An update on Cryptosporidium biology and therapeutic avenues

Abstract

Cryptosporidium species has been identified as an important pediatric diarrheal pathogen in resource-limited countries, particularly in very young children (0–24 months). However, the only available drug (nitazoxanide) has limited efficacy and can only be prescribed in a medical setting to children older than one year. Many drug development projects have started to investigate new therapeutic avenues. Cryptosporidium ’s unique biology is challenging for the traditional drug discovery pipeline and requires novel drug screening approaches. Notably, in recent years, new methods of oocyst generation, in vitro processing, and continuous three-dimensional cultivation capacities have been developed. This has enabled more physiologically pertinent research assays for inhibitor discovery. In a short time, many great strides have been made in the development of anti- Cryptosporidium drugs. These are expected to eventually turn into clinical candidates for cryptosporidiosis treatment in the future. This review describes the latest development in Cryptosporidium biology, genomics, transcriptomics of the parasite, assay development, and new drug discovery.

Pyroptosis Tuning in Intestinal Cryptosporidiosis via the Natural Histone Deacetylase Inhibitor Romidepsin

“…In previous research studies by Chua [8], and a strong anti-plasmodial effect in mosquitoes [14]. Their results endorse the current study's findings, because romidepsin succeeded in decreasing the cryptosporidial parasitic load, even more than the standard anti-cryptosporidial drug nitazoxanide.…”

“…In vitro cultivation of Cryptosporidium oocysts is a new method under development that can deliver deeper insights about the parasite pathophysiology and provide researchers with more precise tools to assess new drugs [8,52]. Thereon, an ex vivo ileal explant was included in this study.…”

“…To combat the minimal invasive nature of Cryptosporidium , a strong innate immune response is needed [8]. Moreover, interferon‐gamma is considered a major immune weapon during cryptosporidiosis because it is responsible for the activation of inflammosomes in response to infection [9].…”

Cryptosporidium parvum parasite microscopic and molecular diagnostics in the Holy Karbala/ Iraq .

“…In addition to the fact that there are different rates of parasite infection diagnosed by PCR method, including the study of Al-Shabani (2014) [44] with a percentage of 72.64% in Al-Diwaniyah Governorate, and the study of El-Settawy and Fathy (2012) [45] with a percentage of 24.4% in Egypt, as well as Lim et al (2011) [46] by 64% in Malaysia. The reason for the difference in ratios is due to several factors, including the methods of preserving and storing samples, as well as the number of samples and the method used to extract DNA, as well as the accuracy of microscopic diagnosis and the extent of distinction between parasite egg sacs and other parasite egg sac…”

In vivo evaluation the efficiency of nitazoxanide with cationic Gemini surfactant on Cryptosporidiosis

“…Nitazoxanide is the only drug approved by the U.S. Food and Drug Administration, and it is not effective in patients with immunodeficiency and not approved in infants younger than 1 year 7 . It acts by inhibiting pyruvate ferredoxin oxidoreductase (PFOR), thereby impeding anaerobic energy transfer reactions 8 . As nitazoxanide is used to treat cryptosporidiosis in children, its efficacy is limited in malnourished people and compromised immune systems, this highlights the significance of research towards medication development for the treatment of cryptosporidiosis.…”