Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 1.428
Filter
Add more filters

Publication year range
1.
N Engl J Med ; 388(20): 1863-1875, 2023 May 18.
Article in English | MEDLINE | ID: mdl-37195942

ABSTRACT

BACKGROUND: Current treatments for soil-transmitted helminth infections in humans have low efficacy against Trichuris trichiura. Emodepside - a drug in veterinary use and under development for the treatment of onchocerciasis in humans - is a leading therapeutic candidate for soil-transmitted helminth infection. METHODS: We conducted two phase 2a, dose-ranging, randomized, controlled trials to evaluate the efficacy and safety of emodepside against T. trichiura and hookworm infections. We randomly assigned, in equal numbers, adults 18 to 45 years of age in whom T. trichiura or hookworm eggs had been detected in stool samples to receive emodepside, at a single oral dose of 5, 10, 15, 20, 25, or 30 mg; albendazole, at a single oral dose of 400 mg; or placebo. The primary outcome was the percentage of participants who were cured of T. trichiura or hookworm infection (the cure rate) with emodepside 14 to 21 days after treatment, determined with the use of the Kato-Katz thick-smear technique. Safety was assessed 3, 24, and 48 hours after the receipt of treatment or placebo. RESULTS: A total of 266 persons were enrolled in the T. trichiura trial and 176 in the hookworm trial. The predicted cure rate against T. trichiura in the 5-mg emodepside group (85% [95% confidence interval {CI}, 69 to 93]; 25 of 30 participants) was higher than the predicted cure rate in the placebo group (10% [95% CI, 3 to 26]; 3 of 31 participants) and the observed cure rate in the albendazole group (17% [95% CI, 6 to 35]; 5 of 30 participants). A dose-dependent relationship was shown in participants with hookworm: the observed cure rate was 32% (95% CI, 13 to 57; 6 of 19 participants) in the 5-mg emodepside group and 95% (95% CI, 74 to 99.9; 18 of 19 participants) in the 30-mg emodepside group; the observed cure rates were 14% (95% CI, 3 to 36; 3 of 21 participants) in the placebo group and 70% (95% CI, 46 to 88; 14 of 20 participants) in the albendazole group. In the emodepside groups, headache, blurred vision, and dizziness were the most commonly reported adverse events 3 and 24 hours after treatment; the incidence of events generally increased in a dose-dependent fashion. Most adverse events were mild in severity and were self-limited; there were few moderate and no serious adverse events. CONCLUSIONS: Emodepside showed activity against T. trichiura and hookworm infections. (Funded by the European Research Council; ClinicalTrials.gov number, NCT05017194.).


Subject(s)
Albendazole , Antinematodal Agents , Depsipeptides , Hookworm Infections , Trichuriasis , Adult , Animals , Humans , Albendazole/administration & dosage , Albendazole/adverse effects , Albendazole/therapeutic use , Feces/parasitology , Hookworm Infections/drug therapy , Soil/parasitology , Trichuriasis/drug therapy , Trichuris , Depsipeptides/administration & dosage , Depsipeptides/adverse effects , Depsipeptides/therapeutic use , Antinematodal Agents/administration & dosage , Antinematodal Agents/adverse effects , Antinematodal Agents/therapeutic use , Young Adult , Middle Aged , Administration, Oral , Dose-Response Relationship, Drug
2.
Clin Exp Dermatol ; 47(3): 593-594, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34700361

ABSTRACT

Cutaneous larva migrans acquired in western Scotland. A reminder that with a warming climate, conditions conventionally restricted to the tropics may be contracted in the British Isles in the absence of foreign travel.


Subject(s)
Foot Dermatoses/diagnosis , Larva Migrans/diagnosis , Travel-Related Illness , Adult , Albendazole/therapeutic use , Antinematodal Agents/therapeutic use , Female , Foot Dermatoses/drug therapy , Foot Dermatoses/pathology , Humans , Larva Migrans/drug therapy , Larva Migrans/pathology , Scotland
3.
Dig Dis Sci ; 66(1): 105-113, 2021 01.
Article in English | MEDLINE | ID: mdl-32107679

ABSTRACT

BACKGROUND: The accidental ingestion of the third larval stage of Anisakis can cause acute clinical symptoms, which are relieved via extraction of the larvae. Although this is a highly effective technique, it can only be practiced when the larvae are found in accessible areas of the gastrointestinal tract, and therefore instead the condition has often been treated using various different drugs. AIMS: This study evaluates the effectiveness of gastric acid secretion inhibitors (omeprazole and ranitidine), gastric mucosal protectants (sucralfate) and anthelmintics (mebendazole and flubendazole) in treating anisakiasis in Wistar rats. METHODS: Rats were infected with Anisakis-type I larvae and administered the drugs via a gastric probe. Data were recorded regarding the number of live and dead larvae, their location both within the animal and in its feces, and the presence of gastrointestinal lesions. Additionally, gastric pH was measured and histology performed. RESULTS: While rats in all experimental groups exhibited lesions; those treated with ranitidine and mebendazole showed significantly fewer lesions (50% and 35% of rats exhibited lesions, respectively). Histological examination of the gastric lesions revealed infection-induced changes, but no significant differences were observed between the treated and untreated rats. CONCLUSIONS: Mebendazole was found to be most efficacious in preventing gastrointestinal lesions, followed by ranitidine, which was the most effective antacid of those studied. Both these drugs could thus be considered as part of the conservative management of anisakiasis.


Subject(s)
Anisakiasis/drug therapy , Anthelmintics/therapeutic use , Anti-Ulcer Agents/therapeutic use , Antinematodal Agents/therapeutic use , Disease Models, Animal , Sucralfate/therapeutic use , Acute Disease , Animals , Anisakiasis/pathology , Anthelmintics/pharmacology , Anti-Ulcer Agents/pharmacology , Antinematodal Agents/pharmacology , Drug Evaluation, Preclinical/methods , Female , Fishes/parasitology , Gastrointestinal Tract/drug effects , Gastrointestinal Tract/parasitology , Gastrointestinal Tract/pathology , Mebendazole/pharmacology , Mebendazole/therapeutic use , Omeprazole/pharmacology , Omeprazole/therapeutic use , Ranitidine/pharmacology , Ranitidine/therapeutic use , Rats , Rats, Wistar , Sucralfate/pharmacology
4.
BMC Vet Res ; 17(1): 102, 2021 Mar 04.
Article in English | MEDLINE | ID: mdl-33663511

ABSTRACT

BACKGROUND: In free-ranging reptile populations, bacterial, fungal, viral and parasitic pathogens may affect hosts through impairment in movements, thermoregulation, reproduction, survival, and population dynamics. The speckled dwarf tortoise (Chersobius [Homopus] signatus) is a threatened species that is mostly restricted to the Succulent Karoo biome in South Africa, and little information on pathogens of this species is available yet. We derived baseline parameters for five males and five females that were captured to genetically enhance a conservation breeding program in Europe. Upon collection of the tortoises, ticks were removed and identified. Immediately upon arrival in Europe, ocular, nasal, oral and cloacal swabs were taken for viral, bacteriological and mycological examinations. Fecal samples were collected before and 1 month after fenbendazole treatment, and analyzed for parasites. A panel of PCR, aiming to detect herpesviruses, adenoviruses and iridoviruses, was carried out. RESULTS: Samples were negative for viruses, while bacteriological examination yielded detectable growth in 82.5% of the swabs with a mean load of 16 × 107 ± 61 × 108 colony forming units (CFU) per swab, representing 34 bacterial species. Cloacal and oral swabs yielded higher detectable growth loads than nasal and ocular swabs, but no differences between sexes were observed. Fungi and yeasts (mean load 5 × 103 ± 13 × 103 CFU/swab) were detected in 25% of the swabs. All pre-treatment fecal samples were positive for oxyurid eggs, ranging from 200 to 2400 eggs per gram of feces, whereas after the treatment a significantly reduced egg count (90-100% reduction) was found in seven out of 10 individuals. One remaining individual showed 29% reduction, and two others had increased egg counts. In five tortoises, Nycthocterus spp. and coccidian oocysts were also identified. Soft ticks were identified as Ornithodoros savignyi. CONCLUSIONS: Our baseline data from clinically healthy individuals will help future studies to interpret prevalences of microorganisms in speckled dwarf tortoise populations. The study population did not appear immediately threatened by current parasite presence.


Subject(s)
Tick Infestations/veterinary , Turtles/microbiology , Turtles/parasitology , Animals , Antinematodal Agents/therapeutic use , Bacteria/classification , Ciliophora/isolation & purification , Coccidia/isolation & purification , Female , Fenbendazole/therapeutic use , Fungi/classification , Male , Ornithodoros , Oxyurida Infections/drug therapy , South Africa/epidemiology
5.
Parasitol Res ; 120(1): 109-115, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33079268

ABSTRACT

This study describes two different manifestations of Dirofilaria repens infection in sibling dogs with microfilaremia. Dog 1, asymptomatic, harbored a gravid female of D. repens on the parietal layer of tunica vaginalis of one testicle and showed a marked circulating eosinophilia (3.3·103/µL). Both testicles were normal in shape and size without any gross lesions. Dog 2 had a pyotraumatic dermatitis. The cases were confirmed by PCR and sequencing. The sequences obtained showed 100% identity with those of D. repens isolated from human scrotum in Croatia. The treatment with moxidectin 2.5% and imidacloprid 10%/kg was effective in eliminating microfilariae after just one application, as demonstrated by negative modified Knott's tests and PCR analyses of blood samples. This status was maintained during the post-treatment observation period. The classical localization of D. repens in dogs is in subcutaneous tissues, within nodules or free; however, it can also occur with some frequency in testicles, as described in humans. The infection can be associated with circulating eosinophilia or pyotraumatic dermatitis, as reported in this study. Thus, in endemic areas, it is advisable to carefully inspect the removed testicles at neutering since parasite localization can take place without any macroscopic changes. Moreover, in the case of circulating eosinophilia or pyotraumatic dermatitis, investigations should include modified Knott's test and PCR to ensure that D. repens is not the cause of these alterations. Rapid and sensitive tests for the early detection of infected animals would help to prevent or limit the spread of this zoonosis.


Subject(s)
Dirofilaria repens/isolation & purification , Dirofilariasis/diagnosis , Dirofilariasis/parasitology , Dog Diseases/diagnosis , Dog Diseases/parasitology , Animals , Antinematodal Agents/therapeutic use , DNA, Helminth/genetics , Dirofilaria repens/genetics , Dirofilariasis/drug therapy , Dog Diseases/drug therapy , Dogs , Female , Male , Siblings , Testis/parasitology , Treatment Outcome
6.
Parasitol Res ; 120(3): 1137-1141, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33103217

ABSTRACT

Pulmonary capillariasis is a parasitic disease caused by the nematode Eucoleus aerophilus which affects wild and domestic carnivores. Currently, there are no anthelmintics approved for use in the treatment of dogs infected with E. aerophilus. The use of several anthelmintics has been reported in a few case reports and field efficacy studies in cats; much less is known on the treatment of dogs infected with E. aerophilus. The paper describes a case of a 4-month-old, mixed breed intact male referred to the Veterinary Teaching Hospital (VTH) of the Department of Veterinary Medical Science of the University of Bologna for a routine vaccination and tested positive for E. aerophilus. The dog has not been responding to three different administered treatments, such as moxidectin, fenbendazole, and milbemycin oxime. Eighteen months after the first fecal examination, owner has brought in the dog for a routine visit; a coprological examination was requested and performed resulting negative for parasites. Veterinary practitioners, parasitologists, diagnostic laboratories, and dog owners need to be aware of the increased danger of possible treatment failure when attempting to control parasitic infections for which there are no approved anthelmintics with established efficacies available for use.


Subject(s)
Antinematodal Agents/therapeutic use , Dog Diseases/drug therapy , Nematoda/classification , Nematode Infections/veterinary , Animals , Antinematodal Agents/pharmacology , Dog Diseases/parasitology , Dogs , Feces/parasitology , Fenbendazole/pharmacology , Fenbendazole/therapeutic use , Macrolides/pharmacology , Macrolides/therapeutic use , Male , Nematoda/drug effects , Nematoda/isolation & purification , Nematode Infections/drug therapy , Nematode Infections/parasitology , Treatment Failure
7.
Bioorg Med Chem Lett ; 30(2): 126814, 2020 01 15.
Article in English | MEDLINE | ID: mdl-31740248

ABSTRACT

A series of α-haloacetophenones and analogues were synthesized. The bioassays show that some target compounds have good antibacterial activity against Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas axonopodis pv. citri (Xac) and Meloidogyne incognita (M. incognita). Especially, the compound 24 has good in vitro and in vivo antibacterial activities against Xoo, the EC50 value, curative and protection activities are 0.09 mg/L, 48.9%, and 52.3%, respectively, which are better than the thiodiazole copper and bismerthiazol. Meanwhile, the compound 24 has good in vitro antibacterial activity against Xac, and has an EC50 value of 1.6 mg/L. Moreover, the compound 19 exhibits good nematicidal activity M. incognita, with the LC50 value of 1.0 mg/L, which is better than the positive control avermectin. In addition, the compound 24 can inhibit the formation of extracellular polysaccharide and biofilm of Xoo, and change the permeability of cell membrane. α-haloacetophenone and analogues have the advantages of simple structure, high efficiency, broad spectrum of biological activity, and can be used as antibacterial agents and nematicides or lead compounds in the future.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Antinematodal Agents/therapeutic use , Xanthomonas/pathogenicity , Anti-Bacterial Agents/pharmacology , Antinematodal Agents/pharmacology , Structure-Activity Relationship
8.
Bioorg Chem ; 102: 104055, 2020 09.
Article in English | MEDLINE | ID: mdl-32663666

ABSTRACT

The UDP-2,3-diacylglucosamine pyrophosphate hydrolase LpxH is essential in lipid A biosynthesis and has emerged as a promising target for the development of novel antibiotics against multidrug-resistant Gram-negative pathogens. Recently, we reported the crystal structure of Klebsiella pneumoniae LpxH in complex with 1 (AZ1), a sulfonyl piperazine LpxH inhibitor. The analysis of the LpxH-AZ1 co-crystal structure and ligand dynamics led to the design of 2 (JH-LPH-28) and 3 (JH-LPH-33) with enhanced LpxH inhibition. In order to harness our recent findings, we prepared and evaluated a series of sulfonyl piperazine analogs with modifications in the phenyl and N-acetyl groups of 3. Herein, we describe the synthesis and structure-activity relationship of sulfonyl piperazine LpxH inhibitors. We also report the structural analysis of an extended N-acyl chain analog 27b (JH-LPH-41) in complex with K. pneumoniae LpxH, revealing that 27b reaches an untapped polar pocket near the di-manganese cluster in the active site of K. pneumoniae LpxH. We expect that our findings will provide designing principles for new LpxH inhibitors and establish important frameworks for the future development of antibiotics against multidrug-resistant Gram-negative pathogens.


Subject(s)
Antinematodal Agents/therapeutic use , Enzyme Inhibitors/therapeutic use , Piperazine/chemical synthesis , Piperazine/therapeutic use , Antinematodal Agents/pharmacology , Enzyme Inhibitors/pharmacology , Humans , Piperazine/pharmacology , Structure-Activity Relationship
9.
BMC Vet Res ; 16(1): 311, 2020 Aug 26.
Article in English | MEDLINE | ID: mdl-32847583

ABSTRACT

BACKGROUND: The adult worms of Angiostrongylus vasorum reside in the pulmonary artery of dogs and can lead to cardiac, respiratory, and central neurologic signs. Due to luminal obstruction and perivascular inflammation of the pulmonary artery branches, pulmonary hypertension can arise. Pulmonary hypertension, in turn, can lead to severe damage of the right-sided cardiac structures, leading to right ventricular remodeling and tricuspid valve regurgitation. CASE PRESENTATION: An 8-year-old neutered female English Cocker Spaniel was presented to the author's institution because of abdominal distention and exercise intolerance. Ascites caused by congestive right-sided heart failure was found to be responsible for these problems. The underlying etiology of the right-sided heart failure was a severe pulmonary hypertension caused by Angiostrongylus vasorum infection. Echocardiography revealed, in addition to a severe concentric and eccentric right ventricular hypertrophy, right atrial and pulmonary trunk dilation, severe tricuspid valve regurgitation, and a systolic flail of the anterior leaflet of the tricuspid valve, resulting from ruptured chordae tendineae. As a coincidental finding, a congenital mitral stenosis was found. Oral therapy was initiated with daily administration of fenbendazole for 2 weeks along with daily administration of oral sildenafil until the re-check examination. At the 6-week re-check the dog showed full clinical and partial echocardiographic recovery, and both the blood antigen test for Angiostrongylus vasorum and the fecal Baermann larva isolation test were negative. When the sildenafil therapy was ceased after tapering the daily dosage, the owner reported recurrence of abdominal distension. Re-starting the sildenafil therapy resulted in resolution of this problem. The dog was reported to be clinically healthy with daily sildenafil administration 7 months after the initial presentation. CONCLUSIONS: The present case report describes a dog where angiostrongylosis led to congestive right-sided heart failure resulting from severe pulmonary hypertension. The secondary right ventricular eccentric hypertrophy together with suspected papillary muscular ischemia were the suspected cause of the ruptured major tricuspid chordae tendineae, which led to a severe tricuspid valve regurgitation. Despite eradication of the worms, the severe pulmonary hypertension persisted. Treatment with daily oral sildenafil, a pulmonary arterial vasodilator, was enough to keep the dog free of clinically apparent ascites.


Subject(s)
Dog Diseases/diagnosis , Heart Failure/veterinary , Heart Valve Diseases/veterinary , Strongylida Infections/veterinary , Angiostrongylus , Animals , Antinematodal Agents/therapeutic use , Dog Diseases/drug therapy , Dog Diseases/parasitology , Dogs , Female , Fenbendazole/therapeutic use , Heart Failure/drug therapy , Heart Valve Diseases/complications , Heart Valve Diseases/diagnosis , Heart Valve Diseases/parasitology , Hypertension, Pulmonary/complications , Hypertension, Pulmonary/veterinary , Sildenafil Citrate/therapeutic use , Strongylida Infections/complications , Strongylida Infections/drug therapy , Tricuspid Valve , Vasodilator Agents/therapeutic use
10.
Exp Parasitol ; 218: 107982, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32866584

ABSTRACT

Ancylostoma caninum is a gastrointestinal parasite that affect dogs and humans, considered a worldwide public health problem. The control of these parasitosis is increasingly difficult due to the development of multi-drug resistance. Bacillus thuringiensis is an insecticidal, spore forming bacterium, often species specific. The strain GP526 of B. thuringiensis has toxic effect on the cestode Dipylidium caninum and the trematode Centrocestus formosanus, both of them zoonotic parasites. The high degrees of specificity and environment safe make B. thuringiensis suitable for use against pathogen parasites, especially those resistant to synthetic chemical insecticides. The objective of the current work was to evaluate the in vitro effect of B. thuringiensis on Ancylostoma caninum. Spore-crystal mixture of the strains was co-incubated with 120 adult nematodes (males, non-pregnant females and pregnant females) or with 4800 eggs. GP526 showed a nematicidal effect with an LT50 of 35.8 h and an LC50 of 60 µg/ml. It also showed an ovicidal effect with an LC50 of 94.9 µg/ml. Histological analyses showed detachment of the cuticle and of the uterus in adult females, and vacuolization with destruction of the eggs. The effects of GP526 strain were comparable to those of albendazole, allowing us to propose GP526 for A. caninum control, in both, the adult stage at a gastrointestinal level, and in egg stage in the environment. In addition, GP526 can be proposed as a potential broad spectrum antiparasitic drug.


Subject(s)
Ancylostoma/microbiology , Ancylostomiasis/prevention & control , Bacillus thuringiensis/physiology , Zoonoses/parasitology , Albendazole/pharmacology , Albendazole/therapeutic use , Ancylostoma/drug effects , Animals , Antinematodal Agents/pharmacology , Antinematodal Agents/therapeutic use , Bacillus thuringiensis/chemistry , Bacterial Proteins/analysis , Dog Diseases/parasitology , Dogs , Electrophoresis, Polyacrylamide Gel , Female , Lethal Dose 50 , Male , Pest Control, Biological/methods , Zoonoses/prevention & control
11.
Proc Biol Sci ; 286(1910): 20191356, 2019 09 11.
Article in English | MEDLINE | ID: mdl-31480973

ABSTRACT

Field experiments where parasites are removed through treatment and contaminant levels in host tissues are recorded can provide insight into the combined effects of parasitism and contaminants in wild populations. In 2013 and 2014, we treated northern common eider ducks (Somateria mollissima) arriving at a breeding colony with either a broad-spectrum antihelminthic (PANACUR®) or distilled water, and measured their blood lead (Pb) levels. Breeding propensity and clutch sizes were inversely related to Pb in both treatment groups. In comparison, a negative effect of Pb on resight probability the following year was observed only in the anti-parasitic treatment (APT) group. These contrasting patterns suggest a long-term benefit to survival of intestinal parasitism in eiders experiencing Pb exposure. The arrival date of hens explained some, but not all, of the effects of Pb. We weigh the merits of different hypotheses in explaining our results, including protective bioaccumulation of Pb by parasites, condition-linked thresholds to costly reproduction and the direct effects of APT on eider health. We conclude that variation in helminth parasitism influences survival in this migratory bird in counterintuitive ways.


Subject(s)
Ducks/parasitology , Environmental Pollutants/metabolism , Lead/metabolism , Animals , Antinematodal Agents/therapeutic use , Bird Diseases/parasitology , Environmental Monitoring , Fenbendazole/therapeutic use , Parasites
12.
Blood ; 129(5): 547-552, 2017 02 02.
Article in English | MEDLINE | ID: mdl-27956388

ABSTRACT

Autophagy is a lysosomal pathway involved in degradation of intracellular material. It appears as an adaptation mechanism that is essential for cellular homeostasis in response to various stress conditions. Over the past decade, many studies have linked alteration of autophagy with cancer initiation and progression, autoimmune, inflammatory, metabolic, and degenerative diseases. This review highlights recent findings on the impact of autophagy on leukemic transformation of normal hematopoietic stem cells and summarizes its role on leukemic cell response to chemotherapy.


Subject(s)
Autophagy , Cell Transformation, Neoplastic/pathology , Hematopoietic Stem Cells/pathology , Leukemia/pathology , Animals , Antinematodal Agents/pharmacology , Antinematodal Agents/therapeutic use , Autophagy/drug effects , Carcinogenesis/drug effects , Carcinogenesis/pathology , Cell Transformation, Neoplastic/drug effects , Drug Resistance, Neoplasm , Hematopoietic Stem Cells/drug effects , Humans , Leukemia/drug therapy
13.
BMC Vet Res ; 15(1): 184, 2019 Jun 04.
Article in English | MEDLINE | ID: mdl-31164118

ABSTRACT

BACKGROUND: Since pastoralists in South Darfur, Sudan, had complained about lack of albendazole (ABZ) efficacy to control nematodes in goats, the frequency of infection with gastrointestinal helminths was studied before in vivo faecal egg count reduction tests (FECRT) were conducted using ABZ orally either at the dose recommended for sheep, 5 mg/kg body weight (bw) or at 10 mg/kg bw. Experiments included goats naturally infected with gastrointestinal nematodes or experimentally infected with local Haemonchus contortus isolates. Three study areas (Nyala, Beleil and Kass) were visited in autumn or winter. RESULTS: Out of 478 screened goats, 82.4% were infected with gastrointestinal helminths and 82% were shedding eggs of strongyle nematodes with 90% of the strongyle larvae representing Haemonchus spp. A FECRT using naturally infected goats (n = 225: 71 untreated, 104 and 50 treated with 5 and 10 mg ABZ/kg bw, respectively) detected reduced ABZ efficacy in Nyala and Kass. Paired and unpaired FECRT calculations detected reductions of 72-92% with samples taken at 8 days post treatment with 5 mg ABZ/kg bw and of 85-94% with 10 mg ABZ/kg bw. The FECRT based on day 14 post treatment samples showed reductions of 69-77% with 5 mg/kg and of 75-87% with 10 mg ABZ/kg bw. In Beleil, ABZ efficacy was 95%. In the egg hatch test EC50 values for Nyala and Kass ranged from 0.12-0.24 µg thiabendazole/ml, corresponding to benzimidazole resistant phenotypes. Only Haemonchus spp. larvae were present after treatments in coprocultures. When the efficacy was evaluated experimentally using isolates of H. contortus from Nyala and Kass, the 5 mg ABZ/kg dose revealed reductions of 76-78% on day 8 and of 62-70% on day 14 with the unpaired method. Using 10 mg ABZ/kg, the FECR was still only 77-82%. CONCLUSIONS: Both, in vivo and in vitro methods detected resistant H. contortus populations in goats from South Darfur State. The time point 14 days post treatment was more sensitive for detection of ABZ resistance than 8 days post treatment. This is the first report on the occurrence of anthelmintic resistance in Sudan confirming that anthelmintic resistance selection is occurring in African subsistence farming systems.


Subject(s)
Albendazole/therapeutic use , Antinematodal Agents/therapeutic use , Goat Diseases/parasitology , Haemonchiasis/epidemiology , Haemonchus/drug effects , Intestinal Diseases, Parasitic/veterinary , Animals , Drug Resistance , Female , Goat Diseases/drug therapy , Goat Diseases/epidemiology , Goats , Haemonchiasis/drug therapy , Haemonchiasis/parasitology , Intestinal Diseases, Parasitic/epidemiology , Male , Parasite Egg Count/veterinary , Prevalence , Sudan/epidemiology
14.
Acta Derm Venereol ; 99(9): 805-808, 2019 Jul 01.
Article in English | MEDLINE | ID: mdl-31073620

ABSTRACT

Cutaneous larva migrans is a dermatitis, typically acquired in warm tropical or sub-tropical countries, caused by migration of the larvae of nematodes (hookworm; mainly Ancylostoma braziliense and, occasionally, Ancylostoma caninum or Uncinaria stenocephala), which are parasitic on animals such as cats and dogs, into the patient's skin. The larvae penetrate the skin after contact with infected soil and cause a typical creeping eruption. Patients with cutaneous larva migrans seen in Europe have usually acquired the disease following a stay in a tropical or sub-tropical area. How-ever, some cases of cutaneous larval migrans are acquired in Europe. We report here 5 autochthonous cases in France and give an overview of European autochthonous cases.


Subject(s)
Ancylostoma/isolation & purification , Disease Transmission, Infectious , Larva Migrans/parasitology , Skin/parasitology , Adult , Ancylostoma/drug effects , Animals , Antinematodal Agents/therapeutic use , Female , France , Humans , Infant , Ivermectin/therapeutic use , Larva Migrans/drug therapy , Larva Migrans/transmission , Male , Middle Aged , Remission Induction , Skin/drug effects , Treatment Outcome , Young Adult
15.
Exp Parasitol ; 199: 52-58, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30831078

ABSTRACT

Ascaris suum is a widespread parasitic nematode that causes infection in pigs with high prevalence rates. Oxfendazole (OFZ) is effective against A. suum when used at a single high oral dose of 30 mg/kg. The aim of this study was to assess the pattern of distribution/accumulation of OFZ and its metabolites, in bloodstream (plasma), mucosal tissue and contents from small and large intestine and adult specimens of A. suum collected from infected and treated pigs. The activity of glutathione-S-transferases (GSTs) in A. suum was also investigated. Infected pigs were orally treated with OFZ (30 mg/kg) and sacrificed at 0, 3, 6 and 12 h after treatment. Samples of blood, mucosa and contents from both small and large intestine as well as adult worms were obtained and processed for quantification of OFZ/metabolites by HPLC. OFZ was the main analyte measured in all of the evaluated matrixes. The highest drug concentrations were determined in small (AUC0-t 718.7 ±â€¯283.5 µg h/g) and large (399.6 ±â€¯110.5 µg h/g) intestinal content. Concentrations ranging from 1.35 to 2.60 µg/g (OFZ) were measured in adult A. suum. GSTs activity was higher after exposure to OFZ both in vivo and ex vivo. The data obtained here suggest that the pattern of OFZ accumulation in A. suum would be more related to the concentration achieved in the fluid and mucosa of the small intestine than in other tissues/fluids. It is expected that increments in the amount of drug attained in the tissues/fluids of parasite location will correlate with increased drug concentration within the target parasite, and therefore with the resultant treatment efficacy. The results are particularly relevant considering the potential of OFZ to be used for soil transmitted helminths (STH) control programs and the advantages of pigs as a model to assess drug treatment to be implemented in humans.


Subject(s)
Antinematodal Agents/pharmacokinetics , Ascariasis/drug therapy , Ascaris suum/metabolism , Benzimidazoles/pharmacokinetics , Animals , Antinematodal Agents/therapeutic use , Area Under Curve , Ascariasis/metabolism , Ascariasis/parasitology , Benzimidazoles/therapeutic use , Chromatography, High Pressure Liquid , Cytosol/enzymology , Dinitrochlorobenzene/metabolism , Feces/parasitology , Female , Fenbendazole/analysis , Glutathione Transferase/metabolism , Intestinal Mucosa/metabolism , Intestinal Mucosa/parasitology , Intestine, Large/metabolism , Intestine, Small/metabolism , Parasite Egg Count , Spectrophotometry , Swine
16.
J Clin Pharm Ther ; 44(6): 985-987, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31423600

ABSTRACT

WHAT IS KNOWN AND OBJECTIVE: Mebendazole (MBZ) is a broad-spectrum antihelminthic agent of the benzimidazole type. Although MBZ has been reported to cause hepatic injury, case reports of severe hepatic injury are very rare. We report a case of severe hepatitis after administration of MBZ in a patient with Gilbert's syndrome affected by pinworms infestation. CASE SUMMARY: Differently from other cases of hepatitis due to MBZ reported in the scientific literature, our patient received standard doses of MBZ for a short period of time. After 18 days from the start of therapy, he developed hepatomegaly, and increases in hepatic enzymes and bilirubin. Hepatic enzymes returned to normal over the following 5 weeks. WHAT IS NEW AND CONCLUSION: This is the first case report of important liver injury after administration of MBZ in a patient with Gilbert's syndrome. We suspected that a diminished hepatic glucuronidation of MBZ due to the reduced activity of the glucuronosyltransferase enzyme in our patient could have caused an increase in unconjugated toxic metabolites of MBZ and the consequent liver damage.


Subject(s)
Antinematodal Agents/adverse effects , Antinematodal Agents/therapeutic use , Chemical and Drug Induced Liver Injury/etiology , Gilbert Disease/drug therapy , Mebendazole/adverse effects , Mebendazole/therapeutic use , Bilirubin/metabolism , Chemical and Drug Induced Liver Injury/metabolism , Gilbert Disease/metabolism , Humans , Liver/drug effects , Liver/metabolism , Male , Middle Aged
17.
Mar Drugs ; 17(4)2019 Apr 06.
Article in English | MEDLINE | ID: mdl-30959907

ABSTRACT

Lymphangiogenesis is an important biological process associated with cancer metastasis. The development of new drugs that block lymphangiogenesis represents a promising therapeutic strategy. Marine fungus-derived compound phomaketide A, isolated from the fermented broth of Phoma sp. NTOU4195, has been reported to exhibit anti-angiogenic and anti-inflammatory effects. However, its anti-lymphangiogenic activity has not been clarified to date. In this study, we showed that phomaketide A inhibited cell growth, migration, and tube formation of lymphatic endothelial cells (LECs) without an evidence of cytotoxicity. Mechanistic investigations revealed that phomaketide A reduced LECs-induced lymphangiogenesis via vascular endothelial growth factor receptor-3 (VEGFR-3), protein kinase Cδ (PKCδ), and endothelial nitric oxide synthase (eNOS) signalings. Furthermore, human proteome array analysis indicated that phomaketide A significantly enhanced the protein levels of various protease inhibitors, including cystatin A, serpin B6, tissue factor pathway inhibitor (TFPI), and tissue inhibitor matrix metalloproteinase 1 (TIMP-1). Importantly, phomaketide A impeded tumor growth and lymphangiogenesis by decreasing the expression of LYVE-1, a specific marker for lymphatic vessels, in tumor xenograft animal model. These results suggest that phomaketide A may impair lymphangiogenesis by suppressing VEGFR-3, PKCδ, and eNOS signaling cascades, while simultaneously activating protease inhibitors in human LECs. We document for the first time that phomaketide A inhibits lymphangiogenesis both in vitro and in vivo, which suggests that this natural product could potentially treat cancer metastasis.


Subject(s)
Angiogenesis Inhibitors/pharmacology , Antinematodal Agents/pharmacology , Ascomycota/chemistry , Lymphangiogenesis/drug effects , Polyketides/pharmacology , A549 Cells , Angiogenesis Inhibitors/isolation & purification , Angiogenesis Inhibitors/therapeutic use , Animals , Antinematodal Agents/isolation & purification , Antinematodal Agents/therapeutic use , Aquatic Organisms/chemistry , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Humans , Lymphatic Metastasis , Lymphatic Vessels/cytology , Male , Mice , Mice, Nude , Neoplasms/drug therapy , Neoplasms/pathology , Nitric Oxide Synthase Type III/metabolism , Polyketides/isolation & purification , Polyketides/therapeutic use , Protein Kinase C-delta/metabolism , Signal Transduction/drug effects , Vascular Endothelial Growth Factor Receptor-3/metabolism , Xenograft Model Antitumor Assays
18.
Parasitol Res ; 118(10): 2877-2883, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31422463

ABSTRACT

Anthelmintic resistance in equine cyathostomin parasites is widespread. A surveillance-based parasite control program using fecal egg counts (FECs) and fecal egg count reduction tests (FECRTs) to decrease anthelmintic use and monitor treatment efficacy is recommended. The purpose of this study was to examine shifts in equine parasite control program management practices via a short course presented by the Penn State Extension, and to highlight how data collected from these programs is useful for monitoring anthelmintic efficacy on a large scale. Horse owners were enrolled after participating in a short course and filled out questionnaire surveys about their parasite management programs pre and post study, horse information, and farm information. FECs were performed at three time points, and horses above a 300 strongyle eggs per gram cut-off were treated with pyrantel pamoate, fenbendazole, or ivermectin. Two weeks post-treatment, FECRTs were performed to determine treatment efficacy, which included 29 farms with 513 individual treatments. Prior to the study, only 30.6% of farms used FECs, but after the study, 97.3% of farms said they would use FECs in the future. Horses were given an average of 4.1 anthelmintic treatments per year before the study, and post study 89.2% of farms were able to reduce the number of anthelmintic treatments used. Fenbendazole was effective on zero farms, pyrantel pamoate on 7.4% of farms, and ivermectin on 92.9% of farms. This outreach project helped generate information about anthelmintic efficacy levels, causing a shift in practices on participating farms, and collected useful anthelmintic resistance data.


Subject(s)
Antinematodal Agents/therapeutic use , Fenbendazole/therapeutic use , Horse Diseases/epidemiology , Ivermectin/therapeutic use , Parasite Egg Count/veterinary , Pyrantel Pamoate/therapeutic use , Animals , Drug Resistance/drug effects , Farms , Feces/parasitology , Horse Diseases/drug therapy , Horse Diseases/parasitology , Horses , Surveys and Questionnaires
19.
Vet Dermatol ; 30(1): 68-e20, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30474318

ABSTRACT

BACKGROUND: Cercopithifilaria bainae is a tick-vectored filarioid nematode associated with erythematous dermatitis in dogs. It has not been reported previously in the United States. HYPOTHESIS/OBJECTIVE: To describe clinical, histological and parasitological diagnosis and treatment of C. bainae in a dog. ANIMALS: An 11-month-old golden retriever/standard poodle mixed breed dog from Florida (USA). METHODS AND MATERIALS: The dog had no travel history within or outside the United States, was presented with a one month history of annular erythematous plaques on the head and ulcers on the medial canthi. Lesions were unresponsive to antibiotic treatment. RESULTS: Histopathological evaluation of skin biopsies revealed an eosinophilic to lymphohistiocytic perivascular dermatitis with multiple microgranulomas and rare 5-10 µm diameter microfilariae within microgranulomas. Microfilarial morphology was consistent with C. bainae. PCR and sequencing of 18S rRNA and mitochondrial cytochrome oxidase subunit I genes confirmed the nematodes as C. bainae. The dog was treated with a commercial spot-on containing imidacloprid and moxidectin, and clinical resolution occurred. CONCLUSIONS AND CLINICAL IMPORTANCE: To the best of the authors' knowledge, this is the first report of C. bainae in a dog in the United States and the first description of dermatological lesions caused primarily by C. bainae.


Subject(s)
Dog Diseases/parasitology , Ectoparasitic Infestations/veterinary , Filariasis/veterinary , Filarioidea , Nematoda , Administration, Cutaneous , Animals , Antinematodal Agents/administration & dosage , Antinematodal Agents/therapeutic use , Disease Transmission, Infectious/veterinary , Dog Diseases/diagnosis , Dog Diseases/drug therapy , Dog Diseases/pathology , Dogs , Drug Therapy, Combination , Ectoparasitic Infestations/diagnosis , Ectoparasitic Infestations/parasitology , Ectoparasitic Infestations/pathology , Female , Filariasis/diagnosis , Filariasis/parasitology , Filariasis/pathology , Florida , Macrolides/administration & dosage , Macrolides/therapeutic use , Neonicotinoids/administration & dosage , Neonicotinoids/therapeutic use , Nitro Compounds/administration & dosage , Nitro Compounds/therapeutic use , Rhipicephalus sanguineus/parasitology , Skin/parasitology , Skin/pathology
20.
J Helminthol ; 93(4): 434-439, 2019 Jul.
Article in English | MEDLINE | ID: mdl-29729678

ABSTRACT

The in vitro nematicidal effect of Chenopodium ambrosioides and Castela tortuosa n-hexane extracts (E-Cham and E-Cato, respectively) on Haemonchus contortus infective larvae (L3) and the anthelmintic effect of these extracts against the pre-adult stage of the parasite in gerbils were evaluated using both individual and combined extracts. The in vitro confrontation between larvae and extracts was performed in 24-well micro-titration plates. The results were considered 24 and 72 h post confrontation. The in vivo nematicidal effect was examined using gerbils as a study model. The extracts from the two assessed plants were obtained through maceration using n-hexane as an organic agent. Gerbils artificially infected with H. contortus L3 were treated intraperitoneally with the corresponding extract either individually or in combination. The results showed that the highest individual lethal in vitro effect (96.3%) was obtained with the E-Cham extract at 72 h post confrontation at 40 mg/ml, followed by E-Cato (78.9%) at 20 mg/ml after 72 h. The highest combined effect (98.7%) was obtained after 72 h at 40 mg/ml. The in vivo assay showed that the individual administration of the E-Cato and E-Cham extracts reduced the parasitic burden in gerbils by 27.1% and 45.8%, respectively. Furthermore, the anthelmintic efficacy increased to 57.3% when both extracts were administered in combination. The results of the present study show an important combined nematicidal effect of the two plant extracts assessed against L3 in gerbils.


Subject(s)
Antinematodal Agents/therapeutic use , Bird Diseases/drug therapy , Chenopodium ambrosioides/chemistry , Haemonchus/drug effects , Plant Extracts/therapeutic use , Simaroubaceae/chemistry , Animals , Bird Diseases/parasitology , Disease Models, Animal , Drug Therapy, Combination , Female , Gerbillinae/parasitology , Hexanes , Injections, Intraperitoneal , Larva/drug effects , Male
SELECTION OF CITATIONS
SEARCH DETAIL