Aid and the Control of Tuberculosis in Papua New Guinea: Is Australia's Assistance Cost-Effective?

Australia supports the control of tuberculosis in Papua New Guinea for reasons of aid effectiveness and a desire to decrease the chance of importing tuberculosis to Australia. This paper analyses the case for this support using both cost-utility and cost-benefit analysis. We reach three conclusions. First, Australia directly benefits from its investment in controlling tuberculosis in Papua New Guinea, with a cost of $US 13 million (in 2012 prices) over 10 years earning a net present value of$US 22 million. Second, the longer and more extensive the basic directly observed short course therapy, or basic DOTS, to control tuberculosis, the higher are the returns for Australia. Finally, in addition to surpassing all commonly used benchmarks for being a cost-effective investment for Australia, a basic DOTS expansion also generates a health benefit for Papua New Guinea that compares well as one of the 'ten best health buys' in developing countries. � 2014 The Authors

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

A Multiscale Mathematical Model of Plasmodium Vivax Transmission

Malaria is caused by Plasmodium parasites which are transmitted to humans by the bite of an infected Anopheles mosquito. Plasmodium vivax is distinct from other malaria species in its ability to remain dormant in the liver (as hypnozoites) and activate later to cause further infections (referred to as relapses). Mathematical models to describe the transmission dynamics of P. vivax have been developed, but most of them fail to capture realistic dynamics of hypnozoites. Models that do capture the complexity tend to involve many governing equations, making them difficult to extend to incorporate other important factors for P. vivax, such as treatment status, age and pregnancy. In this paper, we have developed a multiscale model (a system of integro-differential equations) that involves a minimal set of equations at the population scale, with an embedded within-host model that can capture the dynamics of the hypnozoite reservoir. In this way, we can gain key insights into dynamics of P. vivax transmission with a minimum number of equations at the population scale, making this framework readily scalable to incorporate more complexity. We performed a sensitivity analysis of our multiscale model over key parameters and found that prevalence of P. vivax blood-stage infection increases with both bite rate and number of mosquitoes but decreases with hypnozoite death rate. Since our mathematical model captures the complex dynamics of P. vivax and the hypnozoite reservoir, it has the potential to become a key tool to inform elimination strategies for P. vivax

Estimating the Distribution of Japanese Encephalitis Vectors in Australia Using Ecological Niche Modelling

Recent Japanese encephalitis virus (JEV) outbreaks in southeastern Australia have sparked interest into epidemiological factors surrounding the virus’ novel emergence in this region. Here, the geographic distribution of mosquito species known to be competent JEV vectors in the country was estimated by combining known mosquito occurrences and ecological drivers of distribution to reveal insights into communities at highest risk of infectious disease transmission. Species distribution models predicted that Culex annulirostris and Culex sitiens presence was mostly likely along Australia’s eastern and northern coastline, while Culex quinquefasciatus presence was estimated to be most likely near inland regions of southern Australia as well as coastal regions of Western Australia. While Culex annulirostris is considered the dominant JEV vector in Australia, our ecological niche models emphasise the need for further entomological surveillance and JEV research within Australia

Japanese Encephalitis Enzootic and Epidemic Risks across Australia

Japanese encephalitis virus (JEV) is an arboviral, encephalitogenic, zoonotic flavivirus characterized by its complex epidemiology whose transmission cycle involves reservoir and amplifying hosts, competent vector species and optimal environmental conditions. Although typically endemic in Asia and parts of the Pacific Islands, unprecedented outbreaks in both humans and domestic pigs in southeastern Australia emphasize the virus’ expanding geographical range. To estimate areas at highest risk of JEV transmission in Australia, ecological niche models of vectors and waterbirds, a sample of piggery coordinates and feral pig population density models were combined using mathematical and geospatial mapping techniques. These results highlight that both coastal and inland regions across the continent are estimated to have varying risks of enzootic and/or epidemic JEV transmission. We recommend increased surveillance of waterbirds, feral pigs and mosquito populations in areas where domestic pigs and human populations are present

Optimal Interruption of P. vivax Malaria Transmission Using Mass Drug Administration

Plasmodium vivax is the most geographically widespread malaria-causing parasite resulting in significant associated global morbidity and mortality. One of the factors driving this widespread phenomenon is the ability of the parasites to remain dormant in the liver. Known as ‘hypnozoites’, they reside in the liver following an initial exposure, before activating later to cause further infections, referred to as ‘relapses’. As around 79–96% of infections are attributed to relapses from activating hypnozoites, we expect it will be highly impactful to apply treatment to target the hypnozoite reservoir (i.e. the collection of dormant parasites) to eliminate P. vivax. Treatment with radical cure, for example tafenoquine or primaquine, to target the hypnozoite reservoir is a potential tool to control and/or eliminate P. vivax. We have developed a deterministic multiscale mathematical model as a system of integro-differential equations that captures the complex dynamics of P. vivax hypnozoites and the effect of hypnozoite relapse on disease transmission. Here, we use our multiscale model to study the anticipated effect of radical cure treatment administered via a mass drug administration (MDA) program. We implement multiple rounds of MDA with a fixed interval between rounds, starting from different steady-state disease prevalences. We then construct an optimisation model with three different objective functions motivated on a public health basis to obtain the optimal MDA interval. We also incorporate mosquito seasonality in our model to study its effect on the optimal treatment regime. We find that the effect of MDA interventions is temporary and depends on the pre-intervention disease prevalence (and choice of model parameters) as well as the number of MDA rounds under consideration. The optimal interval between MDA rounds also depends on the objective (combinations of expected intervention outcomes). We find radical cure alone may not be enough to lead to P. vivax elimination under our mathematical model (and choice of model parameters) since the prevalence of infection eventually returns to pre-MDA levels

A scoping review of mathematical models of Plasmodium vivax

Plasmodium vivax is one of the most geographically widespread malaria parasites in the world due to its ability to remain dormant in the human liver as hypnozoites and subsequently reactivate after the initial infection (i.e. relapse infections). More than 80% of P. vivax infections are due to hypnozoite reactivation. Mathematical modelling approaches have been widely applied to understand P. vivax dynamics and predict the impact of intervention outcomes. In this article, we provide a scoping review of mathematical models that capture P. vivax transmission dynamics published between January 1988 and May 2023 to provide a comprehensive summary of the mathematical models and techniques used to model P. vivax dynamics. We aim to assist researchers working on P. vivax transmission and other aspects of P. vivax malaria by highlighting best practices in currently published models and highlighting where future model development is required. We provide an overview of the different strategies used to incorporate the parasite's biology, use of multiple scales (within-host and population-level), superinfection, immunity, and treatment interventions. In most of the published literature, the rationale for different modelling approaches was driven by the research question at hand. Some models focus on the parasites' complicated biology, while others incorporate simplified assumptions to avoid model complexity. Overall, the existing literature on mathematical models for P. vivax encompasses various aspects of the parasite's dynamics. We recommend that future research should focus on refining how key aspects of P. vivax dynamics are modelled, including the accumulation of hypnozoite variation, the interaction between P. falciparum and P. vivax, acquisition of immunity, and recovery under superinfection

A model for malaria treatment evaluation in the presence of multiple species

Plasmodium (P.) falciparum and P. vivax are the two most common causes of malaria. While the majority of deaths and severe morbidity are due to P. falciparum, P. vivax poses a greater challenge to eliminating malaria outside of Africa due to its ability to form latent liver stage parasites (hypnozoites), which can cause relapsing episodes within an individual patient. In areas where P. falciparum and P. vivax are co-endemic, individuals can carry parasites of both species simultaneously. These mixed infections complicate dynamics in several ways; treatment of mixed infections will simultaneously affect both species, P. falciparum can mask the detection of P. vivax, and it has been hypothesised that clearing P. falciparum may trigger a relapse of dormant P. vivax. When mixed infections are treated for only blood-stage parasites, patients are at risk of relapse infections due to P. vivax hypnozoites. We present a stochastic mathematical model that captures interactions between P. falciparum and P. vivax, and incorporates both standard schizontocidal treatment (which targets blood-stage parasites) and radical treatment (which additionally targets liver-stage parasites). We apply this model to assess the implications of different treatment coverage of radical cure for mixed and P. vivax infections and a so-called "unified radical cure" treatment strategy for P. falciparum, P. vivax and mixed infections. We find that a unified radical cure strategy, with G6PD screening, leads to a substantially lower incidence of malaria cases and deaths overall. We perform a one-way sensitivity analysis to highlight important model 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. doi:10.1017/S144618111200013