The Hygiene Hypothesis and Its Inconvenient Truths about Helminth Infections

Current iterations of the hygiene hypothesis suggest an adaptive role for helminth parasites in shaping the proper maturation of the immune system. However, aspects of this hypothesis are based on assumptions that may not fully account for realities about human helminth infections. Such realities include evidence of causal associations between helminth infections and asthma or inflammatory bowel disease as well as the fact that helminth infections remain widespread in the United States, especially among populations at greatest risk for inflammatory and autoimmune diseases

Climate change and water in the UK: past changes and future prospects

Climate change is expected to modify rainfall, temperature and catchment hydrological responses across the world, and adapting to these water-related changes is a pressing challenge. This paper reviews the impact of anthropogenic climate change on water in the UK and looks at projections of future change. The natural variability of the UK climate makes change hard to detect; only historical increases in air temperature can be attributed to anthropogenic climate forcing, but over the last 50 years more winter rainfall has been falling in intense events. Future changes in rainfall and evapotranspiration could lead to changed flow regimes and impacts on water quality, aquatic ecosystems and water availability. Summer flows may decrease on average, but floods may become larger and more frequent. River and lake water quality may decline as a result of higher water temperatures, lower river flows and increased algal blooms in summer, and because of higher flows in the winter. In communicating this important work, researchers should pay particular attention to explaining confidence and uncertainty clearly. Much of the relevant research is either global or highly localized: decision-makers would benefit from more studies that address water and climate change at a spatial and temporal scale appropriate for the decisions they mak

Climate change and water in the UK : past changes and future prospects: a climate change report card for water: Working technical paper

Climate change is expected to modify rainfall, temperatures and catchment hydrological responses across the world, and adapting to these water-related changes is a pressing challenge. This paper reviews the impact of climate change on water in the UK and looks at projections of future change. The natural variability of the UK climate makes change hard to detect; only historical increases in air temperature can be attributed to climate change, but over the last fifty years more winter rainfall has been falling in intense events. Future changes in rainfall and evapotranspiration could lead to changed flow regimes and impacts on water quality, aquatic ecosystems and the water available for use by people. Summer flows may decrease on average, but floods may become larger and more frequent. Water quality may decline as a result of higher water temperatures, lower river flows and increased algal blooms. Water demand may increase in response to higher summer temperatures, placing additional pressure on water resources. These changes affect many parts of everyday life, emphasising the importance of long-term adaptation that takes these possible changes into account

IgG Induced by Vaccination With Ascaris suum Extracts Is Protective Against Infection

Human ascariasis has a global and cosmopolitan distribution, and has been characterized as the most prevalent neglected tropical disease worldwide. The development of a preventive vaccine is highly desirable to complement current measures required for this parasitic infection control and to reduce chronic childhood morbidities. In the present study, we describe the mechanism of protection elicited by a preventive vaccine against ascariasis. Vaccine efficacy was evaluated after immunization with three different Ascaris suum antigen extracts formulated with monophosphoryl lipid A (MPLA) as an adjuvant: crude extract of adult worm (ExAD); crude extract of adult worm cuticle (CUT); and crude extract of infective larvae (L3) (ExL3). Immunogenicity elicited by immunization was assessed by measuring antibody responses, cytokine production, and influx of tissue inflammatory cells. Vaccine efficacy was evaluated by measuring the reductions in the numbers of larvae in the lungs of immunized BALB/c mice that were challenged with A. suum eggs. Moreover, lung physiology and functionality were tested by spirometry to determine clinical efficacy. Finally, the role of host antibody mediated protection was determined by passive transfer of serum from immunized mice. Significant reductions in the total number of migrating larvae were observed in mice immunized with ExL3 61% (p < 0.001), CUT 59% (p < 0.001), and ExAD 51% (p < 0.01) antigens in comparison with non-immunized mice. For the Ascaris antigen-specific IgG antibody levels, a significant and progressive increase was observed with each round of immunization, in association with a marked increase of IgG1 and IgG3 subclasses. Moreover, a significant increase in concentration of IL-5 and IL-10 (pre-challenge) in the blood and IL-10 in the lung tissue (post-challenge) was induced by CUT immunization. Finally, ExL3 and CUT-immunized mice showed a marked improvement in lung pathology and tissue fibrosis as well as reduced pulmonary dysfunction induced by Ascaris challenge, when compared to non-immunized mice. Moreover, the passive transfer of specific IgG antibodies from ExL3, CUT, and ExAD elicited a protective response in naïve mice, with significant reductions in parasite burdens in lungs of 65, 64, and 64%, respectively. Taken together, these studies indicated that IgG antibodies contribute to protective immunity

Airway Mycosis and the Regulation of Type 2 Immunity

Filamentous fungi of the Aspergillus genus and others have long been linked to the induction of type 2 immunity that underlies IgE-mediated hypersensitivity responses. This unique immune response is characterized by the production of the allergy-associated T helper cell type 2 (Th2) and Th17 cytokines interleukin 4 (IL-4), IL-13, and IL-17 that drive IgE, eosinophilia, airway hyperresponsiveness and other manifestations of asthma. Proteinases secreted by filamentous fungi promote type 2 immunity, but the mechanism by which this occurs has long remained obscure. Through detailed biochemical analysis of household dust, microbiological dissection of human airway secretions, and extensive modeling in mice, our laboratory has assembled a detailed mechanistic description of how type 2 immunity evolves after exposure to fungi. In this review we summarize three key discoveries: (1) fungal proteinases drive the type 2 immune response; (2) the relationship between fungi, proteinases, and type 2 immunity is explained by airway mycosis, a form of non-invasive fungal infection of the airway lumen; and (3) the innate component of proteinase-driven type 2 immunity is mediated by cleavage of the clotting protein fibrinogen. Despite these advances, additional work is required to understand how Th2 and Th17 responses evolve and the role that non-filamentous fungi potentially play in allergic diseases

Maternal Hookworm Infection and Its Effects on Maternal Health: A Systematic Review and Meta-Analysis.

Hookworm is an intestinal parasite that infects nearly 230 million people, with another 5.1 billion at risk, especially in poverty-stricken tropical and subtropical regions. Pregnancy is an especially vulnerable time for hookworm infection because of its effect on both maternal and subsequently fetal health. A systematic review and meta-analysis was conducted. The meta-analysis was performed on the association between maternal hookworm and maternal anemia, as well as maternal hookworm coinfection with malaria. The prevalence of hookworm ranged from 1% to 78% in pregnant women, whereas malaria prevalence ranged from 11% to 81%. Pregnant women with hookworm infection were more likely to have anemia (combined odds ratio [cOR] 2.55 [2.20, 2.96]

Maternal Hookworm Infection and Its Effects on Maternal Health: A Systematic Review and Meta-Analysis.

Hookworm is an intestinal parasite that infects nearly 230 million people, with another 5.1 billion at risk, especially in poverty-stricken tropical and subtropical regions. Pregnancy is an especially vulnerable time for hookworm infection because of its effect on both maternal and subsequently fetal health. A systematic review and meta-analysis was conducted. The meta-analysis was performed on the association between maternal hookworm and maternal anemia, as well as maternal hookworm coinfection with malaria. The prevalence of hookworm ranged from 1% to 78% in pregnant women, whereas malaria prevalence ranged from 11% to 81%. Pregnant women with hookworm infection were more likely to have anemia (combined odds ratio [cOR] 2.55 [2.20, 2.96]

Host gastric corpus microenvironment facilitates Ascaris suum larval hatching and infection in a murine model.

Ascariasis (roundworm) is the most common parasitic helminth infection globally and can lead to significant morbidity in children including chronic lung disease. Children become infected with Ascaris spp. via oral ingestion of eggs. It has long been assumed that Ascaris egg hatching and larval translocation across the gastrointestinal mucosa to initiate infection occurs in the small intestine. Here, we show that A. suum larvae hatched in the host stomach in a murine model. Larvae utilize acidic mammalian chitinase (AMCase; acid chitinase; Chia) from chief cells and acid pumped by parietal cells to emerge from eggs on the surface of gastric epithelium. Furthermore, antagonizing AMCase and gastric acid in the stomach decreases parasitic burden in the liver and lungs and attenuates lung disease. Given Ascaris eggs are chitin-coated, the gastric corpus would logically be the most likely organ for egg hatching, though this is the first study directly evincing the essential role of the host gastric corpus microenvironment. These findings point towards potential novel mechanisms for therapeutic targets to prevent ascariasis and identify a new biomedical significance of AMCase in mammals