Unhealthy landscapes: policy recommendations on land use change and infectious disease emergence

Anthropogenic land use changes drive a range of infectious disease outbreaks and emergence events and modify the transmission of endemic infections. These drivers include agricultural encroachment, deforestation, road construction, dam building, irrigation, wetland modification, mining, the concentration or expansion of urban environments, coastal zone degradation, and other activities. These changes in turn cause a cascade of factors that exacerbate infectious disease emergence, such as forest fragmentation, disease introduction, pollution, poverty, and human migration. The Working Group on Land Use Change and Disease Emergence grew out of a special colloquium that convened international experts in infectious diseases, ecology, and environmental health to assess the current state of knowledge and to develop recommendations for addressing these environmental health challenges. The group established a systems model approach and priority lists of infectious diseases affected by ecologic degradation. Policy-relevant levels of the model include specific health risk factors, landscape or habitat change, and institutional (economic and behavioral) levels. The group recommended creating Centers of Excellence in Ecology and Health Research and Training, based at regional universities and/or research institutes with close links to the surrounding communities. The centers' objectives would be 3-fold: a) to provide information to local communities about the links between environmental change and public health ; b) to facilitate fully interdisciplinary research from a variety of natural, social, and health sciences and train professionals who can conduct interdisciplinary research ; and c) to engage in science-based communication and assessment for policy making toward sustainable health and ecosystems.

Measuring underreporting and under-ascertainment in infectious disease datasets: a comparison of methods

 Background: Efficient and reliable surveillance and notification systems are vital for monitoring public health and disease outbreaks. However, most surveillance and notification systems are affected by a degree of underestimation (UE) and therefore uncertainty surrounds the 'true' incidence of disease affecting morbidity and mortality rates. Surveillance systems fail to capture cases at two distinct levels of the surveillance pyramid: from the community since not all cases seek healthcare (under-ascertainment), and at the healthcare-level, representing a failure to adequately report symptomatic cases that have sought medical advice (underreporting). There are several methods to estimate the extent of under-ascertainment and underreporting. Methods. Within the context of the ECDC-funded Burden of Communicable Diseases in Europe (BCoDE)-project, an extensive literature review was conducted to identify studies that estimate ascertainment or reporting rates for salmonellosis and campylobacteriosis in European Union Member States (MS) plus European Free Trade Area (EFTA) countries Iceland, Norway and Switzerland and four other OECD countries (USA, Canada, Australia and Japan). Multiplication factors (MFs), a measure of the magnitude of underestimation, were taken directly from the literature or derived (where the proportion of underestimated, under-ascertained, or underreported cases was known) and compared for the two pathogens. Results: MFs varied between and within diseases and countries, representing a need to carefully select the most appropriate MFs and methods for calculating them. The most appropriate MFs are often disease-, country-, age-, and sex-specific. Conclusions: When routine data are used to make decisions on resource allocation or to estimate epidemiological parameters in populations, it becomes important to understand when, where and to what extent these data represent the true picture of disease, and in some instances (such as priority setting) it is necessary to adjust for underestimation. MFs can be used to adjust notification and surveillance data to provide more realistic estimates of incidence. © 2014 Gibbons et al.; licensee BioMed Central Ltd.

Teachers' risk perception and needs in addressing infectious disease outbreak

The outbreak of the Influenza A (H1N1) virus has led to numerous precautionary school closures in several countries. No research is available on the school teachers’ perceptions as a health protective resource in controlling communicable disease outbreaks. The purposes of this study were to examine the risk perception, the perceived understanding of preventive measures and contingency plans, and the needs of school teachers before the imminent outbreak of H1N1. This survey was conducted with 1,169 Hong Kong school teachers before school closures due to the H1N1 outbreak. The results showed that the teachers were well aware of H1N1 but were still worried about the spread of H1N1 infection. The teachers’ worries depended on their psychological reaction, the adequacy of the control measures, government support in providing infectious disease knowledge, perceived understanding of preventive measures and contingency plans, students and parents’ awareness, and the need for support from health professionals.

Drought-rainfall cycles as potential environmental drivers of fowl plague and Newcastle disease uutbreaks in Australian poultry

Climatic conditions in Australia are erratic and characterised by periods of intense rainfall followed by periods of intense drought. This has considerable impact on the population dynamics and ecology of many Australian species of waterfowl, which are thought to form the reservoir of avian influenza viruses (AIV) but may also be important carriers (and possibly reservoirs) of other diseases (e.g. bursal disease, Newcastle disease). During the wet, waterfowl numbers increase with many serologically naive juveniles entering the population. During the subsequent period of drought, bird densities increase in the few remaining wetlands. We hypothesise that it is during this period of increasing densities of naive birds that the population’s viral prevalence of some infectious diseases may increase dramatically. Indeed, there exists a remarkable and suggestive coincidence between outbreaks of fowl plaque and Newcastle disease in Australian poultry farms and the periods of drought following a very wet period. In other words, we suspect a link between increased risk for disease outbreaks in poultry farms and the hypothesised high in the prevalences of the viruses causing these diseases in waterfowl. Given that poultry farms may provide ideal conditions for development of high-pathogenic strains, there is also a reciprocal risk for wildlife involved during these periods.

Market failure, policy failure and other distortions in chronic disease markets

Background: The increasing prevalence of chronic disease represents a significant burden on most health systems. This paper explores the market failures and policy failures that exist in the management of chronic diseases.
Discussion: There are many sources of market failure in health care that undermine the efficiency of chronic disease management. These include incomplete information as well as information asymmetry between providers and consumers, the effect of externalities on consumer behaviour, and the divergence between social and private time preference rates. This has seen government and policy interventions to address both market failures and distributional issues resulting from the inability of private markets to reach an efficient and equitable distribution of resources. However, these have introduced a series of policy failures such as distorted re-imbursement arrangements across modalities and delivery settings.
Summary: The paper concludes that market failure resulting from a preference of individuals for 'immediate gratification' in the form of health care and disease management, rather than preventative services, where the benefits are delayed, has a major impact on achieving an efficient allocation of resources in markets for the management of chronic diseases. This distortion is compounded by government health policy that tends to favour medical and pharmaceutical interventions further contributing to distortions in the allocation of resources and inefficiencies in the management of chronic disease.

Nano-lactoferrin in diagnostic, imaging and targeted delivery for cancer and infectious diseases

Lactoferrin (Lf) is a natural occurring iron binding protein present in many mammalian excretions and involved in various physiological processes. Lf is used in the transport of iron along with other molecules and ions from the digestive system. However its the modulatory functions exhibited by Lf in connection to immune response, disease regression and diagnosis that has made this protein an attractive therapeutic against chronic diseases. Further, the exciting potentials of employing nanotechnology in advancing drug delivery systems, active disease targeting and prognosis have also shown some encouraging outcomes. This review focuses on the role of Lf in diagnosing infection, cancer, neurological and inflammatory diseases and the recent nanotechnology based strategies.

Managing the risks from new and emerging infectious disease: the 'one health' paradigm

The global risk from new and emerging infectious diseases continues to grow with recognition that, for the most part, the pathogens involved emerge from animals to infect humans. Recognizing the complexity of these interactions and the need for a strong interdisciplinary approach to effectively manage these risks, new partnerships are being forged under the general umbrella of 'one health'. Involving human health, animal health, and environmental health exponents, solutions are sought for how to prevent as well as respond to the threats. But is this approach working? Whilst a number of key meetings continue to be held under the One Health umbrella, are we really seeing measureable progress in risk prevention and mitigation? Focusing research on the drivers for emergence, on modeling the risks, on improved diagnostics, and on targeted vaccines could considerably enhance our ability to prevent and respond. Ensuring the uptake and applications of new diagnostics and vaccines will be the key to prevention and response, but achieving this will require policies that drive further the One Health collaborations. Such policies should ensure that scant available resources are targeted toward the identified outcomes through research delivery and uptake, and that we genuinely work as "one world" in tackling the very real risks we face

Wildlife infectious disease dynamics in the context of seasonality and bird migration

The thesis contains chapters that elucidate questions with regards to wildlife infectious disease dynamics - avian influenza in particular - and how those dynamics are affected by seasonality and avian migration.

Geographic variation in seasonality and its influence on the dynamics of an infectious disease

Seasonal changes in environmental drivers - such as temperature, rainfall, and resource availability - have the potential to shape infection dynamics through their reverberating effects on biological processes including host abundance and susceptibility to infection. However, seasonality varies geographically. We therefore expect marked differences in infection dynamics between regions with different seasonal patterns. By pairing extensive Avian Influenza Virus (AIV) surveillance data - 65 358 individual bird samples from 12 species of dabbling ducks sampled at 174 locations across North America - with quantification of seasonality using remote sensed data indicative for primary productivity (normalised differenced vegetation index, NDVI), we provide evidence that seasonal dynamics influence infection dynamics across a continent. More pronounced epidemics were seen to occur in regions experiencing a higher degree of seasonality, and epidemics of lower amplitude and longer duration occurred in regions with a more protracted and lower seasonal amplitude. These results demonstrate the potential importance of geographic variation in seasonality for explaining geographic variation in the dynamics of infectious diseases in wildlife.

Transport of cryptotanshinone, a major active triterpenoid in Salvia miltiorrhiza Bunge widely used in the treatment of stroke and Alzheimers disease, across the blood-brain

Cryptotanshinone (CTS), a major constituent from the roots of Salvia miltiorrhiza (Danshen), is widely used in the treatment of coronary heart disease, stroke and less commonly Alzheimer's disease. Our recent study indicates that CTS is a substrate for Pglycoprotein (PgP/MDR1/ABCB1). This study has investigated the nature of the brain distribution of CTS across the brain-blood barrier (BBB) using several in vitro and in vivo rodent models. A polarized transport of CTS was found in rat primary microvascular endothelial cell (RBMVEC) monolayers, with facilitated efflux from the abluminal side to luminal side. Addition of a PgP (e.g. verapamil and quinidine) or multi-drug resistance protein 1/2 (MRP1/2) inhibitor (e.g. probenecid and MK-571) in both luminal and abluminal sides attenuated the polarized transport. In a bilateral in situ brain perfusion model, the uptake of CTS into the cerebrum increased from 0.52 ± 0.1% at 1 min to 11.13 ± 2.36 ml/100 g tissue at 30 min and was significantly greater than that of sucrose. Co-perfusion of a PgP/MDR1 (e.g. verapamil) or MRP1/2 inhibitor (e.g. probenecid) significantly increased the brain distribution of CTS by 35.1-163.6%. The brain levels of CTS were only about 21% of those in plasma, and were significantly increased when coadministered with verapamil or probenecid in rats. The brain levels of CTS in rats subjected to middle cerebral artery occlusion and rats treated with quinolinic acid (a neurotoxin) were about 2- to 2.5-fold higher than the control rats. Moreover, the brain levels in mdr1a(-/-) and mrp1(-/-) mice were 10.9- and 1.5-fold higher than those in the wild-type mice, respectively. Taken collectively, these findings indicate that PgP and Mrp1 limit the brain penetration of CTS in rodents, suggesting a possible role of PgP and MRP1 in limiting the brain penetration of CTS in patients and causing drug resistance to Danshen therapy and interactions with conventional drugs that are substrates of PgP and MRP1. Further studies are needed to explore the role of other drug transporters in restricting the brain penetration of CTS and the clinical relevance.

HOMA insulin sensitivity index and the risk of all-cause mortality and cardiovascular disease events in the general population : the Australian diabetes, obesity and lifestyle study (AusDiab) study

Aims/hypothesis We assessed whether the relationships between insulin sensitivity and all-cause mortality as well as fatal or non-fatal cardiovascular disease (CVD) events are independent of elevated blood glucose, high blood pressure, dyslipidaemia and body composition in individuals without diagnosed diabetes.
Methods Between 1999 and 2000, baseline fasting insulin, glucose and lipids, 2 h plasma glucose, HbA1c, anthropometrics, blood pressure, medication use, smoking and history of CVD were collected from 8,533 adults aged >35 years from the population-based Australian Diabetes, Obesity and Lifestyle study. Insulin sensitivity was estimated by HOMA of insulin sensitivity (HOMA-%S). Deaths and fatal or non-fatal CVD events were ascertained through linkage to the National Death Index and medical records adjudication.
Results After a median of 5.0 years there were 277 deaths and 225 CVD events. HOMA-%S was not associated with all-cause mortality. Compared with the most insulin-sensitive quintile, the combined fatal or non-fatal CVD HR (95% CI) for quintiles of decreasing HOMA-%S were 1.1 (0.6–1.9), 1.4 (0.9–2.3), 1.6 (1.0–2.5) and 2.0 (1.3–3.1), adjusting for age and sex. Smoking, CVD history, hypertension, lipid-lowering medication, total cholesterol and waist-to-hip ratio moderately attenuated this relationship. However, the association was rendered non-significant by adding HDL. Fasting plasma glucose, but not HOMA-%S significantly improved the prediction of CVD, beyond that seen with other risk factors.
Conclusions/interpretation In this cohort, HOMA-%S showed no association with all-cause mortality and only a modest association with CVD events, largely explained by its association with HDL. Fasting plasma glucose was a better predictor of CVD than HOMA-%S.

Development and evaluation of an ELISA for the detection and 3D antibodies to foot and mouth disease virus

A group specific ELISA (enzyme-linked immunosorbent assay) was developed to detect virus infection associated antibodies in the serum of animals infected with any serotype of foot and mouth disease virus. The assay was developed from non-infectious sources, and is therefore suitable for use in countries where FMDV is exotic.

The neuronal noradrenaline transporter, anxiety and cardiovascular disease

Panic disorder can serve as a clinical model for testing whether mental stress can cause heart disease. Potential neural mechanisms of cardiac risk are the sympathetic activation during panic attacks, continuing release of adrenaline as a co-transmitter in the cardiac sympathetic nerves, and impairment of noradrenaline neuronal reuptake, augmenting sympathetic neural respnses.

The phenotype of impaired neuronal reuptake of noradrenaline: an epigenetic mechanism? We suspect that this phenotype, in sensitizing people to heart symptom development, is a cause of panic disorder, and by magnifying the sympathetic neural signal in the heart, underlies increased cardiac risk. No loss of function mutations of the coding region of the norepinephrine transporter (NET) are evident, but we do detect hypermethylation of CpG islands in the NET gene promoter region. Chromatin immunoprecipitation methodology demonstrates binding of the inhibitory transcription factor, MeCP2, to promoter region DNA in panic disorder patients.

Cardiovascular illnesses co-morbid with panic disorder. Panic disorder commonly coexists with essential hypertension and the postural tachycardia syndrome. In both of these cardiovascular disorders the impaired neuronal noradrenaline reuptake phenotype is also present and, as with panic disorder, is associated with NET gene promoter region DNA hypermethylation. An epigenetic ‘co-morbidity’ perhaps underlies the clinical concordance.

Brain neurotransmitters. Using internal jugular venous sampling, in the absence of a panic attack we find normal norepinephrine turnover, but based on measurements of the overflow of the serotonin metabolite, 5HIAA, a marked increase (six to sevenfold) in brain serotonin turnover in patients with panic disorder. This appears to represent the underlying neurotransmitter substrate for the disorder. Whether this brain serotonergic activation is a prime mover, or consequential on other primary causes of panic disorder, including cardiac sensitization by faulty neuronal noradrenaline reuptake leading to cardiac symptoms and the enhanced vigilance which accompanies them, is unclear at present.

The effect of fiscal policy on diet, obesity and chronic disease : a systematic review

Objective To assess the effect of food taxes and subsidies on diet, body weight and health through a systematic review of the literature.

Methods We searched the English-language published and grey literature for empirical and modelling studies on the effects of monetary subsidies or taxes levied on specific food products on consumption habits, body weight and chronic conditions. Empirical studies were dealing with an actual tax, while modelling studies predicted outcomes based on a hypothetical tax or subsidy.

Findings Twenty-four studies met the inclusion criteria: 13 were from the peer-reviewed literature and 11 were published on line. There were 8 empirical and 16 modelling studies. Nine studies assessed the impact of taxes on food consumption only, 5 on consumption and body weight, 4 on consumption and disease and 6 on body weight only. In general, taxes and subsidies influenced consumption in the desired direction, with larger taxes being associated with more significant changes in consumption, body weight and disease incidence. However, studies that focused on a single target food or nutrient may have overestimated the impact of taxes by failing to take into account shifts in consumption to other foods. The quality of the evidence was generally low. Almost all studies were conducted in high-income countries.

Conclusion Food taxes and subsidies have the potential to contribute to healthy consumption patterns at the population level. However, current evidence is generally of low quality and the empirical evaluation of existing taxes is a research priority, along with research into the effectiveness and differential impact of food taxes in developing countries.