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Identification of human hookworm in failed-treatment cases using Chinese hamsters (Cricetulus griseus) and scanning electron microscopy.

An attempt was made to identify the human hookworm involved in failed-treatment cases using abnormal hosts and scanning electron microscopy. Thirty-seven, 2 to 6 month old Chinese hamsters (Cricetulus griseus) from a closed, outbred, conventional colony, were each given between 20 and 120 filariform larvae per os. The larvae were cultured from faeces from mebendazole (Vermox) 500 mg single-dose, failed-treatment cases living in the lowveld farming area of the Transvaal Province, South Africa. About 60 to 78 days after inoculation, the animals were killed and adult worms were removed from their small intestines. Eleven (30%) of the 37 hamsters harboured a total of 31 adult worms (19 males and 12 females), while 26 hamsters were refractory to infection. The greatest number of worms recovered from a single animal was six. A total of 27 worms (17 males and 10 females) were subjected to examination by scanning electron microscopy. Micrographs showed male and female worms to be morphologically all of the Necator americanus species, as identified by a pair of ventral and dorsal cutting plates, a dorsal tooth and the fused terminus of spicules in the male bursa. The transverse cuticular striations were distinct and smooth. Several points of interest arose from the results of this study and are discussed.

Animals↗

Evidence for predisposition in humans to infection with Ascaris, hookworm, Enterobius and Trichuris in a South Indian fishing community.

Studies of patterns of reinfection with four species of intestinal nematodes (Ascaris, hookworm, Trichuris and Enterobius) in 174 individual patients following chemotherapeutic treatment revealed statistical evidence for predisposition to heavy or light infection (relative to the average level in the overall population). Analyses of associations between the abundances of the four species of nematodes within a combined sample of 525 worm burdens showed significant correlations between 5 out of the 6 possible pair-wise comparisons between species. The relevance of these results to the design of control programmes based on chemotherapeutic application is discussed.

Adolescent↗

Strongyloides and hookworm in Papua New Guinea: longitudinal studies on treated and untreated children.

Helminth egg counts were made on 86 treated and 38 untreated children in an isolated Papua New Guinea community before treatment and on nine subsequent occasions over an 18-month period. No predisposition could be detected to heavy or light infection with hookworm, either in the rate of reinfection or in the maximum post-treatment egg counts. Indications of predisposition in Strongyloides cf. fuelleborni were not statistically significant. In untreated children, sequential age-standardized hook-worm egg counts remained significantly correlated with each other at time lags up to nine months, but those for Strongyloides showed good correlation if made up to 14 months apart. Possible explanations include a surprising longevity of Strongyloides worms or unexpected external auto-infection.

Animals↗

Physical activity and growth of Kenyan school children with hookworm, Trichuris trichiura and Ascaris lumbricoides infections are improved after treatment with albendazole.

Growth, activity, appetite and intestinal helminth infections were compared for 55 Kenyan primary school children with hookworm (93% prevalence), T. trichiura (84% prevalence) and A. lumbricoides (29% prevalence) before and 9 wk after treatment with three 400-mg doses of albendazole (Zentel) or placebo. Fecal samples were examined for helminth eggs using a modified Kato technique. Activity was measured during free-play with motion recorders on the dominant thigh. Children rated their appetites on a 5-point scale. After baseline measurements, children were randomly allocated to the albendazole-treated (n = 28) and placebo (n = 27) groups, treated, and re-examined 9 wk later. At follow-up, egg counts were significantly lower than at baseline in the albendazole-treated group (P < or = 0.002), and gains in activity, reported appetite and most indices of growth were significantly greater for the albendazole-treated group than for the placebo group. We conclude that treatment of undernourished school children for intestinal helminth infections with albendazole may improve growth and appetite and increase spontaneous physical activity.

Albendazole↗

Distinction of human hookworm larvae based on lectin-binding characteristics.

A comparative study of lectin binding to ensheathed (EnL3) and exsheathed (ExL3) L3 larvae of Necator americanus, Ancylostoma duodenale and Ancylostoma ceylanicum revealed a number of differences between these hookworm species. These differences could provide a novel approach to distinguish infective L3 larvae in field conditions. For example, binding of Ulex europaeus agglutinin (UEA) and Ricinus communis agglutinin (RCA120) to N. americanus EnL3 distinguished them from those of A. duodenale and A. ceylanicum. Furthermore, UEA and RCA120 negative EnL3 could be separated into the two Ancylostoma sps. tested, as Dolichos biflorus agglutinin and Soybean agglutinin bound to EnL3 of A. ceylanicum but not to those of A. duodenale.

Ancylostoma↗

Transient non-thrombocytopenic purpura in hookworm infestation.

The transient purpura in 3 young men with marked eosinophilia and hookworm infestation was found to be caused by a qualitative platelet defect which manifested as a failure of platelets to aggregate with collagen and an absence of the secondary phase aggregation with epinephrine. These aggregation abnormalities could not be normalized with normal plasma, nor did patient plasma inhibit normal platelets, implying that the dysfunction was not caused by an abnormality in the plasma but was an intrinsic platelet defect. Arachidonic acid induced enhanced aggregation and a mutual correction of the absent secondary epinephrine-induced aggregation was observed when patient and aspirin-treated platelets were mixed together, suggesting that the defect was unlikely to be related to the platelet prostaglandin synthesis pathway. We propose that the acquired platelet dysfunction was caused by impaired ADP release due possibly to a transient platelet storage pool abnormality.

Adult↗

Predisposition to hookworm infection in humans.

Frequency distributions of parasitic helminths within human communities are invariably highly aggregated, the majority of worms occurring in relatively small fractions of the host populations. It has been suggested that the heavily infected individuals are predisposed to this state, not by chance, but by as yet undefined genetic, ecological, behavioral, or social factors. Analyses of individual post-treatment patterns of hookworm reinfection among 112 villagers in an endemic area of West Bengal provide quantitative evidence of predisposition to heavy infection. This observation has implications for the design of control programs based on chemotherapy because of the potential economic advantage of selective or targeted treatment as opposed to mass or blanket treatment.

Ancylostoma↗

Intraperitoneal blood transfusion in African adults with hookworm anaemia.

Twenty-nine patients were given an intraperitoneal transfusion of blood. The procedure was found to be free of serious complications. Study of the absorption of an (51)Cr-labelled cells from the peritoneum in 14 patients showed that between 35 and 100% of the blood was absorbed intact in 6 to 10 days. Intraperitoneal transfusion may be indicated as an alternative or as an addition to exchange transfusion in severe hookworm anaemia.

Absorption↗

Gastric acid secretory responses to graded intravenous doses of histamine in hookworm anemia.

Dose-response curves for the effect of continuous infusion of histamine on gastric acid secretion were obtained in 10 patients with iron deficiency anemia due to hookworm infection. Each patient was studied with 4 doses (40, 60, 80 and 100 mug/kg/h) of histamine acid phosphate administered for 3 h, on separate days, in random fashion. The acid output increased with the dose of histamine, the maximal acid output was reached in all patients at the dose of 100 mug/kg/h. The dose of histamine when calculated according to body weight correlated well with the maximal acid output; the absolute dose of histamine had no correlation with the maximal acid response. The dose-response curve of stimulated acid output in anemia patients was much flatter than in control patients.

Adolescent↗

Immunogenicity of the hookworm Na-ASP-2 vaccine candidate: characterization of humoral and cellular responses after vaccination in the Sprague Dawley rat.

The recombinant larval protein Na-ASP-2 from the human helminth parasite Necator americanus is a lead candidate for a human hookworm vaccine. We have characterized the humoral and cellular immune responses elicited by the Na-ASP-2 formulated with the aluminum-based adjuvant Alhydrogel in the Sprague Dawley rat. We demonstrated that Na-ASP-2 vaccine induced a strong antibody response at all doses tested, as evidenced by high specific IgG1, IgG2a and IgM titers. High IgG antibody titers were maintained up to three months post vaccination and were boosted by an additional vaccine dose. Specific cell proliferation and a Th2 cytokine profile were also observed in peripheral blood of all rats immunized with the formulated vaccine. Host IL-6 levels were also significantly elevated. These data provide evidence that the immune response of the Na-ASP-2 vaccine is robust and durable and therefore suitable for the further clinical development of the Na-ASP-2 vaccine.

Adjuvants, Immunologic↗

Clinical trials of a new anthelmintic, 4-isothiocyanato-4'-nitrodiphenylamine (C.9333-Go/CGP 4540), for the cure of hookworm infection.

A new compound, 4-isothiocyanato-4'-nitrodiphenylamine (C.9333-Go/CGP 4540), was tried in 39 hospitalized patients with hookworm infection, using several treatment schedules. At effective dose schedules (125 mg X 3 given 4-hourly; 250 mg X 3, 8-hourly; 1,000 mg X 3, 12-hourly), the egg reduction was 96% to 100%; the zero egg-counts were confirmed by coproculture for larvae. The compound was very well tolerated. Transient and mild side effects--giddiness, diarrhea and sweating--were observed in only three patients. No toxic effects were seen as judged by serial organ function tests, except a transient and mild asymptomatic elevation of transaminases in one patient.

Adult↗

Population biology of hookworms in children in rural West Bengal. I. General parasitological observations.

Hookworm infection was studied over a 22-month period in 31-49% of a population of 1,803 1- to 10-year-old children in a rural area near Calcutta where both Necator americanus and Ancylostoma duodenale were prevalent. Half of the children were infected before age 5 and 90% were infected by age 9, when the mean egg count reached 2,000 eggs/g of feces. Infection was significantly heavier and more prevalent among males than among females, and greater among Muslims than among Hindus. These differences were apparent in children less than 2 years of age. Numerical factors were devised to adjust fecal egg counts for both the smaller fecal output of children and the increased dilution of eggs in watery feces as compared to formed feces. It is proposed that egg counts from 1- to 3-year-olds be multiplied by 0.3, those from 4- to 6-year-olds by 0.5, those from 7- to 9-year-olds by 0.6, and those from 10 to 12-year-olds by 0.7; differences in mean egg density among various fecal consistencies produced factors of 1, 1.5, 2, 3, and 3.5 by which the egg counts in formed, mushy-formed, mushy, mushy-diarrheic, and diarrheic feces should be increased.

Age Factors↗

Single dose metrifonate or praziquantel treatment in Kenyan children. II. Effects on growth in relation to Schistosoma haematobium and hookworm egg counts.

We studied the growth of comparable groups of children with light to moderate Schistosoma haematobium infections who received a single dose of metrifonate (MT, 10 mg/kg), praziquantel (PR, 40 mg/kg), or a placebo (PL). Children were re-examined 8 months later. The MT and PR groups gained significantly more than the placebo group in weight, percent weight for age, percent weight for height, arm circumference, and in triceps and subscapular skinfold thicknesses. The MT and PR groups did not differ significantly from each other. The placebo group showed statistically significant decreases or no change between exams in percent weight for age, percent weight for height, percent arm circumference, and both skinfold thicknesses; the MT and PR groups exhibited highly significant increases in these parameters (P less than 0.0002). The intensity of S. haematobium infection had decreased significantly in both the MT and PR groups, but especially in the PR group. Multiple regression analyses showed that a decrease in the intensity of S. haematobium infection was by far the most important predictor of growth rate after treatment for all 5 anthropometric measures tested; decreases in the intensity of hookworm infection was also significant for 2 of the 5 measures.

Adolescent↗

An in vitro larval motility assay to determine anthelmintic sensitivity for human hookworm and Strongyloides species.

With the implementation of programs to control lymphatic filariasis and soil-transmitted helminths using broad spectrum anthelmintics, including albendazole and ivermectin, there is a need to develop an in vitro assay for detection of drug resistance. This report describes an in vitro assay for measuring the effects of ivermectin and benzimidazoles on the motility of larvae of the hookworm species Ancylostoma ceylanicum, A. caninum, and Necator americanus, and Strongyloides species including Strongyloides stercoralis, and S. ratti. A dose-response relationship was demonstrated with each of the parasite species, with distinct differences observed between the various species. In pilot field testing of the assay with N. americanus larvae recovered from human fecal samples, a dose-response relationship was observed with ivermectin. While the assay has demonstrated the ability to determine drug responsiveness, its usefulness in resistance detection will require correlation with the clinical outcome among individuals infected with parasite strains showing different drug sensitivities.

Ancylostomatoidea↗

Efficacy of ivermectin and pyrantel pamoate combined in a chewable formulation against heartworm, hookworm, and ascarid infections in dogs.

Eight trials were conducted in dogs to document the efficacy of ivermectin (6 micrograms/kg of body weight) and pyrantel pamoate (5 mg of active pyrantel/kg) in a beef-based chewable formulation against Dirofilaria immitis, Ancylostoma caninum, Uncinaria stenocephala, Toxocara canis, and Toxascaris leonina. Three studies involved induced infection with D immitis, and 5 studies involved induced or natural infection with hookworms and ascarids. In 3 intestinal parasite trials, the efficacy of the combination chewable tablet was compared with each of its components. Results indicated that 1 component did not interfere with the activity of the other. In 1 heartworm and 2 intestinal parasite trials, the efficacy of pyrantel, ivermectin/pyrantel combination, or ivermectin with pyrantel dosage of 10 mg/kg was evaluated. The ivermectin/pyrantel combination was 100% effective in preventing development of D immitis larvae. Efficacy of the combined product against T canis, Toxascaris leonina, A caninum, and U stenocephala was 90.1, 99.2, 98.5, and 98.7%, respectively. In the intestinal parasite trials, each individual component was found not to interfere with the anthelmintic action of the other. Increasing the dosage of pyrantel to 10 mg/kg (2 x that in the combination) did not interfere with the efficacy of ivermectin against heartworm or increase the activity of pyrantel against intestinal parasites.

Administration, Oral↗

Coincident filarial, intestinal helminth, and mycobacterial infection: helminths fail to influence tuberculin reactivity, but BCG influences hookworm prevalence.

The prevalence of helminth and tuberculosis infections is high in South India, whereas Bacille-Calmette-Guerin (BCG) vaccine efficacy is low. Our aim was to determine whether concurrent helminth infection alters the ability to mount a delayed-type hypersensitivity response to tuberculin. In a cross-sectional study in southern India, individuals 6-65 years of age were screened for intestinal helminths, circulating filarial antigenemia, tuberculin reactivity, active tuberculosis, and history of BCG vaccination; 54% were purified protein derivative (PPD) positive, 32% had intestinal helminth infection, 9% were circulating filarial antigen positive, and 0.5% had culture-confirmed active tuberculosis. Only age and BCG vaccination were significantly associated with PPD reactivity; however, BCG vaccination was associated with a lower prevalence of hookworm infection relative to those without prior BCG vaccination. Neither intestinal helminth infection nor filarial infection was associated with diminished frequencies of PPD positivity. Our findings suggest that preceding helminth infection does not influence significantly the delayed-type hypersensitivity response to tuberculin.

Adolescent↗

Evaluation of a new antihelminthic for trichuriasis, hookworm, and stronglyloidiasis.

Mebendazole was tested in a double-blind trial for its efficacy in the treatment and control of enteric helminths. One hundred and twenty-two children from a community near the Gulf of Carpentaria, and from a community in Cape York Peninsula in northern Queensland were divided into two equal groups to receive a course of either mebendazole or placebo after the identification of one or more intestinal helminths in a single pretreatment specimen of faeces. Between the tenth and twentieth days after a four-day course of treatment, three specimens of faeces were collected from each child. Mebendazole cured trichuriasis in 75% of cases, and over-all egg reduction rate was 96%. The drug also cured hookworm in 13 out of 15 cases and Strongyloides sterocoralis infestation in 14 out of 21 cases. Mebendazole was ineffective against Hymenolepis nana. No cases of Ascaris lumbricoides infestation were present. No side effects or adverse reactions to the drug were noted and patient acceptance was excellent. Mebendazole appears to be a safe drug for use in the treatment of human parasitic intestinal nematode infestations, and should be especially useful in the treatment and control of trichuriasis.

Adolescent↗