Molecular and functional characterization of reversible-sunitinib-tolerance state in human renal cell carcinoma.

Therapy failure with the tyrosine kinase inhibitor (TKI) sunitinib remains a great challenge in metastatic renal cell carcinoma (mRCC). Growing evidence indicates that the tumour subpopulation can enter a transient, non-mutagenic drug-tolerant state to endure the treatment underlying the minimal residual disease and tumour relapse. Drug tolerance to sunitinib remains largely unexplored in RCC. Here, we show that sunitinib-tolerant 786-O/S and Caki-2/S cells are induced by prolonged drug treatment showing reduced drug sensitivity, enhanced clonogenicity, and DNA synthesis. Sunitinib-tolerance developed via dynamic processes, including (i) engagement of c-MET and AXL pathways, (ii) alteration of stress-induced p38 kinase and pro-survival BCL-2 signalling, (iii) extensive actin remodelling, which was correlated with activation of focal adhesion proteins. Remarkably, the acute drug response in both sensitive and sunitinib-tolerant cell lines led to dramatic fine-tuning of the actin-cytoskeleton and boosted cellular migration and invasion, indicating that the drug-response might depend on cell state transition rather than pre-existing mutations. The drug-tolerant state was transiently acquired, as the cells resumed initial drug sensitivity after >10 passages under drug withdrawal, reinforcing the concept of dynamic regulation and phenotypic heterogeneity. Our study described molecular events contributing to the reversible switch into sunitinib-tolerance, providing possible novel therapeutic opportunities in RCC.

Nestedness and beta diversity of gastrointestinal helminth communities in common warthogs, Phacochoerus africanus (Suidae), at 2 localities in South Africa.

Few studies have investigated the ecological interactions between wild species of Suidae and their parasites, leaving our knowledge concerning this host­parasite system fragmented. In the present study, we applied network studies to analyse community nestedness in helminth assemblages of common warthogs, Phacochoerus africanus (Gmelin) (Suidae). Helminth data were compiled from 95 warthogs, including young and adult males and females, from 2 different conservation areas in Mpumalanga and Limpopo Provinces, South Africa, collected monthly over a period of 1 year each. The aim was to study the effect of host sex, age and season of sampling on the structure of helminth infracommunities harboured by the warthogs and to search for non-random structural patterns in the warthog­helminth interaction networks. Furthermore, we investigated the influence of a warthog's age, sex and season of sampling on beta diversity and dark diversity of their helminth infracommunities. Lastly, we asked whether the effects of host sex, age and sampling season on helminth communities differed between the 2 localities. We found that helminth communities of warthogs were nested and host­parasite interactions were influenced by all 3 factors as well as combinations thereof. However, the resulting patterns differed at the 2 localities, indicating that local environmental processes are important drivers of community structure.

An In Vitro Analysis of TKI-Based Sequence Therapy in Renal Cell Carcinoma Cell Lines.

The tyrosine kinase inhibitor (TKI) cabozantinib might impede the growth of the sunitinib-resistant cell lines by targeting MET and AXL overexpression in metastatic renal cell carcinoma (mRCC). We studied the role of MET and AXL in the response to cabozantinib, particularly following long-term administration with sunitinib. Two sunitinib-resistant cell lines, 786-O/S and Caki-2/S, and the matching 786-O/WT and Caki-2/WT cells were exposed to cabozantinib. The drug response was cell-line-specific. The 786-O/S cells were less growth-inhibited by cabozantinib than 786-O/WT cells (p-value = 0.02). In 786-O/S cells, the high level of phosphorylation of MET and AXL was not affected by cabozantinib. Despite cabozantinib hampering the high constitutive phosphorylation of MET, the Caki-2 cells showed low sensitivity to cabozantinib, and this was independent of sunitinib pretreatment. In both sunitinib-resistant cell lines, cabozantinib increased Src-FAK activation and impeded mTOR expression. The modulation of ERK and AKT was cell-line-specific, mirroring the heterogeneity among the patients. Overall, the MET- and AXL-driven status did not affect cell responsiveness to cabozantinib in the second-line treatment. The activation of Src-FAK might counteract cabozantinib activity and contribute to tumor survival and may be considered an early indicator of therapy response.

Over-Expression of LEDGF/p75 in HEp-2 Cells Enhances Autoimmune IgG Response in Patients with Benign Prostatic Hyperplasia-A Novel Diagnostic Approach with Therapeutic Consequence?

Lens epithelium-derived growth factor splice variant of 75 kDa (LEDGF/p75) is an autoantigen over-expressed in solid tumors and acts as a stress-related transcriptional co-activator. Participation of autoimmune responses in the pathophysiology of benign prostatic hyperplasia (PBH) and a corresponding immunosuppressive therapy by TNFalpha antagonists has been recently suggested. Thus, autoAb testing could aid in the diagnosis of BPH patients profiting from such therapy. We generated CRISPR/Cas9 modified HEp-2 LEDGF knock-out (KO) and HEp-2 LEDGF/p75 over-expressing (OE) cells and examined IgG autoantibody reactivity to LEDGF/p75 in patients with prostate cancer (PCa, n = 89), bladder cancer (BCa, n = 116), benign prostatic hyperplasia (BPH, n = 103), and blood donors (BD, n = 60) by indirect immunofluorescence assay (IFA). Surprisingly, we could not detect elevated binding of autoAbs against LEDGF/p75 in cancer patients, but autoAb reactivity to LEDGF/p75 OE cells in about 50% of patients with BPH was unexpectedly significantly increased. Furthermore, a line immunoassay enabling the detection of 18 different autoAbs revealed a significantly increased occurrence of anti-dsDNA autoAbs in 34% of BPH patients in contrast to tumor patients and BD. This finding was confirmed by anti-mitochondrial (mDNA) autoAb detection with the Crithidia luciliae immunofluorescence test, which also showed a significantly higher prevalence (34%) of anti-mDNA autoAbs in BPH. In summary, our study provided further evidence for the occurrence of autoimmune responses in BPH. Furthermore, LEDGF/p75 over-expression renders HEp-2 cells more autoantigenic and an ideal target for autoAb analysis in BPH with a potential therapy consequence.

Diagnostics and prognostic evaluation in renal cell tumors: the German S3 guidelines recommendations.

The German guidelines on renal cell carcinoma (RCC) have been developed at highest level of evidence based on systematic literature review. In this paper, we are presenting the current recommendations on diagnostics including preoperative imaging and imaging for stage evaluation as well as histopathological classification. The role of tumor biopsy is further discussed. In addition, different prognostic scores and the status of biomarkers in RCC are critically evaluated.

Similarity in ixodid tick communities harboured by wildlife and livestock in the Albany Thicket Biome of South Africa.

South Africa has a diverse fauna of ixodid tick species, several of which are of medical or veterinary importance. Elucidation of which host or environmental characteristics determine the composition and abundance of tick assemblages is, therefore, highly relevant to disease management and wildlife conservation efforts. Here, we analysed the similarity in ixodid tick assemblages of three wildlife and three livestock species in a natural (Great Fish River Reserve) and anthropogenic (an adjacent farm) habitat in South Africa. We compared tick infracommunities of three wild host species between the reserve and the farm; of three wild host species within the reserve and of wild and livestock species on the farm (considering body size). Hosts examined in this study harboured the adults and immature stages of 11 tick species belonging to five ixodid genera. Notably, several tick species of South African wildlife have successfully made the switch to livestock and thus both wild hosts and livestock now contribute to the pool of maintenance hosts for these ticks as well as their associated pathogens. This is an important consideration when translocating wildlife or livestock as part of farming or conservation activities.

Impact of host sex and age on the diversity of endoparasites and structure of individual-based host-parasite networks in nyalas (Tragelaphus angasii Angas) from three game reserves in KwaZulu-Natal province, South Africa.

In recent years, numerous studies have examined the effect of host sex and age on the structure of parasite communities in several host taxa under various environmental conditions and in different geographic regions. However, the influence of such factors on the structure of host-parasite networks has received less attention, and remarkably few studies have been carried out on large terrestrial mammals. In this study, we investigated the effects of host age and sex on the parasite infra- and component communities of nyalas (Tragelaphus angasii) and on the structure of individual-based nyala-endoparasite networks. We also aimed to evaluate to what extent these effects vary spatially and if they are mediated by conservation management. Based on a data set of internal macroparasites of 74 nyalas from three game reserves in KwaZulu-Natal province, we found that host age strongly influenced parasite community structure as well as the structure of parasite-nyala networks, whereas host sex played a minor role. However, the effects of both host sex and age were mediated by environmental conditions and thus led to different patterns at the three localities. Our findings highlight that host-parasite communities from different localities should not be pooled when conducting host-parasite network and community studies as this may bias results and mask patterns that are typical for a given locality.

Robotic Salvage Lymph Node Dissection in Recurrent Prostate Cancer: Lessons Learned from 68 Cases and Implications for Future Clinical Management.

PURPOSE: Salvage lymph node dissection is a rescue treatment for patients with nodal recurrence after radical prostatectomy. Very limited data are available on robotic salvage lymph node dissection. Our purpose was to investigate perioperative and oncological outcomes of robotic salvage lymph node dissection in a large monocentric series. MATERIALS AND METHODS: Perioperative data, complications within 30 days after surgery and oncological outcomes as assessed by histology, prostate specific antigen changes, prostate specific antigen nadir after salvage lymph node dissection, and time to further therapy were analyzed. To identify predictive factors for oncological outcome, Kaplan-Meier and Cox-regression analyses were performed. For cases with a mismatch between preoperative positron emission tomography/computed tomography and the number of histologically positive lymph nodes, prostate specific membrane antigen immunohistochemistry was performed on removed lymph nodes. RESULTS: A total of 68 patients underwent robotic salvage lymph node dissection with a median operation time of 126 minutes, a blood loss of 50 ml, and a length of stay of 4 days. No major complications (>Clavien 3) occurred. Median followup was 12.1 months. Median time to further therapy was 12.4 months, 37% of patients experienced complete biochemical response (prostate specific antigen <0.2 ng/ml) and 11% reached an undetectable prostate specific antigen, which was maintained for >1 year in 3 cases. Lower preoperative prostate specific antigen, longer time between radical prostatectomy and salvage lymph node dissection, preoperative prostate specific membrane antigen positron emission tomography/computed tomography and complete biochemical response after salvage lymph node dissection were significant predictors of longer therapy-free survival (all p <0.005). Prostate specific membrane antigen immunohistochemistry revealed that prostate specific membrane antigen positron emission tomography/computed tomography tends to miss small lymph node metastases <5 mm. CONCLUSIONS: Robotic salvage lymph node dissection is a feasible approach with low perioperative morbidity and delays further systemic therapy in most patients. Prostate specific membrane antigen positron emission tomography/computed tomography detection is mostly limited to tumor foci >5 mm.

Can local treatment prolong the sensitivity of metastatic prostate cancer to androgen deprivation or even prevent castration resistance?

PURPOSE: A number of observational clinical studies suggest that prior primary tumor treatment favorably influences the course of metastatic prostate cancer (PCa), but its mechanisms of action are still speculative. Here, we describe the long-lasting sensitivity to various forms of androgen deprivation in patients after radical prostatectomy (RP) for locally advanced PCa as one potential mechanism. METHODS: A consecutive series of 115 radical prostatectomies after inductive therapy for T4 prostate cancer was re-analyzed, and long-term survival, as well as recurrence patterns and responses to different forms of hormonal manipulation, were assessed. RESULTS: The estimated biochemical response-free, PCa-specific, and overall survival rates after 200 months were 20%, 65%, and 47% with a median overall survival of 156 months. The majority of patients, although not cured of locally advanced PCa (84/115), showed long-term survival after RP. PCa-specific and overall survival rates of these 84 patients with biochemical recurrence were 61% and 44% at 150 months. Long-term sensitivity to ADT was found to be the main reason for the favorable tumor-specific survival in spite of biochemical recurrence. CONCLUSIONS: Sensitivity to primary or secondary hormonal manipulation was the main reason for the long-term survival of patients who had not been cured by surgery only. The results suggest that treatment of the primary tumor-bearing prostate delays castration-resistant PCa and enhances the effect of hormonal therapies in a previously unknown manner. The underlying cellular and molecular mechanisms need to be explored in more detailed analyses, which could profoundly impact treatment concepts of locally advanced and metastatic PCa.

Some gastrointestinal nematodes and ixodid ticks shared by several wildlife species in the Kruger National Park, South Africa.

Parasite surveys were conducted for 1­2 years in the Kruger National Park (KNP), South Africa on blue wildebeest, impalas, greater kudus, common warthogs and scrub hares. The host associations of some of the gastrointestinal nematode species infecting ≥60% of at least one of the five host species, were determined. These were Agriostomum gorgonis, Cooperia acutispiculum, Cooperia connochaeti, Cooperia hungi, Cooperia neitzi, Cooperioides hamiltoni, Gaigeria pachyscelis, Haemonchus bedfordi, Haemonchus krugeri, Haemonchus vegliai, Impalaia tuberculata, Longistrongylus sabie, Strongyloides papillosus, Trichostrongylus deflexus and Trichostrongylus thomasi. Although the prevalence of Trichostrongylus falculatus did not exceed 50% in any host species, it was present in all five hosts. Nematodes in the KNP range from those exhibiting strict host associations to generalists. Nematode-host associations may be determined by host feeding patterns and habitat use. Eight ixodid tick species were commonly collected from the same animals and in 2­3 year long surveys from plains zebras and helmeted guinea fowls: Amblyomma hebraeum, Amblyomma marmoreum, Hyalomma truncatum, Rhipicephalus appendiculatus, Rhipicephalus decoloratus, Rhipicephalus evertsi evertsi, Rhipicephalus simus and Rhipicephalus zambeziensis. Host specificity was less pronounced in ixodid tick species than in nematodes and the immature stages of five tick species infested all host species examined.

Gastrointestinal nematodes in two galliform birds from South Africa: patterns associated with host sex and age.

Parasite ecology has recently focused on elucidating patterns and processes that shape helminth communities in avian hosts. However, helminths parasitizing gamebirds are still poorly understood. Here we describe the gastrointestinal nematode fauna of Swainson's spurfowl, Pternistis swainsonii (Phasianidae) and helmeted guineafowl, Numida meleagris (Numididae), collected at three and four localities, respectively, in South Africa and analyze the prevalence, mean abundance and diversity of their helminth communities. Eleven nematode species were collected from spurfowl, which had a mean number of nematode species per host of 3.01 ± 0.18, whereas guineafowl harboured 15 nematode species, with a mean number of nematode species per host of 3.93 ± 0.12. Focusing on the most prevalent species, we also asked if host sex and/or age were associated with infracommunity structure with regard to nematode counts and species richness, as well as the species and taxonomic composition of infracommunities. While pooling data of nematode species masked the influence of host characteristics on helminth communities, analysis of individual nematode species revealed a number of patterns. In particular, adult female bias was seen in Tetrameres swainsonii in spurfowl and in Allodapa dentigera and Gongylonema congolense in guineafowl; Acuaria gruveli reached higher numbers in adult spurfowl than in juveniles, and helminth infracommunities in juvenile male guineafowl were more species rich than those in adult males. Combined, our results suggest that helminth communities of spurfowl and guineafowl are associated with a complex interplay of numerous factors, including host characteristics, parasite traits and environmental conditions.

Parasite counts or parasite incidences? Testing differences with four analyses of infracommunity modelling for seven parasite-host associations.

One of the challenges in studies of parasite community ecology is whether the input data for analyses should be parasite abundances/counts, i.e. count data (CD), or parasite incidences (presences/absences), i.e. incidence data (ID). We analysed species responses to environmental factors and species associations in the infracommunities of helminths and ectoparasites in four hosts from Europe (Sorex araneus and Myodes glareolus) and South Africa (Rhabdomys pumilio and Rhabdomys dilectus) and compared the results of four analyses [redundancy analysis (RD), RLQ analysis, joint species distribution modelling (JSDM) and Markov random fields (MRF)] that used either CD or ID as an input. In addition, we compared the differences between the CD and ID results of two analyses (JSDM and MRF) across parasite species between (a) host species within helminths and ectoparasites; (b) helminths and ectoparasites within a host species; and (c) parasite species with contrasting levels of intensity. The results of most analyses for the majority of parasite-host associations were qualitatively similar. However, models based on the ID input performed better than models based on the CD input in three out of four types of analyses (RDA, JSDM and MRF). The differences between the CD and ID models varied between host species (being the lowest in R. pumilio for JSDM and in S. araneus for MRF). However, they were not affected by the level of parasite intensity.

Compositional turnover in ecto- and endoparasite assemblages of an African bat, Miniopterus natalensis (Chiroptera, Miniopteridae): effects of hierarchical scale and host sex.

We studied the compositional turnover in infracommunities and component communities of ecto- and endoparasites infesting a bat, Miniopterus natalensis (Chiroptera, Miniopteridae), across seven sampling sites using the zeta diversity metric (measuring similarity between multiple communities) and calculating zeta decline and retention rate (both scales) and zeta decay (component communities). We asked whether the patterns of zeta diversity differ between (a) infracommunities and component communities; (b) ecto- and endoparasites and (c) subsets of communities infecting male and female bats. The pattern of compositional turnover differed between infracommunities and component communities in endoparasites only. The shape of zeta decline for infracommunities indicated that there were approximately equal probabilities of ecto- and endoparasitic species to occur on/in any bat individual within a site. The shape of zeta decline for component communities suggested the stochasticity of ectoparasite turnover, whereas the turnover of endoparasites was driven by niche-based processes. Compositional turnover in component communities of ectoparasites was more spatially dependent than that of endoparasites. Spatial independence of compositional turnover in endoparasites was due to subcommunities harboured by female bats. We conclude that the patterns of compositional turnover in infracommunities were similar in ecto- and endoparasites, whereas the patterns of turnover in component communities differed between these groups.

Metastatic risk stratification of clear cell renal cell carcinoma patients based on genomic aberrations.

Prognostic markers for the definition of the individual metastatic risk in renal cell carcinoma are still missing. The aim of our study was to establish a total number of specific aberrations (TNSA) genetic score as a new prognostic test for metastatic risk evaluation. Fluorescence in situ hybridization (FISH) was performed on isolated cell nuclei of 100 ccRCCs (50 M1/50 M0) and 100 FFPE sections (second cohort, 32 M1/68 M0). For each chromosomal region (1q21.3, 7q36.3, 9p21.3p24.1, 20q11.21q13.32) cut-off values were determined by receiver-operator curve (ROC)-curve analysis. TNSA was calculated based on the dichotomized specific CNVs. The prognostic significance of CNVs was proven by Cox and logistic regression. TNSA was the best predictor of metastasis and recurrence free survival in both cohorts. We derived an algorithm for risk stratification by combining TNSA and T-category, which increased the prognostic accuracy to 87% (specificity = 86%, sensitivity = 88%). This model divides patients into two risk groups with significantly different RFS, CSS, and OS (P = 3.8×10-5 , P = 5×10-6 and P = 3.57×10-8 respectively). The genetic risk model was superior to Leibovich score and was able to identify patients with metachronous metastatic spread which were incorrectly classified as "low" or "intermediate risk." We present a new tool for individual risk stratification by combining genetic alterations with clinico-pathologic parameters. Interphase FISH proves to be a dependable method for prognostic evaluation in primary tumor tissue on isolated cell nuclei as well as on FFPE sections. Especially in organ-confined tumors the genetic score seems to be an important tool to identify patients at high risk for metastatic disease.

Phylogeny and systematics of the Proterodiplostomidae Dubois, 1936 (Digenea: Diplostomoidea) reflect the complex evolutionary history of the ancient digenean group.

The Proterodiplostomidae Dubois, 1936 is a relatively small family of diplostomoidean digeneans parasitising the intestines of reptilian hosts associated with freshwater environments in tropical and subtropical regions. The greatest diversity of proterodiplostomids is found in crocodilians, although some parasitise snakes and turtles. According to the most recent revision, the Proterodiplostomidae included 17 genera within 5 subfamilies. Despite the complex taxonomic structure of the family, availability of testable morphology-based phylogenetic hypotheses and ancient hosts, molecular phylogenetic analyses of the group were practically lacking. Herein, we use novel DNA sequence data of the nuclear lsrRNA gene and mitochondrial cox1 gene from a broad range of proterodiplostomid taxa obtained from crocodilian, fish, and snake hosts on four continents to test the monophyly of the family and evaluate the present morphology-based classification system of the Proterodiplostomidae in comparison with the molecular phylogeny. This first detailed phylogeny for the Proterodiplostomidae challenges the current systematic framework. Combination of molecular phylogenetic data with examination of freshly collected quality specimens and re-evaluation of morphological criteria resulted in a number of systematic and nomenclatural changes along with a new phylogeny-based classification of the Proterodiplostomidae. As the result of our molecular and morphological analyses: (i) the current subfamily structure of the Proterodiplostomidae is abolished; (ii) three new genera, Paraproterodiplostomum n. g., Neocrocodilicola n. g. and Proteroduboisia n. g., are described and Pseudoneodiplostomoides Yamaguti, 1954 is restored and elevated from subgenus to genus level; (iii) two new species, Paraproterodiplostomum currani n. g., n. sp. and Archaeodiplostomum overstreeti n. sp., are described from the American alligator in Mississippi, USA. Comparison of the structure of terminal ducts of the reproductive system in all proterodiplostomid genera did not support the use of these structures for differentiation among subfamilies (or major clades) within the family, although they proved to be useful for distinguishing among genera and species. Our study includes the first report of proterodiplostomids from Australia and the first evidence of a snake acting as a paratenic host for a proterodiplostomid. A key to proterodiplostomid genera is provided. Questions of proterodiplostomid-host associations parasitic in crocodilians are discussed in connection with their historical biogeography. Our molecular phylogeny of the Proterodiplostomidae closely matches the current molecular phylogeny of crocodilians. Directions for future studies of the Proterodiplostomidae are outlined.

4-miRNA Score Predicts the Individual Metastatic Risk of Renal Cell Carcinoma Patients.

BACKGROUND: In order to improve individual prognostication as well as stratification for adjuvant therapy in patients with clinically localized clear cell renal cell carcinoma (ccRCC), reliable prognostic biomarkers are urgently needed. In this study, microRNAs (miRNAs) have emerged as promising candidates. We investigated whether a combination of differently expressed miRNAs in primary tumors can predict the individual metastatic risk. METHODS: Using two prospectively collected biobanks of academic centers, 108 ccRCCs were selected, including 57 from patients with metastatic disease at diagnosis or during follow-up and 51 without evidence of metastases. Fourteen previously identified candidate miRNAs were tested in 20 representative formalin-fixed and paraffin embedded samples in order to select the best discriminators between metastatic and nonmetastatic ccRCC. These miRNAs were approved in 108 tumor samples. We evaluated the association of altered miRNA expression with the metastatic potential of tumors using quantitative polymerase chain reaction. A prognostic 4-miRNA model has been established using a random forest classifier. Cox regression analyses were performed for correlation of the miRNA model and clinicopathological parameters to metastasis-free and overall survival. RESULTS: Nine miRNAs indicated significant expression alterations in the small cohort. These miRNAs were validated in the whole cohort. The established 4-miRNA score (miR-30a-3p/-30c-5p/-139-5p/-144-5p) has been identified as a superior predictor for metastasis-free survival (hazard ratio 12.402; p = 7.0E-05) and overall survival (p = 1.1E-04) compared with clinicopathological parameters, and likewise in the Leibovich score subgroups. CONCLUSIONS: We identified a 4-miRNA model that was found to be superior to clinicopathological parameters in accurately predicting individual metastatic risk and can support patient selection for risk-stratified follow-up and adjuvant therapy studies.

Gastrointestinal helminths from the common warthog, Phacochoerus africanus (Gmelin) (Suidae), in KwaZulu-Natal Province, South Africa, with comments on helminths of Suidae and Tayassuidae worldwide.

Thirty warthogs, Phacochoerus africanus, were collected in the Pongola Game Reserve, South Africa and examined for helminths. Gastrointestinal helminth assemblages comprised Gastrodiscus aegyptiacus, the cestode genus Moniezia and seven species of nematodes. A single warthog harboured a metacestode of Taenia hydatigena in the mesenteries. No helminths were found in the heart, lungs or liver of the warthogs. Probstmayria vivipara and Murshidia spp. were the most prevalent as well as abundant helminth species, followed by Physocephalus sexalatus. The incidence of Moniezia did not differ between hosts of different sex or age. Numbers of Murshidia spp. were not affected by host sex, but were higher in adults than in juveniles. Conversely, burdens of Trichostrongylus thomasi were not affected by host age, but were higher in males than in females. While not highly significant, helminth assemblages in male warthogs were more species rich than in females. Helminth communities in the three genera of wild sub-Saharan suids are largely unique, but Ph. africanus and Hylochoerus meinertzhageni share more worm species with each other than with Potamochoerus larvatus, possibly because the former two are more closely related. Overlap between helminth communities of African wild suids and those of other suids and Tayassuidae worldwide is limited.

Human Papillomavirus-Associated Invasive Condylomas in a Man with Immunosuppressive Comorbidities.

Human papilloma virus (HPV) infections are one of the most common sexually transmitted diseases. We present the case of a 77-year-old Caucasian male with enormous genital warts of the penis, scrotum, groins and anus. Lesions were excised by electrosurgery. The histological examination revealed Condylomata gigantea as well as an invasive perianal squamous cell carcinoma. Mucosal "low-risk" HPV type 6 was detected. The patient had a history of an immunosuppressing disease. During the 4-year follow-up, multiple relapses occurred. Thus, particularly in immunosuppressed patients, early prophylactic HPV vaccination seems to be indicated for use in the prevention of HPV-associated mutilating and life-threatening disease. Vaccination should also protect from "low-risk" HPV.

Beta diversity of gastrointestinal helminths in two closely related South African rodents: species and site contributions.

A fundamental aim of parasite ecology is to understand the mechanisms behind spatial variation in diversity and structure of parasite assemblages. To understand the contribution of individual parasite species and their assemblages to spatial variation in parasite communities, we examined species contributions to beta diversity (SCBD) and local contributions to beta diversity (LCBD) of parasitic gastrointestinal helminths (nematodes and cestodes) in two closely related rodents, Rhabdomys dilectus and Rhabdomys pumilio, from 20 localities across South Africa. Although the two Rhabdomys spp. are morphologically similar, they differ substantially in body size, habitat preference, and sociality. We asked whether the variation in life history traits and infection parameters are associated with SCBD of helminths and whether variation in environmental factors, host population density, and species richness of host communities are associated with LCBD of component assemblages of helminths. We also considered spatial factors to test whether LCBD of helminth assemblages demonstrate geographic structure. We found that the contribution of helminth species parasitic in both hosts to beta diversity significantly increased with characteristic prevalence of these species, whereas mean abundance, type of life cycle, and location in the host's gut had no effect on SCBD. The LCBD of helminth assemblages showed a significant positive correlation with environmental factors in both host species. Our results suggest that predictors of variation in SCBD and LCBD may substantially differ between parasites with different infection parameters and/or parasite communities at different hierarchical scales.