An evaluation of the potential use of<i>Cryptosporidium</i>species as agents for deliberate release

Hagen, Ralf Matthias; Loderstaedt, Ulrike; Frickmann, Hagen

doi:10.1136/jramc-2013-000186

Cited by 3 publications

(2 citation statements)

References 64 publications

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“…Human cryptosporidiosis, which typically affects immunocompromised patients, has traditionally been diagnosed with acid-fast staining and subsequent microscopical assessment [ 1 , 2 , 3 , 4 ]. However, skilful microscopy is difficult to maintain in non-endemic settings [ 5 ], resulting in limited diagnostic accuracy even in European reference centres [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Comparison of Three Real-Time PCR Assays Targeting the SSU rRNA Gene, the COWP Gene and the DnaJ-Like Protein Gene for the Diagnosis of Cryptosporidium spp. in Stool Samples

Weinreich

Hahn²,

Eberhardt

et al. 2021

Pathogens

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As qualified microscopy of enteric parasitoses as defined by high diagnostic accuracy is difficult to maintain in non-endemic areas due to scarce opportunities for practicing with positive sample materials, molecular diagnostic options provide less investigator-dependent alternatives. Here, we compared three molecular targets for the real-time PCR-based detection of Cryptosporidium spp. From a population of 1000 individuals comprising both Ghanaian HIV (human immunodeficiency virus) patients and military returnees after deployment in the tropics, stool samples were assessed for Cryptosporidium spp. by real-time PCR targeting the small subunit ribosomal RNA (SSU rRNA) gene, the Cryptosporidium oocyst wall (COWP) gene, and the DnaJ-like protein gene (DnaJ), respectively. In declining order, sensitivity of 100% for the SSU rRNA gene PCR, 90.0% for the COWP PCR and 88.8% for the DnaJ PCR, respectively, as well as specificity of 99.6% for the COWP PCR and 96.9% for both the SSU rRNA gene PCR and the DnaJ PCR, respectively, were recorded. Substantial agreement (kappa value 0.663) between the three assays was observed. Further, an accuracy-adjusted Cryptosporidium spp. prevalence of 6.0% was calculated for the study population. In conclusion, none of the assessed real-time PCR assays were associated with perfect test accuracy. However, a combination of highly sensitive SSU rRNA gene PCR for screening purposes and more specific COWP PCR for confirmatory testing should allow reliable diagnosis of Cryptosporidium spp. in stool samples even in low prevalence settings.

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Section: Introductionmentioning

confidence: 99%

Comparison of Three Real-Time PCR Assays Targeting the SSU rRNA Gene, the COWP Gene and the DnaJ-Like Protein Gene for the Diagnosis of Cryptosporidium spp. in Stool Samples

Weinreich

Hahn²,

Eberhardt

et al. 2021

Pathogens

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“…Cryptosporidium infection can also cause an unrecoverable growth deficit in young children, making these parasites a major cause of the "vicious cycle" of diarrhea and malnutrition in the developing world (7). C. parvum oocysts can be obtained with relative ease, and the water supply is readily accessed, so there is also a credible concern that these organisms could be used maliciously (8). The 1993 natural Milwaukee outbreak illustrates the potential damage of such an act of bioterrorism: contaminated drinking water resulted in approximately 403,000 cases of disease, the hospitalization of 4,400 patients, and an estimated 69 deaths (9).…”

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confidence: 99%

Validation of IMP Dehydrogenase Inhibitors in a Mouse Model of Cryptosporidiosis

Gorla

McNair

Yang

et al. 2014

Antimicrob Agents Chemother

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f Cryptosporidium parasites are a major cause of diarrhea and malnutrition in the developing world, a frequent cause of waterborne disease in the developed world, and a potential bioterrorism agent. Currently, available treatment is limited, and Cryptosporidium drug discovery remains largely unsuccessful. As a result, the pharmacokinetic properties required for in vivo efficacy have not been established. We have been engaged in a Cryptosporidium drug discovery program targeting IMP dehydrogenase (CpIMPDH). Here, we report the activity of eight potent and selective inhibitors of CpIMPDH in the interleukin-12 (IL-12) knockout mouse model, which mimics acute human cryptosporidiosis. Two compounds displayed significant antiparasitic activity, validating CpIMPDH as a drug target. The best compound, P131 (250 mg/kg of body weight/day), performed equivalently to paromomycin (2,000 mg/kg/day) when administered in a single dose and better than paromomycin when administered in three daily doses. One compound, A110, appeared to promote Cryptosporidium infection. The pharmacokinetic, uptake, and permeability properties of the eight compounds were measured. P131 had the lowest systemic distribution but accumulated to high concentrations within intestinal cells. A110 had the highest systemic distribution. These observations suggest that systemic distribution is not required, and may be a liability, for in vivo antiparasitic activity. Intriguingly, A110 caused specific alterations in fecal microbiota that were not observed with P131 or vehicle alone. Such changes may explain how A110 promotes parasitemia. Collectively, these observations suggest a blueprint for the development of anticryptosporidial therapy.

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A methodological framework for the evaluation of syndromic surveillance systems: a case study of England

et al. 2018

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BackgroundSyndromic surveillance complements traditional public health surveillance by collecting and analysing health indicators in near real time. The rationale of syndromic surveillance is that it may detect health threats faster than traditional surveillance systems permitting more timely, and hence potentially more effective public health action. The effectiveness of syndromic surveillance largely relies on the methods used to detect aberrations. Very few studies have evaluated the performance of syndromic surveillance systems and consequently little is known about the types of events that such systems can and cannot detect.MethodsWe introduce a framework for the evaluation of syndromic surveillance systems that can be used in any setting based upon the use of simulated scenarios. For a range of scenarios this allows the time and probability of detection to be determined and uncertainty is fully incorporated. In addition, we demonstrate how such a framework can model the benefits of increases in the number of centres reporting syndromic data and also determine the minimum size of outbreaks that can or cannot be detected. Here, we demonstrate its utility using simulations of national influenza outbreaks and localised outbreaks of cryptosporidiosis.ResultsInfluenza outbreaks are consistently detected with larger outbreaks being detected in a more timely manner. Small cryptosporidiosis outbreaks (<1000 symptomatic individuals) are unlikely to be detected. We also demonstrate the advantages of having multiple syndromic data streams (e.g. emergency attendance data, telephone helpline data, general practice consultation data) as different streams are able to detect different outbreak types with different efficacy (e.g. emergency attendance data are useful for the detection of pandemic influenza but not for outbreaks of cryptosporidiosis). We also highlight that for any one disease, the utility of data streams may vary geographically, and that the detection ability of syndromic surveillance varies seasonally (e.g. an influenza outbreak starting in July is detected sooner than one starting later in the year). We argue that our framework constitutes a useful tool for public health emergency preparedness in multiple settings.ConclusionsThe proposed framework allows the exhaustive evaluation of any syndromic surveillance system and constitutes a useful tool for emergency preparedness and response.Electronic supplementary materialThe online version of this article (10.1186/s12889-018-5422-9) contains supplementary material, which is available to authorized users.

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An evaluation of the potential use ofCryptosporidiumspecies as agents for deliberate release

Abstract: Intentional transmission should be suspected in cases of sudden outbreaks of cryptosporidiosis, particularly where adequate food and drinking water hygiene precautions are being enforced. Appropriate diagnostic procedures should be available so that the diagnosis is not missed.

Cited by 3 publications

References 64 publications

Comparison of Three Real-Time PCR Assays Targeting the SSU rRNA Gene, the COWP Gene and the DnaJ-Like Protein Gene for the Diagnosis of Cryptosporidium spp. in Stool Samples

Comparison of Three Real-Time PCR Assays Targeting the SSU rRNA Gene, the COWP Gene and the DnaJ-Like Protein Gene for the Diagnosis of Cryptosporidium spp. in Stool Samples

Validation of IMP Dehydrogenase Inhibitors in a Mouse Model of Cryptosporidiosis

A methodological framework for the evaluation of syndromic surveillance systems: a case study of England

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