A research agenda for helminth diseases of humans: towards control and elimination

Human helminthiases are of considerable public health importance in sub-Saharan Africa, Asia, and Latin America. The acknowledgement of the disease burden due to helminth infections, the availability of donated or affordable drugs that are mostly safe and moderately efficacious, and the implementation of viable mass drug administration (MDA) interventions have prompted the establishment of various large-scale control and elimination programmes. These programmes have benefited from improved epidemiological mapping of the infections, better understanding of the scope and limitations of currently available diagnostics and of the relationship between infection and morbidity, feasibility of community-directed or school-based interventions, and advances in the design of monitoring and evaluation (M&E) protocols. Considerable success has been achieved in reducing morbidity or suppressing transmission in a number of settings, whilst challenges remain in many others. Some of the obstacles include the lack of diagnostic tools appropriate to the changing requirements of ongoing interventions and elimination settings; the reliance on a handful of drugs about which not enough is known regarding modes of action, modes of resistance, and optimal dosage singly or in combination; the difficulties in sustaining adequate coverage and compliance in prolonged and/or integrated programmes; an incomplete understanding of the social, behavioural, and environmental determinants of infection; and last, but not least, very little investment in research and development (R&D). The Disease Reference Group on Helminth Infections (DRG4), established in 2009 by the Special Programme for Research and Training in Tropical Diseases (TDR), was given the mandate to undertake a comprehensive review of recent advances in helminthiases research, identify research gaps, and rank priorities for an R&D agenda for the control and elimination of these infections. This review presents the processes undertaken to identify and rank ten top research priorities; discusses the implications of realising these priorities in terms of their potential for improving global health and achieving the Millennium Development Goals (MDGs); outlines salient research funding needs; and introduces the series of reviews that follow in this PLoS Neglected Tropical Diseases collection, "A Research Agenda for Helminth Diseases of Humans."     

Introductory conference: on the relevance of protected areas for the research on conservation ecology: from fundaments to applications

Regarding the present rate of species extinction, preservation of biodiversity has become a prerequisite to achieve sustainable development. Among major challenges an urgent need in research in biological conservation is required to reach this goal. Protected areas deserve special importance due to their relevance for development of research both in fundamental and applied ecology. This papers aims at making a critical review of possibilities and priorities in conservation ecology in these areas.     

生物信息技术发展态势分析

随着计算机科学和互联网技术的进步,生物信息学得到了长足的发展。综述了国际生物信息技术的发展态势,分析了生物信息技术研发和应用的热点和重点,并且在概述国内生物信息发展状况的基础上,提出发展我国生物信息技术的建议。     

Research questions and priorities for tuberculosis: a survey of published systematic reviews and meta-analyses

Background

Systematic reviews are increasingly informing policies in tuberculosis (TB) care and control. They may also be a source of questions for future research. As part of the process of developing the International Roadmap for TB Research, we did a systematic review of published systematic reviews on TB, to identify research priorities that are most frequently suggested in reviews.

Methodology/Principal Findings

We searched EMBASE, MEDLINE, Web of Science, and the Cochrane Library for systematic reviews and meta-analyses on any aspect of TB published between 2005 and 2010. One reviewer extracted data and a second reviewer independently extracted data from a random subset of included studies. In total, 137 systematic reviews, with 141 research questions, were included in this review. We used the UK Health Research Classification System (HRCS) to help us classify the research questions and priorities. The three most common research topics were in the area of detection, screening and diagnosis of TB (32.6%), development and evaluation of treatments and therapeutic interventions (23.4%), and TB aetiology and risk factors (19.9%). The research priorities determined were mainly focused on the discovery and evaluation of bacteriological TB tests and drug-resistant TB tests and immunological tests. Other important topics of future research were genetic susceptibility linked to TB and disease determinants attributed to HIV/TB. Evaluation of drug treatments for TB, drug-resistant TB and HIV/TB were also frequently proposed research topics.

Conclusions

Systematic reviews are a good source of key research priorities. Findings from our survey have informed the development of the International Roadmap for TB Research by the TB Research Movement.     

Careers in academic general practice: problems,constraints, and opportunities.

Changing priorities in the NHS have underlined the crucial importance of academic general practice in providing quality training and research to underpin developments in general practice. Unfortunately, several problems and constraints mean that the full potential of general practitioners to make a contribution to teaching and research has not been realised. These issues are examined and recommendations for improvements are made. Obstacles to career development for academics in general practice should be removed. The funding of academic general practice should be the same as for other medical disciplines. Vocational training for general practice should be extended to include research and audit methods, particularly for doctors interested in an academic career. Above all, the long term objective should be to integrate undergraduate and post-graduate general practice to increase the overall effectiveness of teaching and research and hence the quality of service general practice.     

Reinterpreting Responsiveness for Health Systems Research in Low and Middle‐Income Countries

The ethical concept of responsiveness has largely been interpreted in the context of international clinical research. In light of the increasing conduct of externally funded health systems research (HSR) in low‐ and middle‐income countries (LMICs), this article examines how responsiveness might be understood for such research and how it can be applied. It contends that four features (amongst others) set HSR in LMICs apart from international clinical research: a focus on systems; being context‐driven; being policy‐driven; and being closely linked to development objectives. These features support reinterpreting responsiveness for HSR in LMICs as responsiveness to systems needs, where health system performance assessments can be relied upon to identify systems needs, and/or responsiveness to systems priorities, which entails aligning research with HSR priorities set through country‐owned processes involving national and sub‐national policymakers from host countries. Both concepts may be difficult to achieve in practice. Country ownership is not an established fact for many countries and alignment to their priorities may be meaningless without it. It is argued that more work is, therefore, needed to identify strategies for how the responsiveness requirement can be ethically fulfilled for HSR in LMICs under non‐ideal conditions such as where host countries have not set HSR priorities via country‐owned processes. Embeddedness is proposed as one approach that could be the focus of further development.     

Conducting clinical research in the new NHS: the model of cancer. United Kingdom Coordinating Committee on Cancer Research.

The United Kingdom Coordinating Committee on Cancer Research represents the major organizations funding cancer research in the United Kingdom. The deliberations of a working party convened by the committee to evaluate recently expressed concerns that the changes in the NHS threaten research, especially clinical trials to evaluate new treatments, are reported. A survey of contributors to trials coordinated by the committee showed that half are now experiencing difficulties in continuing to participate in clinical trials. The two major problems identified were lack of time and of staff, especially for NHS staff in non-teaching hospitals. Recent changes in junior doctors'' hours and proposed reductions in the length of time for training will exacerbate this. It is possible to identify the direct and indirect excess costs of conducting research in the NHS, but currently the mechanism does not exist to designate funds specifically for this purpose. Consultation with the regional directors of research and development confirmed that the service increment for teaching and research is not the solution for this. Proposals are made to secure future clinical research in the NHS, including finance, indemnity, the licensing of new drugs, the greater use of nurse counsellors, and the value of cancer registries.     

A research agenda for helminth diseases of humans: diagnostics for control and elimination programmes

Diagnostic tools appropriate for undertaking interventions to control helminth infections are key to their success. Many diagnostic tests for helminth infection have unsatisfactory performance characteristics and are not well suited for use in the parasite control programmes that are being increasingly implemented. Although the application of modern laboratory research techniques to improve diagnostics for helminth infection has resulted in some technical advances, uptake has not been uniform. Frequently, pilot or proof of concept studies of promising diagnostic technologies have not been followed by much needed product development, and in many settings diagnosis continues to rely on insensitive and unsatisfactory parasitological or serodiagnostic techniques. In contrast, PCR-based xenomonitoring of arthropod vectors, and use of parasite recombinant proteins as reagents for serodiagnostic tests, have resulted in critical advances in the control of specific helminth parasites. The Disease Reference Group on Helminths Infections (DRG4), established in 2009 by the Special Programme for Research and Training in Tropical Diseases (TDR) was given the mandate to review helminthiases research and identify research priorities and gaps. In this review, the diagnostic technologies relevant to control of helminth infections, either available or in development, are reviewed. Critical gaps are identified and opportunities to improve needed technologies are discussed.     

The policy context.

The final article in the series considers the ways in which the methods described previously are used in the formation of policy. When health authorities are making decisions about how to spend their money they have to draw on several sources of information about priorities: diktats from policy makers, opinions of consumers and of the professional bodies involved, and evidence gained from research. They must also consider the various methods of costing and select the right one for their circumstances. Some of these methods are still in the early stages of development, but more are being developed all the time and they have a valuable role in helping decision making throughout the NHS.     

Commissioning a national programme of research and development on the interface between primary and secondary care.

The first call for applications to the NHS research and development programme on the interface between primary and secondary care was advertised in February 1994. A total of 674 outline proposals were submitted and 54 (8%) secured funding. Projects have been commissioned in 16 of the 21 priority areas and around 6m pounds has been committed. Analysis shows that multidisciplinary applications are more likely to be funded and that the odds for a successful application are on average nearly doubled for each discipline represented up to five. A survey of applicants and peer reviewers found satisfaction with much of the commissioning process, but peer review and feedback were subject to criticism, particularly by unsuccessful applicants. The programme shows that it is possible to commission a large number of projects in an innovative area of research and development and has identified refinements that will further increase the efficiency and acceptability of the process.     

Biotechnology and bioeconomy in China

From the review of the achievements and advantages in the development of biotechnology (BT) and bioindustry in China, it is clear that the bioeconomy would provide a tremendous opportunity for China to develop sustainably or even surpass a few developed countries. A long-term vision has been made to guide the research and development and industrialization of BT in China. This review detailed the strategies, targets, priorities, and key technologies in each stage. Furthermore, the reviewers expatiated on the establishment of the favorable policies, the foundation of the professional groups, the establishment of the advanced laboratories or centers, the investment mechanisms, the development and evaluation of biosafety, the encouragement and support for the international collaborations and exchanges, and the establishment of the general organizational structure.     

Mutations in a novel gene, NHS, cause the pleiotropic effects of Nance-Horan syndrome, including severe congenital cataract, dental anomalies, and mental retardation

Nance-Horan syndrome (NHS) is an X-linked disorder characterized by congenital cataracts, dental anomalies, dysmorphic features, and, in some cases, mental retardation. NHS has been mapped to a 1.3-Mb interval on Xp22.13. We have confirmed the same localization in the original, extended Australian family with NHS and have identified protein-truncating mutations in a novel gene, which we have called "NHS," in five families. The NHS gene encompasses approximately 650 kb of genomic DNA, coding for a 1,630-amino acid putative nuclear protein. NHS orthologs were found in other vertebrates, but no sequence similarity to known genes was identified. The murine developmental expression profile of the NHS gene was studied using in situ hybridization and a mouse line containing a lacZ reporter-gene insertion in the Nhs locus. We found a complex pattern of temporally and spatially regulated expression, which, together with the pleiotropic features of NHS, suggests that this gene has key functions in the regulation of eye, tooth, brain, and craniofacial development.     

National nutrition surveillance

National Nutrition Surveillance includes nutritional assessment surveys to ascertain the extent of malnutrition in populations, to identify possible causes, to establish baseline data for monitoring nutrition, and to select mechanisms for nutrition surveillance (in a restricted sense). An example of the results from a recent nutritional assessment survey in the United States is the negative association of obesity with energy intake, exercise and socioeconomic status, which has implications for public nutritional policy. Nutritional monitoring measures changes in population nutrition over time. An example of the results from nutritional monitoring is the unexpected and presently unexplained decrease in serum cholesterol levels of middle-aged women in the United States over the past decade. Nutritional surveillance in the restricted sense not only identifies malnutrition but is administratively organized to intervene rapidly. National Nutrition Surveillance depends on metabolic and clinical research to decide on its priorities. This research indicates that malnutrition involves more than under-nutrition, and greater emphasis should be given in National Nutrition Surveillance to this wider context of malnutrition. These results will in turn help set priorities for basic and applied research in nutrition. It is important that the research community participate in the review presently under way of the role of the National Center for Health Statistics in National Nutrition Surveillance.     

Funding the NHS. Is the NHS sustainable?

The survival of the NHS lies largely in the hands of government, and this article suggests steps that it should take to deal with pressures on the NHS in terms of funding, managing efficiency, and demands. Changes to the system of funding may be unfeasible, but management could be improved by research to allow greater understanding of the local effects of national policies. Alternatively health authorities could be given more freedom to manage funds, although this would have to be accompanied by stiff sanctions for those who failed. Demand could be contained by strengthening policies to ensure that new technologies are cost effective. The government could try to reduce demands arising from increased expectations by encouraging informed public debate about priorities and influencing the availability of private health care. All these efforts should be guided by the values underpinning the NHS, which should be debated and decided collectively and confirmed in a new charter for NHS''s 50th anniversary in 1998.     

Invertebrate pests and diseases of sweetpotato (Ipomoea batatas): a review and identification of research priorities for smallholder production

Sweetpotato has been the subject of little research worldwide compared with other major crop staples, and this is especially so for less developed countries where sweetpotato is critical for food security. This review synthesises information on plant protection issues that affect smallholder sweetpotato farmers in less developed countries to identify major issues and suggest research priorities. Though the pests and diseases of sweetpotato in less developed countries are largely common to industrialised systems, their relative importance differs and losses tend to be more severe as a result of differing agronomic practices and relative unavailability of management options and technical support that are important in developed countries. Smallholders are heavily reliant on cultural practices such as traditional forms of biological control using ants and livestock, fallowing and composting (sometimes with plant materials having biocidal properties). Crop protection methods that have been developed for use in sweetpotato production in developed countries, such as pathogen‐tested planting material, early maturing varieties, pheromone trapping and pesticides are less accessible to, and relevant for, smallholders. Smallholders also typically harvest a given crop progressively which extends the period over which storage roots are potentially vulnerable to attack but reduces the risk of post‐harvest losses. Human population growth in developing countries is leading to an increase in cropping intensity with shorter fallow periods and more years of continuous crops. This has the dual effect of depleting soil nutrients and increasing the potential for pest and pathogen build‐up. Associated with this, the adoption of strategies to manage crop nutrition, such as not burning crop residues, promote carryover of pests and pathogen inocula. As a consequence of these factors, sweetpotato yield losses from diseases, especially viruses, and pests, particularly weevils, can be high. Climate change is likely to result in more frequent drought and this will increase losses caused by sweetpotato weevils that are favoured by dry conditions. This review of sweetpotato pests and their management options concludes with suggestions for some future research priorities including the combination of traditional practices that have pest management outcomes with relevant practices from industrial production that are able to be transferred or modified for use in smallholder production. Increased technical support for decision making and diagnostics, including molecular approaches that have scope for field use, will be important in reducing the burden imposed by biotic threats to this important global crop.     

A research agenda for helminth diseases of humans: basic research and enabling technologies to support control and elimination of helminthiases

Successful and sustainable intervention against human helminthiases depends on optimal utilisation of available control measures and development of new tools and strategies, as well as an understanding of the evolutionary implications of prolonged intervention on parasite populations and those of their hosts and vectors. This will depend largely on updated knowledge of relevant and fundamental parasite biology. There is a need, therefore, to exploit and apply new knowledge and techniques in order to make significant and novel gains in combating helminthiases and supporting the sustainability of current and successful mass drug administration (MDA) programmes. Among the fields of basic research that are likely to yield improved control tools, the Disease Reference Group on Helminth Infections (DRG4) has identified four broad areas that stand out as central to the development of the next generation of helminth control measures: 1) parasite genetics, genomics, and functional genomics; 2) parasite immunology; 3) (vertebrate) host-parasite interactions and immunopathology; and 4) (invertebrate) host-parasite interactions and transmission biology. The DRG4 was established in 2009 by the Special Programme for Research and Training in Tropical Diseases (TDR). The Group was given the mandate to undertake a comprehensive review of recent advances in helminthiases research in order to identify notable gaps and highlight priority areas. This paper summarises recent advances and discusses challenges in the investigation of the fundamental biology of those helminth parasites under the DRG4 Group's remit according to the identified priorities, and presents a research and development agenda for basic parasite research and enabling technologies that will help support control and elimination efforts against human helminthiases.     

国家自然科学基金资助微生物组研究的现状与效果分析*

国家自然科学基金项目对科学研究具有扶持、引导作用,其资助和成果情况可在一定程度上反映出我国前沿科技领域的研究重点和发展趋势。选取2010—2021年国家自然科学基金资助微生物组基础研究情况为分析对象,对资助年度、资助金额、资助类别、资助单位、项目成果等内容进行统计分析,反映国家自然科学基金资助微生物组基础研究的现状、特点以及资助效果,为微生物组相关领域的研究和管理人员提供参考和支撑。     

The trypanosome lytic factor of human serum and the molecular basis of sleeping sickness

Trypanosoma brucei brucei infects a wide range of mammals but is unable to infect humans because this subspecies is lysed by normal human serum (NHS). The trypanosome lytic factor is associated with High Density Lipoproteins (HDLs). Several HDL-associated components have been proposed as candidate lytic factors, and contradictory hypotheses concerning the mechanism of lysis have been suggested. Elucidation of the process by which Trypanosoma brucei rhodesiense resists lysis and causes human sleeping sickness has indicated that the HDL-bound apolipoprotein L-I (apoL-I) could be the long-sought after lytic component of NHS. This research also allowed the identification of a specific diagnostic DNA probe for T. b. rhodesiense, and may lead to the development of novel anti-trypanosome strategies for use in the field.     

Accuracy of Probabilistic Linkage Using the Enhanced Matching System for Public Health and Epidemiological Studies

Background

The Enhanced Matching System (EMS) is a probabilistic record linkage program developed by the tuberculosis section at Public Health England to match data for individuals across two datasets. This paper outlines how EMS works and investigates its accuracy for linkage across public health datasets.

Methods

EMS is a configurable Microsoft SQL Server database program. To examine the accuracy of EMS, two public health databases were matched using National Health Service (NHS) numbers as a gold standard unique identifier. Probabilistic linkage was then performed on the same two datasets without inclusion of NHS number. Sensitivity analyses were carried out to examine the effect of varying matching process parameters.

Results

Exact matching using NHS number between two datasets (containing 5931 and 1759 records) identified 1071 matched pairs. EMS probabilistic linkage identified 1068 record pairs. The sensitivity of probabilistic linkage was calculated as 99.5% (95%CI: 98.9, 99.8), specificity 100.0% (95%CI: 99.9, 100.0), positive predictive value 99.8% (95%CI: 99.3, 100.0), and negative predictive value 99.9% (95%CI: 99.8, 100.0). Probabilistic matching was most accurate when including address variables and using the automatically generated threshold for determining links with manual review.

Conclusion

With the establishment of national electronic datasets across health and social care, EMS enables previously unanswerable research questions to be tackled with confidence in the accuracy of the linkage process. In scenarios where a small sample is being matched into a very large database (such as national records of hospital attendance) then, compared to results presented in this analysis, the positive predictive value or sensitivity may drop according to the prevalence of matches between databases. Despite this possible limitation, probabilistic linkage has great potential to be used where exact matching using a common identifier is not possible, including in low-income settings, and for vulnerable groups such as homeless populations, where the absence of unique identifiers and lower data quality has historically hindered the ability to identify individuals across datasets.     

The role of public policy in biological control: Some global trends

The past decade has been a rapid development in the view that contemporary agricultural practices should meet the needs of the present without compromising the ability of future generations. This philosophy has broadened the priorities for research and development in primary production systems. Now there is reduced emphasis on efficiency and productivity, and an increased concern for ecological sustainability. This has had an impact on policies relating to biological control technologies and associated policies have been developed to enhance the uptake of biopesticides. At the same time international agreements on climate change, biodiversity and global trading have potential influences on the use of biological control agents and biological technologies. In this review some of these trends in public policy are highlighted as well as the likely effect they may have in the adoption, implementation and ongoing development of biological control technologies.