Diospyros perigrena bark extract induced apoptosis in filarial parasite Setaria cervi through generation of reactive oxygen species.

CONTEXT: Lymphatic filariasis is a major neglected tropical disease. Diospyros perigrena Gurke (Ebenaceae) was selected for antifilarial chemotherapy because of unavailability of proper medicine. In India, different parts of this plant were used for the treatment of diabetes, diarrhea, dysentery, cholera, mouth ulcers, and wounds. OBJECTIVE: The present study was undertaken to access antifilarial potential and mechanism of action of n-butanol extract (NBE) of D. perigrena stem bark on Setaria cervi Rudolphi (Onchocercidae). MATERIALS AND METHODS: In vitro efficacy and apoptotic mechanism were evaluated by Hoechst, TUNEL, DNA fragmentation assay, pro- and anti-apoptotic gene expression in NBE (250, 125, 62.5, 31.25, and 15.6 µg/ml)-treated S. cervi after 24 h of incubation. Reactive oxygen species (ROS) up-regulation was also determined by GSH, GST, SOD assays, and super oxide anion level. RESULTS: Significant in vitro antifilarial activity of NBE was found 50% inhibitory concentration (IC50): adult = 57.6 µg/ml, microfilariae (mf) = 56.1 µg/ml, and lethal dose (LD100) in mf is 187.17 µg/ml) after 24 h of treatment. NBF-induced apoptosis was proved by Hoechst, TUNEL, RT-PCR, and Western blot method. NBF (250 µg/ml) decreased the level of GSH (17.8%) and GST (65.4%), increased SOD activity (1.42-fold) and super oxide anion production (1.32-fold) in the treated parasite which culminated into ROS up-regulation. DISCUSSION AND CONCLUSION: NBE induced apoptosis in different life cycle stages of S. cervi. In future, a detailed study of NBF will give us a novel antifilarial compound which will be used for antifilarial chemotherapy.

Factors influencing drug compliance in the mass drug administration programme against filariasis in the Western province of Sri Lanka.

This descriptive, comparative, cross-sectional, randomized community-based study was done to determine factors influencing drug compliance in the mass drug administration (MDA) programme against filariasis in selected urban and rural populations within the Western province of Sri Lanka. The study population was selected using the cluster sampling method. Factors influencing drug compliance were determined by administration of an interviewer-based pre-tested questionnaire eliciting information regarding drug compliance, socio-economic status, educational background, knowledge, attitudes and practices with regard to the 2004 MDA. A total of 2319 people aged between 10 and 90 years (median 40) responded to the questionnaire. The belief that the MDA programme was beneficial was the most important factor affecting drug compliance, as revealed by multivariate analysis of the combined populations (P<0.001). This was so even in the urban population (P<0.001), while the belief regarding the severity (danger) of filariasis was important in the rural population (P=0.013), when the areas were considered individually. Therefore, it is essential for awareness programmes to highlight the dangers (complications) of the disease and to influence the community to perceive the benefits of a filariasis-free community as well as 'beyond filariasis' benefits of having albendazole given in combination in the MDA programme.

Stigma reduction and improved knowledge and attitudes towards filariasis using a comic book for children.

WHO has initiated a global program for lymphatic filariasis (LF) elimination by year 2020. A comic book was designed to improve knowledge and attitudes of Egyptian school children, which included messages on the acceptability of Mass Drug Administration (MDA) and stigma reduction. Comic book administration significantly reduced the fear of the studied children from LF as a killer disease. It helped in positively changing the attitudes of the children towards Elephantiasis patients (p-value <.001). The comic book also reduced the number of children who had earlier stated that they would avoid someone with LF. Knowledge about the ability of treating and preventing LF was also significantly increased among the children after reading the comic book. Moreover, comic book reading helped in raising the awareness towards MDA as the method of choice in preventing LF. Most of the children liked the comic book and its contents. Importantly, 96.2% found this book easy to understand. Many of relatives and friends read the comic book within 2 weeks after distribution. A well-accepted comic book for children is a proven way to reduce stigma and increase knowledge about disease prevention and treatment.

Filarial elephantiasis among Haitian women: social context and behavioural factors in treatment.

Few studies have addressed the social and behavioural aspects of lymphatic filariasis. The research reported here investigated the ethnographic context of filarial elephantiasis among women in Léogane, Haiti, and focused on explanatory models of the illness, the impact of the disease on women's lives, and the difficulties patients experienced in following a therapeutic regimen provided at a local hospital. Qualitative data were collected through focus group and individual interviews and direct observation of patients enrolled in the treatment programme. Results indicate that traditional understanding and treatment for the disease are prevalent in the community, although biomedical explanations are gaining credence as a consequence of long-term filariasis control activities in this area. Women's lives are substantially burdened both socially and economically by the physical impairment of elephantiasis, most notably in the loss of income due to restrictions on mobility. The degree of social discrimination encountered varies by the timing of onset of symptoms in the life course. Difficulties encountered with the physical therapy regimen included maintenance of the compressive bandage and availability of suitable foot wear. Similarities between these findings and those reported for other parts of the world are noted. Recommendations from the study cite the need for community education and peer support activities to provide a knowledge base and support structure for current and future intervention programmes.

Epoxyethane-/ethynesulfonamides with antifilarial activities. Degradation kinetics and inhibitory effect on filarial malate dehydrogenase and lactate dehydrogenase.

Some epoxyethane-/ethynesulfonamides had shown strong filaricidal activity with inconstant reproducibility as a result of a lack of stability in aqueous solution. The degradation in hydroxylic and aprotic solutions of two epoxyethanesulfonamides and one ethynesulfonamide was investigated using TLC, HPLC, GC and mass spectrometry. For both epoxydes, the degradation rate followed first-order kinetics and was more rapid in hydroxylic than in aprotic solutions. The degradation increased with the temperature whereas it was not modified with and without light exposure. Four kinds of degradation products were found: the first one involved the oxidation of the epoxyde bond, the second the breaking of the N-S bond, the third a desulfonation product and the fourth was not identified. In contrast, the stability of ethynesulfonamide was better than those of epoxyethanesulfonamide. These results suggest that epoxyethanesulfonamides should be kept at +4 degrees C before being injected to animals during the study of biological activity. Since epoxyde compounds are known to have inhibitory effects on parasite energy metabolism enzymes, the compunds were evaluated on two major filarial enzymes: lactate dehydrogenase (LDH) and cytoplasmic malate dehydrogenase (MDH). Both epoxyethanesulfonamides showed only a slight inhibitory effect on filarial LDH and MDH confirming the evidence that the main mode of action of these compounds remains to discover. Moreover, ethynesulfonamide and the degradation products of both epoxyethane-sulfonamides had no effect on LDH and MDH.

Recent advances in the social and behavioral aspects of filariasis.

Despite an increased awareness of the significance of social and behavioral influences upon various aspects of filariasis, there has been a relative lack of research that has specifically attempted to assess such factors from the outset. Instead, the norm has been to indirectly discover social and behavioral patterns primarily as a byproducts of epidemiological and clinical surveys. The exception to this has been a recent surge of research interest in this domain that was initiated by a commitment by the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR), although it is clear that more research is needed. The results of those few studies that have been conducted concerning the roles of behavioral (knowledge, attitudes, beliefs, practice) and socio-cultural factors are reviewed in this paper, highlighting how an acknowledgement of such factors contributes of a greater understanding of the relevant issues, thus allowing for more relevant and feasible health education/intervention programs. Finally, recent research conducted by two of the present authors in Nakhon Si Thammarat Province in Southern Thailand, which is noted for having the highest filariasis morbidity rate in the country, is presented and discussed. This is followed by recommendations for appropriate health education programs, and suggestions for future research.