Treatment with Letrazuril of Refractory Cryptosporidial Diarrhea Complicating AIDS

Loeb, Mark; Walach, Christine; Phillips, Joseph; Fong, I. W.; Salit, Irving E.; Rachlis, Anita; Walmsley, Sharon

doi:10.1097/00042560-199509000-00007

Cited by 11 publications

(4 citation statements)

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“…Renewed awareness of potential waterborne transmission of both organisms is based on the number of well-documented outbreaks during the past few years and the publicity surrounding water regulations and testing. The importance of an early diagnosis and appropriate therapy cannot be overemphasized, particularly for immunocompromised patients (17,20,21,25,34,36).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of nine immunoassay kits (enzyme immunoassay and direct fluorescence) for detection of Giardia lamblia and Cryptosporidium parvum in human fecal specimens

1997

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It is well known that Giardia lamblia and Cryptosporidium parvum can cause severe symptoms in humans, particularly those who are immunologically compromised. Immunoassay procedures offer both increased sensitivity and specificity compared to conventional staining methods. These reagents are also helpful when screening large numbers of patients, particularly in an outbreak situation or when screening patients with minimal symptoms. The data obtained by using 9 diagnostic kits were compared: direct fluorescent-antibody assay (DFA) kits (TechLab Giardia/Crypto IF kit, TechLab Crypto IF kit, and Meridian Merifluor Cryptosporidium/Giardia) and enzyme immunoassay (EIA) kits (Alexon ProSpecT Giardia EZ Microplate Assay, Alexon ProSpecT Cryptosporidium Microplate Assay, Cambridge Giardia lamblia Antigen Microwell ELISA, Meridian Premier Giardia lamblia, Meridian Premier Cryptosporidium, TechLab Giardia CELISA, Trend Giardia lamblia EIA). The test with the Meridian Merifluor Cryptosporidium/Giardia kit was used as the reference method. In various combinations, 60 specimens positive for Giardia, 60 specimens positive for Cryptosporidium, 40 specimens positive for a Giardia-Cryptosporidium mix, and 50 negative fecal specimens were tested. Different species (nine protozoa, three coccidia, one microsporidium, five nematodes, three cestodes, and one trematode) were included in the negative specimens. The sensitivity of EIA for Giardia ranged from 94% (Alexon) to 99% (Trend and Cambridge); the specificity was 100% with all EIA kits tested. The sensitivity of EIA for Cryptosporidium ranged from 98% (Alexon) to 99% (Meridian Premier); specificities were 100%. All DFA results were in agreement, with 100% sensitivity and specificity; however, the TechLab reagents resulted in fluorescence intensity that was generally one level below that seen with the reagents used in the reference method. In addition to sensitivity and specificity, factors such as cost, simplicity, ease of interpretation of results (color, intensity of fluorescence), equipment, available personnel, and number of tests ordered are also important considerations prior to kit selection.

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Section: Discussionmentioning

confidence: 99%

Evaluation of nine immunoassay kits (enzyme immunoassay and direct fluorescence) for detection of Giardia lamblia and Cryptosporidium parvum in human fecal specimens

1997

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“…These include letrazuril [17], spiramycin [5], diclazuril [18], azithromycin [19], roxithromycin [20], and oral bovine immunoglobulin to Cryptosporidium [21]. Paromomycin is a nonabsorbable aminoglycoside [22] that has activity against C. parvum in vitro [23] and in animal models at high doses.…”

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confidence: 99%

Paromomycin: No More Effective than Placebo for Treatment of Cryptosporidiosis in Patients with Advanced Human Immunodeficiency Virus Infection

et al. 2000

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To evaluate the efficacy of paromomycin for the treatment of symptomatic cryptosporidial enteritis in human immunodeficiency virus-infected adults, we conducted a prospective, randomized, double-blind, placebo-controlled trial before the widespread introduction of highly active antiretroviral therapy (HAART). Seven units under the auspices of the AIDS Clinical Trials Group enrolled 35 adults with CD4 cell counts of < or = 150/mm(3). Initially, 17 patients received paromomycin (500 mg 4 times daily) and 18 received matching placebo for 21 days. Then all patients received paromomycin (500 mg q.i.d.) for an additional 21 days. Clinical definitions of response were measured by an average number of bowel movements per day in association with concurrent need for antidiarrheal agents that was lower than that before study entry. There was no treatment response during the placebo-controlled phase of the study according to protocol-defined criteria (P=.88). Three paromomycin recipients (17.6%) versus 2 placebo recipients (14.3%) responded completely. Rates of combined partial and complete responses in the paromomycin arm (8 out of 17, 47.1%) and the placebo arm (5 out of 14, 35.7%) of the study were also similar (P=.72). The clinical course of cryptosporidiosis was quite variable. Paromomycin was not shown to be more effective than placebo for the treatment of symptomatic cryptosporidial enteritis. However, inadequate statistical power prevents definitive rejection of the usefulness of paromomycin as therapy for this infection.

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“…In another study, a single patient showed both clinical and parasitological response to diclazuril treatment but the infection was less severe and the patient also received antiretroviral therapy during and after the treatment course ( Menichetti et al., 1991 ). Additionally, letrazuril, the p-fluor analog of diclazuril, shows only partial efficacy against advanced AIDS-related cryptosporidial diarrhea ( Harris et al., 1994 ; Loeb et al., 1995 ; Blanshard et al., 1997 ) and treated patients develop temporary drug-related side-effects including abnormal liver function tests and skin rashes that tend to resolve after treatment discontinuation ( Murdoch et al., 1993 ; Harris et al., 1994 ; Loeb et al., 1995 ).…”

Section: Treatment Options In Humans and Animals: The Past And Curren...mentioning

confidence: 99%

Past, current, and potential treatments for cryptosporidiosis in humans and farm animals: A comprehensive review

Khan

Witola

2023

Front. Cell. Infect. Microbiol.

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The intracellular protozoan parasite of the genus Cryptosporidium is among the leading causes of waterborne diarrheal disease outbreaks throughout the world. The parasite is transmitted by ingestion of infective oocysts that are highly stable in the environment and resistant to almost all conventional disinfection methods and water treatments. Control of the parasite infection is exceedingly difficult due to the excretion of large numbers of oocysts in the feces of infected individuals that contaminate the environment and serve as a source of infection for susceptible hosts including humans and animals. Drug development against the parasite is challenging owing to its limited genetic tractability, absence of conventional drug targets, unique intracellular location within the host, and the paucity of robust cell culture platforms for continuous parasite propagation. Despite the high prevalence of the parasite, the only US Food and Drug Administration (FDA)-approved treatment of Cryptosporidium infections is nitazoxanide, which has shown moderate efficacy in immunocompetent patients. More importantly, no effective therapeutic drugs are available for treating severe, potentially life-threatening cryptosporidiosis in immunodeficient patients, young children, and neonatal livestock. Thus, safe, inexpensive, and efficacious drugs are urgently required to reduce the ever-increasing global cryptosporidiosis burden especially in low-resource countries. Several compounds have been tested for both in vitro and in vivo efficacy against the disease. However, to date, only a few experimental compounds have been subjected to clinical trials in natural hosts, and among those none have proven efficacious. This review provides an overview of the past and present anti-Cryptosporidium pharmacotherapy in humans and agricultural animals. Herein, we also highlight the progress made in the field over the last few years and discuss the different strategies employed for discovery and development of effective prospective treatments for cryptosporidiosis.

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Treatment with Letrazuril of Refractory Cryptosporidial Diarrhea Complicating AIDS

Cited by 11 publications

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Evaluation of nine immunoassay kits (enzyme immunoassay and direct fluorescence) for detection of Giardia lamblia and Cryptosporidium parvum in human fecal specimens

Evaluation of nine immunoassay kits (enzyme immunoassay and direct fluorescence) for detection of Giardia lamblia and Cryptosporidium parvum in human fecal specimens

Paromomycin: No More Effective than Placebo for Treatment of Cryptosporidiosis in Patients with Advanced Human Immunodeficiency Virus Infection

Past, current, and potential treatments for cryptosporidiosis in humans and farm animals: A comprehensive review

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