Dietary Iron Content Mediates Hookworm Pathogenesis In Vivo

Abstract

Hookworm infection is associated with growth delay and iron deficiency anemia in developing countries. A series of experiments were designed in order to test the hypothesis that host dietary iron restriction mediates susceptibility to hookworm infection using the hamster model of Ancylostoma ceylanicum. Animals were maintained on diets containing either 10 ppm iron (iron restricted) or 200 ppm iron (standard/high iron), followed by infection with A. ceylanicum third-stage larvae. Infected animals fed the standard diet exhibited statistically significant growth delay and reduced blood hemoglobin levels compared to uninfected controls on day 20 postinfection. In contrast, no statistically significant differences in weight or hemoglobin concentration were observed between infected and uninfected animals fed the iron-restricted diet. Moreover, iron-restricted animals were observed to have reduced intestinal worm burdens on day 10 and day 20 postinfection compared to those of animals maintained on the standard/high-iron diet. In a subsequent study, animals equilibrated on diets containing a range of iron levels (10 ppm, 40 ppm, 100 ppm, or 200 ppm) were infected with A. ceylanicum and followed for evidence of hookworm disease. Infected animals from the intermediate-dietary iron (40-and 100-ppm) groups exhibited greater weight loss and anemia than those in the low (10-ppm)-or high (200-ppm)-iron diet groups. Mortality was also significantly higher in the intermediate-dietary-iron groups. These data suggest that severe dietary iron restriction impairs hookworm development in vivo but that moderate iron restriction enhances host susceptibility to severe disease.

Epidemiology of Hookworm Infection in Kintampo North Municipality, Ghana: Patterns of Malaria Coinfection, Anemia, and Albendazole Treatment Failure

“…There is a large body of evidence from animal studies of intestinal nematode infections, including hookworm, to suggest that micronutrient intake as well as underlying nutritional status can play a significant role in susceptibility and the host's capacity to control intensity of infection. [66][67][68][69][70][71] Several recent studies have followed infected children after deworming to determine the influence of nutritional factors on reinfection. Hagel and others 72 in Venezuela found that children aged 6-11 years with lower height for age z score (HAZ) and weight for age z score (WAZ) scores had significantly higher risks of reinfection with Ascaris 8 months after completing treatment .…”

Early Helminth Infections Are Inversely Related to Anemia, Malnutrition, and Malaria and Are Not Associated with Inflammation in 6- to 23-Month-Old Zanzibari Children

“…36,37 For instance, helminths have been found to have specific physico-chemical requirements of their host gut environment, and nutritionally mediated changes have a direct influence on the parasite population. 36 Similarly, iron supplementation in iron replete individuals has been associated with an increased risk of malaria.…”

Role for Nitric Oxide in Hookworm-Associated Immune Suppression

“…The A. ceylanicum life cycle was maintained by passage through Syrian hamsters as described previously (9,30). Animals were housed in the Yale School of Medicine, and all experiments were carried out with prior approval of the Yale Animal Care and Use Committee.…”

“…), six animals (and an equal number of uninfected controls) were sacrificed, and blood, spleens, and mesenteric lymph nodes (MLN) were collected for analyses. Blood hemoglobin levels were measured using a total hemoglobin assay (Sigma Diagnostics, St. Louis, MO) as previously described (30), and intestinal worm burdens were evaluated at each time point.…”