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PubMed1995

An initial characterization of the proteolytic enzymes secreted by the adult stage of the human hookworm Necator americanus.

The proteolytic activities present in adult Necator americanus excretory-secretory products have been assessed using biologically relevant, naturally occurring substrates (haemoglobin and fibrinogen) and a number of synthetic fluorogenic and chromogenic substrates. One broad peak of activity was observed against haemoglobin in the pH range 5 to 7, with maximum activity at pH 6.6, while fibrinogenolytic activity was shown to be greater at pH 3.5. Inhibition studies against haemoglobin, fibrinogen and synthetic substrates using a battery of appropriate protease inhibitors indicated the presence of a mixture of aspartyl, cysteinyl and serine proteases. Metal ion (Ca2+, Zn2+ and Fe2+) stimulation was demonstrated, with stimulation by Zn2+ being the most marked. These results are discussed in the context of recent developments in the field of parasite proteolytic enzymes, where they have been suggested as targets for immuno- and chemotherapy.

Amino Acid Sequence↗
PubMed1994

Density-dependent regulation of the growth of the hookworms Necator americanus and Ancylostoma ceylanicum.

Laboratory bred DSN hamsters were exposed to varying doses of infective larvae of Ancylostoma ceylanicum (orally) or Necator americanus (percutaneously) and were autopsied at times which corresponded to a period immediately before cessation of growth of worms or soon afterwards. A total of 829 (404 male and 425 female) A. ceylanicum and 1582 (781 male and 801 female) N. americanus were measured. At worm burdens of fewer than 100, the length of A. ceylanicum appeared to increase with infection intensity and no evidence was found that growth was retarded under crowded conditions. In an experiment comparing directly low (mean worm burden = 22) and heavy infections (mean worm burden = 180) significant negative associations between both weight and width, and worm burden were detected, but length again increased with worm burden. In contrast, 5 experiments with N. americanus indicated negative relationships between measures of worm size (length, width, wet and dry weight) and worm burden. It was concluded that N. americanus is subject to regulation by density-dependent processes within the host while A. ceylanicum is not sensitive to the same degree.

Analysis of Variance↗
PubMed1995

Hookworm infection.

It retards growth and intellectual development in millions of children yet is largely ignored by researchers. New findings suggest excellent possibilities for a vaccine.

Adolescent↗
PubMed1999

Cu/Zn superoxide dismutase in excretory-secretory products of the human hookworm Necator americanus. An electron paramagnetic spectrometry study.

EPR spectrometry was used to investigate the effect of excretory/secretory product from Necator americanus on superoxide radical anions generated by xanthine/xanthine oxidase as a measure of excretory/secretory product superoxide dismutase activity. Using 1,1',5,5'-dimethylpyrollidine-N-oxide (DMPO) as a superoxide spin-trapping agent a 12-line EPR spectrum characteristic of the DMPO-OOH adduct was observed to decrease in the presence of excretory/secretory product. Superoxide dismutase activity was proportional to excretory/secretory protein concentration, was inhibited with cyanide treatment and was progressively destroyed with increasing time of heat denaturation of excretory/secretory product. Using a purpose-built chamber the superoxide dismutase activity of excretory/secretory product from live worms in culture was shown to accumulate with time to a maximum at 4 h. The electron paramagnetic resonance spectrum obtained for the frozen excretory/secretory product of N. americanus recorded at 77 K is typical of Cu(II) in a protein matrix. The results are consistent with the presence of an active Cu/Zn superoxide dismutase in excretory/secretory product from N. americanus and demonstrate a method for the unequivocal determination of the fate of superoxide anions in the presence of live worms.

Animals↗
PubMed1976

The role of the house fly (Musca domestica) in the dissemination of hookworm.

Eggs and larvae of Ancylostoma caninum were recovered from the crop, mid-gut and hind-gut of Musca domestica; only larvae were recovered from the vomitus and one dead infective larva was recovered from the faeces on one occasion. All eggs recovered from the gut hatched after incubation for 48 hours. Up to 319 eggs and 1485 larvae were recovered from the legs of experimentally contaminated flies. The viability of the eggs and the longevity of the larvae recovered from the gut and external surface of the flys varied but larvae survived longer in the gut than on the external surface.

Ancylostoma↗
PubMed2002

Emerging patterns of hookworm infection: influence of aging on the intensity of Necator infection in Hainan Province, People's Republic of China.

We examined risk factors associated with Necator americanus infection among persons aged > or =50 years in Hainan Province, People's Republic of China. Age and sex made the most important contributions to the variation in infection intensity (28%-30%), with age alone responsible for 27% of this variation. When stratified by 20-year age intervals, the influence of shared residence was 23% for persons aged > or =50 years and 27% for those aged <20 years, who had the highest and lowest levels of infection intensity, respectively. This points to shared residence as a means of capturing the complex relationship between aging and shared socioeconomic, environmental, and behavioral factors that influence transmission of Necator infection. None of the other 26 personal or 32 household risk factors were found to be significant. The importance of aging in Necator infection reveals an emerging public health problem among the elderly population of developing countries.

Adolescent↗
PubMed1987

Antigen expression during development of the human hookworm, Necator americanus (Nematoda).

The accumulated and de novo synthesized antigens expressed by L3, L4 and adult Necator americanus, recognized by both the natural host, man, and the experimental host, the hamster, were identified by immunoblotting and immunoprecipitation analysis. Following infection of neonatal hamsters serum samples were taken on days 17, 35 and 117. Only serum taken 117 days after infection showed significant reactivity in immunoblotting experiments, recognizing adult epitopes of 30,000, 33,000, 48,000 and 69,000 mol. wt thereby suggesting that few accumulated antigens are shared between developmental stages. By contrast, immunoprecipitation analysis of metabolically labelled proteins suggested that L3 and in particular L4 larvae synthesize some antigens which comigrate with those synthesized and accumulated by adult worms. In addition, L4 larvae synthesize a 41,000 mol. wt excretory/secretory (ES) stage specific antigen. Parallel experiments using serum samples from infected humans, demonstrated that hamsters and man recognize many antigens of identical molecular weight. Notable in this respect are accumulated adult antigens of 30,000, 33,000, 48,000 and 69,000 and de novo synthesized antigens of 30,000, 33,000, 44,000, 46,000 and 69,000 mol. wt. Some individual human sera mainly recognized L3 antigens of 47,000-69,000 mol. wt in immunoblotting experiments whilst others simultaneously recognized adult epitopes. This differential recognition of developmental stages by individual human sera suggests that genetic or epidemiological factors are operative and warrants further study. Overall, these studies confirm the pronounced immunogenicity of Necator americanus in both man and an animal model and pave the way for analysis of the relevance of these antigens to field situations.

Animals↗
PubMed1988

Acquired resistance to the human hookworm Necator americanus in mice.

BALB/c mice were exposed to primary or secondary infection with the hamster-adapted strain of Necator americanus, and the course of infection was monitored through worm recovery and immunological assays. Significantly fewer viable larvae were recovered from the skin site of reinfected mice on day 2 post-infection, and fewer larvae resided in the lungs of challenged mice 3-5 days after infection, suggesting that the skin was involved in resistance to secondary infection. The serum antibody response to L3 antigen was enhanced during secondary infection, peaking on day 9, and the bronchoalveolar leucocyte (BAL) response was more intense at this stage. Thus the secondary BAL response was initiated more promptly than the primary response, peaking on day 13 at twice the intensity of the primary response and five times above the resting level. Differential counts revealed that by far the most significant changes in cell populations were those observed for eosinophils in lavage fluid. At the peak of the response a 925-fold increase over control levels was detected in mice undergoing a challenge infection. Some cellular and serological components of the secondary response were defined in the present work and it was concluded that reinfected mice have the capacity to trap parasites during their passage through the skin and development in the lungs.

Animals↗