Hookworm Disease: Nutritional Implications

Variyam, Easwaran P.; Banwell, John G.

doi:10.1093/4.4.830

Cited by 12 publications

(7 citation statements)

References 47 publications

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“…Although malnutrition, which is often manifested as a growth delay, is a well-recognized consequence of hookworm infection, the molecular mechanisms underlying this clinical effect remain to be elucidated (58,59,64). There are a number of potential mechanisms by which hookworms may cause malnutrition.…”

Section: Discussionmentioning

confidence: 99%

“…Such a strategy potentially allows the worm to avoid substantial proteolytic damage while feeding on the submucosa. However, a secondary effect of AceKI might be impairment of host nutrient absorption through the inhibition of pancreatic enzymes, thus lending further credence to Darke's original yet somewhat controversial hypothesis (45,64). In light of the accumulating evidence that malnutrition is associated with increased susceptibility to infection by a variety of pathogens, the presence of a chronic malnourished state could potentially favor repeated infection with soil-transmitted helminths, including hookworms (3,17,38,40,50,59,63).…”

Section: Discussionmentioning

confidence: 99%

“…Hookworms, which are bloodfeeding intestinal nematodes, are a major cause of iron deficiency anemia and malnutrition (15,20,(59)(60)(61)64). While the anemia is presumably due to the cumulative effect of chronic intestinal blood loss, the molecular mechanisms underlying the pathogenesis of hookworm malnutrition remain unknown.…”

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confidence: 99%

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Molecular Characterization ofAncylostoma ceylanicumKunitz-Type Serine Protease Inhibitor: Evidence for a Role in Hookworm-Associated Growth Delay

Chu¹,

Bungiro²,

Ibanez³

et al. 2004

Infect Immun

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Hookworm infection is a major cause of iron deficiency anemia and malnutrition in developing countries. The Ancylostoma ceylanicum Kunitz-type inhibitor (AceKI) is a 7.9-kDa broad-spectrum inhibitor of trypsin, chymotrypsin, and pancreatic elastase that has previously been isolated from adult hookworms. Site-directed mutagenesis of the predicted P1 inhibitory reactive site amino acid confirmed the role of Met 26 in mediating inhibition of the three target serine proteases. By using reverse transcription-PCR, it was demonstrated that the level of AceKI gene expression increased following activation of third-stage larvae with serum and that the highest level of expression was reached in the adult stage of the parasite. Immunohistochemistry studies performed with polyclonal immunoglobulin G raised against recombinant AceKI showed that the inhibitor localized to the subcuticle of the adult hookworm, suggesting that it has a potential in vivo role in neutralizing intestinal proteases at the surface of the parasite. Immunization with recombinant AceKI was shown to confer partial protection against hookworm-associated growth delay without a measurable effect on anemia. Taken together, the data suggest that AceKI plays a role in the pathogenesis of hookworm-associated malnutrition and growth delay, perhaps through inhibition of nutrient absorption in infected hosts.Hookworm infection remains a major global health problem, and over one billion people are reportedly infected in developing countries (9, 14). Hookworms, which are bloodfeeding intestinal nematodes, are a major cause of iron deficiency anemia and malnutrition (15,20,(59)(60)(61)64). While the anemia is presumably due to the cumulative effect of chronic intestinal blood loss, the molecular mechanisms underlying the pathogenesis of hookworm malnutrition remain unknown. Although it has been suggested that hookworm malnutrition and growth delay occur secondary to chronic iron deficiency, particularly in children, evidence from prior clinical studies suggests that hookworm infection is also associated with various degrees of intestinal malabsorption (18,35,54,57,62). It has been hypothesized that this hookworm malabsorption syndrome might occur secondary to mucosal inflammation triggered by the adult worm attached to the intestinal epithelium or might be a result of secretion of parasite inhibitors of host digestive enzymes (18).As part of a series of ongoing studies aimed at characterizing adult hookworm secretory proteins, a cDNA corresponding to the gene encoding a putative Kunitz-type serine protease inhibitor was previously identified from adult Ancylostoma ceylanicum RNA by using a PCR-based approach (48). The A. ceylanicum Kunitz-type inhibitor (AceKI) cDNA was expressed in Escherichia coli, and the recombinant protein was found to inhibit the pancreatic enzymes chymotrypsin, pancreatic elastase, and trypsin in vitro, with equilibrium inhibitory dissociation constant (K i ) values ranging from picomolar levels to low nanomolar levels. The native AceKI prote...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Molecular Characterization ofAncylostoma ceylanicumKunitz-Type Serine Protease Inhibitor: Evidence for a Role in Hookworm-Associated Growth Delay

Chu¹,

Bungiro²,

Ibanez³

et al. 2004

Infect Immun

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“…Hookworms are hematophagous intestinal parasites and are a major cause of iron-deficiency anemia and malnutrition in children [2]–[7]. Adult worms cause intestinal bleeding, resulting in blood in the stool in amounts proportional to the parasite load in the intestine [7].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Biochemical, Hematological and Parasitological Parameters of Protein-Deficient Hamsters Infected with Ancylostoma ceylanicum

et al. 2014

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BackgroundHookworms infect millions of people worldwide and can cause severe clinical symptoms in their hosts. Prospective cohort studies in Brazil show high rates of hookworm reinfection in malnourished children compared to well-nourished children, despite previous treatment. Additionally, soil-transmitted helminth (STH) infections can worsen the nutritional status of affected populations. Therefore, this study aims to clarify the effects of host malnutrition during Ancylostoma ceylanicum infection and how this infection affects host physiological parameters using a hamster model.Methodology/Principal FindingsHamsters were divided into four experimental groups: normal diet or low-protein diet (also referred to as “malnourished”) and A. ceylanicum infection or no infection. More severe pathogenesis was observed in the infected malnourished group, as demonstrated by significant decreases in the hemoglobin concentration, erythrocyte number and packed-cell volume compared to the non-infected malnourished group. Greater numbers of adult parasites and eggs were observed in the malnourished group compared to the control group; however, the oviposition rate was lower in the malnourished group. In general, greater values of total lipids were observed in malnourished animals compared to control animals, including lipids excreted in the stool.ConclusionsIn this work, we have demonstrated that animals fed an isocaloric low-protein diet presented more severe pathogenesis when infected with A. ceylanicum. The increased lipid concentration in the liver and blood is related to the conversion of the excess carbohydrate into fatty acids that increase the concentration of triglycerides in general. Triglycerides were excreted in the feces, indicating that infection associated with malnutrition caused a greater loss of these molecules for this group of animals and confirming the hypothesis that both nutrition and infection are responsible for the malabsorption syndrome. Taken together, the results found in this work confirm the hypothesis that the nutritional condition of the host greatly influences the course of the infection.

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“…Anemia is a significant public health problem in India 10 , with more than half of its women between 15 and 49 years diagnosed with the condition 11 . Reasons for these are multifactorial and include consumption of a predominantly plant based diet 12 ; micronutrient deficiencies, such as vitamin B12 13 , 14 ; and hookworm and malarial infections 15 , 16 . Physical and cognitive productivity losses associated with anemia in India are estimated to be 6% of Gross Domestic Product (GDP ) 17 .…”

Section: Introductionmentioning

confidence: 99%

The RANI Project: A socio-normative intervention to reduce anemia in Odisha, India: A formative research protocol

et al. 2018

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Background: More than half of women of reproductive age in India are anemic. Anemia is associated with increased risk of preterm delivery, higher maternal mortality and contributes to fatigue, which affects women’s work productivity. The World Health Organization (WHO) recommends daily oral iron and folic acid (IFA) supplements during pregnancy and weekly supplements for women of reproductive age. Government programs and global donors have distributed and promoted IFA supplements in India for over four decades. However, initial intake and compliance remain inadequate. Objectives: This protocol describes the formative research phase of a larger study, called the Reduction in Anemia through Normative Innovations (RANI) Project, which will test, through a randomized controlled trial, the hypothesis that a social norms-based behavioral intervention in Odisha, India will improve uptake of IFA supplements and reduce anemia among reproductive age women as compared to usual care. The focus of this paper is on the formative research required to develop a sound intervention. We will examine socio-normative barriers to and facilitators of IFA supplement uptake. Methods and analysis: Based on the Theory of Normative Social Behavior, we will adopt a mixed-method, multilevel approach. We will collect data using focus groups, in-depth interviews, observations, Rapid Participatory Ethnographic Evaluation and Research (PEER) techniques, and perceptual mapping methods. Our sample includes reproductive age women (pregnant and not pregnant), their husbands, their mothers/in law and key stakeholders. Before collecting the data, and after analyzing the results, we will hold convenings in India to engage key stakeholders in collaborative design. Following the intervention design, we will test components of the intervention, gather user feedback and fine-tune as necessary. Impact: This study will contribute to the social norms and behavioral intervention research and inform policymakers about the value of adopting a socio-normative approach.

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Hookworm Disease: Nutritional Implications

Cited by 12 publications

References 47 publications

Molecular Characterization ofAncylostoma ceylanicumKunitz-Type Serine Protease Inhibitor: Evidence for a Role in Hookworm-Associated Growth Delay

Molecular Characterization ofAncylostoma ceylanicumKunitz-Type Serine Protease Inhibitor: Evidence for a Role in Hookworm-Associated Growth Delay

Evaluation of Biochemical, Hematological and Parasitological Parameters of Protein-Deficient Hamsters Infected with Ancylostoma ceylanicum

The RANI Project: A socio-normative intervention to reduce anemia in Odisha, India: A formative research protocol

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