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PubMed1989

Single dose metrifonate or praziquantel treatment in Kenyan children. I. Effects on Schistosoma haematobium, hookworm, hemoglobin levels, splenomegaly, and hepatomegaly.

The relationships between S. haematobium, hookworm, malaria, hemoglobin level, splenomegaly, and hepatomegaly before and 8 months after treatment with a single dose of metrifonate or praziquantel were studied in Kenyan primary schoolchildren in an area where anemia, S. haematobium, and hookworm are common and malaria is holoendemic. Children with light to moderate S. haematobium infection were examined (Exam 1), assigned at random to groups receiving placebo (PL, n = 104), metrifonate (MT, n = 103, dose 10 mg/kg body weight) or praziquantel (PR, n = 105, dose 40 mg/kg body weight), treated, and examined 8 months later (Exam 2). At Exam 2, 62% of the MT group still passed S. haematobium eggs vs. 13% in the PR group. Egg reduction rates were substantial in both groups, but greater in the PR group; geometric mean egg counts in both groups were very low. Prevalence and intensity in the PL group had not changed between exams. Hookworm egg counts were significantly reduced in the MT group (59% egg reduction rate); malarial infection had increased in all 3 groups, presumably due to the long rainy season between exams. Hookworm egg count was the most significant predictor of initial hemoglobin level, followed by S. haematobium egg count and presence of malarial infection. Treatment with a single dose of MT or PR can produce substantial decreases in S. haematobium infection 8 months later.

Adolescent↗

PubMed2005

Hookworm infections in human and laboratory animals--differences and similarities in immune responses.

Hookworm infection is one of the most important parasitic infections of humans. About 740 million people are infected with Ancylostoma duodenale and Necator americanus in the tropics and subtropics. Unlike most other human helminth infections, neither age nor exposure-related immunity develops in the majority of infected people. This review presents the contemporary knowledge concerning the immune response to this complex eukaryotic parasite, recent findings on the human cellular immune responses to hookworms, as well as mechanisms used by the parasite to modulate the immune response in its favor. Also immunological responses in animal models of hookworm infection are presented. Animals in contrast to humans seem to easily deal with hookworm infections and gain protection during re-exposure.

Ancylostomatoidea↗

PubMed1991

Studies on the control of hookworm and other soil-transmitted helminthiases in farmers in Zhejiang Province, China.

Different periodic selective chemotherapeutic schemes were used to control hookworm and other soil-transmitted helminthiases in eight villages in five counties in Zhejiang Province, China, 1985-1988. The results showed that the prevalence rates of hookworm, ascariasis, and trichuriasis decreased from 35.0-74.4%, 47.0-.76% and 22.9-47.5% to 3.2-15.8%, 9.9-47.8%, and 3.5-31.2%, respectively, using pyrantel pamoate (10 mg/kg for 1-2 days) or albendazole (400 mg for 1-2 days, once or twice a year for 2-3 years). The eggs per gram of feces of hookworm and Trichuris trichiura also dropped markedly after control. Moreover, the mean hemoglobin levels of sampled populations increased after several treatments. The authors recommend periodic selective chemotherapy as the main method to control soil-transmitted helminthiases, especially hookworm infections.

Agriculture↗

PubMed1991

Effects of improved water supply and sanitation on ascariasis, diarrhoea, dracunculiasis, hookworm infection, schistosomiasis, and trachoma.

A total of 144 studies were analysed to examine the impact of improved water supply and sanitation facilities on ascariasis, diarrhoea, dracunculiasis, hookworm infection, schistosomiasis, and trachoma. These diseases were selected because they are widespread and illustrate the variety of mechanisms through which improved water and sanitation can protect people. Disease-specific median reduction levels were calculated for all studies, and separately for the more methodologically rigorous ones. For the latter studies, the median reduction in morbidity for diarrhoea, trachoma, and ascariasis induced by water supplies and/or sanitation was 26%, 27%, and 29%, respectively; the median reduction for schistosomiasis and dracunculiasis was higher, at 77% and 78%, respectively. All studies of hookworm infection were flawed apart from one, which reported a 4% reduction in incidence. For hookworm infection, ascariasis, and schistosomiasis, the reduction in disease severity, as measured in egg counts, was greater than that in incidence or prevalence. Child mortality fell by 55%, which suggests that water and sanitation have a substantial impact on child survival. Water for personal and domestic hygiene was important in reducing the rates of ascariasis, diarrhoea, schistosomiasis, and trachoma. Sanitation facilities decreased diarrhoea morbidity and mortality and the severity of hookworm infection. Better water quality reduced the incidence of dracunculiasis, but its role in diarrhoeal disease control was less important than that of sanitation and hygiene.

Ascariasis↗

PubMed1991

Parasitic diseases. Other roundworms. Trichuris, hookworm, and Strongyloides.

Trichuriasis may be asymptomatic or, in heavy infection, lead to profuse, bloody diarrhea and rectal prolapse. Diagnosis is made by finding the distinctive barrel shaped eggs in the stool or in the heavily infested patient, by anoscopy and identification of worms attached to reddened and ulcerated rectal mucosa. Mebendazole is the drug of choice in treatment. Capillariasis, a parasitic infection encountered mainly in the Philippine Islands, is of interest in that the eggs may be confused with the eggs of trichuris. Hookworm disease is generally asymptomatic, but in heavy infection, leads to iron deficiency and hypochromic, microcytic anemia. Diagnosis is made by finding the characteristic hookworm eggs on a examination of a direct fecal film. Accidental invasion of humans by dog and cat hookworm leads to cutaneous larva migrans, also known as "creeping eruption." Human hookworm is treated most effectively with mebendazole, while the rash produced by creeping eruption responds to topical thiabendazole. Strongyloides is fairly common in rural areas of the southeastern United States and may be seen in the urban setting among inmates of mental institutions, prisons, and in immigrants who formerly resided in endemic tropical regions. Because of its remarkable capacity for dissemination of larvae throughout the body, this parasite is now recognized as a serious problem for the patient who is immunocompromised. Diagnosis is made by finding larvae in the stool or by the Enterotest. All infected patients should be treated with thiabendazole. I consider the issue on Drugs For Parasitic Infections, published annually or biannually by The Medical Letter on Drugs and Therapeutics, to be the single best source of information on the treatment of parasitic diseases for primary care physicians.

Ancylostomatoidea↗

PubMed1989

Treatment with a single dose of albendazole improves growth of Kenyan schoolchildren with hookworm, Trichuris trichiura, and Ascaris lumbricoides infections.

We studied the growth of primary schoolchildren with hookworm (87%), T. trichiura (97%), and A. lumbricoides (49%) who received a single 400 mg dose of albendazole or an identical placebo. Children were allocated at random to placebo (PL, n = 72) or albendazole (A, n = 78) groups, treated, and re-examined 6 months later. The A group gained significantly more than the PL group in weight (1.3 kg), percent weight for age (4.5% age points), percent height for age (0.5% age points), percent weight for height (4.3% age points), percent arm circumference (2.9% age points), and in triceps and subscapular skinfold thicknesses (1.2 mm). The PL group showed significant decreases between exams in percent weight for age, percent height for age, percent weight for height, percent arm circumference for age, and skinfold thicknesses for age. The A group had highly significant increases (P less than 0.0002) in all of these parameters except height for age. From Exam 1 to 2, the A group exhibited decreases (P less than 0.0002) in geometric means eggs per gram of feces (epg): for hookworm, means = 1,183 epg at Exam 1 vs. 136 epg at Exam 2 (67% egg reduction); for T. trichiura, means = 2,857 epg at Exam 1 vs. 1,061 epg at Exam 2 (28% egg reduction); and for A. lumbricoides, means = 86 epg at Exam 1 vs. 2 epg at Exam 2 (91% egg reduction). The PL group had a borderline increase in geometric means hookworm egg count, no significant change in T. trichiura egg count, and a small but significant decrease in A. lumbricoides egg count. Decreases in intensities of all infections were significant predictors of growth improvement. Hookworm egg count entered the equations for all 6 measurements, and A. lumbricoides and T. trichiura entered 4/6 equations. Single dose treatment with albendazole, despite continual exposure to infection, can permit improved growth rates in areas where intestinal helminths and protein-energy malnutrition are highly prevalent.

Adolescent↗

PubMed1995

Molecular pathobiology of hookworm infection.

Within the past 2 years, progress has been made in the identification, isolation, and cDNA cloning of several macromolecules from hookworms. While the predicted amino acid sequences of some cDNAs resemble those from other nematodes, such as Caenorhabditis elegans, other cDNAs are unique to hookworms. Studies are under way to evaluate the function of these recombinant hookworm polypeptides with respect to the biology of hookworms in experimental animal models. The recombinant polypeptides are also under evaluation as vaccine targets and as natural products used in the treatment of human cardiovascular and autoimmune diseases.

Ancylostomatoidea↗

PubMedDate not supplied

Measurement of hookworm infection intensity and circulating levels of IgE and autoantibodies to IgE in atopics and nonatopics living in a parasitized community in Papua New Guinea.

We have compared hookworm infection intensity, as determined by fecal egg count, and circulating levels of IgE and autoantibodies to IgE in atopic and nonatopic parasitized (predominantly hookworm-infected) patients from Kebasob village on Karkar Island, Papua New Guinea. Our study has clearly established that parasitized atopic individuals have significantly higher levels of IgE and autoanti-IgE than their nonatopic counterparts, and that atopy does not appear to influence accumulated levels of hookworm infection. These data, therefore, do not support an earlier report that suggested that the atopic state may confer increased resistance to hookworm infestation in a parasitized community in Papua New Guinea.

Adolescent↗

PubMed1998

Eradication, control or neither? Hookworm vs malaria strategies and Rockefeller Public Health in Mexico.

Malaria's epidemiological importance in Mexico greatly exceeded that of hookworm, but the Rockefeller Foundation (RF) paid far more attention to hookworm. Although the RF collaborated with malaria campaigns around the world, malaria was only incidental to the RF's activities in Mexico. The hookworm campaign, on the other hand, involved the RF at every stage, from conceptualization and design to financing, hiring, and day-to-day administration. This paper seeks to understand why the RF's involvement in Mexico differed for the two diseases and what the organizational, political, and health implications were for these divergent approaches. Beginning in the mid 1920s the Mexican government developed a modest anti-larval service, periodically draining and filling ditches and swamps, dusting Paris green, petrolizing stagnant water, and administering quinine. Following the RF's 1927 shift towards scientific investigation, it began to sponsor small-scale malaria research, collecting climatological, entomological, epidemiological, and clinical information. The Mexican government eagerly petitioned the RF to join a national effort, but it was reluctant to become involved. A National Malaria Campaign was established in 1935 under President Lázaro Cárdenas to coordinate education, sanitary engineering, and treatment. The popular Campaign followed RF strategies even without its direct participation. Meanwhile, the RF avidly pursued modest malaria research in Mexico, funding U.S. investigators to conduct experiments on pesticides, mosquito-trapping, and controversially, watering methods for rice. These efforts culminated in the world's first field trial of DDT against louse-borne typhus and later as a residual spray for malaria. In the end the RF used Mexico as a convenient locale for scientific research that had global implications but only an incidental relationship to Mexico's own Malaria Campaign. Likewise, the RF's much more active hookworm program was more a means than an end, leading not to eradication of the disease, but to Mexico's commitment to modern public health organization and methods.

Animals↗

PubMed1994

Resistance of the hookworms Ancylostoma ceylanicum and Necator americanus to intestinal inflammatory responses induced by heterologous infection.

Experiments were carried out to ascertain whether the acute inflammatory phase of the intestinal response of hamsters to infection with Trichinella spiralis would adversely affect hookworms in concurrently infected animals. The survival and growth of hookworms were unaffected. However, the presence of hookworms reduced the establishment of T. spiralis, the initial growth of female worms and their fecundity. The expulsion of T. spiralis was also significantly slower in concurrently infected animals and there was significant depression of the serum IgG antibody response to muscle stage and adult worm antigens of T. spiralis in concurrently infected animals. These results are discussed in relation to the chronicity of human hookworm infections.

Acute Disease↗

PubMed1985

Hookworm burdens and faecal egg counts: an analysis of the biological basis of variation.

The relationships between various measures of faecal egg output and hookworm burdens were investigated in 84 villagers from West Bengal with mixed Necator americanus and Ancylostoma duodenale infections. The pattern of day to day variability in egg counts from individuals can be characterized by the linear relationship between the logarithms of the variances and means. Egg output is shown to be non-periodic in long runs of day-to-day records. The distribution of worm numbers per host is well described by the negative binomial probability model, and the relationship between per capita egg output and worm burden is non-linear where egg output declines as parasite burden rises. Density-dependent effects on fecundity are shown to act at comparatively low worm burdens in relation to the range of observed parasite loads. Egg output measures are shown to be qualitative as opposed to quantitative measures of worm burdens as a consequence of inherent sampling heterogeneity and variability induced by biological processes, such as density-dependent depression of parasite fecundity. The analyses suggest that it is possible, on the basis of egg counts, to discriminate between individuals with low and high hookworm burdens. The intrinsic per capita fecundities of the two species of hookworms are shown to be similar, but density-dependent constraints on egg production by N. americanus appear to be more severe than those acting on A. duodenale. This observation may help explain why A. duodenale appears to produce larger numbers of eggs per unit of time than N. americanus. The regulatory role of density-dependent fecundity and aggregated distributions of worm numbers per person are discussed in relation to the over-all transmission dynamics of hookworm parasites.

Adolescent↗

PubMed1985

Hookworm infection in Kweneng District, Botswana, A prevalence survey and a controlled treatment trial.

Stool specimens from a sample of schoolchildren at six schools in Kweneng District were examined for hookworm infection, using the brine flotation method. Necator americanus was the only hookworm identified. The western part of the District forms part of the Kalahari Desert, and in four villages here 90%, 88%, 88% and 86% of the children were infected. In two villages in the eastern non-desert part, only 13% and 9% were infected. Most infections were light. There was no significant correlation between severity of infection and anaemia. In one school (228 pupils; 86% infected with hookworm), half the children were treated with tetrachloroethylene (0.1 ml/kg, maximum 5 ml) and the other half with placebo. Two weeks after treatment the prevalence of infection were 28% and 75% respectively (p less than 0.001), and five months after treatment 51% and 69% (p less than 0.05). Measured over the five-month period there were no significant changes in haemoglobin and nutritional status (weight/height). Based on the results of the survey, a hookworm mass treatment programme was not recommended.

Adolescent↗

PubMed1986

Response of dogs to challenge with Ancylostoma ceylanicum during the tenure of a primary hookworm infection.

A model of human hookworm infection has been developed which shows that dogs currently infected with small numbers of hookworms are considerably resistant to a challenge infection with a large inoculum of infective larvae. Two groups of dogs were infected with 500 larvae and four weeks after infection one group together with a previously uninfected control group were infected with 5,000 larvae and followed for six weeks. When compared with the secondary infection control dogs, faecal egg excretion and adult worm burdens were reduced by an average of 83 and 78% respectively. Infections had no significant effect on total white cell counts, platelet levels or spontaneous, phytohaemagglutinin- and antigen-induced lymphocyte transformation among the three groups of dogs. Dogs previously uninfected with hookworm developed a marked anaemia when infected with 5,000 larvae but this was not observed in the superinfected group. An eosinophilia developed in all groups and there were no significant differences among the three groups of animals. Specific IgM antibodies developed transiently in all groups of dogs two weeks after infection. IgG antibody levels were significantly greater in the superinfected animals one, two and three weeks after challenge infection compared with the secondary infection control animals; by four weeks there was no significant difference between the two groups of animals. Both groups given the large inoculum of larvae developed specific IgA antibodies one week after the challenge infection and these continued to rise in the superinfected group until termination of the experiment. It is concluded that dogs currently infected with the hookworm, Ancylostoma ceylanicum, demonstrate the development of functional protective immunity.

Ancylostomiasis↗

PubMed2004

A pore-forming haemolysin from the hookworm, Ancylostoma caninum.

Hookworms feed on blood, but the mechanism by which they lyse ingested erythrocytes is unknown. Here we show that Ancylostoma caninum, the common dog hookworm, expresses a detergent soluble, haemolytic factor. Activity was identified in both adult and larval stages, was heat-stable and unaffected by the addition of protease inhibitors, metal ions, chelators and reducing agents. Trypsin ablated lysis indicating that the haemolysin is a protein. A closely migrating doublet of hookworm proteins with apparent molecular weights of 60-65 kDa bound to the erythrocyte membrane after lysis of cells using both unlabeled and biotinylated detergent-solubilised hookworm extracts. In addition, separation of detergent-soluble parasite extracts using strong cation-exchange chromatography, resulted in purification of 60-65 kDa proteins with trypsin-sensitive haemolytic activity. Erythrocytes lysed with particulate, buffer-insoluble worm extracts were observed using scanning electron microscopy and appeared as red cell ghosts with approximately 100 nm diameter pores formed in the cell membranes. Red blood cell ghosts remained visible indicating that lysis was likely caused by pore formation and followed by osmotic disruption of the cell.

Ancylostoma↗

PubMed2005

X-ray structure of Na-ASP-2, a pathogenesis-related-1 protein from the nematode parasite, Necator americanus, and a vaccine antigen for human hookworm infection.

Human hookworm infection is a major cause of anemia and malnutrition of adults and children in the developing world. As part of on-going efforts to control hookworm infection, The Human Hookworm Vaccine Initiative has identified candidate vaccine antigens from the infective L3 larval stages of the parasite, including a family of pathogenesis-related (PR) proteins known as the Ancylostoma-secreted proteins (ASPs). A novel crystal structure of Na-ASP-2, a PR-1 protein secreted by infective larvae of the human hookworm Necator americanus, has been solved to resolution limits of 1.68 A and to an R-factor of 17% using the recombinant protein expressed in and secreted by Pichia pastoris. The overall fold of Na-ASP-2 is a three-layer alphabetaalpha sandwich flanked by an N-terminal loop and a short, cysteine-rich C terminus. Our structure reveals a large central cavity that is flanked by His129 and Glu106, two residues that are well conserved in all parasitic nematode L3 ASPs. Na-ASP-2 has structural and charge similarities to chemokines, which suggests that Na-ASP-2 may be an extra-cellular ligand of an unknown receptor. Na-ASP-2 is a useful homology model for NIF, a natural antagonistic ligand of CR3 receptor. From these modeling studies, possible binding modes were predicted. In addition, this first structure of a PR-1 protein from parasitic helminths may shed light on the molecular basis of host-parasite interactions.

Amino Acid Sequence↗

PubMedDate not supplied

Patterns of concurrent hookworm infection and schistosomiasis in schoolchildren in Tanzania.

A cross-sectional study of 6897 schoolchildren in 59 out of the 155 primary schools in Magu District on the shores of Lake Victoria, Tanzania, was undertaken in 1997 to determine the prevalence of single- and multiple-species helminth infection. Schistosoma haematobium, hookworm (primarily Necator americanus) and S. mansoni were the most common helminth species infecting schoolchildren in the district. The prevalences of Ascaris lumbricoides and Trichuris trichiura were negligible (< 1%). Anaemia and stunting were highly prevalent and widespread. Hookworm and S. mansoni occurred more frequently in multiple infections with other helminths than as single-species infections, but triple-species infection was rare. Analysis of the frequency distribution of infection amongst schools showed that prevalences of S. haematobium and hookworm tended to be normally distributed, with medians 75% and 45%, respectively, while the distribution of S. mansoni was markedly skewed such that only 17% schools had a prevalence greater than 20%. An inverse association between S. mansoni and S. haematobium was observed. Geographical information system (GIS) analysis indicated that S. mansoni infection was highly prevalent only along the shore of Lake Victoria, whilst S. haematobium was homogeneously prevalent everywhere except the lakeshore. This pattern appears to reflect the distribution of schistosome species-specific snail intermediate hosts. The results imply that joint treatment for hookworm infection and schistosomiasis would be beneficial throughout the district.

Age Distribution↗

PubMed2001

Ancylostoma caninum anticoagulant peptide-5: immunolocalization and in vitro neutralization of a major hookworm anti-thrombotic.

Hookworm infection is a major cause of gastrointestinal blood loss and iron deficiency anemia in the developing world. Recently two major anticoagulant serine protease inhibitors have been identified and cloned from adult Ancylostoma caninum hookworms. One of these, A. caninum anticoagulant peptide 5 (AcAP5), is a potent and specific inhibitor of human coagulation factor Xa. A polyclonal IgG has been purified from rabbits immunized with recombinant AcAP5 using affinity chromatography. Using immunohistochemistry, the polyclonal alpha-rAcAP5 IgG localized to the cephalic or amphidial glands, confirming previous biochemical studies that had identified this secretory gland as the primary source of anticoagulant activity in the adult worm. This polyclonal IgG also neutralized the inhibitory activity of recombinant and native AcAP using a single stage chromogenic assay of coagulation factor Xa activity. In addition, the polyclonal IgG also neutralized the anticoagulant activity of native and recombinant AcAP5 as measured by the activated partial thromboplastin time clotting assay. Importantly, this neutralizing activity is species specific, as the polyclonal IgG failed to neutralize the anticoagulant activity of A. ceylanicum. Taken together, these data suggest that the hookworm anticoagulant AcAP5 represents a viable target for future immunization strategies aimed at inhibiting the ability of the adult hookworm to feed on blood in vivo.

Ancylostoma↗

PubMed1996

Structural analysis of the catalytic site of AcCP-1, a cysteine proteinase secreted by the hookworm Ancylostoma caninum.

Previously, we have reported that hookworms secrete cysteine proteinase activity that is capable of cleaving the cathepsin L-specific substrate Z-Phe-Arg-AMC. We have also reported the gene sequences of novel cathepsin B-like proteinases from hookworms, but have been unable to locate cathepsin L-like genes that could account for the presence of the cathepsin L activity in these parasites. Here we present an homology model for the secreted hookworm cysteine proteinase AcCP-1 based upon the crystal structure co-ordinates of human cathepsin B. The model predicts that substrate binding and specificity differs between AcCP-1 and cathepsin B, and demonstrates that AcCP-1 would preferentially cleave Phe-Arg over Arg-Arg. This thereby provides an explanation for our previous observations that the hookworm proteinase, while structurally cathepsin B-like, displays a cathepsin L-like substrate specificity.

Amino Acid Sequence↗