibiotics, aiming to treat infections caused by multidrug-resistant pathogens. One advantage of AMP molecules is their adaptability, as they can be easily fine-tuned for broad-spectrum or targeted activity by changing the amino acid residues in their sequence. Consequently, these variations in structural and physicochemical properties can alter the antimicrobial activities of AMPs and decrease resistance development. This article presents an overview of peptide activities against amebiasis, giardiasis, trichomoniasis, Chagas disease, leishmaniasis, malaria, and toxoplasmosis. AMPs and their analogs demonstrate great potential as therapeutics, with potent and selective activity, when compared with commercially available drugs, and hold the potential to act as new scaffolds for the development of novel anti-protozoal drugs.


Assuntos
Anti-Infecciosos , Animais , Humanos , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Peptídeos Antimicrobianos , Antibacterianos/uso terapêutico , Mamíferos
20.
Multimedia | Recursos Multimídia, MULTIMEDIA-SMS-SP | ID: multimedia-12759

RESUMO

A Série Educativa Fauna Sinantrópica é um informativo elaborado pela Divisão de Vigilância de Zoonoses (DVZ), que pretende orientar o cidadão sobre o manejo adequado relativo aos animais sinantrópicos, em especial aqueles que podem transmitir doenças, causar agravos à saúde do homem ou de outros animais e que estão presentes na nossa cidade. A série destaca ainda a biologia desse grupo de animais como ciclo de vida, formas de reprodução, como vivem e medidas preventivas para se evitar acidentes.


Assuntos
Educação em Saúde , Triatominae , Doença de Chagas/prevenção & controle , Zoonoses ,
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