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1.
Front Immunol ; 11: 609994, 2020.
Article in English | MEDLINE | ID: mdl-33281832

ABSTRACT

Blood flukes of the genus Schistosoma are covered by a protective heptalaminated, double lipid bilayer surface membrane. Large amounts of sphingomyelin (SM) in the outer leaflet form with surrounding water molecules a tight hydrogen bond barrier, which allows entry of nutrients and prevents access of host immune effectors. Excessive hydrolysis of SM to phosphoryl choline and ceramide via activation of the parasite tegument-associated neutral sphingomyelinase (nSMase) with the polyunsaturated fatty acid, arachidonic acid (ARA) leads to parasite death, via allowing exposure of apical membrane antigens to antibody-dependent cell-mediated cytotoxicity (ADCC), and accumulation of the pro-apoptotic ceramide. Surface membrane nSMase represents, thus, a worm Achilles heel, and ARA a valid schistosomicide. Several experiments conducted in vitro using larval, juvenile, and adult Schistosoma mansoni and Schistosoma haematobium documented ARA schistosomicidal potential. Arachidonic acid schistosomicidal action was shown to be safe and efficacious in mice and hamsters infected with S. mansoni and S. haematobium, respectively, and in children with light S. mansoni infection. A combination of praziquantel and ARA led to outstanding cure rates in children with heavy S. mansoni infection. Additionally, ample evidence was obtained for the powerful ARA ovocidal potential in vivo and in vitro against S. mansoni and S. haematobium liver and intestine eggs. Studies documented ARA as an endogenous schistosomicide in the final mammalian and intermediate snail hosts, and in mice and hamsters, immunized with the cysteine peptidase-based vaccine. These findings together support our advocating the nutrient ARA as the safe and efficacious schistosomicide of the future.


Subject(s)
Antigens, Helminth/administration & dosage , Arachidonic Acid/therapeutic use , Cysteine Proteases/administration & dosage , Schistosoma/drug effects , Schistosomiasis/drug therapy , Schistosomicides/therapeutic use , Vaccines/administration & dosage , Animals , Antigens, Helminth/immunology , Arachidonic Acid/adverse effects , Arachidonic Acid/metabolism , Cysteine Proteases/immunology , Disease Models, Animal , Host-Parasite Interactions , Humans , Parasite Egg Count , Schistosoma/immunology , Schistosoma/pathogenicity , Schistosomiasis/immunology , Schistosomiasis/metabolism , Schistosomiasis/parasitology , Schistosomicides/adverse effects , Treatment Outcome , Vaccination , Vaccines/immunology
3.
East Mediterr Health J ; 20(10): 605-13, 2014 Oct 20.
Article in English | MEDLINE | ID: mdl-25356691

ABSTRACT

Hepatitis B and C virus (HBV and HCV) infections remain major public health problems in Egypt and data are needed on risk factors for infection. This study determined the prevalence of anti-HCV and HBV surface antigen seropositivity in Damietta Governorate, Egypt, and evaluated potential risk factors for infection and the impact of HBV vaccination on seroprevalence. A household, cross-sectional study was conducted of 2977 individuals. About 20% were vaccinated against HBV. Only 1.1% were infected with HBV and 9.3% with HCV; both infections coexisted in 12 people (0.4%) (all unvaccinated). The main risk factors for both HCV and HBV were exposure to dental procedures, surgery, stitches, schistosomiasis treatment and contact with infected person. HBV and HCV prevalences in Damietta were lower than the national rate, likely due to the routine compulsory HBV vaccination in those aged < 19 years. There is a need to educate the general population about HBV and HCV transmission routes and avoidance of risky behaviours.


Subject(s)
Hepatitis B/epidemiology , Hepatitis C/epidemiology , Schistosomicides/adverse effects , Surgical Procedures, Operative/adverse effects , Transfusion Reaction , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Cross-Sectional Studies , Egypt/epidemiology , Female , Hepatitis B/prevention & control , Hepatitis B/transmission , Hepatitis B Surface Antigens/blood , Hepatitis B Surface Antigens/immunology , Hepatitis B Vaccines/administration & dosage , Hepatitis C/prevention & control , Hepatitis C/transmission , Humans , Interviews as Topic , Male , Middle Aged , Oral Surgical Procedures/adverse effects , Risk Factors , Risk-Taking , Schistosomicides/therapeutic use , Seroepidemiologic Studies , Young Adult
4.
Am J Trop Med Hyg ; 87(6): 1065-72, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23091190

ABSTRACT

Abstract. The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) includes communitywide treatment in areas with ≥ 25% prevalence of schistosomiasis along the shores of Lake Victoria using community health workers (CHWs). The CHWs are key drivers in community-owned mass drug administration (MDA) intervention programs. We explored their experiences and perceptions after initial MDA participation. Unstructured open-ended group discussions were conducted after completion of MDA activities. Narratives were obtained from CHWs using a digital audio recorder during the group discussion, transcribed verbatim and translated into English where applicable. Thematic decomposition of data was done using ATLAS.t.i. software. From the perspective of the CHWs, factors influencing MDA compliance included drug side effects, food supply stability, and conspiracy theories about the "real" purpose of treatment. The interest of CHWs to serve as community drug distributors stemmed from both intrinsic and extrinsic factors. Feedback from CHWs can promote more effective MDA in rural Kenyan communities.


Subject(s)
Community Health Workers , Schistosomiasis/epidemiology , Schistosomiasis/prevention & control , Schistosomicides/therapeutic use , Adult , Female , Humans , Kenya/epidemiology , Male , Middle Aged , Schistosomiasis/drug therapy , Schistosomicides/administration & dosage , Schistosomicides/adverse effects , Young Adult
5.
J Travel Med ; 19(4): 264-7, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22776392

ABSTRACT

Paradoxical reactions (Jarish Herxheimer-like reactions) have been described in patients treated with praziquantel (PZQ) during acute schistosomiasis (infected≤ 3 mo), while PZQ treatment of chronic schistosomiasis is generally considered to be safe. We report an acute febrile reaction with respiratory decompensation following PZQ treatment in a 17-year-old male patient who had no potential (re)exposure to infection for at least 5 months and was therefore considered to have reached the chronic stage of disease. We speculate that the clinical manifestations in our patient constitute a very late paradoxical reaction in an unusually long acute phase of infection.


Subject(s)
Dyspnea/chemically induced , Praziquantel/adverse effects , Schistosomiasis/drug therapy , Schistosomicides/adverse effects , Acute Disease , Adolescent , Cough/chemically induced , Diagnosis, Differential , Fever/chemically induced , Humans , Male , Praziquantel/therapeutic use , Schistosomicides/therapeutic use
6.
Pharm Biol ; 50(9): 1144-50, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22486556

ABSTRACT

CONTEXT: Holothuria polii (H. polii) Linnaeus (Holothuriidae), Actinopyga mauritiana (A. mauritiana) Quoy & Gaimard (Holothuriidae) and Bohadschia vitiensis (B. vitiensis) Semper (Holothuriidae) are sea cucumbers inhabiting the coasts of Egypt. Their tegument and the cuvierian gland contained a substance called holothurin that was used in traditional medicine. These three species are abundant in the Egyptian coast, however there are no reports about their efficacy as antiparasitic agent. OBJECTIVE: The antischistosomal effect of the holothurin extracted from the three species of sea cucumber is investigated. MATERIALS AND METHODS: The ethanol extract was made from the tegument of both H. polii and A. mauritiana while it was made from the cuvierian gland of B. vitiensis. The body wall (or cuvierian gland) of the sea cucumber was blended with 95% ethanol in a volume = 4 × tissue weight. Extraction was done at room temperature for one day then filtered. The ethanol was removed by evaporation using Rotavapour (BÜCHI 461 water bath REIII) at 40°C. Later the aqueous residue was placed in a vacuum oven at 20°C for about 48 h to remove water. The resulting dried mass was then stored at -4°C until use. The percentage yield and the LD50 were calculated for each extract. Each extract was administered orally to Shistosoma mansoni infected mice in acute and chronic phases of infection. The dose of one-tenth of LD50 of each extract was administrated to mice (5.4, 62.2, and 10 mg/kg body weight/mouse for H. polii extract (HPE), A. mauritiana extract (AME), and cuvierian gland of B. vitiensis, respectively) for 24 h. The effects of each extract on the worm burden and total egg count was studied. The effects of each extract on the worm tegument using scanning electron microscope (SEM) were investigated in vivo and in vitro. RESULTS: The percentage yield of cuvierian gland extract (CGE) was higher (70%) than the tegument AME (33.4%) and HPE (9.3%). The 24 h LD50 of investigated sea cucumber ethanol extracts were 54.46, 627, and 100 mg/kg body weight/mouse for HPE, AME, and CGE. Oral administration of HPE caused decrease in male and female worm burden of 30-day infected mice to reach 60 and 90%, respectively. HPE decreased the egg count significantly in those mice with 30-day (1.75 egg counts/g tissue, p < 0.05) and 45-day (3.25 egg counts/g tissue, p < 0.05) infections. SEM studies of recovered worms from treated mice with all extracts showed different tegumental changes like formation of blebs, wrinkling, formation of numerous pores, and rupturing of some tubercles. These effects were more pronounced in those worms treated in vitro represented by severe shrinkage of the tegument, deformation of spines, rupturing, and collapsing of tubercles. DISCUSSION AND CONCLUSION: Results support the hypothesis that holothurin is a promising antischistosomal agent.


Subject(s)
Complex Mixtures/therapeutic use , Schistosoma mansoni/drug effects , Schistosomiasis mansoni/drug therapy , Schistosomicides/therapeutic use , Sea Cucumbers/chemistry , Animals , Complex Mixtures/adverse effects , Complex Mixtures/isolation & purification , Disease Progression , Egypt , Female , Holothuria/chemistry , Holothuria/growth & development , Indian Ocean , Lethal Dose 50 , Liver/drug effects , Liver/parasitology , Male , Medicine, African Traditional , Mediterranean Sea , Mice , Parasite Egg Count , Parasite Load , Schistosoma mansoni/isolation & purification , Schistosoma mansoni/ultrastructure , Schistosomiasis mansoni/parasitology , Schistosomiasis mansoni/physiopathology , Schistosomicides/adverse effects , Schistosomicides/isolation & purification , Sea Cucumbers/growth & development , Surface Properties
7.
Asian Pac J Trop Biomed ; 2(3): 235-9, 2012 Mar.
Article in English | MEDLINE | ID: mdl-23569905

ABSTRACT

OBJECTIVE: To evaluate the efficacy and side effects of praziquantel (PZQ) in the treatment of schistosomiasis in Ethiopia. METHODS: In a cross-sectional study, stool specimens were collected from randomly selected 299 school children in Shesha Kekele Elementary School, Wondo Genet, Southern Ethiopia, in April 2010. Stool specimens were examined using a single Kato-Katz thick smear for Schistosoma mansoni (S. mansoni) ova. Children who were found positive for S. mansoni were treated with a single oral dose of PZQ at 40 mg/kg bw and interviewed for treatment-related symptoms 24 hours after drug administration. Four weeks post-treatment, stool specimens were collected from the same children and examined following the same procedure as in the pre-treatment. Drug efficacy was determined based on cure and egg reduction rates. RESULTS: Pre-treatment prevalence of S. mansoni infection was 74.9% with geometric mean egg count of 268. The evaluated generic PZQ produced an overall cure rate of 73.6% (P<0.000 1, OR: 8.33, CI: 5.3-13.1) and egg reduction rate of 68.2% (P=0.03, F=0.64). The cure rate showed significant association with age (χ(2)=11, P=0.004), the highest rate being observed in the 15-22 age group. 83% of S. mansoni infected children showed various treatment-related symptoms, the most frequent being headache, nausea, and abdominal pain. These symptoms were associated with age (P<0.001) and pre-treatment intensity of infection (P<0.05). CONCLUSIONS: The present observations revealed relatively lower cure and egg reduction rates of the PZQ evaluated as compared to previous reports for other PZQ brands in Ethiopia. Hence, in depth studies are recommended to clarify whether the present relatively lower cure rate is the actual cure rate of the praziquantel evaluated, treatment failure, or reduced susceptibility of the parasite. Treatment-related side effects observed were transient and tolerable.


Subject(s)
Praziquantel/adverse effects , Praziquantel/therapeutic use , Schistosomiasis mansoni/drug therapy , Schistosomicides/adverse effects , Schistosomicides/therapeutic use , Adolescent , Adult , Child , Cross-Sectional Studies , Ethiopia/epidemiology , Feces/parasitology , Female , Humans , Male , Prevalence , Schistosomiasis mansoni/epidemiology , Schistosomiasis mansoni/parasitology , Students , Young Adult
8.
Parasitol Res ; 109(6): 1501-7, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21984370

ABSTRACT

Praziquantel, due to high efficacy, excellent tolerability, few and transient side effects, simple administration, and competitive cost, is virtually the only drug of choice for treatment of human schistosomiasis. Treatment of schistosomiasis has shown great advances with the introduction of the drug into the therapeutic arsenal in areas that are endemic for the parasite. However, the drug presents various efficacies against different developmental stages of schistosomes, appearing an oddity intermitted mode. The present review article reviews the effects and mechanism of action of praziquantel against schistosomes briefly and suggests the research on this oddity phenomenon.


Subject(s)
Praziquantel/pharmacology , Schistosoma/drug effects , Schistosomicides/pharmacology , Animals , Humans , Praziquantel/adverse effects , Praziquantel/therapeutic use , Schistosoma/growth & development , Schistosomiasis/drug therapy , Schistosomiasis/parasitology , Schistosomicides/adverse effects , Schistosomicides/therapeutic use
9.
Mem Inst Oswaldo Cruz ; 105(4): 445-8, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20721488

ABSTRACT

The efficacy of oral praziquantel in the treatment of schistosomiasis has been considered low by most public health institutions. In this paper, we compared the efficacy of two dosages of praziquantel (80 mg/kg vs. 50 mg/kg) in patients with chronic schistosomiasis mansoni. Two hundred eighty-eight patients with schistosomiasis from a community in Brazil were randomly divided into two groups: 145 patients (Group 1) received 80 mg/kg body weight of oral praziquantel divided in two equal doses with 1 h interval and 143 patients (Group 2) received 50 mg/kg body weight of oral praziquantel. To keep the study masked, patients in Group 2 received placebo 1 h after the first dose. All patients were subjected to clinical and ultrasonographic examination. Cure assessment was performed by repeating two stool examinations, by a quantitative method, at 30, 90 and 180 days after treatment. The morbidity of schistosomiasis was low, with a few cases of light periportal thickening and 16 cases of mild splenomegaly. The cure rates were 89.7% for Group 1 and 83.9% for Group 2. There was no difference in the efficacy of both therapeutic dosages of praziquantel assayed. The adverse reactions were more frequent with higher dosage.


Subject(s)
Praziquantel/administration & dosage , Schistosomiasis mansoni/drug therapy , Schistosomicides/administration & dosage , Administration, Oral , Adult , Chronic Disease , Dose-Response Relationship, Drug , Feces/parasitology , Female , Humans , Male , Parasite Egg Count , Praziquantel/adverse effects , Schistosomicides/adverse effects , Time Factors
10.
Mem. Inst. Oswaldo Cruz ; 105(4): 445-448, July 2010. tab
Article in English | LILACS | ID: lil-554810

ABSTRACT

The efficacy of oral praziquantel in the treatment of schistosomiasis has been considered low by most public health institutions. In this paper, we compared the efficacy of two dosages of praziquantel (80 mg/kg vs. 50 mg/kg) in patients with chronic schistosomiasis mansoni. Two hundred eighty-eight patients with schistosomiasis from a community in Brazil were randomly divided into two groups: 145 patients (Group 1) received 80 mg/kg body weight of oral praziquantel divided in two equal doses with 1 h interval and 143 patients (Group 2) received 50 mg/kg body weight of oral praziquantel. To keep the study masked, patients in Group 2 received placebo 1 h after the first dose. All patients were subjected to clinical and ultrasonographic examination. Cure assessment was performed by repeating two stool examinations, by a quantitative method, at 30, 90 and 180 days after treatment. The morbidity of schistosomiasis was low, with a few cases of light periportal thickening and 16 cases of mild splenomegaly. The cure rates were 89.7 percent for Group 1 and 83.9 percent for Group 2. There was no difference in the efficacy of both therapeutic dosages of praziquantel assayed. The adverse reactions were more frequent with higher dosage.


Subject(s)
Adult , Female , Humans , Male , Praziquantel , Schistosomiasis mansoni , Schistosomicides , Administration, Oral , Chronic Disease , Dose-Response Relationship, Drug , Feces , Parasite Egg Count , Praziquantel/adverse effects , Schistosomicides/adverse effects , Time Factors
11.
Parasitology ; 136(13): 1759-69, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19695107

ABSTRACT

Schistosomiasis is widespread in Uganda along large lakes and rivers with approximately 4 million people infected. Hookworm infections also prevalent throughout the country, while infections with Ascaris lumbricoides and Trichuris trichiura are mainly found in south-western Uganda. A national programme aimed at controlling morbidity due to these infections was launched in 2003. This article describes the perceptions, attitudes, constraints and experiences of those implementing the programme and those receiving the treatment. The study used qualitative data collected largely in two districts but also from 18 other districts implementing the programme. Results showed that mass treatment was perceived to be beneficial because the drugs make people feel better. However, side-effects of praziquantel (PZQ), the smell and size of the tablets and the use of height, not weight, to determine dose were raised as major factors discouraging people from taking the drug. Generally, most of the end-users were appreciative of the programme and were beginning to demand regular treatment. Nevertheless, intensive and sustained health education is still vital for improvement of treatment coverage, especially among the non-compliers. It was repeatedly highlighted that there is a need to stock PZQ in all health facilities in endemic areas. Provision of incentives to drug distributors and to involve as many stakeholders as possible in the planning phase were also raised by respondents. Lessons learned for the development and success of a helminth control programme at a national scale are discussed.


Subject(s)
National Health Programs/organization & administration , Schistosomiasis/epidemiology , Schistosomiasis/prevention & control , Communicable Disease Control , Data Collection , Health Knowledge, Attitudes, Practice , Humans , National Health Programs/standards , National Health Programs/trends , Patient Compliance , Schistosomiasis/drug therapy , Schistosomicides/administration & dosage , Schistosomicides/adverse effects , Schistosomicides/therapeutic use , Uganda/epidemiology
12.
PLoS Negl Trop Dis ; 3(1): e357, 2009.
Article in English | MEDLINE | ID: mdl-19159015

ABSTRACT

BACKGROUND: Praziquantel (PZQ) is the drug compound of choice in the control and treatment of schistosomiasis. PZQ is administered as a racemate, i. e. 1ratio1 mixture of enantiomers. The schistosomicidal activity arises from one PZQ-enantiomer, whereas the other enantiomer does not contribute to the activity. The WHO's Special Programme for Research and Training in Tropical Diseases (TDR) has assigned the low-cost preparation of pure schistosomicidal (-)-PZQ a key priority for future R&D on PZQ, but so far this transition has not happened. PZQ has two major administration drawbacks, the first being the high dose needed, and its well documented bitter and disgusting taste. Attempts of taste-masking by low-cost means have not been successful. We hypothesized that the non-schistosomicidal component in PZQ would be the main contributor to the unpleasant taste of the drug. If the hypothesis was confirmed, the two major administration drawbacks of PZQ, the high dose needed and its bitter taste, could be addressed in one go by removing the component contributing to the bitter taste. METHODS AND FINDINGS: PZQ was separated into its schistosomicidal and the non-schistosomicidal component, the absolute stereochemical configuration of (-)-PZQ was determined to be (R)-PZQ by X-ray crystallography, and the extent of bitterness was determined for regular racemic PZQ and the schistosomicidal component in a taste study in humans. FINDING: The schistosomicidal component alone is significantly less bitter than regular, racemic PZQ. CONCLUSION: Our hypothesis is confirmed. We propose to use only the pure schistosomicidal component of PZQ, offering the advantage of halving the dose and expectedly improving the compliance due to the removal of the bitter taste. Therefore, (R)-PZQ should be specifically suitable for the treatment of school-age children against schistosomiasis. With this finding, we would like to offer an additional incentive to the TDR's recommendation to switch to the pure schistosomicidal (R)-PZQ.


Subject(s)
Praziquantel/adverse effects , Praziquantel/chemistry , Schistosomiasis/drug therapy , Schistosomicides/adverse effects , Schistosomicides/chemistry , Taste , Child , Crystallography, X-Ray , Humans , Molecular Structure , Praziquantel/administration & dosage , Schistosomicides/administration & dosage , Stereoisomerism
13.
Trends Parasitol ; 23(4): 159-64, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17336160

ABSTRACT

Currently, schistosomes infect approximately 40 million women of child-bearing age, yet little is known about schistosome-associated morbidity in pregnant women and their offspring. Animal models indicate a deleterious effect of schistosome infection on maternal, fetal and neonatal outcomes. Case reports have documented maternal infection in association with poor birth outcomes, and two observational studies indicate that maternal schistosome infection might be associated with decreased birth weight. Rigorously identifying and quantifying the impact of schistosome infection on pregnancy outcomes with well-designed observational and treatment studies are crucial for improving birth outcomes in schistosome-endemic areas. In addition, studies that address the safety of praziquantel during pregnancy could lead to further adoption of the recent informal recommendation by the World Health Organization to treat schistosome-infected pregnant and lactating women.


Subject(s)
Praziquantel/adverse effects , Pregnancy Complications, Parasitic/epidemiology , Schistosomiasis/epidemiology , Schistosomicides/adverse effects , Animals , Female , Genitalia, Female/parasitology , Humans , Mice , Morbidity , Placenta/parasitology , Praziquantel/therapeutic use , Pregnancy , Pregnancy Outcome/epidemiology , Schistosoma/drug effects , Schistosoma/physiology , Schistosomiasis/drug therapy , Schistosomicides/therapeutic use
14.
Mem Inst Oswaldo Cruz ; 99(5 Suppl 1): 5-11, 2004.
Article in English | MEDLINE | ID: mdl-15486628

ABSTRACT

The way the researches established the lines of direction for considering fight against schistosomiasis on the double aspect of transmission and morbidity control is outstanding. Chemotherapy in the morbidity control is emphasized. The research priorities for schistosomiasis control are mentioned.


Subject(s)
Biomedical Research , Endemic Diseases/prevention & control , Schistosomiasis/prevention & control , Age Distribution , Animals , Brazil/epidemiology , Humans , Prevalence , Schistosomiasis/epidemiology , Schistosomiasis/transmission , Schistosomicides/adverse effects , Schistosomicides/therapeutic use
15.
Ann Trop Med Parasitol ; 98(5): 491-9, 2004 Jul.
Article in English | MEDLINE | ID: mdl-15257799

ABSTRACT

The efficacy and tolerability of oral artesunate for the treatment of urinary schistosomiasis was assessed among schoolchildren aged 5-18 years in Adim community, Nigeria. Overall, 500 children, randomly selected from those attending the Presbyterian primary school, were each invited to provide two consecutive urine samples. Using standard parasitological procedures, Schistosoma haematobium ova were found in the samples from 145 (29.0%) of the subjects. Most (87) of the infected subjects were then treated orally with artesunate, using two doses, each of 6 mg/kg, given 2 weeks apart. When the treated children were re-examined 4 weeks after the second dose of artesunate, 61 (70.1%) appeared egg-negative and were therefore considered cured. Post-treatment, the geometric mean egg count (GMEC) for the treated subjects who were not cured was significantly lower than the pre-treatment GMEC for all the treated subjects, with log10[(eggs/10 ml urine) + 1] values of 0.9 v. 1.75 (t = 4.45; P < 0.05). The cure 'rate' for the subjects aged > or = 10 years was slightly higher than that among the younger subjects. It was lowest for the heavier subjects (70% for those weighing 41-50 kg) and highest (79%) for the subjects who weighed 31-40 kg. The artesunate was well tolerated. This observation of a therapeutic effect of artesunate against S. haematobium in Nigeria confirms recent observations from Senegal. In the Adim community at least, it would be more cost-effective to treat urinary schistosomiasis with artesunate than with praziquantel. The wide-spread use of artesunate against schistosomiasis has to be considered carefully, however, if it is not to compromise the efficacy of the drug as an antimalarial, by increasing the risk of resistance developing in local Plasmodium.


Subject(s)
Artemisinins/therapeutic use , Endemic Diseases , Schistosomiasis haematobia/drug therapy , Schistosomicides/therapeutic use , Sesquiterpenes/therapeutic use , Adolescent , Animals , Artemisinins/adverse effects , Artemisinins/economics , Artesunate , Child , Child, Preschool , Cost-Benefit Analysis , Drug Costs , Female , Humans , Male , Nigeria/epidemiology , Parasite Egg Count , Praziquantel/economics , Schistosoma haematobium/isolation & purification , Schistosomiasis haematobia/epidemiology , Schistosomiasis haematobia/parasitology , Schistosomicides/adverse effects , Schistosomicides/economics , Sesquiterpenes/adverse effects , Sesquiterpenes/economics , Treatment Outcome
16.
J Egypt Soc Parasitol ; 34(1): 1-21, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15125513

ABSTRACT

In the present work, the efficacy of purified oloe-resin extract of myrrh derived from Commiphora molmol tree (commercially known as Mirazid) as a new, natural antischistosomal drug was investigated. The effect of myrrh on the ultrastructural profile of the non infected normal mice liver was also studied. Sixty male mice were used throughout this work and they were divided into 3 main groups (20 animals each): group I, non infected control animals, group II, infected animals and group III, infected animals treated with myrrh extract 8 weeks post infection (500 mg/kg body weight). The drug was given orally on an empty stomach after overnight fasting for five successive days. All animals were sacrificed after 12 weeks from the beginning of the experiment and small pieces of the liver were excised and prepared for ultrastructural study. The liver of the non infected animals which received myrrh extract (group IA) showed a more or less normal ultrastructural profile. Infected groups showed alterations of the ultrastructure of most of the hepatocytes with extensive intercellular fibrosis with abundant granulomas in the portal tract. In the infected treated group, most of the hepatocytes showed normal organelles with numerous microvilli extending into patent spaces of Disse. Marked reduction of granulomas in the portal areas and amelioration of intercellular fibrosis was also observed. On the basis of the observed results, it was concluded that myrrh extract has a promising antischistosomal non hepatotoxic activity.


Subject(s)
Commiphora , Liver/drug effects , Phytotherapy , Plant Extracts/pharmacology , Schistosomiasis/drug therapy , Schistosomicides/pharmacology , Animals , Disease Models, Animal , Liver/parasitology , Liver/ultrastructure , Male , Mice , Plant Extracts/adverse effects , Random Allocation , Schistosomicides/adverse effects , Terpenes/adverse effects , Terpenes/pharmacology , Treatment Outcome
17.
Zhonghua Yi Xue Za Zhi ; 83(14): 1219-24, 2003 Jul 25.
Article in Chinese | MEDLINE | ID: mdl-12930634

ABSTRACT

OBJECTIVE: To assess the benefits and harms of artemisinin-type compounds for preventing schistosomiasis. METHOD: The quality of included randomised controlled trials with the people at risk of contacting schistosomiasis were evaluated and Meta-analysis was conducted. RESULTS: We found ten randomised controlled trials relating to our question. Of them, four trials were multi-centre studies, others were single centre studies. Numbers of participants in the trials ranged from 318 to 5,098, total 12,829. The total OR of 0.11 (95% CI 0.06 to 0.21) indicated that those who were administrated artemisinin-type compounds were significantly less infected with Schistosoma japonica than those who were administrated placebo. CONCLUSION: Artemisinin-type compounds are effective drug for preventing Schistosomiasis japonica infection. Fifteen days interval schemes of artesunate and artemether be considered preferable to seven days interval scheme and were associated with very few side effects. More high quality controlled trials are required for assessing which scheme is the better. These studies should be large.


Subject(s)
Artemisinins/therapeutic use , Schistosomiasis japonica/prevention & control , Schistosomicides/therapeutic use , Sesquiterpenes/therapeutic use , Adult , Artemether , Artemisinins/adverse effects , Artesunate , Double-Blind Method , Female , Humans , Male , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Schistosomicides/adverse effects , Sesquiterpenes/adverse effects
18.
Am J Trop Med Hyg ; 68(1): 24-32, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12556143

ABSTRACT

Artemether is an efficacious antimalarial drug that also displays antischistosomal properties. Laboratory studies have found that artemether curtails the development of adult worms of Schistosoma japonicum, S. mansoni and S. haematobium, and thus prevents morbidity. These findings have been confirmed in clinical trials for the former two parasites; administered orally once every 2-3 weeks, artemether significantly reduced the incidence and intensity of patent infections. Here, we present the first randomized, double-blind, placebo-controlled trial of artemether against S. haematobium, done in a highly endemic area of Côte d'Ivoire. Urine specimens from 440 schoolchildren were examined over 4 consecutive days, followed by two systematic praziquantel treatments 4 weeks apart. S. haematobium-negative children were randomized to receive 6 mg/kg artemether (N = 161) or placebo (N = 161). Medication was administered orally for a total of six doses once every 4 weeks. Adverse events were assessed 72 hours after medication, and perceived illness episodes were monitored throughout the study period. Incidence and intensity of S. haematobium infections, and microhematuria and macrohematuria were assessed 3 weeks after the final dosing. We also monitored malaria parasitemia and treated positive cases with sulfadoxine-pyrimethamine (SP). Oral artemether was well tolerated. The incidence of patent S. haematobium infections in artemether recipients was significantly lower than in placebo recipients (49% versus 65%, protective efficacy: 0.25, 95% CI: 0.08-0.38, P = 0.007). The geometric mean infection intensity in the artemether group was less than half that of the placebo recipients (3.4 versus 7.4 eggs/10 mL urine, P < 0.001). Heavy S. haematobium infections, microhematuria and macrohematuria, and the incidence of malaria parasitemia were all significantly lower in artemether recipients. In conclusion, previous findings of efficacy of artemether against S. japonicum and S. mansoni were confirmed for S. haematobium, although the protective efficacy was considerably lower. These findings enlarge the scope and potential of artemether and further contribute to discussions of its role as an additional tool for integrated schistosomiasis control.


Subject(s)
Artemisinins/therapeutic use , Schistosomiasis haematobia/prevention & control , Schistosomicides/therapeutic use , Sesquiterpenes/therapeutic use , Administration, Oral , Adolescent , Artemether , Artemisinins/administration & dosage , Artemisinins/adverse effects , Capsules , Child , Child, Preschool , Cote d'Ivoire/epidemiology , Double-Blind Method , Female , Fresh Water , Humans , Incidence , Male , Parasite Egg Count , Schistosomiasis haematobia/epidemiology , Schistosomicides/administration & dosage , Schistosomicides/adverse effects , Sesquiterpenes/administration & dosage , Sesquiterpenes/adverse effects , Urine/parasitology
19.
Acta Trop ; 82(2): 175-81, 2002 May.
Article in English | MEDLINE | ID: mdl-12020890

ABSTRACT

Two decades ago, a group of Chinese scientists discovered the antischistosomal properties of artemether, a derivative of the antimalarial drug artemisinin. However, it was only recently that the importance of this finding was recognized internationally, following a collaborative effort between Chinese, European and African scientists, who investigated the effects of artemether against the major human schistosome species. Laboratory studies revealed that artemether exhibits the highest activity against juvenile stages of the parasites, while adult worms are significantly less susceptible. There was no indication of neurotoxicity following repeated high doses of artemether given fortnightly for up to 5 months. Randomized controlled clinical trials confirmed that artemether, orally administered at a dose of 6 mg/kg once every 2-3 weeks, results in no drug-related adverse effects, and significantly reduces the incidence and intensity of schistosome infections. The risk that these treatment regimens might select for resistance, particularly for resistant-plasmodia, appears to be low. Combined treatment with artemether and praziquantel, given to animals harbouring juvenile and adult schistosome worms, resulted in significantly higher worm burden reductions than each drug administered singly. In conclusion, artemether-integrated with other control strategies-has considerable potential for reducing the current burden of schistosomiasis in different epidemiological settings.


Subject(s)
Artemisinins , Praziquantel/therapeutic use , Schistosoma japonicum/drug effects , Schistosomiasis , Schistosomicides/therapeutic use , Sesquiterpenes/therapeutic use , Administration, Oral , Animals , Artemether , Drug Resistance , Drug Therapy, Combination , Humans , Praziquantel/administration & dosage , Praziquantel/adverse effects , Randomized Controlled Trials as Topic , Schistosomiasis/drug therapy , Schistosomiasis/prevention & control , Schistosomicides/administration & dosage , Schistosomicides/adverse effects , Sesquiterpenes/administration & dosage , Sesquiterpenes/adverse effects
20.
Int J Parasitol ; 32(4): 461-71, 2002 Apr.
Article in English | MEDLINE | ID: mdl-11849642

ABSTRACT

The present study using a murine model heavily infected with Schistosoma japonicum aimed to elucidate the pathogenesis of adverse effects of praziquantel treatment of schistosome-infected subjects. Inbred BALB/c mice were infected with S. japonicum (Yamanashi strain) before being treated with a single dose of praziquantel at 4 or 8 weeks p.i. All the mice treated at 8 weeks p.i. exhibited signs typical of systemic anaphylaxis until half of them died shortly after praziquantel administration. At autopsy, these mice exhibited remarkable intestinal alterations characterised by increased mucosal permeability, mucosal oedema and petechial haemorrhage, which are changes typical of immediate intestinal anaphylaxis. In these mice treated at 8 weeks p.i., degranulation of intestinal mast cells was frequently observed, which was particularly remarkable around S. japonicum eggs hatched as an effect of praziquantel. Furthermore, the plasma histamine concentration just after praziquantel treatment was much higher in mice at 8 weeks p.i. than that in uninfected mice or in S. japonicum-infected mice without drug treatment. In contrast, none of these intestinal changes was observed in untreated or uninfected control mice, or in mice administered praziquantel at 4 weeks p.i., in which worm pairs had just reached sexual maturation and begun egg-laying. The finding by ELISA that serum IgM and IgA levels specific to S. japonicum eggs decreased immediately after praziquantel treatment, together with the results of immunohistochemistry, revealed the sudden release of parasite antigens from the eggs hatched by praziquantel treatment. The results of this study demonstrate that adverse effects of praziquantel treatment of schistosomiasis characterised by abdominal signs depend on anaphylactic reactions due to parasite antigens, especially antigens from eggs hatched as an effect of praziquantel.


Subject(s)
Anaphylaxis/etiology , Antigens, Helminth/immunology , Praziquantel/adverse effects , Schistosoma japonicum/immunology , Schistosomiasis japonica/drug therapy , Schistosomicides/adverse effects , Animals , Antibodies, Helminth/blood , Disease Models, Animal , Female , Humans , Immunohistochemistry , Intestine, Small/parasitology , Mice , Mice, Inbred BALB C , Ovum/immunology , Parasite Egg Count , Praziquantel/therapeutic use , Schistosoma japonicum/drug effects , Schistosoma japonicum/growth & development , Schistosomiasis japonica/immunology , Schistosomiasis japonica/parasitology , Schistosomicides/therapeutic use
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