Advances in therapeutic and vaccine targets for Cryptosporidium: Challenges and possible mitigation strategies

Rahman, Sajid Ur; Mi, Rongsheng; Zhou, Shasha; Gong, Haiyan; Ullah, Munib; Huang, Yan; Han, Xiangan; Chen, Zhaoguo

doi:10.1016/j.actatropica.2021.106273

Cited by 14 publications

(9 citation statements)

References 160 publications

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“…Despite the recognised impact on human health and livestock production, no effective drugs or vaccines are available for controlling C. parvum infections. An urgent need for new control tools has been repeatedly underlined (Chavez and White 2018; Khan and Witola 2023; Rahman et al 2022). Recent WGS studies have started to provide insights into the genetics of C. parvum , proposing a role of recombination events in the evolution of this species and have allowed to identify a number of genes under positive selection, potentially involved in host-parasite interactions (Corsi et al 2023; T. Wang et al 2022).…”

Section: Discussionmentioning

confidence: 99%

Comparative genomics reveals the emergence of an outbreak-associatedCryptosporidium parvumpopulation in Europe and its spread to the USA

Bellinzona,

Nardi,

Castelli

et al. 2023

Preprint

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The zoonotic parasiteCryptosporidium parvumis a global cause of gastrointestinal disease in humans and ruminants. Sequence analysis of the highly polymorphic gp60 gene enabled the classification of C. parvum isolates into multiple groups (e.g. IIa, IIc, Id) and a large number of subtypes. In Europe, subtype IIaA15G2R1 is largely predominant and has been associated with many water- and food-borne outbreaks. In this study, we generated new whole genome sequence (WGS) data from 123 human- and ruminant-derived isolates collected in 13 European countries and included other available WGS data from Europe, Egypt, China and the USA (n=72) in the largest comparative genomics study to date. We applied rigorous filters to exclude mixed infections and analysed a dataset from 141 isolates from the zoonotic groups IIa (n=119) and IId (n=22). Based on 28,047 high quality, biallelic genomic SNPs, we identified three distinct and strongly supported populations: isolates from China (IId) and Egypt (IIa and IId) formed population 1, a minority of European isolates (IIa and IId) formed population 2, while the majority of European (IIa, including all IIaA15G2R1 isolates) and all isolates from the USA (IIa) clustered in population 3. Based on analyses of the population structure, population genetics and recombination, we show that population 3 has recently emerged and expanded throughout Europe to then, possibly from the UK, reach the USA where it also expanded. In addition, genetic exchanges between different populations led to the formation of mosaic genomes. The reason(s) for the successful spread of population 3 remained elusive, although genes under selective pressure uniquely in this population were identified.

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Section: Discussionmentioning

confidence: 99%

Comparative genomics reveals the emergence of an outbreak-associatedCryptosporidium parvumpopulation in Europe and its spread to the USA

Bellinzona,

Nardi,

Castelli

et al. 2023

Preprint

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“…Halofuginone shows promise as a treatment for coccidiosis in animals by targeting a specific parasite enzyme [62,63]; its use in humans is limited. This compound is even licensed for cryptosporidiosis in calves in some countries [62,63] However, unfavorable side effects on the gastrointestinal system and higher toxicity compared to other options prevent its use for human cryptosporidiosis treatment [63]. These limitations on effective drug treatments force many developing countries to rely on basic strategies like rehydration and electrolyte replacement for managing Cryptosporidiosis.…”

Section: Present Therapeutic Optionsmentioning

confidence: 99%

Cryptosporidium spp.: Challenges in Control and Potential Therapeutic Strategies

Akinnubi

2024

Intestinal Parasites - New Developments in Diagnosis, Treatment, Prevention and Future Directions [Working Title]

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Cryptosporidium parasites (Cryptosporidium hominis and Cryptosporidium parvum) are prominent for playing a crucial role in the high prevalence of diarrheal infection across the globe, with immunocompromised individual at risk. The parasites’ remarkable resilience in the environment due to several adaptive strategies is responsible for persistent challenge in control especially in regions with inadequate sanitation. In tackling these challenges, exploring promising potential therapeutic strategies to combat Cryptosporidium infections is of critical importance. This encompasses investigations into experimental drugs, immunotherapies, and vaccine development efforts, all aimed at reducing the burden these parasites impose. This review aims to present the current state of research and development to shed light on the future prospects for managing Cryptosporidium infections and their profound impact on public health.

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“…Thus, natural products signify some good opportunities to discover novel therapeutic molecules ( 16 , 17 ). On the other hand, the occurrence of partial immunity after exposure suggests the potential for a successful and effective vaccine, yet the identification of exact markers for protection remains a complex task ( 21 ). The control of parasitic infections needs great attention in the fields of public health, parasitology research, medical science, and political will.…”

Section: Challenges In Parasitic Diseases and The Need For Therapeuti...mentioning

confidence: 99%

Omega-3 and omega-6 polyunsaturated fatty acids and their potential therapeutic role in protozoan infections

Rahman,

Weng,

Qadeer

et al. 2024

Front. Immunol.

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Protozoa exert a serious global threat of growing concern to human, and animal, and there is a need for the advancement of novel therapeutic strategies to effectively treat or mitigate the impact of associated diseases. Omega polyunsaturated fatty acids (ω-PUFAs), including Omega-3 (ω-3) and omega-6 (ω-6), are constituents derived from various natural sources, have gained significant attention for their therapeutic role in parasitic infections and a variety of essential structural and regulatory functions in animals and humans. Both ω-3 and ω-6 decrease the growth and survival rate of parasites through metabolized anti-inflammatory mediators, such as lipoxins, resolvins, and protectins, and have both in vivo and in vitro protective effects against various protozoan infections. The ω-PUFAs have been shown to modulate the host immune response by a commonly known mechanism such as (inhibition of arachidonic acid (AA) metabolic process, production of anti-inflammatory mediators, modification of intracellular lipids, and activation of the nuclear receptor), and promotion of a shift towards a more effective immune defense against parasitic invaders by regulation the inflammation like prostaglandins, leukotrienes, thromboxane, are involved in controlling the inflammatory reaction. The immune modulation may involve reducing inflammation, enhancing phagocytosis, and suppressing parasitic virulence factors. The unique properties of ω-PUFAs could prevent protozoan infections, representing an important area of study. This review explores the clinical impact of ω-PUFAs against some protozoan infections, elucidating possible mechanisms of action and supportive therapy for preventing various parasitic infections in humans and animals, such as toxoplasmosis, malaria, coccidiosis, and chagas disease. ω-PUFAs show promise as a therapeutic approach for parasitic infections due to their direct anti-parasitic effects and their ability to modulate the host immune response. Additionally, we discuss current treatment options and suggest perspectives for future studies. This could potentially provide an alternative or supplementary treatment option for these complex global health problems.

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Advances in therapeutic and vaccine targets for Cryptosporidium: Challenges and possible mitigation strategies

Cited by 14 publications

References 160 publications

Comparative genomics reveals the emergence of an outbreak-associatedCryptosporidium parvumpopulation in Europe and its spread to the USA

Comparative genomics reveals the emergence of an outbreak-associatedCryptosporidium parvumpopulation in Europe and its spread to the USA

Cryptosporidium spp.: Challenges in Control and Potential Therapeutic Strategies

Omega-3 and omega-6 polyunsaturated fatty acids and their potential therapeutic role in protozoan infections

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