Impact of ivermectin on onchocerciasis transmission: assessing the empirical evidence that repeated ivermectin mass treatments may lead to elimination/eradication in West-Africa

BACKGROUND: The Onchocerciasis Control Program (OCP) in West Africa has been closed down at the end of 2002. All subsequent control will be transferred to the participating countries and will almost entirely be based on periodic mass treatment with ivermectin. This makes the question whether elimination of infection or eradication of onchocerciasis can be achieved using this strategy of critical importance. This study was undertaken to explore this issue. METHODS: An empirical approach was adopted in which a comprehensive analysis was undertaken of available data on the impact of more than a decade of ivermectin treatment on onchocerciasis infection and transmission. Relevant entomological and epidemiological data from 14 river basins in the OCP and one basin in Cameroon were reviewed. Areas were distinguished by frequency of treatment (6-monthly or annually), endemicity level and additional control measures such as vector control. Assessment of results were in terms of epidemiological and entomological parameters, and as a measure of inputs, therapeutic and geographical coverage rates were used. RESULTS: In all of the river basins studied, ivermectin treatment sharply reduced prevalence and intensity of infection. Significant transmission, however, is still ongoing in some basins after 10-12 years of ivermectin treatment. In other basins, transmission may have been interrupted, but this needs to be confirmed by in-depth evaluations. In one mesoendemic basin, where 20 rounds of four-monthly treatment reduced prevalence of infection to levels as low as 2-3%, there was significant recrudescence of infection within a few years after interruption of treatment. CONCLUSIONS: Ivermectin treatment has been very successful in eliminating onchocerciasis as a public health problem. However, the results presented in this paper make it almost certain that repeated ivermectin mass treatment will not lead to the elimination of transmission of onchocerciasis from West Africa. Data on 6-monthly treatments are not sufficient to draw definitive conclusions.     

Reduced effect on apoptosis of 4-hydroxyhexenal and oxidized LDL enriched with n-3 fatty acids from postmenopausal women

BACKGROUND: Oxidized low-density lipoprotein (oxLDL) promotes apoptosis in atherosclerotic plaques in the vascular wall, a process mediated through its oxidized lipids. 4-Hydroxynonenal (HNE) and 4-hydroxyhexenal (HHE), derived from oxidation of n-6 and n-3 fatty acids, respectively, are among the major oxidized products in oxLDL. HYPOTHESIS: This study hypothesized that eicosapentaenoic acid/docosahexaenoic acid (EPA/DHA)-rich versus linoleic acid-rich oxLDL obtained from postmenopausal women and HNE versus HHE differentially influence apoptosis in U937 cells. EXPERIMENTAL DESIGN: Thirty healthy postmenopausal women were supplemented with 14 g/day safflower oil (SO), 7 g/day of both fish oil and SO (low dose LFO) or 14 g/day fish oil (high dose HFO) for 5 weeks. Low-density lipoprotein, obtained after supplementation, was oxidized with 5 microM CuSO(4) at 37 degrees C for 6 h. The concentration of cholesteryl ester hydroperoxides (CEOOH) and conjugated dienes was measured in the oxidized LDL (oxLDL). U937 cells were incubated with the oxLDL, 10 microM of HHE, 7 muM of HHE plus 3 microM of HNE, 5 microM of both HHE and HNE or 10 microM of HNE and the extent of apoptosis measured three ways. RESULTS: The concentration of CEOOH and conjugated dienes in oxLDL did not differ among the three treatment groups. The percent of apoptotic cells was approximately 40% lower when incubated with oxLDL obtained from the HFO-supplemented group than the SO-supplemented group measured by both the Annexin V and the DNA fragmentation assays (P = .04 and .004, respectively). Apoptosis of U937 cells was significantly lower in cells incubated with 10 microM of HHE, and mixtures of HHE and HNE than the 10 microM HNE when measured by the Annexin V, DNA fragmentation and 4,6-diamidino-2-phenylindole (DAPI) staining. CONCLUSIONS: These data suggest that the cardioprotective properties of n-3 fatty acids may derive in part from their less reactive oxidized lipid metabolites.     

The energy metabolism of <Emphasis Type="Italic">Methanomicrococcus blatticola</Emphasis>: physiological and biochemical aspects

Methanomicrococcus blatticola, a methanogenic archaeon isolated from the cockroach Periplaneta americana, is specialised in methane formation by the hydrogen-dependent reduction of methanol, monomethyl-, dimethyl- or trimethylamine. Experiments with resting cells demonstrated that the capability to utilise the methylated one-carbon compounds was growth substrate dependent. Methanol-grown cells were unable of methylamine conversion, while cells cultured on one of the methylated amines did not metabolise methanol. Unlike trimethylamine, monomethyl- and dimethylamine metabolism appeared to be co-regulated. The central reaction in the energy metabolism of all methanogens studied so far, the reduction of CoM-S-S-CoB, was catalysed with high specific activity by a cell-free system. Activity was associated with the membrane fraction. Phenazine was an efficient artificial substrate in partial reactions, suggesting that the recently discovered methanophenazine might act in the organism as the physiological intermediary electron carrier. Our experiments also showed that M. blatticola apparently lacks the pathway for methyl-coenzyme oxidation to CO₂, explaining the strict requirement for hydrogen in methanogenesis and the obligately heterotrophic character of the organism.     

Blue Light Overrides Repression of Asexual Sporulation by Mating Type Genes in the Basidiomycete Coprinus cinereus

Monokaryotic mycelia of the homobasidiomycete Coprinus cinereus form asexual spores (oidia) constitutively in abundant numbers. Mycelia with mutations in both mating type loci (Amut Bmut homokaryons) also produce copious oidia but only when exposed to blue light. We used such an Amut Bmut homokaryon to define environmental and inherent factors that influence the light-induced oidiation process. We show that the Amut function causes repression of oidiation in the dark and that light overrides this effect. Similarly, compatible genes from different haplotypes of the A mating type locus repress sporulation in the dark and not in the light. Compatible products of the B mating type locus reduce the outcome of light on A-mediated repression but the mutated B function present in the Amut Bmut homokaryons is not effective. In dikaryons, the coordinated regulation of asexual sporulation by compatible A and B mating type genes results in moderate oidia production in light. Copyright 1998 Academic Press.     

Production and characterization of a monoclonal antibody able to discriminate galectin-1 from galectin-2 and galectin-3

Antisera raised against galectin-1 exhibit crossreactivities with other galectins or related molecules. In order to overcome this problem, a monoclonal antibody to human brain galectin-1 was obtained by selecting clones without reactivity toward galectin-3. This mAb specifically bound galectin-1 of various animal origins but neither galectin-2 nor galectin-3. Western-blotting analysis of soluble human brain extracts after 2D gel electrophoresis revealed only the two most acidic isoforms of galectin-1. The ability of this mAb to bind galectin-1/asialofetuin complexes indicates that its epitope is not localized in the carbohydrate recognition domain of galectin-1. This particularity induces with efficiency its monospecificity.      

An anchored restriction-mapping approach applied to the genetic analysis of the Anopheles gambiae malaria vector complex 1

We introduce here a simple approach for rapidly determining restriction maps for a number of regions of a genome; this involves "anchoring" a map with a rare restriction site (in this case the seldom-cutting EagI) followed by partial digestion of a frequent-cutting enzyme (e.g., Sau 3A). We applied this technology to five species of the Anopheles gambiae complex. In a single Southern blot we obtained about a 15-kb restriction map each for the mtDNA, rRNA gene, and a scnDNA region for each of five species. Phylogenetic analyses of these regions yield trees at odds with the more traditional chromosome inversion-based trees. The value of the approach for systematic purposes is the ease with which several large, independent regions of the genome can be quickly assayed for molecular variation.      

Development of DNA puffs and patterns of polypeptide synthesis in the salivary glands of Bradysia hygida

In the three salivary gland regions of Bradysia hygida (Diptera, Sciaridae) the patterns of polypeptide synthesis, as revealed by electrophoresis and fluorography, are very stable during the fourth larval instar until about 30 h before the pupal molt. At this age the patterns of polypeptide synthesis start to undergo marked changes. The striking correlations between these changes and the development of two distinct groups of DNA puffs support the proposal that DNA puffs are causally related to the synthesis of specific proteins in the salivary glands.     

Organic N and particulate organic matter fractions in organic and conventional farming systems with a history of manure application

Indicators of soil fertility are needed for the effective management of organic farming systems. Sustainable management hinges upon our gaining an improved understanding of C and N dynamics. The influence of cropping systems and amendments applied in the Lakeland Wisconsin Integrated Cropping Systems Trial on total hydrolyzable organic N (THN) fractions and particulate organic matter (POM) was investigated after a decade in a conventional cash grain system (Conv) of continuous maize amended with inorganic fertilizer, an organic cash-grain system (Org-CG) that relied on legume N, and an organic animal-based system (Org-AN) that included alfalfa and manure additions. Maize yields had consistently ranked Org-CG < Conv < Org-AN. The THN and amino acid-N (AA-N) contents were ranked Org-AN > Org-CG > Conv. Amino sugar-N (AS-N) contents, which reflect microbially derived N, did not differ among systems and concentrations were quite high (346.5 mg AS-N/kg soil in the 0–50 cm depth). This, and soil variability were attributed to the sites’ history of manure application. The amount (1.3 g POM-C/kg soil) and proportion (≈7.5% of total SOC) of POM-C were quite low and did not differ among systems. Failure to accumulate SOC or POM in these soils, even under organic management, is attributed to rapid C decay and/or limited root growth. An N rate study was added the fall before samples were taken and N addition did increase yield in the Conv and Org-CG systems despite evidence of soil N surplus. This suggests that either amino N is unavailable to plants or that root N acquisition is limited by other constraints. Low POM-C contents accompanied by high AS-N and AA-N levels reveal an imbalance in these soils which are likely to be C limited. Based on this, we conclude excess N has prevented use of organic practices from enhancing soil quality at this site.     

Effects of the herbicide trifluralin in the initial development of Piptadenia gonoacantha (Fabales: Fabaceae)

Abstract

Trifluralin, a pre-emergent herbicide, is widely used in Brazil in the weed grass management in restoration areas. The objective was to evaluate the tolerance of Piptadenia gonoacantha to trifluralin. The treatments had three trifluralin doses (445, 890, and 1335?g a.i. ha^?1), applied in pre-sowing, as well as the control, without herbicide. Visual intoxication, seed germination, survival rate, emergence speed index (EMI), mean germination period, seedling height, and diameter, micromorphometric parameters of plant roots collected at 60 d after sowing, root length (RL) and volume, leaf area (LA), leaf numbers, root and shoot dry matter, and fluorescence of chlorophyll a at 30, 45, and 60 d after sowing were analyzed. Visual intoxication values above 50% were observed only with 1335?g a.i. ha^?1. The herbicide did not affect seed germination, EMI, average germination period, seedling height, and diameter, root micromorphometric parameters, length, dry matter or root volume, and chlorophyll a fluorescence. The dose 1335?g a.i. ha^?1 caused a reduction of 41.5% in survival, 50.3% in the LA, 36.7% in the number of leaves (LN), and 59.8% in the aerial dry mass of seedlings. The trifluralin presents potential for restoration programs of degraded areas with this forest species.