Pulmonary Infiltrates and Eosinophilia in a 25-Year-Old Traveler

A 25-year-old Spanish male travelled to Senegal in September 2009, where he swam near the Dindefelo fresh-water falls. Five weeks later, he presented with fever, myalgia, and dry cough. His complete blood count showed a hemoglobin level of 157 g/L, platelet count of 123.000 platelets/µL, and a leukocyte count of 8.670 cells/µL, with 9% eosinophils. Malaria smear, blood cultures, and serologies for common viral and bacterial infections were negative. Titers of an indirect hemagglutination test for Schistosoma mansoni were 1∶80. The patient was treated with a single dose of praziquantel (40 mg/kg) and prednisone (30 mg) for three days. After treatment, the dry cough increased and he developed moderate dyspnea, with increasing malaise and myalgia. A second blood sample revealed eosinophilia of 1.200 cells/µL. A chest X-ray showed patchy infiltrates in both lungs (Figure 1), and a CT scan showed multiple peripheral bilateral pseudonodular lesions with surrounding ground-glass-opacity halo

Socio-cultural aspects of Chagas disease: a systematic review of qualitative research.

BACKGROUND: Globally, more than 10 million people are infected with Trypanosoma cruzi, which causes about 20 000 annual deaths. Although Chagas disease is endemic to certain regions of Latin America, migratory flows have enabled its expansion into areas where it was previously unknown. Economic, social and cultural factors play a significant role in its presence and perpetuation. This systematic review aims to provide a comprehensive overview of qualitative research on Chagas disease, both in endemic and non-endemic countries. METHODOLOGY/PRINCIPAL FINDINGS: Searches were carried out in ten databases, and the bibliographies of retrieved studies were examined. Data from thirty-three identified studies were extracted, and findings were analyzed and synthesized along key themes. Themes identified for endemic countries included: socio-structural determinants of Chagas disease; health practices; biomedical conceptions of Chagas disease; patient's experience; and institutional strategies adopted. Concerning non-endemic countries, identified issues related to access to health services and health seeking. CONCLUSIONS: The emergence and perpetuation of Chagas disease depends largely on socio-cultural aspects influencing health. As most interventions do not address the clinical, environmental, social and cultural aspects jointly, an explicitly multidimensional approach, incorporating the experiences of those affected is a potential tool for the development of long-term successful programs. Further research is needed to evaluate this approach

Factors associated with risk behavior in travelers to tropical and subtropical regions

BACKGROUND: Recent decades have seen a rise in population movements and, therefore, the spread of tropical diseases and changes in the epidemiology of global disease patterns. Only 50% of travelers to tropical areas receive pre-travel advice and most of them present risk behaviors for acquiring infections. The aim of this study was to describe the clinical and epidemiological characteristics of travelers and identify factors associated with risk behaviors. METHODS: We made a retrospective, descriptive and analytical study of 772 travelers consulting a tropical medicine clinic in Barcelona in 2010. Data on demographic and clinical variables, travel characteristics and risk behaviors were collected. RESULTS: Among all travelers studied, 65.8% (466/708) received pre-travel advice and 30.7% (209/680) took malaria prophylaxis. At least one risk behavior was reported by 82.6% (587/711) of travelers. People travelling for 1-6 months had a 3-fold higher likelihood of experiencing risk behaviors than people travelling for <1 month (95% CI 1.54-5.81, p=0.001), and those travelling for >6 months had a 13-fold higher likelihood (95% CI 3.11-56.14, p<0.001) compared with the same group. Increasing age was associated with presenting less risk behaviors. CONCLUSIONS: Younger travelers and those making longer trips have a higher number of risk behaviors. Strategies emphasizing advice on risk behavior should focus on these groups

Population pharmacokinetics of benznidazole in adult patients with Chagas disease

AIM: To build a population pharmacokinetic (PopPK) model to characterize benznidazole (BNZ) pharmacokinetics in adults with chronic Chagas disease. METHODS: Prospective, open-label, single-center clinical trial(EudraCT:2011-002900-34;CINEBENZclinicaltrials.govnumber:NCT01755403), approved by the local ethics committee. Patients received 2.5mg/kg/12h (Abarax(R), Elea Laboratory, Argentina) for 60 days. Plasma BZN samples were taken at several times along the study and analyzed by HPLC-UV. The PopPK analysis was done with NONMEMv.7.3. Demographic and biological data were tested as covariates. Intraindividual, interoccasion and residual variability were modeled. Internal and external validations were completed to assess the robustness of the model. Later on, simulations were performed to generate the BNZ concentration-time course profile for different dosage regimens. RESULTS: A total of 358 plasma BZN concentrations from 39 patients were included in the analysis. A one-compartment-PK-model characterized by clearance(CL/F) and apparent volume of distribution(V/F) with first order absorption(Ka) and elimination, adequately described the data (CL/F:1.73 L/h; V/F:89.6 L; Ka:1.15 h-1). No covariates were found to be significant for CL/F and V/F. Internal and external validation of the final model showed adequate results. Data from simulations revealed that a dose of 2.5mg/kg/12h might lead to overexposure in the most of the patients. A lower dose (2.5mg/kg/24h) was able to achieve trough BNZ plasma concentrations within the accepted therapeutic range of 3-6 mg/L. CONCLUSION: A population PK model for BNZ in adults with chronic Chagas disease has been developed. Dosing simulations showed that a BNZ dose of 2.5 mg/kg/24h would adequately keep BNZ trough plasma concentrations within the recommended target range concentrations for the majority of patients

Characterization of digestive involvement in patients with chronic T. cruzi infection in Barcelona, Spain

Background: 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. Methods: 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. Principal findings: 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. Conclusions: 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

Cost-effectiveness of Chagas disease screening in Latin American migrants at primary health-care centres in Europe: a Markov model analysis

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

What to expect and when: benznidazole toxicity in chronic Chagas' disease treatment

Background: Benznidazole is one of the two most effective antiparasitic drugs for Chagas' disease treatment. However, knowledge about its toxicity profile is mostly based on post-marketing observational studies. Objectives: Our study combines data from two prospective clinical trials designed to assess the safety of the drug newly produced by ELEA Laboratories (Abarax(R)). Methods: Eligible participants were selected using a consecutive sampling strategy in the CINEBENZ and BIOMARCHA studies between 2013 and 2016 (EUDRACT 2011-002900-34 and 2012-002645-38, respectively, and clinicaltrials.gov NCT01755403 and NCT01755377, respectively). Enrolled subjects received treatment with 5 mg/kg/day benznidazole orally in two divided doses for 8 weeks and were followed up fortnightly. Results: We observed 305 adverse reactions in 85 of 99 participants (85.9%). Each patient had a median of three adverse reactions, 89.5% were mild and the median duration was 12 days. Most adverse reactions appeared in the first month of treatment except arthritis and peripheral neuropathy. Twenty-six patients did not complete treatment: 2 were withdrawn, 1 for ectopic pregnancy and 1 for epilepsy relapse due to cysticercosis; 2 were lost to follow-up; and 22 were owing to adverse reactions, two of them severe. We observed some unexpected adverse reactions that have not been described previously, such as psychiatric symptoms, erectile dysfunction, menstrual cycle alterations and lung infiltration. Conclusions: There is a very high frequency of adverse reactions to benznidazole. Most adverse reactions are mild, but the treatment burden is significant and unexpected reactions are not rare. Severe reactions are uncommon, but they can be life-threatening. Further studies are necessary to optimize treatment

Immunosuppression and Chagas disease: a management challenge

Immunosuppression, which has become an increasingly relevant clinical condition in the last 50 years, modifies the natural history of Trypanosoma cruzi infection in most patients with Chagas disease. The main goal in this setting is to prevent the consequences of reactivation of T. cruzi infection by close monitoring. We analyze the relationship between Chagas disease and three immunosuppressant conditions, including a description of clinical cases seen at our center, a brief review of the literature, and recommendations for the management of these patients based on our experience and on the data in the literature. T. cruzi infection is considered an opportunistic parasitic infection indicative of AIDS, and clinical manifestations of reactivation are more severe than in acute Chagas disease. Parasitemia is the most important defining feature of reactivation. Treatment with benznidazole and/or nifurtimox is strongly recommended in such cases. It seems reasonable to administer trypanocidal treatment only to asymptomatic immunosuppressed patients with detectable parasitemia, and/or patients with clinically defined reactivation. Specific treatment for Chagas disease does not appear to be related to a higher incidence of neoplasms, and a direct role of T. cruzi in the etiology of neoplastic disease has not been confirmed. Systemic immunosuppressive diseases or immunosuppressants can modify the natural course of T. cruzi infection. Immunosuppressive doses of corticosteroids have not been associated with higher rates of reactivation of Chagas disease. Despite a lack of evidence-based data, treatment with benznidazole or nifurtimox should be initiated before immunosuppression where possible to reduce the risk of reactivation. Timely antiparasitic treatment with benznidazole and nifurtimox (or with posaconazole in cases of therapeutic failure) has proven to be highly effective in preventing Chagas disease reactivation, even if such treatment has not been formally incorporated into management protocols for immunosuppressed patients. International consensus guidelines based on expert opinion would greatly contribute to standardizing the management of immunosuppressed patients with Chagas disease

The Use of Quinacrine in Nitroimidazole-Resistant Giardia Duodenalis: An Old Drug for an Emerging Problem

Background: There is little evidence in the management of refractory giardiasis after treatment with nitroimidazoles. This study estimates the proportion of persistent giardiasis in 3 hospitals in Barcelona, describes risk factors and genotype associated and evaluates the efficacy rate of quinacrine in those with persistent giardiasis. METHODS: A clinical prospective observational study was conducted in patients with giardiasis treated with nitroimidazoles. Those with persistent giardiasis were provided quinacrine. Molecular characterization of Giardia isolates was performed by PCR amplification of a fragment of tpi and bg genes. RESULTS: Seventy-seven patients were recruited and treated with nitroimidazoles and in 14/71 of patients followed-up(20%), Giardia persisted. Refractory giardiasis was associated with malaise(p:0.007) and anorexia(p:0.019), with previous giardiasis(p:0.034) and with previous antibiotic(p:0.02) or antiparasitic(p:0.037). Quinacrine had an effectiveness rate of 100% in refractory giardiasis(n=13,95%CI 75-100). Molecular characterization showed that 17(25%) Giardia isolates belonged to assemblage A, 31(43%) to assemblage B. In refractory giardiasis, assemblage B and A were found as responsible in 6 and 4 cases respectively. CONCLUSIONS: Almost 20% of patients presented persistent giardiasis after nitroimidazole being both assemblage A and B involved. Short course of quinacrine was effective in treating refractory cases and further controlled studies should evaluate its efficacy and safety