In vitro and in silico evaluation of the schistosomicidal activity of eugenol derivatives using biochemical, molecular, and morphological tools

Background Eugenol shows both antibacterial and antiparasitic activities, suggesting that it might be evaluated as an option for the treatment of praziquantel-resistant schistosome. Methods The in vitro activities of three eugenol derivatives (FB1, FB4 and FB9) on adult worms from Schistosoma mansoni were examined by fluorescence and scanning electron microscopy to analyze effects on the excretory system and integument damage, respectively. Biochemical tests with verapamil (a calcium channel antagonist) and ouabain (a Na+/K+-ATPase pump inhibitor) were used to characterize eugenol derivative interactions with calcium channels and the Na+/K+-ATPase, while in silico analysis identified potential Na+/K+-ATPase binding sites. Results The compounds showed effective doses (ED50) of 0.324 mM (FB1), 0.167 mM (FB4), and 0.340 mM (FB9). In addition, FB4 (0.322 mM), which showed the lowest ED50, ED90 and ED100 (p < 0.05), caused the most damage to the excretory system and integument, according to both fluorescence and scanning electron microscopy analysis. The death of adult worms was delayed by ouabain treatment plus FB1 (192 versus 72 hours) and FB9 (192 versus 168 hours), but the response to FB4 was the same in the presence or absence of ouabain. Besides, no changes were noted when all of the eugenol derivatives were combined with verapamil. Moreover, FB1 and FB9 inhibited Na+/K+-ATPase activity according to in silico analysis but FB4 did not show a time-dependent relationship and may act on targets other than the parasite Na+/K+-ATPase. Conclusion Eugenol derivatives, mainly FB4 when compared to FB1 and FB9, seem to act more effectively on the integument of adult S. mansoni worms.(AU)

Esquistossomose: uma endemia de importância no Brasil / Schistosomosis: an important endemic disease in Brazil

A esquistossomose mansônica é uma enfermidade parasitária causada por um trematódeo digenético da família Schistosomatidae, gênero Schistosoma, que vive na corrente sanguínea do hospedeiro definitivo, o homem. As suas formas variam quanto à evolução clínica de maneira assintomática até agudamente grave, podendo levar ao óbito. É um parasita que tem afinidade por regiões tropicais, como o Brasil, onde a temperatura é elevada, principalmente no Norte e Nordeste do país. Junto com a clínica do paciente e exames laboratoriais é possível ter-se um diagnóstico fidedigno dessa enfermidade. As formas de tratamento para essa patologia segue o farmacológico e depende da fase em que se encontra a infecção, havendo necessidade de implantação de medidas preventivas para o controle dessa doença. Com base no exposto, este estudo, por meio da revisão de literatura, tem como objetivo explorar os aspectos clínicos e laboratoriais da esquistossomose mansônica, agente etiológico, tratamento e medida de profilaxia e controle. Portanto, a revisão literária foi feito a partir das bases de dados Scielo, Pubmed assim como livros, guias, textos sobre o assunto, visando conceber um apurado de publicações no sentido de sintetizar um objeto de consulta para uma melhor conscientização da comunidade médico-científica.

Schistosomiasis mansoni is a parasitic disease caused by a digenético trematódeo of the family Schistosomatidae, genus Schistosoma that lives in the sanguineous blood of the definitive host, the man. Its forms vary in clinical evolution from asymptomatic to acutely severe, leading to death. It is a parasite that has affinity for tropical regions, such as Brazil, where the temperature is high, mainly in the North and Northeas of the country. Together with the patient's clinic and laboratory tests, it is possible to have a reliable diagnosis of this disease. The forms of treatment for this pathology follow the pharmacological and depends on the stage of the infection and there is a need to implement preventive measures for the control of this disease. Based on the foregoing, this study, through the literature review, aims to explore the clinical and laboratory aspects of schistosomiasis mansoni, etiologic agent, treatment and measurement of prophylaxis and control. Therefore, the literary review was done from the Scielo, Pubmed databases as well as books, guides, texts on the subject, aiming at conceiving a publication search to synthesize an object of consultation for a better awareness of the scientific medical community.

From Medicinal Chemistry to Human Health: Current Approaches to Drug Discovery for Cancer and Neglected Tropical Diseases

ABSTRACT Scientific and technological breakthroughs have compelled the current players in drug discovery to increasingly incorporate knowledge-based approaches. This evolving paradigm, which has its roots attached to the recent advances in medicinal chemistry, molecular and structural biology, has unprecedentedly demanded the development of up-to-date computational approaches, such as bio- and chemo-informatics. These tools have been pivotal to catalyzing the ever-increasing amount of data generated by the molecular sciences, and to converting the data into insightful guidelines for use in the research pipeline. As a result, ligand- and structure-based drug design have emerged as key pathways to address the pharmaceutical industry's striking demands for innovation. These approaches depend on a keen integration of experimental and molecular modeling methods to surmount the main challenges faced by drug candidates - in vivo efficacy, pharmacodynamics, metabolism, pharmacokinetics and safety. To that end, the Laboratório de Química Medicinal e Computacional (LQMC) of the Universidade de São Paulo has developed forefront research on highly prevalent and life-threatening neglected tropical diseases and cancer. By taking part in global initiatives for pharmaceutical innovation, the laboratory has contributed to the advance of these critical therapeutic areas through the use of cutting-edge strategies in medicinal chemistry.

Ortho-nitrobenzyl derivatives as potential anti-schistosomal agents

ABSTRACT In the search for new anti-schistosomal agents, a series of fifteen ortho-nitrobenzyl derivatives was assayed in vitro against both the schistosomulum (somule) and adult forms of Schistosoma mansoni. Compounds 8 and 12 showed significant activity against somules at low micromolar concentrations, but none was active against adults. The SAR demonstrated that the compounds most active against the parasite were mutagenic to the human cell line RKO-AS45-1 only at concentrations 10- to 40-fold higher than the worm-killing dose. Given their electrophilicity, compounds were also screened as inhibitors of the S. mansoni cysteine protease (cathepsin B1) in vitro. Amides 5 and 15 exhibited a modest inhibition activity with values of 55.7 and 50.6 % at 100 µM, respectively. The nitrobenzyl compounds evaluated in this work can be regarded as hits in the search for more active and safe anti-schistosomal agents.

O tratamento para a esquistossomose e seu efeito nas morbidades: revisão sistemática e metanálise

A esquistossomose ainda é um importante problema de saúde pública em regiões tropicais e subtropicais. Em áreas endêmicas, o estado crônico da infecção gera impacto na saúde dos indivíduos decorrente da patologia desencadeada. Desde a década de 1980, a OMS elegeu a quimioterapia como o método mais adequado para controlar as morbidades associadas à infecção por espécies de Schistosoma. Assim, o uso extensivo do medicamento requer uma compreensão abrangente do seu impacto no controle das morbidades relacionadas. Diante disto, o estudo teve como objetivo avaliar o impacto do tratamento medicamentoso nas morbidades e manifestações clínicas associados à infecção por espécies de Schistosoma por meio de uma revisão sistemática e metanálise. O projeto de revisão foi registrado na plataforma PROSPERO (CRD42015026080)...

Schistosomiasis is an important public health problem in tropical and subtropical regions. In endemic areas, the chronic state of the infection generates an impact on the health of the individuals due to the disease. Since the 1980s, WHO has chosen chemotherapy as the most appropriate method to control the morbidities associated with infection with Schistosoma species. Thus, extensive use of the drug requires a comprehensive understanding of its impact on the control of related morbidities. The objective of this study was to evaluate the impact of drug treatment on the morbidities and symptoms associated with Schistosoma species infection through a systematic review and meta-analysis. The review project was registered on the PROSPERO (CRD42015026080)...

Prevalence of Schistosomes and Soil-Transmitted Helminths among Schoolchildren in Lake Victoria Basin, Tanzania

The objectives of this study was to conduct a survey on schistosomiasis and soil-transmitted helminth (STH) infections in order to come up with feasible control strategies in Lake Victoria basin, Tanzania. Depending on the size of the school, 150-200 schoolchildren were recruited for the study. Duplicate Kato-Katz stool smears were prepared from each child and microscopically examined for Schistosoma mansoni and STHs. Urine specimens were examined for Schistosoma haematobium eggs using the filtration technique. After the survey, mass drug administration was done using praziquantel and albendazole for schistosomiasis and STHs infections, respectively. A total of 5,952 schoolchildren from 36 schools were recruited for the study and had their stool and urine specimens examined. Out of 5,952 schoolchildren, 898 (15.1%) were positive for S. mansoni, 754 (12.6%) for hookworms, 188 (3.2%) for Ascaris lumblicoides, and 5 (0.008%) for Trichuris trichiura. Out of 5,826 schoolchildren who provided urine samples, 519 (8.9%) were positive for S. haematobium eggs. The results revealed that intestinal schistosomiasis, urogenital schistosomiasis, and STH infections are highly prevalent throughought the lake basin. The high prevalence of intestinal and urogenital schistosomisiasis in the study area was a function of the distance from Lake Victoria, the former being more prevalent at localities close to the lake, whilst the latter is more so away from it. Control of schistosomiasis and STHs in the study area requires an integrated strategy that involves provision of health education to communities, regular treatments, and provision of adequate safe water supply and sanitation facilities.

Prevalence of Schistosomes and Soil-Transmitted Helminths and Morbidity Associated with Schistosomiasis among Adult Population in Lake Victoria Basin, Tanzania

The objective of this study was to carry out a community survey on schistosomiais and soil-transmitted helminth (STH) infections in order to suggest feasible and effective intervention strategies in Lake Victoria basin, Tanzania. A total of 37 communities selected from 23 districts of the 4 regions in the Lake Victoria basin of Tanzania were involved in the study. From each of the selected locality, 50 adult community members, 25 males and 25 females, were recruited for the study. Each study participant was requested to submit stool and urine specimens. From each stool specimen, duplicate Kato-Katz thick smears were prepared and microscopically examined for Schistosoma mansoni and STH eggs. Urine specimens were processed by the filtration technique and microscopically examined for Schistosoma haematobium eggs. Ultrasound examination for morbidity due to schistosomiasis was performed. Mass treatment was done using praziquantel and albendazole for schistosome and STHs infections, respectively. Out of 1,606 adults who provided stool specimens, 199 (12.4%) were positive for S. mansoni, 349 (21.7%) for hookworms, 133 (8.3%) for Ascaris lumbricoides, and 33 (2.0%) for Trichuris trichiura. Out of 1,400 participants who provided urine specimens, 25 (1.8%) were positive for S. haematobium eggs. Because of the co-endemicity of these afflictions and their impact on vulnerable population groups, the helminthiasis could be simultaneously treated with 2 drugs, praziquantel for schistosomiasis and albendazole for STHs.

Improved Socio-Economic Status of a Community Population Following Schistosomiasis and Intestinal Worm Control Interventions on Kome Island, North-Western Tanzania

Research on micro-level assessment of the changes of socio-economic status following health interventions is very scarce. The use of household asset data to determine wealth indices is a common procedure for estimating socio-economic position in resource poor settings. In such settings information about income is usually lacking, and the collection of individual consumption or expenditure data would require in-depth interviews, posing a considerable risk of bias. In this study, we determined the socio-economic status of 213 households in a community population in an island in the north-western Tanzania before and 3 year after implementation of a participatory hygiene and sanitation transformation (PHAST) intervention to control schistosomiasis and intestinal worm infections. We constructed a household 'wealth index' based housing construction features (e.g., type of roof, walls, and floor) and durable assets ownership (e.g., bicycle, radio, etc.). We employed principal components analysis and classified households into wealth quintiles. The study revealed that asset variables with positive factor scores were associated with higher socio-economic status, whereas asset variables with negative factor scores were associated with lower socio-economic status. Overall, households which were rated as the poorest and very poor were on the decrease, whereas those rated as poor, less poor, and the least poor were on the increase after PHAST intervention. This decrease/increase was significant. The median shifted from -0.4376677 to 0.5001073, and the mean from -0.2605787 (SD; 2.005688) to 0.2605787 (SD; 1.831199). The difference in socio-economic status of the people between the 2 phases was highly statistically significant (P<0.001). We argue that finding of this study should be treated with caution as there were other interventions to control schistosomiasis and intestinal worm infections which were running concurrently on Kome Island apart from PHAST intervention.

Ectopic cutaneous schistosomiasis - Case report

Schistosomiasis is best known in its visceral form but it can attack the skin, its ectopic cutaneous manifestation being rare and clinically difficult to diagnose. It is characterized by isolated or coalescent papules, erythematous, pruritic or asymptomatic, with zosteriform distribution, often located on the trunk. The authors report a case of a 28-year-old female patient with lesions on the abdomen, with positive stool results for Schistosoma and absence of active symptoms of visceral disease. The case reveals rare exuberant cutaneous manifestation and the importance of the diagnosis of this entity in patients from endemic regions.

Role of berberine in ameliorating Schistosoma mansoni-induced hepatic injury in mice

BACKGROUND: Schistosomiasis is caused by helminth parasites of the genus Schistosoma. Berberine chloride (BER), an isoquinoline alkaloid, has been used in vivo for its antiparasitic, antioxidant and hepatoprotective properties. In this study, the protective effect of BER and praziquantel has been compared for the extent of schistosomiasis-induced oxidative stress in hepatic tissue of mice. RESULTS: S. mansoni was able to induce inflammation and injury to the liver, evidenced (i) by an increase in inflammatory cellular infiltrations, dilated sinusoids and vacuolated hepatocytes, (ii) by decreased levels of alanine and aspartate aminotransferases and increased levels of alkaline phosphatase, γ-glutamyl transferase in the liver homogenate, (iii) by increased production of nitric oxide and thiobarbituric acid reactive substances, and (iv) by lowered glutathione levels and decreased activities of catalase and superoxide dismutase, respectively. All these infection-induced parameters were significantly altered during BER treatment. In particular, berberine counteracted the S. mansoni-induced loss of glutathione and the activities of catalase and superoxide dismutase. CONCLUSION: Based on these results, it is concluded that berberine could ameliorate pre-existing liver damage and oxidative stress conditions due to schistosomiasis.

Ectopic cutaneous schistosomiasis - Case report / Esquistossomose cutanea ectopica - Relato de caso

Schistosomiasis mansoni is a systemic disease caused by a helminth of the schistosoma genus. The disease is generally asymptomatic or gastrointestinal symptoms may predominate. Skin lesions related to the disease are rarely diagnosed, even in endemic areas. The authors report the case of a young girl diagnosed with cutaneous schistosomiasis with involvement of the abdomen, back and scapular region. Schistosoma eggs were found in the lesions by histopathologic exam. There was no evidence of systemic involvement. Schistosomiasis must be included in the list of differential diagnosis of skin damage, especially in endemic areas, due to the potential consequences, in case of late diagnosis and treatment.

A esquistossomose mansônica é uma doença sistêmica causada por um helminto do gênero Schistosoma, geralmente assintomática ou com predomínio de manifestações gastrointestinais. Lesões cutâneas relacionadas à doença são raramente diagnosticadas, mesmo em áreas endêmicas. Relata-se um caso de uma jovem com história de lesões papulosas no abdome, no dorso e na região escapular direita, de distribuição zosteriforme. O exame histopatológico demonstrou a presença de ovos de Schistosoma nessas lesões. Não havia evidências de esquistossomose visceral ativa. Reforça-se a necessidade de que essa doença seja incluída no rol de diagnósticos diferenciais de lesões cutâneas, principalmente em áreas endêmicas, em razão das possíveis consequências em caso de diagnóstico e tratamento tardios.

Proteínas quinase eucarióticas (ePKs) de Schistosoma: identificação, anotação funcional e seleção de potenciais alvos terapêuticos

Apesar do praziquantel ser uma droga eficiente para o tratamento da esquistossomose, a prevalência da doença não mostrou redução significativa nos últimos anos e, até o momento, não existe uma alternativa eficaz para o tratamento dessa doença. Dessa forma, optamos por utilizar as poderosas ferramentas genômicas para identificar potenciais alvos para o desenvolvimento de um medicamento alternativo. Já que proteínas quinase eucarióticas (ePKs) são consideradas alvos para o desenvolvimento de drogas do ponto de vista médico e químico, e um número crescente de inibidores ePKs foram desenvolvidos e aprovados para o tratamento de diferentes doenças humanas, estas se tornaram o foco de estudo desse trabalho. As ePKs de S. mansoni, S. japonicum e S. haematobium foram identificadas nos proteomas preditos e classificadas em seus devidos grupos, famílias e subfamílias a partir de abordagens filogenéticas. Utilizando as informações dos ortólogos identificados, foi possível selecionar um grupo de ePKs com função predita essencial nesse parasito. A anotação funcional mostrou ainda que grande parte das ePKs selecionadas são ativadoras/efetoras da via de sinalização MAPK. Dessa forma, proteínas chave da via MAPK (SmRas, SmERK1, SmERK2, SmJNK e SmCaMK2), foram as escolhidas para validação experimental. Após redução significativa no nível de transcrito dos genes selecionados, nenhuma alteração fenotípica visível foi relatada em cultura de esquistossomulos.

Contudo, o efeito da diminuição transcricional dos genes no desenvolvimento dos vermes diante do sistema imune do hospedeiro foi avaliado. Evidenciamos que proteínas MAPK JNK quando silenciada causa efeitos devastadores no tegumento de vermes adultos de S. mansoni que leva a morte dos mesmos. E, ePKs da subfamília ERK1 estão relacionadas com a produção de ovos, já que fêmeas com baixos níveis de transcritos SmERK1 e SmERK2 apresentam ovários pouco desenvolvidos e produção de ovos significativamente baixa. Além disso, foi comprovado que o fator de transcrição c-fos está diferencialmente expresso em parasitos silenciados para as proteínas MAPK SmJNK, SmCaMK2 e SmERK1/2. Dessa forma concluímos que o dado genômico, acoplado a ferramentas computacionais preditoras e abordagem experimental, compõem uma metodologia poderosa para o estudo dessa espécie. As proteínas MAPK, SmERK e SmJNK, são alvos de interesse para o desenvolvimento de drogas para tratamento da esquistossomose já que um inibidor contra essas proteínas provavelmente irá interromper o ciclo de vida de Schistosoma e impedir o progresso da doença

Proteínas quinase eucarióticas (ePKs) de Schistosoma: identificação, anotação funcional e seleção de potenciais alvos terapêuticos / Eukaryotic protein kinase (ePKs) Schistosoma: identification, functional annotation and selection of potential therapeutic targets

Apesar do praziquantel ser uma droga eficiente para o tratamento da esquistossomose, a prevalência da doença não mostrou redução significativa nos últimos anos e, até o momento, não existe uma alternativa eficaz para o tratamento dessa doença. Dessa forma, optamos por utilizar as poderosas ferramentas genômicas para identificar potenciais alvos para o desenvolvimento de um medicamento alternativo. Já que proteínas quinase eucarióticas (ePKs) são consideradas alvos para o desenvolvimento de drogas do ponto de vista médico e químico, e um número crescente de inibidores ePKs foram desenvolvidos e aprovados para o tratamento de diferentes doenças humanas, estas se tornaram o foco de estudo desse trabalho. As ePKs de S. mansoni, S. japonicum e S. haematobium foram identificadas nos proteomas preditos e classificadas em seus devidos grupos, famílias e subfamílias a partir de abordagens filogenéticas. Utilizando as informações dos ortólogos identificados, foi possível selecionar um grupo de ePKs com função predita essencial nesse parasito. A anotação funcional mostrou ainda que grande parte das ePKs selecionadas são ativadoras/efetoras da via de sinalização MAPK. Dessa forma, proteínas chave da via MAPK (SmRas, SmERK1, SmERK2, SmJNK e SmCaMK2), foram as escolhidas para validação experimental. Após redução significativa no nível de transcrito dos genes selecionados, nenhuma alteração fenotípica visível foi relatada em cultura de esquistossomulos.

Contudo, o efeito da diminuição transcricional dos genes no desenvolvimento dos vermes diante do sistema imune do hospedeiro foi avaliado. Evidenciamos que proteínas MAPK JNK quando silenciada causa efeitos devastadores no tegumento de vermes adultos de S. mansoni que leva a morte dos mesmos. E, ePKs da subfamília ERK1 estão relacionadas com a produção de ovos, já que fêmeas com baixos níveis de transcritos SmERK1 e SmERK2 apresentam ovários pouco desenvolvidos e produção de ovos significativamente baixa. Além disso, foi comprovado que o fator de transcrição c-fos está diferencialmente expresso em parasitos silenciados para as proteínas MAPK SmJNK, SmCaMK2 e SmERK1/2. Dessa forma concluímos que o dado genômico, acoplado a ferramentas computacionais preditoras e abordagem experimental, compõem uma metodologia poderosa para o estudo dessa espécie. As proteínas MAPK, SmERK e SmJNK, são alvos de interesse para o desenvolvimento de drogas para tratamento da esquistossomose já que um inibidor contra essas proteínas provavelmente irá interromper o ciclo de vida de Schistosoma e impedir o progresso da doença

Impacto do tratamento com praziquantel na infecção por Schistosoma mansoni em adolescentes do município de São Lourenço da Mata, área endêmica da esquistossomose em Pernambuco / Impact of treatment with praziquantel on Schistosoma mansoni infection in adolescents from the municipality of São Lourenço da Mata, an endemic area of schistosomiasis in Pernambuco

A esquistossomose é uma das doenças parasitárias mais prevalentes no mundo, sendo a quimioterapia com praziquantel (PZQ) a principal estratégia adotada para seu controle. No entanto, faltam informações sobre o impacto da quimioterapia com PZQ sobre a infecção por Schistosoma mansoni nas condições enfrentadas pelos programas de controle, e ainda não há prova de princípio sobre o melhor regime de dosagem a ser utilizado. Um ensaio clínico randomizado duplo-cego foi realizado com o objetivo de avaliar o impacto do tratamento em dose única de PZQ 60 mg/kg na infecção por S. mansoni comparado à dose padrão de PZQ 40 mg/kg em adolescentes do município de São Lourenço da Mata. Um inquérito coproscópico preliminar selecionou indivíduos para a triagem e aqueles que se adequaram aos critérios de inclusão/exclusão foram recrutados e tratados com dose única de 40 mg/kg ou 60 mg/kg de PZQ. Inquéritos coproscópicos de acompanhamento foram realizados aos 21, 180 e 360 dias pós-tratamento. A prevalência e a intensidade de infecção foram comparadas nos quatro momentos do estudo nos dois grupos de tratamento utilizando tabelas de contingência (Qui-quadrado ou teste exato de Fisher) e ANOVA. A influência de outras variáveis no estudo foi avaliada através da análise de regressão logística. Um levantamento malacológico foi realizado para verificar a infecção natural da espécie hospedeira local, Biomphalaria straminea. A análise da distribuição espacial da infecção nos dois grupos antes e depois (180 e 360 dias) do tratamento foi realizada pela estimativa de densidade de kernel para a detecção de aglomerados de casos...

Potential relation ibetween the appearance of biomphalaria alexandrina- biomphalaria glabrata hybrid in the irrigation system and the evolution of resistance to praziquntel lyeatment in Egypt

In the last decade, partial resistance to Praziquantel [PZQ] in treatment of schistosomiasis appeared in some villages in Egypt. This happened following the invasion of the irrigation system by hybrid snails of the indigenous, vector snail Biomphalaria alexandrina and the introduced Biomphalaria glabrata. The objective of this study was to investigate if the distribution of the hybrid snails in the irrigation system represents a factor, between others, which is related to the appearance of [PZQ] resistance. Therefore, three groups of mice were infected with Schistosoma mansoni cercariae obtained from infected B. alexandrina, B.glabrata and hybrid snails. Six weeks later, the animals were treated with.the usual curative dose of PZQ [500mg/kg body weight for two consecutive days] and sacrificed two weeks post-treatment. The results showed that worms reduction in the group infected with cercariae from hybrid snails was significantly less than that in the other two groups 86.1% versus 95.1% and 92.8%, respectively. The number of dead ova in the same group was also less, being 81.5% versus 97.5%, and 95.1% respectively. The numbers of ova/g liver was 56.6%, in the same group while 64.2 and 70.9 in the other two groups. The reduction in numbers of ova/g intestine was 81.9% in this group versus 86.1% and 88.4% in the other two groups.The present results give indication that the appearance of PZQ resistance against schistosomiasis in Egypt may return at least partially to the wide distribution of the hybrid Biomphalaria snails in this country

Testicular schistosomiasis mimicking tumour

Schistosomiasis or bilharziasis is a disease caused by Schistosoma. When infecting men the most common parasites are Schistosoma mansoni, Schistosoma japonicum and Schistosoma haematobium. The Schistosoma mansoni is the only endemic parasite in Brazil. We present a case of testicular schistosomiasis simulating malignancy. The case was treated successfully by excisional biopsy and praziquantel therapy. A review of the literature is discussed.

Investigation of Induced biochemical and histopathological parameters of acetonitril extract of Jatropha carcus in albino rats

Toxicological and histopathological investigations were carried on the acetonitrile extract from J. Carcus in comparison with praziquantel, the known anti-schistosomal drug. On a constant weight dose bases [single dose of 50 mg/kg body weight injected orally to albino rats], the acetonitrile extract from J. carcus showed mild toxicological parameters, biochemical parameters as well as histopathological profile in comparison with the control. However, these side effects were nonsignificant compared with the severe side effects caused by praziquantel

Schistosomiasis epidemiology and control: how did we get here and where should we go?

Although a disease of great antiquity, scientific studies of schistosomiasis began only 150 years ago. The complete life-cycle was not described until just before the First World War, making it possible at last to plan proper community control programmes. Inadequate tools prevented their effective implementation until well after the Second World War when new tools became available, thanks to the newly formed World Health Organization. Molluscicides spearheaded control programmes until the late 1970s but were then replaced by the newly developed, safe drugs still used today. Whatever the method used, the initial goal of eradication was, in the light of experience and cost, gradually replaced by less ambitious targets; first to stop transmission and then to reduce morbidity. The most successful programmes combined several methods to minimise reinfection after chemotherapy. Comparisons between different programmes are difficult without using appropriate, standardised diagnostic techniques and the correct epidemiological measurements. Some examples will be presented, mainly from our studies on Schistosoma mansoni in Kenya. Drug resistance on a scale comparable with malaria has not occurred in schistosomiasis but the likely withdrawal of all drugs except praziquantel leaves its control extremely vulnerable to this potential problem. An effective, affordable vaccine for use in endemic countries is unlikely to be ready for at least 5 years, and developing strategies for its use could take a further decade or more, judging from experience with drugs and molluscicides. In the interim, by analogy with malaria, the most cost-effective approach would the use of drugs combined with other methods to stop transmission, including molluscicides. The cost of molluscicides needs to be reduced and fears allayed about their supposedly adverse ecological effects