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PubMed1975

Clinical trials with mebendazole a new broad spectrum anthelmintic.

This paper presents our experience with mebendazole, a new broad-spectrum anthelmintic, in 91 cases with ascariasis, 71 cases with necatoriasis 54 cases with trichuriasis and 10 cases with T. saginata infection. Various dosage schedules were evaluated. In ascariasis, a single dose of 200 mg was effective in totally clearing the infection in 100 per cent cases. In necatoriasis 200 mg twice daily for four days was found to be the most effective dose. With this dose total eradication of the infection was seen in 92 per cent cases. In trichuriasis, 200 mg twice daily for four days totally eradicated the infection in 90 per cent cases. In T. saginata infection, the drug was totally ineffective. The anthelminitic activity of the drug was demonstrated by the recovery of roundworms, hookworms and whipworms from the stools. The drug was well tolerated. No side effects or toxic effects were seen in any of the cases.

Adolescent↗
PubMedDate not supplied

[1st clinical therapeutic trial of mebendazole in some cases of helmenthiasis in Cuba].

Due to the difficulties faced in the etiologic approach of trichuriasis as a result of the intolerance, reduced efficacy and toxicity of some drugs a clinical-therapeutic trial of mebendazole was started in 5-64 year-old patients with some form of helmynthiasis as trichuriasis, enterobiasis or necatoriasis. Coproparasitological examinations carried out 15, 30 and 45 days after the ingestion of the drug depicted an excellent cure rate (98% in trichuriasis; 100% in enterobiasis; and 85% in necatoriasis). Very few side-effects were found. This is the first clinical-therapeutic trial of mebendazole in parasitic diseases in our country, and it can be affirmed that results have been very positive and also that they are similar to those obtained by foreign authors.

Adolescent↗
PubMed2005

Cytokine and chemokine responses in patients co-infected with Entamoeba histolytica/dispar, Necator americanus and Mansonella perstans and changes after anti-parasite treatment.

This study examined the impact of concurrent parasite infections (amoebiasis, filariasis, necatoriasis) and the effect of anti-parasite treatment on cytokine and chemokine responses in singly and poly-parasitized patients. Cellular reactivity and parasite-specific Th1- and Th2-type cytokine and chemokine profiles were investigated before and six weeks after treatment. In those patients infected with three parasite species, cellular secretion of interleukin 5 (IL-5) and IL-12p40 by PBMC was strongly diminished (p<0.005) but IL-10 was elevated in parasite-infected patients (p<0.0001) in response to protozoa- and helminth-specific as well as bacteria-specific antigens. Macrophage inflammatory chemokines (MIP-1alpha/CCL3 and MIP-1beta/CCL4), macrophage-derived chemokine (MDC/CCL22) and neutrophil activating chemokine (IL-8/CXCL8) were produced by PBMC in similar amounts in endemic controls and singly and poly-parasitized patients, but thymus and activation-regulated chemokine (TARC/CCL17) was produced the highest by PBMC from patients with triple parasite infections (p<0.0001). Following anti-parasite therapy, secretion of IL-12p40 and IL-5 augmented significantly in treated patients while IL-10, MDC, MIP-1alpha, TARC and IL-8 substantially diminished (all p<10(-5)) when their PBMC were activated with parasite- and bacteria-specific antigens. In summary, PBMC from poly-parasitized patients responded to protozoa- and helminth-specific antigens with a compromised IL-5 and IL-12p40 but high IL-10 and a substantial chemokine release. Chemokines may attract and activate effector cells in peri-parasitic tissues to limit parasite proliferation and dissemination, while depressed IL-5 and IL-12p40 but prominent IL-10 may prevent eosinophil and cytotoxic cell-mediated inflammatory processes and pathogenesis to the host. The changes in this profile following anti-parasite therapy disclosed the dynamics of an immune adaptation associated with parasite accumulation and also with clearance of parasite infections.

Adult↗
PubMed1990

Necator americanus in the DSN hamster: density-dependent expulsion of adult worms during primary infection.

Neonatal hamsters were exposed to varying doses of Necator americanus larvae and changes in the stability of the resulting worm burdens were monitored over a period of 25 weeks. No change in worm burdens was evident for the first 5 weeks of infection, irrespective of the infection intensity, but the more heavily infected groups subsequently lost worms in a density-dependent manner. Male and female hamsters lost comparable proportions of their established parasite burdens indicating that there was no host sex-linked difference in this respect. By week 15 infections had stabilized and the residual worm burdens, usually a maximum of 30 worms survived for a considerably longer period of time. Initially the percentage of male worms varied from 45% to 50% but as infection progressed male worms comprised a significantly increasing proportion of the total worm burden. By week 25 the percentage of male worms was usually in excess of 60%. The growth of infected animals was not severely affected by N. americanus, even when heavy worm burdens established initially, but a significant effect was detected particularly in week 5, prior to worm loss, when the adult worms would have been feeding on intestinal tissues and causing blood loss for a period of about 2 weeks. The most severe depression in the packed cell volume was also recorded in week 5, indicating that anaemia had been initiated in infected hamsters. Whilst, the regulation of parasite burdens in weeks 5-10 post-infection may have resulted from host immunity, the persistence of the residual worm burdens, the marked density-dependent anaemia and the subtle effect on host weight, all reflected well-documented aspects of chronic human necatoriasis.

Animals↗
PubMed1985

Single dose mebendazole therapy for soil-transmitted nematodes.

Four hundred and fifty subjects were included in a study of the prevalence of soil-transmitted nematodes in Ujung Pandang, South-Sulawesi, Indonesia. Trichuriasis was the most prevalent infection (93.3%), followed by ascariasis (80.2%) and hookworm infection (19.5%). Among 156 subjects who were given 500 mg of mebendazole in a single dose, treatment resulted in cure rates of 93.4%, 77.6%, and 91.1%, and average egg-count reduction rates of 99.0%, 92.8%, and 98.3%, for ascariasis, trichuriasis, and hookworm infections, respectively. Mebendazole appeared to be equally effective against necatoriasis and ancylostomiasis. The drug was well tolerated and almost no side effects were observed. Single dose mebendazole treatment appears to be relatively inexpensive, convenient, and effective in mass treatment for the control of intestinal nematode infections, especially in highly infected communities.

Ascariasis↗
PubMed1991

Mass treatment of intestinal parasites among Ethiopian immigrants.

Intestinal parasites are common among the Ethiopian immigrants to Israel and mass treatment is necessary to prevent local transmission. For this purpose, stool samples obtained from the immigrants in absorption centers were examined. Of 5,412 samples obtained, 4,399 (81.3%) were positive: 2,644 (54.2%) for Necator americanus, 2,273 (46.6%) for Schistosoma mansoni, 990 (20.3%) for Ascaris lumbricoides, 1,040 (21.3%) for Hymenolepsis nana, 940 (19.2%) for Trichuris trichiura, 219 (4.5%) for Strongyloides stercoralis, 17 (0.4%) for Fasciola hepatica, 551 (11.3%) for Giardia lamblia, and 499 (9.2%) for Entamoeba histolytica. The cure rate for necatoriasis by treatment with 400 mg of albendazole was 84.4% (better than with other drugs), either alone or in combination (pyrantel with bephenium or pyrantel with praziquantel, or praziquantel with albendazole). Albendazole, 400 mg for 3 days, cured 92% of the cases of S. stercoralis infection. Praziquantel, 40 mg/kg body weight, in a single dose was effective in 89.7% of cases of S. mansoni, and 60% of cases of H. nana, although a 100% cure rate for H. nana was achieved with praziquantel at a dose of 20 mg/kg per day for 2 days. Two persons infected with F. hepatica were cured by 40 mg/kg praziquantel for 7 days. Tinidazole, 2 g in a single dose, cured 100% of persons infected with G. lamblia, while 60% of persons infected with E. histolytica were cured when treated with 2 g tinidazole for 3 days. Mass treatment of all the immigrants with 400 mg albendazole and 40 mg/kg praziquantel concomitantly resulted in a cure rate of 84.4% of all intestinal worms.

Adolescent↗
PubMed1996

[Epidemiology of certain endemic parasitic diseases in the town of Guadalupe (Republic of Sao Tome and Principe) I. Schistosomiasis intercalatum and intestinal worms].

Schistosomiasis intercalatum in known to exist in Saõ Tomé since 1988, (Corachan et al.). It is transmitted by Bulinus forskalii, (Brown et al., 1989). Stool, blood and urine specimens have been collected from 380 inhabitants of all age groups living in the small town of Guadalupe close to the Agua Traź river and Agua Polino. The prevalence of schistosomiasis by detection of S. intercalatum eggs in a 10 mg stool thick smear (Kato technique) is 25.5%. An excreted Schistosoma polysaccharide antigen, detected by means of a monoclonal antibody (Ripert et al., 1992), is found in 49.1% of the urine samples. Patients voiding S. intercalatum eggs in stools have been treated with praziquantel (40 mg/kg body weight), as recommended by WHO Expert Committee on Schistosomiasis, but it might be wise to also treat persons excreting antigen in urine. The prevalence of intestinal helminthiasis, ascariasis (73.7%), trichuriasis (73.7%) and necatoriasis have been measured.

Adolescent↗
PubMed2002

Innate and cognate mechanisms of pulmonary eosinophilia in helminth infection.

Passage of helminth larvae through the lungs can cause pulmonary eosinophilia that may have evolved as a means of parasite attrition. If allergic responses represent a misdirected activation of this arm of the immune system, then mechanisms governing eosinophil recruitment during infection would be expected to be closely related to those seen in allergy. We studied primary Necator americanus infection and compared this to multiply-infected or vaccinated mice. The arrival of larvae in the lungs triggered rapid eosinophil recruitment, which was greatly enhanced in previously sensitized mice. Interestingly, the presence of larvae in the lung was sufficient to trigger eosinophil chemoattractant production, including the chemokines eotaxin and MIP-1alpha, and was not enhanced by prior exposure to the parasites. Infection stimulated IL-5 production in all groups; however, this and IgE production were greatly enhanced in sensitized animals. Elevated IL-5 increased bone marrow production of eosinophils, and eosinophilia was abrogated by treatment with anti-IL-5 antibody. Therefore, trapping of larvae in the pulmonary vasculature is sufficient to trigger eosinophil recruitment, by induction of chemokines and IL-5. Primed cognate Th2 immunity does not increase local chemokine production, but does increase IL-5 production, which greatly enhances the availability of eosinophils for recruitment to the lung.

Animals↗
PubMed1990

Necator americanus in the mouse: histopathological changes associated with the passage of larvae through the lungs of mice exposed to primary and secondary infection.

The mouse/Necator americanus model was studied to assess the histopathological changes that occur in the lungs following primary and secondary exposure to infective larvae. Groups of BALB/c mice were infected percutaneously and killed on various days post infection. Parasite numbers were counted, the bronchoalveolar leukocyte response was quantified and histological sections of lung material were examined for evidence of host protective inflammatory reactions. An increase in the inflammatory infiltration was observed between days 5 and 9 in both primary and secondary infections but was considerably more intense in re-infected animals. This involved a marked change in the character of the infiltrate, particularly in the number of eosinophils that were recovered in lavage fluid. More worms were trapped in the lungs of challenged mice, as assessed through their inability to escape from lung material incubated in vitro. Overall, the results were found to be compatible with the development of acquired resistance to N. americanus and the expression of host protective immunity during the development of challenge-infection larvae in the lungs.

Animals↗
PubMed1980

IgE levels in intestinal juice.

This investigation was performed to determine the possible significance of the IgE levels in intestinal secretions for the recognition of type I food allergy (immediate hypersensitivity). Four groups of individuals were studied and compared with each other: (1) healthy controls and patients with gastrointestinal disorders not affecting the small intestine; (2) patients with small intestinal disease; (3) patients with various manifestations of allergy but without food intolerance; and (4) patients with atopic sensitivity to foods. Despite the presence of proteolysis in the intestinal fluid, a statistically highly significant increase of the intestinal IgE level was observed in patients of group 4 with type I food allergy and in patients of group 3 as compared with normals. This was associated with an increase in the serum IgE level. An increased synthesis of the IgE in the lamina propria of the small intestine is most probable, but not yet adequately established.

Ancylostomiasis↗
PubMed1987

Differential efficacy of mebendazole and albendazole against Necator americanus but not for Trichuris trichiura infestations.

The effect of single oral doses of albendazole 600 mg and mebendazole 1 g given to 56 and 60 men, respectively, with T. trichiura and/or N. americanus infestation has been studied. Both albendazole and mebendazole cured more than 90% of T. trichiura infestations, but only albendazole (95%) and not mebendazole (21%) had a high cure rate for N. americanus infestations. Thus, albendazole is the preferred benzimidazole derivate for the mass treatment of subjects with T. trichiura and/or N. americanus infestations.

Albendazole↗
PubMed2004

Behavioural strategies used by the hookworms Necator americanus and Ancylostoma duodenale to find, recognize and invade the human host.

The infective third-stage larvae of the hookworms Necator americanus and Ancylostoma duodenale infect their human hosts by active skin invasion, but A. duodenale is in addition capable of oral infection. The behaviour of the larvae when crawling on surfaces has already been described. Here we analyse in various in vitro systems the other behavioural invasion phases: activation, penetration, and orientation within the host. The larvae normally remained in a motionless, energy-saving, resting posture. An activation to sinusoidal locomotion was stimulated in both species by similar cues such as touch, vibration, water currents, heat, light, and chemicals. Human breath in addition stimulated searching and waving ("nictating") behaviour, which facilitates a change-over to the host. Activating cues in air streams were warmth and moisture; CO2 activated only in combination with warmth and/or moisture. Penetration behaviour in both species was stimulated by warmth and skin extracts. The stimulating components of skin extracts were fatty acids, but their stimulating characteristics differed from those inducing schistosome cercarial skin penetration. After penetration into agar substrates, both species showed thermo-orientation, but only A. duodenale followed gradients of serum. The directing serum cues were not amino acids and glucose (the supposed cues for schistosome blood vessel localization), but Ringer's solution attracted the larvae. The host-finding and host-invasion behaviour of both hookworm species is well adapted to the invasion of the human skin, and there seems to be no particular adaptation of A. duodenale behaviour to the oral infection mode. Hookworm host-finding behaviour is not as complex as that of schistosome cercariae but seems well adapted to the ecological conditions in the transmission sites.

Ancylostoma↗
PubMed2006

Development and characterization of microsatellite markers for the canine hookworm, Ancylostoma caninum.

Microsatellites are repetitive genomic elements that show high levels of variation and therefore provide excellent tools to study the genetics of eukaryotic organisms. Hookworms are extremely common and important nematode parasites of humans and animals, causing potentially serious disease morbidity. Control of hookworms in dogs is achieved by frequent treatment with anthelmintics, and in humans, anthelmintics are frequently administered in a mass-treatment community-wide approach. Understanding the population genetics of hookworms has important implications for studies on the development and spread of drug resistance. We investigated the genome of Ancylostoma caninum for microsatellites by developing and then screening an enriched genomic library as well as by data mining published sequences of a whole genome shotgun library. Investigations revealed a high abundance of trinucleotide repeats. Dinucleotide repeats were characterized by a high number of AT, GA, and GT repeats. After testing and optimization of 68 markers, a panel of 34 polymorphic microsatellite markers were selected. Microsatellite analysis of hookworm isolates revealed a high degree of polymorphism, which was not influenced by the length of the repeats. This panel of microsatellite markers makes it possible to pursue investigations on the population genetics of A. caninum. Furthermore, a number of the markers demonstrated suitability for analysis of the human hookworm species Necator americanus and A. duodenale.

Ancylostoma↗
PubMed2001

Parasite-specific antibody and cellular immune responses in human infected with Necator americanus and Oesophagostomum bifurcum.

In this study parasite-specific antibody, cellular reactivity and Thl-type or Th2-type cytokine responses were investigated in humans concurrently infected with Necator americanus and Oesophagostomum bifurcum. The prospects for O. bifurcum-specific serodiagnosis based on IgG4 and IgE were evaluated. IgG4 showed low specificity for O. bifurcum due to antigen cross-reactivity with N. americanus, while IgE specifically distinguished between hookworm and O. bifurcum, and, in doubly infected patients, levels of O. bifurcum-specific as well as N. americanus-specific IgE were significantly elevated compared to those with N. americanus mono-infections. Cellular immunity was not strictly dominated by a Thl- or Th2- type reactivity. In co-infected patients cellular unresponsiveness to parasite antigens was observed, while cellular production of tumour necrosis factor alpha (TNF-alpha) and gamma-interferon (IFN-gamma) was greater in those doubly infected. Th2-type cytokines (interleukin-5 and interleukin-10) were produced in equal amounts by peripheral blood mononuclear cells from individuals with mono- and coinfections. Such mixed Thl-type and Th2-type immune responsiveness associated with persisting gastrointestinal parasitic nematodes may reflect a state of infection at which parasite-induced inflammatory and enteropathogenic responses co-exist, and furthermore, helminth coinfection will not only suppress parasite-specific cellular responsiveness but may also direct cytokine production towards a "permissive Th1-type cytokine profile" that favours parasite persistence.

Adolescent↗
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↗