Israel Molina

Evaluation of a latex agglutination test (KAtex) for detection of Leishmania antigen in urine of patients with HIV-Leishmania coinfection: value in diagnosis and post-treatment follow-up

The usefulness of antigen detection in urine as an alternative tool for diagnosis of leishmaniasis and post-treatment follow-up in patients with Leishmania-HIV coinfection was evaluated with a latex agglutination test (KAtex; Kalon Biological, UK). Forty-nine HIV-infected patients with visceral leishmaniasis were included in the study. Antigen detection in urine (ADU) was positive in 42 of 49 (sensitivity, 85.7%) samples obtained during a primary episode. After treatment, a follow-up study in 23 patients was performed by simultaneous ADU and culture of peripheral blood mononuclear cells in 148 determinations. The two methods gave concordant results in 94 cases, 38 of which were positive and 56 negative. In five cases, ADU was negative and culture of peripheral blood mononuclear cells was positive: two of these cases corresponded to clinical relapses. In 49 cases, culture of peripheral blood mononuclear cells was negative and ADU was positive. In the absence of clinical symptoms, the detection of parasite antigens in 71 of 130 (54.6%) urine samples was not associated with clinical disease. The Kaplan-Meier estimates of the probability of relapse at 6, 12, 18, and 24 months were 16% (95%CI, 15–17%), 20% (95%CI, 18–22%), 31% (95%CI, 27–35%), and 71% (95%CI, 52–89%), respectively, in patients with a positive ADU result. In contrast, when ADU was negative, the probability of relapse was 5% at 6 months (95%CI, 2–8%) (only 2 of 11 patients who relapsed had a negative test). ADU by KAtex is appropriate for primary diagnosis of visceral leishmaniasis, for monitoring the efficacy of treatment, and for detection of subclinical infection.

Prolonged Zika Virus Viremia during Pregnancy

The presence of Zika virus in the blood may be prolonged during pregnancy. In this letter, Zika virus remained detectable for more than 3 months in a pregnant woman.

Trypanosoma cruzi infection in a non-endemic country: epidemiological and clinical profile.

Chagas disease has been increasingly diagnosed in non-endemic countries. This is a prospective observational study performed at the Tropical Medicine Units of the International Health Program of the Catalan Health Institute, Barcelona (PROgrama de Salud Internacional del Instituto Catalán de la Salud, PROSICS Barcelona, Spain), that includes all patients with Chagas disease who attended from June 2007 to May 2012. Clinical and epidemiological data were collected. Overall, 1274 patients were included, the mean age of the patients was 37.7 years, 67.5% were women and 97% came from Bolivia. Thirteen patients had immunosuppressive conditions. The prevalence of cardiac involvement was 16.9%, lower than in previous studies performed in endemic areas (20-60%). Cardiac alterations were found in 33.8% of symptomatic and 14.1% of asymptomatic patients. The prevalence of digestive involvement was 14.8%. The rate of digestive involvement is very different among previous studies because of different diagnostic tools and strategies used. Barium enema alterations were found in 21.4% of symptomatic and 10.3% of asymptomatic patients, and oesophageal alterations were found in 3.7% of symptomatic and in 2.3% of asymptomatic patients. As shown in previous studies, Chagas disease in non-endemic countries affects younger patients and has lower morbidity.

Travel-associated Zika virus disease acquired in the americas through February 2016: A GeoSentinel analysis

Background Zika virus has spread rapidly in the Americas and has been imported into many nonendemic countries by travelers. Objective To describe clinical manifestations and epidemiology of Zika virus disease in travelers exposed in the Americas. Design Descriptive, using GeoSentinel records. Setting 63 travel and tropical medicine clinics in 30 countries. Patients Ill returned travelers with a confirmed, probable, or clinically suspected diagnosis of Zika virus disease seen between January 2013 and 29 February 2016. Measurements Frequencies of demographic, trip, and clinical characteristics and complications. Results Starting in May 2015, 93 cases of Zika virus disease were reported. Common symptoms included exanthema (88%), fever (76%), and arthralgia (72%). Fifty-nine percent of patients were exposed in South America; 71% were diagnosed in Europe. Case status was established most commonly by polymerase chain reaction (PCR) testing of blood and less often by PCR testing of other body fluids or serology and plaque-reduction neutralization testing. Two patients developed Guillain-Barré syndrome, and 3 of 4 pregnancies had adverse outcomes (microcephaly, major fetal neurologic abnormalities, and intrauterine fetal death). Limitation Surveillance data collected by specialized clinics may not be representative of all ill returned travelers, and denominator data are unavailable. Conclusion These surveillance data help characterize the clinical manifestations and adverse outcomes of Zika virus disease among travelers infected in the Americas and show a need for global standardization of diagnostic testing. The serious fetal complications observed in this study highlight the importance of travel advisories and prevention measures for pregnant women and their partners. Travelers are sentinels for global Zika virus circulation and may facilitate further transmission. Primary Funding Source Centers for Disease Control and Prevention, International Society of Travel Medicine, and Public Health Agency of Canada.

Ultrasensitive Real-Time PCR for the Clinical Management of Visceral Leishmaniasis in HIV-Infected Patients

Molecular methods have been proposed as an alternative tool for the diagnosis of visceral leishmaniasis (VL), but no data are available regarding use for monitoring clinical outcome. A prospective cohort study of human immunodeficiency virus-(HIV) and VL-coinfected patients was conducted in a university-affiliated hospital in Barcelona, Spain. Leishmania parasite load was monitored using a real-time polymerase chain reaction (PCR) at baseline and every 3 months. Cutoff values for PCR were determined using receiver operating characteristic (ROC) curves. Overall, 37 episodes were analyzed, and 25 of these episodes were considered as relapsing episodes. A significant decrease of parasite load measured 3 months after treatment could predict the clinical evolution of VL. A parasite load over 0.9 parasites/mL measured 12 months after treatment could predicts relapse with a sensitivity of 100% and a specificity of 90.9%. Monitoring parasite load by an ultrasensitive quantitative Leishmania PCR is useful to predict the risk of relapse after a VL episode in HIV-infected patients.

Usefulness of Strongyloides stercoralis serology in the management of patients with eosinophilia.

Strongyloides stercoralis infection is being increasingly diagnosed out of endemic areas. The aim of this study is to evaluate the usefulness of S. stercoralis serology for the management of probable strongyloidiasis in patients presenting with eosinophilia. Overall, 147 patients were included, 89 (60.5%) patients had a positive S. stercoralis serology. Strongyloides stercoralis larvae were detected only in 15 (10.2%) patients. Twenty-eight patients had human immunodeficiency virus infection. Eighty patients received ivermectin 200 mcg/Kg/day for 2 days, and follow-up 6 months after treatment could be performed in 32 patients: 26 (81.3%) patients reached the response to treatment criteria (negative serology 6 months after treatment or when by enzyme-linked immunosorbent assay the optical density ratio of post-treatment to pre-treatment decreased to 0.6), and 11 (34.4%) patients fulfilled the cure criteria (negative serology 6 months after treatment). Strongyloides stercoralis serology is a useful diagnostic tool both in the diagnosis of probable strongyloidiasis and follow-up after treatment.

Toxic Profile of Benznidazole in Patients with Chronic Chagas Disease: Risk Factors and Comparison of the Product from Two Different Manufacturers

ABSTRACT Benznidazole is considered the first-line treatment option against Chagas disease. The major drawback of benznidazole is its toxicity profile. The main objectives of this study were to describe the adverse events (AEs) in patients with chronic Chagas disease treated with benznidazole, determine the risk factors involved and compare the toxic profiles of two different preparations of the drug from ELEA and Roche. A total of 746 patients were diagnosed with Chagas disease in a 5-year period, and of these 472 were treated with benznidazole. A high proportion of patients (n = 360 [76%]) suffered AEs, the most frequent being those related to hypersensitivity (52.9% of patients), headache (12.5%), and epigastric pain (10.4%). In 72 (12.7%) cases, treatment was discontinued. Overall, women had a higher incidence of AEs compared to men (81.3% versus 66%, P = 0.001) and were subject to higher levels of hypersensitivity-related events. Dermatological events, digestive tract manifestations, and general symptoms had a greater likelihood to appear around day 10 and neurological AEs around day 40 after starting treatment. With respect to liver function and hematological tests, the majority of patients did not suffer significant perturbation of liver enzymes or altered blood cell counts. However, 14 patients suffered from neutropenia, and 14 patients had aminotransferase levels that were more than four times the upper limit of the normal range. Patients treated with the ELEA benznidazole product experienced more arthromyalgia, neutropenia, and neurological disorders (mainly paresthesias) than those treated with the Roche product. Both drug products resulted in approximately the same percentage of permanent withdrawals.

Posaconazole versus benznidazole for chronic Chagas' disease.

To the Editor: In the CHAGASAZOL study, Molina et al. (May 15 issue)1 report on the use of posaconazole, as compared with benznidazole, in adults with chronic Trypanosoma cruzi infection. Significantly more patients receiving posaconazole had treatment failure than those receiving benznidazole. Benznidazole showed sustained trypanocidal activity in 94% of patients who completed treatment and follow-up. The major problem was discontinuation of benznidazole because of allergic dermatitis (in 19% of patients). In order to improve the side-effect profile of benznidazole, we have adopted the following strategies. First, we avoid the use of a daily dose of more than 300 mg, which in our patients seemed to be the cutoff for an increased incidence of side effects. Since the recommended dose of benznidazole for adults is 5 mg per kilogram of body weight per day for 60 days, patients weighing more than 60 kg would typically receive more than 300 mg daily. So in such patients, we administer a fixed dose of 300 mg per day for a total number of days that is equivalent to their weight.2 Second, in patients in whom mild-to-moderate allergic dermatitis develops, we administer low-dose systemic glucocorticoids (20 mg per day of oral prednisone or its equivalent for 10 days, followed by 10 mg per day for 10 more days) without interrupting benznidazole therapy.2,3 In a series of 35 patients who had discontinued benznidazole because of severe dermatitis but still wanted to be treated, we reinitiated benznidazole along with prednisone, with a prednisone dose of 20 mg per day for the first 14 days, followed by 10 mg per day during the remaining days of treatment. With this regimen, 72% of the patients completed the full course of therapy with little or no dermatitis. Anis Rassi, M.D. Anis Rassi, Jr., M.D., Ph.D.

The use of posaconazole against Chagas disease.

Purpose of review The current therapeutic scenario against Chagas disease has been recently updated with the use of the triazoles in clinical trials and several experimental assays (in-vitro and in-vivo models) which are bringing novel and promising evidence for the treatment of Chagas diseases, mainly in its chronic phase. We pretend to analyze all the evidence extracted from the in-vitro and in-vivo assays, and try to understand the poor outcome of posaconazole (POS) in the clinical experience. Recent findings POS is the drug with more advanced development in both experimental model and clinical trial. Despite the promising results initially obtained in the animal model, the clinical trial did not meet expectations. Nevertheless, it has documented the activity against Trypanosoma cruzi either in the animal model or in humans. Also new treatment strategies, combination or sequential schemes, have been evaluated in the animal model. Summary POS has been tested in humans showing activity against T. cruzi, but not enough to reach cure by itself. Those results represent one of the most important breakthroughs in the treatment of Chagas disease, and open a window to new strategies as combination therapies or even sequential treatments.

Tratamiento de la neumonía por Legionella pneumophila. ¿Macrolidos o quinolonas?

Antecedentes Los nuevos macrolidos y las fluorquinolonas constituyen actualmente el tratamiento de eleccion de la neumonia por Legionella pneumophila (NLP). El objetivo de nuestro estudio es analizar la eficacia de claritromicina, azitromicina y levofloxacino en el tratamiento de la NLP. Metodos Estudio prospectivo observacional de todos los pacientes adultos diagnosticados de NLP en el Hospital Universitario Vall d’Hebron de Barcelona entre enero de 2001 y diciembre de 2004. Se han comparado variables clinicas evolutivas (duracion de la fiebre, duracion del ingreso hospitalario y mortalidad) entre 52 pacientes tratados con claritromicina, 43 con azitromicina y 18 con levofloxacino. Resultados No se observaron diferencias significativas en cuanto a la presencia de factores de riesgo, porcentaje de pacientes inmunodeprimidos, gravedad inicial de la neumonia o necesidad de ingreso en la unidad de cuidados intensivos entre los pacientes tratados con claritromicina, azitromicina o levofloxacino. La mortalidad hospitalaria fue del 5,3%. No encontramos diferencias significativas con respecto al tiempo que se tardo en conseguir la apirexia, la media de estancia hospitalaria y la mortalidad entre ninguno de los 3 grupos. Conclusion En nuestra experiencia, la eficacia clinica de claritromicina, azitromicina y levofloxacino es similar para el tratamiento de la NLP.