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.

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Figure 1: Distribution of hookworm infection and estimated prevalence of anaemia due to hookworm infection.
Figure 2: Life cycle of Necator americanus.
Figure 3: Developmental stages of the intra-host phase of the hookworm life cycle.
Figure 4: Hookworms induce a T helper 2 immune response in the early phase of intestinal infection.
Figure 5: Immune pathways for parasite tolerance.
Figure 6: Controlled human hookworm infection restores gluten tolerance.

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Acknowledgements

The authors thank Dr K. Trenholme for her contribution to the design of Figure 2 and Dr P. Giacomin for his help with preparing the histology images for Figure 6.

Author information

Introduction (A.L.); Epidemiology (J.M.B. and P.J.H.); Mechanisms/pathophysiology (A.L., M.Y. and J.C.); Diagnosis, screening and prevention (J.M.B., R.C.-O., P.J.H., J.C., D.D. and J.S.M.); Management (D.D., P.J.H. and J.S.M.); Quality of life (P.J.H.); Outlook (A.L.); Overview of Primer (A.L.).

Correspondence to Alex Loukas.

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Competing interests

A.L., P.J.H. and J.M.B. are co-inventors on patents for the use of hookworm proteins as subunit vaccines against human hookworm disease. A.L. is an inventor on patents for the use of hookworm proteins as therapeutics for the treatment of inflammatory diseases and has received funding for such projects from Janssen R&D, USA. All other authors declare no competing interests.

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Loukas, A., Hotez, P., Diemert, D. et al. Hookworm infection. Nat Rev Dis Primers 2, 16088 (2016). https://doi.org/10.1038/nrdp.2016.88

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