All Hands on Deck: Transdisciplinary Approaches to Emerging Infectious Disease

The increasing burden of emerging infectious diseases worldwide confronts us with numerous challenges, including the imperative to design research and responses that are commensurate to understanding the complex social and ecological contexts in which infectious diseases occur. A diverse group of scientists met in Hawaii in March 2005 to discuss the linked social and ecological contexts in which infectious diseases emerge. A subset of the meeting was a group that focused on ‘‘transdisciplinary approaches’’ to integrating knowledge across and beyond academic disciplines in order to improve prevention and control of emerging infections. This article is based on the discussions of that group. Here, we outline the epidemiological legacy that has dominated infectious disease research and control up until now, and introduce the role of new, transdisciplinary and systems-based approaches to emerging infectious diseases.Wedescribe four cases of transboundary health issues and use them to discuss the potential benefits, as well as the inherent difficulties, in understanding the social–ecological contexts in which infectious diseases occur and of using transdisciplinary approaches to deal with them.

Community-onset Staphylococcus aureus infections presenting to general practices in South-eastern Australia

Community-acquired Staphylococcus aureus infections are a public health concern, yet little is known about infections that do not present to hospital. We identified community-onset S. aureus infections via specimens submitted to a community-based pathology service. Referring doctors confirmed eligibility and described infection site, severity and treatment. Isolates were characterized on antibiotic resistance, PFGE, MLST/SCCmec, and Panton–Valentine leukocidin (PVL), representing 106 community-onset infections; 34 non-multiresistant methicillin-resistant S. aureus (nmMRSA) (resistant to <3 non-β-lactam antibiotics), 15 multiply antibiotic-resistant MRSA (mMRSA) and 57 methicillin-sensitive S. aureus (MSSA). Most (93%) were skin and soft tissue infections. PVL genes were carried by 42% of nmMRSA isolates [95% confidence interval (CI) 26–61] and 15% of MSSA (95% CI 8–28). PVL was associated with infections of the trunk, head or neck (56·4% vs. 24·3%, P= 0·005) in younger patients (23 vs. 52 years, P< 0·001), and with boils or abscesses (OR 8·67, 95% CI 2·9–26·2), suggesting underlying differences in exposure and/or pathogenesis.

Outpatient Parenteral Antimicrobial Therapy Practices among Adult Infectious Disease Physicians

Objective. To identify current outpatient parenteral antibiotic therapy practice patterns and complications. Methods. We administered an 11-question survey to adult infectious disease physicians participating in the Emerging Infections Network (EIN), a Centers for Disease Control and Prevention-sponsored sentinel event surveillance network in North America. The survey was distributed electronically or via facsimile in November and December 2012. Respondent demographic characteristics were obtained from EIN enrollment data. Results. Overall, 555 (44.6%) of EIN members responded to the survey, with 450 (81%) indicating that they treated 1 or more patients with outpatient parenteral antimicrobial therapy (OPAT) during an average month. Infectious diseases consultation was reported to be required for a patient to be discharged with OPAT by 99 respondents (22%). Inpatient (282 [63%] of 449) and outpatient (232 [52%] of 449) infectious diseases physicians were frequently identified as being responsible for monitoring laboratory results. Only 26% (118 of 448) had dedicated OPAT teams at their clinical site. Few infectious diseases physicians have systems to track errors, adverse events, or "near misses" associated with OPAT (97 [22%] of 449). OPAT-associated complications were perceived to be rare. Among respondents, 80% reported line occlusion or clotting as the most common complication (occurring in 6% of patients or more), followed by nephrotoxicity and rash (each reported by 61%). Weekly laboratory monitoring of patients who received vancomycin was reported by 77% of respondents (343 of 445), whereas 19% of respondents (84 of 445) reported twice weekly laboratory monitoring for these patients. Conclusions. Although use of OPAT is common, there is significant variation in practice patterns. More uniform OPAT practices may enhance patient safety.

Shigellosis in Hidalgo County, Texas 2005--2009: A descriptive study

Shigellosis is a communicable disease harbored primarily by humans. The low infective dose, no vaccine availability, and mild or asymptomatic nature of disease has prevented eradication of Shigella in the United States. In addition, the lack of water and sewage infrastructures which normally contribute to the spread of disease in developing countries, for the most part, is a non-issue in the U.S. making surveillance and risk factor identification important prevention and control measures utilized to reduce the incidence rates of Shigellosis.^ The purpose of this study was to describe the Shigellosis disease burden among the Hidalgo County, Texas population during the 2005-2009 study period and compare these findings with national data available. The potential identification and publication of a health disparity in the form of increased Shigellosis rates among Hidalgo County residents when compared to national rates, especially age-specific rates, are intended to generate public health attention and public health action that will address this issue.^ There were 1,007 confirmed Shigellosis cases reported in Hidalgo County, Texas. An overwhelming majority (79%) of the Shigellosis cases during this time frame occurred in children less than ten years of age. Over the age of 10 through the age of 39, females constituted the majority of cases. Age-specific rates for children four years of age and younger were compared to national rates. The rates for Hidalgo County were higher at 9.2 and 1.8 cases for every one case reported nationally in 2005 and 2006, respectively. The total crude rates of Shigellosis were also higher than the rates available from the Foodborne Diseases Active Surveillance Network (FoodNet) of CDC’s Emerging Infections Program from 2005-2009. As a result, compared to the FoodNet surveillance rates, Hidalgo County experienced above average rates of Shigellosis throughout the study period. The majority of cases were identified in young children under the age of ten.^ The information gathered in this analysis could be used to implement and monitor infection control measures such as hand washing education at facilities that tend to the groups identified at higher risk of infection. In addition, the higher burden of disease found in Hidalgo County requires further study to determine if there are factors associated with an increased risk of Shigellosis in this community and other border communities along the U.S.-Mexico border exist.^

Improving T cell-induced response to subunit vaccines:opportunities for a proteomic systems approach

Prophylactic vaccines are an effective strategy to prevent development of many infectious diseases. With new and re-emerging infections posing increasing risks to food stocks and the health of the population in general, there is a need to improve the rationale of vaccine development. One key challenge lies in development of an effective T cell-induced response to subunit vaccines at specific sites and in different populations. Objectives: In this review, we consider how a proteomic systems-based approach can be used to identify putative novel vaccine targets, may be adopted to characterise subunit vaccines and adjuvants fully. Key findings: Despite the extensive potential for proteomics to aid our understanding of subunit vaccine nature, little work has been reported on identifying MHC 1-binding peptides for subunit vaccines generating T cell responses in the literature to date. Summary: In combination with predictive and structural biology approaches to mapping antigen presentation, proteomics offers a powerful and as yet un-tapped addition to the armoury of vaccine discovery to predict T-cell subset responses and improve vaccine design strategies.

Epidemiology and Emergence of Schmallenberg Virus Part 2: Pathogenesis and Risk of Viral Spread

Schmallenberg virus (SBV) is a novel Orthobunyavirus causing mild clinical signs in cows and malformations in aborted and neonatal ruminants in Europe. SBV belongs to the family Bunyaviridae and is transmitted by biting midges. This new virus was identified for the first time in blood samples of cows in the city of Schmallenberg in North-Rhine Westphalia in November 2011. Since then, the virus spread to several European countries. Here, we describe the pathogenesis and the risk of viral spread in the Portuguese territory.

Epidemiology and Emergence of Schmallenberg Virus Part 1: Origin, Transmission and Differential Diagnosis

Schmallenberg virus (SBV) is a novel Orthobunyavirus causing mild clinical signs in cows and malformations in aborted and neonatal ruminants in Europe. SBV belongs to the family Bunyaviridae and is transmitted by biting midges. This new virus was identified for the first time in the blood samples of cows in the city of Schmallenberg in NorthRhine-Westphalia in November 2011. Since then the virus spread to several European countries. Here we describe the origin and emergence, as well as the transmission and the differential diagnosis of this virus, now known to be a serious threat to Veterinary Public Health.

Chlamydial infections of fish: Diverse pathogens and emerging causes of disease in aquaculture species

Chlamydial infections of fish are emerging as an important cause of disease in new and established aquaculture industries. To date, epitheliocystis, a skin and gill disease associated with infection by these obligate intracellular pathogens, has been described in over 90 fish species, including hosts from marine and fresh water environments. Aided by advances in molecular detection and typing, recent years have seen an explosion in the description of these epitheliocystis-related chlamydial pathogens of fish, significantly broadening our knowledge of the genetic diversity of the order Chlamydiales. Remarkably, in most cases, it seems that each new piscine host studied has revealed the presence of a phylogenetically unique and novel chlamydial pathogen, providing researchers with a fascinating opportunity to understand the origin, evolution and adaptation of their traditional terrestrial chlamydial relatives. Despite the advances in this area, much still needs to be learnt about the epidemiology of chlamydial infections in fish if these pathogens are to be controlled in farmed environments. The lack of in vitro methods for culturing of chlamydial pathogens of fish is a major hindrance to this field. This review provides an update on our current knowledge of the taxonomy and diversity of chlamydial pathogens of fish, discusses the impact of these infections on the health, and highlights further areas of research required to understand the biology and epidemiology of this important emerging group of fish pathogens of aquaculture species.

Aspergillus flavus infections in Galleria mellonella : a pathogen-host model system for the study of emerging diseases

To study emerging diseases, I employed a model pathogen-host system involving infections of insect larvae with the opportunistic fungus Aspergillus flavus, providing insight into three mechanisms ofpathogen evolution namely de novo mutation, genome decay, and virulence factoracquisition In Chapter 2 as a foundational experiment, A. flavus was serially propagated through insects to study the evolution of an opportunistic pathogen during repeated exposure to a single host. While A. flavus displayed de novo phenotypic alterations, namely decreased saprobic capacity, analysis of genotypic variation in Chapter 3 signified a host-imposed bottleneck on the pathogen population, emphasizing the host's role in shaping pathogen population structure. Described in Chapter 4, the serial passage scheme enabled the isolation of an A. flavus cysteine/methionine auxotroph with characteristics reminiscent of an obligate insect pathogen, suggesting that lost biosynthetic capacity may restrict host range based on nutrient availability and provide selection pressure for further evolution. As outlined in Chapter 6, cysteine/methionine auxotrophy had the pleiotrophic effect of increasing virulence factor production, affording the slow-growing auxotroph with a modified pathogenic strategy such that virulence was not reduced. Moreover in Chapter 7, transformation with a virulence factor from a facultative insect pathogen failed to increase virulence, demonstrating the necessity of an appropriate genetic background for virulence factor acquisition to instigate pathogen evolution.

Economic evaluation and catheter-related bloodstream infections

Catheter-related bloodstream infections are a serious problem. Many interventions reduce risk, and some have been evaluated in cost-effectiveness studies. We review the usefulness and quality of these economic studies. Evidence is incomplete, and data required to inform a coherent policy are missing. The cost-effectiveness studies are characterized by a lack of transparency, short time-horizons, and narrow economic perspectives. Data quality is low for some important model parameters. Authors of future economic evaluations should aim to model the complete policy and not just single interventions. They should be rigorous in developing the structure of the economic model, include all relevant economic outcomes, use a systematic approach for selecting data sources for model parameters, and propagate the effect of uncertainty in model parameters on conclusions. This will inform future data collection and improve our understanding of the economics of preventing these infections.

Maize streak virus: An old and complex 'emerging' pathogen

Maize streak virus (MSV; Genus Mastrevirus, Family Geminiviridae) occurs throughout Africa, where it causes what is probably the most serious viral crop disease on the continent. It is obligately transmitted by as many as six leafhopper species in the Genus Cicadulina, but mainly by C. mbila Naudé and C. storeyi. In addition to maize, it can infect over 80 other species in the Family Poaceae. Whereas 11 strains of MSV are currently known, only the MSV-A strain is known to cause economically significant streak disease in maize. Severe maize streak disease (MSD) manifests as pronounced, continuous parallel chlorotic streaks on leaves, with severe stunting of the affected plant and, usuallly, a failure to produce complete cobs or seed. Natural resistance to MSV in maize, and/or maize infections caused by non-maize-adapted MSV strains, can result in narrow, interrupted streaks and no obvious yield losses. MSV epidemiology is primarily governed by environmental influences on its vector species, resulting in erratic epidemics every 3-10 years. Even in epidemic years, disease incidences can vary from a few infected plants per field, with little associated yield loss, to 100% infection rates and complete yield loss. Taxonomy: The only virus species known to cause MSD is MSV, the type member of the Genus Mastrevirus in the Family Geminiviridae. In addition to the MSV-A strain, which causes the most severe form of streak disease in maize, 10 other MSV strains (MSV-B to MSV-K) are known to infect barley, wheat, oats, rye, sugarcane, millet and many wild, mostly annual, grass species. Seven other mastrevirus species, many with host and geographical ranges partially overlapping those of MSV, appear to infect primarily perennial grasses. Physical properties: MSV and all related grass mastreviruses have single-component, circular, single-stranded DNA genomes of approximately 2700 bases, encapsidated in 22 × 38-nm geminate particles comprising two incomplete T = 1 icosahedra, with 22 pentameric capsomers composed of a single 32-kDa capsid protein. Particles are generally stable in buffers of pH 4-8. Disease symptoms: In infected maize plants, streak disease initially manifests as minute, pale, circular spots on the lowest exposed portion of the youngest leaves. The only leaves that develop symptoms are those formed after infection, with older leaves remaining healthy. As the disease progresses, newer leaves emerge containing streaks up to several millimetres in length along the leaf veins, with primary veins being less affected than secondary or tertiary veins. The streaks are often fused laterally, appearing as narrow, broken, chlorotic stripes, which may extend over the entire length of severely affected leaves. Lesion colour generally varies from white to yellow, with some virus strains causing red pigmentation on maize leaves and abnormal shoot and flower bunching in grasses. Reduced photosynthesis and increased respiration usually lead to a reduction in leaf length and plant height; thus, maize plants infected at an early stage become severely stunted, producing undersized, misshapen cobs or giving no yield at all. Yield loss in susceptible maize is directly related to the time of infection: Infected seedlings produce no yield or are killed, whereas plants infected at later times are proportionately less affected. Disease control: Disease avoidance can be practised by only planting maize during the early season when viral inoculum loads are lowest. Leafhopper vectors can also be controlled with insecticides such as carbofuran. However, the development and use of streak-resistant cultivars is probably the most effective and economically viable means of preventing streak epidemics. Naturally occurring tolerance to MSV (meaning that, although plants become systemically infected, they do not suffer serious yield losses) has been found, which has primarily been attributed to a single gene, msv-1. However, other MSV resistance genes also exist and improved resistance has been achieved by concentrating these within individual maiz genotypes. Whereas true MSV immunity (meaning that plants cannot be symptomatically infected by the virus) has been achieved in lines that include multiple small-effect resistance genes together with msv-1, it has proven difficult to transfer this immunity into commercial maize genotypes. An alternative resistance strategy using genetic engineering is currently being investigated in South Africa. Useful websites: 〈http://www.mcb.uct.ac.za/MSV/mastrevirus.htm〉; 〈http://www. danforthcenter.org/iltab/geminiviridae/geminiaccess/mastrevirus/Mastrevirus. htm〉. © 2009 Blackwell Publishing Ltd.

In Response: "Oral versus IV treatment for catheter-related bloodstream infections - by Burke A. Cunha"

In his letter Cunha suggests that oral antibiotic therapy is safer and less expensive than intravenous therapy via central venous catheters (CVCs) (1). The implication is that costs will fall and increased health benefits will be enjoyed resulting in a gain in efficiency within the healthcare system. CVCs are often used in critically ill patients to deliver antimicrobial therapy, but expose patients to a risk of catheter-related bloodstream infection (CRBSI). Our current knowledge about the efficiency (i.e. costeffectiveness) of allocating resources toward interventions that prevent CRBSI in patients requiring a CVC has already been reviewed (2). If for some patient groups antimicrobial therapy can be delivered orally, instead of through a CVC, then the costs and benefits of this alternate strategy should be evaluated...