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Parasites & Vectors Nov 2023Alveolar echinococcosis (AE) is a lethal zoonosis caused by the fox tapeworm Echinococcus multilocularis. The disease is difficult to treat, and an effective therapeutic...
BACKGROUND
Alveolar echinococcosis (AE) is a lethal zoonosis caused by the fox tapeworm Echinococcus multilocularis. The disease is difficult to treat, and an effective therapeutic drug is urgently needed. Echinococcus multilocularis-associated angiogenesis is required by the parasite for growth and metastasis; however, whether antiangiogenic therapy is effective for treating AE is unclear.
METHODS
The in vivo efficacy of sunitinib malate (SU11248) was evaluated in mice by secondary infection with E. multilocularis. Enzyme-linked immunosorbent assays (ELISAs) were used to evaluate treatment effects on serum IL-4 and vascular endothelial growth factor A (VEGFA) levels after SU11248 treatment. Gross morphological observations and immunohistochemical staining were used to evaluate the impact of SU11248 on angiogenesis and the expression of pro-angiogenic factors VEGFA and VEGF receptor 2 (VEGFR2) in the metacestode tissues. Furthermore, the anthelmintic effects of SU11248 were tested on E. multilocularis metacestodes in vitro. The effect of SU11248 on the expression of VEGFA, VEGFR2, and phosphorylated VEGFR2 (p-VEGFR2) in liver cells infected with protoscoleces in vitro was detected by western blotting, reverse transcription quantitative polymerase chain reaction (RT-qPCR), and enzyme-linked immunosorbent assay (ELISA). The influence of SU11248 on endothelial progenitor cell (EPC) proliferation and migration was determined using CCK8 and transwell assays.
RESULTS
In vivo, SU11248 treatment markedly reduced neovascular lesion formation and substantially inhibited E. multilocularis metacestode growth in mice. Further, it exhibited high anti-hydatid activity as efficiently as albendazole (ABZ), and the treatment resulted in reduced protoscolex development. In addition, VEGFA, VEGFR2, and p-VEGFR2 expression was significantly decreased in the metacestode tissues after SU11248 treatment. However, no effect of SU11248 on serum IL-4 levels was observed. In vitro, SU11248 exhibited some anthelmintic effects and damaged the cellular structure in the germinal layer of metacestodes at concentrations below those generally considered acceptable for treatment (0.12-0.5 μM). Western blotting, RT-qPCR, and ELISA showed that in co-cultured systems, only p-VEGFR2 levels tended to decrease with increasing SU11248 concentrations. Furthermore, SU11248 was less toxic to Reuber rat hepatoma (RH) cells and metacestodes than to EPCs, and 0.1 μM SU11248 completely inhibited EPC migration to the supernatants of liver cell and protoscolex co-cultures.
CONCLUSIONS
SU11248 is a potential candidate drug for the treatment of AE, which predominantly inhibits parasite-induced angiogenesis. Host-targeted anti-angiogenesis treatment strategies constitute a new avenue for the treatment of AE.
Topics: Mice; Animals; Echinococcus multilocularis; Sunitinib; Vascular Endothelial Growth Factor A; Interleukin-4; Anthelmintics
PubMed: 37936208
DOI: 10.1186/s13071-023-05999-4 -
Molecular and Biochemical Parasitology Sep 2024Spirocerca lupi is a parasitic nematode affecting predominantly domestic dogs. It causes spirocercosis, a disease that is often fatal. The assembled draft genome of S....
Spirocerca lupi is a parasitic nematode affecting predominantly domestic dogs. It causes spirocercosis, a disease that is often fatal. The assembled draft genome of S. lupi consists of 13,627 predicted protein-coding genes and is approximately 150 Mb in length. Several known anthelmintic gene targets such as for β-Tubulin, glutamate, and GABA receptors as well as known vaccine gene targets such as cysteine protease inhibitor and cytokines were identified in S. lupi by comparing orthologs of C. elegans anthelmintic gene targets as well as orthologs to known vaccine candidates. New anthelmintic targets were predicted through an inclusion-exclusion strategy and new vaccine targets were predicted through an immunoinformatics approach. New anthelminthic targets include DNA-directed RNA polymerases, chitin synthase, polymerases, and other enzymes. New vaccine targets include cuticle collagens. These gene targets provide a starting platform for new drug identification and vaccine design.
Topics: Animals; Anthelmintics; Genome, Helminth; Vaccines; Thelazioidea; Dogs; Spirurida Infections; Dog Diseases; Helminth Proteins
PubMed: 38834134
DOI: 10.1016/j.molbiopara.2024.111632 -
International Journal For Parasitology.... Aug 2023Ancylostoma caninum is the most common and important gastrointestinal nematode of dogs in the United States. Despite recent reports of A. caninum isolates resistant to...
Ancylostoma caninum is the most common and important gastrointestinal nematode of dogs in the United States. Despite recent reports of A. caninum isolates resistant to all classes of anthelmintics, little is known about the frequency and extent of this anthelmintic resistance. The study aim was to evaluate the efficacy of three commercial anthelmintic products in the treatment of foxhound dogs with a history of persistent A. caninum infections. In the first phase of this study, 35 foxhounds were randomly divided into three treatment groups: moxidectin/imidacloprid (MI), pyrantel pamoate/febantel/praziquantel (PFP), and emodepside/praziquantel (EP). Fecal samples were collected on day 0, 11, and 33 post-treatment (PT), and hookworm eggs were quantified using the mini-FLOTAC technique with a multiplication factor of 5 eggs per gram (EPG). The fecal egg count reduction (FECR) on day 11 PT was 65% (95% CI: 62%-68%) for MI, 69% (95% CI: 66%-72%) for PFP, and 96% (95% CI: 94%-97%) for EP. On day 33 PT, the FEC in the MI and PFP groups returned to almost the same values as on day 0, while in the EP group, the FEC remained low. Since MI and PFP proved ineffective, 32 animals were randomly divided into two groups in the second phase. They were treated either with a combination of MI/PFP or EP. The FECR at day 13 PT for the combination MI/PFP was 89% (95% CI: 87%-91%) and 99% (95% CI: 98%-99%) for EP. These results suggest that this A. caninum population is resistant to multiple anthelmintics. Although the combination of MI/PFP improved the anthelmintic efficacy, the FECR remained below 90%. Future studies are indicated to evaluate further the epidemiology of persistent hookworm infections in dogs in the US and to identify more effective treatment protocols as they pose a significant health risk to canine and human health.
Topics: Animals; Dogs; Ancylostoma; Ancylostomatoidea; Anthelmintics; Dog Diseases; Feces; Hookworm Infections; Nematoda; Parasite Egg Count; Praziquantel
PubMed: 37481894
DOI: 10.1016/j.ijpddr.2023.07.001 -
Journal of Parasitology Research 2023Goats are an important source of livelihood especially for smallholder communities. But gastrointestinal nematodosis is the greatest threats of goat production. A...
Goats are an important source of livelihood especially for smallholder communities. But gastrointestinal nematodosis is the greatest threats of goat production. A repeated cross-sectional and field experimental study design was conducted from December 2020 to August 2021 in Mirab Abaya district, with the aim of seasonal prevalence gastrointestinal nematode infection and assessment of anthelmintic resistance. A systematic random sampling strategy was used to select the study goats. The overall prevalence of gastrointestinal nematode infections of goats in the study area was 57.9% (95% CI: 54.4-61.4), of which 48.7% (95% CI: 43.7-53.7) and 67.2% (95% CI: 62.3-71.7) accounted to dry and wet seasons, respectively. The multivariable logistic regression analysis showed that season, age, sex, and flock size were significantly ( < 0.05) influenced the prevalence of gastrointestinal nematode infection of goats. The number of eggs per gram of faeces (EPG) was ranged from 100 to 2500. The overall mean egg per gram of faeces (EPG) was 461.1 ± 20.9. The mean EPG of wet season (532.7 ± 28.6) was higher than the dry season (362.3 ± 29.1). From faecal culture, 552 nematode larvae were recovered, and the most commonly identified nematode genera were (36.4%) that followed by (28.1%), (15.4%), (11.4), (5.4%), and (3.0%) species. From the anthelmintic resistance test in the field, the percentage reduction and 95% confidence limit of albendazole were 96% (84.2-99.0) and 97.0% (84.6-99.4) in dry and wet seasons, respectively. Here, the lower limit of 95% CI was less than 90% both in dry and wet seasons; and hence, albendazole was suspected for resistance development by gastrointestinal nematode. From a pooled faecal culture that collected from albendazole-treated goats, species was recovered. Therefore, due attention shall be by animal health professionals in the area in the use of albendazole. Animal health extension work to create awareness of how anthelmintic is used is helpful in reducing the risk. Changing the type of anthelmintic drug after using for some period will minimize the risk of anthelmintic resistance development.
PubMed: 37790288
DOI: 10.1155/2023/9945998 -
Wellcome Open Research 2023Mozambique has the 4 highest malaria incidence and mortality globally. Despite the existing malaria control strategies, malaria prevalence remains stagnant. These...
Mozambique has the 4 highest malaria incidence and mortality globally. Despite the existing malaria control strategies, malaria prevalence remains stagnant. These challenges have increased calls for innovative strategies in areas with the highest disease burden. Community mass treatment with anthelmintic agents have been used as an effective tool for the control of major helminth infections and has emerged as a potential tool for vector control in the fight against malaria. This was an analysis of data from a cross-sectional community-based survey designed to study malaria risk, prevention, and health seeking behaviors in Sussundenga, Mozambique. Using logistic regression models, we quantified the association between ever receiving anthelmintic treatment and infection. We also fit models to determine the association between recent anthelmintic treatment and malaria infection. Two-hundred, seventy-seven (277) participants from 83 households were included in this analysis. The prevalence of infection measured by rapid diagnostic test (RDT) was 30%. 77% of participants reported having ever received anthelmintics. The prevalence of malaria was slightly higher among participants who reported ever taking anthelmintics. There was no statistically significant association between prior receipt of anthelmintic and malaria infection after adjusting for age, ITN use and head of household full-time employment (OR = 1.37, 95% CI, 0.70-2.70, p = 0.36). However, recent intake of anthelmintics was associated with lower odds of testing positive for in the adjusted models (OR = 0.35, 95% CI, 0.07-1.80, p = 0.21), but this was not statistically significant. Our findings show that the benefit of anthelmintics treatment as a control tool for malaria infection is likely tied to when it is administered rather than if it was ever administered. These findings offer evidence for making decisions in planning mass community deworming in sub-Saharan Africa.
PubMed: 38623173
DOI: 10.12688/wellcomeopenres.19548.1 -
Australian Veterinary Journal Sep 2023The Australian ruminant livestock industries are faced with the need to control parasitic infectious diseases that can seriously impact the health of animals. However,... (Review)
Review
The current status and outlook for insecticide, acaricide and anthelmintic resistances across the Australian ruminant livestock industries: assessing the threat these resistances pose to the livestock sector.
The Australian ruminant livestock industries are faced with the need to control parasitic infectious diseases that can seriously impact the health of animals. However, increasing levels of resistance to insecticides, anthelmintics and acaricides are substantially reducing the ability to control some of these parasites. Here we review the current situation with regard to chemical resistances in parasites across the various sectors of the Australian ruminant livestock industries and assess the level of threat that these resistances pose to the sustainability of these sectors in the short to long terms. We also look at the extent to which testing for resistance occurs across the various industry sectors, and hence how well-informed these sectors are of the extent of chemical resistance. We examine on-farm management practices, breeding of parasite-resistant animals, and non-chemical therapeutics that may act as short to long term means to reduce the current reliance on chemicals for parasite control. Finally, we look at the balance between the prevalence and magnitude of current resistances and the availability and adoption rates of management, breeding and therapeutic alternatives in order to assess the parasite control outlook for the various industry sectors.
Topics: Animals; Livestock; Acaricides; Insecticides; Australia; Ruminants; Anthelmintics; Drug Resistance
PubMed: 37401786
DOI: 10.1111/avj.13267 -
International Journal For Parasitology.... Dec 2023Reports of Ascaridia galli in laying hens in Europe have increased since the ban on conventional battery cages in 2012. As this parasite is transmitted directly via the... (Review)
Review
Reports of Ascaridia galli in laying hens in Europe have increased since the ban on conventional battery cages in 2012. As this parasite is transmitted directly via the faecal-oral route by parasite eggs containing a larva, it is reasonable to assume that the escalating problem is related to the increased exposure now occurring in modern welfare-friendly cage-free housing systems. On many farms, A. galli reappears in subsequent flocks, even though the birds have no access to the outdoors, biosecurity is high and empty houses are cleaned and disinfected during downtime. Since the egg production cycle lasts only ≈80 weeks and recombinant antigen production for helminth vaccines has not yet been solved, the development of a vaccine seems to be an unrealistic option. Therefore, disrupting the life cycle of the parasite by other means, including the strategic use of dewormers, appears to be the key to controlling infection. Of concern is that only one class of anthelmintics is licenced for poultry in Europe and that are usually administered indiscriminately through the birds' drinking water and often too late when the parasite is already established. If current calendar-based parasite control strategies are not changed, there is a risk that resistance to anthelmintics may develop, as has already been demonstrated with nematodes in livestock. We insist that treatments can be more effective and the risk of developing drug resistance can be mitigated if we invest in a better understanding of A. galli responses to more prudent and judicious use of anthelmintics. This review identifies knowledge gaps and highlights aspects of sustainable parasite control that require further research to support commercial egg producers.
Topics: Animals; Female; Ascaridia; Ascaridiasis; Chickens; Anthelmintics; Feces
PubMed: 37516026
DOI: 10.1016/j.ijpddr.2023.07.003 -
Acta Tropica Jun 2024The drug of choice for the treatment of opisthorchiasis caused by trematodes Opisthorchis viverrini and O. felineus is praziquantel (PZQ), but there is a constant search... (Comparative Study)
Comparative Study
BACKGROUND
The drug of choice for the treatment of opisthorchiasis caused by trematodes Opisthorchis viverrini and O. felineus is praziquantel (PZQ), but there is a constant search for new anthelmintics, including those of plant origin. Positive results on the use of artemisinin derivatives against O. viverrini opisthorchiasis have been shown previously, but the effect of these compounds on O. felineus has not been studied. Therefore, here, a comparative analysis of anthelmintic properties of artemisinin derivatives (artesunate [AS], artemether [AM], and dihydroartemisinin [DHA]) was carried out in vitro in relation to PZQ. Experiments were performed on newly excysted metacercariae (NEMs) and adult flukes of O. felineus.
RESULTS
Dose- and time-dependent effects of artemisinin derivatives and of PZQ were assessed in terms of motility and mortality of both NEMs and adult flukes. The most pronounced anthelmintic action was exerted by DHA, whose half-maximal inhibitory concentrations (IC) of 1.9 (NEMs) and 2.02 µg/mL (adult flukes) were lower than those of PZQ (0.56 and 0.25 µg/mL, respectively). In contrast to PZQ, the effects of DHA and AS were similar when we compared the two developmental stages of O. felineus (NEMs and adult flukes). In addition, AM, AS, and especially DHA at doses of 100 µg/mL disrupted tegument integrity in adult flukes, which was not observed with PZQ.
CONCLUSIONS
Artemisinin derivatives (AS, AM, and DHA) have good anthelmintic efficacy against the trematode O. felineus, and the action of these substances is comparable to (and sometimes better than) the effects of PZQ.
Topics: Animals; Artemisinins; Opisthorchis; Anthelmintics; Inhibitory Concentration 50; Praziquantel; Survival Analysis; Artemether; Artesunate; Dose-Response Relationship, Drug
PubMed: 38521124
DOI: 10.1016/j.actatropica.2024.107196 -
Parasitology Oct 2023In June 2022, at the XXXII Conference of the Italian Society of Parasitology, the parallels of the main endoparasitic infections of horses and donkeys were discussed.... (Review)
Review
In June 2022, at the XXXII Conference of the Italian Society of Parasitology, the parallels of the main endoparasitic infections of horses and donkeys were discussed. Although these 2 species are genetically different, they can be challenged by a similar range of parasites (i.e. small and large strongyles, and spp.). Although equids can demonstrate some level of resilience to parasites, they have quite distinct helminth biodiversity, distribution and intensity among different geographical locations and breeds. Heavily infected donkeys may show fewer clinical signs than horses. Although parasite control is primarily provided to horses, we consider that there may be a risk of drug-resistance parasitic infection through passive infection in donkeys when sharing the same pasture areas. Knowing the possible lack of drug efficacy (<90 or 80%), it is advocated the use of selective treatment for both species based on fecal egg counts. Adult horses should receive treatment when the threshold exceeds 200–500 eggs per gram (EPG) of small strongyles. Moreover, considering that there are no precise indications in donkeys, a value >300 EPG may be a safe recommendation. We have highlighted the main points of the discussion including the dynamics of helminth infections between the 2 species.
Topics: Horses; Animals; Equidae; Horse Diseases; Parasite Egg Count; Helminthiasis; Helminths; Feces; Anthelmintics
PubMed: 37221816
DOI: 10.1017/S0031182023000525 -
The American Journal of Tropical... May 2024Biliary taeniasis is uncommon in clinical practice. We report two cases in our hospital. The first patient was diagnosed with acute biliary pancreatitis. Endoscopic... (Review)
Review
Biliary taeniasis is uncommon in clinical practice. We report two cases in our hospital. The first patient was diagnosed with acute biliary pancreatitis. Endoscopic retrograde cholangiopancreatography (ERCP) showed a white, flat, segmented 1-cm-wide tapeworm drilling into the duodenal papilla that was identified as Taenia saginata. After tapeworm removal, bile duct sweeping, and anthelmintic therapy, the patient recovered uneventfully. The second patient was diagnosed with acute cholangitis and multiple stones in the common bile duct and gallbladder. Emergency ERCP showed no tapeworm in the duodenum. During a subsequent ERCP 6 days later, a flat tapeworm, also T. saginata, was identified drilling into the duodenal papilla. We review five patients cases with acute acalculous cholecystitis or cholangitis caused by T. saginata or Taenia solium, and 1 patient with T. saginata drilling into the T-tube. Taeniasis should be taken into consideration when dealing with biliary and pancreatic disease.
Topics: Humans; Taeniasis; Male; Animals; Female; Middle Aged; Cholangiopancreatography, Endoscopic Retrograde; Aged; Taenia saginata; Adult; Anthelmintics; Cholangitis
PubMed: 38531099
DOI: 10.4269/ajtmh.23-0814