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In a pilot study in 17 children, oxantel-pyrantel as one single dose of 10 to 20mg/kg of each, gave good results in ascariasis but poor cure rates in both trichuriasis and necatoriasis. However in the latter groups the infection was extremely heavy. In a controlled trial in 51 children, using oxantel-pyrantel at the same dose, but given daily for 3 consecutive days, or mebendazole 100mg twice daily for 3 days, the drugs gave similar response rates. Both gave 100% cure rates, as assessed by the absence of ova by both Beaver and brine-flotation techniques, in Ascaris lumbricoides infection. The percentage cures and egg reduction rates were 66.7 and 94.5 in trichuriasis and 53 and 93.6 in necatoriasis respectively. Those for mebendazole were 52 and 91.2 in trichuriasis and 37.5 and 89.7 in necatoriasis. Oxante-pyrantel treatment was associated with more cures, and a marginally greater reduction in ovum excretion than mebendazole but the differences were not statistically significant. No side-effects were seen with either treatment.
This article discusses the anthelmintics now in common use and describes their mode of action and toxic side effects. The drugs reviewed include: pyrantel pamoate, mebendazole, piperazine, thiabendazole, niclosamide, praziquantel, niridazole, oxamniquine and diethylcarbamazine. Most of the common roundworm intestinal infections respond to treatment with pyrantel pamoate, which has the advantage of single-dose therapy. Trichuriasis requires therapy with mebendazole, while the filariases are treated with diethylcarbamazine. There is no specific therapy for trichinellosis, but its symptoms can be alleviated. Intestinal cestode infections respond to treatment with niclosamide and cerebral cysticercosis to praziquantel, but echinococcal hydatid disease still requires surgical intervention in certain cases, although prolonged treatment with mebendazole shows promise. The greatest recent advance in the therapy of helminthiases is the development of praziquantel which effectively treats the most severe of these infections.
Resistance to many intestinal nematodes is dependent on the induction of polarized type 2 cytokine responses, whereas type 1 responses can exacerbate these infections. The contributions of IL-4 and IL-13 to the development of resistance have been well described for a variety of intestinal parasites; however, the role of IL-10 has not been previously investigated. In this study we infected IL-10-, IL-10/IL-4-, IL-10/IL-12-, IL-4-, and IL-12-deficient mice with Trichuris muris to determine whether IL-10 contributes to the development of immunity. Interestingly, T. muris-infected IL-10-, IL-4-, and IL-10/IL-4-deficient mice failed to expel the parasite, and animals deficient in IL-10 displayed marked morbidity and mortality. In contrast, double IL-10/IL-12-deficient mice were completely resistant and mounted a highly polarized type 2 cytokine response, demonstrating that the increased susceptibility of IL-10-deficient mice was dependent on IL-12. Further study suggested that the susceptibility of IL-10- and IL-10/IL-4-deficient mice was probably attributable to a marked increase in type 1 cytokine production in those animals. The mortality observed in T. muris-infected IL-10- and IL-10/IL-4-deficient mice correlated with increased inflammation, loss of Paneth cells, and absence of mucus in the cecum. Interestingly, survival was enhanced in T. muris-infected IL-10/IL-4-deficient mice if a broad spectrum antibiotic was administered, suggesting that an outgrowth of opportunistic bacteria was contributing to the high degree of morbidity and mortality. Overall, these studies reveal a critical role for IL-10 in the polarization of Th2 responses, development of resistance during T. muris infection, and maintenance of barrier function in the colon.
Mice infected with Schistosoma mansoni develop polarized Th2 responses in which Th1 responses are prevented by IL-10-mediated suppression of IL-12 production. We show that dendritic cells from infected mice are primed to make IL-12 in response to CD40 ligation, and that IL-10 acts by inhibiting this process. In infected mice, two subpopulations of CD4(+) cells, separable by their expression of CD25, make IL-10. CD25(+)CD4(+) cells expressed forkhead box P3, inhibited proliferation of CD4(+) T cells, and made IL-10, but little IL-5. In contrast, CD25(-)CD4(+) cells failed to express forkhead box P3 or to inhibit proliferation and accounted for all the IL-5, IL-6, and IL-13 produced by unseparated splenic populations. Thus, CD25(+) and CD25(-) subpopulations could be characterized as regulatory T cells (Treg cells) and Th2 cells, respectively. Consistent with their ability to make IL-10, both CD25(+) and CD25(-)CD4(+) T cells from infected mice were able, when stimulated with egg Ag, to suppress IL-12 production by CD40 agonist-stimulated dendritic cells. Additionally, in adoptive transfer experiments, both CD4(+) subpopulations of cells were able to partially inhibit the development of Th1 responses in egg-immunized IL-10(-/-) mice. The relationship of Treg cells in infected mice to natural Treg cells was strongly suggested by the ability of CD25(+)CD4(+) cells from naive mice to inhibit Th1 response development when transferred into egg-immunized or infected IL-10(-/-) mice. The data suggest that natural Treg cells and, to a lesser extent, Th2 cells play roles in suppressing Th1 responses and ensuring Th2 polarization during schistosomiasis.
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A randomized trial carried out in rural Zanzibar comparing a single dose of 200 micrograms/kg of ivermectin and 400 mg/day for three days of albendazole for treatment of strongyloidiasis and other intestinal nematodes is described. In 301 children with Strongyloides stercoralis infection, treatment with ivermectin or albendazole resulted in cure rates of 83% and 45%, respectively. While both drugs were very effective against Ascaris lumbricoides, Trichuris trichiura was cured only in 11% (ivermectin) and 43% (albendazole) of the subjects, although the mean eggload was reduced by 59% and 92%, respectively. Ivermectin was ineffective against hookworms, while albendazole resulted in a cure rate of 98%. No severe side effects were recorded and mild side effects were of transient nature for both treatments. Therefore, ivermectin provides a safe and a highly effective single dose treatment for S. stercoralis and A. lumbricoides, while it is not an alternative for the treatment of T. trichiura and hookworm infections.
Infection prevalences of Ascaris lumbricoides, Trichuris trichiura and the hookworms in school children in several communities of three altitudinal regions in Ethiopia have been analyzed. The prevalence of A. lumbricoides infection was 29% in the highlands, 35% in the temperate areas and 38% in the lowlands. The prevalence of hookworm infection was highest in the lowlands (24%) followed by the temperate (15%) and highland (7%) areas and the difference was significant (p < 0.0001). T. trichiura infection exhibited similar prevalences in all altitudinal regions (13% on the average). The prevalence of infection due to Ascaris lumbricoides and Trichuris trichiura was significantly correlated (rs = 0.55, p < 0.001) in the lowlands hinting the closely related distribution and co-occurrence of these parasites. The prevalence of infection due to the hookworms and T. trichiura in the temperate areas showed some pattern of association (rs = 0.29). A similar pattern has also been noted between the prevalence of infection due to A. lumbricoides and T. trichiura in the highland areas (rs = 0.48). The co-occurrence of A. lumbricoides and T. trichiura infections in the lowlands and in the highlands suggest that a concurrent intervention against infection due to these two parasites using the same control methods would be advantageous.
A questionnaire survey with parasitological study was carried out on the inhabitants of 4 villages in Barru district, Sulawesi, Indonesia from 1994 to 1995. The questionnaire dealt with life style and sanitary conditions. In 482 houses in the 4 villages, interviews for the items of the questionnaire were conducted with the owner, housekeeper and children of the same family. In Pancana and Lalolang, 37.7% and 50% respectively of man inhabitants surveyed were fishermen, while in Lompo Riaja and Pattappa, 38.6% and 65.5% respectively were farmers. The highest proportion of official workers was 33.7% in Lompo Riaja. Educational level was low; 88.4% in Pancana, 90.4% in Lalolang, 62.1% in Lompo Riaja and 91.2% in Pattappa had elementary or below elementary school education. In Lompo Riaja, 30.8% of the inhabitants graduated from senior high school or university. The percentage of families having their own latrine was 30.3% in Pancana, 13.2% in Lalolang, 31.9% in Pattapa and 60% in Lompo Riaja. The people without latrines usually defecated in rice fields, seaside or riverside. A total of 654 fecal samples was examined by the modified Kato-Katz thick smear method. Five nematode species, Ascaris lumbricoides, Trichuris trichiura, Necator americanus, Strongyloides stercoralis and unidentified Rhabditoids of free-living nature were detected. Cestode, Hymenolepis nana infection was confirmed. All the hookworms examined by the modified Harada-Mori culture technic were Necator americanus. Trichuris infection was most common, followed by hookworm and Ascaris infections, both in young (aged 4-14) and older (aged over 15) age groups. The prevalence of hookworm infection was significantly higher in males than in females of older age. Among the older age group, the prevalence of Trichuris infection was significantly lower in Lompo Riaja, while hookworm infection was the highest in Pattappa. Among all the inhabitants examined for parasite infection, 17.4% had 3 kinds of nematode, Ascaris, Trichuris and hookworm. However, egg counts revealed that most of the inhabitants with Trichuris or hookworm had light infections. The inhabitants with higher education background had significantly lower infection rates of Ascaris and Trichuris. The prevalence of hookworm infection was not significantly different between the inhabitants owning latrine and without it, but the prevalence of Ascaris and Trichuris, differed significantly.
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We are interested in understanding the role of epithelial cells during inflammation, and we previously reported that rat small intestinal epithelial cells express interleukin-1beta (IL-1beta) during infection by Trichinella spiralis. We now report that the epithelium also produces the potent neutrophil chemotactic factor, macrophage inflammatory protein-2 (MIP-2), and an IL-1 antagonist: the type II IL-1 receptor. Consequently we investigated the pattern of neutrophil infiltration into the infected intestine, which closely paralleled the epithelial cytokine expression. Speculating that neutrophil infiltration may provoke epithelial cytokine expression, neutrophil migration into the infected gut was reduced by depleting circulating cells through the use of a specific antibody, or by preventing migration through the use of a function-blocking anti-CD18 monoclonal antibody. Either treatment reduced the number of neutrophils recoverable from the small intestinal epithelium and was paralleled by reduced mRNA levels for epithelial cytokines. These results demonstrate that neutrophil infiltration of the small intestinal epithelium contributes to the stimulation of epithelial cell cytokines.
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