A multicenter,community-based,mixed methods assessment of the acceptability of a triple drug regimen for elimination of lymphatic filariasis

BackgroundMany countries will not reach elimination targets for lymphatic filariasis in 2020 using the two-drug treatment regimen (diethylcarbamazine citrate [DEC] and albendazole [DA]). A cluster-randomized, community-based safety study performed in Fiji, Haiti, India, Indonesia and Papua New Guinea tested the safety and efficacy of a new regimen of ivermectin, DEC and albendazole (IDA).Methodology/Principal findingsTo assess acceptability of IDA and DA, a mixed methods study was embedded within this community-based safety study. The study objective was to assess the acceptability of IDA versus DA. Community surveys were performed in each country with randomly selected participants (>14 years) from the safety study participant list in both DA and IDA arms. In depth interviews (IDI) and focus group discussions (FGD) assessed acceptability-related themes. In 1919 individuals, distribution of sex, microfilariae (Mf) presence and circulating filarial antigenemia (CFA), adverse events (AE) and age were similar across arms. A composite acceptability score summed the values from nine indicators (range 9–36). The median (22.5) score indicated threshold of acceptability. There was no difference in scores for IDA and DA regimens. Mean acceptability scores across both treatment arms were: Fiji 33.7 (95% CI: 33.1–34.3); Papua New Guinea 32.9 (95% CI: 31.9–33.8); Indonesia 30.6 (95% CI: 29.8–31.3); Haiti 28.6 (95% CI: 27.8–29.4); India 26.8 (95% CI: 25.6–28) (P<0.001). AE, Mf or CFA were not associated with acceptability. Qualitative research (27 FGD; 42 IDI) highlighted professionalism and appreciation for AE support. No major concerns were detected about number of tablets. Increased uptake of LF treatment by individuals who had never complied with MDA was observed.Conclusions/SignificanceIDA and DA regimens for LF elimination were highly and equally acceptable in individuals participating in the community-based safety study in Fiji, Haiti, India, Indonesia, and Papua New Guinea. Country variation in acceptability was significant. Acceptability of the professionalism of the treatment delivery was highlighted.     

Polymorphism of the prion protein gene (<Emphasis Type="Italic">PRNP</Emphasis>) in Polish cattle affected by classical bovine spongiform encephalopathy

Recent attempts to discover genetic factors affecting cattle resistance/susceptibility to bovine spongiform encephalopathy (BSE) have led to the identification of two insertion/deletion (indel) polymorphisms, located within the promoter and intron 1 of the prion protein gene PRNP, showing a significant association with the occurrence of classical form of the disease. Because the effect of the polymorphisms was studied only in few populations, in this study we investigated whether previously described association of PRNP indel polymorphisms with BSE susceptibility in cattle is also present in Polish cattle population. We found a significant relation between the investigated PRNP indel polymorphisms (23 and 12 bp indels), and susceptibility of Polish Holstein-Friesian cattle to classical BSE (P < 0.05). The deletion variants of both polymorphisms were related to increased susceptibility, whereas insertion variants were protective against BSE.     

Lipid peroxidation in the fungus Curvularia lunata exposed to nickel

The effect of Ni²⁺ on fungal growth, cellular fatty acid profile and lipid peroxidation was studied (with an emphasis on the kinetics of these processes) in the strain of filamentous fungus Curvularia lunata. In the cultures supplemented with 0.2 and 0.6 mM Ni²⁺ the lag phase was extended and the specific growth rate decreased, however, the maximum yield of biomass at the stationary phase reached, respectively, 97 and 27% of the control. The treatment with Ni²⁺ changed the proportion of 18 C atom fatty acids, with the most significant decrease in the content of linoleic acid (18:2) followed by a rise in the degree of fatty acid saturation. In the mycelia exposed to Ni²⁺ the levels of TBARS (lipid peroxidation products) increased and ranged between 156 and 823% over the control. The presented data reveal that the oxidative stress resulting, among others, in membrane lipid peroxidation is involved in the mechanisms of the nickel toxicity towards C. lunata and suggest that this fungus exhibits an ability to cope, to some extent, with the increased level of lipid peroxides.     

The effect of soil drought on the composition of carbohydrates in yellow lupin seeds and triticale kernels

Carbohydrate analysis was made of yellow lupin seeds (cv. Juno) and triticale kernels (cv. Dagro), produced by plants exposed to drought stress for 21 days after the initial flowering of the first node of lupin and initial earing of triticale. The seeds of all experimental variants were harvest at full maturity, dried and stored in linen bags at 18–20 °C. Soluble carbohydrates were extracted and analysed as described by Horbowicz and Obendorf (1994). Gas chromatographic separation of carbohydrates showed that raffinose family oligosaccharides (RFO) were dominant in lupin seeds. The other carbohydrates present were sucrose (10 %), cyclitols and galactosyl cyclitols (12–13 %). Soil drought resulted in higher levels of verbascose, but decreased the quantities of the other carbohydrates in lupine seeds. In triticale kernels, over 50 % of soluble sugars were composed of sucrose and maltose, while 17.7 % were raffinose and stachyose. In response to drought the content of mono- and oligosaccharides declined. The decrease of soluble carbohydrates content in seeds of lupin and triticale kernels has no effect on the seed germination and vigour. It is assumed that the changes in the concentration of soluble sugars observed under drought may impair the storability of triticale kernels, but improve it for lupine seeds.     

Formaldehyde and methanol biodegradation with the methylotrophic yeast Hansenula polymorpha. An application to real wastewater treatment

The application of methylotrophic yeast Hansenula polymorpha to the treatment of methanol and formaldehyde-containing wastewater was experimentally verified. Avariety of real wastewater samples originating from chemical industry effluent were examined. The yeast cell culture could grow in the wastewater environment, revealing low trophic requirements and a very high adaptation potential to poor cultivation conditions.The proliferation of cells was accompanied by a concomitant xenobiotic biodegradation. Grown, preadapted cellular suspension at a density of about 1 × 10⁷ cells/ml proved to be able to utilize formaldehyde present in wastewater at concentrations up to1750 mg/l, levels toxic to most microorganisms. The biological waste treatment method presented shows the enhanced potential by means of specific enzymatic activities of monocarbonic compound oxidations through methylotrophic pathway reactions. The need to obtain mutants highly resistant to formaldehyde has also been rationalized.     

Lactones 32 : New aspects of the application of Fusarium strains to production of alkylsubstituted ɛ-lactones

Wild strains Fusarium oxysporum and Fusarium avenaceum were chosen among six to the Baeyer–Villiger oxidation of alkylsubstituted cyclohexanones (1a–e) to the corresponding highly enantiomerically enriched ?-lactones. Besides the oxidation activity, the biocatalysts were also able to the reduction of carbonyl group. Only cis-methylcyclohexanols turned out to be further transformed to lactones. Biotransformations of optically enriched ketones and alcohols were also studied to give an overall view of stereoselectivity of the enzymes involved in biocatalytic pathway.     

A multiplex real-time PCR assay for detection of oseltamivir-resistant strains of influenza virus

Influenza is a contagious disease of humans and animals caused by viruses belonging to the Orthomyxoviridae family. The influenza A virus genome consists of negative sense, single-stranded, segmented RNA. Influenza viruses are classified into subtypes based on two surface antigens known as hemagglutinin (H) and neuraminidase (N). The main problem with influenza A viruses infecting humans is drug resistance, which is caused by antigenic changes. A few antiviral drugs are available, but the most popular is the neuraminidase inhibitor — oseltamivir. The resistance against this drug has probably developed through antigenic drift by a point mutation in one amino acid at position 275 (H275Y). In order to prevent a possible influenza pandemic it is necessary to develop fast diagnostic tests. The aim of this project was to develop a new test for detection of influenza A virus and determination of oseltamivir resistance/sensitivity in humans. Detection and differentiation of oseltamivir resistance/sensitivity of influenza A virus was based on real-time PCR. This test contains two TaqMan probes, which work at different wavelengths. Application of techniques like multiplex real-time PCR has greatly enhanced the capability for surveillance and characterization of influenza viruses. After its potential validation, this test can be used for diagnosis before treatment.     

Hematological Parameters,and Hematopoietic Growth Factors: Epo and IL-3 in Response to Whole-Body Cryostimulation (WBC) in Military Academy Students

The effects of extreme cold on the human body are not fully understood, there are also no reports on the effect of cryogenic temperatures on the levels of erythropoietin (EPO) and interleukin 3 (IL-3), two important factors that regulate hematopoiesis. Aim: determination of changes in peripheral blood cell counts and EPO and IL-3 levels induced by a series of 10, 20 and 30 standard whole-body cryostimulation (WBC) treatments. The study involved 45 men, experimental group (EXP, n = 30) subjected to 30 WBC treatments (−130°C, treatment duration: 3 minutes) and a control group (CON, n = 15). Blood samples were collected before the series of treatments and after 10, 20 and 30 treatments. After 10 and 20 treatments we observed lower red blood cell counts and hematocrit and hemoglobin levels compared to baseline (p<0.05) and the control group (p<0.05). Additionally we observed an increase in hemoglobin concentration in plasma (p<0.05), and bilirubin after 10 and 20 treatments, and a decrease in plasma concentration of haptoglobin after 10, 20 and 30 treatments (p<0.05). The number of leukocytes was higher after 10 and 20 WBC treatments compared to baseline and the CON group. EPO concentration in plasma was elevated and the concentration of IL-3 was lower after 10, 20 and 30 WBC treatments. The decrease in indices of the erythrocytic system, plasma hemoglobin and bilirubin, with a simultaneous decrease in haptoglobin concentrations after 10 and 20 WBC treatments, may be due to increased intravascular hemolysis. At the same time there was a small, but statistically significant increase in the concentration of EPO stimulated erythropoiesis which could facilitate a return of erythrocytic system indices to initial levels after 30 WBC treatments. Changes in the white blood cell system showed transient mobilization of this system under the influence of WBC.