Eliminating the Neglected Tropical Diseases: Translational Science and New Technologies

Today, the World Health Organization recognizes 17 major parasitic and related infections as the neglected tropical diseases (NTDs). Despite recent gains in the understanding of the nature and prevalence of NTDs, as well as successes in recent scaled-up preventive chemotherapy strategies and other health interventions, the NTDs continue to rank among the world’s greatest global health problems. For virtually all of the NTDs (including those slated for elimination under the auspices of a 2012 London Declaration for NTDs and a 2013 World Health Assembly resolution [WHA 66.12]), additional control mechanisms and tools are needed, including new NTD drugs, vaccines, diagnostics, and vector control agents and strategies. Elimination will not be possible without these new tools. Here we summarize some of the key challenges in translational science to develop and introduce these new technologies in order to ensure success in global NTD elimination efforts.     

Analysis of Parasitic Diseases Diagnosed by Tissue Biopsy Specimens at KyungHee Medical Center (1984-2005) in Seoul, Korea

We analyzed parasitic diseases diagnosed by tissue biopsy specimens at KyungHee Medical Center (KMC) from 1984 to 2005. The total number of parasite infection cases was 150 (0.07%) out of the total 211,859 biopsy specimens submitted for histopathological examinations. They consisted of 62 cysticercosis, 23 sparganosis, 16 paragonimiasis, 15 amebiasis, 11 anisakiasis, 11 clonorchiasis, 3 ascariasis, 2 scabies, 2 enterobiasis, 2 trichuriasis, 1 leishmaniasis, 1 taeniasis, and 1 thelaziasis. Out of 62 cysticercosis cases, 55 were detected in subcutaneous tissues or the central nerve system. Eighteen out of 23 sparganosis cases were involved in muscular and subcutaneous tissues. In most anisakiasis cases, the involved organ was the stomach. The lung and the pleura were the most common site of paragonimiasis. The incidence of parasitic diseases during the first 5 years (1984-1988) was the highest of all observed periods. After 1989, similar incidences were shown throughout the period. Whereas cysticercosis was diagnosed in 34 cases during 1984-1988, no case has been diagnosed since 2000. In the case of sparganosis, the chronological incidence was almost uniform throughout the period 1984-2005. Paragonimiasis showed a similar tendency to cysticercosis. In gender and age distribution of parasitic diseases, men showed higher incidence rates than females, and the age groups of the 40s or older indicated higher infection frequencies than other age groups. Therefore, these results are a significant report to appear the tendency of human parasitic disease diagnosed by tissue biopsy in association with parasitosis at KMC in Seoul.     

Parasitic Infections Based on 320 Clinical Samples Submitted to Hanyang University,Korea (2004-2011)

We analyzed 320 clinical samples of parasitic infections submitted to the Department of Environmental Biology and Medical Parasitology, Hanyang University from January 2004 to June 2011. They consisted of 211 nematode infections, 64 trematode or cestode infections, 32 protozoan infections, and 13 infections with arthropods. The nematode infections included 67 cases of trichuriasis, 62 of anisakiasis (Anisakis sp. and Pseudoterranova decipiens), 40 of enterobiasis, and 24 of ascariasis, as well as other infections including strongyloidiasis, thelaziasis, loiasis, and hookworm infecions. Among the cestode or trematode infections, we observed 27 cases of diphyllobothriasis, 14 of sparganosis, 9 of clonorchiasis, and 5 of paragonimiasis together with a few cases of taeniasis saginata, cysticercosis cellulosae, hymenolepiasis, and echinostomiasis. The protozoan infections included 14 cases of malaria, 4 of cryptosporidiosis, and 3 of trichomoniasis, in addition to infections with Entamoeba histolytica, Entamoeba dispar, Entamoeba coli, Endolimax nana, Giardia lamblia, and Toxoplasma gondii. Among the arthropods, we detected 6 cases of Ixodes sp., 5 of Phthirus pubis, 1 of Sarcoptes scabiei, and 1 of fly larva. The results revealed that trichuriasis, anisakiasis, enterobiasis, and diphyllobothriasis were the most frequently found parasitosis among the clinical samples.     

Challenges facing European agriculture and possible biotechnological solutions

Agriculture faces many challenges to maximize yields while it is required to operate in an environmentally sustainable manner. In the present study, we analyze the major agricultural challenges identified by European farmers (primarily related to biotic stresses) in 13 countries, namely Belgium, Bulgaria, the Czech Republic, France, Germany, Hungary, Italy, Portugal, Romania, Spain, Sweden, UK and Turkey, for nine major crops (barley, beet, grapevine, maize, oilseed rape, olive, potato, sunflower and wheat). Most biotic stresses (BSs) are related to fungi or insects, but viral diseases, bacterial diseases and even parasitic plants have an important impact on yield and harvest quality. We examine how these challenges have been addressed by public and private research sectors, using either conventional breeding, marker-assisted selection, transgenesis, cisgenesis, RNAi technology or mutagenesis. Both national surveys and scientific literature analysis followed by text mining were employed to evaluate genetic engineering (GE) and non-GE approaches. This is the first report of text mining of the scientific literature on plant breeding and agricultural biotechnology research. For the nine major crops in Europe, 128 BS challenges were identified with 40% of these addressed neither in the scientific literature nor in recent European public research programs. We found evidence that the private sector was addressing only a few of these “neglected” challenges. Consequently, there are considerable gaps between farmer’s needs and current breeding and biotechnology research. We also provide evidence that the current political situation in certain European countries is an impediment to GE research in order to address these agricultural challenges in the future. This study should also contribute to the decision-making process on future pertinent international consortia to fill the identified research gaps.     

Scoping review of Neglected Tropical Disease Interventions and Health Promotion: A framework for successful NTD interventions as evidenced by the literature

BackgroundNeglected Tropical Diseases (NTDs) affect more than one billion people globally. A Public Library of Science (PLOS) journal dedicated to NTDs lists almost forty NTDs, while the WHO prioritises twenty NTDs. A person can be affected by more than one disease at the same time from a range of infectious and non-infectious agents. Many of these diseases are preventable, and could be eliminated with various public health, health promotion and medical interventions. This scoping review aims to determine the extent of the body of literature on NTD interventions and health promotion activities, and to provide an overview of their focus while providing recommendations for best practice going forward. This scoping review includes both the identification of relevant articles through the snowball method and an electronic database using key search terms. A two-phased screening process was used to assess the relevance of studies identified in the search–an initial screening review followed by data characterization using the Critical Appraisal Skills Program (CASP). Studies were eligible for inclusion if they broadly described the characteristics, methods, and approaches of (1) NTD interventions and/or (2) community health promotion.Principal findings90 articles met the CASP criteria partially or fully and then underwent a qualitative synthesis to be included in the review. 75 articles specifically focus on NTD interventions and approaches to their control, treatment, and elimination, while 15 focus specifically on health promotion and provide a grounding in health promotion theories and perspectives. 29 of the articles provided a global perspective to control, treatment, or elimination of NTDs through policy briefs or literature reviews. 19 of the articles focused on providing strategies for NTDs more generally while 12 addressed multiple NTDs or their interaction with other infectious diseases. Of the 20 NTDs categorized by the WHO and the expanded NTD list identified by PLOS NTDs, several NTDs did not appear in the database search on NTD interventions and health promotion, including yaws, fascioliasis, and chromoblastomycosis.ConclusionsBased on the literature we have identified the four core components of best practices including programmatic interventions, multi sectoral and multi-level interventions, adopting a social and ecological model and clearly defining ‘community.’ NTD interventions tend to centre on mass drug administration (MDA), particularly because NTDs were branded as such based on their being amenable to MDA. However, there remains a need for intervention approaches that also include multiple strategies that inform a larger multi-disease and multi-sectoral programme. Many NTD strategies include a focus on WASH and should also incorporate the social and ecological determinants of NTDs, suggesting a preventative and systems approach to health, not just a treatment-based approach. Developing strong communities and incorporating social rehabilitation at the sublocation level (e.g. hospital) could benefit several NTDs and infectious diseases through a multi-disease, multi-sectoral, and multi-lateral approach. Finally, it is important the ‘community’ is clearly defined in each intervention, and that community members are included in intervention activities and viewed as assets to interventions.     

Cystic Echinococcosis Epidemiology in Spain Based on Hospitalization Records, 1997-2012

BackgroundCystic echinococcosis (CE) is a parasitic disease caused by the tapeworm Echinococcus granulosus. Although present throughout Europe, deficiencies in the official reporting of CE result in under-reporting and misreporting of this disease, which in turn is reflected in the wrong opinion that CE is not an important health problem. By using an alternative data source, this study aimed at describing the clinical and temporal-spatial characteristics of CE hospitalizations in Spain between 1997 and 2012.ConclusionsHospitalizations distribution was uneven by year and autonomous region. Although CE hospitalization rates have decreased considerably due to the success of control programs, it remains a public health problem due to its severity and economic impact. Therefore, it would be desirable to improve its oversight and surveillance, since officially reported data are underestimating the real burden of CE in Spain.     

Economic losses caused by foodborne parasitic diseases

Fragmentary data indicate that zoonotic parasites cause human illnesses with medical costs and productivity and disability losses totalling billions of dollars annually. Food is an important vehicle for some of these parasitic diseases. The cost to public health is not reflected in the priorities given to these parasitic diseases in either research or public health planning. In this article, Tanya Roberts, Darwin Murrell and Suzanne Marks discuss the cost of toxoplasmosis, taeniasis, cysticercosis, trichinellosis and other foodborne parasitic diseases.     

Development of impact factors on damage to health by infectious diseases caused by domestic water scarcity

Background, aim, and scope  

Water scarcity is a critical environmental issue. In particular, domestic water is a necessary resource for our fundamental activities, and poor water quality may lead to damage to health caused by infectious diseases. However, there is no methodology to assess the damage of domestic water scarcity (low accessibility to safe water) caused by water consumption. The main objectives of this study are to model the health damage assessment of infectious diseases (ascariasis, trichuriasis, hookworm disease, and diarrhea) caused by domestic water scarcity and calculate damage factors on a country scale.     

RNAi pathways in parasitic protists and worms

Tropical diseases caused by parasitic worms and protists are of major public health concern affecting millions of people worldwide. New therapeutic and diagnostic tools would be of great help in dealing with the public health and economic impact of these diseases. RNA interference (RNAi) pathways utilize small non-coding RNAs to regulate gene expression in a sequence-specific manner. In recent years, a wealth of data about the mechanisms and biological functions of RNAi pathways in distinct groups of eukaryotes has been described. Often, RNAi pathways have unique features that are restricted to groups of eukaryotes. The focus of this review will be on RNAi pathways in specific groups of parasitic eukaryotes that include Trypanosoma cruzi, Plasmodium and Schistosoma mansoni. These parasites are the causative agents of Chagas disease, Malaria, and Schistosomiasis, respectively, all of which are tropical diseases that would greatly benefit from the development of new diagnostic and therapeutic tools. In this context, we will describe specific features of RNAi pathways in each of these parasitic eukaryotic groups and discuss how they could be exploited for the treatment of tropical diseases.     

Reviewing Dengue: Still a Neglected Tropical Disease?

Dengue is currently listed as a “neglected tropical disease” (NTD). But is dengue still an NTD or not? Classifying dengue as an NTD may carry advantages, but is it justified? This review considers the criteria for the definition of an NTD, the current diverse lists of NTDs by different stakeholders, and the commonalities and differences of dengue with other NTDs. We also review the current research gaps and research activities and the adequacy of funding for dengue research and development (R&D) (2003–2013). NTD definitions have been developed to a higher precision since the early 2000s, with the following main features: NTDs are characterised as a) poverty related, b) endemic to the tropics and subtropics, c) lacking public health attention, d) having poor research funding and shortcomings in R&D, e) usually associated with high morbidity but low mortality, and f) often having no specific treatment available. Dengue meets most of these criteria, but not all. Although dengue predominantly affects resource-limited countries, it does not necessarily only target the poor and marginalised in those countries. Dengue increasingly attracts public health attention, and in some affected countries it is now a high profile disease. Research funding for dengue has increased exponentially in the past two decades, in particular in the area of dengue vaccine development. However, despite advances in dengue research, dengue epidemics are increasing in frequency and magnitude, and dengue is expanding to new areas. Specific treatment and a highly effective vaccine remain elusive. Major research gaps exist in the area of integrated surveillance and vector control. Hence, although dengue differs from many of the NTDs, it still meets important criteria commonly used for NTDs. The current need for increased R&D spending, shared by dengue and other NTDs, is perhaps the key reason why dengue should continue to be considered an NTD.     

Parasites that cause problems in Malaysia: soil-transmitted helminths and malaria parasites

Malaysia is a developing country with a range of parasitic infections. Indeed, soil-transmitted helminths and malaria parasites continue to have a significant impact on public health in Malaysia. In this article, the prevalence and distribution of these parasites, the problems associated with parasitic infections, the control measures taken to deal with these parasites and implications for the future will be discussed.     

Molecular cross-talk in host-parasite relationships: the intriguing immunomodulatory role of Echinococcus antigen B in cystic echinococcosis

Cystic echinococcosis (CE), a zoonosis caused by the development of Echinococcus granulosus tapeworm larvae in the internal organs of ungulates and humans, continues to pose a major public health burden in underdeveloped and industrialised areas worldwide. Research designed to improve parasitic disease control and find out more about parasite biology has already identified a number of E. granulosus antigenic molecules. The major E. granulosus immunomodulant antigen isolated from hydatid fluid is antigen B, a 120kDa polymeric lipoprotein consisting of various 8kDa subunits. By inhibiting elastase activity and neutrophil chemotaxis and eliciting a non-protective Th2 cell response, antigen B helps the parasite evade the human response. In this review, we briefly discuss current information on the molecular characteristics and immunomodulatory properties of E. granulosus antigen B. Besides focusing on findings that provide intriguing insights into the complex interplay between host and parasite, we suggest how this information could extend the current therapeutic options in inflammatory diseases.     

Malaria in the whole world and in Romania

Malaria is the world's most important tropical parasitic disease. Malaria is a public health problem today in more than 90 countries. Worldwide prevalence of the disease is estimated to be in the order of 300-500 million clinical cases each year. Malaria is endemic in a total of 101 countries and territories. In Romania, malaria does not represent an important public health problem. In 1999, there were reported a total number of 32 malaria cases in Romanian people. 78% from these recognized as etiological agent Pl. falciparum. The malaria cases imported from Turkey (5) have had as etiological agent Pl. vivax. The most affected age group is between 21-50 years and a distribution by profession shows that sailor personnel accounts for 65.6% of all cases. Africa remains the most important endemic region from where the malaria cases in Romanian people are imported. An adequate chemoprophylaxis is not, yet, easy to obtain for Romanian people who are travelling abroad in endemic countries because of the lack of specific drugs (especially for resistant forms of Pl. falciparum). Even if the Romanian Ministry of Health had elaborated orders regarding malaria and Cloroquine is the usual drug administered, as chemoprophylaxis, to Romanian people who travel abroad, in each year in our country appears around 30-60 imported malaria cases. That is the cause why Romanian Ministry of Health wants to solve this problem which is the major cause of the malaria cases in Romanian people.     

Effect of a One-Off Educational Session about Enterobiasis on Knowledge,Preventative Practices,and Infection Rates among Schoolchildren in South Korea

Although health education has proven to be cost-effective in slowing the spread of enterobiasis, assessments of the effectiveness of health education to reduce infectious diseases specifically in children are rare. To evaluate the effect of health education on knowledge, preventative practices, and the prevalence of enterobiasis, 319 children from 16 classes were divided into experimental and control groups. Data were collected from May 2012 to March 2013. A 40-minute in-class talk was given once in the experimental group. There were significant differences over the time in the mean scores for children''s knowledge of Enterobius vermicularis infection in the intervention group compared to the control group (p<0.001). After the educational session, the score for knowledge about E. vermicularis infection increased from 60.2±2.32 to 92.7±1.19 in the experimental group; this gain was partially lost 3 months later, decreasing to 83.6±1.77 (p<0.001). Children''s enterobiasis infection prevention practice scores also increased, from 3.23±0.27 to 3.73±0.25, 1 week after the educational session, a gain that was partially lost at 3 months, decreasing to 3.46±0.36 (p<0.001). The overall E. vermicularis egg detection rate was 4.4%; the rates for each school ranged from 0% to 12.9% at screening. The infection rate at 3 months after the treatment sharply decreased from 12.3% to 0.8% in the experimental group, compared to a decrease from 8.5% to 3.7% in the control group during the same period. We recommend that health education on enterobiasis be provided to children to increase their knowledge about enterobiasis and improve prevention practices.     

Trends in incidence of AIDS associated with transfusion of blood and blood products in Europe and the United States, 1985-93.

OBJECTIVE--To quantify patterns and trends in incidence of AIDS associated with transfusion of blood and its products in 14 European countries and the United States. DESIGN--Data were derived from the World Health Organisation''s European non-aggregate AIDS dataset and, for the United States, from the Centers for Disease Control AIDS public information dataset. Rates were standardised by using the world standard populations and adjusted for reporting delays in each country. SUBJECTS--Cases of AIDS in patients with haemophilia and recipients of transfusions. RESULTS--Overall, between 1985 and 1993 almost 6000 cases of AIDS associated with transfusions were registered in the 14 European countries considered and over 8000 in the United States between 1985 and 1992. Most European countries had annual age adjusted rates lower than 0.5 per million children aged 12 or less and between 1 and 2 per million adults. The United States had rates around 1 per million children and 5 per million adults in the most recent period. For children, the highest rates were generally reached in 1985-7, whereas in adults the highest rates were in the late 1980s. France had the highest overall incidence of AIDS related to transfusion in Europe (3.3 per million). Romania had a major epidemic in children (over 30 cases per million children in 1988-90). Incidence rates of AIDS associated with transfusion were still increasing in some southern European countries in the early 1990s. CONCLUSIONS--Apart from in France and Romania it is clear that rates of bloodborne AIDS in European countries are lower than those registered in the United States.     

The Contributions of Onchocerciasis Control and Elimination Programs toward the Achievement of the Millennium Development Goals

In 2000, 189 member states of the United Nations (UN) developed a plan for peace and development, which resulted in eight actionable goals known as the Millennium Development Goals (MDGs). Since their inception, the MDGs have been considered the international standard for measuring development progress and have provided a blueprint for global health policy and programming. However, emphasis upon the achievement of priority benchmarks around the “big three” diseases—namely HIV, tuberculosis (TB), and malaria—has influenced global health entities to disproportionately allocate resources. Meanwhile, several tropical diseases that almost exclusively impact the poorest of the poor continue to be neglected, despite the existence of cost-effective and feasible methods of control or elimination. One such Neglected Tropical Disease (NTD), onchocerciasis, more commonly known as river blindness, is a debilitating and stigmatizing disease primarily affecting individuals living in remote and impoverished areas. Onchocerciasis control is considered to be one of the most successful and cost-effective public health campaigns ever launched. In addition to improving the health and well-being of millions of individuals, these programs also lead to improvements in education, agricultural production, and economic development in affected communities. Perhaps most pertinent to the global health community, though, is the demonstrated effectiveness of facilitating community engagement by allowing communities considerable ownership with regard to drug delivery. This paper reviews the contributions that such concentrated efforts to control and eliminate onchocerciasis make to achieving select MDGs. The authors hope to draw the attention of public policymakers and global health funders to the importance of the struggle against onchocerciasis as a model for community-directed interventions to advance health and development, and to advocate for NTDs inclusion in the post 2015 agenda.     

Visceral larva migrans: examinations by means of enzyme-linked immunosorbent assay of human sera for antibodies to excretory-secretory antigens of the second-stage larvae of Toxocara canis

An enzyme-linked immunosorbent assay is described for the detection of serum antibodies to visceral larva migrans (Toxocariasis). Excretory-secretory antigens of the second-stage larvae of Toxocara canis were used as antigen to coat the polystyrene plates. With sera from patients high antibody titers were observed in both ocular and visceral disorders. Cross-reactions due to other parasitic infections could be excluded, including other migrating larval infections such as ascariasis, trichinellosis, strongyloidiasis, filariasis, and anisakiasis. In a small seroepidemiologic survey of healthy primary schoolchildren, a remarkably high percentage (7.1) reacted positively to this method. These children showed eosinophilia as compared to the seronegative group. The data were compared with those observed in other countries and the results prompt reconsideration of the significance of T. canis for public health.     

Study of the variability and evolution of Orobanche cumana populations infesting sunflower in different European countries

 The parasitic plant Orobanche cumana Wallr. has become a limiting factor for sunflower crops in infested countries. Over the past few years the progression of this parasitic plant, its introduction into new countries, and the development of new and more virulent races have all been observed. Consequently, the survey and understanding of broomrape population evolution is now crucial for the establishment of efficient breeding programmes. With this in prospect, the genetic variability of O. cumana populations from infested European countries, Bulgaria, Romania, Turkey and Spain, was studied using RAPD markers. Eight populations with a total of 180 plants were analysed. Twenty three primers were used to obtain 133 reproducible bands which led to a binary matrix. This matrix was subjected to various complementary analyses including pairwise distances computed with the Nei and Li coefficient, AMOVA, Nei’s genetic diversity statistics, and an estimation of gene flow among populations with the infinite-island formula. The results gave consistent conclusions whatever the method used for data treatment. We show that this parasitic plant is probably self-pollinated, that there is little intra-population variability, and very little gene exchange appears to occur between different geographic regions. Populations were well structured and organized into two distinct groups (one group corresponding to the East European countries, Bulgaria, Romania and Turkey, and the other group corresponding to Spanish populations) and could have a monophyletic origin. These results are discussed in relation to the applied uses of RAPD markers in the determination of true O. cumana races instead of populations. Received: 20 December 1997 / Accepted: 4 February 1998     

Notes on cystic echinococcosis in the Mediterranean

Cystic Echinococcosis (CE), caused by Echinococcus granulosus, is present from the beginning of history and in the Mediterranean it is linked to the dog-sheep cycle. The Mediterranean area possesses many features favouring CE. Positive and negative influences derived from the action of the European Community and from recent developments. The control measures of CE have political, economic, public health and environmental implications. Dog population and dog-transmitted zoonoses control, improvement of slaughtering procedures and the destruction of infected viscera, health education, interprofessional cooperation are able individually to constitute a contraposition to CE and combined to compose a control program. Epidemiological surveillance and control of CE in the Mediterranean are coordinated by the WHO Mediterranean Zoonoses Control Centre of Athens.     

Safely resuming neglected tropical disease control activities during COVID-19: Perspectives from Nigeria and Guinea

Since its early spread in early 2020, the disease caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Coronavirus Disease 2019 (COVID-19) has caused mass disruptions to health services. These have included interruptions to programs that aimed to prevent, control, and eliminate neglected tropical diseases (NTDs). In March 2020, the World Health Organization (WHO) released interim guidelines recommending the temporary cessation of mass drug administration (MDA), community-based surveys, and case detection, while encouraging continuation of morbidity management and vector control where possible. Over the course of the following months, national programs and implementing partners contributed to COVID-19 response efforts, while also beginning to plan for resumption of NTD control activities. To understand the challenges, opportunities, and recommendations for maximizing continuity of disease control during public health emergencies, we sought perspectives from Nigeria and Guinea on the process of restarting NTD control efforts during the COVID-19 pandemic. Through semistructured interviews with individuals involved with NTD control at the local and national levels, we identified key themes and common perspectives between the 2 countries, as well as observations that were specific to each. Overall, interviewees stressed the challenges posed by COVID-19 interruptions, particularly with respect to delays to activities and related knock-on impacts, such as drug expiry and prolonged elimination timelines, as well as concerns related to funding. However, respondents in both countries also highlighted the benefits of a formal risk assessment approach, particularly in terms of encouraging information sharing and increasing coordination and advocacy. Recommendations included ensuring greater availability of historical data to allow better monitoring of how future emergencies affect NTD control progress; continuing to use risk assessment approaches in the future; and identifying mechanisms for sharing lessons learned and innovations between countries as a means of advancing postpandemic health systems and disease control capacity strengthening.