Hookworms, parasitic nematodes that infect nearly one billion people worldwide, are a major cause of anemia and malnutrition. We hypothesize that hookworms actively manipulate the host immune response through the production of specific molecules designed to facilitate infection by larval stages and adult worm survival within the intestine. A full-length cDNA encoding a secreted orthologue of the human cytokine, Macrophage Migration Inhibitory Factor (MIF) has been cloned from the hookworm Ancylostoma ceylanicum. Elucidation of the three-dimensional crystal structure of recombinant AceMIF (rAceMIF) revealed an overall structural homology with significant differences in the tautomerase sites of the human and hookworm proteins. The relative bioactivities of human and hookworm MIF proteins were compared using in vitro assays of tautomerase activity, macrophage migration, and binding to MIF receptor CD74. The activity of rAceMIF was not inhibited by the ligand ISO-1, which was previously determined to be an inhibitor of the catalytic site of human MIF. These data define unique immunological, structural, and functional characteristics of AceMIF, thereby establishing the potential for selectively inhibiting the hookworm cytokine as a means of reducing parasite survival and disease pathogenesis.Hookworms are bloodfeeding intestinal nematodes that currently infect more than 700 million people in developing countries (1). The hookworm life cycle begins when eggs excreted in the feces of an infected individual hatch in soil and undergo successive molts to the infectious L 3 stage. After contacting the skin of a permissive host, larvae migrate to the pulmonary vasculature, traverse alveolar capillaries, ascend the respiratory tree and are swallowed. Hookworms molt to the adult stage in the intestine, where they attach to the mucosal surface and feed on blood and tissue. Chronic blood and serum protein loss attributable to hookworm infection is associated with anemia, malnutrition, and growth/developmental delay, resulting in the loss of tens of millions of disability adjusted life-years annually (2).There is no clear evidence of sterile immunity in humans following naturally acquired infection, suggesting that hookworms may modulate the host immune response, perhaps during tissue migration, and/or while attached to the intestinal mucosa. The fact that adult hookworms can survive within a single human host for many years (3) further suggests that these worms are capable of evading or dampening host immune responses that might kill parasites and/or trigger expulsion. Of the immunomodulatory activities that have been identified from the hookworms Ancylostoma or Necator, none has yet been shown to play a definitive role in the pathogenesis of infection or intestinal disease (4 -7).Macrophage migration inhibitory factor (MIF) 4 is a pro-inflammatory cytokine first identified as a product of activated T cells, and subsequently demonstrated to have diverse biological functions (8). Mammalian MIF inhibits the random migration of ma...

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Background:Soil transmitted helminths (STH) remain a global public health concern in spite of occasional dosing campaigns.Aims:To determine baseline prevalence and intensity of STH infection in east Guatemalan school children, and describe the associated epidemiology of anemia, stunting, and wasting in this population. Setting and design: Ten schools in Izabal province (eastern Guatemala) were identified, and 1,001 school children were selected for this study. Half of the schools were used as clinical testing sites (blood and stool).Materials and Methods:Anthropometric measures were collected from all children. Over 300 children were tested for anemia and 229 for helminth infection. Ova and parasite specimens were examined via Direct, Kato Katz, and McMaster techniques. Hemoglobin was measured from venipuncture following the hemacue system. Statistical analysis: Correlation between infection intensities and growth indicators were examined. Chi Square or t tests were used for bivariate analysis. Multiple logistic regression was performed on significant variables from bivariate techniques.Results:Over two-thirds of school children were positive for infection by any STH. Prevalence of Hookworm was 30%; Ascaris, 52%; and Trichuris, 39%, most as low-intensity infection. Over half of the children were co-infected. In bivariate analysis, anemia was significantly associated with polyparasitism.Conclusions:For a Guatemalan child who experiences a unit decrease in hemoglobin, one expects to see a 24% increase in the odds of being infected with STH, controlling for age, sex, lake proximity, and growth characteristics. Infection with more than one STH, despite low intensity, led to a significant decrease in hemoglobin.