Digestive damage due to Chagas disease (CD) occurs in 15-20% of patients diagnosed as a result of peristaltic dysfunction in some endemic areas. The symptoms of chronic digestive CD are non-specific, ...and there are numerous confounders. Diagnosis of CD may easily be missed if symptoms are not evaluated by a well trained physician. Regular tests, as barium contrast examinations, probably lack the necessary sensitivity to detect early digestive damage.
71 individuals with T. cruzi infection (G1) and 18 without (G2) coming from Latin American countries were analyzed. They were asked for clinical and epidemiological data, changes in dietary habits, and history targeting digestive and cardiac CD symptoms. Serological tests for T. cruzi, barium swallow, barium enema, an urea breath test, and esophageal manometry were requested for all patients.
G1 and G2 patients did not show differences in lifestyle and past history. Fifteen (21.1%) of G1 had digestive involvement. Following Rezende criteria, esophagopathy was observed in 8 patients in G1 (11.3%) and in none of those in G2. Manometry disorders were recorded in 34 G1 patients and in six in G2. Isolated hypotensive lower esophageal sphincter (LES) was found in sixteen G1 patients (23.9%) and four G2 patients (28.8%). Achalasia was observed in two G1 patients. Among G1 patients, ineffective esophageal motility was seen in six (five with symptoms), diffuse esophageal spasm in two (one with dysphagia and regurgitation), and nutcracker esophagus in three (all with symptoms). There were six patients with hypertonic upper esophageal sphincter (UES) among G1. Following Ximenes criteria, megacolon was found in ten G1 patients (13.9%), and in none of the G2 patients.
The prevalence of digestive chronic CD in our series was 21.1%. Dysphagia is a non-pathognomonic symptom of CD, but a good marker of early esophageal involvement. Manometry could be a useful diagnostic test in selected cases, mainly in patients with T. cruzi infection and dysphagia in whose situation barium swallow does not evidence alterations. Constipation is a common but non-specific symptom that can be easily managed. Testing for CD is mandatory in a patient from Latin America with constipation or dysphagia, and if diagnosis is confirmed, megacolon and esophageal involvement should be investigated.
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•Despite recent advances, Chagas disease remains a muted public health problem.•Control programs of vertical transmission should be implemented everywhere.•A multidisciplinary ...approach is essential to address a multifaceted health problem.
There are currently two major factors that have modified the epidemiology of Chagas disease in the last decades: climate change and migration flows. In this new scenario, there are new challenges to control and prevent Trypanosoma cruzi infection in endemic countries, such as the control of a wider distribution of triatomine vectors or the reinforcement of vertical transmission programs. In non-endemic areas, few countries are aware of the emergence of this new disease and have established changes in their health systems. To address this new public health challenge, the priorities should be control programs to avoid new cases of T. cruzi infection acquired through vertical transmission, blood transfusion or organ transplant.
In both, endemic and non-endemic areas, the international community and all the actors involved in Chagas disease must join efforts mainly in two directions: better management of the infection in affected individuals and more research to cover the knowledge gap mainly in physiopathology, diagnosis and treatment.
Mounting a balanced and robust humoral immune response is of utmost importance for reducing the infectivity of
. While the role of such a response in controlling the infection is well known, there is ...a lack of tools that can be used to quickly evaluate it. We developed a serum parasite inhibition assay (to evaluate changes in the parasite infection after exposing infective
trypomastigotes to serum samples from infected patients). It is based on Vero cells as the hosts and the Tulahuen β-galactosidase parasite strain, genetically engineered to be quantifiable by spectrophotometry. In parallel, we developed an in-house ELISA to correlate the anti-
antibody titres of the clinical samples with their observed anti-parasitic effect in the serum parasite inhibition assay. Serum samples from chronically
-infected patients significantly inhibited parasite invasion in a titre-dependant manner, regardless of the patient's clinical status, compared to samples from the non-infected controls. In addition, there was a clear correlation between the reactivity of the samples to the whole-parasite lysates by ELISA and the inhibitory effect. The results of this work confirm the previously described anti-parasitic effect of the serum of individuals exposed to
and present a framework for its large-scale evaluation in further studies. The serum parasite inhibition assay represents a reproducible way to evaluate the intensity and anti-parasitic effect of humoral responses against
, which could be applied to the evaluation of candidate antigens/epitopes in the design of Chagas disease vaccine candidates.
There is limited data on the epidemiology of Immune Reconstitution Inflammatory Syndrome (IRIS) in rural sub-Saharan Africa. A prospective observational cohort study was conducted to assess the ...incidence, clinical characteristics, outcome and predictors of IRIS in rural Mozambique.
One hundred and thirty-six consecutive antiretroviral treatment (ART)-naïve HIV-1-infected patients initiating ART at the Manhiça district hospital were prospectively followed for development of IRIS over 16 months. Survival analysis by Cox regression was performed to identify pre-ART predictors of IRIS development.
Thirty-six patients developed IRIS 26.5%, incidence rate 3.1 cases/100 persons-month of ART (95% CI 2.2-4.3). Median time to IRIS onset was 62 days from ART initiation (IQR 35.5-93.5). Twenty-five cases (69.4%) were "unmasking", 10 (27.8%) were "paradoxical", and 1 (2.8%) developed a paradoxical worsening followed by the unmasking of another condition. Systemic OI (OI-IRIS) accounted for 47% (17/36) of IRIS cases, predominantly of KS (8 cases) and TB (6 cases) IRIS. Mucocutaneous IRIS manifestations (MC-IRIS) accounted for 53% (19/36) of IRIS events, mostly tinea (9 cases) and herpes simplex infection (3 cases). Multivariate analysis identified two independent predictors of IRIS development: pre-ART CD4 count <50 cells/µl (HR 2.3, 95% CI 1.19-4.44, p = 0.01) and body mass index (BMI) <18.5 (HR 2.15, 95% CI 1.07-4.3, p = 0.03). The pre-cART proportion of activated T-cells, as well as the immunologic and virologic response to ART were not associated with IRIS development. All patients continued on ART, 7 (19.4%) required hospitalization and there were 3 deaths (8.3%) attributable to IRIS.
IRIS is common in patients initiating ART in rural Mozambique. Pre-ART CD4 counts and BMI can easily be assessed at ART initiation in rural sub-Saharan Africa to identify patients at high risk of IRIS, for whom close supervision is warranted.
Malaria and Chagas disease, caused by Plasmodium spp. and Trypanosoma cruzi parasites, remain important global health problems. Available treatments for those diseases present several limitations, ...such as lack of efficacy, toxic side effects, and drug resistance. Thus, new drugs are urgently needed. The discovery of new drugs may be benefited by considering the significant biological differences between hosts and parasites. One of the most striking differences is found in the purine metabolism, because most of the parasites are incapable of de novo purine biosynthesis. Herein, we have analyzed the in vitro anti-P. falciparum and anti-T. cruzi activity of a collection of 81 purine derivatives and pyrimidine analogs. We firstly used a primary screening at three fixed concentrations (100, 10, and 1 µM) and progressed those compounds that kept the growth of the parasites < 30% at 100 µM to dose–response assays. Then, we performed two different cytotoxicity assays on Vero cells and human HepG2 cells. Finally, compounds specifically active against T. cruzi were tested against intracellular amastigote forms. Purines 33 (IC50 = 19.19 µM) and 76 (IC50 = 18.27 µM) were the most potent against P. falciparum. On the other hand, 6D (IC50 = 3.78 µM) and 34 (IC50 = 4.24 µM) were identified as hit purines against T. cruzi amastigotes. Moreover, an in silico docking study revealed that P. falciparum and T. cruzi hypoxanthine guanine phosphoribosyltransferase enzymes could be the potential targets of those compounds. Our study identified two novel, purine-based chemotypes that could be further optimized to generate potent and diversified anti-parasitic drugs against both parasites.
Schistosomiasis is a parasitic disease reported in 78 countries, with an additional recent outbreak in Corsica. Generally, Schistosoma haematobium causes urogenital problems, whereas S. mansoni, S. ...japonicum, S. mekongi, S. guineensis, and S. intercalatum generate intestinal symptoms. Occasionally, ectopic tissue tropisms and infections by parasites resulting from hybridization occur. Geographical distribution and transmission of Schistosoma species depend on the presence of suitable intermediate snail hosts to complete the life cycle. Here we report on an unusual case of urogenital schistosomiasis in a Dominican adult male, living in Spain, with no history of visiting a known endemic area.
Abstract Background Enteric fever's incidence is decreasing among residents of high-income countries, although it's rising in travelers coming from low-resource endemic settings. The study's aim is ...to describe epidemiological, clinical and laboratory features of patients with enteric fever. Methods Retrospective descriptive study of enteric fever cases diagnosed at a Tropical Medicine Unit in Barcelona, 1993–2012. Results Out of 40 patients, 31(77,5%) were returning travelers, and 70% of them had been in Southern Asia. In the rest of patients without an antecedent of a recent travel, the infection occurred mainly before year 2000. The more frequently reported symptoms were fever and diarrhea, lacking significant differences between S. typhi and S. paratyphi infections. Quinolones were used as empiric treatment in 47.2% of patients, 36.1% received 3rd generation cephalosporins, 2.78% azithromycin and 13.89% other combinations. Resistance to quinolones in the S. paratyphi group (66.7%) was significantly higher compared with the S. typhi group (20%) (p:0.02). 22.5% of patients had treatment failure and 23.6% patients presented complications, none of them had been previously vaccinated. Conclusions The diagnosis of enteric fever was more frequent among travelers coming from Southern-East Asia. Quinolone resistance is widely spread, particularly in S. paratyphi serotypes and should not be considered as first choice treatment anymore.
Summary Background Chagas disease is currently prevalent in European countries hosting large communities from Latin America. Whether asymptomatic individuals at risk of Chagas disease living in ...Europe should be screened and treated accordingly is unclear. We performed an economic evaluation of systematic Chagas disease screening of the Latin American population attending primary care centres in Europe. Methods We constructed a decision tree model that compared the test option (screening of asymptomatic individuals, treatment, and follow-up of positive cases) with the no-test option (screening, treating, and follow-up of symptomatic individuals). The decision tree included a Markov model with five states, related to the chronic stage of the disease: indeterminate, cardiomyopathy, gastrointestinal, response to treatment, and death. The model started with a target population of 100 000 individuals, of which 4·2% (95% CI 2·2–6·8) were estimated to be infected by Trypanosoma cruzi . The primary outcome was the incremental cost-effectiveness ratio (ICER) between test and no-test options. Deterministic and probabilistic analyses (Monte Carlo simulations) were performed. Findings In the deterministic analysis, total costs referred to 100 000 individuals in the test and no-test option were €30 903 406 and €6 597 403 respectively, with a difference of €24 306 003. The respective number of quality-adjusted life-years (QALYs) gained in the test and no-test option were 61 820·82 and 57 354·42. The ICER was €5442. In the probabilistic analysis, total costs for the test and no-test option were €32 163 649 (95% CI 31 263 705–33 063 593) and €6 904 764 (6 703 258–7 106 270), respectively. The respective number of QALYs gained was 64 634·35 (95% CI 62 809·6–66 459·1) and 59 875·73 (58 191·18–61 560·28). The difference in QALYs gained between the test and no test options was 4758·62 (95% CI 4618·42–4898·82). The incremental cost-effectiveness ratio (ICER) was €6840·75 (95% CI 2545–2759) per QALY gained for a treatment efficacy of 20% and €4243 per QALY gained for treatment efficacy of 50%. Even with a reduction in Chagas disease prevalence to 0·05% and with large variations in all the parameters, the test option would still be more cost-effective than the no-test option (less than €30000 per QALY). Interpretation Screening for Chagas disease in asymptomatic Latin American adults living in Europe is a cost-effective strategy. Findings of our model provide an important element to support the implementation of T cruzi screening programmes at primary health centres in European countries hosting Latin American migrants. Funding European Commission 7th Framework Program.
infection causes Chagas disease, which affects 7 million people worldwide. Two drugs are available to treat it: benznidazole and nifurtimox. Although both are efficacious against the acute stage of ...the disease, this is usually asymptomatic and goes undiagnosed and untreated. Diagnosis is achieved at the chronic stage, when life-threatening heart and/or gut tissue disruptions occur in ~30% of those chronically infected. By then, the drugs' efficacy is reduced, but not their associated high toxicity. Given current deficiencies in diagnosis and treatment, a vaccine to prevent infection and/or the development of symptoms would be a breakthrough in the management of the disease. Current vaccine candidates are mostly based on the delivery of single antigens or a few different antigens. Nevertheless, due to the high biological complexity of the parasite, targeting as many antigens as possible would be desirable. In this regard, an epitope-based vaccine design could be a well-suited approach. With this aim, we have gone through publicly available databases to identify
epitopes from several antigens. By means of a computer-aided strategy, we have prioritized a set of epitopes based on sequence conservation criteria, projected population coverage of Latin American population, and biological features of their antigens of origin. Fruit of this analysis, we provide a selection of CD8
T cell, CD4
T cell, and B cell epitopes that have <70% identity to human or human microbiome protein sequences and represent the basis toward the development of an epitope-based vaccine against
.
Chagas disease (CD) has significant global health impact, but safe, effective treatments remain elusive. The nitroimidazole fexinidazole is a potential treatment.
This double-blind, randomized, ...placebo-controlled, dose-finding, proof-of-concept study was conducted in Bolivia. Adults with serologically confirmed chronic indeterminate CD and positive PCR were randomly assigned to 1 of 6 fexinidazole regimens (1200 or 1800 mg/day for 2, 4, or 8 weeks) or placebo. Target recruitment was 20 patients/arm. The primary endpoint was sustained parasitological clearance by serial negative qPCR from end of treatment (EOT) until 6 months follow-up in the intention-to-treat (ITT) population. Follow-up was extended to 12 months.
Enrollment was interrupted after 4/47 patients presented with transient asymptomatic grade 3 and 4 neutropenia. Treatment of ongoing patients was stopped in all patients administered >2 weeks. A total of 40 patients received treatment with fexinidazole from 3 days to 8 weeks. Delayed-onset neutropenia (n = 8) and increased liver enzymes (n = 8) were found in fexinidazole patients vs none in the placebo arm. In the ITT analysis, sustained parasitological clearance from EOT to 12 months follow-up varied between 66.7% (1200 mg-2 week) and 100.0% (1800 mg-2 week). Rapid, sustained clearance of parasitemia was observed in all treated patients with available data, but not in any patients in the placebo group, at 12 months (P = .0056). Further exploratory exposure-response analysis suggested low dosages of fexinidazole may be safe and effective.
Further evaluation is needed to establish fexinidazole's minimum effective dosage and risk-benefit relationship. Results suggest potential for effective treatment regimens <10 days.
NCT02498782.
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