Vaccination or mass drug administration against schistosomiasis: a hypothetical cost-effectiveness modelling comparison

Background Schistosomiasis is a neglected tropical disease, targeted by the World Health Organization for reduction in morbidity by 2020. It is caused by parasitic flukes that spread through contamination of local water sources. Traditional control focuses on mass drug administration, which kills the majority of adult worms, targeted at school-aged children. However, these drugs do not confer long-term protection and there are concerns over the emergence of drug resistance. The development of a vaccine against schistosomiasis opens the potential for control methods that could generate long-lasting population-level immunity if they are cost-effective. Methods Using an individual-based transmission model, matched to epidemiological data, we compared the cost-effectiveness of a range of vaccination programmes against mass drug administration, across three transmission settings. Health benefit was measured by calculating the heavy-intensity infection years averted by each intervention, while vaccine costs were assessed against robust estimates for the costs of mass drug administration obtained from data. We also calculated a critical vaccination cost, a cost beyond which vaccination might not be economically favorable, by benchmarking the cost-effectiveness of potential vaccines against the cost-effectiveness of mass drug administration, and examined the effect of different vaccine protection durations. Results We found that sufficiently low-priced vaccines can be more cost-effective than traditional drugs in high prevalence settings, and can lead to a greater reduction in morbidity over shorter time-scales. MDA or vaccination programmes that target the whole community generate the most health benefits, but are generally less cost-effective than those targeting children, due to lower prevalence of schistosomiasis in adults. Conclusions The ultimate cost-effectiveness of vaccination will be highly dependent on multiple vaccine characteristics, such as the efficacy, cost, safety and duration of protection, as well as the subset of population targeted for vaccination. However, our results indicate that if a vaccine could be developed with reasonable characteristics and for a sufficiently low cost, then vaccination programmes can be a highly cost-effective method of controlling schistosomiasis in high-transmission areas. The population-level immunity generated by vaccination will also inevitably improve the chances of interrupting transmission of the disease, which is the long-term epidemiological goal

The Gut Fungus Basidiobolus ranarum Has a Large Genome and Different Copy Numbers of Putatively Functionally Redundant Elongation Factor Genes

Fungal genomes range in size from 2.3 Mb for the microsporidian Encephalitozoon intestinalis up to 8000 Mb for Entomophaga aulicae, with a mean genome size of 37 Mb. Basidiobolus, a common inhabitant of vertebrate guts, is distantly related to all other fungi, and is unique in possessing both EF-1α and EFL genes. Using DNA sequencing and a quantitative PCR approach, we estimated a haploid genome size for Basidiobolus at 350 Mb. However, based on allelic variation, the nuclear genome is at least diploid, leading us to believe that the final genome size is at least 700 Mb. We also found that EFL was in three times the copy number of its putatively functionally overlapping paralog EF-1α. This suggests that gene or genome duplication may be an important feature of B. ranarum evolution, and also suggests that B. ranarum may have mechanisms in place that favor the preservation of functionally overlapping genes

A role for diatom-like silicon transporters in calcifying coccolithophores

Biomineralization by marine phytoplankton, such as the silicifying diatoms and calcifying coccolithophores, plays an important role in carbon and nutrient cycling in the oceans. Silicification and calcification are distinct cellular processes with no known common mechanisms. It is thought that coccolithophores are able to outcompete diatoms in Si-depleted waters, which can contribute to the formation of coccolithophore blooms. Here we show that an expanded family of diatom-like silicon transporters (SITs) are present in both silicifying and calcifying haptophyte phytoplankton, including some globally important coccolithophores. Si is required for calcification in these coccolithophores, indicating that Si uptake contributes to the very different forms of biomineralization in diatoms and coccolithophores. Significantly, SITs and the requirement for Si are absent from highly abundant bloom-forming coccolithophores, such as Emiliania huxleyi. These very different requirements for Si in coccolithophores are likely to have major influence on their competitive interactions with diatoms and other siliceous phytoplankton

Forest Biomass Density across Large Climate Gradients in Northern South America is related to Water Availability but not with Temperature

Understanding and predicting the likely response of ecosystems to climate change are crucial challenges for ecology and for conservation biology. Nowhere is this challenge greater than in the tropics as these forests store more than half the total atmospheric carbon stock in their biomass. Biomass is determined by the balance between biomass inputs (i.e., growth) and outputs (mortality). We can expect therefore that conditions that favor high growth rates, such as abundant water supply, warmth, and nutrient-rich soils will tend to correlate with high biomass stocks. Our main objective is to describe the patterns of above ground biomass (AGB) stocks across major tropical forests across climatic gradients in Northwestern South America. We gathered data from 200 plots across the region, at elevations ranging between 0 to 3400 m. We estimated AGB based on allometric equations and values for stem density, basal area, and wood density weighted by basal area at the plot-level. We used two groups of climatic variables, namely mean annual temperature and actual evapotranspiration as surrogates of environmental energy, and annual precipitation, precipitation seasonality, and water availability as surrogates of water availability. We found that AGB is more closely related to water availability variables than to energy variables. In northwest South America, water availability influences carbon stocks principally by determining stand structure, i.e. basal area. When water deficits increase in tropical forests we can expect negative impact on biomass and hence carbon storage

Experimental traumatic brain injury

Traumatic brain injury, a leading cause of death and disability, is a result of an outside force causing mechanical disruption of brain tissue and delayed pathogenic events which collectively exacerbate the injury. These pathogenic injury processes are poorly understood and accordingly no effective neuroprotective treatment is available so far. Experimental models are essential for further clarification of the highly complex pathology of traumatic brain injury towards the development of novel treatments. Among the rodent models of traumatic brain injury the most commonly used are the weight-drop, the fluid percussion, and the cortical contusion injury models. As the entire spectrum of events that might occur in traumatic brain injury cannot be covered by one single rodent model, the design and choice of a specific model represents a major challenge for neuroscientists. This review summarizes and evaluates the strengths and weaknesses of the currently available rodent models for traumatic brain injury

Long-term decline of the Amazon carbon sink

Atmospheric carbon dioxide records indicate that the land surface has acted as a strong global carbon sink over recent decades1, 2, with a substantial fraction of this sink probably located in the tropics3, particularly in the Amazon4. Nevertheless, it is unclear how the terrestrial carbon sink will evolve as climate and atmospheric composition continue to change. Here we analyse the historical evolution of the biomass dynamics of the Amazon rainforest over three decades using a distributed network of 321 plots. While this analysis confirms that Amazon forests have acted as a long-term net biomass sink, we find a long-term decreasing trend of carbon accumulation. Rates of net increase in above-ground biomass declined by one-third during the past decade compared to the 1990s. This is a consequence of growth rate increases levelling off recently, while biomass mortality persistently increased throughout, leading to a shortening of carbon residence times. Potential drivers for the mortality increase include greater climate variability, and feedbacks of faster growth on mortality, resulting in shortened tree longevity5. The observed decline of the Amazon sink diverges markedly from the recent increase in terrestrial carbon uptake at the global scale1, 2, and is contrary to expectations based on models6

Modeling methicillin-resistant Staphylococcus aureus in hospitals: Transmission dynamics, antibiotic usage and its history

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is endemic in many hospital settings, posing substantial threats and economic burdens worldwide. METHODS: We propose mathematical models to investigate the transmission dynamics of MRSA and determine factors that influence the prevalence of MRSA infection when antibiotics are given to patients to treat or prevent infections with either MRSA itself or other bacterial pathogens. RESULTS: Our results suggest that: (i) MRSA always persists in the hospital when colonized and infected patients are admitted; (ii) the longer the duration of treatment of infected patients and the lower the probability of successful treatment will increase the prevalence of MRSA infection; (iii) the longer the duration of contamination of health care workers (HCWs) and the more their contacts with patients may increase the prevalence of MRSA infection; (iv) possible ways to control the prevalence of MRSA infection include treating patients with antibiotic history as quickly and efficiently as possible, screening and isolating colonized and infected patients at admission, and compliance with strict hand-washing rules by HCWs. CONCLUSION: Our modeling studies offer an approach to investigating MRSA infection in hospital settings and the impact of antibiotic history on the incidence of infection. Our findings suggest important influences on the prevalence of MRSA infection which may be useful in designing control policies

Contingency planning for a deliberate release of smallpox in Great Britain : the role of geographical scale and contact structure

Background: In the event of a release of a pathogen such as smallpox, which is human-to-human transmissible and has high associated mortality, a key question is how best to deploy containment and control strategies. Given the general uncertainty surrounding this issue, mathematical modelling has played an important role in informing the likely optimal response, in particular defining the conditions under which mass-vaccination would be appropriate. In this paper, we consider two key questions currently unanswered in the literature: firstly, what is the optimal spatial scale for intervention; and secondly, how sensitive are results to the modelling assumptions made about the pattern of human contacts? Methods: Here we develop a novel mathematical model for smallpox that incorporates both information on individual contact structure (which is important if the effects of contact tracing are to be captured accurately) and large-scale patterns of movement across a range of spatial scales in Great Britain. Results: Analysis of this model confirms previous work suggesting that a locally targeted ‘ring’ vaccination strategy is optimal, and that this conclusion is actually quite robust for different socio-demographic and epidemiological assumptions. Conclusions: Our method allows for intuitive understanding of the reasons why national mass vaccination is typically predicted to be suboptimal. As such, we present a general framework for fast calculation of expected outcomes during the attempted control of diverse emerging infections; this is particularly important given that parameters would need to be interactively estimated and modelled in any release scenario