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Host Defense and Parasite Evasion
Published in Eric S. Loker, Bruce V. Hofkin, Parasitology, 2023
Eric S. Loker, Bruce V. Hofkin
The antibodies generated against a parasite may be rendered ineffective in any of several ways. One way used by various parasites is to cause a general nonspecific activation of B cells. Such activation, termed polyclonal activation, leads to the proliferation of many B cell clones, regardless of antigen specificity. The serum is consequently flooded with antibodies, much of which is nonreactive with the parasite. In malaria infections, for example, it is estimated that only about 10% of serum antibody is specific for Plasmodium antigens. The remaining nonspecific antibodies contribute nothing to immune defense but may actually impede the ability of Plasmodium-specific antibodies to bind and neutralize the parasite. Trypanosoma cruzi, unlike the African trypanosomes previously discussed, does not undergo antigenic variation. Instead, the entire parasite population within a given host expresses a large variety of antigenic surface proteins simultaneously. These diverse proteins, encoded by highly polymorphic, multigene families, create what in effect, becomes an antigenic “smoke screen,” in which the majority of antibodies are non-neutralizing for any given parasite. These non-neutralizing antibodies interfere with any specific antibodies that have been generated against individual parasites. T. cruzi also appears to secrete B cell mitogens: molecules that cause a general proliferation of B cells that results in polyclonal activation and a delayed specific antibody response.
Antiprotozoal Effects of Wild Plants
Published in Mahendra Rai, Shandesh Bhattarai, Chistiane M. Feitosa, Ethnopharmacology of Wild Plants, 2021
Muhammad Subbayyal Akram, Rao Zahid Abbas, José L. Martinez
Trypanosoma cruzi infection has an acute and chronic phase, which lasts for a few weeks to months. In acute phase, disease signs are seen immediately after the host is infected by the infection, which includes fever, and swelling at the bite site and rarely, the acute phase ends with inflammation of the brain, heart muscles and behavioral abnormalities (Vilar-Pereira et al. 2015). During this phase, Trypanosoma cruzi is found in the bloodstream and is usually mild or maybe asymptomatic in nature. Predominantly, the acute phase enters in a prolonged asymptomatic phase or chronic phase during which hardly any or no parasites are present in the bloodstream. As in chronic phase, host never develops symptoms related to Chagas disease which results in life-threatening health problems with the passage of time (Hotez et al. 2013).
The Application of Fragment-based Approaches to the Discovery of Drugs for Neglected Tropical Diseases
Published in Venkatesan Jayaprakash, Daniele Castagnolo, Yusuf Özkay, Medicinal Chemistry of Neglected and Tropical Diseases, 2019
Christina Spry, Anthony G. Coyne
Chagas disease and Sleeping Sickness are two NTDs caused by protozoan parasites of the genus Trypanosoma. Chagas disease, which is also known as American trypanosomiasis, affects approximately 6–7 million people, predominantly in Latin America (although increasing numbers of cases are being detected elsewhere around the world (Schmunis and Yadon 2010)), and results in over 10,000 deaths annually (WHO 2017, 2018b). The disease is caused by Trypanosoma cruzi, which is primarily transmitted by the triatomine bug, but can also be transmitted through blood transfusion from infected donors, or from mother to child during pregnancy or childbirth. There is no vaccine for Chagas disease, but the disease can be cured with the antiparasitic drugs benznidazole or nifurtimox if treatment is initiated during onset of the acute phase of the disease. Unfortunately, however, drug efficacy diminishes with time since infection and 40% of patients suffer from adverse effects due to treatment (WHO 2017). Hence, new drugs with improved safety and efficacy are needed.
Promiscuity in drug discovery on the verge of the structural revolution: recent advances and future chances
Published in Expert Opinion on Drug Discovery, 2023
Sarah Naomi Bolz, Michael Schroeder
Chagas disease is a potentially life-threatening infection caused by the protozoan parasite Trypanosoma cruzi that affects about 6–7 million people globally. It is recognized as a neglected tropical disease that primarily affects poor and marginalized populations in Latin America, leading to serious health consequences and socioeconomic burdens [96,97]. There are currently limited treatment options for Chagas disease, which have severe side effects and are only partially effective [98]. To identify novel medications, Adasme et al. performed a structure-based drug repositioning screening using interaction fingerprints [99]. They extracted the non-covalent protein–ligand interaction patterns from the available complex structures of 16 Chagas targets and screened the PDB to identify complexes with a similar binding mode. The screening yielded 38 top-hit compounds that showed high chemical diversity. Three of these repositioning candidates – ciprofloxacin, naproxen, and folic acid – displayed activity against the parasite when tested in vivo [99].
Plant-made vaccines against parasites: bioinspired perspectives to fight against Chagas disease
Published in Expert Review of Vaccines, 2021
Abel Ramos-Vega, Elizabeth Monreal-Escalante, Eric Dumonteil, Bernardo Bañuelos-Hernández, Carlos Angulo
Chagas disease–one of the most important neglected tropical diseases (NTDs)–affects around 10 million people worldwide and entails nearly 10 000 deaths each year [1]. This disease is caused by the intracellular parasite Trypanosoma cruzi, which is transmitted mostly by the triatomine bite. Skin lesions upon bites – or permissive mucosal and conjunctival surfaces – are in contact with triatomine feces that contain the protozoon trypomastigote, infecting neighbor cells, entering into the bloodstream and resulting in systemic complications, such as cardiomyopathy and enteropathies [2,3]. Other infective routes are blood transfusion [4], organ transplantation [5], congenital transmission [6,7], and oral contagion by consuming contaminated food and drinks [8]. Initially, Chagas disease was distributed and considered endemic in low-income regions of Latin America [9], but due to globalization and migration increase around the world, the disease has been observed in other continents [10,11].
Assessing and mitigating risk of infection in patients with multiple sclerosis on disease modifying treatment
Published in Expert Review of Clinical Immunology, 2021
Susana Otero-Romero, Adrián Sánchez-Montalvá, Angela Vidal-Jordana
The initial assessment should cover medical, travel, sexual, vaccine and previous infections history, including prior tuberculosis (TB) history or contact, and prior immunosuppressive history. Blood sample tests should include a serological assessment testing for at least: VZV, measles, mumps, rubella, hepatitis A, B and C virus (HAV, HBV, HCV), and human immunodeficiency virus (HIV). Additionally, cytomegalovirus (CMV), EBV, HPV, JCV, and TB screening is also recommended specially when planning to start some specific treatments [7,12] (Table 1). Use of a standardized questionnaire may help to guide the initial screening (Figure 1). Attending to country of origin and travel history, patients living for more than 3 months in Latin America should be tested for Trypanosoma cruzi infection. Patients living for more than 3 months in Sub-Saharan African should be tested for Schistosoma species (spp.) and malaria (preferably by molecular biology tests), other malaria-endemic and schistosoma-endemic areas of the world should also be included. All patients living for more than 3 months in middle – or low-income countries should consider Strongyloides spp. serology (IgG) and microscopic examination of the stools.