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The Parasitic Protozoa and Helminth Worms
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
Coccidia are important sporozoan infections causing a condition known as coccidi-osis in farmed animals, especially fowl bred under conditions of intensive rearing. Humans are infected with three intestinal coccidians Cryptosporidium parvum, isospora belli, and Cyclospora cayetanensis, but little is known about the immune responses to any of these. Cryptosporidiosis is an increasingly important disease that is self-limiting and characterized by mild to severe watery diarrhea in healthy individuals but is more persistent and severe and may cause death in AIDS patients. Specific antibodies are found in the serum of infected individuals but nothing is known about their possible relevance.
Cryptosporidium spp
Published in Peter D. Walzer, Robert M. Genta, Parasitic Infections in the Compromised Host, 2020
Difficulty in separating or identifying the roles of the different components of the neonatal calf diarrhea complex, along with the finding of asymptomatic Cryptosporidium sp. infections has led some to question the role of this coccidian as a primary pathogen (94). The controversy as to whether Cryptosporidium sp. is a true enteropathogen in the absence of other agents of enteric disease in calves has, to my satisfaction, been resolved. The typical clinical signs of diarrhea and malabsorption, and the characteristic lesions of villous blunting, atrophy, and fusion noted in naturally and experimentally infected animals also occur in gnotobiotic calves monoinfected with C. parvum (79). Heine et al. (79) suggested that malabsorption caused by villous atrophy resulting from accelerated loss of epithelium was the basis for Cryptosporidium-induced diarrhea in these calves. Similar findings also have been published for gnotobiotic pigs (95) and gnotobiotic lambs (96) that were reported to be moninfected with C. patvum. Thus, it appears that most of the C. parvum isolates studied to date are primary pathogens that cause diarrhea in calves. As with any primary enteropathogen, one should expect to find some animals infected with C. parvum that have no clinical signs of illness. The finding of large numbers of infected calves without diarrhea in a herd would suggest that different isolates of C. parvum may vary markedly in their virulence. Such differences in virulence have been suggested by others (1,94).
Unexplained Fever Associated with Diseases of the Gastrointestinal Tract
Published in Benedict Isaac, Serge Kernbaum, Michael Burke, Unexplained Fever, 2019
Two protozoa of the Coccidia subclass, Cryptosporidium and Isospora belli, may cause a protracted enteritis, manifested by diarrhea, fever, abdominal pain, weight loss, and malabsorption. Cryptosporidium may produce copious amounts of watery diarrhea. These organisms have become increasingly important in recent years because of their propensity to infect the immunocompromised host, especially those suffering from AIDS, although immunocompetent individuals may also become infected. The diagnosis is established by identifying oocysts in the stool using a special acid-fast stain.
Discovery of novel drugs for Chagas disease: is carbonic anhydrase a target for antiprotozoal drugs?
Published in Expert Opinion on Drug Discovery, 2022
Alane Beatriz Vermelho, Giseli Capaci Rodrigues, Alessio Nocentini, Felipe R. P. Mansoldo, Claudiu T. Supuran
Among the various classes of existing CAIs, sulfonamides and inorganic anions are the most investigated inhibitors [51,54]. However, in addition to these, other classes have different action mechanisms when compared to sulfonamides, such as coumarins and their derivatives [42,89]. Sulfonamides linked to heterocyclic rings are candidates for antiprotozoal drugs. Discovered in the 1930s as an agent with antibacterial properties, nowadays, several studies have shown that the sulfonamide group has diverse biological activities, including antiparasitic [90]. Sulfonamides exhibit inhibitory activity for protozoans such as Toxoplasma and Coccidia [91]; whereas inhibitory action on CA interferes in the growth of the parasites in vitro and in vivo in L. donovani chagasi, Trypanosoma cruzi, Plasmodium falciparum [92], Entamoeba histolytica [93], and Trichomonas vaginalis [34]. A summary of sulfonamides with inhibitory action on CA families of protozoa is presented in Table 3.
Structure-activity relationships of Toxoplasma gondii cytochrome bc 1 inhibitors
Published in Expert Opinion on Drug Discovery, 2022
P. Holland Alday, Aaron Nilsen, J. Stone Doggett
DCQ is highly lipophilic and has a very low aqueous solubility (0.06 µg/mL) [47]. Although these physicochemical properties do not decrease the efficacy of DCQ for intestinal coccidian infections, they are highly undesirable for the treatment of a systemic illness, such as toxoplasmosis. Recently, a series of quinoline-O-carbamate derivatives were synthesized and evaluated (Table 2) with the goal of improving the aqueous solubility of DCQ [48,49]. Compound RMB060 had an EC50 of 0.07 nM against T. gondii tachyzoites in a 72-h assay when added prior to infection compared to DCQ at 1.1 nM. The efficacy of DCQ and RMB060 in preventing vertical transmission was investigated using female mice that were infected orally with T. gondii oocysts on day 7 post-mating and then given DCQ or RMB060 orally at 10 mg/kg on days 9–13 post-mating. While treatment with DCQ resulted in higher neonatal (DCQ, 70% vs control, 40%) and postnatal mortality (DCQ, 11% vs control, 0%), RMB060 resulted in both lower neonatal (RMB060, 17% vs control, 23%) and postnatal mortality (RMB060, 3.8% vs control, 9.2%). Neither compound adversely affected fertility, but neither was able to eliminate vertical transmission.
How relevant are in vitro culture models for study of tick-pathogen interactions?
Published in Pathogens and Global Health, 2021
Cristiano Salata, Sara Moutailler, Houssam Attoui, Erich Zweygarth, Lygia Decker, Lesley Bell-Sakyi
Besnoitia besnoiti is the causative agent of bovine besnoitiosis. It is an obligate intracellular cyst-forming coccidium and affects mainly young cattle. Cattle act as intermediate hosts and the final host is unknown. Experimentally, B. besnoiti can be transmitted between cattle by bloodsucking insects [180]; although there is no evidence that ticks are involved in transmission, it was suggested that this avenue should be explored [181]. In a series of studies, B. besnoiti was cultured in four different tick cell lines, RA243, BmVIII-SCC, RML-15, and RAE25, for up to 7 months [182–184]. The authors did not find appreciable differences in parasite proliferation in the various cell lines; however, the yield of parasites was lower in tick cells than in mammalian Vero cells.