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Hookworm infections and human iron metabolism.

Ancylostoma duodenale and Necator americanus are extremely common species of soil-transmitted helminth which flourish where poverty and malnutrition prevail. Hookworms contribute significantly to iron-deficiency anaemia, which remains one of the world's major nutritional problems, through the feeding activities of intestinal stages leading to chronic blood loss into the gut. In this article, a mathematical model is proposed to explain how human iron metabolism may respond to hookworm infection of varying intensity. The model draws attention to the importance of the regulation of stored iron levels in the process. The results from the model are presented for the effects of hookworm infection on the iron metabolism of a healthy adult male. Calculations are also presented in which the effects of hookworms on the iron metabolism of a non-pregnant woman are compared with those of a pregnant woman. Use of the model may help develop a better understanding of the pathology of hookworm disease.

Adolescent↗

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↗

An investigation of hookworm infection and reinfection following mass anthelmintic treatment in the south Indian fishing community of Vairavankuppam.

Hookworm infections, as assessed by counting worms expelled following anthelmintic treatment and by egg output, were found to be of low prevalence and intensity in a South Indian fishing community. The initial overall prevalence of infection in the community was 43%, and the average burden was estimated at 2.2 hookworms per person. The age profiles of prevalence and intensity differed between males and females, with the latter harbouring significantly higher levels of infection. Children of both sexes under 10 years of age rarely harboured hookworms. Treatment with pyrantel pamoate was estimated to be 91% effective in clearing hookworm infections. Egg counts made on stools collected during an 11-month period of reinfection indicated that female patients became reinfected soon after treatment, while little hookworm egg excretion was observed in males during the observation period following treatment. Females acquired a significantly higher number of worms during the reinfection period compared with males, although the average burden in females reached only 28% of the initial, pre-treatment level. The hookworm population consisted of predominantly Necator americanus, and less than 10% of Ancylostoma duodenale. The parasites were highly aggregated within the host population with 10% of the community harbouring over 65% of the total hookworms. Low values of the negative binomial aggregation parameter, k, (indicating extreme over-dispersion) were recorded in groups stratified by age and sex. Highly significant positive correlations were observed between the initial (pre-treatment) and reinfection worm burdens of female (but not of male) patients. It is suggested that occupational practices related to walking through areas contaminated with hookworm larvae play an important role in generating the observed patterns of infection within this community.

Adult↗

Experimental and field studies on the viability of eggs, and the infectivity of third-stage larvae of the human hookworm Necator americanus recovered from the creek waters of the Niger Delta, Nigeria, and their epidemiological significance.

In a combined field and laboratory study, the eggs and 3rd-stage infective larvae of the human hookworm Necator americanus were recovered from the creek waters of the Niger Delta, Nigeria. They were tested for viability and infectivity. Eggs recovered from fresh water creeks showed a viability or hatching index of between 17.5 and 23.7%. Eggs recovered from brackish water showed a viability index of 18.8-21.4% in 'normal' cultures, and a maximum index of 6.3% when cultured in brackish water. The differences in the viability indices of these eggs were not significant (P greater than 0.05). Infective 3rd-stage larvae were recovered from both fresh creek water (205-258 L3/litre of water), and brackish water (45 L3/litre of water). Larvae hatched from brackish water eggs that were cultured in the brackish water were 20% infective by 3 days, but lost all infective potential by 7 days post-hatching. Larvae from fresh water eggs, cultured in fresh water and 'normal' laboratory cultures reached 50% infectivity in 3-5 days, losing potential infectivity in 11-15 days post-hatching. The infectivity patterns of larvae recovered directly from fresh and brackish waters did not differ significantly (P greater than 0.05) from the infectivity patterns of larvae recovered from laboratory cultures of eggs from all the experimental sources. Although larvae recovered directly from fresh and brackish waters survived in these respective media under laboratory conditions, there was a significant difference (P less than 0.05) in their survival patterns. The survival and infectivity rates of field larvae were considerably reduced over time relative to control larvae.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Necator americanus in inbred mice: evidence in support of genetically determined differences in the cellular immune response to a primary infection.

The blood and broncho-alveolar leucocyte (BAL) responses, to a primary Necator americanus infection, were studied in male BALB/c and NIH mice. Following percutaneous infection, a significant blood leucocytosis occurred in both the BALB/c and NIH strains. The peak response occurred, in both strains, on day 10 p.i. and this was reflected in the eosinophil response which peaked at the same time-point. The change in blood eosinophil numbers, as a result of infection, was found to be the greatest recorded for any cell type. In BALB/c mice, however, infection elicited a significantly more intense total leucocyte, lymphocyte and eosinophil response than in NIH mice. In contrast, the BAL response was more intense in the NIH strain. Peak BAL responses were observed between days 12 and 16 p.i., in both strains, and the change in broncho-alveolar eosinophil numbers, as a result of infection, was found to be the greatest recorded for any cell type. The relationship between the observed leucocyte responses and resistance to the migrating larvae of a primary infection is discussed.

Animals↗

A survey of genes expressed in adults of the human hookworm, Necator americanus.

Hookworms are gut-dwelling, blood-feeding nematodes that infect hundreds of millions of people, particularly in the tropics. As part of a program aiming to define novel drug targets and vaccine candidates for human parasitic nematodes, genes expressed in adults of the human hookworm Necator americanus were surveyed by the expressed sequence tag approach. In total 161 new hookworm genes were identified. For the majority of these, a function could be assigned by homology. The dataset includes proteases, protease inhibitors, a lipid binding protein, C-type lectins, an anti-bacterial factor, globins and other genes of interest from a drug or vaccine development viewpoint. Three different classes of small, secreted proteins were identified that may be involved in the host-parasite interaction, including potential potassium channel blocking peptides. One third of the genes were novel. These included highly expressed, secreted (glyco)proteins which may be part of the excretory-secretory products of these important pathogens. Of particular interest are a family of 9 genes with similarity to the immunomodulatory protein, neutrophil inhibitory factor, that may play a role in establishing an immunocompromised niche for this successful parasite.

Amino Acid Sequence↗

A new approach to morbidity risk assessment in hookworm endemic communities.

The relationship between paired hookworm prevalence and mean intensity of infection data from geographically defined communities was examined. The results show that, in spite of major socio-economic and environmental differences between communities, the relationship is consistent and non-linear. A generalized value of k (the exponent of the negative binomial distribution) for hookworms was estimated to be 0.34, which is consonant with previous estimates from cross-sectional data. Maximum likelihood analysis indicates that the severity of hookworm aggregation in humans has an inverse relationship to mean worm burden which is less marked than for Ascaris lumbricoides. A simple model, based on published estimates of hookworm burdens associated with hookworm anaemia, was used to predict prevalence of morbidity from prevalence of infection data for Tanzania, Kenya and Zambia. Predictions correspond to the observation that hookworm anaemia is highly focal, and largely coastal, in distribution. These analyses suggest that locality-targeting of chemotherapy is particularly appropriate for the control of hookworm morbidity.

Ancylostomiasis↗

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↗

A hookworm allergen which strongly resembles calreticulin.

Immmoglobulin E-rich plasma from patients from Papua New Guinea infected with Necator americanus has been used to probe an adult N. americanus cDNA library for the presence of hookworm allergens. Using this approach, one hookworm allergen has been identified as calreticulin, which was subsequently expressed in Escherichia coli. Little serological cross reactivity was seen between the recombinant calreticulins of this hookworm and its host. Prospective roles for hookworm calreticulin in the host-parasite relationship are discussed in depth.

Allergens↗

Determining the prevalence of Oesophagostomum bifurcum and Necator americanus infections using specific PCR amplification of DNA from faecal samples.

Until recently infection of humans with Oesophagostomum bifurcum was regarded as a rare zoonosis. But in northern Togo and Ghana its prevalence is 50% or more in certain villages. Diagnosis is hampered by the fact that the eggs of O. bifurcum are morphologically identical to those of the hookworm Necator americanus. Stools have to be cultured for 7 days to allow eggs to hatch to the characteristic third-stage (L3) larvae. We evaluated the applicability of specific polymerase chain reactions (PCRs) to amplify DNA from faecal samples as an alternative method for the differential diagnosis of the two infections. Oesophagostomum bifurcum-PCR was positive in 57 of 61 faecal samples known to contain O. bifurcum L3 larvae in coproculture. Necator americanus PCR was positive in 137 of 146 faecal samples known to contain N. americanus L3 larvae in coproculture. PCR also detected 26 additional O. bifurcum cases in 72 samples from O. bifurcum endemic villages in which no O. bifurcum larvae were found and 45 N. americanus cases in 78 samples in which no N. americanus larvae were found in coproculture. No O. bifurcum DNA was detected in 91 stool samples from individuals from two non-endemic villages. These results prove the usefulness of specific PCR assays as epidemiological tools to estimate the prevalence of O. bifurcum and N. americanus infections in human populations.

Animals↗

Allergy controls the population density of Necator americanus in the small intestine.

BACKGROUND & AIMS: Nearly 700 million people remain infected with hookworms. Although allergy is intuitively linked to immunity against helminths, few positive examples have been characterized. Larval migration through the lungs has been considered the likely interface at which hookworm attrition occurs. As part of a study evaluating a potential role for hookworms in the modulation of human autoimmunity, we examined parasite migration and intestinal colonization. METHODS: Capsule and conventional endoscopies supplemented the evaluation of healthy volunteers and Crohn's disease patients recently inoculated with larvae of the human hookworm Necator americanus. Two healthy volunteers with a previously established and stable hookworm infection were inoculated with 50 larvae and had serial capsule endoscopies performed. RESULTS: Eosinophilic enteritis developed in all subjects after the initial inoculation. Newly inoculated larvae in the 2 subjects with an established infection reliably reached the intestine within 4 weeks. Thereafter, the colony diminished to the host's constitutive status quo because mostly immature worms failed to attach. The intensity of the eosinophilic response correlated negatively with the time available for hookworms to feed and positively with hookworm attrition. CONCLUSIONS: Necator larval migration to the intestine is uncontested. We propose that allergic inflammation purposefully degrades the hookworm's bite, causing premature detachment, restricted feeding, and expulsion. This novel biological dynamic suggests a new paradigm of hookworm resistance.

Animals↗

Endoscopic discovery and capture of Necator americanus in the stomach.

We report a case of the endoscopic discovery and removal of a specimen of Necator americanus hooked into the gastric mucosa of a black woman from Zaire. We extracted the parasite by means of biopsy forceps. Signs of previous bites were seen in the antrum. This exceptional localization might be due to a jejuno-duodeno-gastric reflux.

Adult↗

A comparative study of the relative efficacy of pyrantel pamoate, bephenium hydroxynaphthoate and tetrachlorethylene in the treatment of Necator americanus infection in Ceylon.

The clearance of hookworm (Necator americanus) ova by a single dose of tetrachlorethylene (T.C.E.) was compared with that produced by single and multiple dose regimes of bephenium hydroxynaphthoate and pyrantel pamoate. Single doses of bephenium and pyrantel were inferior to T.C.E. Three daily doses of bephenium or pyrantel produced effects comparable with a single dose of T.C.E. Because of the low cost and lack of side effects, T.C.E. remains the drug of choice in the treatment of N. americanus in infections; the only disadvantage of T.C.E. is its unnoticed deterioration under tropical conditions.

Administration, Oral↗

Human Ancylostoma infections in Nigeria.

An estimate of the proportion of infections with Ancylostoma duodenale and Necator americanus by the examination of larvae collected from the stools of 220 persons infected with hookworm was made. Fifty-nine per cent of the infections were due to N. americanus only: A. duodenale always occurred in association with N. americanus. In 12% of the infections it is suggested that there were approximately three female A. duodenale to 95 female N. americanus. The highest numbers of A. duodenale in mixed infections (28 female A. duodenale with 45 female N. americanus) occurred in only 1% of the infections. Evidence is given that egg size can be important in the differentiation of the two species. A method of calculating the proportion of the two hookworms, and hence of other intestinal nematodes, in mixed infections in an individual as well as in the general population, is also described.

Adolescent↗