Hookworm infection

Abstract

Hookworms are soil-transmitted nematode parasites that can reside for many years in the small intestine of their human hosts; Necator americanus is the predominant infecting species. Adult worms feed on the blood of a host and can cause iron deficiency anaemia, especially in high-risk populations (children and women of childbearing age). Almost 500 million people in developing tropical countries are infected, and simulation models estimate that hookworm infection is responsible for >4 million disability-adjusted life years lost annually. Humans mount an immune response to hookworms, but it is mostly unsuccessful at removing adult worms from the bowel. Accordingly, the host switches to an immune-tolerant state that enables hookworms to reside in the gut for many years. Although anthelmintic drugs are available and widely used, their efficacy varies and the drugs do not prevent reinfection. Thus, other control strategies aimed at improving water quality, sanitation and hygiene are needed. In addition, efforts are underway to develop a human hookworm vaccine through public-private partnerships. However, hookworms could also be a resource; as hookworms have the capability to regulate the host's inflammation, researchers are experimentally infecting patients to treat some inflammatory diseases as an approach to discover new anti-inflammatory molecules. This area of endeavour might well yield new biotherapeutics for autoimmune and allergic diseases.

Cooperative Metabolic Adaptations in the Host Can Favor Asymptomatic Infection and Select for Attenuated Virulence in an Enteric Pathogen

“…It is important to note that the strain of mouse used for most of these studies has been C57BI/6 mice, which has a nonfunctional allele of Nramp1, a divalent metal (iron and manganese) transporter that renders them more susceptible to infections (Canonne-Hergaux et al, 1999; Fritsche et al, 2012; Loomis et al, 2014; Powell and Frelinger, 2017; Soe-Lin et al, 2009). In humans, clinical data support our findings that dietary iron supplementation provides beneficial outcomes, especially in developing countries where low iron status may be prevalent (Loukas et al, 2016; Mwangi et al, 2017; Oppenheimer, 1989, 1998, 2001). However in malaria endemic areas, iron supplementation was associated with a negative outcome for patients (Clark et al, 2014).…”

Helminth Immunomodulation in Autoimmune Disease

“…Regulatory T cell (Treg) development is also stimulated during hookworm infection (11) that enhances the cloaking effect through the release of the regulatory cytokines IL-10 and transforming growth factor (TGF) β (12). In addition, hookworms induce activation of parasite-specific and total immunoglobulin E (IgE) and the mobilization of the innate immune systems including mast cells, eosinophils, and basophils (13). Indeed, a recent large-scale community deworming study showed that helminths actively decrease immune responsiveness and modulate immune checkpoint expression in infected individuals (14).…”

Immunity to gastrointestinal nematode infections

“…Much of our current understanding comes from wild rodent parasites that have been adopted for laboratory use, including Heligmosomoides polygyrus, 10 Nippostrongylus brasiliensis, 11 Trichinella spiralis, 12 and Trichuris muris, 13 that closely mimic human helminth infections. Although the life cycles of these nematodes vary greatly, a crucial part of their lifespans is spent in the intestinal tract where a distinct form of protective immunity is elicited, namely type 2 immunity.…”