Environmental disease: environmental alteration and infectious disease

Humans have changed their environment to survive and to achieve a safer and more comfortable life. For example, drinking water and wastewater infrastructures are indispensable for civilized societies to flourish and to prevent water-borne infectious diseases. However, excessive loading on environments might disturb microbial ecosystems, resulting in outbreaks of pathogenic microbes and the expansion of infectious diseases. Clarifying the relationship between environmental alterations and changes in microbial ecosystems is thus important to prevent further outbreaks of infectious diseases. The present study aims to understand the links between the following factors: environmental alterations; ecosystem disturbance and the occurrence of infectious disease; and impact on society. We focus on legionellosis and nontuberculous mycobacterial diseases from the viewpoint of their environmental linkage. While Legionella spp. are ubiquitous in aquatic environments, Legionella pneumophila often increases in anthropogenic environments, such as cooling towers or spas, and can cause outbreaks of legionellosis. Recently, travel-associated Legionnaires’ disease has caused concern in many countries. The numbers of patients infected with nontuberculous Mycobacteria (NTM) have increased worldwide since the 1990s. Disturbances to microbial ecosystems caused by changes in water usage might be one cause of NTM diseases. Clarifying the dynamics of Legionella pneumophila and NTM in aquatic environments should help prevent outbreaks of diseases associated with these bacteria.     

CRISPR-Cas9应用于病毒性传染病防控的研究进展

病毒性传染病是威胁人类健康的重要因素,迫切需要新的治疗方法来降低由急性病毒感染如鼻病毒和登革热病毒以及慢性病毒感染如人类免疫缺陷病毒1和乙型肝炎病毒引起的发病率和死亡率.随着分子生物学技术的发展,靶向序列特异性的基因编辑技术成为传染病治疗的有力工具.其中规律成簇间隔短回文重复序列(clustered regularly interspaced short palindromic repeats,CRISPR)-CRISPR相关蛋白9(CRISPR associated protein 9,Cas9)凭借其高效、简便、高特异性等特点被广泛应用于细胞系和动物模型中的传染病治疗,从而成为有前景的新型传染病治疗模式.目前,利用病毒和非病毒载体将Cas9以DNA、m RNA或蛋白质的形式递送到细胞中的可行性研究和评估CRISPR-Cas9体内适用性的临床试验已经在进行中.本篇综述中,我们将对CRISPR-Cas9的原理,其应用于传染病治疗的最新研究进展以及该技术面临的挑战和可预测性的解决方法等加以概述,并进一步展望其未来的发展方向.     

Prophylactic and Therapeutic Efficacy of Avian Antibodies Against Influenza Virus H5N1 and H1N1 in Mice

Background

Pandemic influenza poses a serious threat to global health and the world economy. While vaccines are currently under development, passive immunization could offer an alternative strategy to prevent and treat influenza virus infection. Attempts to develop monoclonal antibodies (mAbs) have been made. However, passive immunization based on mAbs may require a cocktail of mAbs with broader specificity in order to provide full protection since mAbs are generally specific for single epitopes. Chicken immunoglobulins (IgY) found in egg yolk have been used mainly for treatment of infectious diseases of the gastrointestinal tract. Because the recent epidemic of highly pathogenic avian influenza virus (HPAIV) strain H5N1 has resulted in serious economic losses to the poultry industry, many countries including Vietnam have introduced mass vaccination of poultry with H5N1 virus vaccines. We reasoned that IgY from consumable eggs available in supermarkets in Vietnam could provide protection against infections with HPAIV H5N1.

Methods and Findings

We found that H5N1-specific IgY that are prepared from eggs available in supermarkets in Vietnam by a rapid and simple water dilution method cross-protect against infections with HPAIV H5N1 and related H5N2 strains in mice. When administered intranasally before or after lethal infection, the IgY prevent the infection or significantly reduce viral replication resulting in complete recovery from the disease, respectively. We further generated H1N1 virus-specific IgY by immunization of hens with inactivated H1N1 A/PR/8/34 as a model virus for the current pandemic H1N1/09 and found that such H1N1-specific IgY protect mice from lethal influenza virus infection.

Conclusions

The findings suggest that readily available H5N1-specific IgY offer an enormous source of valuable biological material to combat a potential H5N1 pandemic. In addition, our study provides a proof-of-concept for the approach using virus-specific IgY as affordable, safe, and effective alternative for the control of influenza outbreaks, including the current H1N1 pandemic.     

Metal pollution-induced immunomodulation in fish

The exact relationship between disease incidence in aquatic organisms and environmental pollution is not well defined. A number of mechanisms by which aquatic pollutants may act to increase disease incidence in fish have been speculated, many suggesting immunosuppression as a link in the etiology of disease among fishes in highly contaminated areas. This article will review the effects of metal pollutants on the immune responses of fish by examining in vitro and in vivo laboratory studies carried out since 1980. It will also describe how those alterations may be responsible for pollution-associated diseases in directly exposed fish. While a large number of environmental contaminants represent aquatic pollutants of concern (e.g. polycyclic aromatic hydrocarbons, chlorinated organics, and pesticides), heavy metals were selected as the pollutants for this review because of their: (a) prevalence in polluted aquatic environments; (b) immunotoxic potential in mammalian systems; (c) ability to induce tumors in exposed rodents; and (d) their overall toxicity in a variety of species. It can be concluded that a number of heavy metal pollutants shown to be immunotoxic in mammalian systems, including cadmium, chromium, copper, lead, manganese, nickel, and zic, also alter immunoregulatory functions in a variety of fish species. These alterations may ultimately lead to increased host susceptibility to infectious and malignant diseases in fish inhabiting heavy metal-contaminated waters.     

Characterization of specific egg yolk immunoglobulin (IgY) against mastitis-causing Staphylococcus aureus

Aims: To evaluate the in vitro activity of egg yolk immunoglobulin (IgY) against mastitis-causing Staphylococcus aureus. Methods and Results: Specific IgY was produced by immunizing hens with formaldehyde-killed Staph. aureus, using a bacterial strain known to cause mastitis. The IgY, of 94% purity, was obtained from yolks by water dilution, salt precipitations, ultrafiltration and gel filtration. ELISA indicated that the IgY produced was specific to the antigen and five Staph. aureus isolates obtained from mastitic cows. The growth of Staph. aureus was inhibited by specific IgY at concentrations from 1 to 10 mg ml⁻¹ in a dose-dependent manner. The phagocytosis of Staph. aureus by milk macrophages was enhanced in the presence of specific IgY with the highest phagocytic percentage being 30% higher than that without IgY (P < 0·05). Conclusions: The specific IgY against mastitis-causing Staph. aureus inhibited the growth of Staph. aureus and enhanced the phagocytosis of Staph. aureus by milk macrophages. Significance and Impact of the Study: Specific IgY would be a potential treatment for bovine mastitis.     

Free radical scavenging activity of Cleome gynandra L. leaves on adjuvant induced arthritis in rats

The generation of free radicals has been implicated in the causation of several diseases of known and unknown etiologies such as, rheumatoid arthritis, diabetes, cancer, etc., and compounds that can scavenge free radicals have great potential in ameliorating these disease processes. The present study was aimed to investigate the possible anti-oxidant potential of Cleome gynandra leaf extract at a dose of 150 mg/kg body weight for 30 days on adjuvant induced arthritis in experimental rats. Oral administration of C. gynandra leaf extract significantly increased the levels of lipid peroxides and activities of catalase, glutathione peroxidase and decreased the levels of reduced glutathione and superoxide dismutase activity in arthritis induced rats. The free radical scavenging activity of the plant was further evidenced by histological observations made on the limb tissue. The presence of biologically active ingredients and vital trace elements in the leaves readily account for free radical scavenging property of C. gynandra. (Mol Cell Biochem 276: 71–80, 2005)     

The Decline of the Sharp-Snouted Day Frog (Taudactylus acutirostris): The First Documented Case of Extinction by Infection in a Free-Ranging Wildlife Species?

Infectious diseases are increasingly recognized as the cause of mass mortality events, population declines, and the local extirpation of wildlife species. In a number of cases, it has been hypothesized that pathogens have caused species extinctions in wildlife. However, there is only one definitively proven case of extinction by infection, and this was in a remnant captive population of a Polynesian tree snail. In this article, we review the potential involvement of infectious disease in the recent extinction of the sharp-snouted day frog Taudactylus acutirostris. Our review of available evidence suggests that a virulent pathogen of amphibians, Batrachochytrium dendrobatidis, caused a rapid, catastrophic decline of this species, from which it did not recover. We propose that this is the first case of extinction by infection of a free-ranging wildlife species where disease acted as both the proximate and ultimate cause of extinction. This highlights a probable underreporting of infectious disease as a cause of biodiversity loss historically and currently.     

代谢组学技术在水产动物疾病研究中的应用

代谢组学是定量描述生物内源性代谢物质的整体及其对内因和外因变化应答规律的的一门新学科。近年来,代谢组学技术在水产动物疾病中的研究备受关注,特别是为感染性疾病发生机制及防控研究提供了一种新的手段。本文介绍了代谢组学技术及其在水产动物研究中的应用,包括代谢组学技术在水产动物感染性疾病、细菌耐药及环境应激等方面应用进行综述,分析了代谢组学在水产动物疾病研究中面临的问题与挑战,并对未来水产动物代谢组学研究趋势进行了展望,以期为代谢组学技术在水产动物疾病发病机制和药物研发方面更深入的运用提供参考。     

A review on anti‐tuberculosis peptides: Impact of peptide structure on anti‐tuberculosis activity

Antibiotic resistance is a major public health problem globally. Particularly concerning amongst drug‐resistant human pathogens is Mycobacterium tuberculosis that causes the deadly infectious tuberculosis (TB) disease. Significant issues associated with current treatment options for drug‐resistant TB and the high rate of mortality from the disease makes the development of novel treatment options against this pathogen an urgent need. Antimicrobial peptides are part of innate immunity in all forms of life and could provide a potential solution against drug‐resistant TB. This review is a critical analysis of antimicrobial peptides that are reported to be active against the M tuberculosis complex exclusively. However, activity on non‐TB strains such as Mycobacterium avium and Mycobacterium intracellulare, whenever available, have been included at appropriate sections for these anti‐TB peptides. Natural and synthetic antimicrobial peptides of diverse sequences, along with their chemical structures, are presented, discussed, and correlated to their observed antimycobacterial activities. Critical analyses of the structure allied to the anti‐mycobacterial activity have allowed us to draw important conclusions and ideas for research and development on these promising molecules to realise their full potential. Even though the review is focussed on peptides, we have briefly summarised the structures and potency of the various small molecule drugs that are available and under development, for TB treatment.     

Efficacy of specific IgY for treatment of lipopolysaccharide-induced endotoxemia using a mouse model

Aims: To estimate the efficacy of specific egg yolk immunoglobulin (IgY) for the treatment of lipopolysaccharide (LPS)‐induced endotoxemia using a mouse model. Methods and Results: Specific IgY was obtained from the yolk of hens immunized with formaldehyde‐killed Escherichia coli O111 and showed a high binding activity to LPS when subjected to an ELISA. Endotoxemia was induced in mice by intraperitoneal injection of LPS at a dose of 20 mg kg^?1 for measuring survival rate and 10 mg kg^?1 for cytokine measurement. The survival rate of mice treated with 200 mg kg^?1 specific IgY or 5 mg kg^?1 dexamethasone was 70% while none of the mice in the normal saline–treated group survived more than 7 days. Specific IgY significantly (P < 0·05) decreased tumour necrosis factor‐α (TNF‐α) level and increased interleukin‐10 (IL‐10) level in the serum of endotoxemia mice. Specific IgY had less of an effect on TNF‐α than dexamthasone, while its effect on increasing IL‐10 was stronger than dexamethasone. Haematoxylin and eosin–stained sections indicated that IgY attenuated the damage to the lung and liver observed in mice with endotoxemia. Conclusions: The specific IgY increased the survival rate of mice with endotoxemia induced by LPS, down‐regulated TNF‐α and up‐regulated IL‐10 in serum and attenuated the extent of damage to the lung and liver. Significance and Impact of the Study: The specific IgY has potential for the treatment of LPS‐induced endotoxemia.     

Recent updates on drug resistance in Mycobacterium tuberculosis

Tuberculosis (TB) along with acquired immune deficiency syndrome and malaria rank among the top three fatal infectious diseases which pose threat to global public health, especially in middle and low income countries. TB caused by Mycobacterium tuberculosis (Mtb) is an airborne infectious disease and one-third of the world's population gets infected with TB leading to nearly 1·6 million deaths annually. TB drugs are administered in different combinations of four first-line drugs (rifampicin, isoniazid, pyrazinamide and ethambutol) which form the core of treatment regimens in the initial treatment phase of 6–9 months. Several reasons account for the failure of TB therapy such as (i) late diagnosis, (ii) lack of timely and proper administration of effective drugs, (iii) lower availability of less toxic, inexpensive and effective drugs, (iv) long treatment duration, (v) nonadherence to drug regimen and (vi) evolution of drug-resistant TB strains. Drug-resistant TB poses a significant challenge to TB therapy and control programs. In the background of worldwide emergence of 558 000 new TB cases with resistance to rifampicin in the year 2017 and of them, 82% becoming multidrug-resistant TB (MDR-TB), it is essential to continuously update the knowledge on the mechanisms and molecular basis for evolution of Mtb drug resistance. This narrative and traditional review summarizes the progress on the anti-tubercular agents, their mode of action and drug resistance mechanisms in Mtb. The aim of this review is to provide recent updates on drug resistance mechanisms, newly developed/repurposed anti-TB agents in pipeline and international recommendations to manage MDR-TB. It is based on recent literature and WHO guidelines and aims to facilitate better understanding of drug resistance for effective TB therapy and clinical management.     

Global mapping of infectious disease

The primary aim of this review was to evaluate the state of knowledge of the geographical distribution of all infectious diseases of clinical significance to humans. A systematic review was conducted to enumerate cartographic progress, with respect to the data available for mapping and the methods currently applied. The results helped define the minimum information requirements for mapping infectious disease occurrence, and a quantitative framework for assessing the mapping opportunities for all infectious diseases. This revealed that of 355 infectious diseases identified, 174 (49%) have a strong rationale for mapping and of these only 7 (4%) had been comprehensively mapped. A variety of ambitions, such as the quantification of the global burden of infectious disease, international biosurveillance, assessing the likelihood of infectious disease outbreaks and exploring the propensity for infectious disease evolution and emergence, are limited by these omissions. An overview of the factors hindering progress in disease cartography is provided. It is argued that rapid improvement in the landscape of infectious diseases mapping can be made by embracing non-conventional data sources, automation of geo-positioning and mapping procedures enabled by machine learning and information technology, respectively, in addition to harnessing labour of the volunteer ‘cognitive surplus’ through crowdsourcing.     

Aquatic models of human ciliary diseases

Cilia are microtubule‐based structures that either transmit information into the cell or move fluid outside of the cell. There are many human diseases that arise from malfunctioning cilia. Although mammalian models provide vital insights into the underlying pathology of these diseases, aquatic organisms such as Xenopus and zebrafish provide valuable tools to help screen and dissect out the underlying causes of these diseases. In this review we focus on recent studies that identify or describe different types of human ciliopathies and outline how aquatic organisms have aided our understanding of these diseases.     

Production and characterization of a conserved M2e peptide-based specific IgY antibody: evaluation of the diagnostic potential via conjugation with latex nanoparticles

Abstract

Antibodies play an important role in combating and controlling viral diseases such as influenza. Immunoglobulin Y (IgY) antibodies have several advantages such as a less invasive manufacturing process, ease of isolation, higher affinity compared with IgG antibodies, and cost-effectiveness. To date, although specific IgY production has been performed for different strains of influenza A, to the best of our knowledge, an IgY against the M2e peptide has not been produced. In the current study, IgY antibodies are produced, purified, and characterized using the M2e peptide sequence for the first time with the intent to apply them for the diagnosis of influenza A virus. Anti-M2e IgY antibodies are obtained from eggs using a two-step purification method. The activity and characterization of the antibodies are determined using an enzyme-linked immunosorbent assay, a nano-spectrophotometer, an SDS-Page assay, and a Western Blot analysis. Finally, anti-M2e IgY antibodies are conjugated to the latex nanoparticles, and the reaction between the influenza A virus and the nanoparticles is demonstrated using light microscopy, transmission electron microscopy, and energy dispersive X-ray spectroscopy. In conclusion, this study shows that anti-M2e IgY antibodies can contribute to the diagnosis, treatment, and prevention of the influenza A virus.     

嗜黏蛋白阿克曼氏菌治疗疾病的潜力与作用机制研究进展

嗜黏蛋白阿克曼氏菌(Akkermansia muciniphila, AKK)可促进肠道黏液分泌,维持肠道黏液动态平衡,调节肠黏膜屏障功能,在机体代谢调节、免疫应答中发挥重要作用。AKK对肠道炎症、神经炎症、机体代谢紊乱和癌症等疾病具有显著改善作用,被视为极具潜力的下一代益生菌。本文分别从消化系统、神经系统、代谢性紊乱和癌症等角度入手,系统概述AKK在疾病治疗中的潜力及作用分子机制。     

IgY在胃肠感染性疾病中的应用

卵黄抗体（1mmunoglobulinofyolk,IgY）是通过使用特种抗原免疫产蛋鸡,由其卵黄中提取的抗体,与哺乳动物的IgG相似,IgY性质稳定,在控制胃肠道感染性疾病方面存在许多独特的优点,可用于相应疾病的预防和治疗。研究表明,口服特种的IgY对大肠埃希菌、沙门菌、轮状病毒等引起的胃肠感染性疾病可起到免疫保护作用,有望成为抗生素的替代制剂。目前IgY正成为生物技术领域和医药研究中的新热点。     

Leprosy as a genetic model for susceptibility to common infectious diseases

Leprosy (Hansen’s disease) is a human infectious disease that can be effectively treated with long-term administration of multi-drug therapy. In 2006, over 250,000 new cases were reported to the World Health Organization. In the nineteenth century, disagreement among leprologists regarding the hereditary or infectious nature of leprosy was resolved with the identification of the etiological agent, Mycobacterium leprae. However, epidemiological studies maintain the importance of host genetics in leprosy susceptibility. A model free genome-wide linkage scan in multi-case families from Vietnam led to the positional cloning of global genetic risk factors in the PARK2/PACRG and LTA genes. The process of identifying the susceptibility variants provided invaluable insight into the replication of genetic effects, particularly the importance of considering population-specific linkage-disequilibrium structure. As such, these studies serve to improve our understanding of leprosy pathogenesis by implicating novel biological pathways while simultaneously providing a genetic model for common infectious diseases.     

嗜粘蛋白阿克曼菌在糖尿病和肥胖中的作用

肠道微生物在平衡健康与疾病的过程中起着重要作用。嗜粘蛋白阿克曼菌(Akkermansia muciniphila)是肠道微生物中的一种,其在降解肠道粘蛋白方面的特性使其成为肠腔与宿主细胞黏膜界面的关键生物。嗜粘蛋白阿克曼菌与肥胖、糖尿病、心血管代谢疾病和低度炎症呈负相关。口服嗜粘蛋白阿克曼菌可改善小鼠代谢疾病的相关症状,嗜粘蛋白阿克曼菌有望成为治疗2型糖尿病和肥胖的候选药物。本综述通过总结现有关于嗜粘蛋白阿克曼菌在糖尿病和肥胖症中发挥作用的研究,指出嗜粘蛋白阿克曼菌调节宿主和肠道微生物群之间相互作用可能存在的机制,为嗜粘蛋白阿克曼菌的进一步研究和糖尿病的新药研发提供思路。