A Research Agenda for Helminth Diseases of Humans: Modelling for Control and Elimination

Mathematical modelling of helminth infections has the potential to inform policy and guide research for the control and elimination of human helminthiases. However, this potential, unlike in other parasitic and infectious diseases, has yet to be realised. To place contemporary efforts in a historical context, a summary of the development of mathematical models for helminthiases is presented. These efforts are discussed according to the role that models can play in furthering our understanding of parasite population biology and transmission dynamics, and the effect on such dynamics of control interventions, as well as in enabling estimation of directly unobservable parameters, exploration of transmission breakpoints, and investigation of evolutionary outcomes of control. The Disease Reference Group on Helminth Infections (DRG4), established in 2009 by the Special Programme for Research and Training in Tropical Diseases (TDR), was given the mandate to review helminthiases research and identify research priorities and gaps. A research and development agenda for helminthiasis modelling is proposed based on identified gaps that need to be addressed for models to become useful decision tools that can support research and control operations effectively. This agenda includes the use of models to estimate the impact of large-scale interventions on infection incidence; the design of sampling protocols for the monitoring and evaluation of integrated control programmes; the modelling of co-infections; the investigation of the dynamical relationship between infection and morbidity indicators; the improvement of analytical methods for the quantification of anthelmintic efficacy and resistance; the determination of programme endpoints; the linking of dynamical helminth models with helminth geostatistical mapping; and the investigation of the impact of climate change on human helminthiases. It is concluded that modelling should be embedded in helminth research, and in the planning, evaluation, and surveillance of interventions from the outset. Modellers should be essential members of interdisciplinary teams, propitiating a continuous dialogue with end users and stakeholders to reflect public health needs in the terrain, discuss the scope and limitations of models, and update biological assumptions and model outputs regularly. It is highlighted that to reach these goals, a collaborative framework must be developed for the collation, annotation, and sharing of databases from large-scale anthelmintic control programmes, and that helminth modellers should join efforts to tackle key questions in helminth epidemiology and control through the sharing of such databases, and by using diverse, yet complementary, modelling approaches

Estimating the burden of antimicrobial resistance: a systematic literature review.

Background: Accurate estimates of the burden of antimicrobial resistance (AMR) are needed to establish the magnitude of this global threat in terms of both health and cost, and to paramaterise cost-effectiveness evaluations of interventions aiming to tackle the problem. This review aimed to establish the alternative methodologies used in estimating AMR burden in order to appraise the current evidence base. Methods: MEDLINE, EMBASE, Scopus, EconLit, PubMed and grey literature were searched. English language studies evaluating the impact of AMR (from any microbe) on patient, payer/provider and economic burden published between January 2013 and December 2015 were included. Independent screening of title/abstracts followed by full texts was performed using pre-specified criteria. A study quality score (from zero to one) was derived using Newcastle-Ottawa and Philips checklists. Extracted study data were used to compare study method and resulting burden estimate, according to perspective. Monetary costs were converted into 2013 USD. Results: Out of 5187 unique retrievals, 214 studies were included. One hundred eighty-seven studies estimated patient health, 75 studies estimated payer/provider and 11 studies estimated economic burden. 64% of included studies were single centre. The majority of studies estimating patient or provider/payer burden used regression techniques. 48% of studies estimating mortality burden found a significant impact from resistance, excess healthcare system costs ranged from non-significance to $1 billion per year, whilst economic burden ranged from$21,832 per case to over $3 trillion in GDP loss. Median quality scores (interquartile range) for patient, payer/provider and economic burden studies were 0.67 (0.56-0.67), 0.56 (0.46-0.67) and 0.53 (0.44-0.60) respectively. Conclusions: This study highlights what methodological assumptions and biases can occur dependent on chosen outcome and perspective. Currently, there is considerable variability in burden estimates, which can lead in-turn to inaccurate intervention evaluations and poor policy/investment decisions. Future research should utilise the recommendations presented in this review. Trial registration: This systematic review is registered with PROSPERO (PROSPERO CRD42016037510)

Wilms' Tumor In Children: An Overview

Wilms' tumor is the most frequently occurring renal tumor in children and is one of the most treatment-responsive tumors. A tumor-suppressor gene and other genetic abnormalities have been implicated in its etiology. In addition, patients with several congenital anomalies, such as Beck-with-Wiedemann syndrome, WAGR syndrome, and Denys-Drash syndrome, have an increased risk of Wilms' tumor. Previously, a three-drug chemotherapy regimen with surgery and radiotherapy was used with patients in all stages. Now, patients with early-stage Wilms' tumor are treated with a two-drug regimen without radiotherapy, whereas those in advanced stages still receive the three-drug regimen and radiotherapy. Two large collaborative groups - the National Wilms' Tumor Study Group (NWTS) in the United States and the International Society of Pediatric Oncology (SIOP) in Europe - are involved in Wilms' tumor management, which differs in some aspects. Multimodality treatment has been used successfully, and in Europe preoperative strategies are used as well. As the survival rate has now reached 90%, the primary objectives of the physician are to perform nephron-sparing surgery in selected cases and to reduce the dosage and duration of chemotherapy and radiotherapy in appropriate cases. Other renal tumors occur rarely, but have also been treated successfully in the last decade. Copyright (C) 2008 S. Karger AG, Basel.Wo

Importance of primary metabolites in canola in mediating interactions between a specialist leaf-feeding insect and its specialist solitary endoparasitoid

The role of primary plant chemistry on trophic interactions is not well studied. We examined the effect of primary plant metabolites, focusing on nitrogen, on several biological indices of second and third trophic level insects in a model tritrophic system, consisting of two strains of the crucifer, Brassica napus (canola) (SLM046 and RGS(003)), the specialist insect herbivore Plutella xylostella (L.) (Lepidoptera: Plutellidae), and its specialist koinobiont larval-pupal parasitoid Diadegma semiclausum (Hell,n) (Hymenoptera: Ichneumonidae). In particular, we measured relative growth rate of the herbivore in relation to an index for plant quality (nitrogen content of leaf tissues), developmental time of the herbivore (sum of second, third, and fourth larval instars durations), and intrinsic rate of increase (r (m) ) of the herbivore and the parasitoid. Tritrophic studies were conducted on development, survivorship curve analysis, reproductive potential, life history, parasitism, and several other fitness correlates of the parasitoid. The life table parameters of D. semiclausum were determined under laboratory conditions. The intrinsic rate of increase (r (m) ) of the parasitoid was significantly higher on RGS(003) than SLM046. In this tritrophic model, the results indicated that the bottom-up direct effect on the herbivore population growth rate was marginally as strong as the direct effect of top-down force due to the parasitoid population growth rate; but it was higher than its indirect counterpoint mediated with the parasitoid population growth rate. Consequently, D. semiclausum performed better on RGS(003), which was the most inferior host to P. xylostella in comparison with another plant cultivar and had the lowest content of nitrogen in its leaves