Efficacy and Safety of Artemether in the Treatment of Chronic Fascioliasis in Egypt: Exploratory Phase-2 Trials

Fasciola hepatica and F. gigantica are two liver flukes that parasitize herbivorous large size mammals (e.g., sheep and cattle), as well as humans. A single drug is available to treat infections with Fasciola flukes, namely, triclabendazole. Recently, laboratory studies and clinical trials in sheep and humans suffering from acute fascioliasis have shown that artesunate and artemether (drugs that are widely used against malaria) also show activity against fascioliasis. Hence, we were motivated to assess the efficacy and safety of oral artemether in patients with chronic Fasciola infections. The study was carried out in Egypt and artemether administered according to two different malaria treatment regimens. Cure rates observed with 6×80 mg and 3×200 mg artemether were 35% and 6%, respectively. In addition, high efficacy was observed when triclabendazole, the current drug of choice against human fascioliasis, was administered to patients remaining Fasciola positive following artemether treatment. Concluding, monotherapy with artemether does not represent an alternative to triclabendazole against fascioliasis, but its role in combination chemotherapy regimen remains to be investigated

A Comparison of Initial Antiretroviral Therapy in the Swiss HIV Cohort Study and the Recommendations of the International AIDS Society-USA

BACKGROUND: In order to facilitate and improve the use of antiretroviral therapy (ART), international recommendations are released and updated regularly. We aimed to study if adherence to the recommendations is associated with better treatment outcomes in the Swiss HIV Cohort Study (SHCS). METHODS: Initial ART regimens prescribed to participants between 1998 and 2007 were classified according to IAS-USA recommendations. Baseline characteristics of patients who received regimens in violation with these recommendations (violation ART) were compared to other patients. Multivariable logistic and linear regression analyses were performed to identify associations between violation ART and (i) virological suppression and (ii) CD4 cell count increase, after one year. RESULTS: Between 1998 and 2007, 4189 SHCS participants started 241 different ART regimens. A violation ART was started in 5% of patients. Female patients (adjusted odds ratio aOR 1.83, 95%CI 1.28-2.62), those with a high education level (aOR 1.49, 95%CI 1.07-2.06) or a high CD4 count (aOR 1.53, 95%CI 1.02-2.30) were more likely to receive violation ART. The proportion of patients with an undetectable viral load (<400 copies/mL) after one year was significantly lower with violation ART than with recommended regimens (aOR 0.54, 95% CI 0.37-0.80) whereas CD4 count increase after one year of treatment was similar in both groups. CONCLUSIONS: Although more than 240 different initial regimens were prescribed, violations of the IAS-USA recommendations were uncommon. Patients receiving these regimens were less likely to have an undetectable viral load after one year, which strengthens the validity of these recommendations

Pintura facial, patrón de vestido y cabello en las miniaturas textiles de la cultura Chancay

Identifica y describe los diseños, patrones de vestido y pintura facial de las miniaturas textiles masculinas y femeninas. Destaca la poderosa presencia del cabello y las diversas formas de sus tocados resaltando su importancia social y simbólica tanto como las formas y tamaño de las cabezas que representan además, la tercera parte del cuerpo. Demuestra que las miniaturas están íntegramente tejidas y revestidas – de cabeza a pies –, así como los tocados y accesorios que lucen o sujetan con las manos. Son una unidad textil que concentra en un volumen reducido de materia, diversas soluciones técnicas y estéticas de la sociedad Chancay. Esta unidad reúne y sintetiza una sólida y milenaria tradición textil así como la unión equilibrada entre técnica y estética. Evidencia las correspondencias entre la composición de la pintura facial de las miniaturas femeninas y el diseño de sus aksus. Destacar por otro lado, el tratamiento, importancia y capacidad de transformación que operaron e imprimieron sobre el cuerpo los hombres y mujeres Chancay y que se manifiestan en las miniaturas.Tesi

Metabolic Profiling of an Echinostoma caproni Infection in the Mouse for Biomarker Discovery

Consumption of raw fish and other freshwater products can lead to unpleasant worm infections. Indeed, such worm infections are of growing public health and veterinary concern, but they are often neglected, partially explained by the difficulty of accurate diagnosis. In the present study we infected 12 mice with an intestinal worm (i.e., Echinostoma caproni) and collected blood, stool, and urine samples 7 times between 1 and 33 days after the infection. At the same time points, blood, stool, and urine were also sampled from 12 uninfected mice. These biofluid samples were examined with a spectrometer and data were analyzed with a multivariate approach. We observed important differences between the infected and the uninfected control animals. For example, we found an increased level of branched chain amino acids in the stool of infected mice and subsequent depletion in blood plasma. Additionally, we observed changes related to a disturbed intestinal bacterial composition, particularly in urine and stool. The combination of results from the three types of biofluids gave the most comprehensive characterization of an E. caproni infection in the mouse. Urine would be the biofluid of choice for diagnosis of an infection because the ease of sample collection and the high number and extent of changed metabolites

Potential Drug Development Candidates for Human Soil-Transmitted Helminthiases

There are few drugs - none ideal - for the treatment and control of gastrointestinal helminths (soil-transmitted nematodes) which, as chronic infections jeopardize children's growth, learning and ultimately individual, community and country development. Drugs for helminths are not attractive in human medicine, but are lucrative in animal health. Traditionally, investment in veterinary medicines has benefited humans for these diseases. With modern regulations an approved veterinary medicine can be tested in humans with little adaptation, reducing time and cost of development. We searched for products that could easily be transitioned into humans, having the necessary characteristics for use in communities exposed to these infections. A limited number of candidates met the main criteria for selection. We provide here a detailed analysis of two veterinary products, emodepside and monepantel, and nitazoxanide, which is approved for human use. In addition we include a less detailed analysis of all products examined, and the criteria on which the analysis was based. It is clear that the pipeline of easily obtainable human anthelminthics remains extremely limited, and further efforts are needed to find replacements for the inadequate number of products available today

Evaluation and pharmacovigilance of projects promoting cultivation and local use of Artemisia annua for malaria

<p>Abstract</p> <p>Background</p> <p>Several non-governmental organisations (NGOs) are promoting the use of <it>Artemisia annua </it>teas as a home-based treatment for malaria in situations where conventional treatments are not available. There has been controversy about the effectiveness and safety of this approach, but no pharmacovigilance studies or evaluations have been published to date.</p> <p>Method</p> <p>A questionnaire about the cultivation of <it>A. annua</it>, treatment of patients, and side-effects observed, was sent to partners of the NGO Anamed in Kenya and Uganda. Some of the respondents were then selected purposively for more in-depth semi-structured interviews.</p> <p>Results</p> <p>Eighteen partners in Kenya and 21 in Uganda responded. 49% reported difficulties in growing the plant, mainly due to drought. Overall about 3,000 cases of presumed malaria had been treated with <it>A. annua </it>teas in the previous year, of which about 250 were in children and 54 were in women in the first trimester of pregnancy. The commonest problem observed in children was poor compliance due to the bitter taste, which was improved by the addition of sugar or honey. Two miscarriages were reported in pregnant patients. Only four respondents reported side-effects in other patients, the commonest of which was vomiting. 51% of respondents had started using <it>A. annua </it>tea to treat illnesses other than malaria.</p> <p>Conclusions</p> <p>Local cultivation and preparation of <it>A. annua </it>are feasible where growing conditions are appropriate. Few adverse events were reported even in children and pregnant women. Where ACT is in short supply, it would make sense to save it for young children, while using <it>A. annua </it>infusions to treat older patients who are at lower risk. An ongoing pharmacovigilance system is needed to facilitate reporting of any adverse events.</p

The effectiveness of public health interventions to reduce the health impact of climate change:a systematic review of systematic reviews

Climate change is likely to be one of the most important threats to public health in the coming years. Yet despite the large number of papers considering the health impact of climate change, few have considered what public health interventions may be of most value in reducing the disease burden. We aimed to evaluate the effectiveness of public health interventions to reduce the disease burden of high priority climate sensitive diseases

Rural-Urban Differences in Maternal Responses to Childhood Fever in South East Nigeria

Childhood fevers due to malaria remain a major cause of morbidity and mortality among under-five children in Nigeria. The degree of vulnerability perceived by mothers will affect their perception of the severity and threat of their child's fever and the patterns of health care use. This study was undertaken to compare maternal responses to childhood fever in urban and rural areas of Enugu, south east Nigeria.Data was collected with pre-tested interviewer-administered questionnaires from 276 and 124 urban and rural households respectively. In each household, only one woman aged 15-49 years who had lived in each of the urban and rural communities for at least one year and had at least one child less than 5 years old was interviewed. Malaria was mentioned as the commonest cause of childhood fevers. Rural mothers were more likely to recognize danger signs and symptoms than urban mothers. Rural mothers use more of informal than formal health services, and there is more home management of the fever with urban than rural mothers. Chloroquine, ACT, SP and Paracetamol are the main drugs given at home for childhood fevers, but the rural mothers were more likely to use leftover drugs from previous treatment to treat the fevers than urban mothers. The urban respondents were also more likely to use a preventive measure. Urban mothers sought actions faster than rural mothers and the total cost of treatment was also higher in urban areas.Both urban and rural mothers are aware that malaria is the major cause of childhood fevers. Although rural mothers recognize childhood fever and danger signs better than urban mothers, the urban mothers' responses to fever seem to be better than that for rural mothers. These responses and differences may be important for geographical targeting by policy makers for malaria interventions

Prediction of Drug-Target Interactions and Drug Repositioning via Network-Based Inference

Drug-target interaction (DTI) is the basis of drug discovery and design. It is time consuming and costly to determine DTI experimentally. Hence, it is necessary to develop computational methods for the prediction of potential DTI. Based on complex network theory, three supervised inference methods were developed here to predict DTI and used for drug repositioning, namely drug-based similarity inference (DBSI), target-based similarity inference (TBSI) and network-based inference (NBI). Among them, NBI performed best on four benchmark data sets. Then a drug-target network was created with NBI based on 12,483 FDA-approved and experimental drug-target binary links, and some new DTIs were further predicted. In vitro assays confirmed that five old drugs, namely montelukast, diclofenac, simvastatin, ketoconazole, and itraconazole, showed polypharmacological features on estrogen receptors or dipeptidyl peptidase-IV with half maximal inhibitory or effective concentration ranged from 0.2 to 10 µM. Moreover, simvastatin and ketoconazole showed potent antiproliferative activities on human MDA-MB-231 breast cancer cell line in MTT assays. The results indicated that these methods could be powerful tools in prediction of DTIs and drug repositioning