First report of apparent praziquantel resistance in Dipylidium caninum in Europe.

Dipylidium caninum is a common tapeworm of dogs. Two cases of praziquantel resistance have been described in D. caninum in the United States. No further reports have been published to the authors' knowledge. Here, the case of a dog imported to Switzerland from Spain with a history of chronic excretion of tapeworm proglottids and unresponsiveness to praziquantel treatments is reported. Clinical signs were mild (restlessness, tenesmus, anal pruritus, squashy feces) and flea infestation could be ruled out. Infection with D. caninum was confirmed through morphological and genetic parasite identification. Different subsequently applied anthelmintic compounds and protocols, including epsiprantel, did not confer the desired effects. Proglottid shedding only stopped after oral mebendazole administration of 86.2 mg kg−1 body weight for 5 consecutive days. Clinical signs resolved and the dog remained coproscopically negative during a follow-up period of 10 months after the last treatment. This case represents the first reported apparent praziquantel and epsiprantel resistance in D. caninum in Europe. Treatment was extremely challenging especially due to the limited availability of efficacious alternative compounds.

Public health interventions for preventing re-infection of Opisthorchis viverrini: application of the self-efficacy theory and group process in high-prevalent areas of Thailand.

OBJECTIVE: To study the effectiveness of public health interventions in preventing Opisthorchis viverrini (OV) re-infection in high-prevalence areas of Thailand. METHODS: 68 people from Sisaket, the province with the second-highest prevalence in Thailand, who tested positive for OV eggs in faeces and took praziquantel before the start of the study, participated. 34 participants were allocated to the experimental group, which received a 12-week public health intervention based on the self-efficacy theory and group process between July and October 2018. The control group received the usual services. Data were collected using a questionnaire with a reliability of 0.84. Faecal examinations using the formalin-ether concentration technique were conducted before and after the experiment. The re-infection rate was analysed after the experimental 12 weeks and after one year. Descriptive and inferential statistics, including paired t-test and independent t-test, were employed for data analysis. RESULTS: After the experiment, the mean scores of knowledge, perceived self-efficacy, self-efficacy expectation and OV prevention behaviour of the experimental group were significantly higher than before the experiment and also higher than scores of the control group (P < 0.05). CONCLUSION: The public health intervention is useful. It educated the experimental group about OV, perceived self-efficacy and self-efficacy expectation in changing behaviour to prevent OV re-infection. As a result, no re-infections were observed after the 12-week intervention nor at the one-year follow-up. Public health benefits will be evident if the results are extended to other high-prevalence areas.

High compliance and effective treatment of fish endoparasitic infections with oral drug delivery nanobioparticles: Safety of intestinal tissue and blood parameters.

Parasite infections in fish require constant surveillance and strategies for efficient treatments which guarantee the fish health, their sale value and the non-propagation of pathogens in new environments. Fish treatments based on nanotechnology become of increasing interest since nanoparticles have been shown as efficient materials for optimizing administration of bioactives. In this study a chitosan derivative, alginate and praziquantel conjugated nanobioparticle of effective action for oral treatment of digenetic trematodes in highly infected Corydoras schwartzi was evaluated in terms of histological and hematological safety. The inherent absence of alterations in intestinal tissue and the reversible blood cells counting during a period up to 35 days showed the safety of the drug delivery nanobioparticles, which thus represent a promising strategy for effective applications in pathogens treatments by oral administration.

Integration of prevention and control measures for female genital schistosomiasis, HIV and cervical cancer.

Female genital schistosomiasis as a result of chronic infection with Schistosoma haematobium (commonly known as bilharzia) continues to be largely ignored by national and global health policy-makers. International attention for large-scale action against the disease focuses on whether it is a risk factor for the transmission of human immunodeficiency virus (HIV). Yet female genital schistosomiasis itself is linked to pain, bleeding and sub- or infertility, leading to social stigma, and is a common issue for women in schistosomiasis-endemic areas in sub-Saharan Africa. The disease should therefore be recognized as another component of a comprehensive health and human rights agenda for women and girls in Africa, alongside HIV and cervical cancer. Each of these three diseases has a targeted and proven preventive intervention: antiretroviral therapy and pre-exposure prophylaxis for HIV; human papilloma virus vaccine for cervical cancer; and praziquantel treatment for female genital schistosomiasis. We discuss how female genital schistosomiasis control can be integrated with HIV and cervical cancer care. Such a programme will be part of a broader framework of sexual and reproductive health and rights, women's empowerment and social justice in Africa. Integrated approaches that join up multiple public health programmes have the potential to expand or create opportunities to reach more girls and women throughout their life course. We outline a pragmatic operational research agenda that has the potential to optimize joint implementation of a package of measures responding to the specific needs of girls and women.

La schistosomiase génitale féminine, résultant d'une infection chronique à Schistosoma haematobium (également connue sous le nom de bilharziose), continue d'être largement ignorée par les responsables des politiques de santé nationales et internationales. Si le monde lui accorde son attention en vue de mener une action à grande échelle contre la maladie, c'est surtout pour déterminer s'il s'agit d'un facteur de risque pour la transmission du virus de l'immunodéficience humaine (VIH). Pourtant, la schistosomiase génitale féminine est associée à des douleurs, des saignements et peut engendrer l'hypofertilité, voire la stérilité. Par conséquent, celles qui en souffrent sont souvent stigmatisées, et le problème est courant dans les régions endémiques d'Afrique subsaharienne. Cette maladie doit donc être considérée comme composante à part entière d'une approche globale de la santé et des droits humains pour les femmes et filles africaines, à l'instar du VIH et du cancer du col de l'utérus. Chacune de ces trois maladies fait l'objet d'une intervention préventive ciblée qui a déjà fait ses preuves: le traitement antirétroviral et la prophylaxie pré-exposition pour le VIH; le vaccin contre le papillomavirus humain pour le cancer du col de l'utérus; et l'administration de praziquantel pour la schistosomiase génitale féminine. Le présent document se penche sur la manière d'intégrer la schistosomiase génitale féminine dans la prise en charge du VIH et du cancer du col de l'utérus. Un tel programme fera partie d'un cadre plus vaste consacré aux droits et à la santé sexuelle et reproductive, à l'émancipation des femmes et à la justice sociale en Afrique. Les approches intégrées qui regroupent plusieurs programmes de santé publique permettent d'élargir des perspectives ou de créer des opportunités visant à atteindre un plus grand nombre de filles et de femmes tout au long de leur vie. Nous exposons les grandes lignes d'un programme de recherches pragmatiques et opérationnelles capable d'optimiser la mise en œuvre conjointe d'une série de mesures qui répondent aux besoins spécifiques des filles et des femmes.

Los responsables de formular las políticas sanitarias nacionales y globales siguen ignorando en gran medida la esquistosomiasis genital femenina como consecuencia de la infección crónica por Schistosoma haematobium (conocida comúnmente como bilharziasis). La atención internacional para adoptar medidas de gran alcance contra la enfermedad se centra en determinar si es un factor de riesgo para la transmisión del virus de la inmunodeficiencia humana (VIH). Sin embargo, la propia esquistosomiasis genital femenina está vinculada al dolor, las hemorragias y la infertilidad o subfertilidad, lo que conduce al estigma social, además de ser un problema común para las mujeres de las áreas en donde la esquistosomiasis es endémica en el África subsahariana. Por consiguiente, la enfermedad debe ser reconocida como otro componente de un programa integral de salud y de derechos humanos para las mujeres y las niñas de África, junto con el VIH y el cáncer de cuello uterino. Cada una de estas tres enfermedades tiene una intervención preventiva específica y comprobada: la terapia antirretroviral y la profilaxis previa a la exposición para el VIH; la vacuna contra el virus del papiloma humano para el cáncer de cuello uterino; y el tratamiento con praziquantel para la esquistosomiasis genital femenina. Se analiza cómo el control de la esquistosomiasis genital femenina se puede integrar con la atención del VIH y el cáncer de cuello uterino. Ese programa formará parte de un marco más amplio de salud y de derechos sexuales y reproductivos, de empoderamiento de la mujer y de justicia social en África. Los enfoques integrados que unen múltiples programas de salud pública tienen el potencial de ampliar o crear oportunidades para llegar a más niñas y mujeres a lo largo de sus vidas. Se describe a grandes rasgos un programa de investigación operacional pragmático que tiene el potencial de optimizar la implementación conjunta de una serie de medidas que respondan a las necesidades específicas de las niñas y de las mujeres.

Three monthly doses of 60 mg/kg praziquantel for Schistosoma haematobium infection is a safe and effective treatment regimen.

BACKGROUND: Praziquantel (PZQ) is the standard treatment for Schistosomiasis in sub-Saharan Africa. However, there is evidence suggesting praziquantel treatment failure in Schistosome infections with associated potential renal impairment. The objective of this study was to determine the effect of three monthly doses of 60 mg/kg/day PZQ on schistosome egg count, liver and renal function during the treatment of urinary schistosomiasis in Ghana. METHODS: A nested case-control study was designed from a cohort screened for schistosomiasis; 28 schistosomiasis positive cases by microscopy matched with 53 healthy controls by age and gender. The study population was urban dwellers from the Asokwa sub-metropolitan area, Kumasi in Ghana. Participants were within the age range of 6 to 30 years. We assessed Schistosoma haematobium egg counts in urine and its associated impact on liver and renal function at baseline, treatment and post-treatment phases using serum. RESULTS: Of the 28 cases and 53 controls, 78.6% and 81.1% were males respectively. Globulin levels before treatment was higher in cases [36.7 (32.8, 40.1) vrs 30.5 (22.4, 33.8), p = 0.005] at pre-treatment but not at post-treatment [35.8 (31.2, 39.1) vrs 37.4 (29.7, 43.0), p = 0.767]. Estimated cure rate was 42.9, 46.4 and 96.4% after first, second and third dose respectively. Schistosome egg counts dropped significantly (p = 0.001) from before second dose to post-treatment. Similarly, levels of alanine aminotransferase (p = 0.001), aspartate aminotransferase (p = 0.028) and gamma glutamyl transferase (p = 0.001) significantly declined towards post-treatment. Estimated glomerular filtration rate significantly improved from before second dose to post-treatment using both the Chronic Kidney Disease Epidemiology Program (p = 0.001) and 4-variable Modification of Diet in Renal Disease (p = 0.002) equations. CONCLUSION: Treatment of urinary Schistosoma hematobium infections with a repeated high monthly dose of 60 mg/kg of praziquantel for 3 months is safe and effective.

Co-administration of silymarin elevates the therapeutic effect of praziquantel through modulation of specific antibody profiles, Th1/Th2/Tregs cytokines and down-regulation of fibrogenesis in mice with Mesocestoides vogae (Cestoda) infection.

Silymarin (SIL) represents a natural mixture of polyphenols showing an array of health benefits. The present study, carried out on a model cestode infection induced by Mesocestoides vogae tetrathyridia in the ICR strain of mice, was aimed at investigating the impact of SIL as adjunct therapy on the activity of praziquantel (PZQ) in relation to parasite burden, immunity and liver fibrosis within 20 days post-therapy. In comparison with PZQ alone, co-administration of SIL and PZQ stimulated production of total IgG antibodies to somatic and excretory-secretory antigens of metacestodes and modified the expression patterns of immunogenic molecules in both antigenic preparations. The combined therapy resulted in the elevation of IFN-γ and a decline of TNF-α and TGF-ß1 in serum as compared to untreated group; however, SIL attenuated significantly the effect of PZQ on IL-4 and stimulated PZQ-suppressed phagocytosis of peritoneal macrophages. In the liver, SIL boosted the effect of PZQ on gene expression of the same cytokines in a similar way as was found in serum, except for down-regulation of PZQ-stimulated TNF-α. Compared to PZQ therapy, the infiltration of mast cells into liver after SIL co-administration was nearly abolished and correlated with suppressed activities of genes for collagen I, collagen III and α-SMA. In conclusion, co-administration of SIL modified the effects of PZQ therapy on antigenic stimulation of the immune system and modulated Th1/Th2/Tregs cytokines. In liver this was accompanied by reduced fibrosis, which correlated with significantly higher reduction of total numbers of tetrathyridia after combined therapy as compared with PZQ treatment.

Prophylactic versus therapeutic role of the transplanted CD34+ Umbilical Cord Blood Stem Cells and Wharton Jelly Mesenchymal Stem Cells in early / acute hepatic S. mansoni granulomas reversal in mice; a novel approach.

PURPOSE: Praziquantel (PZQ) is the conventional antibilharzial agent. Nevertheless, no antibilharzial prophylactic agents or 100% curable therapy approved and no reported data about use of human CD34+ Umbilical Cord Blood Stem Cells (CD34+UCBSCs) or Wharton Jelly Mesenchymal Stem Cells (WJMSCs) in prevention and/or complete eradication of acute S.mansoni granulomas in liver. We aimed to study possible prophylactic vs therapeutic role of human CD34+UCBSCs and WJMSCs in acute hepatic bilharzial granulomas in pre vs post-infected mice. METHODS: Seventy mice were divided into 7 groups (10 mice each): Normal, S.mansoni-infected, post-infected PZQ-treated, CD34+UCBSCs pre and post-infected, WJMSCs pre and post-infected. Serological, parasitological, histopathological evaluation using OCT4 & TGFB immunohistochemistry and quantitative image analysis assessment of TGFB-stained fibrogenesis in liver granulomas performed. RESULTS: Histopathologically, surprisingly and significantly, the prophylactic pre-infection stem cells (CD34+UCBSCs and WJMSCs) & similarly the post-infection CD34+UCBSCs treatment revealed eradication/reversal of the entire granulomas and no fibrosis. Moreover, post-infection PZQ treatment showed fewer and significantly smaller granulomas than post-infection WJMSCs treatment. Nevertheless, post-infection WJMSCs exhibited non-significant less TGFB-stained fibrogenesis. CONCLUSION: CD34+UCBSCs exerted the best prophylactic and therapeutic roles in prevention and complete cure of acute hepatic S.mansoni granulomas over WJMSCs and PZQ. In contrast, only pre-infection WJMSCs exhibited similar preventive (prophylactic) effect. On the contrary, post-infection WJMSCs were the worst (incompletely reversed granulomas). Post-infection Praziquantel was overall better therapeutically than WJMSCs in this regard. Accordingly, when it comes to WJMSCs application, WJMSCs are better used as a pre-infection prophylactic and preventive tool rather than a post-infection therapy. Further studies are needed.

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

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

Echinostoma aegyptica (Trematoda: Echinostomatidae) Infection in Five Riparian People in Savannakhet Province, Lao PDR.

Human infection with Echinostoma aegyptica Khalil and Abaza, 1924 (Trematoda: Echinostomatidae) is extremely rare. In this study, we confirmed E. aegyptica infection in 5 riparian residents living along the Mekong River in Savannakhet Province, Lao PDR. The patients revealed eggs of Opisthorchis viverrini/minute intestinal flukes, echinostomes, and other parasites in fecal examinations using the Kato-Katz technique. Following treatment with praziquantel 30-40 mg/kg and pyrantel pamoate 10-15 mg/kg in a single dose and purging with magnesium salts, adult specimens of various helminth species were collected. Among the trematodes, echinostome flukes of 4.5-7.6 mm in length (n = 134; av. 22.3 specimens per case) were of taxonomic interest and subjected in this study. The flukes were morphologically characterized by having total 43-45 collar spines arranged in 2 alternating rows (corner spines usually 5 on each side) and compatible with previous descriptions of E. aegyptica. The patients were mixed-infected with other helminths, so specific clinical manifestations due to this echinostome fluke were difficult to determine. The present paper describes for the first time human E. aegyptica infections in Lao PDR. This is the second report of human infection (2nd-6th cases) with E. aegyptica in the world following the first one from China.

Reduction of Reinfection Rates with Opisthorchis viverrini through a Three-Year Management Program in Endemic Areas of Northeastern Thailand.

To clarify the reinfection profile associated with risk factors of opisthorchiasis, we conducted an epidemiological study on the chemotherapeutic effects on reinfection with O. viverrini in the endemic areas of Northeastern Thailand for 3 years. A total of 3,674 fecal samples were collected from participants in villages of 5 provinces. They were examined microscopically using a modified technique of formalin ethyl-acetate concentration. Egg-positive residents were reexamined year (2018) by year (2019) after treatment with a single dose (40 mg/kg) of praziquantel. Health education was provided to the participants yearly. The egg-positive rate of O. viverrini was 14.3%, and was highest (22.2%) in the 20-30 year-old group in 2017. The egg positive rate was 15.3% in dogs and 11.4% cats. Human reinfection rate was 15.5% and 6.3% in next 2 years, and was highest (23.2%) among the fishermen. Relative risk factors of reinfection were significantly higher for males, over 40-year-old age, or working as fishermen or farmers, and eating uncooked fish within the preceding year. A significant difference resulting from a health education program was observed in the third year. Therefore, health education and sustainable surveillance for opisthorchiasis should be maintained to decrease the risk of reinfection.

Glycyrrhizin-Assisted Transport of Praziquantel Anthelmintic Drug through the Lipid Membrane: An Experiment and MD Simulation.

Praziquantel (PZQ) is one of the most widespread anthelmintic drugs. However, the frequent insufficient application of PZQ after oral administration is associated with its low solubility, penetration rate, and bioavailability. In the present study, the permeation of PZQ through a 1,2-dioleoyl- sn-glycero-3-phosphocholine (DOPC) membrane was investigated to probe glycyrrhizin-assisted transport. Glycyrrhizin (or glycyrrhizic acid, GA), a natural saponin, shows the ability to enhance the therapeutic activity of various drugs when it is used as a drug delivery system. However, the molecular mechanism of this effect is still under debate. In the present study, the transport rate was measured experimentally by a parallel artificial membrane permeation assay (PAMPA) and molecular dynamics (MD) simulation with DOPC lipid bilayers. The formation of the noncovalent supramolecular complex of PZQ with disodium salt of GA (Na2GA) in an aqueous solution was proved by the NMR relaxation technique. PAMPA experiments show a strong increase in the amount of the penetrating praziquantel molecules in comparison with a saturated aqueous solution of pure drug used as a control. MD simulation of PZQ penetration through the bilayer demonstrates an increase in permeability into the membrane in the presence of a glycyrrhizin molecule. A decrease in the free energy barrier in the middle of the lipid bilayer was obtained, associated with the hydrogen bond between PZQ and GA. Also, GA reduces the local bilayer surface resistance to penetration of PZQ by rearranging the surface lipid headgroups. This study clarifies the mechanism of increasing the drug's bioavailability in the presence of glycyrrhizin.

The effect of ketoconazole on praziquantel pharmacokinetics and the role of CYP3A4 in the formation of X-OH-praziquantel and not 4-OH-praziquantel.

AIM: The study sought to determine the effect of ketoconazole (KTZ) on the pharmacokinetics of praziquantel (PZQ) and on the formation of its major hydroxylated metabolites, cis- and trans-4-OH-PZQ, and X-OH-PZQ in healthy subjects. METHODS: Two treatments were evaluated by single-dose PK studies; the reference treatment was a 20 mg/kg dose of praziquantel given alone. The test treatment was a 20 mg/kg dose of praziquantel given in combination with 200 mg of ketoconazole. The study had a balanced and randomised cross-over design. Serial blood samples were collected between 0 and 12 h after each drug administration. PZQ, and cis- and trans-4-OH-PZQ and X-OH-PZQ concentrations in plasma were determined by LC-MS. A non-compartmental approach was used for pharmacokinetic analysis. Data were analysed using ANOVA and assessment of the 90% confidence interval of the geometric means of the log-transformed PK parameters obtained for each treatment. RESULTS: The pharmacokinetics of PZQ following the two treatments, PZQ alone and PZQ + KTZ, were not equivalent based on the assessment of the 90% CI of the geometric mean ratios of the AUC and Cmax (α = 0.05). The geometric mean ratios of the AUC and Cmax were found to be 176.8% and 227% respectively. The 90% CI of the AUC and Cmax were found to be 129.8%-239.8% and 151.4%-341.4% respectively. The AUC of PZQ was increased by 75% with KTZ co-administration (3516 vs 6172 ng h/ml) (p < 0.01). Meanwhile, the mean AUC of trans-4-OH-PZQ increased by 67% (61,749 ng h/ml vs 103,105 ng h/ml) (p < 0.01). X-OH-PZQ levels were reduced by about 57% (semi-quantified as 7311 ng h/ml vs 3109 ng h/ml by using trans-4-OH as standards) (p < 0.01) with KTZ co-administration. CONCLUSIONS: The relative bioavailability of praziquantel was increased by concomitant KTZ administration. KTZ preferentially inhibited the formation of X-OH-PZQ rather than 4-OH-PZQ, confirming in vitro data which implicates CYP3A4 in the formation of X-OH-PZQ rather than 4-OH-PZQ. The 4-hydroxylation of PZQ was shown to be the major metabolic pathway of PZQ, as evidenced by larger quantities of 4-OH-PZQ produced, thus explaining the modest albeit significant effect of ketoconazole on PZQ pharmacokinetics.

Combined chemotherapy manifest less severe immunopathology effects in helminth-protozoa comorbidity.

BACKGROUND: Co-infection with Leishmania major and Schistosoma mansoni may have significant consequences for disease progression, severity and subsequent transmission dynamics. Pentavalent antimonials and Praziquantel (PZQ) are used as first line of treatment for Leishmania and Schistosoma infections respectively. However, there is limited insight on how combined therapy with the standard drugs impacts the host in comorbidity. The study aimed to determine the efficacy of combined chemotherapy using Pentostam (P) and PZQ in murine model co-infected with L. major and S. mansoni. METHODS: A 3 × 4 factorial design with three parasite infection groups (Lm, Sm, Lm + Sm to represent L. major, S. mansoni and L. major + S. mansoni respectively) and four treatment regimens [P, PZQ, P + PZQ, and PBS designating Pentostam (GlaxoSmithKline UK), Praziquantel (Biltricide®, Bayer Ag. Leverkusen, Germany), Pentostam + Praziquantel and Phosphate buffered saline] as factors was applied. RESULTS: Significant changes were observed in the serum Interferon gamma (IFN-γ), and Macrophage inflammatory protein-one alpha (MIP-1α) levels among various treatment groups between week 8 and week 10 (p < 0.05). There was increased IFN-γ in the L. major infected mice subjected to PZQ and PBS, and in L. major + S. mansoni infected BALB/c mice treated with P + PZQ. Subsequently, MIP-1α levels increased significantly in both the L. major infected mice under PZQ and PBS and in L. major + S. mansoni infected BALB/c mice undergoing concurrent chemotherapy with P + PZQ between 8 and 10 weeks (p < 0.05). In the comorbidity, simultaneous chemotherapy resulted in less severe histopathological effects in the liver. CONCLUSION: It was evident, combined first line of treatment is a more effective strategy in managing co-infection of L. major and S. mansoni. The findings denote simultaneous chemotherapy compliments immunomodulation in the helminth-protozoa comorbidity hence, less severe pathological effects following the parasites infection. Recent cases of increased incidences of polyparasitism in vertebrates call for better ways to manage co-infections. The findings presented necessitate intrinsic biological interest on examining optimal combined chemotherapeutic agents strategies in helminth-protozoa concomitance and the related infections abatement trends vis-a-vis host-parasite relationships.

Enhancement of the therapeutic efficacy of praziquantel in murine Schistosomiasis mansoni using silica nanocarrier.

The main objective of this work is preparation of mesoporous silica nanoparticles loaded with praziquantel (PZQ-Si) in order to enhance the therapeutic efficacy of praziquantel (PZQ). Mice were experimentally infected with Schistosoma mansoni and treated 6 weeks post-infection with PZQ in different doses via either oral or intraperitoneal (IP) routes. PZQ in the same doses orally administered to S. mansoni-infected mice was used as a drug control, and infected and non-infected non-treated mice served as positive and negative controls, respectively. PZQ-Si exhibited good physicochemical attributes in terms of small uniform size (105 nm), spherical shape, and PZQ entrapment efficiency (83%). A maximum antischistosomal effect was achieved using orally administered PZQ-Si as reflected by total worm burden, tissue egg count, oogram pattern, and hepatic granuloma count and diameter. The biomarkers related to liver oxidative stress status and immunomodulatory effect (serum TNF-α and IL-10) were significantly improved. Data obtained implied that IP route was less efficacious for the delivery of PZQ-Si. Encapsulation of PZQ permits the reduction of the used therapeutic dose of PZQ. Hepatic DNA fragmentation, measured by comet assay, was significantly improved in infected mice treated with maximum dose of PZQ-Si as compared to positive or PZQ control groups. The results indicate that mesoporous silica NP is a promising safe nanocarrier for PZQ potentiating its antischistosomal, antioxidant, immunomodulatory, and anti-inflammatory action in animal model infected with S. mansoni. From a practical standpoint, PZQ-Si using a lower dose of PZQ could be suggested for effective PZQ antischistosomal mass chemotherapy.

Niosomes for enhanced activity of praziquantel against Schistosoma mansoni: in vivo and in vitro evaluation.

Praziquantel (PZQ) is recommended by the WHO as the first line in treatment of schistosomiasis. Unfortunately, it exhibits low oral bioavailability which can compromise its efficacy. Nanostructures showed promising potential to overcome this problem. Accordingly, the aim of this study was to investigate the effect of niosomal encapsulation of PZQ on its activity on Schistosoma mansoni in vitro and in vivo. PZQ was encapsulated in niosomal formulation comprising span 60, cholesterol with peceol being included as absorption enhancer. The in vitro work determined the schistosomicidal activity and morphological changes after incubation with drug solution or PZQ-niosomes. The in vivo study utilized infected mice which received PZQ orally as solution or as niosomes. The activity was assessed by monitoring egg and worm count in addition to histopathological and immunohistochemical studies. The in vitro studies revealed that niosomes alone caused a 30% death of adult parasites and caused completely coiled body, destruction, and peeling of tubercles and spines, with flattening and effacement of gynecophoric canal, blebbing with niosomes vesicles attached to it. Niosomes containing PZQ at a concentration of 0.001 µg/ml increased the death from 30 to 50% with the corresponding PZQ solution causing only 10% death. The in vivo study reflected of niosome-PZQ over PZQ solution as indicated from significant reduction of adult worm count, hepatic and intestinal egg depositions, hepatic granuloma size, and numbers, with marked reduction of vascular endothelial growth factor expression. The study introduced niosomes as promising carriers for enhanced activity of PZQ.

Investigation of pharmacokinetic interaction between ivermectin and praziquantel after oral administration in healthy dogs.

The purpose of this study was to determine the pharmacokinetic interaction between ivermectin (0.4 mg/kg) and praziquantel (10 mg/kg) administered either alone or co-administered to dogs after oral treatment. Twelve healthy cross-bred dogs (weighing 18-21 kg, aged 1-3 years) were allocated randomly into two groups of six dogs (four females, two males) each. In first group, the tablet forms of praziquantel and ivermectin were administered using a crossover design with a 15-day washout period, respectively. Second group received tablet form of ivermectin plus praziquantel. The plasma concentrations of ivermectin and praziquantel were determined by high-performance liquid chromatography using a fluorescence and ultraviolet detector, respectively. The pharmacokinetic parameters of ivermectin following oral alone-administration were as follows: elimination half-life (t1/2λz ) 110 ± 11.06 hr, area under the plasma concentration-time curve (AUC0-∞ ) 7,805 ± 1,768 hr. ng/ml, maximum concentration (Cmax ) 137 ± 48.09 ng/ml, and time to reach Cmax (Tmax ) 14.0 ± 4.90 hr. The pharmacokinetic parameters of praziquantel following oral alone-administration were as follows: t1/2λz 7.39 ± 3.86 hr, AUC0-∞ 4,301 ± 1,253 hr. ng/ml, Cmax 897 ± 245 ng/ml, and Tmax 5.33 ± 0.82 hr. The pharmacokinetics of ivermectin and praziquantel were not changed, except Tmax of praziquantel in the combined group. In conclusion, the combined formulation of ivermectin and praziquantel can be preferred in the treatment and prevention of diseases caused by susceptible parasites in dogs because no pharmacokinetic interaction was determined between them.

Gastrointestinal Parasite Infection in Cats in Daegu, Republic of Korea, and Efficacy of Treatment Using Topical Emodepside/Praziquantel Formulation.

The purpose of this study was 2-fold: 1) to investigate the prevalence of gastrointestinal parasite infection in cats reared in Daegu, Republic of Korea and 2) to assess the efficacy and safety of a topical emodepside/praziquantel formulation for cats with parasitic infections. The gastrointestinal parasite infections were examined microscopically using the flotation method. Of 407 cats, 162 (39.8%) were infected by at least one gastrointestinal parasite, including Toxocara cati (63.0%), Toxascaris leonina (31.5%), Taenia taeniaeformis (3.7%), and Cystoisospora felis (1.9%). None of the infected animals had multiple infections. When the data were analyzed according to sex, age, and type of cat, stray cats showed statistically higher prevalence than companion cats (P<0.05). On the 5th day after treatment, no parasitic eggs were detected using microscopic examination. In addition, no adverse effects, such as abnormal behaviors and clinical symptoms, were observed in the cats treated with the drug. These results quantify the prevalence of gastrointestinal parasites in cats in Daegu, Republic of Korea, and show that topical emodepside/praziquantel is a safe and effective choice for treating the parasitic infections in cats.

Effects of Callistemon citrinus aqueous extract on prepatent and patent infections with Schistosoma mansoni in experimentally infected mice.

Schistosomiasis is a chronic debilitating parasitic disease that causes hepatic damage and is known to be endemic in developing countries. Recent control strategies for schistosomiasis depend exclusively on chemotherapeutic agents, specifically praziquantel. Unfortunately, praziquantel has low efficacy in the early phase of infection, and resistance to treatment is increasingly reported. The aim of this work was to find an alternative treatment by assessing the in vivo activity of aqueous extract of Callistemon citrinus against Schistosoma mansoni in both prepatent and patent phases in experimentally infected mice. The study was conducted on 80 male BALB/c albino mice divided into eight groups. Callistemon was administered at a dose of 200 mg/kg on days 14 and 45 post infection as a single therapy and in combination with praziquantel. Porto-mesenteric worm burden, hepatic and intestinal egg counts, hepatic granuloma number and diameter, and oogram pattern were assessed to evaluate the anti-schistosomal properties of C. citrinus. Liver enzymes and total bilirubin were tested to assess hepatoprotective effects. Results revealed that the use of C. citrinus was associated with a significant decrease in worm burden and tissue egg load together with an increased percentage of dead eggs. In addition, there was a significant reduction in granuloma formation. Callistemon also led to a significant improvement in liver function. The best results were obtained when C. citrinus was given in the prepatent phase of infection and when combined with praziquantel. Although the effects of C. citrinus are considered to be promising, further studies using different extracts, active ingredients and doses are needed.

Immunization with adult Schistosoma mansoni tegument, treated with sub-curative praziquantel, partially protects mice against the infection.

The tegument of schistosomes is a source of many potential anti-Schistosoma vaccine molecules. This work aimed to assess the protective effects of the adult Schistosoma mansoni tegument treated (TT) with sub-curative praziquantel (PZQ), whether in vivo (in vivo TT) or in vitro (in vitro TT), in murine schistosomiasis. In vitro TT and in vivo TT showed great similarity, and they differed from untreated tegument antigen (Teg) in terms of quantity and quality of protein bands on SDS-PAGE. Two immunization trials were performed, each with 50 mice, divided randomly into five groups of 10 mice each: (1) uninfected control mice (UC), (2) infected mice given phosphate buffer saline + adjuvant (PBS + adjuvant), (3) infected, Teg vaccinated, (4) infected, in vivo TT vaccinated, and (5) infected, in vitro TT vaccinated. All the immunizations with antigens induced mixed Th1/Th2 immune responses, as indicated by significantly high (P < 0.001) specific IgG2a and IgG1 levels, with Th1 predominating, as shown by a diminished IgG1/IgG2a ratio, as well as a high serum concentration of IFN-γ, an absence of IL-4 and increased IL-10. In vitro TT gave the most pronounced response. With respect to reduction of total worm burden, relative to PBS + adjuvant mice, in vitro TT achieved the highest significant (P < 0.001) results, followed by in vivo TT and Teg (51.8-57.04%, 44.6-50.2% and 35.2-39.3%, respectively). In scanning electron microscopy studies, all the tested antigens caused tegumental changes in adult worms, with the worst occurring with in vitro TT, such as retracted ventral sucker, an effect on the gynaecophoric canal, and changes to tubercles. In conclusion, in vitro TT, which is cheap to prepare, could be a potential vaccine against S. mansoni.

Schistosomicidal, antifibrotic and antioxidant effects of Cucurbita pepo L. seed oil and praziquantel combined treatment for Schistosoma mansoni infection in a mouse model.

Despite the seriousness of schistosomiasis, its treatment depends only on praziquantel (PZQ), which has begun to lose its efficacy against the emergent Schistosoma mansoni-resistant strains. Therefore, the discovery of a novel schistosomicidal drug is an urgent priority. This study was designed to evaluate treatment with Cucurbita pepo L. (pumpkin) seed oil (PSO) alone and combined with PZQ against S. mansoni in experimentally infected mice. The study involved five groups: GI was the normal control; GII was the infected control; GIII was treated with an oral dose of PZQ of 500 mg/kg/day for two successive days, starting in the sixth week post infection; GIV was treated with an oral dose of PSO of 50 mg/kg/day for four weeks, starting in the fourth week post infection; and GV was treated with combined PSO-PZQ. Worm burden, tissue egg load and oogram pattern were estimated, and the ultrastructure alterations were examined. Histopathological examination of granuloma diameters, collagen deposition (Picro Sirius red stain), and angiogenesis (immunohistochemical expression of CD34+) was conducted and serum liver enzymes were measured to assess the liver condition. Moreover, the oxidative stress was evaluated by determining the amounts of malondialdehyde and superoxide dismutase in liver homogenates. The results revealed significant changes in all the assessed parameters with PSO administration. However, PZQ was significantly more effective as an antiparasitic agent, whereas PSO was better in terms of fibrosis and oxidative stress. The most significant results were obtained in group V, which may be attributed to a synergy between PZQ and PSO, with antiparasitic, antioxidant and antifibrotic properties.