Emerging and re-emerging bacterial diseases in India

There has been a remarkable progress in the prevention, control and even eradication of infectious diseases with improved hygiene and development of antimicrobials and vaccines. However, infectious diseases still remain a leading cause of global disease burden with high morbidity and mortality especially in the developing world. Furthermore, there have been threats of new diseases during the past three decades due to the evolution and adaptation of microbes and the re-emergence of old diseases due to the development of antimicrobial resistance and the capacity to spread to new geographic areas. The impact of the emerging and re-emerging diseases in India has been tremendous at socioeconomic and public health levels. Their control requires continuing surveillance, research and training, better diagnostic facilities and improved public health system. Emerging and reemerging zoonotic diseases, foodborne and waterborne diseases and diseases caused by multiresistant organisms constitute the major threats in India. This review of bacterial emerging and re-emerging diseases should be of critical importance to microbiologists, clinicians, public health personnel and policy makers in India.     

Japan's innovation for global health – GHIT's catalytic role

The global fight against infectious diseases, both emerging and re-emerging, endures. Japan's commitments and reputation as a good global citizen and its responsibility to uphold domestic and international human security mean that it is in Japan's best interest to leverage its innovative and technological capabilities for global infectious disease prevention and control. The Global Health Innovative Technology Fund (GHIT Fund), an international non-profit organization based in Tokyo, Japan, was established by the Japanese government, multiple Japanese pharmaceutical companies, and the Bill & Melinda Gates Foundation as the first fund of its kind, with an aim to tackle the global burden of infectious diseases by facilitating and funding global health R&D of drugs, vaccines, and diagnostics. Since its inception in 2013, the GHIT Fund has invested more than 209 million USD in more than 90 projects, which consist of collaborations among Japanese and non-Japanese entities, six of which have already progressed to clinical stage development. Japan will continue to play a major role in the global health arena by further advancing R&D innovations for infectious diseases.     

Dengue and human health: A global scenario of its occurrence,diagnosis and therapeutics

Dengue is one of the highest and rapidly spreading vector-borne viral diseases with high mortality rates. The infection causes acute febrile illness, a major public health concern in the tropics and subtropics globally. The disease is caused by an RNA virus that belongs to the Flaviviridae family. The virus is transferred to humans by the mosquito vector called Aedvrves aegypti, which is the cause of new prevalent sicknesses worldwide. These vector-borne viral diseases spread very fast and pose public health and economic challenges that deemed various prevention and control techniques. The Flavivirus genus consists of five different types of viruses starting from DENV-1 to DENV-5. Thus, the present review focuses on the origin of the virus, how the Dengue virus can be detected, infection, the morphology of the virus, its classifications as proposed by ICTV, the replication and genome of the dengue virus, translation, receptor binding, and some vaccine trial volunteers. In addition, it highlights the current challenges and limitations of effective dengue treatment.     

The mosquito genome: organization, evolution and manipulation

Apart from the genetic flexibility of the vectors, impediments to the control of vector-borne diseases include the rapid spread of drug resistance throughout parasite populations, the increasing movement of people to and from disease-endemic regions and the limited funds and public health infrastructures of most developing countries. The widely used residual insecticides and antiparasitic drugs have been inadequate solutions to the problem of vector-borne disease control. New approaches are needed. The enormous impact of recent developments in molecular genetics on the understanding of basic biology and human disease has stimulated a re-examination of the prospects for genetic manipulation of vector populations as a means for reducing or eliminating vector-borne diseases, especially malarial. Although control scenarios that exploit this technology may never be realized, Nora Besansky and Frank Collins emphasize that the increase in knowledge of basic mosquito biology on which these ideas depend will inevitably stimulate novel approaches to the control of mosquito-borne diseases.     

Disentangling Vector-Borne Transmission Networks: A Universal DNA Barcoding Method to Identify Vertebrate Hosts from Arthropod Bloodmeals

Emerging infectious diseases represent a challenge for global economies and public health. About one fourth of the last pandemics have been originated by the spread of vector-borne pathogens. In this sense, the advent of modern molecular techniques has enhanced our capabilities to understand vector-host interactions and disease ecology. However, host identification protocols have poorly profited of international DNA barcoding initiatives and/or have focused exclusively on a limited array of vector species. Therefore, ascertaining the potential afforded by DNA barcoding tools in other vector-host systems of human and veterinary importance would represent a major advance in tracking pathogen life cycles and hosts. Here, we show the applicability of a novel and efficient molecular method for the identification of the vertebrate host''s DNA contained in the midgut of blood-feeding arthropods. To this end, we designed a eukaryote-universal forward primer and a vertebrate-specific reverse primer to selectively amplify 758 base pairs (bp) of the vertebrate mitochondrial Cytochrome c Oxidase Subunit I (COI) gene. Our method was validated using both extensive sequence surveys from the public domain and Polymerase Chain Reaction (PCR) experiments carried out over specimens from different Classes of vertebrates (Mammalia, Aves, Reptilia and Amphibia) and invertebrate ectoparasites (Arachnida and Insecta). The analysis of mosquito, culicoid, phlebotomie, sucking bugs, and tick bloodmeals revealed up to 40 vertebrate hosts, including 23 avian, 16 mammalian and one reptilian species. Importantly, the inspection and analysis of direct sequencing electropherograms also assisted the resolving of mixed bloodmeals. We therefore provide a universal and high-throughput diagnostic tool for the study of the ecology of haematophagous invertebrates in relation to their vertebrate hosts. Such information is crucial to support the efficient management of initiatives aimed at reducing epidemiologic risks of arthropod vector-borne pathogens, a priority for public health.     

Climate Change,Vector-borne Disease and Interdisciplinary Research: Social Science Perspectives on an Environment and Health Controversy

Over the last two decades, the science of climate change’s theoretical impacts on vector-borne disease has generated controversy related to its methodological validity and relevance to disease control policy. Critical social science analysis, drawing on science and technology studies and the sociology of social movements, demonstrates consistency between this controversy and the theory that climate change is serving as a collective action frame for some health researchers. Within this frame, vector-borne disease data are interpreted as a symptom of climate change, with the need for further interdisiplinary research put forth as the logical and necessary next step. Reaction to this tendency on the part of a handful of vector-borne disease specialists exhibits characteristics of academic boundary work aimed at preserving the integrity of existing disciplinary boundaries. Possible reasons for this conflict include the leadership role for health professionals and disciplines in the envisioned interdiscipline, and disagreements over the appropriate scale of interventions to control vector-borne diseases. Analysis of the competing frames in this controversy also allows identification of excluded voices and themes, such as international political economic explanations for the health problems in question. A logical conclusion of this analysis, therefore, is the need for critical reflection on environment and health research and policy to achieve integration with considerations of global health equity.     

Decelerating spread of West Nile virus by percolation in a heterogeneous urban landscape

Vector-borne diseases are emerging and re-emerging in urban environments throughout the world, presenting an increasing challenge to human health and a major obstacle to development. Currently, more than half of the global population is concentrated in urban environments, which are highly heterogeneous in the extent, degree, and distribution of environmental modifications. Because the prevalence of vector-borne pathogens is so closely coupled to the ecologies of vector and host species, this heterogeneity has the potential to significantly alter the dynamical systems through which pathogens propagate, and also thereby affect the epidemiological patterns of disease at multiple spatial scales. One such pattern is the speed of spread. Whereas standard models hold that pathogens spread as waves with constant or increasing speed, we hypothesized that heterogeneity in urban environments would cause decelerating travelling waves in incipient epidemics. To test this hypothesis, we analysed data on the spread of West Nile virus (WNV) in New York City (NYC), the 1999 epicentre of the North American pandemic, during annual epizootics from 2000-2008. These data show evidence of deceleration in all years studied, consistent with our hypothesis. To further explain these patterns, we developed a spatial model for vector-borne disease transmission in a heterogeneous environment. An emergent property of this model is that deceleration occurs only in the vicinity of a critical point. Geostatistical analysis suggests that NYC may be on the edge of this criticality. Together, these analyses provide the first evidence for the endogenous generation of decelerating travelling waves in an emerging infectious disease. Since the reported deceleration results from the heterogeneity of the environment through which the pathogen percolates, our findings suggest that targeting control at key sites could efficiently prevent pathogen spread to remote susceptible areas or even halt epidemics.     

Adaptation and Evaluation of a Multi-Criteria Decision Analysis Model for Lyme Disease Prevention

Designing preventive programs relevant to vector-borne diseases such as Lyme disease (LD) can be complex given the need to include multiple issues and perspectives into prioritizing public health actions. A multi-criteria decision aid (MCDA) model was previously used to rank interventions for LD prevention in Quebec, Canada, where the disease is emerging. The aim of the current study was to adapt and evaluate the decision model constructed in Quebec under a different epidemiological context, in Switzerland, where LD has been endemic for the last thirty years. The model adaptation was undertaken with a group of Swiss stakeholders using a participatory approach. The PROMETHEE method was used for multi-criteria analysis. Key elements and results of the MCDA model are described and contrasted with the Quebec model. All criteria and most interventions of the MCDA model developed for LD prevention in Quebec were directly transferable to the Swiss context. Four new decision criteria were added, and the list of proposed interventions was modified. Based on the overall group ranking, interventions targeting human populations were prioritized in the Swiss model, with the top ranked action being the implementation of a large communication campaign. The addition of criteria did not significantly alter the intervention rankings, but increased the capacity of the model to discriminate between highest and lowest ranked interventions. The current study suggests that beyond the specificity of the MCDA models developed for Quebec and Switzerland, their general structure captures the fundamental and common issues that characterize the complexity of vector-borne disease prevention. These results should encourage public health organizations to adapt, use and share MCDA models as an effective and functional approach to enable the integration of multiple perspectives and considerations in the prevention and control of complex public health issues such as Lyme disease or other vector-borne and zoonotic diseases.     

Vector migration and dispersal rates for sylvatic Trypanosoma cruzi transmission

The spread of vector-borne diseases are greatly increased by a vector's ability to migrate. Recent studies of sylvatic Trypanosoma cruzi transmission have motivated the study of vector migration across geographic regions. Due to the natural mechanisms in which vector-borne diseases are transmitted between vectors and hosts, vector dispersal among different host populations is a critical factor in the ability of the parasite to be spread across large regions. In this study we develop a general framework for deriving large-scale, discrete-space migration rates from small-scale, continuous-space dispersal data. We identify three defining characteristics of vector migration: distance, preferred direction of dispersal, and strength of preference for a particular direction. We consider several migration scenarios in which vectors may have no preference for dispersal in a particular direction or may disperse with a preferred direction, such as northeast. We examine what effect preferred direction has on the migration rate, as well as use the local to global framework to calculate numerical estimates for vector migration rates for the primary vectors in the southeast U.S. and northern Mexico, Triatoma sanguisuga and Triatoma gerstaeckeri, based on biological and experimental data. Results from this study can be applied to metapopulation models for species that migrate.     

Local transmission processes and disease-driven host extinctions

Classic infectious disease theory assumes that transmission depends on either the global density of the parasite (for directly transmitted diseases) or its global frequency (for sexually transmitted diseases). One important implication of this dichotomy is that parasite-driven host extinction is only predicted under frequency-dependent transmission. However, transmission is fundamentally a local process between individuals that is determined by their and/or their vector’s behaviour. We examine the implications of local transmission processes to the likelihood of disease-driven host extinction. Local density-dependent transmission can lead to parasite-driven extinction, but extinction is more likely under local frequency-dependent transmission and much more likely when there is active local searching behaviour. Density-dependent directly transmitted diseases spread locally can therefore lead to deterministic host extinction, but locally frequency-dependent passive vector-borne diseases are more likely to cause extinctions. However, it is active searching behaviour either by a vector or between sexual partners that is most likely to cause the host to go extinct. Our work emphasises that local processes are essential in determining parasite-driven extinctions, and the role of parasites in the extinction of rare species may have been underplayed due to the classic assumption of global density-dependent transmission.     

Influence of Vectors’ Risk-Spreading Strategies and Environmental Stochasticity on the Epidemiology and Evolution of Vector-Borne Diseases: The Example of Chagas’ Disease

Insects are known to display strategies that spread the risk of encountering unfavorable conditions, thereby decreasing the extinction probability of genetic lineages in unpredictable environments. To what extent these strategies influence the epidemiology and evolution of vector-borne diseases in stochastic environments is largely unknown. In triatomines, the vectors of the parasite Trypanosoma cruzi, the etiological agent of Chagas’ disease, juvenile development time varies between individuals and such variation most likely decreases the extinction risk of vector populations in stochastic environments. We developed a simplified multi-stage vector-borne SI epidemiological model to investigate how vector risk-spreading strategies and environmental stochasticity influence the prevalence and evolution of a parasite. This model is based on available knowledge on triatomine biodemography, but its conceptual outcomes apply, to a certain extent, to other vector-borne diseases. Model comparisons between deterministic and stochastic settings led to the conclusion that environmental stochasticity, vector risk-spreading strategies (in particular an increase in the length and variability of development time) and their interaction have drastic consequences on vector population dynamics, disease prevalence, and the relative short-term evolution of parasite virulence. Our work shows that stochastic environments and associated risk-spreading strategies can increase the prevalence of vector-borne diseases and favor the invasion of more virulent parasite strains on relatively short evolutionary timescales. This study raises new questions and challenges in a context of increasingly unpredictable environmental variations as a result of global climate change and human interventions such as habitat destruction or vector control.     

以兽类为例探讨我国陆生野生动物疫病监管中面临的问题与对策

近年来, 新型冠状病毒、SARS病毒和鼠疫等新发和再发性动物源疫病多是由兽类及其媒介携带的病原生物直接或间接感染而引发的, 不仅对人类健康和生态系统平衡造成了重大威胁, 而且威胁全球公共卫生安全、粮食安全和生物安全。结合我国重要陆生兽类疫源疫病发生的新情况和新特点, 本文重点总结了我国以陆生野生及非野生兽类(家畜为主)为重点的24种重要人兽共患病的监管情况, 并对这些疫源疫病的监管空缺进行了分析。由于病原生物的种类多及其感染传播方式多样, 我国人间和动物间疫情呈现多发态势, 新发和再发疫病防控面临严峻挑战。从目前情况来看, 我国重要野生动物疫源疫病呈现为多部门、多层监管的局面。全球化贸易剧增、非法猎杀、非法交易、违法违规养殖、滥食野生动物陋习、检疫环节失察等导致了当前我国野生动物疫源疫病的传染源头和传播链错综复杂, 加剧了人类与野生动物所携带的病原接触、感染和传播的风险。极端气候或灾害事件频发以及对新发再发传染病的认知不足导致难以从源头做好疫病防控。针对上述问题, 本文提出了从源头加强基础研究和全链条监管来积极防范陆生野生动物疫病疫情的对策和建议。     

Peptide inhibitors against herpes simplex virus infections

Herpes simplex virus (HSV) is a significant human pathogen causing mucocutaneous lesions primarily in the oral or genital mucosa. Although acyclovir (ACV) and related nucleoside analogs provide successful treatment, HSV remains highly prevalent worldwide and is a major cofactor for the spread of human immunodeficiency virus. Encephalitis, meningitis, and blinding keratitis are among the most severe diseases caused by HSV. ACV resistance poses an important problem for immunocompromised patients and highlights the need for new safe and effective agents; therefore, the development of novel strategies to eradicate HSV is a global public health priority. Despite the continued global epidemic of HSV and extensive research, there have been few major breakthroughs in the treatment or prevention of the virus since the introduction of ACV in the 1980s. A therapeutic strategy at the moment not fully addressed is the use of small peptide molecules. These can be either modeled on viral proteins or derived from antimicrobial peptides. Any peptide that interrupts protein–protein or viral protein–host cell membrane interactions is potentially a novel antiviral drug and may be a useful tool for elucidating the mechanisms of viral entry. This review summarizes current knowledge and strategies in the development of synthetic and natural peptides to inhibit HSV infectivity. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.     

Nudge strategies for behavior-based prevention and control of neglected tropical diseases: A scoping review and ethical assessment

BackgroundNudging, a strategy that uses subtle stimuli to direct people’s behavior, has recently been included as an effective and low-cost behavior change strategy in low- and middle- income countries (LMIC), targeting behavior-based prevention and control of neglected tropical diseases (NTDs). The present scoping review aims to provide a timely overview of how nudge interventions have been applied within this field. In addition, the review proposes a framework for the ethical consideration of nudges for NTD prevention and control, or more broadly global health promotion.MethodsA comprehensive search was performed in several databases: MEDLINE, PsycINFO, and Embase (Ovid), Web of Science Core Collection, CINAHL, ERIC and Econ.Lit (EBSCO), as well as registered trials and reviews in CENTRAL and PROSPERO to identify ongoing or unpublished studies. Additionally, studies were included through a handpicked search on websites of governmental nudge units and global health or development organizations.ResultsThis scoping review identified 33 relevant studies, with only two studies targeting NTDs in particular, resulting in a total of 67 nudge strategies. Most nudges targeted handwashing behavior and were focused on general health practices rather than targeting a specific disease. The most common nudge strategies were those targeting decision assistance, such as facilitating commitment and reminder actions. The majority of nudges were of moderate to high ethical standards, with the highest standards being those that had the most immediate and significant health benefits, and those implemented by agents in a trust relationship with the target audience.ConclusionThree key recommendations should inform research investigating nudge strategies in global health promotion in general. Firstly, future efforts should investigate the different opportunities that nudges present for targeting NTDs in particular, rather than relying solely on integrated health promotion approaches. Secondly, to apply robust study designs including rigorous process and impact evaluation which allow for a better understanding of ‘what works’ and ‘how it works’. Finally, to consider the ethical implications of implementing nudge strategies, specifically in LMIC.     

A network-patch methodology for adapting agent-based models for directly transmitted disease to mosquito-borne disease

Mosquito-borne diseases cause significant public health burden and are widely re-emerging or emerging. Understanding, predicting, and mitigating the spread of mosquito-borne disease in diverse populations and geographies are ongoing modelling challenges. We propose a hybrid network-patch model for the spread of mosquito-borne pathogens that accounts for individual movement through mosquito habitats, extending the capabilities of existing agent-based models (ABMs) to include vector-borne diseases. The ABM are coupled with differential equations representing ‘clouds’ of mosquitoes in patches accounting for mosquito ecology. We adapted an ABM for humans using this method and investigated the importance of heterogeneity in pathogen spread, motivating the utility of models of individual behaviour. We observed that the final epidemic size is greater in patch models with a high risk patch frequently visited than in a homogeneous model. Our hybrid model quantifies the importance of the heterogeneity in the spread of mosquito-borne pathogens, guiding mitigation strategies.     

Deforestation and vector-borne disease: Forest conversion favors important mosquito vectors of human pathogens

The global burden of vector-borne diseases accounts for more than 17% of infectious diseases in humans. Rapid global expansion of previously obscure pathogens, such as Zika and chikungunya viruses in recent years highlights the importance of understanding how anthropogenic changes influence emergence and spillover of vector-borne diseases. Deforestation has been identified as one anthropogenic change that influences vector-borne disease prevalence, although contrasting pictures of the effects of deforestation on vector-borne disease transmission have been reported. These conflicting findings are likely attributable to the inherent complexity of vector-borne disease systems, which involve diverse groups of vectors, hosts and pathogens, depending on geography. The current study represents a quantitative exploration of the link between deforestation and mosquitoes, the most important common constituents of vector-borne disease systems. Analysis of data compiled from published field studies for 87 mosquito species from 12 countries revealed that about half of the species (52.9%) were associated with deforested habitats. Of these species that are favored by deforestation, a much larger percentage (56.5%) are confirmed vectors of human pathogens, compared to those negatively impacted by deforestation (27.5%). Moreover, species that serve as vectors of multiple human pathogens were all favored by deforestation, including Anopheles bancroftii, Anopheles darlingi, Anopheles farauti, Anopheles funestus s.l., Anopheles gambiae s.l., Anopheles subpictus, Aedes aegypti, Aedes vigilax, Culex annulirostris, and Culex quinquefasciatus. Our quantitative analysis of vector and non-vector species, demonstrates that the net effect of deforestation favors mosquitoes that serve as vectors of human disease, while the obverse holds true for non-vectors species. These results begin to unify our understanding of the relationship between deforestation and vector mosquitoes, an important step in quantifying how land use change, specifically deforestation, affects human risk of vector-borne disease.     

Towards a Better Integration of Global Health and Biodiversity in the New Sustainable Development Goals Beyond Rio+20

In June 2012, Brazil hosted Rio+20, the United Nations Conference on Sustainable Development (UNCSD) marking the 20th anniversary of the 1992 Earth Summit. The Rio+20 outcome document entitled The future we want provides general guidance to shape sustainable development policies, but fell short of providing legally binding agreements or pragmatic goals. Negotiators agreed to develop a process for the establishment of new Sustainable Development Goals (SDGs), building upon the Millennium Development Goals, and setting the foundation for the post-2015 UN development agenda. Our objective is to argue that discussions beyond Rio+20 and toward the adoption of SDGs offer a critical opportunity to re-assess the major challenges for global health and sustainable development. There is an urgent need to translate the general aspirations put forth by Rio+20 into concrete health outcomes and greater health equity. The way toward the post-2015 SDGs will likely be more effective if it highlights the full gamut of linkages between ecosystem processes, anthropogenic environmental changes (climate change, biodiversity loss, and land use), socio-economic changes, and global health. Negotiations beyond Rio+20 should strongly acknowledge the global health benefits of biodiversity protection and climate change mitigation and adaptation strategies, which reduce diseases of poverty and protect the health of the most vulnerable. We argue that health and ecosystems are inextricably linked to all development sectors and that health should remain a critical priority for the upcoming SDGs in the context of global environmental change.     

PCR to predict risk of airborne disease

Plant, animal and human diseases spread by microscopic airborne particles have had major economic and social impacts during history. Special air-sampling devices have been used to collect such particles since the 19th century but it has often been impossible to identify them accurately. Exciting new opportunities to combine air sampling with quantitative PCR to identify and count these particles are reviewed, using crop pathogen examples. These methods can be used to predict the risk of unexpected outbreaks of airborne diseases by identifying increases in pathogen inoculum or genetic changes in pathogen populations that render control ineffective. The predictions can provide guidance to policymakers, health professionals or the agricultural industry for the development of strategies to minimise the risk of severe pandemics.     

Zoonotic viruses associated with illegally imported wildlife products

The global trade in wildlife has historically contributed to the emergence and spread of infectious diseases. The United States is the world's largest importer of wildlife and wildlife products, yet minimal pathogen surveillance has precluded assessment of the health risks posed by this practice. This report details the findings of a pilot project to establish surveillance methodology for zoonotic agents in confiscated wildlife products. Initial findings from samples collected at several international airports identified parts originating from nonhuman primate (NHP) and rodent species, including baboon, chimpanzee, mangabey, guenon, green monkey, cane rat and rat. Pathogen screening identified retroviruses (simian foamy virus) and/or herpesviruses (cytomegalovirus and lymphocryptovirus) in the NHP samples. These results are the first demonstration that illegal bushmeat importation into the United States could act as a conduit for pathogen spread, and suggest that implementation of disease surveillance of the wildlife trade will help facilitate prevention of disease emergence.     

Research advances in plant-made flavivirus antigens

Outbreaks of flaviviruses such as dengue (DV), yellow fever (YFV), Japanese encephalitis (JEV), tick-borne encephalitis (TBEV) and West Nile (WNV) affect numerous countries around the world. The fast spread of these viruses is the result of increases in the human population, rapid urbanisation and globalisation. While vector control is an important preventive measure against vector-borne diseases, it has failed to prevent the spread of these diseases, particularly in developing countries where the implementation of control measures is intermittent. As antiviral drugs against flaviviruses are not yet available, vaccination remains the most important tool for prevention. Although human vaccines for YFV, TBEV and JEV are available, on-going vaccination efforts are insufficient to prevent infection. No vaccines against DENV and WNV are available. Research advances have provided important tools for flavivirus vaccine development, such as the use of plants as a recombinant antigen production platform. This review summarises the research efforts in this area and highlights why a plant system is considered a necessary alternative production platform for high-tech subunit vaccines.