Overcoming health systems barriers to successful malaria treatment.

The success of malaria control programmes is recognised to be handicapped by the capacity of the health system to deliver interventions such as first-line treatment at optimal coverage and quality. Traditional approaches to strengthening the health system such as staff training have had a less sustained impact than hoped. However, novel strategies including the use of mobile phones to ease stockouts, task-shifting to community health workers, and inclusion of the informal sector appear more promising. As global health funding slows, it is critical to better understand how to deliver a proven intervention most effectively through the existing system

Insights from unifying modern approximations to infections on networks

Networks are increasingly central to modern science owing to their ability to conceptualize multiple interacting components of a complex system. As a specific example of this, understanding the implications of contact network structure for the transmission of infectious diseases remains a key issue in epidemiology. Three broad approaches to this problem exist: explicit simulation; derivation of exact results for special networks; and dynamical approximations. This paper focuses on the last of these approaches, and makes two main contributions. Firstly, formal mathematical links are demonstrated between several prima facie unrelated dynamical approximations. And secondly, these links are used to derive two novel dynamical models for network epidemiology, which are compared against explicit stochastic simulation. The success of these new models provides improved understanding about the interaction of network structure and transmission dynamics

Generic Fibrational Induction

This paper provides an induction rule that can be used to prove properties of data structures whose types are inductive, i.e., are carriers of initial algebras of functors. Our results are semantic in nature and are inspired by Hermida and Jacobs' elegant algebraic formulation of induction for polynomial data types. Our contribution is to derive, under slightly different assumptions, a sound induction rule that is generic over all inductive types, polynomial or not. Our induction rule is generic over the kinds of properties to be proved as well: like Hermida and Jacobs, we work in a general fibrational setting and so can accommodate very general notions of properties on inductive types rather than just those of a particular syntactic form. We establish the soundness of our generic induction rule by reducing induction to iteration. We then show how our generic induction rule can be instantiated to give induction rules for the data types of rose trees, finite hereditary sets, and hyperfunctions. The first of these lies outside the scope of Hermida and Jacobs' work because it is not polynomial, and as far as we are aware, no induction rules have been known to exist for the second and third in a general fibrational framework. Our instantiation for hyperfunctions underscores the value of working in the general fibrational setting since this data type cannot be interpreted as a set.Comment: For Special Issue from CSL 201

Antigen-driven T-cell turnover.

A mathematical model is developed to characterize the distribution of cell turnover rates within a population of T lymphocytes. Previous models of T-cell dynamics have assumed a constant uniform turnover rate; here we consider turnover in a cell pool subject to clonal proliferation in response to diverse and repeated antigenic stimulation. A basic framework is defined for T-cell proliferation in response to antigen, which explicitly describes the cell cycle during antigenic stimulation and subsequent cell division. The distribution of T-cell turnover rates is then calculated based on the history of random exposures to antigens. This distribution is found to be bimodal, with peaks in cell frequencies in the slow turnover (quiescent) and rapid turnover (activated) states. This distribution can be used to calculate the overall turnover for the cell pool, as well as individual contributions to turnover from quiescent and activated cells. The impact of heterogeneous turnover on the dynamics of CD4(+) T-cell infection by HIV is explored. We show that our model can resolve the paradox of high levels of viral replication occurring while only a small fraction of cells are infected

Fibrational induction meets effects

This paper provides several induction rules that can be used to prove properties of effectful data types. Our results are semantic in nature and build upon Hermida and Jacobs’ fibrational formulation of induction for polynomial data types and its extension to all inductive data types by Ghani, Johann, and Fumex. An effectful data type μ(TF) is built from a functor F that describes data, and a monad T that computes effects. Our main contribution is to derive induction rules that are generic over all functors F and monads T such that μ(TF) exists. Along the way, we also derive a principle of definition by structural recursion for effectful data types that is similarly generic. Our induction rule is also generic over the kinds of properties to be proved: like the work on which we build, we work in a general fibrational setting and so can accommodate very general notions of properties, rather than just those of particular syntactic forms. We give examples exploiting the generality of our results, and show how our results specialize to those in the literature, particularly those of Filinski and Støvring

Mortality in patients with successful initial response to highly active antiretroviral therapy is still higher than in non-HIV-infected individuals.

Mortality in HIV-infected patients has decreased dramatically since the introduction of highly active antiretroviral therapy (HAART). We analyzed progression to death in a population of 3678 antiretroviral treatment-naive patients from the ATHENA national observational cohort from 24 weeks after the start of HAART. Mortality was compared with that in the general population in the Netherlands matched by age and gender. Only log-transformed CD4 cell count (hazard ratio [HR] = 0.50, 95% confidence interval [CI]: 0.40 to 0.61 per unit increase) and plasma viral load (HR = 0.30, 95% CI: 0.15 to 0.60, HIV RNA level or = 100,000 copies/mL) measured at 24 weeks and infection via intravenous drug use (IDU) (HR = 0.16, 95% CI: 0.10 to 0.26, non-IDU vs. IDU) were significantly associated with progression to death. For non-IDU patients with 600 x 10 CD4 cells/L and an HIV RNA level <100,000 copies/mL at 24 weeks, mortality was predicted to be 5.3 (95% CI: 3.5 to 8.4) and 10.4 (95% CI: 6.4 to 17.4) times higher than in the general population for 25-year-old men and women, respectively, and 1.15 (95% CI: 1.08 to 1.25) and 1.29 (95% CI: 1.16 to 1.50) times higher for 65-year-old men and women, respectively. Hence, mortality in HIV-infected patients with a good initial response to HAART is still higher than in the general population

Assessing the impact of imperfect adherence to artemether-lumefantrine on malaria treatment outcomes using within-host modelling.

Artemether-lumefantrine (AL) is the most widely-recommended treatment for uncomplicated Plasmodium falciparum malaria worldwide. Its safety and efficacy have been extensively demonstrated in clinical trials; however, its performance in routine health care settings, where adherence to drug treatment is unsupervised and therefore may be suboptimal, is less well characterised. Here we develop a within-host modelling framework for estimating the effects of sub-optimal adherence to AL treatment on clinical outcomes in malaria patients. Our model incorporates the data on the human immune response to the parasite, and AL's pharmacokinetic and pharmacodynamic properties. Utilising individual-level data of adherence to AL in 482 Tanzanian patients as input for our model predicted higher rates of treatment failure than were obtained when adherence was optimal (9% compared to 4%). Our model estimates that the impact of imperfect adherence was worst in children, highlighting the importance of advice to caregivers

Methods for estimating the case fatality ratio for a novel, emerging infectious disease.

During the course of an epidemic of a potentially fatal disease, it is important that the case fatality ratio be well estimated. The authors propose a novel method for doing so based on the Kaplan-Meier survival procedure, jointly considering two outcomes (death and recovery), and evaluate its performance by using data from the 2003 epidemic of severe acute respiratory syndrome in Hong Kong, People's Republic of China. They compare this estimate obtained at various points in the epidemic with the case fatality ratio eventually observed; with two commonly quoted, naïve estimates derived from cumulative incidence and mortality statistics at single time points; and with estimates in which a parametric mixture model is used. They demonstrate the importance of patient characteristics regarding outcome by analyzing subgroups defined by age at admission to the hospital

The estimation of economic benefits of urban trees using contingent valuation method in Tasik Perdana, Kuala Lumpur

Urban trees provide a multitude of tangible and intangible services which include provisionary, regulatory, as well as cultural and support services to the community. Unfortunately, to set a monetary value on these said services is challenging to say the least. Ignorance of such monetary value is unintentional and this is mainly due to the lack of awareness and the absence of monetary value of the services itself. Hence, the quality of these urban trees degrades over time as no one appreciates its monetary value. In light of this situation, a study was initiated to determine the economic benefits of the urban trees that were planted surrounding Tasik Perdana (TP) area. For this purpose, a total of 313 respondents were interviewed in the TP area using the contingent valuation method (CVM). The objective of this study was to elicit willingness to pay (WTP) for these urban trees. WTP represents the willingness of a person to pay in monetary terms to secure and sustain these urban trees. Hence, seven bid prices were used and distributed to the respondents: RM1.00, RM5.00, RM10.00, RM15.00, RM20.00, RM25.00 and RM30.00. Logit and linear regression models were applied to predict the maximum, mean, and median WTP. The study concludes that the estimated mean WTP is RM10.32 per visit and the estimated median WTP is RM10.08 per visit