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Hookworm (Necator americanus) infection and storage iron depletion.

The relationship between iron status and the intensity of infection with hookworm was investigated in a rural population on Karkar Island, Mandang Province, Papua New Guinea. There was a significant negative correlation between plasma ferritin level and hookworm burden, which was strongest in males. In contrast, there was no correlation between plasma ferritin and hookworm egg count, and no consistent correlation between haemoglobin level or haematocrit and either measure of hookworm intensity. The results suggest that the role of hookworm in the aetiology of anaemia may be difficult to assess without the accurate measurement of hookworm burden.

Age Factors↗

Cytokine and chemokine responses in patients co-infected with Entamoeba histolytica/dispar, Necator americanus and Mansonella perstans and changes after anti-parasite treatment.

This study examined the impact of concurrent parasite infections (amoebiasis, filariasis, necatoriasis) and the effect of anti-parasite treatment on cytokine and chemokine responses in singly and poly-parasitized patients. Cellular reactivity and parasite-specific Th1- and Th2-type cytokine and chemokine profiles were investigated before and six weeks after treatment. In those patients infected with three parasite species, cellular secretion of interleukin 5 (IL-5) and IL-12p40 by PBMC was strongly diminished (p<0.005) but IL-10 was elevated in parasite-infected patients (p<0.0001) in response to protozoa- and helminth-specific as well as bacteria-specific antigens. Macrophage inflammatory chemokines (MIP-1alpha/CCL3 and MIP-1beta/CCL4), macrophage-derived chemokine (MDC/CCL22) and neutrophil activating chemokine (IL-8/CXCL8) were produced by PBMC in similar amounts in endemic controls and singly and poly-parasitized patients, but thymus and activation-regulated chemokine (TARC/CCL17) was produced the highest by PBMC from patients with triple parasite infections (p<0.0001). Following anti-parasite therapy, secretion of IL-12p40 and IL-5 augmented significantly in treated patients while IL-10, MDC, MIP-1alpha, TARC and IL-8 substantially diminished (all p<10(-5)) when their PBMC were activated with parasite- and bacteria-specific antigens. In summary, PBMC from poly-parasitized patients responded to protozoa- and helminth-specific antigens with a compromised IL-5 and IL-12p40 but high IL-10 and a substantial chemokine release. Chemokines may attract and activate effector cells in peri-parasitic tissues to limit parasite proliferation and dissemination, while depressed IL-5 and IL-12p40 but prominent IL-10 may prevent eosinophil and cytotoxic cell-mediated inflammatory processes and pathogenesis to the host. The changes in this profile following anti-parasite therapy disclosed the dynamics of an immune adaptation associated with parasite accumulation and also with clearance of parasite infections.

Adult↗

Density-dependent effects on establishment of Necator americanus and Ancylostoma ceylanicum.

The relationships between the number of infective larvae (L3s) to which animals were exposed and the establishment of A. ceylanicum and N. americanus in hamsters were examined. There was no evidence of density-dependent constraints on the establishment of A. ceylanicum in the range 10-1000 larvae, but an experiment in which the range was extended to 1500 L3s gave a significant negative correlation between the magnitude of the infecting dose and percentage establishment. Even so the percentage reduction was relatively small, approximating to 0.89% per 100 larvae administered, and in practice density-dependent constrains on establishment are unlikely to affect experiments with this species in which much lower doses (< 250 L3) are generally employed. The range of doses for N. americanus L3s was smaller (10-400). Of the four experiments reported, two gave a significant reduction of establishment with increasing dose and two did not. When the data was split into low doses (< 100 L3s) and high doses (> 100 L3s), falling establishment with increasing dose was only detected in the lower dose range. There was no difference in the establishment when doses of 100 L3s were compared with 250 or 400 L3s. On balance, it was concluded that density-dependent constraints on establishment of N. americanus in hamsters were not marked and would have little significant effect on experiments utilizing fewer than 200 L3s (approximately 7.6% reduction between 10 and 200 L3s). These results are discussed in relation to host regulation of hookworm burdens.

Ancylostoma↗

Necator americanus secretory acetylcholinesterase and its purification from excretory-secretory products by affinity chromatography.

Acetylcholinesterase (AChE) secretion by adult N. americanus was enhanced in vitro by incorporating insoluble collagen rafts into culture dishes. Enzyme produced in this way had preferential substrate specificity for acetylthiocholine iodide (ATC), and its activity was inhibited by eserine (1.1 x 10(-8) M). Ancylostoma ceylanicum, another hookworm species, failed to produce comparable amounts of AChE in culture. AChE was efficiently purified from culture medium by affinity chromatography on edrophonium sepharose; 81% of the AChE activity was retained by the affinity matrix, although this fraction contained only 4.3% of the protein loaded. Antisera raised against purified AChE in rabbits immunohistochemically stained the oesophageal glands of the parasite, and reacted with molecules of 32, 60, 80, 140 and 220 kDa in reduced adult ES products on Western blotting, although differential activity was observed against worm homogenates and earlier developmental stages. On IEF, purified AChE resolved predominantly with a pl of 3.55; proteins with a similar pl were recognized by rabbit anti-AChE. IgG preparations of this antiserum inhibited AChE activity in ES products, and inhibited AChE secretion by adult worms in culture. The availability of this immunological probe will allow definitive experiments to be conducted on the role of this enigmatic enzyme in the host-parasite relationship.

Acetylcholinesterase↗

The detection of autoantibodies to IgE in plasma of individuals infected with hookworm (Necator americanus) and the demonstration of a predominant IgG1 anti-IgE autoantibody response.

In this study we have demonstrated significantly elevated levels of circulating IgG autoanti-IgE antibody in hookworm infected individuals from Kebasob village on Karkar Island, Papua New Guinea. Although anti-IgE activity was demonstrable in IgG1, IgG3 and IgG4, IgG1 was by far the most important subclass of IgG anti-IgE in terms of frequency of detection (34/39; 87.2%) and magnitude of increase (P = 0.0000); with IgG3 (16/39; 41.0%) and IgG4 (15/39; 38.5%) antibodies being considerably less prevalent. Plasma levels of IgG1 anti-IgE (P = 0.0019) and IgG3 anti-IgE (P = 0.0034) showed significant correlations with total IgE concentrations, but not with IgE specific to excretory-secretory worm products; thus suggesting that anti-IgE synthesis is more related to polyclonal hyper IgE production than to antigen-specific IgE stimulation. No correlation was seen between IgG subclass anti-IgE levels and faecal egg counts or worm burden. Given that our data failed to show a negative or a positive correlation between anti-IgE and the degree of infection with hookworm, it is tempting to speculate that the main role of autoanti-IgE is to provide the host with protection against immune complex- and IgE-mediated hypersensitivity reactions to parasitic antigens.

Adolescent↗

The specificity of the human IgE response to Necator americanus.

Human IgE responses to helminth infections have been described as both problematic and beneficial, in that type 1 hypersensitivity to parasite infections can reputedly cause pathology and/or parasite expulsion, (Pritchard, Quinnell & Walsh 1995). In the present communication, we can report that the IgE response to helminth infections may be beneficial in a diagnostic sense, in that antibodies of this isotype showed minimal cross-reactivity against antigens from the parasites tested. This information may be of benefit to workers attempting to establish ELISA assays for the specific diagnosis of zoonotic hookworm infections, for example, Ancylostoma caninum (Croese 1988), particularly in regions where human hookworm infection is endemic.

Animals↗

Hookworm (Necator americanus) transmission in inland areas of sandy soils in KwaZulu-Natal, South Africa.

This study extended the association between hookworm transmission in KwaZulu-Natal and the sandy coastal plain by investigating the parasite's occurrence in isolated areas of sandy soils further inland. A school-based prevalence survey was carried out in selected inland sandy areas and in surrounding areas dominated by clay soils within a narrow altitudinal range of between 500 and 700 m to reduce the effect of altitude on climate-related factors (rainfall and temperature). Sandy areas situated on the coastal plain were included in the analysis for comparative purposes. Soil samples (0-50 mm depth) were collected from each locality to assess their nematode loadings and to analyse selected physical and chemical properties. Significant differences were found between the moderate prevalence of hookworm infection among children living in inland areas with sandy soils (17.3%) and the low prevalence in surrounding non-sandy areas (5.3%, P < 0.001), and between infection among children living in all inland areas (9.3%) and the high prevalence on the coastal plain (62.5%, P < 0.001). Amounts of fine and medium sand were highest in both the coastal plain soils and in inland sandy areas and these fractions showed a significant positive correlation with hookworm prevalence and nematode loadings. Clay, coarse sand and organic matter contents were highest in surrounding non-sandy soils and showed a significant negative correlation with the nematode variables. No statistically significant correlations were found with soil pH at study localities. We conclude that properties of inland sandy soils, particularly particle size distribution, correlate well with hookworm prevalence and nematode loadings and therefore provide a more suitable habitat for nematodes than surrounding non-sandy areas. These results suggest that particle size distribution of sand fractions, organic matter and clay content in the soil influence the survival of hookworm larvae and hence the parasite's transmission.

Adolescent↗