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1.
Acta Trop ; 251: 107123, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38242223

ABSTRACT

BACKGROUND: Childhood brain tumors are a significant global health challenge, yet the etiology of these tumors remains elusive. While research has identified potential risk factors, recent studies have explored the involvement of infectious agents, particularly Toxoplasma gondii (T. gondii), in brain tumor development. METHODS: This study aimed to explore the prevalence of T. gondii infection in children diagnosed with brain tumors and to investigate the potential association between T. gondii infection and childhood brain tumors in Egypt. A total of 64 children with brain tumors and 92 healthy controls were enrolled in this study. Demographics and risk factors data were collected using structured questionnaires. Serological assay using ELISA technique was performed to detect anti-T. gondii antibodies in both cases and control groups. RESULTS: This study revealed a significantly higher seroprevalence of T. gondii infection in brain tumor cases (62.5 %) compared to healthy controls (38 %). Furthermore, a strong association was observed between T. gondii seropositivity and childhood brain tumors (odds ratio: 2.7). Notably, the consumption of unwashed vegetables emerged as a significant risk factor for T. gondii infection in Egypt. Analysis of T. gondii seroprevalence across different subtypes of brain tumors revealed varying rates, with glioma cases displaying a striking 100 % seroprevalence. CONCLUSIONS: These findings support the hypothesis that T. gondii infection may be a risk factor for childhood brain tumors and emphasize the need for further research in this area. The study also highlights the potential implications of control of T. gondii infection for prevention and treatment of childhood brain tumors.


Subject(s)
Brain Neoplasms , Toxoplasma , Toxoplasmosis , Humans , Child , Seroepidemiologic Studies , Egypt/epidemiology , Immunoglobulin G , Toxoplasmosis/complications , Toxoplasmosis/epidemiology , Brain Neoplasms/epidemiology , Brain Neoplasms/complications , Risk Factors , Antibodies, Protozoan
2.
Trans R Soc Trop Med Hyg ; 115(10): 1190-1197, 2021 10 01.
Article in English | MEDLINE | ID: mdl-33596320

ABSTRACT

BACKGROUND: Toxoplasma gondii is a worldwide protozoon that can infect all nucleated vertebrate cells. Little information is available about the association between T. gondii infection and coronary atherosclerosis. METHODS: A total of 320 cases were enrolled (160 patients with coronary atherosclerosis and 160 non-atherosclerotic individuals). Blood samples were collected to measure anti-T. gondii immunoglobulin G (IgG) antibodies using enzyme-linked immunosorbent assay (ELISA) and serum lipid profile. Coronary angiogram was also performed. RESULTS: The seroprevalence of anti-Toxoplasma antibodies in atherosclerotic and non-atherosclerotic individuals was 63.1% and 46.2%, respectively, with higher levels of anti-T. gondii IgG in atherosclerotic patients. Consumption of contaminated water, unwashed fruits and vegetables and raw meat and contact with soil were significant risk factors for Toxoplasma infection. Significant differences were detected in serum levels of low-density lipoproteins, triglycerides and cholesterol between both groups. Positive correlations were detected between ELISA titres and serum levels of low-density lipoproteins, triglycerides and cholesterol, disease severity and the number of affected vessels. Male gender and contact with soil had a significant association with positive T. gondii serology in atherosclerotic patients. CONCLUSIONS: Patients with coronary atherosclerosis have a high prevalence of T. gondii infection. More studies are crucial to elucidate the mechanisms underlying the effects of chronic toxoplasmosis on coronary atherosclerosis.


Subject(s)
Coronary Artery Disease , Toxoplasma , Toxoplasmosis , Antibodies, Protozoan , Coronary Artery Disease/epidemiology , Enzyme-Linked Immunosorbent Assay , Humans , Immunoglobulin M , Male , Risk Factors , Seroepidemiologic Studies , Toxoplasmosis/complications , Toxoplasmosis/epidemiology
3.
Parasitol Res ; 120(4): 1379-1388, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33159459

ABSTRACT

Trichomonas vaginalis is one of the most common non-viral sexually transmitted infections (STIs) that has been associated with prostate cancer in some countries. This study aims to investigate if T. vaginalis infection can be a risk factor for prostate cancer in Egypt and its possible relationship with cancer prognostic factors and overall survival. Serum samples were collected from a total of 445 age-matched males; 126 with prostate cancer, 108 with bladder cancer, 91 with different types of cancers, and 120 healthy controls, and then analyzed by ELISA for detection of anti-Trichomonas IgG and prostate-specific antigen (PSA). The results revealed that only 8.3% of controls were seropositive for trichomoniasis, compared with 19% of prostate cancer patients (P = 0.015). There were positive associations between the levels of PSA and tumor stage with T. vaginalis IgG optical density scores among the seropositive cases (P < 0.001 and < 0.05, respectively). However, no significant correlations were detected between seropositivity of T. vaginalis and other prognostic factors or overall survival in those patients. In conclusion, chronic T. vaginalis infection may be associated with prostate cancer, but it does not seem that this STI aggravates the cancer status.


Subject(s)
Prostatic Neoplasms/epidemiology , Trichomonas Infections/epidemiology , Trichomonas vaginalis/immunology , Adult , Aged , Antibodies, Protozoan/blood , Case-Control Studies , Egypt/epidemiology , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunoglobulin G/blood , Male , Middle Aged , Prognosis , Prostate-Specific Antigen/blood , Prostatic Neoplasms/mortality , Prostatic Neoplasms/pathology , Risk Factors , Trichomonas Infections/complications , Trichomonas Infections/mortality
4.
Acta Trop ; 207: 105466, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32302690

ABSTRACT

Omega-3 and omega-6 polyunsaturated fatty acids are synthesized from the essential fatty acids alpha-linolenic acid and linoleic acid, respectively. They are pivotal components of all mammalian cells and were found to be useful in prevention and treatment of a variety of health problems owing to their anti-inflammatory and anti-microbial properties. Omega-3 and omega-6 polyunsaturated fatty acids are further metabolized to anti-inflammatory mediators, such as lipoxins, resolvins, and protectins. Moreover, these polyunsaturated fatty acids were found to have in vivo and in vitro protective efficacies against some parasitic infections. Therefore, dietary intake of polyunsaturated fatty acids should be encouraged because of their considerable beneficial effects.


Subject(s)
Fatty Acids, Omega-3/administration & dosage , Fatty Acids, Omega-6/administration & dosage , Parasitic Diseases/prevention & control , Fatty Acids, Omega-3/pharmacology , Fatty Acids, Omega-6/pharmacology , Fatty Acids, Unsaturated/classification , Humans
5.
Front Immunol ; 11: 622162, 2020.
Article in English | MEDLINE | ID: mdl-33613557

ABSTRACT

Schistosomes are parasitic platyhelminths that currently infect >200 million people globally. The adult worms can live within the vasculature of their hosts for many years where they acquire all nutrients necessary for their survival and growth. In this work we focus on how Schistosoma mansoni parasites acquire and metabolize vitamin B6, whose active form is pyridoxal phosphate (PLP). We show here that live intravascular stage parasites (schistosomula and adult males and females) can cleave exogenous PLP to liberate pyridoxal. Of the three characterized nucleotide-metabolizing ectoenzymes expressed at the schistosome surface (SmAP, SmNPP5, and SmATPDase1), only SmAP hydrolyzes PLP. Heat-inactivated recombinant SmAP can no longer cleave PLP. Further, parasites whose SmAP gene has been suppressed by RNAi are significantly impaired in their ability to cleave PLP compared to controls. When schistosomes are incubated in murine plasma, they alter its metabolomic profile-the levels of both pyridoxal and phosphate increase over time, a finding consistent with the action of host-exposed SmAP acting on PLP. We hypothesize that SmAP-mediated dephosphorylation of PLP generates a pool of pyridoxal around the worms that can be conveniently taken in by the parasites to participate in essential, vitamin B6-driven metabolism. In addition, since host PLP-dependent enzymes play active roles in inflammatory processes, parasite-mediated cleavage of this metabolite may serve to limit parasite-damaging inflammation. In this work we also identified schistosome homologs of enzymes that are involved in intracellular vitamin B6 metabolism. These are pyridoxal kinase (SmPK) as well as pyridoxal phosphate phosphatase (SmPLP-Ph) and pyridox(am)ine 5'-phosphate oxidase (SmPNPO) and cDNAs encoding these three enzymes were cloned and sequenced. The three genes encoding these enzymes all display high relative expression in schistosomula and adult worms suggestive of robust vitamin B6 metabolism in the intravascular life stages.


Subject(s)
Alkaline Phosphatase/metabolism , Pyridoxal Phosphate/blood , Schistosoma mansoni/metabolism , Vitamin B 6/metabolism , Alkaline Phosphatase/genetics , Amino Acid Sequence , Animals , Female , Gene Expression Regulation, Developmental/genetics , Male , Mice , Phosphates/blood , Phosphoric Monoester Hydrolases/blood , Phosphoric Monoester Hydrolases/genetics , Phosphorylation , Phylogeny , Pyridoxal/blood , Pyridoxal Kinase/blood , Pyridoxal Kinase/genetics , Pyridoxal Phosphate/metabolism , Pyridoxaminephosphate Oxidase/blood , Pyridoxaminephosphate Oxidase/genetics , RNA Interference , Recombinant Proteins , Schistosoma mansoni/enzymology , Schistosoma mansoni/genetics , Schistosoma mansoni/growth & development , Sequence Alignment
6.
Mol Biochem Parasitol ; 232: 111190, 2019 09.
Article in English | MEDLINE | ID: mdl-31154018

ABSTRACT

Schistosoma mansoni is a long-lived intravascular trematode parasite that can infect humans causing the chronic debilitating disease, schistosomiasis. We hypothesize that the action of host-interactive proteins found at the schistosome surface allows the worms to maintain a safe, anti-thrombotic and anti-inflammatory environment around them in the bloodstream. One such protein is the ˜60 kDa alkaline phosphatase SmAP which is known to be expressed in the outer tegument of all intravascular life stages. We demonstrate in this work that the parasites (schistosomula as well as adult males and females) can hydrolyze polyphosphate (polyP) - an anionic, linear polymer of inorganic phosphates that is produced and released by immune cells as well as by activated platelets and that induce proinflammatory and prothrombotic pathways. Purified recombinant SmAP can likewise cleave polyP and with a Km of 6.9 ±â€¯1 mM. Finally, parasites whose SmAP gene has been suppressed by RNAi are significantly impaired in their ability to hydrolyze polyP. SmAP-mediated cleavage of polyP may contribute to the armamentarium of schistosomes that promotes their survival in the hostile intravascular habitat. This is the first report of any pathogen cleaving this bioactive metabolite.


Subject(s)
Alkaline Phosphatase/metabolism , Helminth Proteins/metabolism , Polyphosphates/metabolism , Schistosoma mansoni/enzymology , Schistosomiasis mansoni/parasitology , Alkaline Phosphatase/chemistry , Alkaline Phosphatase/genetics , Animals , Blood Platelets/metabolism , Female , Helminth Proteins/chemistry , Helminth Proteins/genetics , Host-Parasite Interactions , Humans , Kinetics , Male , Polyphosphates/chemistry , Schistosoma mansoni/genetics
7.
Acta Trop ; 194: 62-68, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30910394

ABSTRACT

Schistosomiasis is on the top list of endemic diseases in sub-Saharan Africa. Praziquantel is the drug of choice for treatment of human schistosomiasis. Yet, the sole dependence on the drug raises concerns about the potential for increased drug resistance, which would subsequently result in searching for alternative preventive chemotherapy options, ideally among natural compounds. Therefore, we conducted this work to assess the effect of omega-3 polyunsaturated fatty acids [(ω-3) PUFAs] monotherapy or combined therapy with artemether (ART) against Schistosoma mansoni infection in a mouse model. A total of 42 mice were divided into 4 groups and infected with 50 ± 5 S. mansoni cercariae for 10 weeks. Mice were treated orally with either (ω-3) PUFAs as 273 mg/ kg, 4 times/ week throughout the experiment, ART as a single dose of 400 mg/ kg, 3 weeks post-infection, or combined ART + (ω-3) PUFAs using the same respective treatment regimen, while infected untreated mice were served as controls. The study explored that combined administration of (ω-3) PUFAs and ART has the best schistosomicidal efficacy as it significantly reduced liver and spleen indices, worm count, egg burdens, and granulomas count as well as diameter. Besides, the combined regimen was associated with a significant decrease in both hepatic nitric oxide and serum interleukin-4 level. The results highlighted the possibility of using (ω-3) PUFA combined with ART as a novel anti-schistosomal combination therapy. However, further researches should be conducted to clarify the possible synergistic mechanism/s between the two natural compounds.


Subject(s)
Artemether/administration & dosage , Artemether/pharmacology , Fatty Acids, Omega-3/administration & dosage , Fatty Acids, Omega-3/pharmacology , Schistosoma mansoni/drug effects , Schistosomiasis/drug therapy , Schistosomicides/pharmacology , Africa South of the Sahara , Animals , Disease Models, Animal , Drug Combinations , Female , Mice , Mice, Inbred BALB C , Schistosoma mansoni/physiology , Schistosomicides/administration & dosage
8.
Trans R Soc Trop Med Hyg ; 113(6): 320-325, 2019 06 01.
Article in English | MEDLINE | ID: mdl-30668820

ABSTRACT

BACKGROUND: Schistosoma haematobium infection is a major public health problem in most of Africa and the Middle East and praziquantel remains the only drug used for schistosomiasis control, therefore emergence of drug resistance is unavoidable. The antimalarial artemisinin-naphthoquine phosphate combination (co-ArNp) was recently documented to have promising effects on Schistosoma mansoni and its snail host. METHODS: We conducted this in vitro study to assess the bioactivity of co-ArNp on S. haematobium and its snail vector Bulinus truncatus. RESULTS: Treatment of S. haematobium worms with 1 µg/ml co-ArNp for 24 h reduced worm motility, while 20 µg/ml resulted in 25-100% mortality of adult flukes within 48-72 h. Incubation of S. haematobium miracidia and cercariae with the molluscicidal co-ArNp (50% lethal concentration 7.5 µg/ml) killed all the free larval stages within 40 and 15 min, respectively. Also, exposure of B. truncatus adult snails to 20 ppm of the combined regimen caused a mortality rate of 100% within 24 h. CONCLUSIONS: Co-ArNp therapy has also shown encouraging activity against the other major human schistosome, S. haematobium, as well as its vector.


Subject(s)
Antimalarials/pharmacology , Artemisinins/pharmacology , Bulinus/drug effects , Naphthoquinones/pharmacology , Schistosoma haematobium/drug effects , Schistosomiasis haematobia/drug therapy , Animals , Disease Vectors , Larva/drug effects
9.
Trans R Soc Trop Med Hyg ; 112(12): 555-560, 2018 12 01.
Article in English | MEDLINE | ID: mdl-30265366

ABSTRACT

Background: Toxoplasma gondii is a global infection with a crucial role in the development of neurological diseases. Data concerning the association between T. gondii and neurological illnesses in Egyptian children is scarce. Methods: A case-control study was conducted on 60 patients divided into children suffering from central nervous system manifestations without apparent chromosomal anomalies (n=30) and children with Down syndrome (n=30) recruited from Mansoura University Children's Hospital, Mansoura, Egypt. A total of 30 healthy children were included as controls. Demographics and clinical data were collected from all cases and Toxoplasma immunoglobulin (Ig) M and G antibodies were assessed by enzyme-linked immunosorbent assay. Results: Anti-T. gondii IgG was the most frequent antibody detected and the highest seropositivity rates were ranked for the neurologically disabled non-syndromic children, followed by Down syndrome, compared with controls (p≤0.001). Statistically significant (p=0.05) associations were found between Toxoplasma IgG seropositivity and hydrocephalus and between Toxoplasma IgM and a history of contact with farm animals, soil and cats in children with Down syndrome. Conclusions: The association between Toxoplasma infection and neurological disorders in children should be kept in mind by paediatricians and assessment of T. gondii antibodies in early childhood is needed for timely management of afflicted patients.


Subject(s)
Central Nervous System Infections/epidemiology , Central Nervous System Infections/parasitology , Toxoplasma/pathogenicity , Toxoplasmosis/epidemiology , Animals , Animals, Domestic/parasitology , Case-Control Studies , Cats , Child, Preschool , Down Syndrome/epidemiology , Egypt/epidemiology , Female , Humans , Infant , Infant, Newborn , Male , Meat/parasitology , Milk/parasitology , Seroepidemiologic Studies
10.
Front Immunol ; 9: 1746, 2018.
Article in English | MEDLINE | ID: mdl-30105025

ABSTRACT

Schistosomes are parasitic flatworms that infect the vasculature of >200 million people around the world. These long-lived parasites do not appear to provoke blood clot formation or obvious inflammation around them in vivo. Proteins expressed at the host-parasite interface (such as Schistosoma mansoni alkaline phosphatase, SmAP) are likely key to these abilities. SmAP is a glycoprotein that hydrolyses the artificial substrate p-nitrophenyl phosphate in a reaction that requires Mg2+ and at an optimal pH of 9. SmAP additionally cleaves the nucleoside monophosphates AMP, CMP, GMP, and TMP, all with a similar Km (~600-650 µM). Living adult worms, incubated in murine plasma for 1 h, alter the plasma metabolome; a decrease in sphingosine-1-phosphate (S1P) is accompanied by an increase in the levels of its component parts-sphingosine and phosphate. To test the hypothesis that schistosomes can hydrolyze S1P (and not merely recruit or activate a host plasma enzyme with this function), living intravascular life-stage parasites were incubated with commercially obtained S1P and cleavage of S1P was detected. Parasites whose SmAP gene was suppressed using RNAi were impaired in their ability to cleave S1P compared to controls. In addition, recombinant SmAP hydrolyzed S1P. Since extracellular S1P plays key roles in controlling inflammation and platelet aggregation, we hypothesize that schistosome SmAP, by degrading S1P, can regulate the level of this bioactive lipid in the environment of the parasites to control these processes in the worm's local environment. This is the first report of any parasite being able to cleave S1P.


Subject(s)
Alkaline Phosphatase/metabolism , Host-Parasite Interactions/immunology , Lysophospholipids/metabolism , Schistosoma mansoni/enzymology , Schistosoma mansoni/immunology , Schistosomiasis mansoni/immunology , Schistosomiasis mansoni/parasitology , Signal Transduction , Sphingosine/analogs & derivatives , Alkaline Phosphatase/genetics , Animals , CHO Cells , Cricetulus , Disease Models, Animal , Gene Expression , Hemostasis , Male , Mice , Schistosoma mansoni/genetics , Schistosomiasis mansoni/metabolism , Sphingosine/metabolism
11.
Acta Trop ; 186: 16-23, 2018 Oct.
Article in English | MEDLINE | ID: mdl-29963994

ABSTRACT

Schistosomiasis is one of the most important tropical and subtropical devastating diseases, where praziquantel is the sole drug of choice. Praziquantel effectively kills the adult worms, however, drug resistance has been repeatedly reported. Moreover, there is currently no efficient anti-fibrotic therapy available for chronic schistosomiasis. So, novel drugs which exert anti-fibrotic efficacy are urgently needed. This research is complementary to our previous work that evaluated the anti-schistosomal effects of the anti-inflammatory vinpocetine, as well as the vasodilator and the anti-oxidant isosorbide-5-mononitrate. In the present study, we assessed the therapeutic efficacies of drugs in Swiss albino female mice experimentally infected with an Egyptian strain of Schistosoma mansoni, using some biochemical and immunohistochemical parameters. Our results revealed that both vinpocetine and isosorbide-5-mononitrate monotherapy significantly decreased hepatic nuclear factor-kappaB, 10 weeks post infection. The best effects were seen in mice administered praziquantel combined with isosorbide-5-mononitrate, as detected by reduction in hydroxyproline and collagen contents of the liver, and significant increase in the hepatic nitric oxide content. The data provides insight into the potential effects of the assessed drugs with isosorbide-5-mononitrate being more superior to vinpocetine, hence it can be used as novel adjuvant to praziquantel to alleviate schistosomal hepatic fibrosis. However, molecular mechanism/s and clinical trials are worthy to be scrutinized.


Subject(s)
Anthelmintics/pharmacology , Chemical and Drug Induced Liver Injury/pathology , Isosorbide Dinitrate/analogs & derivatives , Schistosoma mansoni/drug effects , Schistosomiasis mansoni/drug therapy , Vinca Alkaloids/pharmacology , Animals , Disease Models, Animal , Drug Resistance , Female , Immunohistochemistry , Isosorbide Dinitrate/pharmacology , Mice
12.
Thromb Haemost ; 118(6): 979-989, 2018 06.
Article in English | MEDLINE | ID: mdl-29669386

ABSTRACT

Schistosomes are intravascular parasitic platyhelminthes infecting > 200 million people globally and causing a debilitating disease, schistosomiasis. Despite the relatively large size of the adult worms and their disruption of blood flow, surprisingly, they do not appear to provoke thrombus formation around them in vivo. We hypothesize that proteins expressed at the host-parasite interface are key to this ability. Here, we functionally express an ectonucleotide pyrophosphatase/phosphodiesterase homologue, SmNPP5, that is expressed at the tegumental surface of intravascular Schistosoma mansoni. We report that SmNPP5, a known virulence factor for the worms, is a type one glycoprotein that cleaves the artificial substrate p-Nph-5'-TMP in a reaction that requires cations and at an optimal pH of 9. Using immunolocalization and enzyme activity measurements, we confirm that SmNPP5 is exclusively expressed at the host interactive surface of all intravascular life stages. SmNPP5 inhibits platelet aggregation in a dose-dependent manner, as measured by multiple electrode aggregometry (MEA) using whole blood. Inhibition is apparent when either collagen or adenosine diphosphate (ADP) is used as agonist but is lost following heat treatment of SmNPP5. Unlike its mammalian homologue, NPP5, the schistosome protein cleaves ADP and with a Km of 246 ± 34 µM. In sum, SmNPP5 is expressed in the intravascular environment where it can degrade ADP and act as an anticoagulant. In this manner, the protein likely helps limit blood clot formation around the worms in vivo to permit the parasites free movement within the vasculature.


Subject(s)
Apyrase/metabolism , Blood Platelets/physiology , Blood Vessels/parasitology , Helminth Proteins/metabolism , Platelet Aggregation Inhibitors/metabolism , Schistosoma mansoni/physiology , Schistosomiasis mansoni/metabolism , Adenosine Diphosphate/metabolism , Animals , Female , Humans , Male , Mice , Phosphoric Diester Hydrolases/genetics , Pyrophosphatases/genetics , Virulence Factors
13.
Acta Trop ; 176: 114-125, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28757393

ABSTRACT

Schistosomiasis is a remarkable public health problem in developing countries. Presently, praziquantel is the optional drug for all human schistosomiasis. Owing to the increased praziquantel resistance, there is an urgent need to develop new alternatives. This study aims at determining the anti-schistosomal and/or the hepatoprotective effects of the anti-inflammatory drug; vinpocetine, and the vasodilator and the nitric oxide donor; isosorbide-5-mononitrate, in comparison to praziquantel. In the present research, the therapeutic efficacies of these drugs were assessed in Swiss albino female mice (CD-I strain) experimentally infected with an Egyptian strain of Schistosoma mansoni, using some general, parasitological, and histopathological parameters. In this work, praziquantel significantly reduced worm burden and hepatic egg load, increased the percentage of dead eggs in the small intestine and decreased granuloma count, but did not reduce granuloma diameter. While, either vinpocetine or isosorbide-5-mononitrate monotherapy did not induce significant reduction in the worm count, hepatic egg load or shift in the oogram pattern, but significantly reduced granuloma count and diameter. Moreover, isosorbide-5-mononitrate significantly reduced hepatic inflammation and necrosis. The best results were obtained in the mice groups treated with isosorbide-5-mononitrate combined with praziquantel or vinpocetine. Our results point to vinpocetine and isosorbide-5-mononitrate as a convenient and promising adjuvant to praziquantel for ameliorating schistosomal liver pathology. Further studies are recommended to reveal the actual pathways responsible for the different activities of vinpocetine and isosorbide-5-mononitrate.


Subject(s)
Chemical and Drug Induced Liver Injury/prevention & control , Isosorbide Dinitrate/analogs & derivatives , Schistosoma mansoni/drug effects , Schistosomiasis mansoni/drug therapy , Vinca Alkaloids/therapeutic use , Animals , Drug Therapy, Combination , Egypt , Female , Isosorbide Dinitrate/administration & dosage , Isosorbide Dinitrate/therapeutic use , Mice , Praziquantel/therapeutic use , Vinca Alkaloids/administration & dosage
14.
Acta Trop ; 141(Pt A): 37-45, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25291045

ABSTRACT

Malaria and schistosomiasis are the two most important parasitic diseases in the tropics and sub-tropics with geographic overlap. Efforts have been made for developing new schistosomicidal drugs, or testing existing drugs originally used for non-related diseases. The antimalarial artemisinin-naphthoquine phosphate combination (CO-ArNp) was recently reported to be a promising novel antischistosomal therapy with potent in vivo activity against Schistosoma mansoni. In this work, we report the in vitro dose- and time-response effect of CO-ArNp against the Egyptian strain of S. mansoni, and its snail host, Biomphalaria alexandrina. Incubation of adult S. mansoni with CO-ArNp at 40 or 20 µg/ml for 48 or 72 h killed all worms. Exposure of S. mansoni miracidia and cercariae to the molluscicidal LC50 of CO-ArNp (16.8 µg/ml) resulted in 100% mortality of the free larval stages within 90 and 15 min, respectively. Moreover, incubation of adult B. alexandrina snails with this drug combination killed all snails at 40 µg/ml within 24h. Scanning electron microscope revealed marked morphological and tegumental alterations on the different stages of the parasite and its snail soft tissue. Our study highlights the schistosomicidal and molluscicidal effects of artemisinin-naphthoquine phosphate. No doubt more studies are needed to clarify its potential value to control schistosomiasis.


Subject(s)
Artemisinins/pharmacology , Biomphalaria/drug effects , Cercaria/drug effects , Naphthoquinones/pharmacology , Schistosoma mansoni/drug effects , Schistosomicides/pharmacology , Animals , Biomphalaria/parasitology , Biomphalaria/ultrastructure , In Vitro Techniques , Microscopy, Electron, Scanning , Schistosoma mansoni/ultrastructure
15.
Parasitol Res ; 112(12): 4221-9, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24096606

ABSTRACT

Currently, praziquantel is the only drug of choice for treatment of schistosomiasis. Reports of praziquantel resistance raise concerns about future control of the disease. Therefore, the search for new schistosomicidal drugs is eminent. In this study, the effect of a novel benzimidazole-derived compound (compound BTP-Iso) was assessed in mice harboring adult Schistosoma mansoni (Egyptian strain). Mice were treated 42 days p.i. with compound BTP-Iso using two treatment regimens (200 or 300 mg/kg). In both regimens, there were significant reductions in the number of recovered S. mansoni worms especially females and in immature ova, in addition to a significant reduction in the number and size of hepatic granulomata. A dose of 300 mg/kg resulted in a significant decrease in intestinal and hepatic tissue egg loads. Effect on schistosomes was confirmed by scanning electron microscopy, where adult worms recovered from mice treated with 200 mg/kg of compound BTP-Iso revealed tegumental alternations, characterised by swelling of tegumental ridges, bleb formation, and mild erosion in male worms; however in females, there were extensive erosion and destruction of the tegumental surface. These promising results may encourage future use of compound BTP-Iso in the treatment of schistosomiasis. However, more research is needed to detect the effect of compound BTP-Iso on early developmental stages of S. mansoni and on other species of human schistosomes.


Subject(s)
Benzimidazoles/pharmacology , Schistosoma mansoni/drug effects , Schistosomiasis mansoni/drug therapy , Schistosomicides/pharmacology , Animals , Female , Intestines/parasitology , Liver/parasitology , Liver/pathology , Male , Mice , Mice, Inbred BALB C , Microscopy, Electron, Scanning , Molecular Structure , Parasite Load , Schistosoma mansoni/ultrastructure , Schistosomicides/therapeutic use
16.
Exp Parasitol ; 135(2): 240-5, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23876575

ABSTRACT

The current treatment and control of schistosomiasis, rely on a single drug, praziquantel, although, it has minor activity against juvenile stages of the parasite. Studies have shown that artemether (ART) exhibits effects against juveniles of Schistosoma mansoni Liberian and Puerto Rican strains, Schistosoma japonicum and Schistosoma haematobium. Aiming to assess the in vivo activity of single oral dose of ART against early juvenile stages of S. mansoni Egyptian strain, this study was established. Mice were treated with ART (400 mg/kg) at two time points evenly spaced over the period of larval development (7 and 21 days post-infection; pi), and a third treatment point (day 49 pi) was included to elucidate when susceptibility decreases. Administration of ART on day 7 pi reduced the total worm burden by 85.94%. The greatest reductions were seen when treatment was given on day 21 pi, with total and female worm burden reductions of 91.52% and 90.57%, respectively, and cessation of oviposition. Similar dose given on day 49 pi reduced total worm burden by 55.17% and female worm burden by 66.51%. Moreover, it induced significant reduction in the tissue egg load and significant alterations in the oogram pattern with decreased immature eggs and increased dead eggs. Antipathological activities were evident in significant reductions in granulomata count and diameter. In conclusion, ART exhibits major in vivo schistosomicidal effects against the early larval migratory stages of S. mansoni Egyptian strain, mainly the 21-day old schistosomula, hence preventing disease progression and morbidity.


Subject(s)
Artemisinins/pharmacology , Schistosoma mansoni/drug effects , Schistosomiasis mansoni/drug therapy , Schistosomicides/pharmacology , Administration, Oral , Animals , Artemether , Biomphalaria , Female , Liver/pathology , Mice , Mice, Inbred BALB C , Schistosoma mansoni/growth & development , Schistosomiasis mansoni/pathology
17.
Parasit Vectors ; 6: 148, 2013 May 24.
Article in English | MEDLINE | ID: mdl-23705584

ABSTRACT

BACKGROUND: Strongyloides venezuelensis has been used as a tool and model for strongyloidiasis research. Elimination of S. venezuelensis adult worms from mice has been particularly associated with proliferation and activation of intestinal mast cells and eosinophils. To date, the role of B-cells in the protective mechanism against adult Strongyloides infection in experimental animals has not been reported in the literature. Therefore, the present study was carried to investigate the role of B-lymphocytes in immunity against adult S. venezuelensis infection using mice with a targeted deletion of the JH locus. METHODS: JHD knockout mice with its wild-type Balb/c mice were infected by intra-duodenal implantation of adult S. venezuelensis. Fecal egg count, intestinal worm recovery, mucosal mast cells and eosinophils were counted. RESULTS: At day 11 post infection, parasites in wild-type mice stopped egg laying, while in JHD knockout mice parasites continued to excrete eggs until the end of the observation period, day 107. The higher number of parasite eggs expelled in the feces of JHD knockout infected mice was a consequence of higher worm burdens, which established in the small intestine of these animals. On the other hand worm fecundity was comparable in both groups of mice. Both B-cell-deficient mice and wild-type mice, showed an influx of mucosal mast cells and eosinophils. The absolute numbers in JHD knockout mice were lower than those seen in wild-type mice at day 11, but not to a level of significance. JHD knockout mice could not recover from infection despite the recruitment of both types of cells. CONCLUSION: Our findings highlight a role of B cells in mucosal immunity against invasion of adult S. venezuelensis and in its expulsion. Therefore, we conclude that B-cells together with mucosal mast cells and eosinophils, contribute to immunity against adult S. venezuelensis by mechanism(s) to be investigated.


Subject(s)
B-Lymphocytes/immunology , Strongyloides/immunology , Strongyloidiasis/immunology , Animals , Disease Models, Animal , Eosinophils/immunology , Feces/parasitology , Immunity, Mucosal , Intestines/parasitology , Male , Mast Cells/immunology , Mice , Mice, Inbred BALB C , Parasite Egg Count
18.
Int J Parasitol ; 43(7): 521-30, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23500074

ABSTRACT

Praziquantel is the current drug of choice against schistosomiasis. The dependency on praziquantel exclusively is problematic, given the spread of the disease and the threat of drug resistance. This study investigates an alternative antischistosomal drug using the compound naphthoquine phosphate tablet, which is a novel single oral dose antimalarial drug, containing a combination of naphthoquine phosphate and artemisinin. In the present study, the therapeutic efficacies of different artemisinin-naphthoquine phosphate combination-dosing protocols were evaluated in experimentally infected mice harbouring juvenile or adult stages of Schistosoma mansoni (Egyptian strain). The study shows that the oral administration of artemisinin-naphthoquine phosphate combination in a single dose of 400 mg/kg on day 7 p.i. resulted in a significant worm burden reduction of 95.07%. When used at a dose of 600 mg/kg on day 21 p.i., all female worms were killed before depositing eggs, resulting in complete absence of eggs in hepatic and intestinal tissues. The same dose given on day 42 p.i. reduced total and female worm burdens by 93.36% and 94.17%, respectively. In addition, artemisinin-naphthoquine phosphate combination induced significant reductions of 80.18% and 76.73% in the hepatic and intestinal tissue egg loads, respectively. Artemisinin-naphthoquine phosphate combination also induced significant alterations in the oogram pattern with elevated levels of dead eggs. Antipathological activities were evident in the amelioration of hepatic granulomata. Our findings hold promise for the development of a novel antischistosomal drug using an artemisinin-naphthoquine phosphate combination. Further in vitro and in vivo studies should be launched to elucidate the possible mechanism/s of action and to study the effect of artemisinin-naphthoquine phosphate combination on other human schistosomes.


Subject(s)
Anthelmintics/administration & dosage , Artemisinins/administration & dosage , Naphthoquinones/administration & dosage , Schistosomiasis mansoni/drug therapy , Administration, Oral , Animals , Disease Models, Animal , Female , Histocytochemistry , Intestines/parasitology , Liver/parasitology , Mice , Mice, Inbred BALB C , Parasite Egg Count , Parasite Load , Schistosoma mansoni/isolation & purification , Treatment Outcome
19.
Parasitol Res ; 112(1): 373-7, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23052776

ABSTRACT

Conflicting reports are found in the literature about the antischistosomal efficacy of Mirazid (MZ), which is a special formulation of myrrh obtained from the stem of the plant Commiphora molmol. This initiated the present study to assess this drug for the first time in experimental schistosomiasis japonicum. Mice were divided into four groups: infected untreated control (I); infected treated with MZ, 500 mg/kg (II); infected treated with MZ, 250 mg/kg (III); and infected treated with praziquantel (PZQ), 200 mg/kg (IV). The drugs were given 7 weeks post-infection for five successive days. All animals were killed 3 weeks posttreatment. Results showed no signs of antibilharzial activity of MZ. Total worms, total tissue egg load, egg developmental stages, and granuloma area were not affected by any of the MZ treatment regimens as compared to the infected untreated group (P > 0.05 for all variables). These results were in contrast to those obtained in PZQ-treated animals in which 82.82 % total worm reduction, 94.62 % egg reduction, and 86.35 % granuloma area reduction were observed. Also, it significantly increased the percentage of dead ova and decreased the percentage of mature ova with complete absence of immature ones in comparison with the control group (P < 0.01 for all variables). In conclusion, the results of the current study raise serious doubts about the antischistosomal activity of MZ.


Subject(s)
Anthelmintics/administration & dosage , Plant Extracts/administration & dosage , Schistosoma japonicum/drug effects , Schistosomiasis japonica/drug therapy , Animals , Commiphora , Disease Models, Animal , Female , Male , Mice , Mice, Inbred C57BL , Parasite Load , Resins, Plant , Schistosomiasis japonica/parasitology , Schistosomiasis japonica/pathology , Treatment Outcome
20.
Parasitol Res ; 110(1): 1-18, 2012 Jan.
Article in English | MEDLINE | ID: mdl-21881948

ABSTRACT

Infectious myositis may be caused by a wide variety of bacterial, fungal, viral, and parasitic agents. Parasitic myositis is most commonly a result of trichinosis, cystericercosis, or toxoplasmosis, but other parasites may be involved. A parasitic cause of myositis is suggested by history of residence or travel to endemic area and presence of eosinophilia. The diagnosis of parasitic myositis is suggested by the clinical picture and radiologic imaging, and the etiologic agent is confirmed by parasitologic, serologic, and molecular methods, together with histopathologic examination of tissue biopsies. Therapy is based on the clinical presentation and the underlying pathogen. Drug resistance should be put into consideration in different geographic areas, and it can be avoided through the proper use of anti-parasitic drugs.


Subject(s)
Myositis/epidemiology , Myositis/parasitology , Parasites/isolation & purification , Parasitic Diseases/epidemiology , Parasitic Diseases/parasitology , Animals , Antiparasitic Agents/administration & dosage , Antiparasitic Agents/pharmacology , Drug Resistance , Humans , Myositis/diagnosis , Myositis/drug therapy , Parasites/pathogenicity , Parasitic Diseases/diagnosis , Parasitic Diseases/drug therapy
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