James E. Truscott

The Early Transmission Dynamics of H1N1pdm Influenza in the United Kingdom.

We analyzed data on all laboratory-confirmed cases of H1N1pdm influenza in the UK to 10th June 2009 to estimate epidemiological characteristics. We estimated a mean incubation period of 2.05 days and serial interval of 2.5 days with infectivity peaking close to onset of symptoms. Transmission was initially sporadic but increased from mid-May in England and from early June in Scotland. We estimated 37% of transmission occurred in schools, 24% in households, 28% through travel abroad and the remainder in the wider community. Children under 16 were more susceptible to infection in the household (adjusted OR 5.80, 95% CI 2.99-11.82). Treatment with oseltamivir plus widespread use of prophylaxis significantly reduced transmission (estimated reduction 16%). Households not receiving oseltamivir within 3 days of symptom onset in the index case had significantly increased secondary attack rates (adjusted OR 3.42, 95% CI 1.51-8.55).

The coverage and frequency of mass drug administration required to eliminate persistent transmission of soil-transmitted helminths

A combination of methods, including mathematical model construction, demographic plus epidemiological data analysis and parameter estimation, are used to examine whether mass drug administration (MDA) alone can eliminate the transmission of soil-transmitted helminths (STHs). Numerical analyses suggest that in all but low transmission settings (as defined by the magnitude of the basic reproductive number, R0), the treatment of pre-school-aged children (pre-SAC) and school-aged children (SAC) is unlikely to drive transmission to a level where the parasites cannot persist. High levels of coverage (defined as the fraction of an age group effectively treated) are required in pre-SAC, SAC and adults, if MDA is to drive the parasite below the breakpoint under which transmission is eliminated. Long-term solutions to controlling helminth infections lie in concomitantly improving the quality of the water supply, sanitation and hygiene (WASH). MDA, however, is a very cost-effective tool in long-term control given that most drugs are donated free by the pharmaceutical industry for poor regions of the world. WASH interventions, by lowering the basic reproductive number, can facilitate the ability of MDA to interrupt transmission.

How Effective Is School-Based Deworming for the Community-Wide Control of Soil-Transmitted Helminths?

Background The London Declaration on neglected tropical diseases was based in part on a new World Health Organization roadmap to “sustain, expand and extend drug access programmes to ensure the necessary supply of drugs and other interventions to help control by 2020”. Large drug donations from the pharmaceutical industry form the backbone to this aim, especially for soil-transmitted helminths (STHs) raising the question of how best to use these resources. Deworming for STHs is often targeted at school children because they are at greatest risk of morbidity and because it is remarkably cost-effective. However, the impact of school-based deworming on transmission in the wider community remains unclear. Methods We first estimate the proportion of parasites targeted by school-based deworming using demography, school enrolment, and data from a small number of example settings where age-specific intensity of infection (either worms or eggs) has been measured for all ages. We also use transmission models to investigate the potential impact of this coverage on transmission for different mixing scenarios. Principal Findings In the example settings <30% of the population are 5 to <15 years old. Combining this demography with the infection age-intensity profile we estimate that in one setting school children output as little as 15% of hookworm eggs, whereas in another setting they harbour up to 50% of Ascaris lumbricoides worms (the highest proportion of parasites for our examples). In addition, it is estimated that from 40–70% of these children are enrolled at school. Conclusions These estimates suggest that, whilst school-based programmes have many important benefits, the proportion of infective stages targeted by school-based deworming may be limited, particularly where hookworm predominates. We discuss the consequences for transmission for a range of scenarios, including when infective stages deposited by children are more likely to contribute to transmission than those from adults.

Control of a highly pathogenic H5N1 avian influenza outbreak in the GB poultry flock

The identification of H5N1 in domestic poultry in Europe has increased the risk of infection reaching most industrialized poultry populations. Here, using detailed data on the poultry population in Great Britain (GB), we show that currently planned interventions based on movement restrictions can be expected to control the majority of outbreaks. The probability that controls fail to keep an outbreak small only rises to significant levels if most transmission occurs via mechanisms which are both untraceable and largely independent of the local density of premises. We show that a predictor of the need to intensify control efforts in GB is whether an outbreak exceeds 20 infected premises. In such a scenario neither localized reactive vaccination nor localized culling are likely to have a substantial impact. The most effective of these contingent interventions are large radius (10 km) localized culling and national vaccination. However, the modest impact of these approaches must be balanced against their substantial inconvenience and cost.

Can chemotherapy alone eliminate the transmission of soil transmitted helminths

BackgroundAmongst the world’s poorest populations, availability of anthelmintic treatments for the control of soil transmitted helminths (STH) by mass or targeted chemotherapy has increased dramatically in recent years. However, the design of community based treatment programmes to achieve the greatest impact on transmission is still open to debate. Questions include: who should be treated, how often should they be treated, how long should treatment be continued for?MethodsSimulation and analysis of a dynamic transmission model and novel data analyses suggest refinements of the World Health Organization guidelines for the community based treatment of STH.ResultsThis analysis shows that treatment levels and frequency must be much higher, and the breadth of coverage across age classes broader than is typically the current practice, if transmission is to be interrupted by mass chemotherapy alone.ConclusionsWhen planning interventions to reduce transmission, rather than purely to reduce morbidity, current school-based interventions are unlikely to be enough to achieve the desired results.

Should the Goal for the Treatment of Soil Transmitted Helminth (STH) Infections Be Changed from Morbidity Control in Children to Community-Wide Transmission Elimination?

Morbidity induced by infection with the major soil transmitted infections (STH—Ascaris lumbricoides, Trichuris trichiura, and hookworms) results in an estimated 5.19 million disability-adjusted life years (DALYs) [1]. The World Health Organization’s (WHO) policy for control centres on three groups, preschool aged children (pre-SAC), school-aged children (SAC), and women of child bearing age, on the basis that heavy infection in these groups will have a detrimental impact on anaemia, child growth, and development. The current WHO guidelines focus on school-aged children, both for monitoring infection and as a target for treatment, although treatment of pre-SAC and women of childbearing age is also recommended where sustainable delivery mechanisms exist, especially in areas of intense transmission [2,3]. The guidelines recommend treating SAC annually where any STH prevalence falls between 20% and 50% and twice a year where it exceeds 50% [3]. The London Declaration on Neglected Tropical Diseases in 2012 endorsed WHO goals to scale up mass drug administration (MDA) for STH, so that by 2020, 75% of the pre-SAC and SAC in need will be treated regularly [4]. Building on an existing roadmap, WHO announced an intention to meet the target [2,5,6]. Progress has been good in some areas, but less so in others. In 2012, global coverage of those in need was 37% for SAC and 29% for pre-SAC [5]. Data for the more recent years is as yet to be published by WHO [5], but a huge gain in coverage is not expected, despite increased drug donations from the pharmaceutical companies who manufacture the main anthelmintics. This is due in part to the logistical challenges in getting even donated drugs to these populations, who are often beyond “the end of the road.” At present, many countries with endemic STH infections are not availing themselves of the freely donated drugs to treat children. We are still a long way from the 2020 target of 75%. Even if this target is reached, will it be enough to eliminate transmission and the disease arising from heavy infections with STH? If not, how should the guidelines be changed to push towards morbidity control, and ideally, the eventual elimination of transmission?

Essential epidemiological mechanisms underpinning the transmission dynamics of seasonal influenza

Seasonal influenza has considerable impact around the world, both economically and in mortality among risk groups, but there is considerable uncertainty as to the essential mechanisms and their parametrization. In this paper, we identify a number of characteristic features of influenza incidence time series in temperate regions, including ranges of annual attack rates and outbreak durations. By constraining the output of simple models to match these characteristic features, we investigate the role played by population heterogeneity, multiple strains, cross-immunity and the rate of strain evolution in the generation of incidence time series. Results indicate that an age-structured model with non-random mixing and co-circulating strains are both required to match observed time-series data. Our work gives estimates of the seasonal peak basic reproduction number, R0, in the range 1.6–3. Estimates of R0 are strongly correlated with the timescale for waning of immunity to current circulating seasonal influenza strain, which we estimate is between 3 and 8 years. Seasonal variation in transmissibility is largely confined to 15–30% of its mean value. While population heterogeneity and cross-immunity are required mechanisms, the degree of heterogeneity and cross-immunity is not tightly constrained. We discuss our findings in the context of other work fitting to seasonal influenza data.

Evaluating the adequacy of gravity models as a description of human mobility for epidemic modelling.

Gravity models have a long history of use in describing and forecasting the movements of people as well as goods and services, making them a natural basis for disease transmission rates over distance. In agent-based micro-simulations, gravity models can be directly used to represent movement of individuals and hence disease. In this paper, we consider a range of gravity models as fits to movement data from the UK and the US. We examine the ability of synthetic networks generated from fitted models to match those from the data in terms of epidemic behaviour; in particular, times to first infection. For both datasets, best fits are obtained with a two-piece ‘matched’ power law distance distribution. Epidemics on synthetic UK networks match well those on data networks across all but the smallest nodes for a range of aggregation levels. We derive an expression for time to infection between nodes in terms of epidemiological and network parameters which illuminates the influence of network clustering in spread across networks and suggests an approximate relationship between the log-likelihood deviance of model fit and the match times to infection between synthetic and data networks. On synthetic US networks, the match in epidemic behaviour is initially poor and sensitive to the initially infected node. Analysis of times to infection indicates a failure of models to capture infrequent long-range contact between large nodes. An assortative model based on node population size captures this heterogeneity, considerably improving the epidemiological match between synthetic and data networks.

Impact of scale on the effectiveness of disease control strategies for epidemics with cryptic infection in a dynamical landscape: an example for a crop disease

We use a spatially explicit, stochastic model to analyse the effectiveness of different scales of local control strategies in containing the long-term, multi-seasonal spread of a crop disease through a dynamically changing population of susceptible crops in which there is cryptic infection. The model distinguishes between susceptible, infested and symptomatic fields. It is motivated by rhizomania disease on sugar beet in the UK as an exemplar of a spatially structured and partially asymptomatic epidemic. Our results show the importance of matching the scales of local control strategies to prevent intensification and regional spread of disease with the inherent temporal and spatial scales of an epidemic. A simple field-scale containment strategy, whereby the susceptible crop is no longer grown on fields showing symptoms, fails for this system with cryptic infection because the locally applied control lags behind the epidemic. A farm-scale strategy, whereby growers respond to the disease status of neighbouring farms by transferring their quota for sugar beet to farmers in regions of reduced risk, succeeds. We conclude that a soil-borne pathogen such as rhizomania could be managed by movement of susceptible crops in the landscape using a strategy that matches the temporal and spatial scales of the epidemic and which take account of risk aversion among growers. We show some parallels and differences in effectiveness between a ‘culling’ strategy involving crop removal around emerging foci and the local deployment of partially resistant varieties that reduce amplification and transmission of inoculum. Some relationships between the control of plant and livestock diseases are briefly discussed.

Quantitative analyses and modelling to support achievement of the 2020 goals for nine neglected tropical diseases

Quantitative analysis and mathematical models are useful tools in informing strategies to control or eliminate disease. Currently, there is an urgent need to develop these tools to inform policy to achieve the 2020 goals for neglected tropical diseases (NTDs). In this paper we give an overview of a collection of novel model-based analyses which aim to address key questions on the dynamics of transmission and control of nine NTDs: Chagas disease, visceral leishmaniasis, human African trypanosomiasis, leprosy, soil-transmitted helminths, schistosomiasis, lymphatic filariasis, onchocerciasis and trachoma. Several common themes resonate throughout these analyses, including: the importance of epidemiological setting on the success of interventions; targeting groups who are at highest risk of infection or re-infection; and reaching populations who are not accessing interventions and may act as a reservoir for infection,. The results also highlight the challenge of maintaining elimination ‘as a public health problem’ when true elimination is not reached. The models elucidate the factors that may be contributing most to persistence of disease and discuss the requirements for eventually achieving true elimination, if that is possible. Overall this collection presents new analyses to inform current control initiatives. These papers form a base from which further development of the models and more rigorous validation against a variety of datasets can help to give more detailed advice. At the moment, the models’ predictions are being considered as the world prepares for a final push towards control or elimination of neglected tropical diseases by 2020.