A review of the global burden, novel diagnostics, therapeutics, and vaccine targets for cryptosporidium

Abstract

Cryptosporidium spp are well recognised as causes of diarrhoeal disease during waterborne epidemics and in immunocompromised hosts. Studies have also drawn attention to an underestimated global burden and suggest major gaps in optimum diagnosis, treatment, and immunisation. Cryptosporidiosis is increasingly identified as an important cause of morbidity and mortality worldwide. Studies in low-resource settings and high-income countries have confirmed the importance of cryptosporidium as a cause of diarrhoea and childhood malnutrition. Diagnostic tests for cryptosporidium infection are suboptimum, necessitating specialised tests that are often insensitive. Antigen-detection and PCR improve sensitivity, and multiplexed antigen detection and molecular assays are underused. Therapy has some effect in healthy hosts and no proven efficacy in patients with AIDS. Use of cryptosporidium genomes has helped to identify promising therapeutic targets, and drugs are in development, but methods to assess the efficacy in vitro and in animals are not well standardised. Partial immunity after exposure suggests the potential for successful vaccines, and several are in development; however, surrogates of protection are not well defined. Improved methods for propagation and genetic manipulation of the organism would be significant advances.

Novel Bumped Kinase Inhibitors Are Safe and Effective Therapeutics in the Calf Clinical Model for Cryptosporidiosis

“…However, the concentrations after the fifth dose were predicted. studies will examine whether BKI-1517, BKI-1553, and other newly identified BKIs will be effective at a dosage similar to that used for nitazoxanide in humans (ie, every 12 hours for 3 days), which is presently the only Food and Drug Administration-approved drug for cryptosporidiosis in humans, although it is marginally effective [15].…”

“…In humans, nitazoxanide was shown in a randomized trial to reduce the duration of cryptosporidial diarrhea by approximately 2 days in immunocompetent individuals [14]. However, nitazoxanide has limited efficacy in immunocompromised individuals and is associated with an unacceptably high relapse rate [15]. Further, the mechanism of action of nitazoxanide against Cryptosporidium is unknown, and it is speculated that it may act via a nonspecific immunomodulatory effect [7,16].…”

In Vitro and In Vivo Effects of the Bumped Kinase Inhibitor 1294 in the Related Cyst-Forming Apicomplexans Toxoplasma gondii and Neospora caninum

“…In turn, chronic infection is characterized by the formation of intracellular tissue cysts in brain and muscular tissues that harbor slowly proliferating bradyzoites. Calcium-dependent protein kinases (CDPKs), encoded by apicoplast-associated genes and, thus, only found in apicomplexan parasites and plants, represent excellent drug targets in several apicomplexans such as Plasmodium falciparum (6), Cryptosporidium parvum (7,8) where novel drug targets are of crucial interest (9), N. caninum (10), Eimeria tenella, and Babesia bovis (11). Excellent correlations between cell activity and CDPK1 inhibition were achieved by compounds from a focused bumped kinase inhibitor (BKI) library.…”

Aspectos epidemiológicos de coccidiosis intestinales en comunidad rural de la Península de Paraguaná, estado Falcón, Venezuela

“…La transmisión de los ooquistes ocurre por la vía fecal-oral, a través de fuentes de agua inadecuadamente tratadas, alimentos contaminados (frutas, vegetales) o inclusive de persona a persona; en el caso de la cryptosporidiosis puede existir un componente zoonótico 1,3 . Para el diagnóstico parasitológico de las coccidiosis intestinales se requiere realizar una técnica con tinción, siendo la de Kinyoun una de las más implementadas; también se han desarrollado técnicas más sensibles y específicas como las de tipo inmunológicas (e.g., inmunoaglutinación de partículas de látex, inmunofluorescencia directa, ELISA) y moleculares (e.g., reacción en cadena de la polimerasa: PCR); sin embargo, las mismas poseen elevados costos 1,3,6,7 .…”