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Nifurtimox

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https://www.readbyqxmd.com/read/29906591/toxicity-of-nifurtimox-as-second-line-treatment-after-benznidazole-intolerance-in-patients-with-chronic-chagas-disease-when-available-options-fail
#1
Clara Crespillo-Andújar, Sandra Chamorro-Tojeiro, Francesca Norman, Begoña Monge-Maillo, Rogelio López-Velez, José A Pérez-Molina
OBJECTIVE: To describe the tolerability and rate of nifurtimox discontinuation when administered as a second-line treatment to patients with previous treatment interruptions due to adverse reactions with benznidazole. METHODS: Prospective cohort study of adult patients with chronic Chagas disease in a referral centre in Spain; study period July 2007 to July 2017. We analysed the tolerability profile and treatment interruption rate due to adverse reactions to nifurtimox in patients previously incompletely treated (less than 30 days) with benznidazole due to adverse reactions (ARs)...
June 12, 2018: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/29897919/mortality-trends-and-risk-factors-in-advanced-stage-2-human-african-trypanosomiasis-a-critical-appraisal-of-23-years-of-experience-in-the-democratic-republic-of-congo
#2
Léon Mbiyangandu Kazumba, Jean-Claude Tshinzobe Kaka, Dieudonné Mumba Ngoyi, Désiré Tshala-Katumbay
We conducted a retrospective study on mortality trends and risk factors in 781 naïve cases of advanced stage-2 sleeping sickness admitted between 1989 and 2012 at the National Reference Center for Human African Trypanosomiasis (HAT), Department of Neurology, Kinshasa University, Democratic Republic of Congo (DRC). Death was the outcome variable whereas age, gender, duration of disease, location of trypanosomes in body fluids, cytorachy, protidorachy, clinical status (assessed on a syndromic and functional basis) on admission, and treatment regimen were predictors in logistic regression models run at the 0...
June 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29879424/trypanosoma-cruzi-analysis-of-two-different-strains-after-piplartine-treatment
#3
Gabriela Alves Licursi Vieira, Marco Túlio Alves da Silva, Luis Octávio Regasini, Fernando Cotinguiba, Helen Julie Laure, José César Rosa, Maysa Furlan, Regina Maria Barretto Cicarelli
The hemoflagellate protozoan, Trypanosoma cruzi, mainly transmitted by triatomine insects through blood transfusion or from mother-to-child, causes Chagas' disease. This is a serious parasitic disease that occurs in Latin America, with considerable social and economic impact. Nifurtimox and benznidazole, drugs indicated for treating infected persons, are effective in the acute phase, but poorly effective during the chronic phase. Therefore, it is extremely urgent to find innovative chemotherapeutic agents and/or effective vaccines...
June 4, 2018: Brazilian Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29846973/biopharmaceutical-optimization-in-neglected-diseases-for-paediatric-patients-by-applying-the-provisional-paediatric-biopharmaceutical-classification-system
#4
Jose Manuel Del Moral Sanchez, Isabel Gonzalez Alvarez, Aaron Cerda Revert, Marta Gonzalez Alvarez, Andres Navarro Ruiz, Gordon L Amidon, Marival Bermejo Sanz
AIMS: Unavailability and lack of appropriate, effective and safe formulations are common problems in paediatric therapeutics. Key factors such as swallowing abilities, organoleptic preferences and dosage requirements determine the need of for optimization of formulations. The provisional Biopharmaceutics Classification System can be used in paediatric formulation design as a risk analysis and optimization tool. The objective of this study was to classify six neglected tropical diseases drugs following a provisional paediatric BCS (pBCS) classification adapted to three paediatric subpopulations (neonates, infants and children)...
May 30, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29741138/insights-into-anti-trypanosomal-agents-based-on-synthetic-glycoconjugates
#5
Vanessa Leiria Campo, Marcelo Fiori Marchiori, Ivone Carvalho
Chagas disease is still a worldwide threat, with estimated 6 to 7 million infected people, mainly in Latin America. Current treatments still rely only on benznidazol and nifurtimox, drugs with poor efficacy in chronic infection phase and recognized toxicity. Thus, there is an urgent need for new therapeutic agents against this disease. In this review we present an updated selection over the last decade of synthetic glycoconjugates as anti-trypanosomal agents, properly addressed as monosaccharide- and disaccharide-based agents, and multivalent-based derivatives, disclosing relevant methods for their synthesis, along with their activities on T...
May 9, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29731387/challenges-of-immunosuppressive-and-antitrypanosomal-drug-therapy-after-heart-transplantation-in-patients-with-chronic-chagas-disease-a-systematic-review-of-clinical-recommendations
#6
REVIEW
Silas Santana Nogueira, Amanda Aparecida Felizardo, Ivo Santana Caldas, Reggiani Vilela Gonçalves, Rômulo Dias Novaes
BACKGROUND: Although contraindicated for decades, heart transplantation (HT) has finally become a feasible therapeutic option for the treatment of Chagasic patients with end-stage heart failure. Part of the success in achieving acceptable survival rates after HT is due to the enhancement of the pharmacological management of allograft rejection and reactivation of Trypanosoma cruzi infection. METHODS: By using the framework of a systematic review, we investigated if Chagasic patients who have undergone a HT are treated with similar immunosuppressive and antitrypanosomal regimens in endemic and non-endemic countries and exhibits similar T...
April 17, 2018: Transplantation Reviews
https://www.readbyqxmd.com/read/29701144/current-and-future-prospects-of-nitro-compounds-as-drugs-for-trypanosomiasis-and-leishmaniasis
#7
Alan H Fairlamb, Stephen Patterson
Interest in nitroheterocyclic drugs for the treatment of infectious diseases has undergone a resurgence in recent years. Here we review the current status of monocyclic and bicyclic nitroheterocyclic compounds as existing or potential new treatments for visceral leishmaniasis, Chagas' disease and human African trypanosomiasis. Both monocyclic (nifurtimox, benznidazole and fexinidazole) and bicyclic (pretomanid (PA-824) and delamanid (OPC-67683)) nitro-compounds are prodrugs, requiring enzymatic activation to exert their parasite toxicity...
April 26, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29669503/evaluation-of-trypanocidal-and-antioxidant-activities-of-a-selected-series-of-3-amidocoumarins
#8
Mauricio Moncada-Basualto, Michel Lapier, Juan Diego Maya, Betty Matsuhiro, Claudio Olea-Azar, Giovanna L Delogu, Eugenio Uriarte, Lourdes Santana, Maria Joao Matose
BACKGROUND: Neglected diseases are becoming more prevalent due to globalization. This has inspired active research in the development of new drugs for the treatment of parasitic diseases such as Chagas disease. OBJECTIVES: With the aim of finding new trypanocidal agents, we report the in vitro evaluation of a new series of 3-amidocoumarins with or without hydroxyl substituents at position 4 of the coumarin ring. METHODS: Electrochemical and biological assays were performed in order to assess the antioxidant and trypanocidal potential of these compounds, and to better understand the mechanisms involved in their activity...
April 18, 2018: Medicinal Chemistry
https://www.readbyqxmd.com/read/29588298/severe-immune-thrombocytopaenia-in-a-patient-taking-benznidazole-for-chronic-chagas-disease
#9
Clara Crespillo-Andújar, María Calbacho Robles, Francesca F Norman, Jose A Pérez-Molina
Chagas disease is a parasitic disease that mostly affects Latin American countries, but it has currently become a worldwide epidemic due to migration. Both drugs marketed for its treatment (benznidazole and nifurtimox) are associated with a high rate of adverse reactions. Benznidazole is preferred initially because of its more favourable toxicity profile and perceived greater efficacy. Hypersensitivity dermatological reactions, gastrointestinal and neurological disturbances represent the most common drug-related adverse events...
March 27, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/29569658/an-update-on-benznidazole-for-the-treatment-of-patients-with-chagas-disease
#10
R Thakare, A Dasgupta, S Chopra
Chagas disease is a vector-borne, systemic and chronic parasitic infection caused by Trypanosoma cruzi with approximately 8 million cases worldwide. The treatment for acute phase of Chagas disease consists of benznidazole and nifurtimox, although this treatment combination falls short in terms of efficacy against chronic phases of infection. This review provides an update on benznidazole progress and approval by the U.S. Food and Drug Administration in 2017 for the treatment of Chagas disease along with its lacunae...
January 2018: Drugs of Today
https://www.readbyqxmd.com/read/29563916/old-yellow-enzyme-from-trypanosoma-cruzi-exhibits-in-vivo-prostaglandin-f-2-%C3%AE-synthase-activity-and-has-a-key-role-in-parasite-infection-and-drug-susceptibility
#11
Florencia Díaz-Viraqué, María Laura Chiribao, Andrea Trochine, Fabiola González-Herrera, Christian Castillo, Ana Liempi, Ulrike Kemmerling, Juan Diego Maya, Carlos Robello
The discovery that trypanosomatids, unicellular organisms of the order Kinetoplastida, are capable of synthesizing prostaglandins raised questions about the role of these molecules during parasitic infections. Multiple studies indicate that prostaglandins could be related to the infection processes and pathogenesis in trypanosomatids. This work aimed to unveil the role of the prostaglandin F2 α synthase Tc OYE in the establishment of Trypanosoma cruzi infection, the causative agent of Chagas disease. This chronic disease affects several million people in Latin America causing high morbidity and mortality...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29494842/identification-of-cisapride-as-new-inhibitor-of-putrescine-uptake-in-trypanosoma-cruzi-by-combined-ligand-and-structure-based-virtual-screening
#12
R C Dietrich, L N Alberca, M D Ruiz, P H Palestro, C Carrillo, A Talevi, L Gavernet
Nowadays, the pharmacological therapy for the treatment of Chagas disease is based on two old drugs, benznidazole and nifurtimox, which have restricted efficacy against the chronic phase of the illness. To overcome the lack of efficacy of the traditional drugs (and their considerable toxicity), new molecular targets have been studied as starting points to the discovery of new antichagasic compounds. Among them, polyamine transporter TcPAT12 (also known as TcPOT1.1) represents an interesting macromolecule, since polyamines are essential for Trypanosoma cruzi, the parasite that causes the illness, but it cannot synthesize them de novo...
April 10, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29473131/searching-for-new-drugs-for-chagas-diseases-triazole-analogs-display-high-in-vitro-activity-against-trypanosoma-cruzi-and-low-toxicity-toward-mammalian-cells
#13
Robson Xavier Faria, Daniel Tadeu Gomes Gonzaga, Paulo Anastácio Furtado Pacheco, André Luis Almeida Souza, Vitor Francisco Ferreira, Fernando de Carvalho da Silva
Chagas disease is one of the most relevant endemic diseases in Latin America caused by the flagellate protozoan Trypanosoma cruzi. Nifurtimox and benzonidazole are the drugs used in the treatment of this disease, but they commonly are toxic and present severe side effects. New effective molecules, without collateral effects, has promoted the investigation to develop new lead compounds with to advance for clinical trials. Previously, 3-nitro-1H-1,2,4-triazole-based amines and 1,2,3-triazoles demonstrated significant trypanocidal activity against T...
April 2018: Journal of Bioenergetics and Biomembranes
https://www.readbyqxmd.com/read/29471865/a-multicentre-randomised-non-inferiority-clinical-trial-comparing-a-nifurtimox-eflornithine-combination-to-standard-eflornithine-monotherapy-for-late-stage-trypanosoma-brucei-gambiense-human-african-trypanosomiasis-in-uganda
#14
Freddie Kansiime, Seraphine Adibaku, Charles Wamboga, Franklin Idi, Charles Drago Kato, Lawrence Yamuah, Michel Vaillant, Deborah Kioy, Piero Olliaro, Enock Matovu
BACKGROUND: While the combination of nifurtimox and eflornithine (NECT) is currently recommended for the treatment of the late stage human African trypansomiasis (HAT), single-agent eflornithine was still the treatment of choice when this trial commenced. This study intended to provide supportive evidence to complement previous trials. METHODS: A multi-centre randomised, open-label, non-inferiority trial was carried out in the Trypanosoma brucei gambiense endemic districts of North-Western Uganda to compare the efficacy and safety of NECT (200 mg/kg eflornithine infusions every 12 h for 7 days and 8 hourly oral nifurtimox at 5 mg/kg for 10 days) to the standard eflornithine regimen (6 hourly at 100 mg/kg for 14 days)...
February 22, 2018: Parasites & Vectors
https://www.readbyqxmd.com/read/29448038/molecular-and-biological-characterization-of-a-highly-pathogenic-trypanosoma-cruzi-strain-isolated-from-a-patient-with-congenital-infection
#15
Julián Ernesto Nicolás Gulin, Margarita Bisio, Daniela Marisa Rocco, Jaime Altcheh, María Elisa Solana, Facundo García-Bournissen
Although many Trypanosoma cruzi (T. cruzi) strains isolated from a wide range of hosts have been characterized, there is a lack of information about biological features from vertically transmitted strains. We describe the molecular and biological characteristics of the T. cruzi VD strain isolated from a congenital Chagas disease patient. The VD strain was typified as DTU TcVI; in vitro sensitivity to nifurtimox (NFX) and beznidazole (BZ) were 2.88 μM and 6.19 μM respectively, while inhibitory concentrations for intracellular amastigotes were 0...
March 2018: Experimental Parasitology
https://www.readbyqxmd.com/read/29340450/therapeutic-drug-monitoring-of-benznidazole-and-nifurtimox-a-systematic-review-and-quality-assessment-of-published-clinical-practice-guidelines
#16
REVIEW
Mario Javier Olivera, Johana Alexandra Fory, Antonio José Olivera
The pharmacological management of adults with chronic-phase Chagas disease is challenging despite it being the recent focus of extensive research. One of the challenges in the current clinical practice guidelines (CPGs) landscape is the existence of non-evidence-based recommendations for the use of laboratory tests in treatment monitoring. This study aimed to systematically assess the quality and consistency of recommendations of CPGs on the pharmacological management of adults with chronic-phase Chagas disease...
November 2017: Revista da Sociedade Brasileira de Medicina Tropical
https://www.readbyqxmd.com/read/29311242/vaccine-linked-chemotherapy-improves-benznidazole-efficacy-for-acute-chagas-disease
#17
Kathryn Jones, Leroy Versteeg, Ashish Damania, Brian Keegan, April Kendricks, Jeroen Pollet, Julio Vladimir Cruz-Chan, Fabian Gusovsky, Peter J Hotez, Maria Elena Bottazzi
Chagas disease affects 6 to 7 million people worldwide, resulting in significant disease burdens and health care costs in countries of endemicity. Chemotherapeutic treatment is restricted to two parasiticidal drugs, benznidazole and nifurtimox. Both drugs are highly effective during acute disease but are only minimally effective during chronic disease and fraught with significant adverse clinical effects. In experimental models, vaccines can be used to induce parasite-specific balanced TH 1/TH 2 immune responses that effectively reduce parasite burdens and associated inflammation while minimizing adverse effects...
April 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29281643/4-aminopyridyl-based-lead-compounds-targeting-cyp51-prevent-spontaneous-parasite-relapse-in-a-chronic-model-and-improve-cardiac-pathology-in-an-acute-model-of-trypanosoma-cruzi-infection
#18
Claudia Magalhaes Calvet, Jun Yong Choi, Diane Thomas, Brian Suzuki, Ken Hirata, Sharon Lostracco-Johnson, Liliane Batista de Mesquita, Alanderson Nogueira, Marcelo Meuser-Batista, Tatiana Araujo Silva, Jair Lage Siqueira-Neto, William R Roush, Mirian Claudia de Souza Pereira, James H McKerrow, Larissa M Podust
BACKGROUND: Chagas disease, caused by the protozoan Trypanosoma cruzi, is the leading cause of heart failure in Latin America. The clinical treatment of Chagas disease is limited to two 60 year-old drugs, nifurtimox and benznidazole, that have variable efficacy against different strains of the parasite and may lead to severe side effects. CYP51 is an enzyme in the sterol biosynthesis pathway that has been exploited for the development of therapeutics for fungal and parasitic infections...
December 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29247858/investigating-the-structure-activity-relationships-of-n-5-nitrofuran-2-yl-methylene-substituted-hydrazides-against-trypanosoma-cruzi-to-design-novel-active-compounds
#19
Fanny Palace-Berl, Kerly Fernanda Mesquita Pasqualoto, Bianca Zingales, Carolina Borsoi Moraes, Mariana Bury, Caio Haddad Franco, Adelson Lopes da Silva Neto, João Sussumu Murayama, Solange Lessa Nunes, Marcelo Nunes Silva, Leoberto Costa Tavares
Chagas disease, caused by the protozoan Trypanosoma cruzi, is a neglected chronic tropical infection endemic in Latin America. New and effective treatments are urgently needed because the two available drugs - benznidazole (BZD) and nifurtimox (NFX) - have limited curative power in the chronic phase of the disease. We have previously reported the design and synthesis of N'-[(5-nitrofuran-2-yl) methylene] substituted hydrazides that showed high trypanocidal activity against axenic epimastigote forms of three T...
January 20, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29113731/oral-fexinidazole-for-late-stage-african-trypanosoma-brucei-gambiense-trypanosomiasis-a-pivotal-multicentre-randomised-non-inferiority-trial
#20
RANDOMIZED CONTROLLED TRIAL
Victor Kande Betu Ku Mesu, Wilfried Mutombo Kalonji, Clélia Bardonneau, Olaf Valverde Mordt, Séverine Blesson, François Simon, Sophie Delhomme, Sonja Bernhard, Willy Kuziena, Jean-Pierre Fina Lubaki, Steven Lumeya Vuvu, Pathou Nganzobo Ngima, Hélène Mahenzi Mbembo, Médard Ilunga, Augustin Kasongo Bonama, Josué Amici Heradi, Jean Louis Lumaliza Solomo, Guylain Mandula, Lewis Kaninda Badibabi, Francis Regongbenga Dama, Papy Kavunga Lukula, Digas Ngolo Tete, Crispin Lumbala, Bruno Scherrer, Nathalie Strub-Wourgaft, Antoine Tarral
BACKGROUND: Few therapeutic options are available to treat the late-stage of human African trypanosomiasis, a neglected tropical disease, caused by Trypanosoma brucei gambiense (g-HAT). The firstline treatment is a combination therapy of oral nifurtimox and intravenous eflornithine that needs to be administered in a hospital setting by trained personnel, which is not optimal given that patients often live in remote areas with few health resources. Therefore, we aimed to assess the safety and efficacy of an oral regimen of fexinidazole (a 2-substituted 5-nitroimidazole with proven trypanocidal activity) versus nifurtimox eflornithine combination therapy in patients with late-stage g-HAT...
January 13, 2018: Lancet
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