Current therapeutic options for Chagas' disease are limited to benznidazole and nifurtimox, which have been associated with low cure rates in the chronic stage of the disease and which have ...considerable toxicity. Posaconazole has shown trypanocidal activity in murine models.
We performed a prospective, randomized clinical trial to assess the efficacy and safety of posaconazole as compared with the efficacy and safety of benznidazole in adults with chronic Trypanosoma cruzi infection. We randomly assigned patients to receive posaconazole at a dose of 400 mg twice daily (high-dose posaconazole), posaconazole at a dose of 100 mg twice daily (low-dose posaconazole), or benznidazole at a dose of 150 mg twice daily; all the study drugs were administered for 60 days. We assessed antiparasitic activity by testing for the presence of T. cruzi DNA, using real-time polymerase-chain-reaction (rt-PCR) assays, during the treatment period and 10 months after the end of treatment. Posaconazole absorption was assessed on day 14.
The intention-to-treat population included 78 patients. During the treatment period, all the patients tested negative for T. cruzi DNA on rt-PCR assay beyond day 14, except for 2 patients in the low-dose posaconazole group who tested positive on day 60. During the follow-up period, in the intention-to-treat analysis, 92% of the patients receiving low-dose posaconazole and 81% receiving high-dose posaconazole, as compared with 38% receiving benznidazole, tested positive for T. cruzi DNA on rt-PCR assay (P<0.01 for the comparison of the benznidazole group with either posaconazole group); in the per-protocol analysis, 90% of the patients receiving low-dose posaconazole and 80% of those receiving high-dose posaconazole, as compared with 6% receiving benznidazole, tested positive on rt-PCR assay (P<0.001 for the comparison of the benznidazole group with either posaconazole group). In the benznidazole group, treatment was discontinued in 5 patients because of severe cutaneous reactions; in the posaconazole groups, 4 patients had aminotransferase levels that were more than 3 times the upper limit of the normal range, but there were no discontinuations of treatment.
Posaconazole showed antitrypanosomal activity in patients with chronic Chagas' disease. However, significantly more patients in the posaconazole groups than in the benznidazole group had treatment failure during follow-up. (Funded by the Ministry of Health, Spain; CHAGASAZOL ClinicalTrials.gov number, NCT01162967.).
The World Health Organization (WHO) estimates that over three billion people are at risk of acquiring malaria, a parasitic infection that produces more than 200 million new infections and nearly half ...a million deaths each year. Expanding the access to early diagnosis and treatment is one of the most effective ways to prevent disease complications, reduce patient mortality, and curb the community transmission. However, none of the diagnostic methods used currently for malaria detection, including light microscopy, polymerase chain reaction (PCR), and rapid diagnostic tests (RDTs), can provide simultaneously fast results, high sensitivity, and parasitaemia quantitation with minimal user intervention. Here, we present a magneto-immunoassay that, based on the unique combination of magnetic beads (MB), an enzymatic signal amplifier (Poly-HRP), and chemiluminescence detection, provides fast, sensitive, and quantitative malaria diagnosis with easy user manipulation. This assay quantifies Plasmodium falciparum lactate dehydrogenase (PfLDH) in lysed whole blood samples in <15 min, exhibiting a limit of detection (LOD) of 0.02 ng mL–1 and providing patient stratification consistent with the reference methods. These figures of merit surpass the performance of the magneto-immunoassays reported previously for Plasmodium detection and demonstrate for the first time that the proposed combination of MB, Poly-HRP, and chemiluminescence detection produces extremely fast, simple, and efficient assays that approach the requirements of point-of-care (POC) malaria surveillance.
Objectives
To provide information regarding the prevalence of strongyloidiasis among migrants coming from Strongyloides stercoralis‐endemic areas who reside in Spain.
Methods
Systematic review of the ...literature and meta‐analysis of studies showing prevalence of S. stercoralis infection among migrants from Latin America, Africa, Eastern Europe, Asia and Oceania who reside in Spain. We included articles published until 30 April 2019 without language restriction. The keywords used for the search included ‘Strongyloides stercoralis’, ‘strongyloidiasis’, ‘Spain’, ‘screening’ and ‘migrants’.
Results
Twenty‐four studies were included in the review and meta‐analysis, comprising 12 386 screened people. Eleven studies (7020 patients) evaluated the presence of S. stercoralis infection only through investigation of larvae in faeces, showing an overall prevalence of 1% (95%CI 1–1%). Thirteen studies (5366 patients) used a serological test, showing an overall prevalence of 14% (95%CI 11–17%). Strongyloidiasis seroprevalence was 20% (95%CI 15–24%) among migrants from sub‐Saharan Africa, 14% (95%CI 10–18%) among those from Latin America and 8% (95%CI 5–11%) among migrants from North Africa.
Conclusions
Migrants coming from strongyloidiasis‐endemic areas living in Spain had a high S. stercoralis infection prevalence, particularly those from sub‐Saharan Africa and Latin America. This population should be screened using serology as the most sensitive test for S. stercoralis infection. This could be easily implemented at primary care level.
Objectifs
Fournir des informations sur la prévalence de la strongyloïdose parmi les migrants résidant en Espagne et provenant de zones endémiques pour Strongyloides stercoralis.
Méthodes
Revue systématique de la littérature et méta‐analyse des études montrant la prévalence de l'infection à S. stercoralis parmi les migrants d'Amérique latine, d'Afrique, d'Europe de l'Est, d'Asie et d'Océanie qui résident en Espagne. Nous avons inclus des articles publiés jusqu'au 30 avril e 2019 sans restriction de langue. Les mots clés utilisés pour la recherche comprenaient "Strongyloides stercoralis", "strongyloïdose", "Espagne", "dépistage" et "migrants".
Résultats
Vingt‐quatre études ont été incluses dans la revue et la méta‐analyse, comprenant 12.386 personnes dépistées. Onze études (7.020 patients) ont évalué la présence d'une infection à S. stercoralis uniquement en examinant les larves dans les selles, montrant une prévalence globale de 1% (IC95%: 1–1%). Treize études (5.366 patients) ont utilisé un test sérologique, montrant une prévalence globale de 14% (IC95%: 11‐17%). La séroprévalence de la strongyloïdose était de 20% (IC95%: 15–24%) chez les migrants d'Afrique subsaharienne, 14% (IC95%: 10–18%) chez ceux d'Amérique latine et 8% (IC95%: 5–11%) chez ceux d'Afrique du Nord.
Conclusions
Les migrants en provenance de zones d'endémie pour la strongyloïdose vivant en Espagne avaient une prévalence élevée d'infection à S. stercoralis, en particulier ceux d'Afrique subsaharienne et d'Amérique latine. Cette population devrait être dépistée en utilisant la sérologie comme le test le plus sensible pour l' infection à S. stercoralis. Cela pourrait être facilement mis en œuvre au niveau des soins primaires.
Malaria, a parasitic infection caused by Plasmodium parasites and transmitted through the bite of infected female Anopheles mosquitos, is one of the main causes of mortality in many developing ...countries. Over 200 million new infections and nearly half a million deaths are reported each year, and more than three billion people are at risk of acquiring malaria worldwide. Nevertheless, most malaria cases could be cured if detected early. Malaria eradication is a top priority of the World Health Organisation. However, achieving this goal will require mass population screening and treatment, which will be hard to accomplish with current diagnostic tools.
We report an electrochemical point-of-care device for the fast, simple and quantitative detection of Plasmodiumfalciparum lactate dehydrogenase (PfLDH) in whole blood samples. Sample analysis includes 5-min lysis to release intracellular parasites, and stirring for 5 more min with immuno-modified magnetic beads (MB) along with an immuno-modified signal amplifier. The rest of the magneto-immunoassay, including sample filtration, MB washing and electrochemical detection, is performed at a disposable paper electrode microfluidic device. The sensor provides PfLDH quantitation down to 2.47 ng mL−1 in spiked samples and for 0.006–1.5% parasitemias in Plasmodium-infected cultured red blood cells, and discrimination between healthy individuals and malaria patients presenting parasitemias >0.3%. Quantitative malaria diagnosis is attained with little user intervention, which is not achieved by other diagnostic methods.
•Electrochemical POC for fast simple and quantitative malaria detection in whole blood.•Single-step magneto-immunoassay for Plasmodiumfalciparum lactate dehydrogenase (PfLDH).•Paper microfluidic electrode for magneto-assay operation with little user intervention.•Quantitation in lysed whole blood in <20 min.
Objectives
Strongyloidiasis is a nematode infection caused by Strongyloides stercoralis. Previous studies have addressed the possibility of the parasite to establish a complex relationship with the ...host that could affect the risk of developing diabetes mellitus or modify its presentation. This study aims to evaluate the potential impact of strongyloidiasis in diabetes mellitus and other metabolic diseases.
Methods
Case–control observational retrospective study that included 95 S. stercoralis‐infected patients and 83 non‐infected individuals. Epidemiological and clinical variables were retrieved from medical records, and a statistical analysis was carried out to explore any association between strongyloidiasis and diabetes mellitus and other metabolic diseases.
Results
Most of the patients were men (99, 55.60%) with a mean age of 42.53 ± SD 14 years. Twelve (6.70%) patients were diabetic; 30 (16.90%) presented arterial hypertension; 28 (15.70%) had dyslipidaemia; and 10 (5.60%) had thyroid pathology. When comparing patients with strongyloidiasis and uninfected patients, no differences were found regarding diabetes mellitus or other metabolic diseases.
Conclusions
The results obtained in the present study do not confirm any type of association between strongyloidiasis and diabetes mellitus or other metabolic diseases.
Chagas disease (CD) is caused by the protozoan parasite
that infects a broad range of triatomines and mammalian species, including man. It afflicts 8 million people in Latin America, and its ...incidence is increasing in nonendemic countries owing to rising international immigration and nonvectorial transmission routes such as blood donation. Since the 1960s, the only drugs available for the clinical treatment of this infection have been benznidazole (BZ) and nifurtimox (NFX). Treatment with these trypanocidal drugs is recommended in both the acute and chronic phases of CD. These drugs have low cure rates mainly during the chronic phase, in addition both drugs present side effects that may result in the interruption of the treatment. Thus, more efficient and better-tolerated new drugs or pharmaceutical formulations containing BZ or NFX are urgently needed. Here, we review the drugs currently used for CD chemotherapy, ongoing clinical assays, and most-promising new experimental drugs. In addition, the mechanism of action of the commercially available drugs, NFX and BZ, the biodistribution of the latter, and the potential for novel formulations of BZ based on nanotechnology are discussed. Taken together, the literature emphasizes the urgent need for new therapies for acute and chronic CD.
Strongyloides stercoralis infection, a neglected tropical disease, is widely distributed. Autochthonous cases have been described in Spain, probably infected long time ago. In recent years the number ...of diagnosed cases has increased due to the growing number of immigrants, travelers and refugees, but endemically acquired cases in Spain remains undetermined.
We systematically searched the literature for references on endemic strongyloidiasis cases in Spain. The articles were required to describe Strongyloides stercoralis infection in at least one Spanish-born person without a history of travel to endemic areas and be published before 31st May 2018. Epidemiological data from patients was collected and described individually as well as risk factors to acquisition of the infection, diagnostic technique that lead to the diagnosis, presence of eosinophilia and clinical symptoms at diagnosis.
Thirty-six studies were included, describing a total of 1083 patients with an average age of 68.3 years diagnosed with endemic strongyloidiasis in Spain. The vast majority of the cases were described in the province of Valencia (n = 1049). Two hundred and eight of the 251 (82.9%) patients in whom gender was reported were male, and most of them had current or past dedication to agriculture. Seventy percent had some kind of comorbidity. A decreasing trend in the diagnosed cases per year is observed from the end of last decade. However, there are still nefigw diagnoses of autochthonous cases of strongyloidiasis in Spain every year.
With the data provided by this review it is likely that in Spain strongyloidiasis might have been underestimated. It is highly probable that the infection remains undiagnosed in many cases due to low clinical suspicion among Spanish population without recent travel history in which the contagion probably took place decades ago.
The use of posaconazole against Chagas disease Molina, Israel; Salvador, Fernando; Sánchez-Montalvá, Adrián
Current opinion in infectious diseases,
2015-October, Letnik:
28, Številka:
5
Journal Article
Recenzirano
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.
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.
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.
Objective
To understand Zika virus (ZIKV) dynamics in fluids of infected individuals and the risk of sexual transmission.
Methods
Prospective study at two centres in Spain. Patients with probable or ...confirmed diagnosis of ZIKV infection were clinically followed up, and fluid samples were collected from saliva, serum, urine and semen or vaginal secretion following the study protocol. Non‐traveller‐sexual partners were offered to participate.
Results
From January 2016 to December 2016, we included a total of 11 traveller patients and six sexual contacts. Six patients were male, with a median age of 38 years (IQR 30–45). We performed 61 RT‐PCR determinations, seven of which were positive. Positive results were retrieved from serum, urine, semen and vaginal tract. One of four women tested positive for ZIKV RNA in vaginal swabs collected during the first 45 days after symptoms onset. Clearance occurred between day 37 and day 69 after symptoms onset. One of five men tested positive for ZIKV RNA in semen collected during the first 45 days after symptoms onset. Clearance occurred between day 23 and 107 after symptoms onset. Six patients had sexual relations during the defined period. All tested patients were negative for ZIKV infection by serological testing.
Conclusion
ZIKV shedding persistence in genital fluids occurs in a significant number of symptomatic patients after visiting an endemic area. We did not find any ZIKV seroconversion among the three male contacts who were investigated. Diagnostic algorithms may be updated to include genital tract fluid specimens in the diagnostic process.
Objectif
Comprendre la dynamique du virus Zika (ZIKV) dans les fluides d'individus infectés et le risque de transmission sexuelle.
Méthodes
Etude prospective dans deux centres en Espagne. Les patients avec un diagnostic probable ou confirmé d'infection au ZIKV ont été cliniquement suivis et des échantillons de fluides ont été prélevés dans la salive, le sérum, l'urine, le sperme ou la sécrétion vaginale selon le protocole de l’étude. Des partenaires sexuels non‐voyageurs ont été invités à participer.
Résultats
De janvier à décembre 2016, nous avons inclus un total de 11 patients voyageurs et 6 contacts sexuels. 6 patients étaient des hommes, avec un âge médian de 38 ans (IQR 30‐45). Nous avons effectué 61 analyses par RT‐PCR, dont 7 étaient positives. Des résultats positifs ont été obtenus à partir du sérum, de l'urine, du sperme et des voies vaginales. Une des 5 femmes a été testée positive pour l’ARN du ZIKV dans les écouvillons vaginaux recueillis au cours des 45 premiers jours après l'apparition des symptômes. La clairance s'est produite entre les jours 37 et 69 après l'apparition des symptômes. Un des 6 hommes a été testé positif pour l’ARN du ZIKV dans le sperme prélevé au cours des 45 premiers jours après l'apparition des symptômes. La clairance s'est produite entre les jours 23 et 107 après l'apparition des symptômes. Six patients ont eu des relations sexuelles au cours de la période définie. Tous les patients testés étaient négatifs par les tests sérologiques pour l'infection par le ZIKV.
Conclusion
La persistance du ZIKV dans les liquides génitaux se manifeste chez un nombre significatif de patients symptomatiques après une visite dans une zone endémique. Nous n'avons trouvé aucune séroconversion au ZIKV parmi les 3 contacts masculins qui ont été investigués. Les algorithmes de diagnostic devraient être mis à jour pour inclure des échantillons de fluides du tractus génital dans le processus de diagnostic.
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