Integration of Management Strategies for Skin-Related Neglected Tropical Diseases.

The concept of skin neglected tropical diseases has been widely adopted into the policy and strategy of various organizations, governments, nongovernmental organizations, and health agencies. By pooling information and resources across different diseases, whose primary manifestations affect the skin, it is possible to deliver integrated surveillance and control programs and promote advocacy and reduction of disability and stigma. A further key part of the skin neglected tropical diseases program is the development and validation of training methods for front-line health workers. Networks that allow those involved in this work to share and compare expertise are being developed through various organizations.

Harnessing helminth-driven immunoregulation in the search for novel therapeutic modalities.

Parasitic helminths have coevolved with humans over millennia, intricately refining and developing an array of mechanisms to suppress or skew the host's immune system, thereby promoting their long-term survival. Some helminths, such as hookworms, cause little to no overt pathology when present in modest numbers and may even confer benefits to their human host. To exploit this evolutionary phenomenon, clinical trials of human helminth infection have been established and assessed for safety and efficacy for a range of immune dysfunction diseases and have yielded mixed outcomes. Studies of live helminth therapy in mice and larger animals have convincingly shown that helminths and their excretory/secretory products possess anti-inflammatory drug-like properties and represent an untapped pharmacopeia. These anti-inflammatory moieties include extracellular vesicles, proteins, glycans, post-translational modifications, and various metabolites. Although the concept of helminth-inspired therapies holds promise, it also presents a challenge to the drug development community, which is generally unfamiliar with foreign biologics that do not behave like antibodies. Identification and characterization of helminth molecules and vesicles and the molecular pathways they target in the host present a unique opportunity to develop tailored drugs inspired by nature that are efficacious, safe, and have minimal immunogenicity. Even so, much work remains to mine and assess this out-of-the-box therapeutic modality. Industry-based organizations need to consider long-haul investments aimed at unraveling and exploiting unique and differentiated mechanisms of action as opposed to toe-dipping entries with an eye on rapid and profitable turnarounds.

Fungal and Parasitic Infections of the Liver.

Hepatosplenic candidiasis and other fungal infections of the liver are uncommon in healthy individuals; however, high index of suspicion is essential in immunocompromised patients with prolonged fever. Parasitic infections are protozoan or helminthic; their distribution and epidemiology are variable among different world regions. Clonorchiasis, opisthorchiasis, fascioliasis, and ascariasis are helminthic infections that commonly involve the biliary systems. Signs and symptoms of cholangitis require prompt management to relieve biliary obstruction; addition of antihelminthic agents is essential. Parasitic infections are mostly transmitted to humans by fecally contaminated food and water. Proper hand and food sanitation measures are essential in preventing disease transmission.

Update on the major imported helminth infections in travelers and migrants.

Helminth infections cause considerable morbidity worldwide and may be frequently underdiagnosed especially in areas of lower endemicity. Patients may harbor latent infections that may become symptomatic years or decades after the initial exposure and timely diagnosis may be critical to prevent complications and improve outcomes. In this context, disease in special populations, such as immunosuppressed patients, may be of particular concern. Heightened awareness and recent diagnostic developments may contribute to the correct management of helminth infections in nonendemic regions. A review of the main helminth infections in travelers and migrants (strongyloidiasis, taeniasis-neurocysticercosis and schistosomiasis) is presented, focusing on epidemiology, developments in diagnosis, treatment and prevention.

A critical analysis of helminth immunotherapy in multiple sclerosis.

Helminthic worms are ancestral members of the intestinal ecosystem that have been largely eradicated from the general population in industrialized countries. Immunomodulatory mechanisms induced by some helminths mediate a "truce" between the mammalian host and the colonizing worm, thus allowing for long-term persistence in the absence of immune-mediated collateral tissue damage. This concept and the geographic discrepancy between global burdens of chronic inflammatory diseases and helminth infection have sparked interest in the potential of using helminthic worms as a therapeutic intervention to limit the progression of autoimmune diseases such as multiple sclerosis (MS). Here, we present and evaluate the evidence for this hypothesis in the pre-clinical animal model of MS, experimental autoimmune encephalitis, in helminth-infected MS patients and in clinical trials of administered helminth immunotherapy (HIT).

Clinical evaluation for morbidity associated with soil-transmitted helminth infection in school-age children on Pemba Island, Tanzania.

BACKGROUND: More than 1.5 billion people are infected with soil-transmitted helminths (Ascaris lumbricoides, hookworm, Strongyloides stercoralis, and Trichuris trichiura), causing an estimated global burden in excess of 3 million disability-adjusted life years. However, the relationship between soil-transmitted helminth infection, adverse health consequences, and beneficial effects of deworming are not well understood. METHODOLOGY: We pursued a detailed longitudinal clinical evaluation of school-age children to evaluate morbidity associated with soil-transmitted helminth infection and responses to treatment. This exploratory study was embedded into a randomized controlled trial. Overall, 434 children, aged 7-14 years, underwent a detailed medical history, physical examination, stool microscopy for soil-transmitted helminths, and hemoglobin (Hb) measurement at baseline. Medical history and stool examination were repeated at 3 and 18 weeks posttreatment. Additionally, Hb measurement was performed at the 18-week treatment follow-up. Logistic regression was employed to assess clinical factors associated with soil-transmitted helminth infection at baseline, and longitudinal data analysis to examine change in health outcomes following treatment over time. PRINCIPAL FINDINGS: All enrolled children were infected with T. trichiura, and randomized into four different treatment interventions. None of the medical history, physical examination, and laboratory (i.e., Hb) findings were associated with A. lumbricoides, hookworm, or S. stercoralis infection at baseline. A composite of physical exam findings for anemia, including pallor of the conjunctiva, nail beds, and palmar creases predicted lower Hb values (-3.8 g/dl, 95% confidence interval (CI): -6.9, -0.6 g/dl). When examining longitudinal trends, we did not find improvements to Hb or face Wong-Baker Likert scale among children with soil-transmitted helminth infection compared to those without infection, although there was a slight trend toward improving Hb values after treating hookworm infection. CONCLUSIONS/SIGNIFICANCE: Our study demonstrates the challenges of measuring morbidity in the context of soil-transmitted helminth infection and treatment, thus confirming the mainly subtle morbidity effects of infection.

On the Work of Alexander of Tralles

Helminthiasis is known to man since antiquity, but it still remains a significant public health problem. In ancient times many plants have been tried as possible therapeutics in search of an effective drug. This manuscript investigates ancient beliefs on parasitic worm infestation. Moreover, Alexander of Tralles' (525 - 605 CE) suggestions on the treatment of this condition are discussed as found in his lesser-known work "A letter on helminths", along with comments on the use of those herbal cures by modern medicine.

Effect of a 20-week physical activity intervention on selective attention and academic performance in children living in disadvantaged neighborhoods: A cluster randomized control trial.

OBJECTIVES: To evaluate the effect of a 20-week school-based physical activity intervention program on academic performance and selective attention among disadvantaged South African primary school children. DESIGN: Cluster randomized control trial. METHODS: The study cohort included 663 children from eight primary schools, aged 8-13 years. Data assessment took place between February 2015 and May 2016 following the implementation of a 20-week school-based physical activity program. The d2 test was employed to assess selective attention, while the averaged end-of-year school results (math, life skills, home language, and additional language) were used as an indicator of academic performance. Physical fitness was assessed using the 20-m shuttle run test (VO2 max) and grip strength tests. We controlled for cluster effects, baseline scores in selective attention or academic performance, and potential confounders, such as children's age, gender, socioeconomic status, self-reported physical activity (as determined by a pre-tested questionnaire), body mass index, hemoglobin (as a proxy for anemia, as measured by blood sampling), and soil-transmitted helminth infections (as assessed by the Kato-Katz technique). RESULTS: Our multivariate analysis suggested that the physical activity intervention had a positive effect on academic performance (p = 0.032), while no effect was found on selective attention (concentration performance; p = 0.469; error percentage; p = 0.237). After controlling for potential confounders, the physical activity condition contributed to the maintenance of academic performance, whereas a decrease was observed in learners in the control condition. Furthermore, physically active and fit children tend to have better concentration performance (CP) than their less fit peers (self-reported activity; p<0.016, grip strength; p<0.009, VO2 max p>0.021). CONCLUSION: A 20-week physical activity intervention contributes to the maintenance of academic performance among socioeconomically deprived school children in South Africa. School administrators should ensure that their school staff implements physical activity lessons, which are a compulsory component of the school by the curriculum.

Effect of an integrated intervention package of preventive chemotherapy, community-led total sanitation and health education on the prevalence of helminth and intestinal protozoa infections in Côte d'Ivoire.

BACKGROUND: Preventive chemotherapy with donated anthelminthic drugs is the cornerstone for the control of helminthiases. However, reinfection can occur rapidly in the absence of clean water and sanitation coupled with unhygienic behaviour. The purpose of this study was to assess the effect of an integrated package of interventions, consisting of preventive chemotherapy, community-led total sanitation (CLTS) and health education, on the prevalence of helminth and intestinal protozoa infections and on participants' knowledge, attitude, practice and beliefs (KAPB) towards these diseases including water, sanitation and hygiene (WASH). METHODS: A cross-sectional survey was carried out in nine communities of south-central Côte d'Ivoire to assess people's infection with helminths and intestinal protozoa and KAPB. Subsequently, interventions were targeted to five communities, while the remaining communities served as control. The intervention encouraged latrine construction and an evaluation was done 6-7 months later to determine open defecation status of the respective communities. Anthelminthic treatment was provided to all community members. A follow-up cross-sectional survey was conducted approximately one year later, using the same procedures. RESULTS: Overall, 810 people had complete baseline and follow-up data and were given anthelminthic treatment. The baseline prevalence of hookworm, Schistosoma haematobium, Trichuris trichiura, Schistosoma mansoni and Ascaris lumbricoides was 31.1%, 7.0%, 2.0%, 1.0% and 0.3%, respectively. Four of the five intervention communities were classified open-defecation free. For hookworm infection, we observed higher negative changes in terms of proportion of decrease (-0.10; 95% confidence interval (CI): - 0.16, -0.04) and higher egg reduction rate (64.9 vs 15.2%) when comparing intervention with control communities. For intestinal protozoa, prevalence reduction was higher in intervention compared to control communities (8.2 vs 2.6%) and WASH indicators and intervention outcomes associated with lower odds for infection at follow-up. The intervention significantly impacted on reported latrine use (before: 15.5%, after: 94.6%), open defecation in the community surroundings (before: 75.0%, after: 16.7%) and awareness for environmental contamination through open defecation (before: 20.4%, after: 52.2%). CONCLUSIONS: An integrated package of interventions consisting of preventive chemotherapy, health education and CLTS reduces the prevalence of helminth and intestinal protozoa infection. Additional studies in other social-ecological settings are warranted to confirm our findings.

Nanomedicine Approaches Against Parasitic Worm Infections.

Nanomedicine approaches have the potential to transform the battle against parasitic worm (helminth) infections, a major global health scourge from which billions are currently suffering. It is anticipated that the intersection of two currently disparate fields, nanomedicine and helminth biology, will constitute a new frontier in science and technology. This progress report surveys current innovations in these research fields and discusses research opportunities. In particular, the focus is on: (1) major challenges that helminth infections impose on mankind; (2) key aspects of helminth biology that inform future research directions; (3) efforts to construct nanodelivery platforms to target drugs and genes to helminths hidden in their hosts; (4) attempts in applying nanotechnology to enable vaccination against helminth infections; (5) outlooks in utilizing nanoparticles to enhance immunomodulatory activities of worm-derived factors to cure allergy and autoimmune diseases. In each section, achievements are summarized, limitations are explored, and future directions are assessed.

Soil-transmitted helminth infections.

More than a quarter of the world's population is at risk of infection with the soil-transmitted helminths Ascaris lumbricoides, hookworm (Ancylostoma duodenale and Necator americanus), Trichuris trichiura, and Strongyloides stercoralis. Infected children and adults present with a range of medical and surgical conditions, and clinicians should consider the possibility of infection in individuals living in, or returning from, endemic regions. Although safe and effective drugs are donated free to endemic countries, only half of at-risk children received treatment in 2016. This Seminar describes the epidemiology, lifecycles, pathophysiology, clinical diagnosis, management, and public health control of soil-transmitted helminths. Previous work has questioned the effect of population-level deworming; however, it remains beyond doubt that treatment reduces the severe consequences of soil-transmitted helminthiasis. We highlight the need for refined diagnostic tools and effective control options to scale up public health interventions and improve clinical detection and management of these infections.

Intestinal microbiota, fecal microbiota transplantation, and inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a complex set of diseases that lead to chronic inflammation in the gastrointestinal tract. Although the etiology of IBD is not fully understood, it is well-known that the intestinal microbiota is associated with the development and maintenance of IBD. Manipulation of the gut microbiota, therefore, may represent a target for IBD therapy. Fecal microbiota transplantation (FMT), where fecal microbiota from a healthy donor is transplanted into a patient's GI tract, is already a successful therapy for Clostridium difficile infection. FMT is currently being explored as a potential therapy for IBD as well. In this review, the associations between the gut microbiota and IBD and the emerging data on FMT for IBD will be discussed.

Anthelmintic Therapy Modifies the Systemic and Mycobacterial Antigen-Stimulated Cytokine Profile in Helminth-Latent Mycobacterium tuberculosis Coinfection.

Helminth infections are known to modulate cytokine responses in latent tuberculosis (LTB). However, very few studies have examined whether this modulation is reversible upon anthelmintic therapy. We measured the systemic and mycobacterial (TB) antigen-stimulated levels of type 1, type 2, type 17, and regulatory cytokines in individuals with LTB and with or without coexistent Strongyloides stercoralis infection before and after anthelmintic therapy. Our data reveal that individuals with LTB and coexistent S. stercoralis infection have significantly lower levels of systemic and TB antigen-stimulated type 1 (gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α], and interleukin-2 [IL-2]) and type 17 (IL-17A and/or IL-17F) cytokines and significantly higher levels of systemic but not TB antigen-stimulated type 2 (IL-4 and IL-5) and regulatory (transforming growth factor beta [TGF-ß]) cytokines. Anthelmintic therapy resulted in significantly increased systemic levels of type 1 and/or type 17 cytokines and in significantly decreased systemic levels of type 2 and regulatory (IL-10 and TGF-ß) cytokines. In addition, anthelmintic therapy resulted in significantly increased TB antigen-stimulated levels of type 1 cytokines only. Our data therefore confirm that the modulation of systemic and TB antigen-stimulated cytokine responses in S. stercoralis-LTB coinfection is reversible (for the most part) by anthelmintic treatment.

Helminths in organ transplantation.

With transplantation becoming an increasingly routine form of treatment for diverse populations, and with international travel becoming ever more accessible and affordable, the danger of transplantation-mediated helminth infections, exacerbated by coincident immunosuppression, must be considered. In this Review, we attempt to catalogue all clinically-relevant helminthiases that have been reported to coincide with transplantation, whether by transplantation-mediated transmission, reactivation of latent infections in an immunosuppressed context, or possible de-novo infection during the immunosuppressed peritransplant period. Helminthiasis has been reported in cases of kidney, liver, bowel, pancreas, heart, lung, and stem-cell transplant, and blood transfusion. For each helminthiasis, known risk factors, symptoms, and suggested options for screening and treatment are given. We conclude that helminths are a small but important and potentially severe source of disease after transplantation, and, with options for diagnosis and treatment, these pathogens warrant greater consideration during organ implantation. The achievement of immunological tolerance using helminth-derived products is also an exciting future prospect.

[Geohelminths]. / Geohelmintos.

Millions of people in in rural areas and deprived tropical and subtropical regions are infected by soil-transmitted helminths: Ascaris lumbricoides, Trichuris trichiura, hookworms (Ancylostoma duodenale and Necator americanus), and Strongyloides stercoralis. Large migratory flows have made their worldwide distribution easier. Besides being debilitating and producing a significant mortality, they cause high morbidity, leading to physical and intellectual impairment in millions of children who live in poverty. Along with the use of benzimidazoles (albendazole and mebendazole), large-scale international campaigns for treatment and prevention have decreased the number of affected individuals. However, re-infestations and benzimidazole-resistance are frequent, so there needs to be awareness about the importance and consequences of these neglected parasites.

Exploring the molecular mechanisms of parasite-host interactions with a view towards new therapeutics and vaccines.

Despite the massive disease burden worldwide caused by parasitic nematodes and other infectious pathogens, the molecular basis of many infectious diseases caused by these pathogens has been unduly neglected for a long time. Therefore, accelerated progress towards novel therapeutics, and ultimately control of such infectious diseases, is of crucial importance. Capitalising on the wealth of data becoming available from proteomic and genomic studies, new protein targets at the pathogen-host interface can be identified and subjected to protein-based explorations of the molecular basis of pathogen-host interactions. By combining the use of systems and structural biology methodologies, insights into the structural and molecular mechanisms of these interactions can assist in the development of therapeutics and/or vaccines. This brief review examines two different proteins from the body wall of blood flukes - annexins and the stress-induced phosphoprotein 1 - both of which are presently interesting targets for the development of therapeutics.

MicroRNAs in Parasitic Helminthiases: Current Status and Future Perspectives.

MicroRNAs (miRNAs) play a variety of roles in diverse biological processes at the post-transcriptional regulatory level. Although numerous miRNAs have been identified in parasitic helminths, we still know little about their biological functions. As molecular signatures that can be stably detectable in serum and plasma, worm-derived miRNAs have shown promise as markers for the early detection of particular helminth infections. In addition, host miRNAs are dysregulated during the development of pathology associated with helminthiases and show potential as therapeutic intervention targets. This review discusses the possible biological roles of helminth miRNAs, the prediction of their specific targets, their application in diagnosis and anti-pathology therapy interventions, and the potential functions of miRNAs in extracellular vesicle cargo, such as exosomes, in helminth-host interplay.

Effect of deworming on Th2 immune response during HIV-helminths co-infection.

BACKGROUND: Helminths infections have been suggested to worsen the outcome of HIV infection by polarizing the immune response towards Th2. The purpose of this study is to determine the activity of Th2 immune response by measuring total serum IgE level during symptomatic and asymptomatic HIV infection with and without helminths co-infection and to define the role of deworming and/or ART on kinetics of serum IgE. METHODS: This prospective comparative study was conducted among symptomatic HIV-1 infected adults, treatment naïve asymptomatic HIV positive individuals and HIV negative apparently healthy controls with and without helminths co-infection. Detection and quantification of helminths and determination of serum IgE level, CD4(+), and CD8(+) T cell count were done at baseline and 12 weeks after ART and/or deworming. RESULTS: HIV patients co-infected with helminths showed a high level of serum IgE compared to HIV patients without helminths co-infection (1,688 [IQR 721-2,473] versus 1,221 [IQR 618-2,289] IU/ml; P = 0.022). This difference was also markedly observed between symptomatic HIV infected patients after with and without helminths infection (1,690 [IQR 1,116-2,491] versus 1,252 [703-2,251] IU/ml; P = 0.047). A significant decline in serum IgE level was observed 12 weeks after deworming and ART of symptomatic HIV infected patients with (1,487 versus 992, P = 0.002) and without (1,233 versus 976 IU/ml, P = 0.093) helminths co-infection. However, there was no significant decrease in serum IgE level among asymptomatic HIV infected individuals (1,183 versus 1,097 IU/ml, P = 0.13) and apparently health controls (666 IU/ml versus 571, P = 0.09) without helminths co-infection 12 weeks after deworming. CONCLUSIONS: The significant decline of serum IgE level 12 weeks after deworming of both symptomatic and asymptomatic patients indicate a tendency to down-regulate the Th2 immune response and is additional supportive evidence that deworming positively impacts HIV/AIDS diseases progression. Thus, deworming should be integrated with ART program in helminths endemic areas of tropical countries.

The helminth parasite proteome at the host-parasite interface - Informing diagnosis and control.

Helminth parasites are a significant health burden for humans in the developing world and also cause substantial economic losses in livestock production across the world. The combined lack of vaccines for the major human and veterinary helminth parasites in addition to the development of drug resistance to anthelmintics in sheep and cattle mean that controlling helminth infection and pathology remains a challenge. However, recent high throughput technological advances mean that screening for potential drug and vaccine candidates is now easier than in previous decades. A better understanding of the host-parasite interactions occurring during infection and pathology and identifying pathways that can be therapeutically targeted for more effective and 'evolution proof' interventions is now required. This review highlights some of the advances that have been made in understanding the host-parasite interface in helminth infections using studies of the temporal expression of parasite proteins, i.e. the parasite proteome, and discuss areas for potential future research and translation.