Guo-Jing Yang

A Research Agenda for Helminth Diseases of Humans: Intervention for Control and Elimination

Recognising the burden helminth infections impose on human populations, and particularly the poor, major intervention programmes have been launched to control onchocerciasis, lymphatic filariasis, soil-transmitted helminthiases, schistosomiasis, and cysticercosis. 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 review helminthiases research and identify research priorities and gaps. A summary of current helminth control initiatives is presented and available tools are described. Most of these programmes are highly dependent on mass drug administration (MDA) of anthelmintic drugs (donated or available at low cost) and require annual or biannual treatment of large numbers of at-risk populations, over prolonged periods of time. The continuation of prolonged MDA with a limited number of anthelmintics greatly increases the probability that drug resistance will develop, which would raise serious problems for continuation of control and the achievement of elimination. Most initiatives have focussed on a single type of helminth infection, but recognition of co-endemicity and polyparasitism is leading to more integration of control. An understanding of the implications of control integration for implementation, treatment coverage, combination of pharmaceuticals, and monitoring is needed. To achieve the goals of morbidity reduction or elimination of infection, novel tools need to be developed, including more efficacious drugs, vaccines, and/or antivectorial agents, new diagnostics for infection and assessment of drug efficacy, and markers for possible anthelmintic resistance. In addition, there is a need for the development of new formulations of some existing anthelmintics (e.g., paediatric formulations). To achieve ultimate elimination of helminth parasites, treatments for the above mentioned helminthiases, and for taeniasis and food-borne trematodiases, will need to be integrated with monitoring, education, sanitation, access to health services, and where appropriate, vector control or reduction of the parasite reservoir in alternative hosts. Based on an analysis of current knowledge gaps and identification of priorities, a research and development agenda for intervention tools considered necessary for control and elimination of human helminthiases is presented, and the challenges to be confronted are discussed.

China’s new strategy to block Schistosoma japonicum transmission: experiences and impact beyond schistosomiasis

Despite sustained efforts for its control made over the past 50+ years, the re‐emergence of schistosomiasis in China was noted around the turn of the new millennium. Consequently, a new integrated strategy was proposed to stop the contamination of schistosome eggs to the environment, which emphasizes health education, access to clean water and adequate sanitation, mechanization of agriculture and fencing of water buffaloes, along with chemotherapy. Validation of this integrated control strategy in four pilot counties in the provinces of Anhui, Hubei, Hunan and Jiangxi revealed significant reductions in the rate of Schistosoma japonicum infection in humans and intermediate host snails. Importantly, this strategy showed an impact on diseases beyond schistosomiasis, signified by concomitant reductions in the prevalence of soil‐transmitted helminth infections. In view of China’s new integrated strategy for transmission control of schistosomiasis showing an ancillary benefit on other helminthic diseases, we encourage others to investigate the scope and limits of integrated control of neglected tropical diseases.

Schistosomiasis japonica: control and research needs.

Schistosomiasis japonica, a chronic and debilitating disease caused by the blood fluke Schistosoma japonicum, is still of considerable economic and public health concern in the Peoples Republic of China, the Philippines, and Indonesia. Despite major progress made over the past several decades with the control of schistosomiasis japonica in the aforementioned countries, the disease is emerging in some areas. We review the epidemiological status and transmission patterns of schistosomiasis japonica, placing it into a historical context, and discuss experiences and lessons with national control efforts. Our analyses reveal that an integrated control approach, implemented through intersectoral collaboration, is essential to bring down the prevalence and intensity of Schistosoma japonicum infections and disease-related morbidity, and to sustain these parameters at low levels. The need for innovation and a sufficiently flexible control approach to adapt interventions in response to the changing nature and challenges of schistosomiasis control from the initial phase of morbidity control to the final state of elimination is emphasised. The aim of the presentation and the analyses is to inspire researchers and disease control managers elsewhere in Asia, Africa, and the Americas to harness the experiences gained and the lessons presented here to improve the control and eventual elimination of schistosomiasis and parasitic diseases.

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.

A Research Agenda for Helminth Diseases of Humans: Modelling for Control and Elimination

Mathematical modelling of helminth infections has the potential to inform policy and guide research for the control and elimination of human helminthiases. However, this potential, unlike in other parasitic and infectious diseases, has yet to be realised. To place contemporary efforts in a historical context, a summary of the development of mathematical models for helminthiases is presented. These efforts are discussed according to the role that models can play in furthering our understanding of parasite population biology and transmission dynamics, and the effect on such dynamics of control interventions, as well as in enabling estimation of directly unobservable parameters, exploration of transmission breakpoints, and investigation of evolutionary outcomes of control. 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 review helminthiases research and identify research priorities and gaps. A research and development agenda for helminthiasis modelling is proposed based on identified gaps that need to be addressed for models to become useful decision tools that can support research and control operations effectively. This agenda includes the use of models to estimate the impact of large-scale interventions on infection incidence; the design of sampling protocols for the monitoring and evaluation of integrated control programmes; the modelling of co-infections; the investigation of the dynamical relationship between infection and morbidity indicators; the improvement of analytical methods for the quantification of anthelmintic efficacy and resistance; the determination of programme endpoints; the linking of dynamical helminth models with helminth geostatistical mapping; and the investigation of the impact of climate change on human helminthiases. It is concluded that modelling should be embedded in helminth research, and in the planning, evaluation, and surveillance of interventions from the outset. Modellers should be essential members of interdisciplinary teams, propitiating a continuous dialogue with end users and stakeholders to reflect public health needs in the terrain, discuss the scope and limitations of models, and update biological assumptions and model outputs regularly. It is highlighted that to reach these goals, a collaborative framework must be developed for the collation, annotation, and sharing of databases from large-scale anthelmintic control programmes, and that helminth modellers should join efforts to tackle key questions in helminth epidemiology and control through the sharing of such databases, and by using diverse, yet complementary, modelling approaches.

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.”

Spatial epidemiology in zoonotic parasitic diseases: insights gained at the 1st International Symposium on Geospatial Health in Lijiang, China, 2007

The 1st International Symposium on Geospatial Health was convened in Lijiang, Yunnan province, Peoples Republic of China from 8 to 9 September, 2007. The objective was to review progress made with the application of spatial techniques on zoonotic parasitic diseases, particularly in Southeast Asia. The symposium featured 71 presentations covering soil-transmitted and water-borne helminth infections, as well as arthropod-borne diseases such as leishmaniasis, malaria and lymphatic filariasis. The work made public at this occasion is briefly summarized here to highlight the advances made and to put forth research priorities in this area. Approaches such as geographical information systems (GIS), global positioning systems (GPS) and remote sensing (RS), including spatial statistics, web-based GIS and map visualization of field investigations, figured prominently in the presentation.

China's sustained drive to eliminate neglected tropical diseases

Non-communicable diseases dominate the public health arena in China, yet neglected tropical diseases (NTDs) are still widespread and create a substantial burden. We review the geographical distribution, prevalence, and epidemic characteristics of NTDs identified in China caused by helminths, protozoa, bacteria, and viruses. Lymphatic filariasis was eliminated in 2007, but schistosomiasis still affects up to 5% of local village residents in some endemic counties with around 300 000 people infected. China harbours more than 90% of the worlds burden of alveolar echinococcosis and food-borne zoonoses are emerging. In 2010, the overall prevalence of soil-transmitted helminth infections caused by Ascaris lumbricoides, Trichuris trichiura, and hookworm was 11·4%, with 6·8% of these infections caused by A lumbricoides. Corresponding figures for food-borne trematodiasis, echinococcosis, and cysticercosis are more than 5%. Dengue, leishmaniasis, leprosy, rabies, and trachoma exist in many areas and should not be overlooked. Transmission of vector-borne diseases can be interrupted; nevertheless, epidemics occur in remote areas, creating a challenge for surveillance and control. Rigorous surveillance, followed by immediate and integrated response packages tailored to specific social and ecological systems, is essential for progress towards the elimination of NTDs in China.

Effect of temperature on the development of Schistosoma japonicum within Oncomelania hupensis, and hibernation of O. hupensis

The objectives of this investigation were to assess the effect of temperature on the development of Schistosoma japonicum harboured in Oncomelania hupensis and to determine the lowest temperature threshold at which the hibernation of O. hupensis occurs. In the first experiment, adult infection-free O. hupensis, collected from Jiangsu province in eastern China, were infected with S. japonicum miracidia and raised at different temperatures under laboratory conditions. The development of miracidia until the release of cercariae was monitored employing the cercarial shedding method. In the second experiment, batches of O. hupensis were kept at temperatures below 13°C with the temperature gradually reduced. Snail activity was assessed by a pin puncture method. We found a positive relationship between the development of S. japonicum within O. hupensis and temperature. In snails kept at 15.3°C, S. japonicum arrested their development, while the fastest development occurred at 30°C. The temperature at which half of the snails were in hibernation (ET50) was 6.4°C. Our results underscore the pivotal role temperature plays on the biological activity of O. hupensis and the development of S. japonicum within the intermediate host. These findings are likely to have implications for the transmission of schistosomiasis in a warmer future China.

Surveillance and response : tools and approaches for the elimination stage of neglected tropical diseases

The presentation of the World Health Organization (WHO)s roadmap for neglected tropical diseases (NTDs) in January 2012 raised optimism that many NTDs can indeed be eliminated. To make this happen, the endemic, often low-income countries with still heavy NTD burdens must substantially strengthen their health systems. In particular, they need not only to apply validated, highly sensitive diagnostic tools and sustainable effective control approaches for treatment and transmission control, but also to participate in the development and use of surveillance-response schemes to ensure that progress made also is consolidated and sustained. Surveillance followed-up by public health actions consisting of response packages tailored to interruption of transmission in different settings will help to effectively achieve the disease control/elimination goals by 2020, as anticipated by the WHO roadmap. Risk-mapping geared at detection of transmission hotspots by means of geospatial and other dynamic approaches facilitates decision-making at the technical as well as the political level. Surveillance should thus be conceived and developed as an intervention approach and at the same time function as an early warning system for the potential re-emergence of endemic infections as well as for new, rapidly spread epidemics and pandemics.