Praziquantel-encapsulated niosomes against Schistosoma mansoni with reduced sensitivity to praziquantel. / Niosomas encapsulados en prazicuantel contra Schistosoma mansoni con sensibilidad reducida al prazicuantel

INTRODUCTION: Praziquantel (PZQ) is the only commercially available drug for schistosomiasis. The current shortage of alternative effective drugs and the lack of successful preventive measures enhance its value. The increase in the prevalence of PZQ resistance under sustained drug pressure is, therefore, an upcoming issue. OBJECTIVE: To overcome the tolerance to PZQ using nanotechnology after laboratory induction of a Schistosoma mansoni isolate with reduced sensitivity to the drug during the intramolluscan phase. MATERIALS AND METHODS: Shedding snails were treated with PZQ doses of 200 mg/kg twice/ week followed by an interval of one week and then repeated twice in the same manner. The success of inducing reduced sensitivity was confirmed in vitro via the reduction of cercarial response to PZQ regarding their swimming activity and death percentage at different examination times. RESULTS: Oral treatment with a single PZQ dose of 500 mg/kg in mice infected with cercariae with reduced sensitivity to PZQ revealed a non-significant reduction (35.1%) of total worm burden compared to non-treated control mice. Orally inoculated PZQ-encapsulated niosomes against S. mansoni with reduced sensitivity to PZQ successfully regained the pathogen's sensitivity to PZQ as evidenced by measuring different parameters in comparison to the non-treated infected animals with parasites with reduced sensitivity to PZQ. The mean total worm load was 1.33 ± 0.52 with a statistically significant reduction of 94.09% and complete eradication of male worms. We obtained a remarkable increase in the percentage reduction of tissue egg counts in the liver and intestine (97.68% and 98.56%, respectively) associated with a massive increase in dead eggs and the complete absence of immature stages. CONCLUSION: PZQ-encapsulated niosomes restored the drug sensitivity against laboratory-induced S. mansoni adult worms with reduced sensitivity to PZQ.

Introducción. El prazicuantel es el único fármaco disponible comercialmente para la esquistosomiasis. La escasez actual de medicamentos alternativos y la falta de medidas preventivas eficaces aumentan su valor. La creciente prevalencia de la resistencia al prazicuantel bajo una presión prolongada del fármaco es, por tanto, un tema emergente. Objetivos. Superar la tolerancia al prazicuantel mediante nanotecnología después de la inducción en laboratorio de un aislamiento de Schistosoma mansoni con sensibilidad reducida al fármaco durante la fase intramolusco. Materiales y métodos. Los caracoles que liberaban cercarias se trataron con prazicuantel en dosis de 200 mg/kg dos veces por semana, seguidas de un intervalo de una semana, y luego se repitieron dos veces de la misma manera. La inducción exitosa de la sensibilidad reducida se confirmó in vitro mediante la reducción de la reacción de las cercarias al prazicuantel con respecto a su actividad de natación y el porcentaje de muerte en diferentes momentos de examen. El éxito en inducir una menor sensibilidad se confirmó in vitro mediante la reducción de la reacción de las cercarias al prazicuantel. Resultados. El tratamiento oral con una dosis única de prazicuantel de 500 mg/kg en ratones infectados con cercarias con sensibilidad reducida al prazicuantel, reveló una reducción no significativa (35,1 %) de la carga total de gusanos en comparación con los ratones de control no tratados. Los niosomas encapsulados en prazicuantel inoculados por vía oral contra S. mansoni con sensibilidad reducida al prazicuantel, permitieron reestablecer con éxito la sensibilidad del patógeno al medicamento, como lo demostró la medición de diferentes parámetros en comparación con los animales infectados no tratados con parásitos con sensibilidad reducida a prazicuantel. La carga media total de gusanos fue de 1,33 ± 0,52, con una reducción estadísticamente significativa del 94,09 %, y la erradicación completa de los gusanos machos adultos. Se obtuvo un aumento notable en el porcentaje de reducción del recuento de huevos en el tejido del hígado y el intestino (97,68 % y 98,56 %, respectivamente), asociado con un aumento masivo de huevos muertos y ausencia total de estadios inmaduros. Conclusión. Los niosomas encapsulados en prazicuantel restauraron la sensibilidad al fármaco contra gusanos adultos de S. mansoni con sensibilidad reducida al prazicuantel inducida en el laboratorio.

A single oral dose of celecoxib-loaded solid lipid nanoparticles for treatment of different developmental stages of experimental schistosomiasis mansoni.

Schistosomiasis, a neglected tropical parasitic disease, is associated with severe pathology, mortality and economic loss. The treatment and control of schistosomiasis depends mainly on a single dose of praziquantel (PZQ). Drug repurposing and nanomedicine attract great attention to improve anti-schistosomal therapy. Previously, we reported that celecoxib (CELE), the non-steroidal anti-inflammatory drug, showed potent anti-schistosomal efficacy in an oral dose of 20 mg/kg/day for five days against different developmental stages of Schistosoma mansoni (S. mansoni) infection in mice. The aim of the current study was to shorten the duration of CELE treatment to reach an effective single oral dose against different developmental stages of S. mansoni infection using solid lipid nanoparticles (SLNs) as nano-carriers. The latter enhance the solubility, bioavailability and drug delivery and hence can decrease the frequency of administration which is of great clinical value. CELE-loaded SLNs showed good colloidal properties, high entrapment efficiency and drug loading, sustained biphasic release pattern with excellent storage stability. The used regimen was efficient against different developmental stages of S. mansoni infection with the most pronounced effect against the juvenile stage where the worm load, the hepatic egg count and the intestinal egg count were reduced by 86.39%, 91.45% and 90.11%, respectively. Meanwhile, when targeting the invasive and the adult stages, it induced reduction in the worm load by 73.55% and 78.22%, the hepatic egg count by 69.99% and 75.39% and the intestinal egg count by 77.57% and 79.89%, respectively. Additionally, CELE-loaded SLNs caused extensive tegumental damage of adult worms and marked improvement in the liver pathology.

Effect of HIV aspartyl protease inhibitors on experimental infection with a cystogenic Me49 strain of Toxoplasma gondii.

Toxoplasmosis is a zoonotic disease of major significant perspectives in public health and veterinary medicine. So far, the available drugs control only the active infection, once the parasite encysts in the tissues, they lose their efficacy. Cytokines; IFN-γ and IL-10, play a critical role in the modulation of toxoplasmic encephalitis and neuro-inflammation in chronic toxoplasmosis. Antiretroviral protease inhibitors applied in the treatment of acquired immunodeficiency syndrome, revealed activity against multiple parasites. Aluvia (lopinavir/ritonavir) (L/R); an aspartyl protease inhibitor, had efficiently treated T. gondii RH strain infection. We investigated the potential activity of L/R against experimental T. gondii infection with a cystogenic Me49 strain in mice, considering the role of IFN-γ and IL-10 in the neuropathology versus pyrimethamine-sulfadiazine combination therapy. Three aluvia regimens were applied; starting on the day of infection (acute phase), 2-week PI (early chronic phase) and eight weeks PI (late chronic phase). L/R reduced the brain-tissue cyst burden significantly in all treatment regimens. It impaired the parasite infectivity markedly in the late chronic phase. Ultrastructural changes were detected in Toxoplasma cyst membrane and wall, bradyzoite membrane and nuclear envelope. The signs of bradyzoite paraptosis and cytoplasmic lipid droplets were observed. L/R had significantly reduced the brain-homogenate levels of IFN-γ and IL-10 in its three regimens however, they could not reach the normal level in chronic phases. Cerebral hypercellularity, perivascular inflammatory response, lymphoplasmacytic infiltrates and glial cellular reaction were ameliorated by L/R treatment. Herein, L/R was proved to possess promising preventive and therapeutic perspectives in chronic cerebral toxoplasmosis.

Effect of celecoxib against different developmental stages of experimental Schistosoma mansoni infection.

Due to the high prevalence of schistosomiasis and the wide use of praziquantel solely for mass drug administration to control the disease, there is a great concern about the potential emergence of reduced susceptibility strains. This, together with the concern that praziquantel is ineffective against juvenile worms highlight the importance of developing an alternative anti-schistosomal drug. Using nonsteroidal anti-inflammatory drugs against schistosome infection is considerable. The present study evaluated the effect of oral administration of five days celecoxib regimen (20 mg/kg/day) against different developmental stages of Schistosoma mansoni infection. This regimen induced significant reduction in worm burden, tissue egg count, individual female fecundity and the mean percentage of immature and mature eggs with increased mean percentage of dead eggs. More importantly, celecoxib was more potent than praziquantel in all these parasitological parameters (except in the worm burden when given against the adult stage where the difference was statistically non-significant). Scanning and transmission electron microscopy of the adult worms revealed severe tegumental damage, laceration of the muscular layers and oedema of the syncytial layer. There was disruption of the testicular, ovarian and vitelline glandular tissues with signs of apoptosis and abnormalities of the spermatozoa and the oocytes. Additionally, celecoxib induced reduction in the number and the size of the hepatic granulomata and also amelioration of the hepatic tissue pathology.

Repurposing auranofin for treatment of Experimental Cerebral Toxoplasmosis.

PURPOSES: Evaluate the effect of auranofin on the early and late stages of chronic infection with Toxoplasma gondii avirulent ME49 strain. METHODS: Swiss albino mice were orally inoculated with 10 cysts of Toxoplasma gondii, and orally treated with auranofin or septazole in daily doses of 20 mg/kg or 100 mg /kg, respectively, for 30 days. Treatment began either on the same day of infection and mice were sacrificed at the 60th day postinfection or the treatment started after 60 days of infection and mice were sacrificed at the 90th day postinfection. RESULTS: Auranofin significantly reduced the brain cyst burden and inflammatory reaction at both stages of infection compared to the infected non-treated control. More remarkably, auranofin significant reduced the brain cyst burden in the late stage, while septazole failed. Hydrogen peroxide level was significantly increased in the brain homogenate of mice treated with auranofin only at the early stage of infection. Ultrastructral studies revealed that the anti-Toxoplasma effect of auranofin is achieved by changing the membrane permeability and inducing apoptosis. CONCLUSIONS: Thus, auranofin could be an alternative for the standard treatment regimen of toxoplasmosis and these results are considered another achievement for the drug against parasitic infection. Being a FDA-approved drug, it can be rapidly evaluated in clinical trials.

In vitro effectivity of three approved drugs and their synergistic interaction against Leishmania infantum. / Efectividad in vitro de tres fármacos aprobados y su interacción sinérgica contra Leishmania infantum

INTRODUCTION: Leishmaniasis remains one of the neglected tropical diseases. Repurposing existing drugs has proven to be successful for treating neglected tropical diseases while combination therapy is a strategic alternative for the treatment of infectious diseases. Auranofin, lopinavir/ritonavir, and sorafenib are FDA approved drugs used in the treatment of diverse diseases by acting on different essential biological enzymes. OBJECTIVE: To evaluate the effects of monotherapy and combined therapies with the three drugs against Leishmania infantum. MATERIALS AND METHODS: We compared the leishmanicidal effects of the three drugs on promastigotes in vitro as regards the parasite count, the drug concentration providing a half-maximal response, and the ultrastructural changes of the parasite. We determined the fractional inhibitory concentration index of combined drugs in two ways, as well as the activity of the three drugs together to establish their synergetic effect. RESULTS: The monotherapy with the three drugs was effective with auranofin showing the best leishmanicidal effect (EC50=1.5 µM), whereas sorafinib reduced parasite growth at EC50=2.5 µM. The scanning electron microscopy of promastigotes from all treated media showed distortion in the shape with loss of flagella and bleb formation. Acidocalcinosis was evident by transmission electron microscopy with all treatments suggesting apoptosis. Treatment with lopinavir/ritonavir showed signs of autophagy. The two-way combination of the drugs led to additive interactions while the combination of the three drugs showed synergistic action. CONCLUSION: Each drug when used as monotherapy against Leishmania spp. was effective, but the combination therapy was more effective than the individual drugs due to the additive or synergistic effects.

Introducción. La leishmaniasis sigue siendo una de las enfermedades tropicales desatendidas. La reutilización de medicamentos existentes ha demostrado ser exitosa para tratar enfermedades tropicales desatendidas y la terapia combinada es una alternativa estratégica para el tratamiento de enfermedades infecciosas. Auranofin, lopinavir/ritonavir y sorafenib son medicamentos aprobados por la Food and Drug Administration (FDA) de Estados Unidos utilizados en el tratamiento de diversas enfermedades, pues actúan sobre diferentes enzimas biológicas esenciales. Objetivo. Evaluar los efectos terapéuticos de la monoterapia y de los tres fármacos combinados contra Leishmania infantum. Materiales y métodos. Los efectos leishmanicidas de los tres fármacos sobre los promastigotes se compararon in vitro en cuanto al recuento de parásitos, la concentración del fármaco que proporcionara una respuesta semimáxima y los cambios ultraestructurales del parásito. Se calculó el índice de concentración inhibitoria de fracciones de fármacos combinados de dos maneras y la actividad de los tres fármacos juntos para determinar el efecto sinérgico. Resultados. La monoterapia con los tres medicamentos fue efectiva, pero la auranofina tuvo el mejor efecto antileishmanicida con un CE50 de 1,5 µM, en tanto que el sorafinib redujo el crecimiento del parásito con un CE50 de 2,5 µM. La microscopía electrónica de barrido de promastigotes de todos los medios tratados mostró una distorsión en la forma, con pérdida de flagelos y formación de ampollas. La acidocalcinosis fue evidente por microscopía electrónica de transmisión con todos los tratamientos, lo que sugiere apoptosis. El tratamiento con lopinavir/ritonavir mostró signos de autofagia. La combinación de dos medicamentos condujo a interacciones aditivas, mientras que la combinación de las tres drogas produjo una acción sinérgica. Conclusión. Los tres medicamentos usados como monoterapia contra Leishmania spp. fueron efectivos, pero el tratamiento combinado lo fue en mayor medida debido a los efectos aditivos o sinérgicos.

In vitro effectivity of three approved drugs and their synergistic interaction against Leishmania infantum / Efectividad in vitro de tres fármacos aprobados y su interacción sinérgica contra Leishmania infantum

Introduction: Leishmaniasis remains one of the neglected tropical diseases. Repurposing existing drugs has proven to be successful for treating neglected tropical diseases while combination therapy is a strategic alternative for the treatment of infectious diseases. Auranofin, lopinavir/ritonavir, and sorafenib are FDA approved drugs used in the treatment of diverse diseases by acting on different essential biological enzymes. Objective: To evaluate the effects of monotherapy and combined therapies with the three drugs against Leishmania infantum. Materials and methods: We compared the leishmanicidal effects of the three drugs on promastigotes in vitro as regards the parasite count, the drug concentration providing a half-maximal response, and the ultrastructural changes of the parasite. We determined the fractional inhibitory concentration index of combined drugs in two ways, as well as the activity of the three drugs together to establish their synergetic effect. Results: The monotherapy with the three drugs was effective with auranofin showing the best leishmanicidal effect (EC50=1.5 µM), whereas sorafinib reduced parasite growth at EC50=2.5 µM. The scanning electron microscopy of promastigotes from all treated media showed distortion in the shape with loss of flagella and bleb formation. Acidocalcinosis was evident by transmission electron microscopy with all treatments suggesting apoptosis. Treatment with lopinavir/ritonavir showed signs of autophagy. The two-way combination of the drugs led to additive interactions while the combination of the three drugs showed synergistic action. Conclusion: Each drug when used as monotherapy against Leishmania spp. was effective, but the combination therapy was more effective than the individual drugs due to the additive or synergistic effects.

Introducción. La leishmaniasis sigue siendo una de las enfermedades tropicales desatendidas. La reutilización de medicamentos existentes ha demostrado ser exitosa para tratar enfermedades tropicales desatendidas y la terapia combinada es una alternativa estratégica para el tratamiento de enfermedades infecciosas. Auranofin, lopinavir/ritonavir y sorafenib son medicamentos aprobados por la Food and Drug Administration (FDA) de Estados Unidos utilizados en el tratamiento de diversas enfermedades, pues actúan sobre diferentes enzimas biológicas esenciales. Objetivo. Evaluar los efectos terapéuticos de la monoterapia y de los tres fármacos combinados contra Leishmania infantum. Materiales y métodos. Los efectos leishmanicidas de los tres fármacos sobre los promastigotes se compararon in vitro en cuanto al recuento de parásitos, la concentración del fármaco que proporcionara una respuesta semimáxima y los cambios ultraestructurales del parásito. Se calculó el índice de concentración inhibitoria de fracciones de fármacos combinados de dos maneras y la actividad de los tres fármacos juntos para determinar el efecto sinérgico. Resultados. La monoterapia con los tres medicamentos fue efectiva, pero la auranofina tuvo el mejor efecto antileishmanicida con un CE50 de 1,5 µM, en tanto que el sorafinib redujo el crecimiento del parásito con un CE50 de 2,5 µM. La microscopía electronica de barrido de promastigotes de todos los medios tratados mostró una distorsión en la forma, con pérdida de flagelos y formación de ampollas. La acidocalcinosis fue evidente por microscopía electrónica de transmisión con todos los tratamientos, lo que sugiere apoptosis. El tratamiento con lopinavir/ritonavir mostró signos de autofagia. La combinación de dos medicamentos condujo a interacciones aditivas, mientras que la combinación de las tres drogas produjo una acción sinérgica. Conclusión. Los tres medicamentos usados como monoterapia contra Leishmania spp. fueron efectivos, pero el tratamiento combinado lo fue en mayor medida debido a los efectos aditivos o sinérgicos.

[Developmental stages and viability of Toxocara canis eggs outside the host].

INTRODUCTION: Toxocariasis is a soil-transmitted zoonotic disease caused mainly by ingestion of larvated eggs of Toxocara canis. OBJECTIVES: To study the morphology of the intraovular developmental stages of Toxocara canis in culture, characterize non-viable eggs and the sequences of larval molting and compare the viability of eggs at the early stages of division and at reaching full maturation. MATERIAL AND METHODS: Observation of developing embryos and characterization of non-viable eggs were done using light microscope. The proportions of viable eggs during embryonation were compared to the proportions of viable mature eggs. RESULTS: Cell division commenced after 24 hours of cultivation. Early stages were found to be present over a period of 3-5 days. The developmental stages identified were eggs with: One cell, two cells, three cells, four cells, early morula, late morula, blastula, gastrula, tadpole, pre-larva, first, second and third stage larva. Two larval molts occurred. Non-viable eggs had degenerated cytoplasm, thin or collapsed shell and the larvae did not move after exposure to light. No significant differences were found between the proportions of viable eggs from day five to day 21 as compared to viability of fully mature eggs (30 days). CONCLUSION: Developing embryos in the environment may be considered as a potential threat to the public health. The precise identification of developmental stages and the clear differentiation of viable and non-viable eggs can help in determining an accurate baseline rate of development that could be used in studies of ovicidal compounds.

Developmental stages and viability of Toxocara canis eggs outside the host / Desarrollo y viabilidad de huevos de Toxocara canis

ABSTRACT Introduction: Toxocariasis is a soil-transmitted zoonotic disease caused mainly by ingestion of larvated eggs of Toxocara canis. Objectives: To study the morphology of the intraovular developmental stages of Toxocara canis in culture, characterize non-viable eggs and the sequences of larval molting and compare the viability of eggs at the early stages of division and at reaching full maturation. Material and methods: Observation of developing embryos and characterization of non-viable eggs were done using light microscope. The proportions of viable eggs during embryonation were compared to the proportions of viable mature eggs. Results: Cell division commenced after 24 hours of cultivation. Early stages were found to be present over a period of 3-5 days. The developmental stages identified were eggs with: One cell, two cells, three cells, four cells, early morula, late morula, blastula, gastrula, tadpole, pre-larva, first, second and third stage larva. Two larval molts occurred. Non-viable eggs had degenerated cytoplasm, thin or collapsed shell and the larvae did not move after exposure to light. No significant differences were found between the proportions of viable eggs from day five to day 21 as compared to viability of fully mature eggs (30 days). Conclusion: Developing embryos in the environment may be considered as a potential threat to the public health. The precise identification of developmental stages and the clear differentiation of viable and non-viable eggs can help in determining an accurate baseline rate of development that could be used in studies of ovicidal compounds.

RESUMEN Introducción. La toxocariasis es una enfermedad zoonótica transmitida por contacto con el suelo contaminado y causada principalmente por la ingestión de huevos larvados de Toxocara canis. Objetivos. Estudiar la morfología de los estadios intraovulares en desarrollo de T. canis en cultivo, caracterizar los huevos no viables y las secuencias de las mudas larvarias, y comparar la viabilidad de los huevos en las etapas tempranas de división y al alcanzar la maduración completa. Materiales y métodos. Se observó el desarrollo de los embriones y se caracterizaron los huevos no viables, mediante microscopía de luz. Se comparó la proporción de huevos viables con embrión con la de huevos maduros viables. Resultados. La división celular comenzó 24 horas después de iniciado el cultivo. Los estadios tempranos estuvieron presentes por un periodo de tres a cinco días. Los estadios de desarrollo identificados fueron: huevos con una célula, con dos células, con tres células y con cuatro células;mórula temprana, mórula tardía, blástula, gástrula, renacuajo, prelarva, primer, segundo y tercer estado larvario. Se presentaron dos mudas larvarias. Los huevos no viables tenían el citoplasma degradado, cubierta exterior delgada o colapsada, y su larva no se movía al exponerla a la luz. No se encontraron diferencias significativas entre la proporción de huevos viables del día 5 al día 21, al compararla con la viabilidad de los huevos completamente maduros (30 días). Conclusión. Los embriones en desarrollo en el medio ambiente pueden considerarse como un riesgo potencial para la salud pública. La identificación precisa de los estadios de desarrollo y la clara diferenciación de huevos viables y no viables, pueden ayudar a determinar con exactitud una tasa basal de desarrollo, la cual sería útil en el estudio de compuestos ovicidas.

The effect of lopinavir/ritonavir and lopinavir/ritonavir loaded PLGA nanoparticles on experimental toxoplasmosis.

A marked reduction has been achieved in the incidence and clinical course of toxoplasmic encephalitis after the introduction of protease inhibitors within the treatment regimen of HIV (HIV-PIs). This work was undertaken to study for the first time, the efficacy of HIV-PIs, lopinavir/ritonavir (L/R), as a therapeutic agent in acute experimental toxoplasmosis. Lopinavir/ritonavir (L/R) were used in the same ratio present in aluvia, a known HIV-PIs drug used in the developing countries in the treatment regimens of AID's patient. Poly lactic-co-glycolic acid (PLGA) nanoparticles were used as a delivery system to L/R therapy. L/R alone or after its encapsulation on PLGA were given to Swiss strain albino mice that were infected with RH virulent toxoplasma strain. Both forms caused parasitological improvement in both mortality rate and parasite count. The higher efficacy was achieved by using L/R PLGA together with minimizing the effective dose. There was significant reduction in the parasite count in the peritoneal fluid and the liver. Parasite viability and infectivity were also significantly reduced. The anti-toxoplasma effect of the drug was attributed to the morphological distortion of the tachyzoites as evident by the ultrastructure examination and suppressed the egress of tachyzoites. L/R also induced changes that suggest apoptosis and autophagy of tachyzoites. The parasitophorous vacuole membrane was disrupted and vesiculated. The nanotubular networks inside the parasitophorous vacuole were disrupted. Therefore, the present work opens a new possible way for the approved HIV-PIs as an alternative treatment against acute toxoplasmosis. Furthermore, it increases the list of the opportunistic parasites that can be treated by this drug. The successful in vivo effect of HIV-PIs against Toxoplasma gondii suggests that this parasite may be a target in HIV treated patients, thus decrease the possibility of toxoplasmic encephalitis development.

Impact of the age of Biomphalaria alexandrina snails on Schistosoma mansoni transmission: modulation of the genetic outcome and the internal defence system of the snail

Of the approximately 34 identified Biomphalariaspecies,Biomphalaria alexandrinarepresents the intermediate host of Schistosoma mansoniin Egypt. Using parasitological and SOD1 enzyme assay, this study aimed to elucidate the impact of the age of B. alexandrinasnails on their genetic variability and internal defence against S. mansoniinfection. Susceptible and resistant snails were reared individually for self-reproduction; four subgroups of their progeny were used in experiment. The young susceptible subgroup showed the highest infection rate, the shortest pre-patent period, the highest total cercarial production, the highest mortality rate and the lowest SOD1 activity. Among the young and adult susceptible subgroups, 8% and 26% were found to be resistant, indicating the inheritance of resistance alleles from parents. The adult resistant subgroup, however, contained only resistant snails and showed the highest enzyme activity. The complex interaction between snail age, genetic background and internal defence resulted in great variability in compatibility patterns, with the highest significant difference between young susceptible and adult resistant snails. The results demonstrate that resistance alleles function to a greater degree in adults, with higher SOD1 activity and provide potential implications for Biomphalariacontrol. The identification of the most susceptible snail age enables determination of the best timing for applying molluscicides. Moreover, adult resistant snails could be beneficial in biological snail control.

Impact of the age of Biomphalaria alexandrina snails on Schistosoma mansoni transmission: modulation of the genetic outcome and the internal defence system of the snail.

Of the approximately 34 identified Biomphalariaspecies,Biomphalaria alexandrinarepresents the intermediate host of Schistosoma mansoniin Egypt. Using parasitological and SOD1 enzyme assay, this study aimed to elucidate the impact of the age of B. alexandrinasnails on their genetic variability and internal defence against S. mansoniinfection. Susceptible and resistant snails were reared individually for self-reproduction; four subgroups of their progeny were used in experiment. The young susceptible subgroup showed the highest infection rate, the shortest pre-patent period, the highest total cercarial production, the highest mortality rate and the lowest SOD1 activity. Among the young and adult susceptible subgroups, 8% and 26% were found to be resistant, indicating the inheritance of resistance alleles from parents. The adult resistant subgroup, however, contained only resistant snails and showed the highest enzyme activity. The complex interaction between snail age, genetic background and internal defence resulted in great variability in compatibility patterns, with the highest significant difference between young susceptible and adult resistant snails. The results demonstrate that resistance alleles function to a greater degree in adults, with higher SOD1 activity and provide potential implications for Biomphalariacontrol. The identification of the most susceptible snail age enables determination of the best timing for applying molluscicides. Moreover, adult resistant snails could be beneficial in biological snail control.

Meta-analysis indicates lack of local adaptation of Schistosoma mansoni to Biomphalaria alexandrina in Egypt.

In Egypt, reclaiming portions of the desert using water from the Nile has resulted in large-scale invasion of Biomphalaria alexandrina in these regions. Studies exploring the local adaptation of Schistosoma mansoni to its snail host have been carried out to predict the extension of schistosomiasis to newly reclaimed areas. A meta-analysis of the relevant reports was conducted to compare the different biological characteristics of sympatric and allopatric Schistosoma mansoni and Biomphalaria alexandrina using different experimental designs. The results showed that there were no significant differences in the biological characteristics of sympatric and allopatric populations. The experimental design of some of the studies analyzed was found to affect the total cercarial production. The distance between the origin of the parasite and that of the snail did not affect any of the biological characteristics. The results showed that there is no evidence of local adaptation between Schistosoma mansoni and Biomphalaria alexandrina; however, the parasite is adapted to its intermediate host throughout the water bodies located in Egypt. The absence of local adaptation between Schistosoma mansoni and Biomphalaria alexandrina is likely of critical importance in predicting public health risks engendered by future reclaimed agriculture projects. Indeed, these results could assist in determining the appropriate balance between the development of water resource projects and schistosomiasis control in Egypt.

New scope on the relationship between rotifers and Biomphalaria alexandrina snails.

OBJECTIVE: To investigate the effect of rotifer internalization into snail tissue on the development of schistosomes. METHODS: Susceptible laboratory-bred Biomphalaria alexandrina (B. alexandrina) snails were exposed to lab-maintained rotifers; Philodina spp., two weeks before and after being infected with Schistosoma mansoni (S. mansoni) miracidia. The consequent histopathological impact on snail tissues and cercarial biology were investigated before and after emergence from snails. RESULTS: Contamination of B. alexandrina snails with philodina, two weeks before miracidial exposure, was found to hinder the preliminary development of S. mansoni cercariae inside the snail tissues. Furthermore, when snails were contaminated with rotifers two weeks post miracidial exposure; growth of already established cercariae was found to be retarded. The consequent influence of internalized rotifers within the snail tissue was clearly reflected on cercarial emergence, activity and infectivity along the four weeks duration of shedding. In the present study, comparison of snail histopathological findings and altered cercarial biology observed between the experimental and control groups indicated that the rotifers may have affected the levels of snail's energy reservoirs, which eventually was found to have had an adverse impact on reproduction, growth and survival of the parasite within the snail host, coupled with its performance outside the snail. CONCLUSIONS: In future biological control strategies of schistosomiasis, ritifers should be considered as a parasitic scourge of humanity.