The schistosomicidal activity of ethanolic extracts from branches, leaves, flowers and fruits of Handroanthus impetiginosus (Mart. ex DC.) Mattos (Bignoniaceae) plant and metabolic profile characterization by UPLC-ESI-QTOF analysis.

Schistosomiasis, caused by Schistosoma mansoni Sambon, 1907, is a severe and widely distributed parasitic disease, affecting about 200 million people worldwide. The disease is recognized by elevated mortality rates, especially among those living in areas of poor sanitation. Currently, the chemotherapeutic treatment is solely based on using the praziquantel drug. Therefore, there is a need for the discovery of new medicines for the treatment of this parasitosis. Thus, this work aimed to evaluate the schistosomicidal activity of ethanolic crude extracts from the branches, leaves, flowers, and fruits of Handroanthus impetiginosus (Mart ex DC.) Masttos and characterize its metabolic profile by UPLC-ESI-QTOF analysis. Evaluation of plant extract on S. mansoni was carried out in adult worms in vitro, in which the mortality rate was quantified, and the damages in the tegument of the worms were monitored. All extracts induced changes in the viability of adult males of S. mansoni, causing the death of the parasites, which was directly dependent of the concentration.

Plant-derived compounds for the treatment of schistosomiasis: Improving efficacy via nano-drug delivery.

Schistosomiasis is a neglected infectious tropical disease that is second in occurrence only to hookworm infection in sub-Saharan Africa. Presently, chemotherapy is the main method of control and treatment of this disease due to the absence of a vaccine. However, Praziquantel, which is the only chemotherapeutic option, lacks efficacy against the early developmental stages of schistosomes. A number of plant-derived compounds, including alkaloids, terpenes and phenolics, have displayed in vitro and in vivo efficacy against Schistosoma species. This review explores how the application of nanotechnology can improve the efficacy of these plant-derived schistosomicidal compounds through the use of nano-enabled drug delivery systems to improve bioavailability.

Schistosomicidal and hepatoprotective activity of gamma-aminobutyric acid (GABA) alone or combined with praziquantel against Schistosoma mansoni infection in murine model.

OBJECTIVE: This study aimed to evaluate the efficacy of gamma-aminobutyric acid (GABA) alone or combined with praziquantel (PZQ) against Schistosoma (S) mansoni infection in a murine model. METHODS: Five groups, 8 mice each, were studied; GI served as normal controls; GII: S. mansoni-infected control group and the other three S. mansoni-infected groups received drug regimens for 5 consecutive days as follows GIII: Infected-PZQ treated group (200 mg/kg/day); GIV: Infected-GABA treated group (300 mg/kg/day) and GV: Infected-PZQ-GABA treated group (100 mg/kg/day for each drug). All animal groups were sacrificed two weeks later and different parasitological, histopathological and biochemical parameters were assessed. RESULTS: Combined GABA-PZQ treated group recorded the highest significant reduction in all parasitological, histopathological and biochemical parameters followed by PZQ and finally GABA groups. Combined GABA-PZQ treatment led to the complete disappearance of immature eggs and marked reduction of deposited eggs in liver tissues and improved liver pathology. Significant improvement in hepatic oxidative stress levels, serum albumin and total protein in response to GABA treatment alone or combined with PZQ. CONCLUSION: GABA had schistosomicidal, hepatoprotective and antioxidant activities against S. mansoni infection, GABA disrupted parasite pairing and activity, reduced the total number of worms recovered and the number of ova in the tissues. GABA may be considered an adjuvant therapy to potentiate PZQ antiparasitic activity and eradicate infection-induced liver damage and oxidative stress.

Parasitological and Biochemical Efficacy of the Active Ingredients of Allium sativum and Curcuma longa in Schistosoma mansoni Infected Mice.

The active ingredients allicin and curcumin have a wide range of actions against fungi, bacteria, and helminths. Therefore, the study was aimed to evaluate the efficacy of allicin (AL) and curcumin (CU) as antischistosomal drugs and their biochemical effects in normal and Schistosoma mansoni-infected mice. Praziquantel (PZQ) was administrated for two successive days while AL or CU was given for two weeks from the week 7th postinfection (PI). The possible effect of different regimens on Schistosoma worms was evaluated by measuring the percentage of the recovered worms, tissue egg load, and oogram pattern. Serum alanine transaminase activity and levels of triglycerides, cholesterol, and uric acid were measured. Liver tissue malondialdehyde and reduced glutathione levels besides, the activities of glutathione-S-transferase, superoxide dismutase and catalase were assessed for the oxidative/antioxidant condition. DNA electrophoresis of liver tissue was used to indicate the degree of fragmentation. There was a significant reduction in the recovered worms and egg load, with a marked change of oogram pattern in all treated groups with PZQ, AL, and CU in comparison with infected-untreated mice. PZQ, AL, and CU prevented most of the hematological and biochemical disorders, as well as significantly improved the antioxidant capacity and enhanced DNA fragmentation in the liver tissue of schistosomiasis mice compared to the infected-untreated group. These promising results suggest that AL and CU are efficient as antischistosomal drugs, and it would be beneficial to test their combination to understand the mechanism of action and the proper period of treatment leading to the best result.

Antiparasitic activity of piplartine (piperlongumine) in a mouse model of schistosomiasis.

Schistosomiasis is one of the most important parasitic infections in terms of its negative effects on public health and economics. Since praziquantel is currently the only drug available to treat schistosomiasis, there is an urgent need to identify new anthelmintic agents. Piplartine, also known as piperlongumine, is a biologically active alkaloid/amide from peppers that can be detected in high amounts in the roots of Piper tuberculatum. Previously, it has been shown to have in vitro schistosomicidal effects. However, its anthelmintic activity in an animal host has not been reported. In the present work, in vivo antischistosomal properties of isolated piplartine were evaluated in a mouse model of schistosomiasis infected with either adult (patent infection) or juvenile (pre-patent infection) stages of Schistosoma mansoni. A single dose of piplartine (100, 200 or 400 mg/kg) or daily doses for five consecutive days (100 mg/kg/day) administered orally to mice infected with schistosomes resulted in a reduction in worm burden and egg production. Treatment with the highest piplartine dose (400 mg/kg) caused a significant reduction in a total worm burden of 60.4% (P < 0.001) in mice harbouring adult parasites. S. mansoni egg production, a process responsible for pathology in schistosomiasis, was also significantly inhibited by piplartine. Studies using scanning electron microscopy revealed substantial tegumental alterations in parasites recovered from mice. Since piplartine has well-characterized mechanisms of toxicity, is easily available, and is cost-effective, our results indicate that this bioactive molecule derived from medicinal plants could be a potential lead compound for novel antischistosomal agents.

Community perceptions of mass drug administration for soil-transmitted helminthiasis and schistosomiasis in selected schools in the Philippines.

BACKGROUND: Soil-transmitted helminthiasis (STH) and schistosomiasis are parasitic infections prevalent in tropical and subtropical countries, such as the Philippines. The prevalence of these infections remain high in certain Philippine provinces, despite established mass drug administration (MDA) programs in endemic communities. This study aimed to understand community knowledge and perceptions of these infections to determine their implications on the current control and elimination strategies, including possible barriers to MDA compliance. METHODS: The study was conducted in Northern Samar and Sorsogon, two provinces with the highest STH and schistosomiasis prevalence in the country. Focus group discussions with separate parent and children groups were utilized to gather knowledge and perceptions on STH and schistosomiasis causes, symptoms, treatment, and prevention; and on the deworming drugs and overall program implementation. Data collection in Northern Samar were done in August 2017, while the sessions in Sorsogon took place in May 2018. A cultural construction of disease framework will show how several factors affect MDA participation. RESULTS: Results showed that participants held mostly correct biomedical notions of the infections and expressed willingness to participate in MDA program. However, reservations remained due to a reported lack of information dissemination, lack of confidence in the drugs used, and widespread fear of adverse side effects. CONCLUSION: Addressing these concerns - improving the conduct of the deworming program, incorporating suggestions from the community, and managing potential adverse events - may help raise MDA participation and encourage better personal preventive practices, reducing STH and schistosomiasis prevalence. TRIAL REGISTRATION: N/A.

Screening a repurposing library, the Medicines for Malaria Venture Stasis Box, against Schistosoma mansoni.

BACKGROUND: The development of new treatments against schistosomiasis is imperative but lacks commercial interest. Drug repurposing represents a suitable strategy to identify potential treatments, which have already unblocked several essential steps along the drug development path, hence reducing costs and timelines. Promoting this approach, the Medicines for Malaria Venture (MMV) recently distributed a drug repurposing library of 400 advanced lead candidates (Stasis Box). METHODS: All 400 compounds were initially tested in vitro against the larval stage of Schistosoma mansoni at 10 µM. Hits progressed to screening on adult worms and were further characterised for IC50, cytotoxicity and selectivity. Ten lead compounds were tested in mice harbouring a chronic S. mansoni infection. RESULTS: Eleven of the 37 compounds active on the larval stage were also highly active on adult worms in vitro (IC50 = 2.0-7.5 µM). IC50 values on adult S. mansoni decreased substantially in the presence of albumin (7.5-123.5 µM). Toxicity to L6 and MRC cells was moderate. A moderate worm burden reduction of 51.6% was observed for MMV690534, while the other 9 compounds showed low activity. None of the in vivo results were statistically significant (P > 0.05). CONCLUSIONS: Phenotypic screening of advanced lead compounds is a simple and resource-low method to identify novel anthelminthics. None of the promising hits of the Stasis Box identified in vitro against S. mansoni yielded acceptable worm burden reductions in vivo, which might be due to the high plasma protein binding. Since the in vitro hits interfere with different drug targets, they might provide a starting point for target based screening and structure-activity relationship studies.

Drugs for treating Schistosoma mansoni infection.

BACKGROUND: Schistosoma mansoni is a parasitic infection common in the tropics and sub-tropics. Chronic and advanced disease includes abdominal pain, diarrhoea, blood in the stool, liver cirrhosis, portal hypertension, and premature death. OBJECTIVES: To evaluate the effects of antischistosomal drugs, used alone or in combination, for treating S. mansoni infection. SEARCH METHODS: We searched MEDLINE, EMBASE and LILACS from inception to October 2012, with no language restrictions. We also searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2012) and mRCT. The reference lists of articles were reviewed and experts were contacted for unpublished studies. SELECTION CRITERIA: Randomized controlled trials of antischistosomal drugs, used alone or in combination, versus placebo, different antischistosomal drugs, or different doses of the same antischistosomal drug for treating S. mansoni infection. DATA COLLECTION AND ANALYSIS: One author extracted data and assessed eligibility and risk of bias in the included studies, which were independently checked by a second author. We combined dichotomous outcomes using risk ratio (RR) and continuous data weighted mean difference (WMD); we presented both with 95% confidence intervals (CI). We assessed the quality of evidence using the GRADE approach. MAIN RESULTS: Fifty-two trials enrolling 10,269 participants were included. The evidence was of moderate or low quality due to the trial methods and small numbers of included participants.Praziquantel: Compared to placebo, praziquantel 40 mg/kg probably reduces parasitological treatment failure at one month post-treatment (RR 3.13, 95% CI 1.03 to 9.53, two trials, 414 participants, moderate quality evidence). Compared to this standard dose, lower doses may be inferior (30 mg/kg: RR 1.52, 95% CI 1.15 to 2.01, three trials, 521 participants, low quality evidence; 20 mg/kg: RR 2.23, 95% CI 1.64 to 3.02, two trials, 341 participants, low quality evidence); and higher doses, up to 60 mg/kg, do not appear to show any advantage (four trials, 783 participants, moderate quality evidence).The absolute parasitological cure rate at one month with praziquantel 40 mg/kg varied substantially across studies, ranging from 52% in Senegal in 1993 to 92% in Brazil in 2006/2007. Oxamniquine: Compared to placebo, oxamniquine 40 mg/kg probably reduces parasitological treatment failure at three months (RR 8.74, 95% CI 3.74 to 20.43, two trials, 82 participants, moderate quality evidence). Lower doses than 40 mg/kg may be inferior at one month (30 mg/kg: RR 1.78, 95% CI 1.15 to 2.75, four trials, 268 participants, low quality evidence; 20 mg/kg: RR 3.78, 95% CI 2.05 to 6.99, two trials, 190 participants, low quality evidence), and higher doses, such as 60 mg/kg, do not show a consistent benefit (four trials, 317 participants, low quality evidence).These trials are now over 20 years old and only limited information was provided on the study designs and methods. Praziquantel versus oxamniquine: Only one small study directly compared praziquantel 40 mg/kg with oxamniquine 40 mg/kg and we are uncertain which treatment is more effective in reducing parasitological failure (one trial, 33 participants, very low quality evidence). A further 10 trials compared oxamniquine at 20, 30 and 60 mg/kg with praziquantel 40 mg/kg and did not show any marked differences in failure rate or percent egg reduction.Combination treatments: We are uncertain whether combining praziquantel with artesunate reduces failures compared to praziquantel alone at one month (one trial, 75 participants, very low quality evidence).Two trials also compared combinations of praziquantel and oxamniquine in different doses, but did not find statistically significant differences in failure (two trials, 87 participants). Other outcomes and analyses: In trials reporting clinical improvement evaluating lower doses (20 mg/kg and 30 mg/kg) against the standard 40 mg/kg for both praziquantel or oxamniquine, no dose effect was demonstrable in resolving abdominal pain, diarrhoea, blood in stool, hepatomegaly, and splenomegaly (follow up at one, three, six, 12, and 24 months; three trials, 655 participants).Adverse events were not well-reported but were mostly described as minor and transient.In an additional analysis of treatment failure in the treatment arm of individual studies stratified by age, failure rates with 40 mg/kg of both praziquantel and oxamniquine were higher in children. AUTHORS' CONCLUSIONS: Praziquantel 40 mg/kg as the standard treatment for S. mansoni infection is consistent with the evidence. Oxamniquine, a largely discarded alternative, also appears effective.Further research will help find the optimal dosing regimen of both these drugs in children.Combination therapy, ideally with drugs with unrelated mechanisms of action and targeting the different developmental stages of the schistosomes in the human host should be pursued as an area for future research.

Effects of garlic on Schistosoma mansoni harbored in albino mice: molecular characterization of the host and parasite.

Garlic has been used for its health benefits for thousands of years. Modern research confirmed many of the healing properties of garlic, including its antiparasitic activity. This study was designed to evaluate the antischistosomal action of garlic through detecting the changes in DNA profile of Schistosoma mansoni worms and the infected mouse. Forty mice were subcutaneously infected with ~200 Schistosoma mansoni cercariae/mouse. Infected mice were divided into four equal groups: non-treated, prophylactic, therapeutic, and continuously-treated. Non-infected control and garlic-treated groups were assigned for the sake of comparison. Garlic extract (50mg/kg bw/mouse) was given orally, day after day, at a fixed daytime. Seven weeks post-infection, adult schistosomes were recovered by perfusion and the livers of the mice were excised out and were processed for DNA extraction and Random Amplification of Polymorphic DNA-Polymerase Chain Reaction (RAPD-PCR). The results showed that garlic exerted no major changes in the genome of schistosomes. Nevertheless, that schistosomal infection induced genetic alterations in the DNA of mice, and garlic was able to ameliorate such alterations to a great extent.

Fungal transformation and schistosomicidal effects of pimaradienoic acid.

The schistosomicidal effects of pimaradienoic acid (PA) and two derivatives, obtained by fungal transformation in the presence of Aspergillus ochraceus, were investigated. PA was the only compound with antischistosomal activity among the three diterpenes studied, with the ability to significantly reduce the viability of the parasites at concentrations ranging from 25 to 100 µM. PA also promoted morphological alterations of the tegument of Schistosoma mansoni, separated all the worm couples, and affected the production and development of eggs. Moreover, this compound was devoid of toxicity toward human fibroblasts. In a preliminary in vivo experiment, PA at a dose of 100 mg/kg significantly diminished the number of parasites in infected Balb/c mice. Taken together, these results show that PA may be potentially employed in the discovery of novel schistosomicidal agents, and that diterpenes are an important class of natural compounds for the investigation of agents capable of fighting the parasite responsible for human schistosomiasis.

Schistosoma mansoni: in vitro schistosomicidal activity of essential oil of Baccharis trimera (less) DC.

Schistosomiasis is a chronic parasitic disease caused by the trematode species Schistosoma mansoni. Chemotherapy is the only immediate recourse to minimize the prevalence and incidence of this disease worldwide. At present, praziquantel (PZQ) is the drug of choice for the treatment of all forms of schistosomiasis. However, dependence on a single drug is concern because some strains can become resistant. In this context, medicinal plants become potential candidates as sources of new drug prototypes. This study provides findings on the schistosomicidal activity of the essential oil of Baccharis trimera in in vitro assays. During the assays parameters such as motility of adult worms, oviposition, morphological changes on the tegument and especially the mortality rate of adult worms of the BH strain were evaluated. The assays, which were carried out with four concentrations - 24, 48, 91 and 130 µg/mL - of the essential oil, have shown a promising activity regarding the parameters under study. It was possible to notice a significant decline in the motility of the worms and a mortality rate of 100% 30 h after they had been exposed to the essential oil in the concentration of 130 µg/mL. Male worms were more susceptible, producing a dose-response effect within a smaller exposition period than female worms. In what refers to morphological changes, the essential oil of B. trimera induced a peeling on the tegument surface, as well as the destruction of tubercles and spines, which resulted in smooth areas on the body surface. The essential oil also caused tegument destruction in female worms, in addition to destruction of the oral and acetabular suckers. It is the first time that the schistosomicidal activity has been reported for essential oil of B. trimera (less) DC.

Antischistosomal effect of holothurin extracted from some Egyptian sea cucumbers.

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.

Quantification and clustering of phenotypic screening data using time-series analysis for chemotherapy of schistosomiasis.

BACKGROUND: Neglected tropical diseases, especially those caused by helminths, constitute some of the most common infections of the world's poorest people. Development of techniques for automated, high-throughput drug screening against these diseases, especially in whole-organism settings, constitutes one of the great challenges of modern drug discovery. METHOD: We present a method for enabling high-throughput phenotypic drug screening against diseases caused by helminths with a focus on schistosomiasis. The proposed method allows for a quantitative analysis of the systemic impact of a drug molecule on the pathogen as exhibited by the complex continuum of its phenotypic responses. This method consists of two key parts: first, biological image analysis is employed to automatically monitor and quantify shape-, appearance-, and motion-based phenotypes of the parasites. Next, we represent these phenotypes as time-series and show how to compare, cluster, and quantitatively reason about them using techniques of time-series analysis. RESULTS: We present results on a number of algorithmic issues pertinent to the time-series representation of phenotypes. These include results on appropriate representation of phenotypic time-series, analysis of different time-series similarity measures for comparing phenotypic responses over time, and techniques for clustering such responses by similarity. Finally, we show how these algorithmic techniques can be used for quantifying the complex continuum of phenotypic responses of parasites. An important corollary is the ability of our method to recognize and rigorously group parasites based on the variability of their phenotypic response to different drugs. CONCLUSIONS: The methods and results presented in this paper enable automatic and quantitative scoring of high-throughput phenotypic screens focused on helmintic diseases. Furthermore, these methods allow us to analyze and stratify parasites based on their phenotypic response to drugs. Together, these advancements represent a significant breakthrough for the process of drug discovery against schistosomiasis in particular and can be extended to other helmintic diseases which together afflict a large part of humankind.

A fatal case of strongyloidiasis stercoralis superinfection in an immunocompromized patient.

Strongyloides stercoralis is a disease of worldwide distribution particularly in the immunocompromized patients, especially who are receiving systemic steroids or immunosuppressant therapy, early diagnosis is the key for life safety. A fatal case of chronic strongyloidiasis is reported in an immunocompromized patient with complicated pulmonary infection.

Parasitological and biochemical parameters in Schistosoma mansoni-infected mice treated with methanol extract from the plants Chenopodium ambrosioides, Conyza dioscorides and Sesbania sesban.

This study aims to detect the antischistosomal properties of the plants' Chenopodium ambrosioides, Conyza dioscorides and Sesbania sesban methanol extract against Schistosoma mansoni in infected mice, including determination of total protein and albumin levels and the activities of alanine and aspartate transaminases (AlT, AsT) and acid and alkaline phosphatases (AcP and AkP) enzymes in the serum of infected treated mice. Male Swiss albino mice were infected with S. mansoni and orally treated with methanol extract of the plants C. ambrosioides (1250 mg/kg/day), C. dioscorides and S. sesban (1000 mg/kg/day from each) for 2 consecutive days 7 weeks post infection (PI). In addition, treatment of mice with the tested dose of each plant extract was successively done (i.e. the 1st extract followed by the 2nd and 3rd one with an hour interval). Parasitological and biochemical parameters were assessed. Nine weeks PI, the reduction rates of worm load/mouse treated with either C. dioscorides (1000 mg/kg), C. ambrosioides (1250 mg/kg) or S. sesban (1000 mg/kg) were 40.9%, 53.7% and 54.4%, respectively. Successive treatment raised the reduction rates of worm load/mouse to 66.3% and the ova/g tissue in liver to 76.9%. Moreover, serum total protein and albumin levels and activities of AlT, Ast, AcP and AkP enzymes of infected treated mice were improved in comparison with those of infected untreated ones. It is concluded that administration of C. dioscorides, C. ambrosioides and S. sesban methanol extract to infected mice exhibited a moderate antischistosomal effect. Successive treatment improved the antischistosomal properties of these plant species, hence ameliorated the liver functions of treated mice that may suggest degenerations of liver granulomas and regenerative changes.

Schistosoma mansoni: antischistosomal activity of the four optical isomers and the two racemates of mefloquine on schistosomula and adult worms in vitro and in vivo.

Recent studies have shown that mefloquine (MQ) reveals interesting antischistosomal properties. We examined the antischistosomal activities of the erythro and threo isomers and racemates of MQ on newly transformed schistosomula (NTS) and adult Schistosoma mansoni in vitro and in mice harbouring adult S. mansoni. The in vitro effects in the presence and absence of haemin were monitored by means of microcalorimetry, scanning electron microscopy and phenotypic evaluation. Incubation of NTS with the erythro derivatives at concentrations of 3 µg/ml and above resulted in convulsions, granularity, decrease in heat flow, and death while NTS incubated with the threo derivatives were only affected at high concentrations (100 µg/ml). Extensive tegumental alterations, decrease in metabolic activity, viability, and death were observed when adult schistosomes had been exposed to 10 µg/ml of the erythro compounds. Moderate tegumental and viability changes but reduced heat production rates were observed with the threo derivatives at 10 µg/ml. In the presence of haemin, all MQ derivatives showed pronounced antischistosomal properties against adult S. mansoni in vitro. In vivo, MQ derivatives achieved statistically significant total and female worm burden reductions ranging between 65.4% and 100%. The highest total worm burden reductions of 93.4% and 90.2% were observed following treatment with the erythro and threo racemates, respectively. In conclusion, the optical isomers and racemates of MQ show only moderate stereoselectivity, in particular in vivo. Our results may enhance our understanding of the mechanism of action and therapeutic profile of MQ derivates on schistosomes.

Soil transmitted helminth infections and schistosomiasis in school age children in sub-Saharan Africa: efficacy of chemotherapeutic intervention since World Health Assembly Resolution 2001.

Soil transmitted helminth infections (STH) and schistosomiasis constitute major public health challenges among school-age children in sub-Saharan Africa. This review assessed the efficacy of chemotherapeutic intervention in line with the World Health Assembly (WHA) resolution since the passage in 2001. Using the Medline Entrez-Pubmed search, relevant publications were identified via combinations of key words such as helminth infection, school children, chemotherapy, Africa. Albendazole, mebendazole, and praziquantel were the antihelminthic drugs most commonly evaluated. Cure rates >80% and egg reduction rates >90% were recorded in most cases of schistosomiasis using praziquantel. Albendazole was very effective against A. lumbricoides and hookworm infections with majority of the studies recording cure rates >75%, but the efficacy of the drug was poor against T. trichiura. To ensure the realization of the WHA resolution, there is need for regular treatment of school children, development of alternative antihelminthic drugs and vaccines, environmental control measures and health education.

Further assessment of Mirazid as antischistosomal drug in experimental schistosomiasis hematobium.

Conflicting reports are found in the literature about the efficacy of Mirazid (MZ), which is a special formulation of myrrh obtained from the stem of Commiphora molmol (Nees), Engl. tree (Burseraceae), as an antischistosomal drug. This initiated the present study to further assess this drug in experimental schistosomiasis hematobium. The drug was administered orally to hamsters infected with Schistosoma hematobium ( Bilharz, 1852 ) using 500 mg/kg body weight for six successive days on an empty stomach. The drug effect was examined after three periods: 4, 8 and 12 weeks post-treatment. Emphasis was given to certain parameters such as change in worm load, number of ova/mg tissue, oogram pattern and number of ova/g stool, and tegumental changes in the worms by electron microscopy after prolonged observation periods. The results showed very slight 3.4% worm reduction by MZ after the longest evaluation period (12 weeks), versus very high reduction (100%) by the reference drug praziquantel (PZQ). In comparison with the untreated control no change was found in the number of ova/mg tissue in MZ-treated hamsters regardless of the date of observation (4-12 weeks), versus significantly high reduction (99.6%) observed in the case of PZQ treatment. However, a significant decrease (22%) in the ratio of immature and increase in dead ova in tissues of MZ-treated hamsters was obvious at 12 weeks post treatment. In MZ-treated animals, a slight reduction (18.3%) in the number of stool eggs versus absence of eggs in PZQ-treated animals 12 weeks after treatment. Scanning electron microscopic examination of S. hematobium worms revealed intact tubercles, spines and sensory bulbs and no effect of the ventral side after MZ treatment. Meanwhile, PZQ treatment revealed extensive disruption of the tegument worm. Therefore, this experimental study gives extra support to previously reported negative evaluation about the effectiveness of this drug in the treatment of schistosomiasis against many other published positive results. This controversy about the efficacy of MZ may be attributed to inconsistency of its material which is obtained from natural origin.

Schistosomiasis and neglected tropical diseases: towards integrated and sustainable control and a word of caution.

In May 2001, the World Health Assembly (WHA) passed a resolution which urged member states to attain, by 2010, a minimum target of regularly administering anthelminthic drugs to at least 75% and up to 100% of all school-aged children at risk of morbidity. The refined global strategy for the prevention and control of schistosomiasis and soil-transmitted helminthiasis was issued in the following year and large-scale administration of anthelminthic drugs endorsed as the central feature. This strategy has subsequently been termed 'preventive chemotherapy'. Clearly, the 2001 WHA resolution led the way for concurrently controlling multiple neglected tropical diseases. In this paper, we recall the schistosomiasis situation in Africa in mid-2003. Adhering to strategic guidelines issued by the World Health Organization, we estimate the projected annual treatment needs with praziquantel among the school-aged population and critically discuss these estimates. The important role of geospatial tools for disease risk mapping, surveillance and predictions for resource allocation is emphasised. We clarify that schistosomiasis is only one of many neglected tropical diseases and that considerable uncertainties remain regarding global burden estimates. We examine new control initiatives targeting schistosomiasis and other tropical diseases that are often neglected. The prospect and challenges of integrated control are discussed and the need for combining biomedical, educational and engineering strategies and geospatial tools for sustainable disease control are highlighted. We conclude that, for achieving integrated and sustainable control of neglected tropical diseases, a set of interventions must be tailored to a given endemic setting and fine-tuned over time in response to the changing nature and impact of control. Consequently, besides the environment, the prevailing demographic, health and social systems contexts need to be considered.