Imaging schistosomes
            <i>in vivo</i>

Krautz‐Peterson, Greice; Ndegwa, David; Vasquez, Kristine; Korideck, Houari; Zhang, Jun; Peterson, Jeffrey D.; Skelly, Patrick J.

doi:10.1096/fj.08-127738

Cited by 21 publications

(26 citation statements)

References 54 publications

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“…A linear correlation between total probe amount and worm burden was observed, but only in mice with less than 60 worms. Similar results were demonstrated in another study, although only animals with less than 35 worms were included [17]. This demonstrates the presence of adult worms in the mesenteric vasculature, which was confirmed at the time the worms were recovered.…”

Section: Discussionsupporting

confidence: 88%

In Vivo Imaging of Schistosomes to Assess Disease Burden Using Positron Emission Tomography (PET)

et al. 2010

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BackgroundSchistosomes are chronic intravascular helminth parasites of humans causing a heavy burden of disease worldwide. Diagnosis of schistosomiasis currently requires the detection of schistosome eggs in the feces and urine of infected individuals. This method unreliably measures disease burden due to poor sensitivity and wide variances in egg shedding. In vivo imaging of schistosome parasites could potentially better assess disease burden, improve management of schistosomiasis, facilitate vaccine development, and enhance study of the parasite's biology. Schistosoma mansoni (S. mansoni) have a high metabolic demand for glucose. In this work we investigated whether the parasite burden in mice could be assessed by positron emission tomography (PET) imaging with 2-deoxy-2[18F]fluoro-D-glucose (FDG).Methodology/Principal FindingsLive adult S. mansoni worms FDG uptake in vitro increased with the number of worms. Athymic nude mice infected with S. mansoni 5–6 weeks earlier were used in the imaging studies. Fluorescence molecular tomography (FMT) imaging with Prosense 680 was first performed. Accumulation of the imaging probe in the lower abdomen correlated with the number of worms in mice with low infection burden. The total FDG uptake in the common portal vein and/or regions of elevated FDG uptake in the liver linearly correlated to the number of worms recovered from infected animals (R2 = 0.58, P<0.001, n = 40). FDG uptake showed a stronger correlation with the worm burden in mice with more than 50 worms (R2 = 0.85, P<0.001, n = 17). Cryomicrotome imaging confirmed that most of the worms in a mouse with a high infection burden were in the portal vein, but not in a mouse with a low infection burden. FDG uptake in recovered worms measured by well counting closely correlated with worm number (R2 = 0.85, P<0.001, n = 21). Infected mice showed a 32% average decrease in total FDG uptake after three days of praziquantel treatment (P = 0.12). The total FDG uptake in untreated mice increased on average by 36% over the same period (P = 0.052).ConclusionFDG PET may be useful to non-invasively quantify the worm burden in schistosomiasis-infected animals. Future investigations aiming at minimizing non-specific FDG uptake and to improve the recovery of signal from worms located in the lower abdomen will include the development of more specific radiotracers.

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Section: Discussionsupporting

confidence: 88%

In Vivo Imaging of Schistosomes to Assess Disease Burden Using Positron Emission Tomography (PET)

et al. 2010

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“…Quantitation of the total signal detected in the S. mansoni infected vs. uninfected mice revealed significantly higher signal in the infected mice with the signal reflecting the localization of the parasites within the infected mice . Not surprisingly, the parasites were not uniformly distributed throughout the abdomen but were accumulated in selected areas.…”

Section: Detecting Schistosomes In Vivo Using Fluorescence Molecular mentioning

confidence: 94%

The use of imaging to detect schistosomes and diagnose schistosomiasis

Skelly¹

2013

Parasite Immunology

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Summary Several imaging modalities have been employed to examine schistosomes and monitor schistosome-induced pathology. Ultrasound is a non-invasive imaging method that has long been used in the laboratory and in the field to evaluate pathological changes, notably fibrosis, that arise as a consequence of the host response to schistosome eggs lodging in a variety of tissues. Ultrasonography has been widely used to monitor changes in the extent of fibrosis and in spleen/liver enlargement following chemotherapeutic treatment for schistosomiasis. Imaging methods to monitor schistosomes themselves in vivo (as opposed to detecting schistosome-induced pathology) include positron emission tomography (PET) and fluorescence molecular tomography (FMT). Both approaches rely on schistosome uptake of tracers that are introduced into infected animals and that can be detected externally. These methods have been used to successfully detect schistosomes in vivo and to monitor their elimination following chemotherapeutic treatment. Direct monitoring of live schistosomes in vivo has been achieved using intravital microscopy (IVM), when the infected tissues of anaesthetized animals are exposed. Finally, schistosome eggs have been visualized by confocal laser scanning microscopy in infected mice as well as in a human patient with schistosomiasis hematobium. Further advances in imaging technologies seem likely to provide greater insight into disease progression and into the biology of schistosomes in the most relevant setting – within a live animal.

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“…The landmark availability of the complete sequences of the S. japonicum (171) and S. mansoni (18) genomes will provide the necessary ancillary information. As well, new approaches in antigen discovery through the generation of a large schistosome transcriptome database, gene finding, and the explosion in postgenome technologies, including DNA microarray profiling, proteomics, glycomics, immunomics, and the application of RNA interference (RNAi) and novel imaging techniques (2,24,25,41,53,72,73,75,76,85,95,109,126,127,179,189,197,205,219,224,230), provide an unprecedented opportunity to identify a new generation of vaccine target molecules that may induce greater potency than the current candidate schistosome antigens (138).…”

Section: Vaccine Developmentmentioning

confidence: 99%

Schistosomiasis in the People's Republic of China: the Era of the Three Gorges Dam

et al. 2010

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SUMMARY The potential impact of the Three Gorges Dam (TGD) on schistosomiasis transmission in China has invoked considerable global concern. The TGD will result in changes in the water level and silt deposition downstream, favoring the reproduction of Oncomelania snails. Combined with blockages of the Yangtze River's tributaries, these changes will increase the schistosomiasis transmission season within the marshlands along the middle and lower reaches of the Yangtze River. The changing schistosome transmission dynamics necessitate a comprehensive strategy to control schistosomiasis. This review discusses aspects of the epidemiology and transmission of Schistosoma japonicum in China and considers the pathology, clinical outcomes, diagnosis, treatment, immunobiology, and genetics of schistosomiasis japonica together with an overview of current progress in vaccine development, all of which will have an impact on future control efforts. The use of synchronous praziquantel (PZQ) chemotherapy for humans and domestic animals is only temporarily effective, as schistosome reinfection occurs rapidly. Drug delivery requires a substantial infrastructure to regularly cover all parts of an area of endemicity. This makes chemotherapy expensive and, as compliance is often low, a less than satisfactory control option. There is increasing disquiet about the possibility that PZQ-resistant schistosomes will develop. Consequently, as mathematical modeling predicts, vaccine strategies represent an essential component in the future control of schistosomiasis in China. With the inclusion of focal mollusciciding, improvements in sanitation, and health education into the control scenario, China's target of reducing the level of schistosome infection to less than 1% by 2015 may be achievable.

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Imaging schistosomes in vivo

Cited by 21 publications

References 54 publications

In Vivo Imaging of Schistosomes to Assess Disease Burden Using Positron Emission Tomography (PET)

In Vivo Imaging of Schistosomes to Assess Disease Burden Using Positron Emission Tomography (PET)

The use of imaging to detect schistosomes and diagnose schistosomiasis

Schistosomiasis in the People's Republic of China: the Era of the Three Gorges Dam

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