Thromboembolic events were described in patients with Chagas disease without cardiomyopathy. We aim to confirm if there is a hypercoagulable state in these patients and to determine if there is an ...early normalization of hemostasis factors after antiparasitic treatment. Ninety-nine individuals from Chagas disease-endemic areas were classified in two groups: G1, with T.cruzi infection (n = 56); G2, healthy individuals (n = 43). Twenty-four hemostasis factors were measured at baseline. G1 patients treated with benznidazole were followed for 36 months, recording clinical parameters and performance of conventional serology, chemiluminescent enzyme-linked immunosorbent assay (trypomastigote-derived glycosylphosphatidylinositol-anchored mucins), quantitative polymerase chain reaction, and hemostasis tests every 6-month visits. Prothrombin fragment 1+2 (F1+2) and endogenous thrombin potential (ETP) were abnormally expressed in 77% and 50% of infected patients at baseline but returned to and remained at normal levels shortly after treatment in 76% and 96% of cases, respectively. Plasmin-antiplasmin complexes (PAP) were altered before treatment in 32% of G1 patients but normalized in 94% of cases several months after treatment. None of the patients with normal F1+2 values during follow-up had a positive qRT-PCR result, but 3/24 patients (13%) with normal ETP values did. In a percentage of chronic T. cruzi infected patients treated with benznidazole, altered coagulation markers returned into normal levels. F1+2, ETP and PAP could be useful markers for assessing sustained response to benznidazole.
Abstract
Background
Chagas disease is a neglected zoonosis caused by the parasite
Trypanosoma cruzi
. It affects over six million people, mostly in Latin America. Drugs available to treat
T. cruzi
...infection have associated toxicity and questionable efficacy at the chronic stage. Hence, the discovery of more effective and safer drugs is an unmet medical need. For this, natural products represent a pool of unique chemical diversity that can serve as excellent templates for the synthesis of active molecules.
Methods
A collection of 79 extracts of Amaryllidaceae plants were screened against
T. cruzi
. Active extracts against the parasite were progressed through two cell toxicity assays based on Vero and HepG2 cells to determine their selectivity profile and discard those toxic to host cells. Anti-
T. cruzi
-specific extracts were further qualified by an anti-amastigote stage assay.
Results
Two extracts, respectively from
Crinum erubescens
and
Rhodophiala andicola
, were identified as highly active and specific against
T. cruzi
and its mammalian replicative form.
Conclusions
The results retrieved in this study encourage further exploration of the chemical content of these extracts in search of new anti-
T. cruzi
drug development starting points.
Graphic abstract
Chagas disease (CD) is caused by the parasite Trypanosoma cruzi and affects 6–7 million people worldwide. The diagnosis is still challenging, due to extensive parasite diversity encompassing seven ...genotypes (TcI-VI and Tcbat) with diverse ecoepidemiological, biological, and pathological traits. Chemotherapeutic intervention is usually effective but associated with severe adverse events. The development of safer, more effective therapies is hampered by the lack of biomarker(s) (BMKs) for the early assessment of therapeutic outcomes. The mammal-dwelling trypomastigote parasite stage expresses glycosylphosphatidylinositol-anchored mucins (tGPI-MUC), whose O-glycans are mostly branched with terminal, nonreducing α-galactopyranosyl (α-Gal) glycotopes. These are absent in humans, and thus highly immunogenic and inducers of specific CD anti-α-Gal antibodies. In search for α-Gal-based BMKs, here we describe the synthesis of neoglycoprotein NGP11b, comprised of a carrier protein decorated with the branched trisaccharide Galα(1,2)Galα(1,6)Galβ. By chemiluminescent immunoassay using sera/plasma from chronic CD (CCD) patients from Venezuela and Mexico and healthy controls, NGP11b exhibited sensitivity and specificity similar to that of tGPI-MUC from genotype TcI, predominant in those countries. Preliminary evaluation of CCD patients subjected to chemotherapy showed a significant reduction in anti-α-Gal antibody reactivity to NGP11b. Our data indicated that NGP11b is a potential BMK for diagnosis and treatment assessment in CCD patients.
We evaluate the association between Trypanosoma cruzi infection and strongyloidiasis in a cohort of Latin American (LA) migrants screened for both infections in a non-endemic setting.
Case-control ...study including LA individuals who were systematically screened for T. cruzi infection and strongyloidiasis between January 2013 and April 2015. Individuals were included as cases if they had a positive serological result for Strongyloides stercoralis. Controls were randomly selected from the cohort of individuals screened for T. cruzi infection that tested negative for S. stercoralis serology. The association between T. cruzi infection and strongyloidiasis was evaluated by logistic regression models.
During the study period, 361 individuals were screened for both infections. 52 (14.4%) individuals had a positive serological result for strongyloidiasis (cases) and 104 participants with negative results were randomly selected as controls. 76 (48.7%) indiviuals had a positive serological result for T. cruzi. Factors associated with a positive T. cruzi serology were Bolivian origin (94.7% vs 78.7%; p = 0.003), coming from a rural area (90.8% vs 68.7%; p = 0.001), having lived in an adobe house (88.2% vs 70%; p = 0.006) and a referred contact with triatomine bugs (86.7% vs 63.3%; p = 0.001). There were more patients with a positive S. stercoralis serology among those who were infected with T. cruzi (42.1% vs 25%; p = 0.023). Epidemiological variables were not associated with a positive strongyloidiasis serology. T. cruzi infection was more frequent among those with strongyloidiasis (61.5% vs 42.3%; p = 0.023). In multivariate analysis, T. cruzi infection was associated with a two-fold increase in the odds of strongyloidiasis (OR 2.23; 95% CI 1.07-4.64; p = 0.030).
T. cruzi infection was associated with strongyloidiasis in LA migrants attending a tropical diseases unit even after adjusting for epidemiological variables. These findings should encourage physicians in non-endemic settings to implement a systematic screening for both infections in LA individuals.
Intravenous artesunate improves survival in severe malaria, but clinical trial data from nonendemic countries are scarce. The TropNet severe malaria database was analyzed to compare outcomes of ...artesunate vs quinine treatment. Artesunate reduced parasite clearance time and duration of intensive care unit and hospital treatment in European patients with imported severe malaria.
Delayed haemolytic anaemia is one of the more frequent events after treatment with intravenous artesunate in patients with severe malaria. Little is known about its frequency and the outcomes of ...patients with this condition.
A retrospective study was conducted to describe the incidence of delayed haemolysis in a cohort of patients with severe malaria by Plasmodium falciparum treated with artesunate between August 2013 and July 2015.
The study included 52 patients with malaria due to Plasmodium falciparum, with 21 having severe malaria. The majority were male (66.7%), and the median age was 43 years. Four patients (19%) presented post-artesunate delayed haemolysis 11•13 days from the initiation of treatment. Two patients required hospital admission and red blood cell transfusion.
Post-artesunate delayed haemolysis is frequent in patients with severe malaria treated with intravenous artemisinins. These patients should be monitored for 4 weeks after treatment is started.
La anemia hemolítica diferida es uno de los acontecimientos más frecuentes tras el tratamiento con artesunato intravenoso en pacientes con malaria grave. Se desconocen con exactitud la frecuencia y evolución de los pacientes que la presentan.
Estudio retrospectivo sobre la incidencia de hemólisis diferida en una cohorte de pacientes con malaria grave por Plasmodium falciparum tratados con artesunato intravenoso entre agosto de 2013 y julio de 2015.
De 52 pacientes con malaria por Plasmodium falciparum, 21 cumplían criterios de gravedad. La mayoría eran hombres (66,7%) y la mediana de edad era de 43 años. Cuatro pacientes (19%) presentaron hemólisis diferida post-artesunato, de 11 a 13 días tras el inicio del tratamiento. Dos pacientes requirieron hospitalización y transfusión de hematíes.
La hemólisis diferida post-artesunato es frecuente en los pacientes con malaria grave tratados con artesunato intravenoso. Estos pacientes deben ser monitorizados al menos 4 semanas tras el tratamiento.
Traveler's diarrhea (TD) is the most frequent health problem in travelers to developing countries. Several personal and environmental risk factors are at the basis of TD acquisition and are discussed ...in this paper. TD is caused by a wide range of infectious organisms, ETEC and EAEC bacteria strains being the main enteropathogens incriminated in TD. Other causative bacteria are: Shigella spp., Campylobacter spp., Vibrio spp., Aeromonas spp., Salmonella spp., and Plesiomonas spp. Parasite species are also included: Cyclospora cayetanensis, Giardia lamblia, Cryptosporidium, Entamoeba histolytica, as well as viruses: rotavirus, adenovirus, Norwalk virus. Due to the great diversity of pathogens incriminated, several pathophysiological mechanisms have been described and some of them are still poorly understood. The clinical symptoms present are also quite variable, although inflammatory and non-inflammatory diarrhea have been established as a classical and basic classification of diarrhea.
Chagas disease is caused by the protozoan parasite
, and it is the most important neglected tropical disease in the Americas. Two drugs are available to treat the infection, but their efficacy in the ...chronic stage of the disease, when most cases are diagnosed, is reduced. Their tolerability is also hindered by common adverse effects, making the development of safer and efficacious alternatives a pressing need.
is unable to synthesize purines de novo, relying on a purine salvage pathway to acquire these from its host, making it an attractive target for the development of new drugs.
We evaluated the anti-parasitic activity of 23 purine analogs with different substitutions in the complementary chains of their purine rings. We sequentially screened the compounds' capacity to inhibit parasite growth, their toxicity in Vero and HepG2 cells, and their specific capacity to inhibit the development of amastigotes. We then used in-silico docking to identify their likely targets.
Eight compounds showed specific anti-parasitic activity, with IC
values ranging from 2.42 to 8.16 μM. Adenine phosphoribosyl transferase, and hypoxanthine-guanine phosphoribosyl transferase, are their most likely targets.
Our results illustrate the potential role of the purine salvage pathway as a target route for the development of alternative treatments against
infection, highlithing the apparent importance of specific substitutions, like the presence of benzene groups in the C8 position of the purine ring, consistently associated with a high and specific anti-parasitic activity.
BackgroundThe best strategy for controlling morbidity due to imported strongyloidiasis in migrants is unclear. We evaluate the cost-effectiveness of six possible interventions.MethodsWe developed a ...stochastic Markov chain model. The target population was adult migrants from endemic countries to the European Union; the time horizon, a lifetime and the perspective, that of the health system. Average and incremental cost-effectiveness ratios (ACER and ICER) were calculated as 2016 EUR/life-year gained (LYG). Health interventions compared were: base case (no programme), primary care-based presumptive treatment (PCPresTr), primary care-based serological screening and treatment (PCSerTr), hospital-based presumptive treatment (HospPresTr), hospital-based serological screening and treatment (HospSerTr), hospital-based presumptive treatment of immunosuppressed (HospPresTrim) and hospital-based serological screening and treatment of the immunosuppressed (HospSerTrim). The willingness to pay threshold (WTP) was €32 126.95/LYG.ResultsThe base case model yielded a loss of 2 486 708.24 life-years and cost EUR 3 238 393. Other interventions showed the following: PCPresTr: 2 488 095.47 life-years (Δ1 387.23LYG), cost: EUR 8 194 563; ACER: EUR 3573/LYG; PCSerTr: 2 488 085.8 life-years (Δ1377.57LYG), cost: EUR 207 679 077, ACER: EUR 148 407/LYG; HospPresTr: 2 488 046.17 life-years (Δ1337.92LYG), cost: EUR 14 559 575; ACER: EUR 8462/LYG; HospSerTr: 2 488 024.33 life-years (Δ1316.08LYG); cost: EUR 207 734 073; ACER: EUR 155 382/LYG; HospPresTrim: 2 488 093.93 life-years, cost: EUR 1 105 483; ACER: EUR −1539/LYG (cost savings); HospSerTrim: 2 488 073.8 life-years (Δ1365.55LYG), cost: EUR 4 274 239; ACER: EUR 759/LYG. One-way and probabilistic sensitivity analyses were undertaken; HospPresTrim remained below WTP for all parameters’ ranges and iterations.ConclusionPresumptively treating all immunosuppressed migrants from areas with endemic Strongyloides would generate cost savings to the health system.
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