Spatial and intra-host distribution of myxozoan parasite Tetracapsuloides bryosalmonae among Baltic sea trout (Salmo trutta).

Proliferative kidney disease caused by the myxozoan parasite Tetracapsuloides bryosalmonae has been actively studied in juvenile salmonids for decades. However, very little is known about parasite prevalence and its geographical and intra-host distribution at older life stages. We screened T. bryosalmonae among adult sea trout (Salmo trutta) (n = 295) collected along the Estonian Baltic Sea coastline together with juvenile trout from 33 coastal rivers (n = 1752) to assess spatial infection patterns of the adult and juvenile fish. The parasite was detected among 38.6% of adult sea trout with the prevalence increasing from west to east, and south to north, along the coastline. A similar pattern was observed in juvenile trout. Infected sea trout were also older than uninfected fish and the parasite was detected in sea trout up to the age of 6 years. Analysis of intra-host distribution of the parasite and strontium to calcium ratios from the otoliths revealed that (re)infection through freshwater migration may occur among adult sea trout. The results of this study indicate that T. bryosalmonae can persist in a brackish water environment for several years and that returning sea trout spawners most likely contribute to the parasite life cycle by transmitting infective spores.

Differentially expressed transcripts of Tetracapsuloides bryosalmonae (Cnidaria) between carrier and dead-end hosts involved in key biological processes: novel insights from a coupled approach of FACS and RNA sequencing.

Tetracapsuloides bryosalmonae is a malacosporean endoparasite that infects a wide range of salmonids and causes proliferative kidney disease (PKD). Brown trout serves as a carrier host whereas rainbow trout represents a dead-end host. We thus asked if the parasite adapts to the different hosts by changing molecular mechanisms. We used fluorescent activated cell sorting (FACS) to isolate parasites from the kidney of brown trout and rainbow trout following experimental infection with T. bryosalmonae. The sorted parasite cells were then subjected to RNA sequencing. By this approach, we identified 1120 parasite transcripts that were expressed differentially in parasites derived from brown trout and rainbow trout. We found elevated levels of transcripts related to cytoskeleton organisation, cell polarity, peptidyl-serine phosphorylation in parasites sorted from brown trout. In contrast, transcripts related to translation, ribonucleoprotein complex biogenesis and subunit organisation, non-membrane bounded organelle assembly, regulation of protein catabolic process and protein refolding were upregulated in rainbow trout-derived parasites. These findings show distinct molecular adaptations of parasites, which may underlie their distinct outcomes in the two hosts. Moreover, the identification of these differentially expressed transcripts may enable the identification of novel drug targets that may be exploited as treatment against T. bryosalmonae. We here also describe for the first time how FACS based isolation of T. bryosalmonae cells from infected kidney of fish fosters research and allows to define differentially expressed parasite transcripts in carrier and dead-end fish hosts.

Tetracapsuloides bryosalmonae and proliferative kidney disease in Icelandic salmonids - Comparative data from two different time periods.

Tetracapsuloides bryosalmonae is a myxozoan parasite and the causative agent of proliferative kidney disease (PKD), a serious, temperature-dependent and emerging disease affecting salmonid fish. It was first identified in Iceland in 2008, from Arctic charr inhabiting a shallow lowland lake. The aim of this study was to investigate the distribution and prevalence of macroscopic and subclinical T. bryosalmonae infections in Icelandic salmonids and compare different time periods, in context with depths, volumes, altitudes and areas of the lakes and fish age. Arctic charr (Salvelinus alpinus) and brown trout (Salmo trutta) from 34 lakes, sampled between 1994-1998 and 2009-2017, were examined for macroscopic signs of PKD (n = 2,151) and the presence of T. bryosalmonae infections (n = 1,424). In the earlier period, 43% of lakes (10/23) harboured T. bryosalmonae -infected fish. The mean prevalence in those lakes was 62.1%, being most common in shallow lowland lakes whilst deeper lakes at high altitudes were all free from infection. Only a single fish from one lake showed macroscopic signs of PKD, a shallow lowland lake in southwestern Iceland. In the latter period, T. bryosalmonae was found in 16/18 lakes studied (89%), with a mean prevalence of 78-79% (excluding T.b. free lakes), being most common in the smaller, shallower lakes at lower alttudes. Macroscopic signs of PKD were observed in 11 of 18 of the lakes studied (61%) with prevalences up to 67%, most common in younger fish inhabiting small shallow lowland lakes. The results indicate that the distribution of T. bryosalmonae and the presence of PKD in Iceland have increased over the last few decades. The disease was almost non-existent in the 1990s but has become very common during the last decade or two. With further water temperature increases, as predicted by climate models, PKD is likely to increasingly affect wild salmonid populations in Iceland.

Distribution and prevalence of the myxozoan parasite Tetracapsuloides bryosalmonae in northernmost Europe: analysis of three salmonid species.

Global climate change is altering the abundance and spread of many aquatic parasites and pathogens. Proliferative kidney disease (PKD) of salmonids caused by the myxozoan Tetracapsuloides bryosalmonae is one such emerging disorder, and its impact is expected to increase with rising water temperature. Yet, the distribution and prevalence of T. bryosalmonae in Northern Europe remain poorly characterized. Here, we studied 43 locations in 27 rivers in northernmost Norway and Finland to describe T. bryosalmonae infection frequency and patterns in 1389 juvenile salmonids. T. bryosalmonae was discovered in 12 out of 27 rivers (44%) and prevalence ranged from 4.2 to 55.5% in Atlantic salmon and from 5.8 to 75% in brown trout among infected rivers. In sympatric populations, brown trout was more frequently infected with T. bryosalmonae than was salmon. Age-specific parasite prevalence patterns revealed that in contrast to lower latitudes, the infection of juvenile fish predominantly occurs during the second summer or later. Temperature monitoring over 2 yr indicated that the mean water temperature in June was 2.1 to 3.2°C higher in rivers containing T. bryosalmonae compared to parasite-free rivers, confirming the important role of temperature in parasite occurrence. Temporal comparison in T. bryosalmonae prevalence over a 10 yr period in 11 rivers did not reveal any signs of contemporary parasite spread to previously uninfected rivers. However, the wide distribution of T. bryosalmonae in rivers flowing to the Barents Sea indicates that climate change and heat waves may cause new disease outbreaks in northern regions.

Mitigating human impacts including climate change on proliferative kidney disease in salmonids of running waters.

Over the last two decades, an increasing number of reports have identified a decline in salmonid populations, possibly linked to infection with the parasite Tetracapsuloides bryosalmonae and the corresponding disease, that is, proliferative kidney disease (PKD). The life cycle of this myxozoan parasite includes sessile bryozoan species as invertebrate host, which facilitates the distribution of the parasite in running waters. As the disease outcome is temperature dependent, the impact of the disease on salmonid populations is increasing with global warming due to climate change. The goal of this review is to provide a detailed overview of measures to mitigate the effects of PKD on salmonid populations. It first summarizes the parasite life cycle, temperature-driven disease dynamics and new immunological and molecular research into disease resistance and, based on this, discusses management possibilities. Sophisticated management actions focusing on local adaptation of salmonid populations, restoration of the riverine ecosystem and keeping water temperatures cool are necessary to reduce the negative effects of PKD. Such actions include temporary stocking with PKD-resistant salmonids, as this may assist in conserving current populations that fail to reproduce.

Potential Biomarkers in Diagnosis of Renal Acanthamoebiasis.

Recent studies indicate that Acanthamoeba spp. may play a significant role in kidney dysfunction. The aim of the study was to examine the levels of kidney injury molecule 1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and monocyte chemotactic protein 1 (MCP-1), as well as an activity of matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9, respectively) in the kidneys of immunocompetent and immunosuppressed mice infected with Acanthamoeba spp. The levels of KIM-1, NGAL, and MCP-1 were analyzed by enzyme-linked immunosorbent assay (ELISA), and the activity of MMPs was determined by gelatin zymography. The elevated KIM-1 level was found in the kidneys of immunocompetent mice at the beginning of Acanthamoeba spp. infection. In the immunosuppressed mice, the KIM-1 level was statistically different. The statistically decreased NGAL level was found in the kidneys of immunocompetent mice compared to the uninfected mice. In the immunocompromised mice, we found statistically significant differences in MCP-1 levels between the uninfected and infected groups. There was an increase in the expression of both MMP-2 and MMP-9 in the kidneys of immunocompetent and immunosuppressed mice infected with Acanthamoeba spp. compared to the uninfected mice. The results indicate that KIM-1, NGAL, MCP-1, MMP-2, MMP-9, and MMP-9/NGAL might be promising biomarkers of renal acanthamoebiasis.

Isolated renal hydatid disease: laparoscopic approach to an uncommon entity (case report).

Hydatidosis is a parasitic disease, endemic in various parts of the World. It frequently involves liver and lungs and, rarely, other organs as well. Isolated renal hydatidosis is a rare entity that accounts for less than 3% of all hydatid cases. Surgery remains the mainstay of treatment. We hereby report a case of isolated renal hydatid cyst involving left kidney that was managed by laparoscopic approach.

Climate change-driven disease in sympatric hosts: Temporal dynamics of parasite burden and proliferative kidney disease in wild brown trout and Atlantic salmon.

Global climate change is altering the abundance and spread of various parasites, which has important consequences not only for host-parasite interactions but also for the relationships between different host species. Here, we focus on the myxozoan endoparasite Tetracapsuloides bryosalmonae that causes temperature-dependent proliferative kidney disease (PKD) in salmonids. We characterized the temporal changes in the parasite load and the severity of PKD signs (renal hyperplasia, haematocrit) in two sympatric populations of wild brown trout (Salmo trutta) and Atlantic salmon (Salmo salar). We found that both the parasite load and disease signs vary considerably between individuals, species, rivers and sampling periods. We showed that Atlantic salmon was able to slow down the initial parasite proliferation rate and subsequently tolerate high parasite burden without obvious disease signs. In contrast, the initial parasite proliferation rate was much higher in brown trout, which was followed by the development of severe PKD signs. Thus, the speed of parasite proliferation, rather than the absolute number of the parasites in the host kidney, may play an important role in interspecific variation in PKD susceptibility. To conclude, this study illustrates the usefulness of temporal perspective for understanding host defence mechanisms and climate change-mediated impacts in the wild.

Know your enemy - transcriptome of myxozoan Tetracapsuloides bryosalmonae reveals potential drug targets against proliferative kidney disease in salmonids.

The myxozoan Tetracapsuloides bryosalmonae is a widely spread endoparasite that causes proliferative kidney disease (PKD) in salmonid fish. We developed an in silico pipeline to separate transcripts of T. bryosalmonae from the kidney tissue of its natural vertebrate host, brown trout (Salmo trutta). After stringent filtering, we constructed a partial transcriptome assembly T. bryosalmonae, comprising 3427 transcripts. Based on homology-restricted searches of the assembled parasite transcriptome and Atlantic salmon (Salmo salar) proteome, we identified four protein targets (Endoglycoceramidase, Legumain-like protease, Carbonic anhydrase 2, Pancreatic lipase-related protein 2) for the development of anti-parasitic drugs against T. bryosalmonae. Earlier work of these proteins on parasitic protists and helminths suggests that the identified anti-parasitic drug targets represent promising chemotherapeutic candidates also against T. bryosalmonae, and strengthen the view that the known inhibitors can be effective in evolutionarily distant organisms. In addition, we identified differentially expressed T. bryosalmonae genes between moderately and severely infected fish, indicating an increased abundance of T. bryosalmonae sporogonic stages in fish with low parasite load. In conclusion, this study paves the way for future genomic research in T. bryosalmonae and represents an important step towards the development of effective drugs against PKD.

Comparative transcriptomics and host-specific parasite gene expression profiles inform on drivers of proliferative kidney disease.

The myxozoan parasite, Tetracapsuloides bryosalmonae has a two-host life cycle alternating between freshwater bryozoans and salmonid fish. Infected fish can develop Proliferative Kidney Disease, characterised by a gross lymphoid-driven kidney pathology in wild and farmed salmonids. To facilitate an in-depth understanding of T. bryosalmonae-host interactions, we have used a two-host parasite transcriptome sequencing approach in generating two parasite transcriptome assemblies; the first derived from parasite spore sacs isolated from infected bryozoans and the second from infected fish kidney tissues. This approach was adopted to minimize host contamination in the absence of a complete T. bryosalmonae genome. Parasite contigs common to both infected hosts (the intersect transcriptome; 7362 contigs) were typically AT-rich (60-75% AT). 5432 contigs within the intersect were annotated. 1930 unannotated contigs encoded for unknown transcripts. We have focused on transcripts encoding proteins involved in; nutrient acquisition, host-parasite interactions, development, cell-to-cell communication and proteins of unknown function, establishing their potential importance in each host by RT-qPCR. Host-specific expression profiles were evident, particularly in transcripts encoding proteases and proteins involved in lipid metabolism, cell adhesion, and development. We confirm for the first time the presence of homeobox proteins and a frizzled homologue in myxozoan parasites. The novel insights into myxozoan biology that this study reveals will help to focus research in developing future disease control strategies.

Medical treatment for an isolated renal multilocular hydatid cyst in an elderly: a case report.

BACKGROUND: Almost all cases of renal hydatid cysts need surgical intervention for treatment. We report a case of isolated renal hydatid cyst treated successfully only with medical therapy. CASE PRESENTATION: This case is a 79-year-old veterinarian presented with right flank pain, hydatiduria and positive echinococcus granulosus serology. A 70*50 mm cyst with daughter cysts in mid-portion of right kidney on presentation was changed into a 60*40 mm cyst without daughter cysts at last follow-up. Due to patient's refusal of surgery, our patient received medical treatment including praziquantel and albendazole. After completion of first round of treatment, recurrence occurred and the same treatment was repeated. At last, the cyst became inactive and calcified with negative serology and no clinical symptoms under medical treatment. CONCLUSION: The treatment of choice in renal hydatid cyst is surgery; although there are some reports about the efficacy of medical treatments for hydatid cysts but lower rates of recurrence and higher efficacy put surgery in a superior position compared to medical approaches. Our case showed relative success of medical treatment, despite the presence of a large multilocular renal involvement. Thus, medical therapy without surgery can be considered in very particular cases with isolated renal hydatid cysts.

Kidney biomarkers in tropical infections: an update.

Neglected tropical diseases affect over 1 billion people, and cause 170,000 deaths each year. They result in disability, stigma and disfigurement, and also push families into poverty. Tropical infections can involve the kidney, presenting as a wide variety of ways, varying from transient urinary abnormalities to severe acute kidney injury (AKI). It is important to assess renal function in patients with tropical infections for earlier detection of AKI, appropriate treatment and prevention of Chronic Kidney Disease (CKD) outcome in some of them. There was an exponential increase in research on new kidney biomarkers that were earlier and specific for renal damage but few in the scope of tropical infections. In this review, we focus on kidney biomarkers that are being studied in some of the most prevalent tropical infections such as visceral leishmaniasis, leptospirosis, malaria, schistosomiasis and leprosy. Further studies are needed to evaluate the usefulness of renal biomarkers in the early diagnosis of renal diseases associated with tropical infections.

Renal echinococcosis; the parasite, host immune response, diagnosis and management.

Renal echinococcosis is a rare parasite-caused disease of humans and animals; it makes up about 4% of confirmed cases of cystic echinococcosis. It is a zoonotic disease that occurs in the intermediate hosts harboring the larval stage, the hydatid cyst, of Echinococcus spp. The renal involvement is often asymptomatic or with unspecific signs. Its diagnosis is mostly based on imaging technique. Immunodiagnostic tests are not applicable. Furthermore, because the disease is not common, our knowledge about its different aspects is scarce. In this review, the parasite, host immune response, diagnosis, and management of renal echinococcosis are described.

Proliferative kidney disease in Alaskan salmonids with evidence that pathogenic myxozoans may be emerging north.

Proliferative kidney disease (PKD) of salmonids, a chronic immunopathology caused by the myxozoan parasite Tetracapsuloides bryosalmonae, is exacerbated by increased water temperatures. PKD causes economic concerns to trout farmers and contributes to the decline of wild salmonid populations in North America and Europe. The parasite occurs as far north as Norway and Iceland in Europe and was confirmed from California to southern British Columbia in the American continent. In mid-September 2011 adult chum salmon (Oncorhynchus keta) were sampled from Kantishna River, a tributary to Yukon River in Alaska. Clinical PKD was diagnosed based on the macroscopic appearance of mottled kidneys that were uniformly swollen and by the detection of tumultuous histozoic extrasporogonic and coelozoic sporogonic stages of T. bryosalmonae in renal tissue by histopathology. Archived samples provided the molecular confirmation and local strain identification, representing the first confirmed case of PKD in wild adult chum salmon, also co-infected with Parvicapsula minibicornis that represents another novel myxozoan detection in Alaska. Our investigation was extended to another case from August/September 1997, with mortality following furunculosis and ectoparasite co-infections, in sockeye salmon (Oncorhynchus nerka) pre-smolts net-pen reared in English Bay Lakes, Alaska. Immunohistochemistry on archived histological preparations confirmed T. bryosalmonae sporogonic and extrasporogonic stages, indicating a severe to resolving PKD, with concomitant Chloromyxum spp. infection. Those cases provide the first documentation that this parasite is present in Alaska and causes PKD in wild and cultured salmonids in the region. The known geographic range of T. bryosalmonae can be extended to ~267 km south of the Arctic Circle, representing the northernmost detection in America. Given the vast size of Alaska and small resident population, it is likely that T. bryosalmonae remained undetected, but more recently became evident due to the clinical manifestation of PKD, possibly linked to increasing water temperatures reported at the sample locations.

A portrait of the immune response to proliferative kidney disease (PKD) in rainbow trout.

Proliferative kidney disease (PKD), caused by the myxozoan Tetracapsuloides bryosalmonae, is one of the most serious parasitic diseases of salmonids in which outbreaks cause severe economic constraints for the aquaculture industry and declines of wild species throughout Europe and North America. Given that rainbow trout (Oncorhynchus mykiss) is one of the most widely farmed freshwater fish and an important model species for fish immunology, most of the knowledge on how the fish immune response is affected during PKD is from this organism. Once rainbow trout are infected, PKD pathogenesis results in a chronic kidney immunopathology mediated by decreasing myeloid cells and increasing lymphocytes. Transcriptional studies have revealed the regulation of essential genes related to T-helper (Th)-like functions and a dysregulated B-cell antibody type response. Recent reports have discovered unique details of teleost B-cell differentiation and functionality and characterized the differential immunoglobulin (Ig)-mediated response. These studies have solidified the rainbow trout T. bryosalmonae system as a sophisticated disease model capable of feeding key advances into mainstream immunology and have contributed essential information to design novel parasite disease prevention strategies. In our following perspective, we summarize these efforts to evaluate the immune mechanisms of rainbow trout during PKD pathogenesis.

Effects of parasite concentrations on infection dynamics and proliferative kidney disease pathogenesis in brown trout (Salmo trutta).

Proliferative kidney disease (PKD) is an emerging disease of salmonids, which is exacerbating with increasing water temperature. Its causative agent, the myxozoan parasite Tetracapsuloides bryosalmonae, exploits freshwater bryozoans as primary hosts and salmonids as intermediate hosts. Our experiments showed that the manipulation of exposure concentrations of infective malacospores had relatively minor impacts for the disease outcomes in the fish host. In this study, brown trout (Salmo trutta) were exposed to three different exposure concentrations of T. bryosalmonae malacospores: (a) a single low parasite concentration (LC), (b) a single high parasite concentration (HC) and (c) three times a low concentration (repeat exposure, RE). Parasite dynamics in the fish host and release of fish malacospores were quantified and fish kidney histopathology was evaluated to determine PKD pathogenesis. Infection prevalence was always lower in the LC group than in the other groups over the course of the study. While the parasite proliferation phase was slower in the LC group, the maximum parasite burden did not differ significantly amongst treatments. The onset of fish malacospore release (day 45 post-exposure), indicated by detection of T. bryosalmonae DNA in the tank water, occurred at the same time point for all groups. Reduced intensity of kidney pathological development was observed in the LC treatment indicating lower disease severity. While the LC treatment resulted in reduced outcomes across several infection parameters (infection prevalence, parasite proliferation, total fish malacospores released), the overall differences were small. The RE and HC treatment outcomes were for most parameters comparable. Our results suggest that repeated exposure, as is likely to occur in the wild during the summer months, might play a more important role in the dynamics of PKD as an emerging infectious disease than the actual concentration of spores.

Hydatid Cyst Treatment and Management in Retroperitoneal Organs; Is Percutaneous Drainage an Option?

PURPOSE: To evaluate patients who cyst hydatid (CH) in their retroperitoneal space and organs in order to determine a standard treatment option for CH. MATERIALS AND METHODS: The files of 56 patients who were treated for CH in our clinic were evaluated retrospectively. All patients underwent either percutaneous drainage (PD) or surgery. Patients were divided into two groups as PD (Group one) and surgery groups (Group two). Preoperative and postoperative results were compared statistically. RESULTS: 31 of 56 patients were male. Mean age of the patient was 39.7 (10-85). 16 patients had been treated with PD and 40 with different surgical interventions such as total cystectomy, partial cystectomy, partial nephrectomy, total nephrectomy, surrenalectomy, and laparoscopic partial surrenalectomy. Patients' followed up was 18 months (6-38m). Relapse was seen in 1 patient who underwent PD. On comparing the results, hospitalization period was prolonged in the surgical group with enlarged cyst presence. CONCLUSION: CH presence in the retroperitoneal area is rare. PD, a minimally invasive method, has the potential to be the standard treatment option as it can be performed safely in selected patients. However, currently surgical treatment is considered as the first treatment option after CH diagnosis.

Transcriptome profiling of posterior kidney of brown trout, Salmo trutta, during proliferative kidney disease.

BACKGROUND: Tetracapsuloides bryosalmonae is a myxozoan parasite which causes economically important and emerging proliferative kidney disease (PKD) in salmonids. Brown trout, Salmo trutta is a native fish species of Europe, which acts as asymptomatic carriers for T. bryosalmonae. There is only limited information on the molecular mechanism involved in the kidney of brown trout during T. bryosalmonae development. We employed RNA sequencing (RNA-seq) to investigate the global transcriptome changes in the posterior kidney of brown trout during T. bryosalmonae development. METHODS: Brown trout were exposed to the spores of T. bryosalmonae and posterior kidneys were collected from both exposed and unexposed control fish. cDNA libraries were prepared from the posterior kidney and sequenced. Bioinformatics analysis was performed using standard pipeline of quality control, reference mapping, differential expression analysis, gene ontology, and pathway analysis. Quantitative real time PCR was performed to validate the transcriptional regulation of differentially expressed genes, and their correlation with RNA-seq data was statistically analyzed. RESULTS: Transcriptome analysis identified 1169 differentially expressed genes in the posterior kidney of brown trout, out of which 864 genes (74%) were upregulated and 305 genes (26%) were downregulated. The upregulated genes were associated with the regulation of immune system process, vesicle-mediated transport, leucocyte activation, and transport, whereas the downregulated genes were associated with endopeptidase regulatory activity, phosphatidylcholine biosynthetic process, connective tissue development, and collagen catabolic process. CONCLUSION: To our knowledge, this is the first RNA-seq based transcriptome study performed in the posterior kidney of brown trout during active T. bryosalmonae development. Most of the upregulated genes were associated with the immune system process, whereas the downregulated genes were associated with other metabolic functions. The findings of this study provide insights on the immune responses mounted by the brown trout on the developing parasite, and the host molecular machineries modulated by the parasite for its successful multiplication and release.

[Leptospirosis and kidneys: a clinical case].

We describe here the case of a young patient, employed in agriculture, who entered the emergency room with fever, headache, hematuria and a worsening of renal function; we diagnosed leptospirosis with renal involvement. As the patient lamented very generic symptoms, the anamnesis was fundamental in leading us to suspect an infection, execute the right laboratory analysis, and correctly diagnose a pathology which is currently very rare in Italy.

Isolated Renal Hydatid Cyst Masquerading as Cystic Renal Tumor.

Hydatid disease or echinococcosis is a zoonotic disease caused by cestode Echinococcus granulosus. In humans, isolated renal involvement or primary renal hydatid cyst of the kidney is rare and accounts for about 1%-5% of all the cases of hydatid cyst. Isolated renal hydatid cyst can mimic cystic renal tumor both clinically and radiologically. We present a rare case of isolated hydatid cyst in a 38-year-old male who was diagnosed as a case of cystic renal tumor on radiology.