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PubMed1993

A comparative study on the efficacy of albendazole and mebendazole in the treatment of ascariasis, hookworm infection and trichuriasis.

A comparative study of the efficacy of albendazole and mebendazole was carried out in Pattani Province in the southern part of Thailand. One hundred and ninety-six patients with single or multiple infections with Ascaris, hookworm, and Trichuris were randomized into 4 groups for different treatments. Stool examination by Kato-Katz technique were done before and on day 14 after treatment. Results of the study showed that (1) a single dose of 300 mg mebendazole (locally produced) resulted in cure rates of 50%, 0% and 0% and egg reduction rates of 87.3%, -15.3%, and 28.3%, for ascariasis, hookworm infection and Trichuris respectively; (2) a single dose of 300 mg mebendazole (original) resulted in cure rates of 100.0%, 9.1%, and 43.3%, and egg reduction rates of 100.0%, 72.0%, and 77.9%, for Ascaris, hookworm, and Trichuris respectively; (3) a single dose 500 mg mebendazole (original) resulted in cure rates of 100.0%, 30.2%, and 70.3%, and egg reduction rates of 100.0%, 70.4% and 89.9%, for Ascaris, hookworm, and Trichuris respectively and (4) a single dose of 400 mg albendazole (original) resulted in cure rates of 100.0%, 84.3%, and 67.4%, and egg reduction rates of 100.0%, 96.0% and 87.0%, for Ascaris, hookworm, and Trichuris respectively. Both mebendazole and albendazole are safe and no side effects were observed. The results of this study suggested that albendazole is the preferred benzimidazole derivative for mass treatment of multiple infections with Ascaris, hookworm, and Trichuris.

Adolescent↗

PubMedDate not supplied

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↗

PubMed1996

Hookworms in the Americas: An alternative to trans-Pacific contact.

Recent New World archaeoparasitological discoveries of hookworm in pre-European contexts have revived a long-standing debate about the origin of hookworms in the Americas. Historically, the climatic conditions of Beringia encountered by migrating people have been considered too harsh for tropical hookworms to survive, suggesting that hookworms must have been introduced into South America by 'storm-tossed' fisherman or explorers from Asia. Here, John Hawdon and Susan Johnston review the history of hookworms in the Americas, and propose an alternative to their trans-Pacific introduction based on the unique natural history of one of the human hookworms.

Journal Article↗

PubMed2002

The mitochondrial genomes of the human hookworms, Ancylostoma duodenale and Necator americanus (Nematoda: Secernentea).

The complete mitochondrial genome sequences were determined for two species of human hookworms, Ancylostoma duodenale (13,721 bp) and Necator americanus (13,604 bp). The circular hookworm genomes are amongst the smallest reported to date for any metazoan organism. Their relatively small size relates mainly to a reduced length in the AT-rich region. Both hookworm genomes encode 12 protein, two ribosomal RNA and 22 transfer RNA genes, but lack the ATP synthetase subunit 8 gene, which is consistent with three other species of Secernentea studied to date. All genes are transcribed in the same direction and have a nucleotide composition high in A and T, but low in G and C. The AT bias had a significant effect on both the codon usage pattern and amino acid composition of proteins. For both hookworm species, genes were arranged in the same order as for Caenorhabditis elegans, except for the presence of a non-coding region between genes nad3 and nad5. In A. duodenale, this non-coding region is predicted to form a stem-and-loop structure which is not present in N. americanus. The mitochondrial genome structure for both hookworms differs from Ascaris suum only in the location of the AT-rich region, whereas there are substantial differences when compared with Onchocerca volvulus, including four gene or gene-block translocations and the positions of some transfer RNA genes and the AT-rich region. Based on genome organisation and amino acid sequence identity, A. duodenale and N. americanus were more closely related to C. elegans than to A. suum or O. volvulus (all secernentean nematodes), consistent with a previous phylogenetic study using ribosomal DNA sequence data. Determination of the complete mitochondrial genome sequences for two human hookworms (the first members of the order Strongylida ever sequenced) provides a foundation for studying the systematics, population genetics and ecology of these and other nematodes of socio-economic importance.

Amino Acid Sequence↗

PubMedDate not supplied

Predisposition to hookworm infection in Papua New Guinea.

Reinfection with hookworm (Necator americanus) following chemotherapy was studied over 8 years in a rural village in Madang Province, Papua New Guinea. Faecal egg counts were performed on up to 202 individuals in July 1988, August 1990 and November 1996; the study population was treated after sampling in 1988 and 1990. Reinfection burdens in 1996 did not differ significantly from pretreatment burdens (in 1988), and were significantly higher than burdens in 1990. However, the prevalence of hookworm infection was significantly lower in 1996 than in either 1988 or 1990. There was significant predisposition to high or low hookworm burden between 1990 and 1996; this predisposition was stronger in children than adults. However, there was no detectable predisposition between 1988 and 1996 in individuals who had been treated 2 or more times between surveys. The mean weight of adult hookworms in individual hosts was measured in 1988 and 1990 using worms expelled after chemotherapy. There was a significant positive correlation between mean male hookworm weight in the 2 years, suggesting that individual hosts are predisposed to infection with heavy or light hookworms. These data suggest that differences in host susceptibility are involved in generating predisposition, but that longer-term variation in either exposure or susceptibility limits the period over which significant predisposition can be detected.

Adolescent↗

PubMed2003

Isolation and molecular cloning of a secreted hookworm platelet inhibitor from adult Ancylostoma caninum.

Hookworms, bloodfeeding intestinal nematodes, are a leading cause of iron deficiency anemia in the developing world. These parasites have evolved potent mechanisms of interfering with mammalian hemostasis, presumably for the purpose of facilitating bloodfeeding. Adult Ancylostoma caninum worm extracts contain an activity that inhibits platelet aggregation and adhesion by blocking the function of two cell surface integrin receptors, Glycoprotein IIb/IIIa and GPIa/IIa. Using rpHPLC, the hookworm platelet inhibitor activities have been purified from protein extracts of A. caninum. Because the two inhibitory activities co-purified through multiple chromatographic steps, have similar molecular masses and share identical N-terminal as well as internal amino acid sequence homology, it is likely that they represent a single gene product. A cDNA corresponding to the purified hookworm platelet inhibitor (HPI) protein has been cloned from adult A. caninum RNA, and the translated amino acid sequence shows significant homology to Neutrophil Inhibitory Factor and Ancylostoma Secreted Proteins, suggesting that these related hookworm proteins represent a novel class of integrin receptor antagonists. Polyclonal antibodies raised against the recombinant HPI protein recognize corresponding native proteins in A. caninum extracts and excretory/secretory products, and immunohistochemistry data have identified the cephalic glands as the major source of the inhibitor within the adult hookworm. These data suggest that HPI is secreted by the adult stage of the parasite at the site of intestinal attachment. As such, it may represent a viable target for a vaccine-based strategy aimed at interfering with hookworm-induced gastrointestinal hemorrhage and iron deficiency anemia.

Amino Acid Sequence↗

PubMed2003

Platelet parameters in subjects infected with hookworm.

Hookworm is an important intestinal parasite infection with high prevalence in tropical countries. In addition to iron deficiency anaemia, the human hookworm appears to have evolved a number of complementary strategies to overcome the host's haemostatic processes. These include the inhibition of blood coagulation, platelet aggregation and mediator release, and the secretion of fibrinogenolytic enzymes. In this work, we studied the platelets in the subjects with detection of hookworm infection from screening stool examination comparing to those without. One hundred subjects were included, studied for stool parasite and platelet parameters. Of our 100 subjects, hookworms were identified in stools of six cases, giving an infection rate equal to 6%. The platelet parameters of the subjects showed a statistically significant lowering of mean platelet volume (MPV) in the subjects with hookworm infection. Also, we detected a non-significant lower platelet count in subjects with hookworm infections. Of interest, the alteration in platelet size, identified by platelet parameters, has never been documented in the literature. This observation might be a pathological process or might be an accidental finding in our study.

Animals↗

PubMed1999

Antibody-dependent reductions in mouse hookworm burden after vaccination with Ancylostoma caninum secreted protein 1.

Vaccination of mice with either third-stage Ancylostoma caninum infective hookworm larvae (L3) or alum-precipitated recombinant Ancylostoma secreted protein 1 from A. caninum (Ac-ASP-1) results in protection against hookworm challenge infections. Vaccine protection is manifested by reductions in lung hookworm burdens at 48 h postchallenge. Mice actively immunized 4 times with Ac-ASP-1 also exhibited reductions in hookworm burden in the muscles. Hookworm burden reductions from Ac-ASP-1 immunization were associated with elevations in all immunoglobulin subclasses, with the greatest rise observed in host IgG1 and IgG2b. The addition of a fourth immunization resulted in even higher levels of IgG and IgE. In contrast, L3-vaccinated mice exhibited marked elevations in IgG1 and IgM, including anti-Ac-ASP-1 IgM antibody. Passive immunization with pooled sera from recombinant Ac-ASP-1-vaccinated mice also resulted in lung hookworm burden reductions. It is hypothesized that recombinant Ac-ASP-1 vaccinations elicit antibody that interferes with parasite larval migration.

Ancylostoma↗

PubMed2004

Vaccination of dogs with a recombinant cysteine protease from the intestine of canine hookworms diminishes the fecundity and growth of worms.

We expressed a catalytically active cysteine protease, Ac-CP-2, from the blood-feeding stage of the canine hookworm Ancylostoma caninum and vaccinated dogs with the purified protease. Dogs acquired high-titer, antigen-specific antibody responses, and adult hookworms recovered from the intestines of vaccinated dogs were significantly smaller than hookworms from control dogs. There was also a marked decrease in fecal egg counts and the number of female hookworms in vaccinated dogs. Ac-CP-2 is expressed by the parasite in the brush-border membrane of its alimentary canal, and anti-Ac-CP-2 antibodies were bound to the gut of hookworms from vaccinated dogs, which suggests that these antibodies were ingested by the parasites with their blood meal. IgG from vaccinated dogs decreased proteolytic activity against a peptide substrate by 73%, which implies that neutralizing antibodies were induced by vaccination. These results indicate that cysteine proteases involved in parasite nutrition are promising candidates as vaccines against hookworm disease.

Adjuvants, Immunologic↗

PubMed2004

Cellular responses and cytokine production in post-treatment hookworm patients from an endemic area in Brazil.

Human hookworm infections are distributed widely in tropical areas and have a significant impact on host morbidity and human health. In the present study, we investigated the cellular responsiveness and cytokine production in peripheral blood mononuclear cells (PBMC) from Necator americanus-infected schoolchildren who had recently received chemotherapy, and compared them with non-infected endemic controls. Hookworm patients and treated, egg-negative individuals showed a lower cellular reactivity against phytohaemagglutinin (PHA) and hookworm antigen when compared with egg-negative endemic controls. The baseline production of proinflammatory tumour necrosis factor-alpha (TNF-alpha) in PBMC from infected patients and treated, egg-negative individuals was elevated. On the other hand, PHA- or hookworm antigen-induced interleukin (IL)-12 and interferon (IFN)-gamma secretion was higher in endemic controls than in hookworm patients, who either continued egg-positive or were egg-negative after treatment. Also, PBMC from endemic controls secreted more IL-5 and IL-13 than the other patient groups. Opposite to that, the spontaneous as well as the antigen-driven IL-10 secretion was lower in endemic controls when compared with the other groups. In summary, patently hookworm-infected as well as egg-negative treated patients disclosed an elevated spontaneous cellular secretion of proinflammatory TNF-alpha, a prominent secretion of regulatory Th2-type IL-10 and an impaired production of IL-12, IFN-gamma, IL-5 and IL-13.

Albendazole↗

PubMed1996

Molecular approaches to vaccinating against hookworm disease.

Anthelminthic drug chemotherapy has failed as an acceptable approach to hookworm control in the less developed countries of the tropics. The development of a genetically engineered vaccine against hookworm infection would be a major advance in our efforts to control this parasitic disease. We have produced several lead recombinant hookworm vaccine antigens. Their development is based on scientific principles that were generated almost 70 years ago when investigators first began to attenuate living infective hookworm larvae. Those early studies on attenuated live vaccines highlighted the importance of secreted larval antigens for eliciting protective immunity in dogs challenged with Ancylostoma caninum. The two major secreted larval antigens have been recently identified as Ancylostoma secreted protein-1 (ASP-1) and ASP-2. The predicted amino acid sequences of the ASP cDNAs together with experimental immunogenicty data using the expressed recombinant protein suggest that the ASPs are promising vaccine antigens. Preliminary hookworm challenge data in mice immunized with recombinant ASP-1 helps to validate this assumption. Alternative vaccines based on either genetic immunization (DNA vaccines) or immunization with recombinant molecules expressed from adult hookworm cDNAs are also under evaluation. Optimization of vaccine route, delivery system, and adjuvant formulations will be required before future planned phase I testing in humans. Vaccine development for a target population living in rural areas of less developed countries will require innovative solutions to financing and manufacture.

Amino Acid Sequence↗

PubMed1996

Differentiation between the human hookworms Ancylostoma duodenale and Necator americanus using PCR-RFLP.

There are 2 major species of hookworms that infect humans. Ancylostoma duodenale and Necator americanus. Although traditionally considered to be identical for treatment purposes, there are significant life history differences between the species that must be considered for the rational design of chemotherapeutic and immunoprophylactic control strategies. However, identification of the species infecting a particular population has been problematic, as the eggs of the 2 species cannot be reliably differentiated by classical parasitological methods. A PCR-based technique for the differentiation of hookworm species that infect humans is reported. A fragment of the 3' untranslated region of the cAMP-dependent protein kinase catalytic subunit gene was amplified from A. duodenale and N. americanus genomic DNA using primers derived from the corresponding A. caninum cDNA. Digestion of the amplified DNA with the restriction enzymes HpaII, MboI, TaqI, and ThaI generated specific restriction fragment patterns unique to each species. The technique can distinguish between pure and mixtures of hookworm DNA and can amplify DNA from a single egg. The primers also amplify the fragment from the DNA of several other species of hookworms that infect humans and other animals. The technique is fast, simple, and hookworm specific and represents a considerable savings in time over current methods used for distinguishing between human hookworm infections.

Ancylostoma↗

PubMed2005

Risk factors and spatial patterns of hookworm infection among schoolchildren in a rural area of western Côte d'Ivoire.

This study is aimed at investigating the risk factors for hookworm infection among schoolchildren in a rural area of western Côte d'Ivoire and predicting and mapping the spatial distribution of infection. We used demographic and socio-economic data from a cross-sectional survey of 6-16-year-old schoolchildren from 56 schools. Infection with hookworm was determined by microscopic examination of stool samples employing the Kato-Katz technique and an ether-concentration method. Environmental data were derived from satellite images and digitised maps. Bayesian variogram models were applied to investigate the variation of hookworm infection in relation to demographic, socio-economic and environmental factors. The overall hookworm infection prevalence, based on the pooled microscopic diagnoses, was 43.3% and ranged from 5.4 to 79.1% in the schools surveyed. Bivariate analyses showed that sex, age, socio-economic status, elevation, rainfall and land cover were significantly associated with the spatial distribution of hookworm infection. The final multivariate spatial model consisted of the covariates age, sex, socio-economic status, elevation and land cover. When assuming non-stationary underlying spatial dependency, the results of the model suggested that spatial correlation depended on the location only marginally. We conclude that, at the current resolution, it seems more reasonable to target interventions based on well-established epidemiologic risk factors, rather than on spatial factors.

Adolescent↗

PubMed2002

Reduction in the prevalence and intensity of hookworm infections after praziquantel treatment for schistosomiasis infection.

Praziquantel exhibits activity against all major human schistosome parasites and has become the cornerstone for treatment and morbidity control of schistosomiasis. Praziquantel is also active against a wide range of trematodes, human and veterinary cestodes and displays cysticidal effects. To the best of our knowledge anthelminthic properties have never been documented. Here, we report a study among 96 schoolchildren from an area highly endemic for Schistosoma mansoni and hookworm infection, and place particular emphasis on the effect of praziquantel on the prevalence and intensity of hookworm infections. Stool specimens were screened over several consecutive days prior and 4 weeks after systematic administration of praziquantel. We found a significant reduction in the prevalence of hookworm infection from 75.0 to 40.6% (odds ratio (OR)=0.21; 95% confidence interval (CI): 0.11-0.40). Infection intensities, expressed by geometric mean egg counts of all children, were also reduced significantly from 10.7 to 2.0 eggs per gram stool (paired t-test=7.78, P<0.001). If these findings are confirmed in other epidemiological settings - following a similarly sensitive diagnostic approach - they might become of considerable relevance. In areas where both schistosome and hookworm coexist, and praziquantel is being recommended for schistosomiasis control, large-scale application of this drug might also reduce the burden of hookworms.

Adolescent↗

PubMedDate not supplied

Increased sensitivity of routine laboratory detection of Strongyloides stercoralis and hookworm by agar-plate culture.

The efficacy of agar-plate culture has been evaluated for the detection of Strongyloides stercoralis and hookworm, compared with direct smear, the formalin-ether sedimentation technique and the filter-paper method. Of 1085 stool samples from the routine laboratory service at King Chulalongkorn Memorial Hospital in Bangkok, 241 samples harboured S. stercoralis, 153 hookworm and 2 Rhabditis hominis. The recovery rate of S. stercoralis by agar-plate culture is significantly superior to the other methods (P < 0.005). The ratios of positive results from the methods used to the total number of S. stercoralis-positive cases were as follows: 1:1.03 by agar-plate culture, 1:1.85 by the filter-paper method, 1:1.98 by the sedimentation technique and 1:10.48 by direct stool smear. A similar trend of the efficacy ratio of each method was obtained for hookworm detection. The characteristic furrows left by hookworm larvae, and larvae and adults of S. stercoralis could be used for preliminary species identification. Daily search for furrows on agar plates for up to 6 consecutive days resulted in an increased sensitivity for diagnosis of both S. stercoralis and hookworm infections.

Adolescent↗

PubMed1987

Hookworms of dogs and cats.

Hookworms are probably the most faithful intestinal parasites of dogs and cats. Infecting all ages, they are life-threatening to the very young and potentially so to the fully mature hookworm-resistant host. Discussed in this article are the diagnosis of hookworm infection, the life cycle of hookworms, the cutaneous and intestinal manifestations of hookworm infection and disease, and the treatment and prevention of infection.

Ancylostomatoidea↗

PubMed2000

The epidemiology of human hookworm infections in the southern region of Mali.

Two surveys of hookworm (Necator americanus) infections, conducted three years apart (December 1994 and January 1998) in a village in the Sikasso region of Mali, revealed that overall prevalence of infection was 68.7% and 53%, respectively. In both years there was a highly significant difference between the sexes in the prevalence and abundance of infection, with male subjects carrying heavier infections than females. Both prevalence and abundance of infection increased with age, although in 1998 there was a strong interaction between sex and age, arising from the declining egg counts among 16-20-year-old females and the continuing increase among males, reinforced by the subsequent reduction among the older males (> or = 61 years) and concomitant increase among females. After controlling for the effects of age, sex and their interaction, a highly significant positive relationship was detected between faecal egg counts of individuals who were examined in both 1994 and 1998 (n = 134), indicating predisposition to infection. This relationship remained significant in each of 4 age classes spanning 7-79 years. The members of some family compounds were shown to carry heavier infections than expected whilst others were less infected, suggesting compound-related clustering of hookworm infections. The use of footwear increased with age but there was no significant relationship between the extent of use of footwear and the abundance of hookworm infection. Eyesight deteriorated with age and impaired vision was particularly prominent among the older sectors of the community, a legacy from the time when onchocerciasis was widely prevalent in the region. Although men with partially damaged eyes carried lower infections than expected for their age, no overall significant relationship was found between quality of vision and hookworm infections. These results are discussed in relation to hookworm epidemiology in general and in Mali in particular.

Adolescent↗

PubMed2001

Efficacy of DEC against Ascaris and hookworm infections in schoolchildren.

Diethylcarbamazine (DEC) is an important drug for treatment and control of lymphatic filariasis. To assess its possible effect on Ascaris and hookworm infections, we conducted a double-blind two-armed study with children in Tanzania. Twenty six Ascaris-infected children were given a single dose of DEC (6 mg/kg body weight) and 25 were given a placebo. Twenty children in the treatment group and eighteen controls were also infected with hookworms. One month after treatment the geometric mean intensity (GMI) of Ascaris egg output was reduced by 60.2% in the treatment group; two children (7.7%) had stopped excreting Ascaris eggs, and some Ascaris worms were also expelled. In hookworm-infected children in the treatment group, the geometric mean intensity of hookworm egg output was reduced by 6.7% 1 month after treatment. Neither for Ascaris nor for hookworm, however, was the observed reduction in egg output at 1 month after treatment statistically significant. The treatment efficacy of a single dose of DEC (6 mg/kg) in these infections therefore was low.

Adolescent↗