Roslyn I. Hickson

Modelling the transmission dynamics of dengue in the presence of Wolbachia

Use of the bacterium Wolbachia is an innovative new strategy designed to break the cycle of dengue transmission. There are two main mechanisms by which Wolbachia could achieve this: by reducing the level of dengue virus in the mosquito and/or by shortening the host mosquitos lifespan. However, although Wolbachia shortens the lifespan, it also gives a breeding advantage which results in complex population dynamics. This study focuses on the development of a mathematical model to quantify the effect on human dengue cases of introducing Wolbachia into the mosquito population. The model consists of a compartment-based system of first-order differential equations; seasonal forcing in the mosquito population is introduced through the adult mosquito death rate. The analysis focuses on a single dengue outbreak typical of a region with a strong seasonally-varying mosquito population. We found that a significant reduction in human dengue cases can be obtained provided that Wolbachia-carrying mosquitoes persist when competing with mosquitoes without Wolbachia. Furthermore, using the Wolbachia strain WMel reduces the mosquito lifespan by at most 10% and allows them to persist in competition with non-Wolbachia-carrying mosquitoes. Mosquitoes carrying the WMelPop strain, however, are not likely to persist as it reduces the mosquito lifespan by up to 50%. When all other effects of Wolbachia on the mosquito physiology are ignored, cytoplasmic incompatibility alone results in a reduction in the number of human dengue cases. A sensitivity analysis of the parameters in the model shows that the transmission probability, the biting rate and the average adult mosquito death rate are the most important parameters for the outcome of the cumulative proportion of human individuals infected with dengue.

A Metapopulation Model of Tuberculosis Transmission with a Case Study from High to Low Burden Areas

Tuberculosis (TB) is a growing problem worldwide, especially with the emergence and high prevalence of multidrug-resistant strains. We develop a metapopulation model for TB spread, which is particularly suited to investigating transmission between areas of high and low prevalence. A case study of cross-border transmission in the Torres Strait region of Australia and Papua New Guinea (PNG) is considered and a sensitivity analysis is conducted. We find that only 6 of the 50 parameters analysed are important to the cumulative number of clinically active TB patients in the entire region. Of these, only the detection rate in PNG is found to be an important intervention parameter. We therefore give insight into the extent the area with the high burden of TB (PNG in the case study) is dominating the TB dynamics of the entire region. Furthermore, the sensitivity analysis results give insight into the data that most important to collect and refine, which is found to be data relating to the PNG parameters.

MODELLING THE INTRODUCTION OF WOLBACHIA INTO AEDES AEGYPTI MOSQUITOES TO REDUCE DENGUE TRANSMISSION

Infecting Aedes aegypti mosquitoes with the bacteria Wolbachia has been proposed as an innovative new strategy to reduce the transmission of dengue fever. Field trials are currently being undertaken in Queensland, Australia. However, few mathematical models have been developed to consider the persistence of Wolbachia- infected mosquitoes in the wild. This paper develops a mathematical model to determine the persistence of Wolbachia-infected mosquitoes by considering the competition between Wolbachia-infected and non-Wolbachia mosquitoes. The model has four steady states that are biologically feasible: all mosquitoes dying out, only non-Wolbachia mosquitoes surviving, and two steady states where non-Wolbachia and Wolbachia- infected mosquitoes coexist. The stability of the steady states is determined with respect to the key parameters in the mosquito life cycle. A global sensitivity analysis of the model is also conducted. The results show that the persistence of Wolbachia-infected mosquitoes is dominated by the reproductive rate, death rate, maturation rate and maternal transmission. For the parameter values where Wolbachia persists, it dominates the population, and hence the introduction of Wolbachia has great potential to reduce dengue transmission. n n doi:10.1017/S1446181112000132

The effect of Wolbachia on dengue outbreaks when dengue is repeatedly introduced

Use of the Wolbachia bacterium is a proposed new strategy to reduce dengue transmission, which results in around 390 million individuals infected annually. In places with strong variations in climatic conditions such as temperature and rainfall, dengue epidemics generally occur only at a certain time of the year. Where dengue is not endemic, the time of year in which imported cases enter the population plays a crucial role in determining the likelihood of outbreak occurrence. We use a mathematical model to study the effects of Wolbachia on dengue transmission dynamics and dengue seasonality. We focus in regions where dengue is not endemic but can spread due to the presence of a dengue vector and the arrival of people with dengue on a regular basis. Our results show that the time-window in which outbreaks can occur is reduced in the presence of Wolbachia-carrying Aedes aegypti mosquitoes by up to six weeks each year. We find that Wolbachia reduces overall case numbers by up to 80%. The strongest effect is obtained when the amplitude of the seasonal forcing is low (0.02-0.30). The benefits of Wolbachia also depend on the transmission rate, with the bacteria most effective at moderate transmission rates ranging between 0.08-0.12. Such rates are consistent with fitted estimates for Cairns, Australia.

The effect of Wolbachia on dengue dynamics in the presence of two serotypes of dengue: symmetric and asymmetric epidemiological characteristics

An innovative strategy to reduce dengue transmission uses the bacterium Wolbachia. We analysed the effects of Wolbachia on dengue transmission dynamics in the presence of two serotypes of dengue using a mathematical model, allowing for differences in the epidemiological characteristics of the serotypes. We found that Wolbachia has a greater effect on secondary infections than on primary infections across a range of epidemiological characteristics. If one serotype is more transmissible than the other, it will dominate primary infections and Wolbachia will be less effective at reducing secondary infections of either serotype. Differences in the antibody-dependent enhancement of the two serotypes have considerably less effect on the benefits of Wolbachia than differences in transmission probability. Even if the antibody-dependent enhancement rate is high, Wolbachia is still effective in reducing dengue. Our findings suggest that Wolbachia will be effective in the presence of more than one serotype of dengue; however, a better understanding of serotype-specific differences in transmission probability may be needed to optimize delivery of a Wolbachia intervention.

Strengthening Tuberculosis Control Overseas: Who Benefits?

BACKGROUNDnAlthough tuberculosis is a major cause of morbidity and mortality worldwide, available funding falls far short of that required for effective control. Economic and spillover consequences of investments in the treatment of tuberculosis are unclear, particularly when steep gradients in the disease and response are linked by population movements, such as that between Papua New Guinea (PNG) and the Australian cross-border region.nnnOBJECTIVEnTo undertake an economic evaluation of Australian support for the expansion of basic Directly Observed Treatment, Short Course in the PNG border area of the South Fly from the current level of 14% coverage.nnnMETHODSnBoth cost-utility analysis and cost-benefit analysis were applied to models that allow for population movement across regions with different characteristics of tuberculosis burden, transmission, and access to treatment. Cost-benefit data were drawn primarily from estimates published by the World Health Organization, and disease transmission data were drawn from a previously published model.nnnRESULTSnInvesting

CRITICAL TIMES OF HEAT AND MASS TRANSPORT THROUGH MULTIPLE LAYERS

16 million to increase basic Directly Observed Treatment, Short Course coverage in the South Fly generates a net present value of roughly

Model-Informed Risk Assessment and Decision Making for an Emerging Infectious Disease in the Asia-Pacific Region

74 million for Australia (discounted 2005 dollars). The cost per disability-adjusted life-year averted and quality-adjusted life-year saved for PNG is

The distribution of the time taken for an epidemic to spread between two communities

7 and

Sensitivity analysis of a model for tuberculosis

4.6, respectively.nnnCONCLUSIONSnWhere regions with major disparities in tuberculosis burden and health system resourcing are connected through population movements, investments in tuberculosis control are of mutual benefit, resulting in net health and economic gains on both sides of the border. These findings are likely to inform the case for appropriate investment in tuberculosis control globally.