Modelling the impact of ivermectin on River Blindness and its burden of morbidity and mortality in African Savannah: EpiOncho projections

BACKGROUND: The African Programme for Onchocerciasis Control (APOC) has refocused its goals on the elimination of infection where possible, seemingly achievable by 15–17 years of annual mass distribution of ivermectin in some African foci. Previously, APOC had focused on the elimination of onchocerciasis as a public health problem. Timeframes have been set by the World Health Organization, the London Declaration on Neglected Tropical Diseases and the World Bank to achieve these goals by 2020–2025. METHODS: A novel mathematical model of the dynamics of onchocercal disease is presented which links documented associations between Onchocerca volvulus infection and the prevalence and incidence of morbidity and mortality to model outputs from our host age- and sex-structured onchocerciasis transmission framework (EpiOncho). The model is calibrated for African savannah settings, and used to assess the impact of long-term annual mass administration of ivermectin on infection and ocular and skin disease and to explore how this depends on epidemiological and programmatic variables. RESULTS: Current onchocerciasis disease projections, which do not account for excess mortality of sighted individuals with heavy microfilarial loads, underestimate disease burden. Long-term annual ivermectin treatment is highly effective at reducing both the morbidity and mortality associated with onchocerciasis, and this result is not greatly influenced by treatment coverage and compliance. By contrast, impact on microfilarial prevalence and intensity is highly dependent on baseline endemicity, treatment coverage and systematic non-compliance. CONCLUSIONS: The goals of eliminating morbidity and infection with ivermectin alone are distinctly influenced by epidemiological and programmatic factors. Whilst the former goal is most certainly achievable, reaching the latter will strongly depend on initial endemicity (the higher the endemicity, the greater the magnitude of inter-treatment transmission), advising caution when generalising the applicability of successful elimination outcomes to other areas. The proportion of systematic non-compliers will become far more influential in terms of overall success in achieving elimination goals

Dialogue management systems: a survey and overview

This report provides an overview of the current issues and techniques for the modelling of dialogues using a computer. A dialogue management system can manage a dialogue between two or more agents, be they human or computer. Recently, increasingly complex dialogues are being modelled which allow a range of discourse phenomena including ellipsis and anaphoric reference. Such dialogues are thought to be similar to those between two humans, and accurate modelling of these phenomena leads to "pleasant", i.e. easy to talk to, and natural human-computer dialogues. Dialogue management can be classified into three often overlapping approaches: discourse grammars, plan-based and collaborative approaches. The design of a system often begins by eliciting the language used initially between two humans and later by Wizard of Oz experiments. Special issues relating to dialogue management systems are discussed including recovery strategies from different types of errors and the coding of dialogue in corpora. Lastly, approaches to evaluation are briefly discussed from the qualitative and quantitative viewpoints, recognising the importance and size of this sub-field

Uncertainty Surrounding Projections of the Long-Term Impact of Ivermectin Treatment on Human Onchocerciasis

BackgroundRecent studies in Mali, Nigeria, and Senegal have indicated that annual (or biannual) ivermectin distribution may lead to local elimination of human onchocerciasis in certain African foci. Modelling-based projections have been used to estimate the required duration of ivermectin distribution to reach elimination. A crucial assumption has been that microfilarial production by Onchocerca volvulus is reduced irreversibly by 30-35% with each (annual) ivermectin round. However, other modelling-based analyses suggest that ivermectin may not have such a cumulative effect. Uncertainty in this (biological) and other (programmatic) assumptions would affect projected outcomes of long-term ivermectin treatment.Methodology/principal findingsWe modify a deterministic age- and sex-structured onchocerciasis transmission model, parameterised for savannah O. volvulus-Simulium damnosum, to explore the impact of assumptions regarding the effect of ivermectin on worm fertility and the patterns of treatment coverage compliance, and frequency on projections of parasitological outcomes due to long-term, mass ivermectin administration in hyperendemic areas. The projected impact of ivermectin distribution on onchocerciasis and the benefits of switching from annual to biannual distribution are strongly dependent on assumptions regarding the drug's effect on worm fertility and on treatment compliance. If ivermectin does not have a cumulative impact on microfilarial production, elimination of onchocerciasis in hyperendemic areas may not be feasible with annual ivermectin distribution.Conclusions/significanceThere is substantial (biological and programmatic) uncertainty surrounding modelling projections of onchocerciasis elimination. These uncertainties need to be acknowledged for mathematical models to inform control policy reliably. Further research is needed to elucidate the effect of ivermectin on O. volvulus reproductive biology and quantify the patterns of coverage and compliance in treated communities

Developing a corpus-based grammar model within a continuous commercial speech recognition package

This paper is derived from experiments with a commercial ’off-the-shelf’ continuous speech recognition system, applied to the apparently restricted domain of Air Traffic Control (ATC) for light aircraft. The system is required to transcribe key sub-phrases in a transmission by the ATC to a particular aircraft, the commercial speech recognition system providing the main recognition component. After the development of a corpus of transmissions, it was realised that key information is often interspersed with unconstrained English. Initial attempts focused on using a wildcard mechanism for the non-key sub- phrases. The mechanism, however, proved to be valuable only in simplistic grammars due to its overgenerative nature. The speech recognition system showed us that whilst useful mechanisms are provided, such as the wildcard mechanism, they tend to make over-simplistic assumptions about English grammar and dialogue structure

Predicting mosquito infection from Plasmodium falciparum gametocyte density and estimating the reservoir of infection

Transmission reduction is a key component of global efforts to control and eliminate malaria; yet, it is unclear how the density of transmission stages (gametocytes) influences infection (proportion of mosquitoes infected). Human to mosquito transmission was assessed using 171 direct mosquito feeding assays conducted in Burkina Faso and Kenya. Plasmodium falciparum infects Anopheles gambiae efficiently at low densities (4% mosquitoes at 1/µl blood), although substantially more (>200/µl) are required to increase infection further. In a site in Burkina Faso, children harbour more gametocytes than adults though the non-linear relationship between gametocyte density and mosquito infection means that (per person) they only contribute slightly more to transmission. This method can be used to determine the reservoir of infection in different endemic settings. Interventions reducing gametocyte density need to be highly effective in order to halt human-mosquito transmission, although their use can be optimised by targeting those contributing the most to transmission. DOI:http://dx.doi.org/10.7554/eLife.00626.001

Multi-Wavelength Modelling of the Beta Leo Debris Disc: 1, 2 or 3 planetesimal populations?

In this paper we present a model of the Beta Leo debris disc, with an emphasis on modelling the resolved PACS images obtained as part of the Herschel key programme DEBRIS. We also present new SPIRE images of the disc at 250 microns, as well as new constraints on the disc from SCUBA-2, mid-IR and scattered light imaging. Combining all available observational constraints, we find three possible models for the Beta Leo (HD102647) debris disc: (i) A 2 component model, comprised of a hot component at 2 AU and a cold component from 15-70 AU. (ii) A 3 component model with hot dust at 2 AU, warm dust at 9 AU, and a cold component from 30-70 AU, is equally valid since the cold emission is not resolved within 30 AU. (iii) A somewhat less likely possibility is that the system consists of a single very eccentric planetesimal population, with pericentres at 2 AU and apocentres at 65 AU. Thus, despite the wealth of observational constraints significant ambiguities remain; deep mid-IR and scattered light imaging of the dust distribution within 30 AU seems the most promising method to resolve the degeneracy. We discuss the implications for the possible planetary system architecture; e.g., the 2 component model suggests planets may exist at 2-15 AU, while the 3 component model suggests planets between 2-30 AU with a stable region containing the dust belt at 9 AU, and there should be no planets between 2-65 AU in the eccentric planetesimal model. We suggest that the hot dust may originate in the disintegration of comets scattered in from the cold disc, and examine all A stars known to harbour both hot and cold dust to consider the possibility that the ratio of hot and cold dust luminosities is indicative of the intervening planetary system architecture.Comment: 20 pages, 14 figures. Accepted to MNRA

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

Volatiles in the Desert: Subtle Remote-sensing Signatures of the Dakhleh Oasis Catastrophic Event, Western Desert, Egypt

Over the past decade members of the Dakhleh Oasis Project have studied enigmatic signatures in the Pleistocene geologic record of portions of the Dakhleh oasis and palaeo-oasis in Egypt's Western Desert [1,2]. In particular, Si-Ca-Al rich glass melt (Dakhleh Glass, Fig. 1) points to a catastrophic event between c.100,000-200,000 years ago [3] in this well-studied African savannah and freshwater lake Middle Stone Age environment [4,5]

Improving statistical inference on pathogen densities estimated by quantitative molecular methods: malaria gametocytaemia as a case study

BACKGROUND: Quantitative molecular methods (QMMs) such as quantitative real-time polymerase chain reaction (q-PCR), reverse-transcriptase PCR (qRT-PCR) and quantitative nucleic acid sequence-based amplification (QT-NASBA) are increasingly used to estimate pathogen density in a variety of clinical and epidemiological contexts. These methods are often classified as semi-quantitative, yet estimates of reliability or sensitivity are seldom reported. Here, a statistical framework is developed for assessing the reliability (uncertainty) of pathogen densities estimated using QMMs and the associated diagnostic sensitivity. The method is illustrated with quantification of Plasmodium falciparum gametocytaemia by QT-NASBA. RESULTS: The reliability of pathogen (e.g. gametocyte) densities, and the accompanying diagnostic sensitivity, estimated by two contrasting statistical calibration techniques, are compared; a traditional method and a mixed model Bayesian approach. The latter accounts for statistical dependence of QMM assays run under identical laboratory protocols and permits structural modelling of experimental measurements, allowing precision to vary with pathogen density. Traditional calibration cannot account for inter-assay variability arising from imperfect QMMs and generates estimates of pathogen density that have poor reliability, are variable among assays and inaccurately reflect diagnostic sensitivity. The Bayesian mixed model approach assimilates information from replica QMM assays, improving reliability and inter-assay homogeneity, providing an accurate appraisal of quantitative and diagnostic performance. CONCLUSIONS: Bayesian mixed model statistical calibration supersedes traditional techniques in the context of QMM-derived estimates of pathogen density, offering the potential to improve substantially the depth and quality of clinical and epidemiological inference for a wide variety of pathogens

Bayesian paternity analysis and mating patterns in a parasitic nematode, Trichostrongylus tenuis

Mating behaviour is a fundamental aspect of the evolutionary ecology of sexually reproducing species, but one that has been under-researched in parasitic nematodes. We analysed mating behaviour in the parasitic nematode Trichostrongylus tenuis by performing a paternity analysis in a population from a single red grouse host. Paternity of the 150 larval offspring of 25 mothers (sampled from one of the two host caeca) was assigned among 294 candidate fathers (sampled from both caeca). Each candidate father's probability of paternity of each offspring was estimated from 10-locus microsatellite genotypes. Seventy-six (51%) offspring were assigned a father with a probability of >0.8, and the estimated number of unsampled males was 136 (95% credible interval (CI) 77-219). The probability of a male from one caecum fathering an offspring in the other caecum was estimated as 0.024 (95% CI 0.003-0.077), indicating that the junction of the caeca is a strong barrier to dispersal. Levels of promiscuity (defined as the probability of two of an adult's offspring sharing only one parent) were high for both sexes. Variance in male reproductive success was moderately high, possibly because of a combination of random mating and high variance in post-copulatory reproductive success. These results provide the first data on individual mating behaviour among parasitic nematodes