Treatment of Cryptosporidiosis in Immunocompromised Hosts

Zardi, Enrico Maria; Picardi, Antonio; Afeltra, Antonella

doi:10.1159/000086920

Cited by 60 publications

(40 citation statements)

References 10 publications

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“…However, the drugs paromomycin, azithromycin (218), and nitazoxanide (249) have been used to treat cryptosporidiosis in HIV-infected patients and have been shown to reduce the parasite load. Resolution of cryptosporidiosis can be maintained with effective highly active antiretroviral therapy (HAART) (191,218,242,292). There is also evidence to suggest that some antiretroviral compounds used in HAART may have a direct inhibitory effect on Cryptosporidium (197).…”

Section: Cryptosporidiummentioning

confidence: 99%

Clinical Significance of Enteric Protozoa in the Immunosuppressed Human Population

et al. 2009

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SUMMARY Globally, the number of immunosuppressed people increases each year, with the human immunodeficiency virus (HIV) pandemic continuing to spread unabated in many parts of the world. Immunosuppression may also occur in malnourished persons, patients undergoing chemotherapy for malignancy, and those receiving immunosuppressive therapy. Components of the immune system can be functionally or genetically abnormal as a result of acquired (e.g., caused by HIV infection, lymphoma, or high-dose steroids or other immunosuppressive medications) or congenital illnesses, with more than 120 congenital immunodeficiencies described to date that either affect humoral immunity or compromise T-cell function. All individuals affected by immunosuppression are at risk of infection by opportunistic parasites (such as the microsporidia) as well as those more commonly associated with gastrointestinal disease (such as Giardia). The outcome of infection by enteric protozoan parasites is dependent on absolute CD4+ cell counts, with lower counts being associated with more severe disease, more atypical disease, and a greater risk of disseminated disease. This review summarizes our current state of knowledge on the significance of enteric parasitic protozoa as a cause of disease in immunosuppressed persons and also provides guidance on recent advances in diagnosis and therapy for the control of these important parasites.

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Section: Cryptosporidiummentioning

confidence: 99%

Clinical Significance of Enteric Protozoa in the Immunosuppressed Human Population

et al. 2009

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“…Octreotide acetate, atovaquone, letrazuril, and lasolacid have been investigated in immunosuppressed persons but with poor efficacy and inconsistent results (Zardi, 2005).…”

Section: Other Antimicrobial Agentsmentioning

confidence: 99%

Drug treatment and novel drug target againstCryptosporidium

Gargala

2008

Parasite

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Summary :Cryptosporidiosis emergence triggered the screening of many compounds for potential anti-cryptosporidial activity in which the majority were ineffective. The outbreak of cryptosporidiosis which occurred in Milwaukee in 1993 was not only the first significant emergence of Cryptosporidium spp. as a major human pathogen but also a huge waterborne outbreak thickening thousands of people from a major city in North America. Since then, outbreaks of cryptosporidiosis are regularly occurring throughout the world. New drugs against this parasite became consequently urgently needed. Among the most commonly used treatments against cryptosporidiosis are paromomycin, and azithromycin, which are partially effective. Nitazoxanide (NTZ)'s effectiveness was demonstrated in vitro, and in vivo using several animal models and finally in clinical trials. It significantly shortened the duration of diarrhea and decreased mortality in adults and in malnourished children. NTZ is not effective without an appropriate immune response. In AIDS patients, combination therapy restoring immunity along with antimicrobial treatment of Cryptosporidium infection is necessary. Recent investigations focused on the potential of molecular-based immunotherapy against this parasite. Others tested the effects of probiotic bacteria, but were unable to demonstrate eradication of C. parvum. New synthetic isoflavone derivatives demonstrated excellent activity against C. parvum in vitro and in a gerbil model of infection. Newly synthesized nitroor non nitro-thiazolide compounds, derived from NTZ, have been recently shown to be at least as effective as NTZ against C. parvum in vitro development and are promising new therapeutic agents.

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“…More striking is the drastic reduction in the prevalence of opportunistic Cryptosporidium spp. infections associated with AIDS patients treated with highly active antiretroviral therapy (Zardi et al 2005). Accordingly, there is an urgent need for the development of novel compounds to eradicate these infections with few or no side effects for the host.…”

Section: Introductionmentioning

confidence: 99%

DNA topoisomerases in apicomplexan parasites: promising targets for drug discovery

et al. 2010

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The phylum Apicomplexa includes a large group of protozoan parasites responsible for a wide range of animal and human diseases. Destructive pathogens, such as Plasmodium falciparum and Plasmodium vivax, causative agents of human malaria, Cryptosporidium parvum, responsible of childhood diarrhoea, and Toxoplasma gondii, responsible for miscarriages and abortions in humans, are frequently associated with HIV immunosuppression in AIDS patients. The lack of effective vaccines, along with years of increasing pressure to eradicate outbreaks with the use of drugs, has favoured the formation of multidrug resistant strains in endemic areas. Almost all apicomplexan of medical interest contain two endosymbiotic organelles that contain their own mitochondrial and apicoplast DNA. Apicoplast is an attractive target for drug testing because in addition to harbouring singular metabolic pathways absent in the host, it also has its own transcription and translation machinery of bacterial origin. Accordingly, apicomplexan protozoa contain an interesting mixture of enzymes to unwind DNA from eukaryotic and prokaryotic origins. On the one hand, the main mechanism of DNA unwinding includes the scission of one-type I-or both DNA strands-type II eukaryotic topoisomerases, establishing transient covalent bonds with the scissile end. These enzymes are targeted by camptothecin and etoposide, respectively, two natural drugs whose semisynthetic derivatives are currently used in cancer chemotherapy. On the other hand, DNA gyrase is a bacterial-borne type II DNA topoisomerase that operates within the apicoplast and is effectively targeted by bacterial antibiotics like fluoroquinolones and aminocoumarins. The present review is an update on the new findings concerning topoisomerases in apicomplexan parasites and the role of these enzymes as targets for therapeutic agents.

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Treatment of Cryptosporidiosis in Immunocompromised Hosts

Cited by 60 publications

References 10 publications

Clinical Significance of Enteric Protozoa in the Immunosuppressed Human Population

Clinical Significance of Enteric Protozoa in the Immunosuppressed Human Population

Drug treatment and novel drug target againstCryptosporidium

DNA topoisomerases in apicomplexan parasites: promising targets for drug discovery

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