Treatment of pre-school children under 6 years of age for schistosomiasis: safety, efficacy and acceptability of praziquantel

BackgroundThe World Health Organization (WHO) recommends praziquantel for the control and treatment of schistosomiasis, with no real alternative. Pre-school children are excluded from population treatment programs mainly due to paucity of safety data on this age group.Objectives: This study investigated safety, efficacy and acceptability of praziquantel for the treatment of S. haematobium and S. mansoni infections among pre-school children aged <6years. The study also investigated the burden of schistosomiasis in this age group.Methods: Pre-school children (n=188) from Sudan were included in the study. The children were treated with praziquantel tablets at a single dose of 40 mg/kg body weight. Adverse events were assessed at 24 hours and 7 days later, via questionnaire administration to parents and guardians.Efficacy of treatment was assessed at 1, 3 and 6 months by examining stool and urine samples for schistosome eggs. Acceptability was determined by the number of children spitting or vomiting during administration of the drug.Results: The burden of schistosomiasis among pre-school children aged <6 years was high (31.1%), and this was comparable to that observed among school children-aged 6 years (32%). Praziquantel treatment achieved high cure rates (egg negative) for both S. haematobium and S.mansoni infections when assessed at 1 month after treatment (89.6-92.1%) and remained high for S. haematobium (89.6-100%) up to 6 months. However, cure rate dropped from 90.5% at one month to 58.8% and 69.2% at 3 and 6 months among S. mansoni-treated children.  Praziquantel treatment decreased egg counts considerably with  post-treatment geometric mean egg reductions rates ranging from 96.4% to 99.4% at 1 month. Acceptability of praziquantel treatment was high, only for one child the dose had to be repeated after initial spitting. Treatment resolved haematuria and improved weight of the children. There were no drug-related adverse events in all the treated children duringfollow-up at 24 hours and 7 days.Conclusions: Praziquantel is safe, effective and acceptable among children aged <6 years. Preschool children represent a high risk group for schistosomiasis and should be included in population treatment programs.Keywords:Schistosomiasis,Praziquantel, Safety,Young Children

Phytochemical, antimicrobial and cytotoxicity screening of ethanol extract of Acacia ehrenbergiana Hayne grown in Jazan Region of Saudi Arabia

Purpose: To explore the phytoconstituents of Acacia ehrenbergiana Hayne as well as its biological effects. Methods: Determination of phytoconstituents of ethanol extract of the plant was performed by gas chromatography-mass spectrometry (GC-MS) technique. Antibacterial screening was conducted against the isolates of Gram-positive and Gram-negative microbes while the anti-carcinogenic properties of the ethanol extract on cancerous cells were investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) cytotoxicity assay against breast MCF7, ovary cancer A2780 and colon cancer HT29 cells, respectively, in addition to normal MRC5 fibroblast cells. Results: GC-MS analysis identified 15 different phytochemicals in the ethanol extract. The extract exerted significant antimicrobial activity with the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) in the range 1.56 - 6.25 and 3.12 – 12.5 mg/L, respectively, against all test bacterial strains. Cytotoxic activity, obtained by MTT assay, was 28.81 ± 0.99, 12.50 ± 2.50, 23.90 ± 0.74 and 50.58 ± 3.24 μg/mL, against the three cancer cell lines and normal fibroblast, respectively. MTT cytotoxicity results was further confirmed by clonogenic survival assay on MCF7 cells. Conclusion: This study highlights the potential interesting ethnopharmacological applications of Acacia ehrenbergiana Hayne to treat drug-resistant pathogens as standardized extract. Keywords: Acacia ehrenbergiana, Phytochemistry, Antimicrobial, Cytotoxicit

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Bioactive principles, antibacterial and anticancer properties of Artemisia arborescens L.

Artemisia arborescens is a medicinal and aromatic plant used in traditionally by the people of Saudi Arabia. This research attempts to evaluate the bioactive constituents of the plant using organic solvents, as well as the antibacterial and anticancer properties of plant extracts. The Phytochemical analysis of methanol extract revealed eleven bioactive constituents, identified by comparing their retention periods and GC-MS profiles to account for 52.45 percent of the studied extract. In the meantime, the extract of pet ether had demonstrated the presence of sixteen significant constituents, six of which were distinct sesquiterpene derivatives. In lipophilic plant extract, three higher alkanes made up 12.49% of the total. These higher alkanes were tetratriacontane (6.55%), hentriacontane (4.17%), and octacosane (1.77%). Studies on antimicrobial activity have revealed that both methanolic and petroleum ether extracts had a broad spectrum of activity against specific human pathogens. Both extracts, however, failed to exhibit any anti-Candida albicans activity. Methanolic extract not shown inhibition in the cell growth of MCF-7 cell, but petroleum ether extract had shown significant anti-cancer activity against MCF-7 cell with an IC50 of 13.49 µg/mL. the results obtained show that A. arborescens have a lot of potential for further research into variety of biological functions, against cancer and microbes.

Angiogenesis and schistosomiasis

Angiogenesis has been recognised as a precursor of fibrosis in several pathologic conditions. Its participation has been demonstrated in schistosomiasis, both during periovular granuloma formation and in the genesis of schistosomal periportal fibrosis. Paradoxically, proliferation of new blood vessels, accompanied by production of vascular-endothelial growth factor, appeared prominent during fibrosis regression months after curative treatment of schistosomiasis. Thus, angiogenesis in schistosomiasis seems to have a two-way mode of action, participating both in fibrogenesis and in fibrosis degradation. Morphological observations presented here are in keeping with the possibility that, in the first case, angiogenesis allows pericytes to come in great numbers to the site of lesions and be detached from capillary walls and transformed into myofibroblasts, which are important extra-cellular matrix forming cells. During post-curative fibrosis regression, actin-containing pericytes appeared at various foci of tissue remodelling, especially at sites of repair of vascular lesions. The molecular and cell factors involved in both situations seem to be important subjects in need of further investigations and the schistosomiasis model certainly will be of great avail in this regard

Integrated Mapping of Neglected Tropical Diseases: Epidemiological Findings and Control Implications for Northern Bahr-el-Ghazal State, Southern Sudan

Integrated control of neglected tropical diseases (NTDs) is being scaled up in a number of developing countries, because it is thought to be more cost-effective than stand-alone control programmes. Under this approach, treatments for onchocerciasis, lymphatic filariasis (LF), schistosomiasis, soil-transmitted helminth (STH) infection, and trachoma are administered through the same delivery structure and at about the same time. A pre-requisite for implementation of integrated NTD control is information on where the targeted diseases are endemic and to what extent they overlap. This information is generated through surveys that can be labour-intensive and expensive. In Southern Sudan, all of the above diseases except onchocerciasis require further mapping before a comprehensive integrated NTD control programme can be implemented. To determine where treatment for which disease is required, integrated surveys were conducted for schistosomiasis, STH infection, LF, and loiasis, throughout one of ten states of the country. Our results show that treatment is only required for urinary schistosomiasis and STH in a few, yet separate, geographical area. This illustrates the importance of investing in disease mapping to minimize overall programme costs by being able to target interventions. Integration of survey methodologies for the above disease was practical and efficient, and minimized the effort required to collect these data

Effect of quercetin on steroidogenesis and folliculogenesis in ovary of mice with experimentally-induced polycystic ovarian syndrome

IntroductionPolycystic Ovary syndrome (PCOS) affects the health of many women around the world. Apart from fundamental metabolic problems connected to PCOS, focus of our study is on the role of quercetin on genes relevant to steroidogenesis and folliculogenesis.MethodsEighteen mature parkes strain mice (4-5 weeks old) weighing 18–21 g were randomly divided into three groups of six each as follows: Group I serves as the control and was given water and a regular chow diet ad lib for 66 days; group II was given oral gavage administration of letrozole (LETZ) (6 mg/kg bw) for 21 days to induce PCOS and was left untreated for 45 days; For three weeks, Group III received oral gavage dose of LETZ (6 mg/kg), after which it received Quercetin (QUER) (125 mg/kg bw orally daily) for 45 days.ResultsIn our study we observed that mice with PCOS had irregular estrous cycle with increased LH/FSH ratio, decreased estrogen level and decline in expression of Kitl, Bmp1, Cyp11a1, Cyp19a1, Ar, lhr, Fshr and Esr1 in ovary. Moreover, we observed increase in the expression of CYP17a1, as well as increase in cholesterol, triglycerides, testosterone, vascular endothelial growth factor VEGF and insulin levels. All these changes were reversed after the administration of quercetin in PCOS mice.DiscussionQuercetin treatment reversed the molecular, functional and morphological abnormalities brought on due to letrozole in pathological and physiological setting, particularly the issues of reproduction connected to PCOS. Quercetin doesn’t act locally only but it acts systematically as it works on Pituitary (LH/FSH)- Ovary (gonad hormones) axis. the Side effects of Quercetin have to be targeted in future researches. Quercetin may act as a promising candidate for medical management of human PCOS

The Pharmacokinetics and Interactions of Ivermectin in Humans—A Mini-review

Ivermectin is an antiparasitic drug with a broad spectrum of activity, high efficacy as well as a wide margin of safety. Since 1987, this compound has a widespread use in veterinary medicine and it use has been extended in humans. Here we present a brief review of the information availabile regarding the pharmacokinetics and interactions of ivermectin in humans. Awareness of these characteristics could improve the clinical efficacy of Ivermectin. All Authors declare that they do not have any Conflict of interest and that the work is original. All Authors agree that the contents of the manuscript are confidential and will not be copyrighted, submitted, or published elsewhere (including the Internet), in any language, while acceptance by the Journal is under consideration