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In 2009, a large outbreak of leishmaniasis, associated with environmental changes, was declared near Madrid (Spain), in which Phlebotomus perniciosus was the vector, whereas the main reservoirs were hares and rabbits. Analysis of isolates from humans, vectors and leporids from the focus identified the Leishmania infantum ITS-Lombardi genotype. However, multilocus enzyme electrophoresis (MLEE), the reference technique for Leishmania typing, and sequencing of the hsp70 gene, a commonly used marker, were not performed. In the present study, 19 isolates from P. perniciosus (n = 11), hares (n = 5) and rabbits (n = 3) from the outbreak area, all characterized as ITS-Lombardi in previous studies, were analysed by MLEE and hsp70 sequencing. The hsp70 results confirmed that all the analysed strains are L. infantum. However, by MLEE, 4 different zymodemes of L. infantum were identified based on variable mobilities of the NP1 enzyme: MON-34 (NP1100, n = 11), MON-80 (NP1130, n = 6), MON-24 (NP1140, n = 1) and MON-331 (NP1150, n = 1). The relative frequency of these zymodemes does not correspond to their usual occurrence in Spain. Moreover, MON-34 and MON-80 were found in P. perniciosus, hares and rabbits for the first time. These findings continue to provide insights into the outbreak and call for further studies with a higher number of strains.
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Liebres , Lagomorpha , Leishmania infantum , Humanos , Animales , Conejos , España/epidemiología , Leishmania infantum/genética , Brotes de Enfermedades , Proteínas HSP70 de Choque Térmico/genéticaRESUMEN
Population movements have turned Chagas disease (CD) into a global public health problem. Despite the successful implementation of subregional initiatives to control vectorial and transfusional Trypanosoma cruzi transmission in Latin American settings where the disease is endemic, congenital CD (cCD) remains a significant challenge. In countries where the disease is not endemic, vertical transmission plays a key role in CD expansion and is the main focus of its control. Although several health organizations provide general protocols for cCD control, its management in each geopolitical region depends on local authorities, which has resulted in a multitude of approaches. The aims of this review are to (i) describe the current global situation in CD management, with emphasis on congenital infection, and (ii) summarize the spectrum of available strategies, both official and unofficial, for cCD prevention and control in countries of endemicity and nonendemicity. From an economic point of view, the early detection and treatment of cCD are cost-effective. However, in countries where the disease is not endemic, national health policies for cCD control are nonexistent, and official regional protocols are scarce and restricted to Europe. Countries of endemicity have more protocols in place, but the implementation of diagnostic methods is hampered by economic constraints. Moreover, most protocols in both countries where the disease is endemic and those where it is not endemic have yet to incorporate recently developed technologies. The wide methodological diversity in cCD diagnostic algorithms reflects the lack of a consensus. This review may represent a first step toward the development of a common strategy, which will require the collaboration of health organizations, governments, and experts in the field.
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Enfermedad de Chagas , Trypanosoma cruzi , Enfermedad de Chagas/diagnóstico , Enfermedad de Chagas/tratamiento farmacológico , Enfermedad de Chagas/epidemiología , Humanos , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , InternacionalidadRESUMEN
Increasing levels of boron in water exceeding acceptable thresholds have triggered concerns regarding environmental pollution and adverse health effects. In response, significant efforts are being made to develop new adsorbents for the removal of boron from contaminated water. Among the various materials proposed, inorganic adsorbents have emerged as promising materials due to their chemical, thermal, and mechanical stability. This review aims to comprehensively examine recent advances made in the development of inorganic adsorbents for the efficient removal of boron from water. Firstly, the adsorption performance of the most used adsorbents, such as magnesium, iron, aluminum, and individual and mixed oxides, are summarized. Subsequently, diverse functionalization methods aimed at enhancing boron adsorption capacity and selectivity are carefully analyzed. Lastly, challenges and future perspectives in this field are highlighted to guide the development of innovative high-performance adsorbents and adsorption systems, ultimately leading to a reduction in boron pollution.
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OBJECTIVE: To describe the clinical findings in patients with incidental prostatic amyloidosis. PATIENTS AND METHODS: Retrospective search in the database of the Department of Pathology, Hospital de Bellvitge, for prostate specimens with amyloid. Congo red and immunohistochemical staining of the sections. Review of the patients' clinical charts for symptoms attributable to systemic amyloidosis. RESULTS: Amyloid deposition in the prostate was identified and reported in 40 patients between 2001 and 2022. Median age was 76.5 years (range = 62-90 years). Prostate cancer was diagnosed in 25 patients. Only four patients had a previous diagnosis of amyloidosis. In the remaining 36 the prostate sample (31 needle biopsies, two transurethral resections (TUR), two simple prostatectomies, one radical cystectomy for bladder cancer) provided the initial diagnosis. Amyloid deposits were mainly located in the wall of small vessels and rarely in the prostatic stroma. Immunohistochemistry was available in 32 cases, 26 of which were positive for TTR. All patients showed at least one symptom indicative of systemic amyloidosis, the most frequent being hearing loss (55%), carpal tunnel syndrome (42,5%) or other osteoarticular symptoms (tendinopathies, osteoarthritis), cataracts (37.5%) and cardiac symptoms (32.5%), among others. CONCLUSION: The prostate is a target tissue for amyloid deposition. The incidental finding of amyloid in prostate corresponds, in the majority of cases, to previously undiagnosed systemic TTR amyloidosis in patients lacking signs of heart involvement but having mainly osteoarticular symptoms, hearing and visual impairment.
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Amiloidosis , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas , Anciano , Anciano de 80 o más Años , Amiloide , Amiloidosis/diagnóstico , Amiloidosis/patología , Humanos , Masculino , Persona de Mediana Edad , Próstata/patología , Estudios RetrospectivosRESUMEN
Nephrolithiasis is a multifactor disease that produces nephrolites in the kidneys. Calcium oxalate hydrate (dihydrated, COD, or monohydrated, COM) stones are the most common ones with more than sixty percent incidence worldwide. They are related to different pathologies, COD with hypercalciuria and COM with hyperoxaluria. COD is an unstable species and transforms into COM (herein named TRA to distinguish the origin of the monohydrated species). TRA and COM are chemically and crystallographically identical leading to misdiagnosis and recurrence increase. In the current study, the composition and crystalline structures of several calcium oxalate stones, classified by morpho-constitutional analysis, were examined by IR and synchrotron through-the-substrate micro-X-ray diffraction (tts-µXRD). Both IR and linear diffractogram studies were able to distinguish between the monohydrated and dihydrated phases but not between COM and TRA, as expected. The analysis of 2D diffraction patterns revealed that TRA showed a lower degree of crystallinity and less texture with respect to COM which can be used as a signature to distinguish between the two. This study confirms that despite the subtle differences between COM and TRA, the origin of the monohydrate oxalates can be unraveled using tts-µXRD. This valuable information should be taken into account in order to improve patients' diagnosis and reduce recurrence by considering and treating the origin of the formed stones.
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Oxalato de Calcio , Cálculos Renales , Humanos , Oxalatos , Sincrotrones , Difracción de Rayos XRESUMEN
In Spain, PCR is the tool of choice for the diagnosis of congenital Chagas disease (CD) and serology for diagnosing chronic CD. A loop-mediated isothermal amplification test for Trypanosoma cruzi DNA detection showed good analytical performance and ease of use. We aimed to evaluate the performance of the Loopamp Trypanosoma cruzi detection kit (Eiken Chemical Co. Ltd., Japan) (Tcruzi-LAMP) for congenital and chronic CD diagnosis using well-characterized samples. We included samples from 39 congenital and 174 chronic CD cases and from 48 uninfected children born to infected mothers and 34 nonchagasic individuals. The sensitivity, specificity, and accuracy of Tcruzi-LAMP were estimated using standard case definitions for congenital CD (positive result by parasitological or PCR tests or serology after 9 months of age) and chronic CD (positive serology by at least two tests). The Tcruzi-LAMP results were read by visual examination and a real-time fluorimeter. For congenital CD, Tcruzi-LAMP sensitivity was 97% for both types of reading; specificity was 92% by visual examination and 94% by fluorimeter. For chronic CD, sensitivity was 47% and specificity 100%. The accuracy in congenital CD was >94% versus 56% in chronic CD. The agreement of Tcruzi-LAMP with PCR tests was better in congenital CD (kappa, 0.86 to 0.91) than in chronic CD (kappa, 0.67 to 0.83). The Loopamp Trypanosoma cruzi detection kit showed good performance for the diagnosis of congenital CD. Tcruzi-LAMP, like PCR, can be useful for the screening and early diagnosis of congenital infection.
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Enfermedad de Chagas , Trypanosoma cruzi , Enfermedad de Chagas/diagnóstico , Niño , Humanos , Japón , Técnicas de Diagnóstico Molecular , Técnicas de Amplificación de Ácido Nucleico , Sensibilidad y Especificidad , España/epidemiología , Trypanosoma cruzi/genéticaRESUMEN
Chagas disease is emerging in countries to which it is not endemic. Biomarkers for earlier therapeutic response assessment in patients with chronic Chagas disease are needed. We profiled plasma-derived extracellular vesicles from a heart transplant patient with chronic Chagas disease and showed the potential of this approach for discovering such biomarkers.
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Enfermedad de Chagas , Vesículas Extracelulares , Trasplante de Corazón , Trypanosoma cruzi , Biomarcadores , Enfermedad de Chagas/diagnóstico , Trasplante de Corazón/efectos adversos , HumanosRESUMEN
Calcium oxalate can be found in humans as kidney stones and in cultural heritage as films in two crystallographic species, dihydrate (COD/weddellite) and/or monohydrate (COM/whewellite). Due to its instability, COD is transformed into COM. Studying this crystalline conversion provides information about the origin of the monohydrated species, which will help in the assessment of prevention measurements to avoid their formation. In the present study, the synthesis of calcium oxalate hydrate microcrystals has been carefully performed to avoid mixture of phases in the final products; the long and short range order structure of both species have been studied by X-ray diffraction (XRD) and X-ray absorption spectroscopy (XAS), respectively. This structural information was considered in the density functional theory (DFT) computational study performed to assign the characteristic vibrational IR and Raman frequencies found. This detailed characterization allows an unambiguous assignment of the vibrations, thus providing the appropriate parameters required to monitor and characterize the transformation process.
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Canine leishmaniosis is an important vector-borne zoonosis caused mainly by Leishmania infantum. Diagnosis and treatment of affected individuals can be particularly complex, hindering infection control in endemic areas. Methods to prevent canine leishmaniosis include the use of topical insecticides, prophylactic immunotherapy and vaccination. Four vaccines against canine leishmaniosis have been licensed since 2004, two in Brazil (Leishmune®, the production and marketing licence of which was withdrawn in 2014, and Leish-Tec®) and two in Europe (CaniLeish® and LetiFend®). After several years of marketing, doubts remain regarding vaccine efficacy and effectiveness, potential infectiousness of vaccinated and infected animals or the interference of vaccine-induced antibodies in L. infantum serological diagnosis. This review summarises the scientific evidence for each of the vaccines commercially approved for canine leishmaniosis, while discussing possible weaknesses of these studies. Furthermore, it raises the need to address important questions related to vaccination impact in Leishmania-endemic countries and the importance of post-marketing pharmacological surveillance.
La leishmaniose canine est une importante zoonose à transmission vectorielle causée principalement par Leishmania infantum. Le diagnostic et le traitement des personnes atteintes peuvent être particulièrement complexes, entravant la lutte contre l'infection dans les zones d'endémie. Les méthodes de prévention de la leishmaniose canine comprennent l'utilisation d'insecticides topiques, l'immunothérapie prophylactique et la vaccination. Quatre vaccins contre la leishmaniose canine ont été homologués depuis 2004, deux au Brésil (Leishmune®, dont la licence de production et de commercialisation a été retirée en 2014 et Leish-Tec®) et deux en Europe (CaniLeish® et LetiFend®). Après plusieurs années de commercialisation, des doutes subsistent quant à l'efficacité et à l'effet du vaccin, au potentiel infectieux des animaux vaccinés et infectés ou à l'interférence des anticorps induits par le vaccin dans le diagnostic sérologique de L. infantum. Cette revue résume les données scientifiques de chacun des vaccins commercialement approuvés pour la leishmaniose canine, tout en discutant des possibles faiblesses de ces études. En outre, il soulève la nécessité de répondre à des questions importantes liées à l'impact de la vaccination dans les pays où la Leishmania est endémique et à l'importance de la surveillance pharmacologique post-marketing.
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Enfermedades de los Perros/prevención & control , Leishmaniasis/veterinaria , Animales , Anticuerpos Antiprotozoarios/sangre , Brasil , Comercio , Enfermedades de los Perros/sangre , Perros , Europa (Continente) , Leishmania infantum/inmunología , Leishmaniasis/prevención & control , Vigilancia de Productos Comercializados , Vacunación/veterinaria , Vacunas/efectos adversosRESUMEN
Human leishmaniases are widespread diseases with different clinical forms caused by about 20 species within the Leishmania genus. Leishmania species identification is relevant for therapeutic management and prognosis, especially for cutaneous and mucocutaneous forms. Several methods are available to identify Leishmania species from culture, but they have not been standardized for the majority of the currently described species, with the exception of multilocus enzyme electrophoresis. Moreover, these techniques are expensive, time-consuming, and not available in all laboratories. Within the last decade, mass spectrometry (MS) has been adapted for the identification of microorganisms, including Leishmania However, no commercial reference mass-spectral database is available. In this study, a reference mass-spectral library (MSL) for Leishmania isolates, accessible through a free Web-based application (mass-spectral identification [MSI]), was constructed and tested. It includes mass-spectral data for 33 different Leishmania species, including species that infect humans, animals, and phlebotomine vectors. Four laboratories on two continents evaluated the performance of MSI using 268 samples, 231 of which were Leishmania strains. All Leishmania strains, but one, were correctly identified at least to the complex level. A risk of species misidentification within the Leishmania donovani, L. guyanensis, and L. braziliensis complexes was observed, as previously reported for other techniques. The tested application was reliable, with identification results being comparable to those obtained with reference methods but with a more favorable cost-efficiency ratio. This free online identification system relies on a scalable database and can be implemented directly in users' computers.
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Bases de Datos Factuales , Leishmania/clasificación , Leishmaniasis/diagnóstico , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Biblioteca de Genes , Humanos , Internet , Leishmania/genética , Leishmaniasis/parasitologíaRESUMEN
The immigration of Latin American women of childbearing age has spread the congenital transmission of Chagas disease to areas of nonendemicity, and the disease is now a worldwide problem. Some European health authorities have implemented screening programs to prevent vertical transmission, but the lack of a uniform protocol calls for the urgent establishment of a new strategy common to all laboratories. Our aims were to (i) analyze the trend of passive IgG antibodies in the newborn by means of five serological tests for the diagnosis and follow-up of congenital Trypanosoma cruzi infection, (ii) assess the utility of these techniques for diagnosing a congenital transmission, and (iii) propose a strategy for a prompt, efficient, and cost-effective diagnosis of T. cruzi infection. In noninfected newborns, a continuous decreasing trend of passive IgG antibodies was observed, but none of the serological assays seroreverted in any the infants before 12 months. From 12 months onwards, serological tests achieved negative results in all the samples analyzed, with the exception of the highly sensitive chemiluminescent microparticle immunoassay (CMIA). In contrast, in congenitally infected infants, the antibody decline was detected only after treatment initiation. In order to improve the diagnosis of congenital T. cruzi infection, we propose a new strategy involving fewer tests that allows significant cost savings. The protocol could start 1 month after birth with a parasitological test and/or a PCR. If negative, a serological test would be carried out at 9 months, which if positive, would be followed by another at around 12 months for confirmation.
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Anticuerpos Antiprotozoarios/sangre , Enfermedad de Chagas/diagnóstico , Inmunidad Materno-Adquirida/inmunología , Inmunoglobulina G/sangre , Transmisión Vertical de Enfermedad Infecciosa , Trypanosoma cruzi/inmunología , Anticuerpos Antiprotozoarios/inmunología , Enfermedad de Chagas/parasitología , Preescolar , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Humanos , Inmunoglobulina G/inmunología , Lactante , Recién Nacido , Tamizaje Masivo/métodos , Reacción en Cadena de la Polimerasa/métodos , Pruebas Serológicas , EspañaRESUMEN
Chagas disease has spread to areas that are nonendemic for the disease with human migration. Since no single reference standard test is available, serological diagnosis of chronic Chagas disease requires at least two tests. New-generation techniques have significantly improved the accuracy of Chagas disease diagnosis by the use of a large mixture of recombinant antigens with different detection systems, such as chemiluminescence. The aim of the present study was to assess the overall accuracy of a new-generation kit, the Architect Chagas (cutoff, ≥1 sample relative light units/cutoff value [S/CO]), as a single technique for the diagnosis of chronic Chagas disease. The Architect Chagas showed a sensitivity of 100% (95% confidence interval [CI], 99.5 to 100%) and a specificity of 97.6% (95% CI, 95.2 to 99.9%). Five out of six false-positive serum samples were a consequence of cross-reactivity with Leishmania spp., and all of them achieved results of <5 S/CO. We propose the Architect Chagas as a single technique for screening in blood banks and for routine diagnosis in clinical laboratories. Only gray-zone and positive sera with a result of ≤6 S/CO would need to be confirmed by a second serological assay, thus avoiding false-positive sera and the problem of cross-reactivity with Leishmania species. The application of this proposal would result in important savings in the cost of Chagas disease diagnosis and therefore in the management and control of the disease.
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Enfermedad de Chagas/diagnóstico , Juego de Reactivos para Diagnóstico , Pruebas Serológicas/métodos , Adulto , Enfermedad Crónica , Reacciones Cruzadas , Reacciones Falso Positivas , Humanos , Leishmania/inmunología , Sensibilidad y Especificidad , Factores de TiempoRESUMEN
INTRODUCTION: Immigration has introduced new diseases into Spanish society, one of which is Chagas disease. Young women of childbearing age and children infected with Trypanosoma cruzi from endemic areas are at risk of developing the disease years later, and pregnant women can transmit the infection through the placenta. METHODS: Serological screening for anti-T.cruzi antibodies was performed on all immigrant children coming from a Chagas endemic area and seen in our Pathology Unit between 2003 and 2008, as well as on newborns of T.cruzi positive infected pregnant women coming from Latin America. Two ELISA tests were used (bioelisa Chagas Biokit® with recombinant antigens, and an 'in house' ELISA with crude antigen). Patients with sufficient sample were also screened by nested PCR (TCZ3/Z4). RESULTS: A total of 202 children, aged 1 day to 14 years old were included in the study, of whom 22 (10.8%) were diagnosed with asymptomatic infection, 5 of which were congenital as they were born in this country. All infected patients received treatment with benznidazole, with three of them currently with a serologically negative result after treatment. CONCLUSION: Chagas disease is a new imported paediatric disease that can affect children from endemic countries, but can also be acquired in our country by vertical transmission. Therefore, we believe that it is essential to perform serological screening on all children and pregnant women in the prenatal care from endemic areas, and provide specific treatment for those infected patients, given the good results observed in the paediatric population.
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Enfermedad de Chagas , Adolescente , Enfermedad de Chagas/diagnóstico , Enfermedad de Chagas/tratamiento farmacológico , Niño , Preescolar , Emigrantes e Inmigrantes , Humanos , Lactante , Recién Nacido , Nitroimidazoles/uso terapéutico , España , Tripanocidas/uso terapéuticoRESUMEN
Chagas disease (CD), caused by Trypanosoma cruzi and endemic in Latin America, has become an emergent health problem in non-endemic countries due to human migration. The United States (US) is the non-Latin American country with the highest CD burden and cannot be considered as non-endemic, since triatomine vectors and reservoir animals have been found. Populations of T. cruzi are divided into genetic subdivisions, which are known as discrete typing units (DTUs): TcI to TcVI and TcBat. Autochthonous human T. cruzi infection in the US is sporadic, but it may change due to environmental factors affecting the geographic distribution of triatomines. We aimed to perform a literature review of the genetic diversity of T. cruzi in triatomine vectors and mammalian hosts, including human cases, in the US. The 34 analyzed studies revealed the presence of T. cruzi in 18 states, which was mainly concentrated in Texas, Louisiana and New Mexico. TcI and TcIV were the principal DTUs identified, being TcI the most genotyped (42.4%; 917/2164). This study represents a first attempt to compile the molecular epidemiology of T. cruzi in the US, which is fundamental for predicting the progression of the infection in the country and could be of great help in its future management.
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Leishmaniases are zoonotic diseases caused by protozoa of the genus Leishmania. In Bolivia, leishmaniasis occurs mainly in the cutaneous form (CL) followed by the mucosal or mucocutaneous form (ML or MCL), grouped as tegumentary leishmaniosis (TL), while cases of visceral leishmaniasis (VL) are rare. The cases of TL are routinely diagnosed by parasitological methods: Direct Parasitological Exam (DPE) and axenic culture, the latter being performed only by specialized laboratories. The aim of the present study was to optimize the parasitological diagnosis of TL in Bolivia, using two sampling methods. Samples from 117 patients with suspected TL, obtained by aspiration (n = 121) and scraping (n = 121) of the edge of the lesion were tested by: direct parasitological exam, culture in TSTB medium, and miniculture and microculture in Schneider's medium. A positive laboratory result by any of the four techniques evaluated using either of the two sampling methods was considered the gold standard. Of the 117 suspected patients included, TL was confirmed in 96 (82 %), corresponding 79 of the confirmed cases (82.3 %) to CL and 16 (16.7 %) to ML. Parasitological techniques specificity was 100 % and their analytical sensitivity was greater with scraping samples in TSTB culture (98 %). Scraping samples in TSTB and miniculture correlated well with the reference (Cohen's kappa coefficient=0.88) and showed good reliability (Cronbach's alpha coefficient ≥0.91). Microculture provided positive results earlier than the other culture methods (mean day 4.5). By day 14, 98 % of positive cultures had been detected. Scraping sampling and miniculture were associated with higher culture contamination (6 % and 17 %, respectively). Bacterial contamination predominated, regardless of the sampling and culture method, while filamentous fungi and mixed contamination were more frequently observed in cultures from scraping samples. In conclusion: (i) scraping samples proved more suitable for the diagnosis of TL as they increased analytical sensitivity, are less traumatic for the patient and are safer for laboratory personnel than aspirates; (ii) culture, mainly in TSBT medium, should be used for the diagnosis of TL due to its high sensitivity (doubling the number of cases diagnosed by DPE) and its low cost compared to other culture media.
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Leishmania , Leishmaniasis Cutánea , Leishmaniasis Visceral , Leishmaniasis , Humanos , Bolivia , Reproducibilidad de los Resultados , Leishmaniasis/diagnóstico , Leishmaniasis Visceral/diagnóstico , Leishmaniasis Visceral/parasitología , Leishmaniasis Cutánea/diagnóstico , Leishmaniasis Cutánea/parasitologíaRESUMEN
BACKGROUND: More than six million people worldwide, particularly in vulnerable communities in Latin America, are infected with Trypanosoma cruzi, the causative agent of Chagas disease. Only a small portion have access to diagnosis and treatment. Both drugs used to treat this chronic, neglected infection, benznidazole and nifurtimox, were developed more than 50 years ago, and adverse drug reactions during treatment pose a major barrier, causing 20% of patients to discontinue therapy. Fexinidazole proved efficacious in an earlier, interrupted clinical trial, but the doses evaluated were not well tolerated. The present study evaluated fexinidazole at lower doses and for shorter treatment durations. METHODS: In this randomised, double-blind, phase 2 trial, we included adult patients (18-60 years old) with confirmed T cruzi infection by serology and PCR and without signs of organ involvement. We evaluated three regimens of fexinidazole-600 mg once daily for 10 days (6·0 g total dose), 1200 mg daily for 3 days (3·6 g), and 600 mg daily for 3 days followed by 1200 mg daily for 4 days (6·6 g)-and compared them with a historical placebo control group (n=47). The primary endpoint was sustained negative results by PCR at end of treatment and on each visit up to four months of follow-up. This study is registered with ClinicalTrials.gov, NCT03587766, and EudraCT, 2016-004905-15. FINDINGS: Between Oct 16, 2017, and Aug 7, 2018, we enrolled 45 patients (n=15 for each group), of whom 43 completed the study. Eight (19%) of 43 fexinidazole-treated patients reached the primary endpoint, compared with six (13%) of 46 in the historical control group. Mean parasite load decreased sharply following treatment but rebounded beginning 10 weeks after treatment. Five participants had seven grade 3 adverse events: carpal tunnel, sciatica, device infection, pneumonia, staphylococcal infection, and joint and device dislocation. Two participants discontinued treatment due to adverse events unrelated to fexinidazole. INTERPRETATION: The fexinidazole regimens in this study had an acceptable safety profile but did not prove effective against T cruzi infection. Development of fexinidazole monotherapy for treating T cruzi infection has been stopped. FUNDING: The Drugs for Neglected Diseases initiative.
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Enfermedad de Chagas , Nitroimidazoles , Trypanosoma cruzi , Adulto , Humanos , Adolescente , Adulto Joven , Persona de Mediana Edad , Resultado del Tratamiento , Enfermedad de Chagas/tratamiento farmacológico , Nifurtimox/efectos adversos , Método Doble CiegoRESUMEN
A synthetic glycoarray containing non-reducing α-galactopyranosyl moieties related to mucin O-glycans of the parasite Trypanosoma cruzi was evaluated by a chemiluminescent enzyme-linked immunosorbent assay with sera from patients with chronic Chagas disease. Our data revealed the disaccharide Galα(1,3)Galß as the immunodominant glycotope, which may eventually be employed as a diagnostic antigen for Chagas disease.
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Enfermedad de Chagas/diagnóstico , Epítopos/química , Galactosa/química , Trypanosoma cruzi/química , Reacciones Antígeno-Anticuerpo , Conformación de Carbohidratos , Enfermedad de Chagas/inmunología , Enfermedad de Chagas/microbiología , Ensayo de Inmunoadsorción Enzimática , Epítopos/inmunología , Galactosa/inmunología , Humanos , Trypanosoma cruzi/inmunologíaRESUMEN
The disappearance of lytic, protective antibodies (Abs) from the serum of patients with Chagas disease is accepted as a reliable indicator of parasitological cure. The efficiency of a chemiluminescent enzyme-linked immunosorbent assay based on a purified, trypomastigote-derived glycosylphosphatidylinositol-anchored mucin antigen for the serologic detection of lytic Abs against Trypanosoma cruzi was evaluated in a nonendemic setting using a panel of 92 positive and 58 negative human sera. The technique proved to be highly sensitive {100%; 95% confidence interval (CI) = 96-100} and specific (98.3%; 95% CI = 90.7-99.7), with a kappa score of 0.99. Therefore, this assay can be used to detect active T. cruzi infection and to monitor trypanosomicidal treatment.
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Anticuerpos Antiprotozoarios/sangre , Enfermedad de Chagas/diagnóstico , Ensayo de Inmunoadsorción Enzimática/métodos , Trypanosoma cruzi/inmunología , Antígenos de Protozoos , Estudios de Casos y Controles , Glicosilfosfatidilinositoles , Humanos , LuminiscenciaRESUMEN
Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) is a proteomic technique with proven efficiency in the identification of microorganisms, such as bacteria, fungi, and parasites. The present study aimed to evaluate the usefulness of MALDI-TOF MS for the characterization of Leishmania species circulating in Bolivia using hsp70 gene sequencing as a reference technique. 55 Leishmania strains that were isolated from patients with tegumentary leishmaniasis were analyzed. MALDI-TOF MS identified two species of the L. braziliensis complex (L. braziliensis, n = 26; L. braziliensis outlier, n = 18), one species of the L. guyanensis complex (L. guyanensis, n = 1), one species of the L. lainsoni complex (L. lainsoni, n = 2), and two species of the L. mexicana complex (L. amazonensis, n = 5; and L. garnhami, n = 3). All of the strains were correctly identified at the subgenus, genus, and complex level, but 10 of them (18%) were misidentified as other species within the same complex by the hsp70 gene sequencing, with 7 of these corresponding to possible hybrids. Thus, one L. braziliensis corresponded to L. peruviana, two L. braziliensis corresponded to L. braziliensis/L. peruviana possible hybrids, two L. amazonensis corresponded to L. mexicana, and three L. garnhami and two L. amazonensis corresponded to L. mexicana/L. amazonensis possible hybrids. Accordingly, MALDI-TOF MS could be used as an alternative to molecular techniques for the identification of Leishmania spp., as it is low cost, simple to apply, and able to quickly produce results. In Bolivia, its application would allow for the improvement of the management of patient follow-ups, the updating of the epidemiological data of the Leishmania species, and a contribution to the control of tegumentary leishmaniasis. IMPORTANCE The objective of the study was to evaluate the usefulness of MALDI-TOF MS for the characterization of Leishmania species circulating in Bolivia, in comparison with the sequencing of the hsp70 gene. In our study, all of the isolates could be identified, and no misidentifications were observed at the complex level. Although the equipment implies a high initial investment in our context, MALDI-TOF MS can be used in different areas of microbiology and significantly reduces the cost of testing. Once the parasite culture is obtained, the technique quickly yields information by accessing a free database that is available online. This would allow for the improvement of the management of patients and follow-ups, the updating of the epidemiological data of the species, and a contribution to the control of tegumentary leishmaniasis in Bolivia. Likewise, it can be used to determine a specific treatment to be given, according to the causal species of Leishmania, when there are protocols in this regard in the area.
Asunto(s)
Leishmania , Leishmaniasis , Humanos , Bolivia/epidemiología , Proteómica , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Rayos LáserRESUMEN
BACKGROUND: Trypanosoma cruzi causes Chagas disease (CD), a potentially fatal disease characterized by cardiac disorders and digestive, neurological or mixed alterations. T. cruzi is transmitted to humans by the bite of triatomine vectors; both the parasite and disease are endemic in Latin America and the United States. In the last decades, population migration has changed the classic epidemiology of T. cruzi, contributing to its global spread to traditionally non-endemic countries. Screening is recommended for Latin American populations residing in non-endemic countries. METHODS: The present study analyzes the epidemiological characteristics of 2,820 Latin American individuals who attended the International Health Service (IHS) of the Hospital Clinic de Barcelona between 2002 and 2019. The initial assessment of organ damage among positive cases of T. cruzi infection was analyzed, including the results of electrocardiogram (ECG), echocardiogram, barium enema and esophagogram. RESULTS: Among all the screened individuals attending the clinic, 2,441 (86.6%) were born in Bolivia and 1,993 (70.7%) were female. Of individuals, 1,517 (81.5%) reported previous exposure to the vector, which is a strong risk factor associated with T. cruzi infection; 1,382 individuals were positive for T. cruzi infection. The first evaluation of individuals with confirmed T. cruzi infection, showed 148 (17.1%) individuals with Chagasic cardiomyopathy, the main diagnostic method being an ECG and the right bundle branch block (RBBB) for the most frequent disorder; 16 (10.8%) individuals had a normal ECG and were diagnosed of Chagasic cardiomyopathy by echocardiogram. CONCLUSIONS: We still observe many Latin American individuals who were at risk of T. cruzi infection in highly endemic areas in their countries of origin, and who have not been previously tested for T. cruzi infection. In fact, even in Spain, a country with one of the highest proportion of diagnosis of Latin American populations, T. cruzi infection remains underdiagnosed. The screening of Latin American populations presenting with a similar profile as reported here should be promoted. ECG is considered necessary to assess Chagasic cardiomyopathy in positive individuals, but echocardiograms should also be considered as a diagnostic approach given that it can detect cardiac abnormalities when the ECG is normal.