The Cost of Annual versus Biannual Community-Directed Treatment of Onchocerciasis with Ivermectin: Ghana as a Case Study

BACKGROUND: It has been proposed that switching from annual to biannual (twice yearly) mass community-directed treatment with ivermectin (CDTI) might improve the chances of onchocerciasis elimination in some African foci. However, historically, relatively few communities have received biannual treatments in Africa, and there are no cost data associated with increasing ivermectin treatment frequency at a large scale. Collecting cost data is essential for conducting economic evaluations of control programmes. Some countries, such as Ghana, have adopted a biannual treatment strategy in selected districts. We undertook a study to estimate the costs associated with annual and biannual CDTI in Ghana. METHODOLOGY: The study was conducted in the Brong-Ahafo and Northern regions of Ghana. Data collection was organized at the national, regional, district, sub-district and community levels, and involved interviewing key personnel and scrutinizing national records. Data were collected in four districts; one in which treatment is delivered annually, two in which it is delivered biannually, and one where treatment takes place biannually in some communities and annually in others. Both financial and economic costs were collected from the health care provider's perspective. PRINCIPAL FINDINGS: The estimated cost of treating annually was US Dollars (USD) 0.45 per person including the value of time donated by the community drug distributors (which was estimated at USD 0.05 per person per treatment round). The cost of CDTI was approximately 50–60% higher in those districts where treatment was biannual than in those where it was annual. Large-scale mass biannual treatment was reported as being well received and considered sustainable. CONCLUSIONS/SIGNIFICANCE: This study provides rigorous evidence of the different costs associated with annual and biannual CDTI in Ghana which can be used to inform an economic evaluation of the debate on the optimal treatment frequency required to control (or eliminate) onchocerciasis in Africa

A fouryear followup of school children after masstreatment for Schistosomiasis and Soil Transmitted Helminths in Mwea, Central Kenya

Poly-parasitism infections are common in school children in tropical regions, especially in Africa. In a school based schistosomiasis and soil-transmitted helminths de-worming model project in Mwea, Kenya, approximately 40,000 school age children from 86 schools were treated annually with a standard dose of praziquantel (40mg/kg body weight) and albendazole (400mg). A cohort of approximately 2,300 children from 5 sentinel schools were followed up at multiple time points each year for four years and examined for intestinal helminths (Schistosoma mansoni, Trichuris trichiura, Hookworm (Necator americanus) and Ascaris lumbricoides). The overall prevalence of infection in the five schools before treatment was 47.4% for S. mansoni, 16.7% for N. americanus, 0.8% for T. trichiura and 1.7% for A. lumbricoides. The mean intensity of infection, as measured by eggs per gram of faeces (epg) was 146.2 for S. mansoni, 36.3 for N. americanus 1.0 for T. trichiura and 35.8 for A. lumbricoides. After 4 rounds of treatment, prevalence of S. mansoni reduced significantly by 88.7% to 5.4% (95%CI=3.6% -7.1%), a 97.1% reduction. The prevalence and intensity of S. mansoni infection varied by school according to its proximity to irrigated area, with those schools closest to the irrigated areas presenting higher infection prevalence and intensity. Re-infection with schistosomiasis following treatment was observed and is likely to reflect continued environmental transmission due to non-treatment of the adult population. Soil-transmitted helminths are less prevalent in the cohort, with corresponding lower intensity. This may allow albendazole treatment to be reduced to every 2 or 3 years. This study has shown that periodic administration of anthelminthic drugs reduces the prevalence and intensity (which is likely to be a close proxy of morbidity) of intestinal parasitic infections in school-age children. Adults in the community could also be targeted where resources allow in order to further increasing the effectiveness of de-worming programmes. Keywords: Soil transmitted helminths, Schistosomiasis, school age, prevalence, Intensity, mass de-worming, school childre

High-throughput clone library analysis of the mucosa-associated microbiota reveals dysbiosis and differences between inflamed and non-inflamed regions of the intestine in inflammatory bowel disease.

BACKGROUND: The gut microbiota is thought to play a key role in the development of the inflammatory bowel diseases Crohn's disease (CD) and ulcerative colitis (UC). Shifts in the composition of resident bacteria have been postulated to drive the chronic inflammation seen in both diseases (the "dysbiosis" hypothesis). We therefore specifically sought to compare the mucosa-associated microbiota from both inflamed and non-inflamed sites of the colon in CD and UC patients to that from non-IBD controls and to detect disease-specific profiles. RESULTS: Paired mucosal biopsies of inflamed and non-inflamed intestinal tissue from 6 CD (n = 12) and 6 UC (n = 12) patients were compared to biopsies from 5 healthy controls (n = 5) by in-depth sequencing of over 10,000 near full-length bacterial 16S rRNA genes. The results indicate that mucosal microbial diversity is reduced in IBD, particularly in CD, and that the species composition is disturbed. Firmicutes were reduced in IBD samples and there were concurrent increases in Bacteroidetes, and in CD only, Enterobacteriaceae. There were also significant differences in microbial community structure between inflamed and non-inflamed mucosal sites. However, these differences varied greatly between individuals, meaning there was no obvious bacterial signature that was positively associated with the inflamed gut. CONCLUSIONS: These results may support the hypothesis that the overall dysbiosis observed in inflammatory bowel disease patients relative to non-IBD controls might to some extent be a result of the disturbed gut environment rather than the direct cause of disease. Nonetheless, the observed shifts in microbiota composition may be important factors in disease maintenance and severity

The molecular basis of color vision in colorful fish: Four Long Wave-Sensitive (LWS) opsins in guppies (Poecilia reticulata) are defined by amino acid substitutions at key functional sites

<p>Abstract</p> <p>Background</p> <p>Comparisons of functionally important changes at the molecular level in model systems have identified key adaptations driving isolation and speciation. In cichlids, for example, long wavelength-sensitive (LWS) opsins appear to play a role in mate choice and male color variation within and among species. To test the hypothesis that the evolution of elaborate coloration in male guppies (<it>Poecilia reticulata</it>) is also associated with opsin gene diversity, we sequenced long wavelength-sensitive (LWS) opsin genes in six species of the family Poeciliidae.</p> <p>Results</p> <p>Sequences of four LWS opsin genes were amplified from the guppy genome and from mRNA isolated from adult guppy eyes. Variation in expression was quantified using qPCR. Three of the four genes encode opsins predicted to be most sensitive to different wavelengths of light because they vary at key amino acid positions. This family of LWS opsin genes was produced by a diversity of duplication events. One, an intronless gene, was produced prior to the divergence of families Fundulidae and Poeciliidae. Between-gene PCR and DNA sequencing show that two of the guppy LWS opsins are linked in an inverted orientation. This inverted tandem duplication event occurred near the base of the poeciliid tree in the common ancestor of <it>Poecilia </it>and <it>Xiphophorus</it>. The fourth sequence has been uncovered only in the genus <it>Poecilia</it>. In the guppies surveyed here, this sequence is a hybrid, with the 5' end most similar to one of the tandem duplicates and the 3' end identical to the other.</p> <p>Conclusion</p> <p>Enhanced wavelength discrimination, a possible consequence of opsin gene duplication and divergence, might have been an evolutionary prerequisite for color-based sexual selection and have led to the extraordinary coloration now observed in male guppies and in many other poeciliids.</p

Numbat nirvana: the conservation ecology of the endangered numbat Myrmecobius fasciatus (Marsupialia: Myrmecobiidae) reintroduced to Scotia and Yookamurra Sanctuaries, Australia

Despite a vigorous reintroduction program between 1985 and 2010, numbat populations in Western Australia are either static or declining. This study aimed to document the population ecology of numbats at two sites that are going against this trend: Scotia Sanctuary in far western New South Wales and Yookamurra Sanctuary in the riverland of South Australia. Scotia (64 659 ha) and Yookamurra (5026 ha) are conservation reserves owned and managed by the Australian Wildlife Conservancy and where numbats were reintroduced in 1999 and 1993 respectively. Both sites have large conservation-fence-protected introduced-species-free areas where there are no cats (Felis catus) or red foxes (Vulpes vulpes). Numbats were sourced from both wild and captive populations. From small founder populations, the Scotia numbats are now estimated to number 169 (113–225) with 44 at Yookamurra. Radio-collared individuals at Scotia were active between 13 and 31°C. Females had home ranges of 28.3 ± 6.8 ha and males 96.6 ± 18.2 ha, which leads to an estimated sustainable population or carrying capacity of 413–502 at Scotia. Captive-bred animals from Perth Zoo had a high mortality rate upon reintroduction at Scotia due to predation by raptors and starvation. The habitat preferences for mallee with a shrub understorey appear to be driven by availability of termites, and other reintroduced ecosystem engineers appear to have been facilitators by creating new refuge burrows for numbats. This study shows that numbats can be successfully reintroduced into areas of their former range if protected from introduced predators, and illustrates the difficulties in monitoring such cryptic species.</jats:p

Costs of crowding for the transmission of malaria parasites

Host-parasite interactio

The transcriptional response of Caenorhabditis elegans to ivermectin exposure identifies novel genes involved in the response to reduced food intake

We have examined the transcriptional response of Caenorhabditis elegans following exposure to the anthelmintic drug ivermectin (IVM) using whole genome microarrays and real-time QPCR. Our original aim was to identify candidate molecules involved in IVM metabolism and/or excretion. For this reason the IVM tolerant strain, DA1316, was used to minimise transcriptomic changes related to the phenotype of drug exposure. However, unlike equivalent work with benzimidazole drugs, very few of the induced genes were members of xenobiotic metabolising enzyme families. Instead, the transcriptional response was dominated by genes associated with fat mobilization and fatty acid metabolism including catalase, esterase, and fatty acid CoA synthetase genes. This is consistent with the reduction in pharyngeal pumping, and consequential reduction in food intake, upon exposure of DA1316 worms to IVM. Genes with the highest fold change in response to IVM exposure, cyp-37B1, mtl-1 and scl-2, were comparably up-regulated in response to short–term food withdrawal (4 hr) independent of IVM exposure, and GFP reporter constructs confirm their expression in tissues associated with fat storage (intestine and hypodermis). These experiments have serendipitously identified novel genes involved in an early response of C. elegans to reduced food intake and may provide insight into similar processes in higher organisms

Extended pharmacodynamic responses observed upon PROTAC-mediated degradation of RIPK2.

Proteolysis-Targeting Chimeras (PROTACs) are heterobifunctional small-molecules that can promote the rapid and selective proteasome-mediated degradation of intracellular proteins through the recruitment of E3 ligase complexes to non-native protein substrates. The catalytic mechanism of action of PROTACs represents an exciting new modality in drug discovery that offers several potential advantages over traditional small-molecule inhibitors, including the potential to deliver pharmacodynamic (PD) efficacy which extends beyond the detectable pharmacokinetic (PK) presence of the PROTAC, driven by the synthesis rate of the protein. Herein we report the identification and development of PROTACs that selectively degrade Receptor-Interacting Serine/Threonine Protein Kinase 2 (RIPK2) and demonstrate in vivo degradation of endogenous RIPK2 in rats at low doses and extended PD that persists in the absence of detectable compound. This disconnect between PK and PD, when coupled with low nanomolar potency, offers the potential for low human doses and infrequent dosing regimens with PROTAC medicines

SPICES: Spectro-Polarimetric Imaging and Characterization of Exoplanetary Systems

SPICES (Spectro-Polarimetric Imaging and Characterization of Exoplanetary Systems) is a five-year M-class mission proposed to ESA Cosmic Vision. Its purpose is to image and characterize long-period extrasolar planets and circumstellar disks in the visible (450 - 900 nm) at a spectral resolution of about 40 using both spectroscopy and polarimetry. By 2020/22, present and near-term instruments will have found several tens of planets that SPICES will be able to observe and study in detail. Equipped with a 1.5 m telescope, SPICES can preferentially access exoplanets located at several AUs (0.5-10 AU) from nearby stars ($<$25 pc) with masses ranging from a few Jupiter masses to Super Earths ($\sim$2 Earth radii, $\sim$10 M$_{\oplus}$) as well as circumstellar disks as faint as a few times the zodiacal light in the Solar System

Estimation of changes in the force of infection for intestinal and urogenital schistosomiasis in countries with Schistosomiasis Control Initiative-assisted programmes

The last decade has seen an expansion of national schistosomiasis control programmes in Africa based on large-scale preventative chemotherapy. In many areas this has resulted in considerable reductions in infection and morbidity levels in treated individuals. In this paper, we quantify changes in the force of infection (FOI), defined here as the per (human) host parasite establishment rate, to ascertain the impact on transmission of some of these programmes under the umbrella of the Schistosomiasis Control Initiative (SCI)