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PubMed1982

Clinical trial of albendazole in hookworm infection.

A clinical trial of albendazole (Zentel R) was carried out at the Hospital for Tropical Diseases in 1981. Thirty-five patients with hookworm infection were divided into 2 groups A, B and treated with a single dose of albendazole 400 mg and 600 mg respectively. The age of the patients ranged from 12 to 66 years and their weights ranged from 25 to 62 kilograms. Concentration and Stoll egg count methods were done at pretreatment, day 14 and day 21. At each interval two aliquots from each of the two faecal specimens were collected. The geometrical mean of EPG in Group A and B were 5406 and 5617 respectively. The cure rate in patients with less than 5000 EPG was 75% on day 21 in Group A and 67% in Group B. The mean percentage egg reduction was 95% in Group A and 99% in Group B. In patients with a higher egg out-put, the cure rate on day 21 was 50% in Group A and 29% in Group B. The mean percentage egg reduction was 91% in Group A and 93% in B. The side effects were mild and transient.

Adolescent↗

PubMed1980

Seasonality in human hookworm infection in an endemic area of Nigeria, and its relationship to rainfall.

Detailed parasitological and climatological examination of two rural communities in a hookworm endemic area of Anambra State Nigeria, has shown that infection with the parasite follows a clearly defined pattern. The results suggested a break in the transmission cycle of the parasite during the dry season December--February when only a few larvae (< 500 L3S) could be recovered from contaminated soils for not more than 4 days. Transmission of the parasite and the manifestation of the disease in infected individuals appeared to be a rainy season phenomenon. The implications of these findings are discussed in relation to possible control of the disease.

Feces↗

PubMed1995

Epidemiology of human hookworm and Ascaris lumbricoides infestations in rural Gambia.

In a cross-sectional study of helminth infections in a rural village in The Gambia, West Africa, hookworm, probably Necator americanus and Ascaris lumbricoides were found to be the most prevalent helminths present at prevalence levels of 30% and 25% respectively. Other parasites present were Trichuris trichiura (2.4%) and Schistosoma mansoni (1.5%). The mean egg counts of N. americanus and A. lumbricoides in all age groups and in the total population were low. Egg counts between age and sex groups were not statistically significant. The frequency distributions of both N. americanus and A. lumbricoides were overdispersed with the majority of the sample population producing none or few eggs, and a small minority producing relatively large amounts of eggs. Large variance: mean ratios within age groups and the total study population suggested a high degree of aggregation of the parasites in this community.

Adolescent↗

PubMed1995

The epidemiology of Ascaris lumbricoides, Trichuris trichiura, and hookworm in children in the Ranomafana rainforest, Madagascar.

An epidemiological study of intestinal nematodes was conducted with 1,292 children, ranging from birth through 11 yr old, living in the Ranomafana rainforest of southeast Madagascar. Fecal examinations revealed prevalences of 78% for Ascaris lumbricoides, 38% for Trichuris trichiura, 16% for hookworm, and 0.4% for Schistosoma mansoni. Infection intensity was measured indirectly by fecal egg counts and directly by A. lumbricoides expulsion following treatment with pyrantel pamoate. The mean A. lumbricoides worm burden for children, 5-11 yr old, was 19.2 (SD 20.4) worms per child, with a median of 13 worms (n = 428). The distributions were overdispersed for all 3 nematodes. The age profiles showed a rapid acquisition of A. lumbricoides during infancy, increasing to 100% prevalence by age 10. After mebendazole anthelmintic treatment and a 12-mo reinfection period, the nematodes had rebounded to pretreatment prevalence and intensity levels. There was evidence for age-dependent predisposition of the children to infection intensity for each of the 3 nematodes. Dual species intensity correlation was consistently strong for A. lumbricoides and T. trichiura. The significantly higher prevalence and intensity of ascariasis in girls were thought to be related to exposure.

Age Distribution↗

PubMed1998

Conforming strategies of public health campaigns to disease specificity and national contexts: Rockefeller Foundation's early campaigns against hookworm and malaria in Brazil.

The early experience of Rockefeller Foundation in Brazil, starting in 1915, reflected the idea of extending learned experience in Southern US to a wide international context. Health education and the creation of permanent local health services were expressed as main guidelines for cooperation with State and federal Brazilian agencies. Translating to the shaping of public health models the terms of scientific hygiene associated with the pastorian revolution, RF pictured different actions as part of a three step rationale of survey, experiment and demonstrations. In this paper we focus on Lewis Hackett's campaign, designed as a demonstration campaign of the "intensive method" of hookworm control, with the final purpose of enlisting local agencies in long-term action (1919-1924) and the malaria campaign in Rio de Janeiro State Lowlands (1922-1928) led initially by Mark Boyd as an "experimental control work" of field observation, campaign, control and maintenance to set guidelines to malaria control in tropical areas. The course and ultimate results of these experiences showed the need to adapt formal models to complex national and State-building context and to disease specificity, leading to pragmatic adaptations in the issue of control and eradication and on the shaping of vertical and horizontal health services. The failure of these two experiences in terms of disease control helped to strengthen the move, predominant in the next two decades, to vertical campaigns with least dependency on local social and political dynamics, as in the exemplar case of Frederick Soper's Anopheles gambiae eradication campaign (1938-1942).

Brazil↗

PubMed2005

Crystal structure of a new class of glutathione transferase from the model human hookworm nematode Heligmosomoides polygyrus.

The crystal structure of GST Nu2-2 (HpolGSTN2-2) from the model hookworm nematode Heligmosomoides polygyrus has been solved by the molecular replacement method and refined to a resolution of 1.71 A, providing the first structural data from a class of nematode-specific GSTs. By structural alignment with two Sigma class GSTs, glutathione could be rationally docked into the G-site of the enzyme. By comparing with all mammalian GST classes, a novel, long, and deep cleft was identified at the H-site, providing a potential site for ligand binding. This new GST class may support the establishment of infection parasitic nematodes by passively neutralizing chemical toxins derived from host environment. The structure serves as a starting point for structure-based drug/inhibitor design that would aim to selectively disrupt nematode chemical defenses.

Animals↗

PubMed1996

Acasp, a gene encoding a cathepsin D-like aspartic protease from the hookworm Ancylostoma caninum.

Intestinal infection with the zoonotic hookworm Ancylostoma caninum can provoke human eosinophilic enteritis. A cDNA was isolated from A. caninum, using an oligonucleotide primer designed to hybridize to the region encoding the consensus, catalytic site residues D32TGSSNLW of aspartic proteases. This novel cDNA encoded an aspartic protease zymogen of 422 amino acids, exhibiting 47% identity to the lysosomal aspartic protease of Aedes aegypti, 46% identity to the aspartic protease of Schistosoma japonicum, and 48.5% to human cathepsin D. Its deduced structure differed from that of cathepsin D in the loop 2 "flap," which holds the substrate at the active site, and by the presence of a COOH-terminal extension of approximately 30 residues.

Amino Acid Sequence↗

PubMed1977

Skin penetration of infective hookworm larvae. II. The path of migration of infective larvae of Ancylostoma braziliense in the metacarpal foot pads of dogs.

The hairless metacarpal foot pads of six hookworm-free puppies were exposed to infective larvae of Ancylostoma braziliense. Serial sections of the biopts stained with Harris' haematoxylin and eosin showed that the infective larvae are able to penetrate the toughest region of canine skin. Pores of eccrine sweat glands did not seem to constitute sites of entry and no larvae were detected in these glands. Larvae were only observed in the epidermis. The histopathology of the infected skin of the foot pads of the puppies was similar to that in human skin with "creeping eruption" as described by Fülleborn (1927). The biopts appeared to consist of hairy skin as well. In the unexposed adjacent hairy skin of the foot pads, larvae were also observed. They were found in the epidermis, hair follicle systems and dermis, suggesting that the migration from the epidermis into deeper tissue depends on the presence of the hair follicle systems.

Ancylostoma↗

PubMed1985

Chemotactic attraction of infective hookworm larvae of Ancylostoma caninum by a dog serum factor.

Infective hookworm larvae of Ancylostoma caninum showed chemotaxis on agar plates in a dog serum gradient. This chemotactic behaviour remain unaltered using an ultrafiltrated serum fraction with a molecular weight less than 500. Gelfiltration of this ultrafiltrated fraction revealed a factor with a molecular weight of 480 causing chemotaxis. The chemotactic activity of the factor was destroyed after a pronase treatment. We conclude that the factor could be a polypeptide.

Ancylostoma↗

PubMed1978

Investigations into the free-living phase of the cat hookworm life cycle.

Laboratory studies were undertaken to evaluate the role of environmental factors on the development of free-living stages of the cat hookworm Ancylostoma tubaeforme. An index of development calculated from the proportion of eggs that developed to the infective stage and the reciprocal of the development period, has suggested that the absence of 'high' temperatures (26 degrees - 30 degrees C) would significantly affect the L3 population in contaminated soils. There were, however, no significant differences in the size and lipid content of L3 that had developed at the different temperatures.

Ancylostoma↗

PubMed2002

An Update on the Geohelminths: Ascaris lumbricoides, Hookworms, Trichuris trichiura, and Strongyloides stercoralis.

Geohelminths remain prevalent throughout the developing world where levels of sanitation, personal hygiene, and maternal education are low. The five species of nematodes responsible for the bulk of disease are Ascaris lumbricoides, the hookworms Ancylostoma duodenale and Necator americanus, Trichuris trichiura, and Strongyloides stercoralis. Geohelminths are acquired through ingestion of fecally contaminated food or water or through contact with infected soil. In developing countries, infection with more than one nematode species and high worm burdens are common. The morbidity is substantial, particularly among children, and deaths occur. Geohelminthic infections are encountered in industrialized countries among immigrants and long-term travelers who have lived in endemic regions where sanitation is poor, and occasionally following autochthonous transmission.

Journal Article↗

PubMed1995

Glutathione S-transferase (GST) expression in the human hookworm Necator americanus: potential roles for excretory-secretory forms of GST.

The difficulty in demonstrating protective immunity to human gastro-intestinal nematodes is thought to be a consequence of the expression of defences by the parasites directed against the toxic metabolites of leukocytes produced during inflammation (Brophy and Pritchard, 1992a). Parasite glutathione S-transferases (GSTs) may provide part of this defence by detoxifying the secondary products of lipid peroxidation produced via immune initiated free-radical attack on host or parasite membranes (Brophy and Pritchard, 1994; Taylor et al., 1988). Neutralisation of parasite immune defence components could tip the molecular balance in favour of the immune response during chronic infections. For example, GSTs have been extensively investigated from the digenean parasites Schistosoma and Fasciola hepatica and provide protection in animal-model systems (Mitchell, 1988; Wijffels et al., 1991). In contrast, although GSTs have been initially characterised in filarial nematodes (Salinas et al., 1994; Leibau et al., 1994; Jaffe and Lambert, 1986), there is limited information on GSTs from human gastro-intestinal nematode parasites. We were particularly interested in analysing the products of hookworms for evidence of the presence of excretory-secretory forms of this putative immune defence protein.

Animals↗

PubMed1990

An immunological and biochemical comparison of hookworm species.

The successful development of diagnostic tests capable of distinguishing human hookworm species will ultimately depend on an increase in our knowledge of their comparative biochemistry. Here, David Pritchard, Paul McKean and Gerry Schad describe some aspects of the comparative biochemistry of Necator americanus and Ancylostoma duodenale, and emphasize differences between the species that could form the basis of discriminatory diagnostic tests.

Journal Article↗

PubMed2005

Cloning and characterisation of genes encoding two transforming growth factor-beta-like ligands from the hookworm, Ancylostoma caninum.

To elucidate the role of transforming growth factor beta (TGF-beta) signalling in the arrest/reactivation pathway of the Ancylostoma caninum hookworm, two parasite-encoded TGF-beta-like ligands were cloned and characterised. Ac-dbl-1 showed 60% amino acid identity to the Caenorhabditis elegansdbl-1 gene, which regulates growth while Ac-daf-7 showed 46% amino acid identity to Ce-daf-7 which regulates arrested development. Exon/intron organisation of the genes for Ac-dbl-1 and Ac-daf-7 were different from that of the corresponding C. elegans genes with nine and 10 exons, respectively, and introns ranging in size from 56 to 2,556 bp. Based on real-time reverse transcriptase (RT)-PCR, Ac-dbl-1 and Ac-daf-7 were expressed in all stages tested, i.e. egg, first/second stage larvae (L1/L2), infective third stage larvae (iL3), serum-stimulated third stage larvae (ssL3), and male and female adult worms. Expression of Ac-dbl-1 peaked in the adult male stage suggesting a similar role to Ce-dbl-1 in regulating male tail patterning. Ac-daf-7 expression was at a maximum in the arrested iL3 and reactivated ssL3 stages, which differs from that of Ce-daf-7 expression and may be unique to parasitic nematodes that have an obligate requirement to undergo developmental arrest. In support of the PCR results, antibodies to the A. caninum TGF-beta-like ligands detected proteins in iL3, ssL3, and adult worm extracts. Immunofluorescent studies showed that Ac-daf-7 is expressed in the anterior region of the iL3 similar to Ce-daf-7, which is localised to the ASI chemosensory neurons.

Amino Acid Sequence↗

PubMed2005

Expression of the Necator americanus hookworm larval antigen Na-ASP-2 in Pichia pastoris and purification of the recombinant protein for use in human clinical trials.

The ASP-2 protein secreted by infective larvae of the human hookworm, Necator americanus, is under development as a recombinant vaccine. Recombinant Na-ASP-2 was expressed in Pichia pastoris, and the purified protein was characterized. At the 60 L scale, the 21.3 kDa recombinant protein was produced at a yield of 0.4 g/L. When formulated with Alhydrogel and injected into rats to determine immunological potency, three 50 microg doses of the formulated recombinant protein elicited geometric mean antibody titers up to 1:234,881. Rat anti-Na-ASP-2 antibody recognized larval-derived ASP-2 and also inhibited larval migration through skin in vitro. The processes developed and tested for the high yield production of recombinant Na-ASP-2 provide a foundation for clinical vaccine development.

Animals↗

PubMed2006

High-level pyrantel resistance in the hookworm Ancylostoma caninum.

While anthelmintic resistance is now a widely recognized issue in the livestock industries, its existence within companion animal medicine has been rarely established conclusively. We undertook a placebo-controlled in vivo trial to measure the efficacy of pyrantel embonate against pooled isolates of the hookworm Ancylostoma caninum from Brisbane, Australia. A statistically significant fall in adult worm burden was observed among dogs in the pyrantel treatment group compared to the control dogs (178.0+/-24.5 versus 239.7+/-14.0; p=0.02), equating to an efficacy of just 25.7% (95% CI, 15.0-35.1%), as based upon reduction in mean worm burden. Analysis of faecal egg count trends through the course of the study revealed that egg counts rose in both control and pyrantel-treated dogs, with a greater rise observed in the latter group (11.6+/-8.3% versus 17.3+/-7.6%; p=0.04), despite the decrease in adult worm numbers in this group. Our results indicate that high-level anthelmintic resistance does occur in companion animal medicine, and highlight the need for greater vigilance and more judicious use of anthelmintics in small animal practice. They further indicate that the faecal egg count reduction test needs to be used with caution with this parasite.

Ancylostoma↗

PubMed1998

Cutaneous and subcutaneous granulomata formation in mice immunized and challenged with third-stage infective hookworm (Ancylostoma caninum) larvae.

To determine the inflammatory and immunological mechanisms associated with live third-stage (L3) hookworm larval vaccines, mice were immunized either subcutaneously or orally with three doses of 500 L3 of Ancylostoma caninum at 2-week intervals, and then challenged percutaneously (via abdominal skin) with 500 L3. Non-immunized mice served as negative controls. Skin was excised from post-challenge mice at intervals between 6 h and 28 days, and then examined by light microscopy. In non-immunized mice the L3 exhibited no structural damage and infiltrating inflammatory cells were absent from the surrounding tissues. There were no changes in the cutaneous architecture. In contrast, skin recovered from the immunized mice was edematous and exhibited marked inflammatory changes with resultant destruction of the challenge L3. At 6 h post-challenge the L3 exhibited cuticular swelling and damage; the surrounding tissue was infiltrated by polymorphonuclear inflammatory cells. By 24 h granulomata in the dermis, subcutaneous tissues and underlying abdominal muscles were first observed surrounding dead L3. The number of granulomata peaked at 72 h, with the majority distributed in the subcutaneous tissues. Plasma cells predominated in the early granulomata, but by 3-7 days post-challenge foreign body giant cells began to appear. In some cases, intact and presumably living L3 were noted in the abdominal muscles 14-28 days post-challenge, which suggested that protection against larval challenge was not absolute. Granuloma formation appears to be a major component of the post-vaccination murine host immune response against challenge larvae. The observation generates several hypotheses to investigate the mechanisms of protection afforded by living helminth vaccines.

Abdominal Muscles↗

PubMed2003

Successful vaccination of BALB/c mice against human hookworm (Necator americanus): the immunological phenotype of the protective response.

In this murine (BALB/c) model of necatoriasis, high levels of protection against challenge infection by Necator americanus larvae (n=300) were afforded by successive vaccinations at 14-day intervals, either subcutaneously or percutaneously, with gamma-irradiated N. americanus larvae (n=300). Percutaneous vaccination was significantly more effective than the subcutaneous route, with pulmonary larval burdens at 3 days post-infection being reduced by 97.8 vs. 89.3%, respectively, after three immunisations (P<0.05). No worms were recovered from the intestines of thrice vaccinated mice. Two percutaneous vaccinations also reduced worm burdens, by 57% in the lungs and 98% in the intestines; P<0.05. In vaccinated animals, lung pathology (mainly haemorrhage) following infection was greatly reduced compared with non-vaccinated animals. In vaccinated mice (but not in non-vaccinated mice) mast cells accumulated in the skin and were degranulated. RT-PCR analyses of mRNAs in the skin of vaccinated animals indicated increased expression of interleukin (IL)-4 relative to gamma-interferon (gamma-IFN). Lymphocytes from the axillary (skin-draining) lymph nodes of vaccinated mice, stimulated in vitro with concanavalin A, exhibited enhanced secretion of IL-4 protein and a higher IL-4/gamma-IFN protein ratio than lymphocytes from non-vaccinated animals. In vaccinated mice, levels of IgG1 and IgG3 (directed against larval excretory/secretory products) were elevated for the most part compared with those in non-vaccinated animals. These data demonstrate the successful vaccination of BALB/c mice against human hookworm infection and suggest that a localised Th2 response may be important for conferring protection against necatoriasis.

Animals↗