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A primary intestinal helminthic infection rapidly induces a gut-associated elevation of Th2-associated cytokines and IL-3.

The immune response that is characteristic of parasitic helminth infections includes components associated with immediate-type hypersensitivity: elevated serum IgE, eosinophilia, and intestinal mast cell hyperplasia. In infection with the parasitic nematode, Heligmosomoides polygyrus, IL-4 mediates protective immunity, suggesting the presence of a host-protective Th2 response. In this investigation, we examined early stages of immune responsiveness to H. polygyrus infection to determine whether and at what stage a specific Th2-like pattern first appears. Using a quantitative reverse transcriptase-polymerase chain reaction assay, we analyzed changes in IL-2, IFN-gamma, IL-3, IL-4, IL-5, IL-6, IL-9, and IL-10 gene expression in the spleen, mesenteric lymph node, and Peyer's patch at various time points after infection. Our results demonstrate a highly specific and reproducible pattern of cytokine gene expression that remains localized to the enteric region. By 6 h after infection, IL-5 and IL-9 mRNA were elevated in the Peyer's patch and IL-3 was elevated by 12 to 24 h after infection. IL-4 RNA became elevated by 4 to 6 days after infection, but little change was observed in IFN-gamma, IL-2, or IL-10 mRNA levels. The early increases in IL-3, IL-5, and IL-9 gene expression after infection were probably T cell-independent, inasmuch as they were observed in Peyer's patches of congenitally athymic mice and anti-CD4, anti-CD8 mAb-treated conventional mice. However, treatment with these mAb considerably decreased cytokine gene expression 6 days after infection, and 8 days after infection, increased IL-4 gene expression in mesenteric lymph node cells was restricted to the CD4+ population. Thus, H. polygyrus infection induces cytokine gene expression that is restricted to some Th2-associated cytokines, is initiated by a T-independent response, and culminates in a T-dependent response.

Animals↗

High prevalence of GB-C/hepatitis G virus in a Brazilian population with helminth infection.

A study of GB-C virus/Hepatitis G virus (GBV-C/ HGV) infection was carried out in a rural population of Northeastern Brazil, in which the prevalence of schistosomiasis is 80-90%. Despite the absence of parenteral risk exposure, the prevalence of GBV-C/HGV markers of infection was found to be unusually increased: viremia, 16.4%; specific antibody, 18.3%. It is therefore suspected that helminth infection influenced the immune response to GBV-C/HGV infection by shifting the balance of cytokine responses from Th1 to Th2, resulting in a delayed viral clearance. Phylogenetic analysis of viral isolates did not provide evidence for high rates of sexual or mother-to-infant viral transmission. The study revealed that viral strains belonged to types 1 and 2 only (predominant in Africa and Europe, respectively), suggesting that GBV-C/HGV was introduced into the New World by white conquerors and black slaves since the 16th century.

5' Untranslated Regions↗

Nitazoxanide for the treatment of intestinal protozoan and helminthic infections in Mexico.

A study to evaluate the efficacy and safety of nitazoxanide as a single agent for the treatment of a broad spectrum of mixed parasitic infections, both protozoa and helminths, was conducted at a primary school in San Pedro Tolimán, Querétaro, Mexico. Three faecal samples from 1824 adults and children were screened for the presence of oocysts, cysts, trophozoites, eggs or larvae of intestinal protozoa or helminths. Two hundred and forty-six adults and children infected with at least one protozoan and 2 helminths were given 7.5 mg/kg of nitazoxanide (500 mg to adults and 200 mg to children less than 12 years old) every 12 h for 3 consecutive days. Faecal samples were examined on days 6, 7, 8, 13, 14 and 15 (+/- 1) following initiation of treatment, using formalin-ether concentration and Kato-Katz egg counting. Treatment with nitazoxanide was 71-100% effective in eliminating evidence of infection with Entamoeba histolytica/E. dispar, Giardia duodenalis, Blastocystis hominis, Isospora belli, Enterobius vermicularis, Ascaris lumbricoides, Trichuris trichiura and Hymenolepis nana. Haematology and clinical chemistry values obtained before and after treatment remained unaffected by nitazoxanide. The drug was well tolerated, with only 15 patients (6.1%) reporting mild abdominal pain that lasted less than 24 h.

Adolescent↗

Prevalence of soil-transmitted helminth infections in the rural population of Bali, Indonesia.

The objectives of this cross-sectional study were to identify the prevalence of soil-transmitted helminth infection in the rural population of Bali and its relation to age, gender, and geoclimatic conditions. The subjects of study were derived from four villages of different geoclimatic conditions, namely wet lowland, dry lowland, wet highland and dry highland, by a multistage, stratified random sampling technique, based on age and gender of the target populations. The technique of Kato-Katz thick smear was used to determine presence of worm eggs in stools, and modified Harada Mori fecal culture technique was used to identify the species of hookworm larvae in stools. The data were analysed descriptively as well as statistically using chi2 test. Of 2,394 completely examined and analysed samples, the results showed as follows: The prevalences of Ascaris lumbricoides, Trichuris trichiura, hookworms and Strongyloides stercoralis were 73.7%, 62.6%, 24.5%, 1.6%, respectively. Of 2,082 infected samples, 33.1% were single infections and 66.9% were mixed infections. Among the mixed infections, dualfection was most frequent (47.8%), followed by single infection (33.1%), triplefection (18.3%), and quadrifection (0.8%). A combination of A. lumbricoides and T. trichiura was predominant in dualfection, while in triplefection a combination of A. lumbricoides, T. trichiura, and hookworms was most frequently identified. The prevalence in males was not statistically different, except for hookworms where it was higher in males than in females. The differences of prevalence of infection according to age groups for A. lumbricoides, T. trichiura and hookworms proved to be highly significant, but not with Strongyloides stercoralis. The prevalence of hookworm infection increased steadily with age to reach its maximum (37.7%) in adulthood (> 18 years), while A. lumbricoides and T. trichiura reached the highest prevalence level in elementary school age (77.3% and 70.7% respectively). The highest prevalence of S. stercoralis infection was found also in elementary school age, but it was not statistically significant. In wet highland the prevalence of infection of A. lumbricoides was 87.6%, T. trichiura 82.4%, hookworms 44.5%, and S. stercoralis 3.3%; these were significantly higher compared to the prevalence of infection in other areas (wet lowland, dry highland, dry lowland).

Adolescent↗

Genetics of susceptibility to human helminth infection.

Recent studies have shown that host genetics is an important determinant of the intensity of infection and morbidity due to human helminths. Epidemiological studies of a number of parasite species have shown that the intensity of infection (worm burden) is a heritable phenotype. The proportion of variance in human worm burden explained by genetic effects varies from 0.21 to 0.44. Human genome scans have identified a locus responsible for controlling Schistosoma mansoni infection intensity on chromosome 5q31-q33, and loci controlling Ascaris lumbricoides intensity on chromosomes 1 and 13, although the genes involved have not yet been identified. There is also evidence for genetic control of pathology due to S. mansoni, and linkage has been reported to a region containing the gene for the interferon-gamma receptor 1 subunit. There is some evidence for genetic control of filarial infection, though little information on filarial disease. Association studies have provided evidence for major histocompatibility complex control of pathology in schistosomiasis and onchocerciasis. Recent candidate gene studies suggest a role of other immune response genes in controlling helminth infection and pathology, but require replication. Identification of the genetic loci involved may be important in the understanding of helminth epidemiology and the mechanisms of resistance and pathology.

Animals↗

Helminth infections: protection from atopic disorders.

Westernized countries are suffering from an epidemic rise in immunologic disorders, such as childhood allergy. A popular explanation is that the increased prevalence in allergy is due to a diminished or altered exposure to gut-dwelling microbes, resulting in a disordered immunoregulation. Various population studies have provided a strong case for the involvement of helminth infections in this respect. Detailed analysis of helminth-induced immune responses showed that helminths not only prime for polarized Th2 responses but also potently induce T-cell hyporesponsiveness. Recently, it has been demonstrated that helminths induce suppressed host immune responses by the priming for regulatory T cells. It is proposed that this regulatory T cell-inducing activity accounts for the protection observed in the development of allergic disorders. It would be interesting to define and characterize particular helminth molecules that have profound immunomodulatory capacities as a target for therapeutic application in the treatment or prophylaxis of allergic manifestations.

Adult↗

IL-4- and IL-5-secreting lymphocyte populations are preferentially stimulated by parasite-derived antigens in human tissue invasive nematode infections.

Helminth infections in humans and animals are associated with strong T helper 2 (Th2) responses. To determine whether parasite-derived Ag preferentially expand a Th2-like cell population, a filter immunoplaque assay was used to enumerate the frequencies (F0) of PBMC and CD4(+)-enriched PBMC from individuals with helminth infections secreting selected cytokines in response to parasite-derived (PAg) and nonparasite antigens (NPAg). In 20 individuals with lymphatic filariasis, frequency analysis of PBMC secreting IL-4 and IFN-gamma indicated that the F0 of PAg-specific IL-4-secreting cells (geometric mean F0 (GM): 1/12,100) was 57-fold higher than the corresponding F0 of NPAg-reactive cells (GM: 1/692,000; p < 0.02). In marked contrast, the F0 of IFN-gamma-secreting cells responding to PAg (GM: 1/2,700) did not differ from those of cells specific for NAPg (GM: 1/3,400; p = 0.83). In another group of helminth-infected individuals, the F0 of highly enriched CD4+ cells secreting IL-4 and IL-5 in response to PAg (GMs: 1/2,600 and 1/5,600 CD4+ cells, respectively) were also found to be significantly higher than those specific for NPAg (GMs: 1/291,000 and 1/303,000 CD4+; p < 0.05 and p < 0.01, respectively), whereas the corresponding F0 of IFN-gamma- and granulocyte-macrophage-CSF-secreting cells were equivalent for PAg and NPag. Furthermore, the proportion of PAg-specific IL-4- and IL-5-secreting CD4+ cells relative to all cells secreting the given cytokine were approximately 29-fold higher than the proportion of NPAg-specific cells secreting these cytokines. Again, the corresponding proportions of Ag-specific IFN-gamma-and GM-CSF-secreting CD4+ cells were equivalent for PAg and NPAg. Thus, in this ex vivo system, a circulating population of IL-4- and IL-5-secreting (Th2-like) cells has been shown to exist in humans; PAg appears to expand these cells preferentially.

Adult↗

Impact of a filariasis control program on intestinal helminthic infections; a pilot study in Narathiwat Province, Thailand.

This study was conducted in 9 villages located in endemic areas for brugian filariasis in Narathiwat Province, Thailand. Parasitological and anthropometric examinations were cross-sectionally performed to assess the prevalence of intestinal parasitic infections of 539 villagers. Paired stool samples were collected before and after mass treatment for the filariasis control program in 150 participants in order to study the impact of the filariasis control program on intestinal helminthiasis. The results found that 50.3% of the villagers were infected with one or more types of intestinal parasites. Double and triple infections were found in 10.9% and 1.6% of infected individuals respectively. The prevalence of intestinal parasitic infections peaked in the 1-10 year old age-group, which are pre-school and young school-age children. A significant reduction of intestinal helminthic infections in the post-treatment stool sample was observed in the 150 participants who were examined six months after mass treatment. Integrating an intestinal helminthic control program alongside the existing filariasis control program would be an appropriate and cost-effective strategy in the control of intestinal helminths. However, reinfection of parasites was observed.

Adolescent↗

IgE production in human helminth infection. Reciprocal interrelationship between IL-4 and IFN-gamma.

To determine whether there is a reciprocal relationship between IL-4 and IFN-gamma production in persons with parasite-induced elevations in serum IgE, PBMC were obtained from helminth-infected individuals with a broad range of serum IgE levels that fell into two distinct groups--extremely elevated (HI; n = 9; range, 4,129 to 18,400 ng/ml) or elevated (EL; n = 6; range, 403 to 1,018 ng/ml), relative to control subjects (NL; n = 7; range, 4 to 159 ng/ml). PBMC were stimulated in vitro, with Ag or mitogens, and IL-4 and IFN-gamma were measured by ELISA in culture supernatants. Helminth Ag- (but not tetanus toxoid) stimulated IL-4 production in eight of nine HI (range, 49 to 150 pg/ml) but was undetectable in either EL or NL (p < 0.01). In contrast, PBMC from EL produced significant levels of IFN-gamma to helminth Ag (GM = 358 pg/ml) compared with HI (GM = 89 pg/ml; p = 0.02) and NL (GM = 9 pg/ml; p < 0.001). Tetanus toxoid induced comparable levels of IFN-gamma among the three groups. Mitogen-driven IL-4 production was ninefold greater in HI [geometric mean (GM) = 913 pg/ml] versus EL (GM = 111 pg/ml; p < 0.01) and NL (GM = 193 pg/ml; p < 0.001) and correlated with serum IgE levels (r = 0.8; p < 0.01). Mitogen-driven IFN-gamma synthesis was equivalent among the groups. Although parasite Ag-driven IL-4 secreting CD4+ cells were detected (by ELISPOT) among infected subjects with both high and low serum IgE levels, the number of IL-4 exceeded that of IFN-gamma-secreting cells among individuals with elevated serum IgE levels, whereas the opposite relationship existed among subjects with normal serum IgE. In a subpopulation of infected individuals (n = 4), parasite-Ag added to PBMC cultures induced polyclonal IgE that was directly associated with the parasite-Ag-driven IL-4 production and inversely related to IFN-gamma synthesis in PBMC supernatants from parallel cultures. Furthermore, neutralizing anti-IFN-gamma antibody augmented both parasite-driven IL-4 synthesis and IgE production in vitro (n = 4). The data indicate that helminth-induced serum IgE levels are directly related to an increased capacity by PBMC to produce IL-4 and inversely associated to IFN-gamma production. It further supports the concept that IL-4 and IFN-gamma reciprocally regulate IgE in vivo.

Acute Disease↗

B cell sensitization to helminthic infection develops in utero in humans.

Human neonates are generally deficient in their ability to generate humoral immunity. This deficiency is thought to reflect physiologic immaturity of T and B cell function and lack of previous exposure to exogenous Ags. To determine whether neonatal humoral immunity can be modified by maternal helminth infection during pregnancy, we assessed Ig production by cord blood lymphocytes from healthy newborns of mothers living in an area of Kenya where schistosomiasis, bancroftian filariasis, and geohelminth infections are endemic. Twelve of 40 and 17 of 39 cord blood lymphocyte preparations from healthy newborns in Coast Province, Kenya, spontaneously made polyclonal IgE (range, 0.15-21 ng/ml) and IgG (1.6-10.1 ng/ml) in vitro. In vitro IgE synthesis by cord blood lymphocytes (CBL) was, on the average, 10-fold less than that of PBMC of Kenyan mothers (1.1-98 ng/ml) and was undetectable for CBL from newborns delivered in the United States. Schistosome and filarial Ags stimulated a 3- to > 100-fold increase in the production of polyclonal IgE and parasite-specific IgG Abs by lymphocytes from 10 of 40 and 6 of 39 Kenyan newborns, respectively. CBL observed to have helminth Ag-driven B cell responses were more likely to be from newborns of schistosome- or filaria-infected mothers than from uninfected mothers (p < 0.05). These data indicate that the human fetus can be sensitized in utero to produce helminth-specific B cells and that neonatal B cells are intrinsically capable of IgE and IgG production.

Antibodies, Helminth↗

Effects of heterologous helminth infections on passive transfer of immunity using a mouse monoclonal IgE antibody against Schistosoma japonicum.

Passive transfer of immunity using a mouse monoclonal IgE antibody against Schistosoma japonicum was found to be enhanced by heterologous helminth infections. BALB/c mice were infected with Toxocara canis or Nippostrongylus brasiliensis so as to induce eosinophilia prior to a challenge infection with S. japonicum. Recovery of adult schistosomes decreased in a group of mice that had been infected with T. canis and challenged with cercariae at the cutaneous site of sensitization with the IgE antibody as compared with that in mice that had been similarly treated with normal serum in the absence of T. canis infection. Histological examinations revealed a close association of polymorphonuclear cells, including eosinophils, with damaged schistosomula in the skin of T. canis-infected mice that had received the IgE antibody. An enhancement in worm reduction was also observed in mice harboring either of both nematodes when the monoclonal antibody had been injected intraperitoneally during the phase of migration of schistosomula from the skin to the lungs. In vitro studies on macrophage-mediated damage to schistosomula suggested that the enhancement in worm reduction was at least partly due to the activation of macrophages induced by the heterologous infections.

Animals↗

Effects of helminth infection on the pre-weaning production of ewes and lambs: comparison between safe and contaminated pasture.

Comparison was made of the performances of cross-bred ewes and their lambs on pastures of low helminth infectivity ("safe" pastures) or contaminated pastures and at high or low stocking rates. Ewes grazing the safe, but not the contaminated, pastures were given a single pre-lambing drench. The largest difference in parasite infection between treatments was the level of exposure of sheep to Trichostrongylus spp, which was negligible on the safe pastures. The effects of parasite control on lamb growth were significant only in twins during the last 2 months before weaning. However, 22% of lambs on contaminated plots became soiled in the breech area and 38% were flystruck, compared with 8% and 10% respectively for lambs on the safe pastures. Ewe bodyweight gains were greater at low than at high stocking rate and were not affected by the parasite control treatments; differences in breech soiling and fly strike were similar to those in the lambs. Most importantly the parasite treatment produced a highly significant effect on ewe fleece weight at weaning. Ewes drenched and lambing on the safe pastures produced an extra 0.43 kg of wool, calculated to represent an increase of at least 40% during this period at the low-level of parasitic infection.

Animals↗

Environmental contamination with helminth infective stages implicated in water and foodborne diseases.

The number of parasites increased followed the rapid growing of human population on the Earth. Zoonoses with other medical disorders such allergy accompanied to the parasitic infection are under very carefull investigation. A zoonosis can be transmitted from animals to humans in various ways, depending on life cycle of parasite, the kind of hosts and geographical distribution of species. There are many diseases that can be linked to transmission from not only domestic but also from wild animals (for example Trichinella, Echinococcus, Toxocara, Anisakis). The greater abundance of wild animals may contribute to the wider distribution and increasing prevalence of their parasites (red fox for Echinococcus multilocularis or Trichinella britovi). Zoonotic infections can be transmissed directly from environment when infective stages of parasite contamine water or food. Very important source of zoonoses in humans comes also from foodstuffs of animal origin. Environmental contamination with helminth infective stages needs regular indication for recognition of parasitic species under molecular data and improvement of effective measures to prevent of human zoonotic diseases.

Animals↗

Reactive oxygen species and 12/15-lipoxygenase contribute to the antiproliferative capacity of alternatively activated myeloid cells elicited during helminth infection.

Understanding the role of CD11b(+)GR-1(+) myeloid suppressor cells in the immune suppression and immunoregulation associated with a variety of diseases may provide therapeutic opportunities. In this article, we show, in a model of helminth infection, that CD11b(+)GR-1(+) myeloid suppressor cells but not CD11b(+)F4/80(high) mature macrophages expanded in the peritoneal cavity of BALB/c mice implanted with Taenia crassiceps. Peritoneal cell populations from early stage-infected animals impaired T cell proliferation by secreting NO. Yet, they lost their ability to secrete NO in the late stage of infection. Concomitantly, their capacity to exert arginase activity and to express mRNAs coding for FIZZ1 (found in inflammatory zone 1), Ym, and macrophage galactose-type C-type lectin increased. Furthermore, cells from early stage-infected mice triggered T cells to secrete IFN-gamma and IL-4, whereas in the late stage of infection, they only induced IL-4 production. These data suggest that CD11b(+)GR-1(+) myeloid suppressor cells displaying an alternative activation phenotype emerged gradually as T. crassiceps infection progressed. Corroborating the alternative activation status in the late stage of infection, the suppressive activity relied on arginase activity, which facilitated the production of reactive oxygen species including H(2)O(2) and superoxide. We also document that the suppressive activity of alternative myeloid suppressor cells depended on 12/15-lipoxygenase activation generating lipid mediators, which triggered peroxisome proliferator-activated receptor-gamma. IL-4 and IL-13 signaling contributed to the expansion of myeloid suppressor cells in the peritoneal cavity of T. crassiceps-infected animals and to their antiproliferative activity by allowing arginase and 12/15-lipoxygenase gene expression.

Animals↗

Relationship between intensity of soil-transmitted helminth infections and anemia during pregnancy.

A direct relationship exists between the intensity of hookworm infection and blood loss. Other parasites may also contribute to blood loss. Our objective was to assess the relationship between the intensity of soil-transmitted helminth infections and anemia in pregnant women in a highly endemic area of Peru. Recruitment occurred between April and November 2003. Overall, 47.31% of 1,042 women had anemia (hemoglobin < 11 g/dL), 47.22% were infected with hookworm and 82.25% with Trichuris. Prevalences of infections were not associated with anemia. However, those infected with moderate and heavy intensities of hookworm infection (OR = 1.84; 95% CI: 1.06, 3.17) and those with moderate and heavy intensities of both hookworm and Trichuris infections (OR = 2.13; 95% CI: 1.10, 4.13) were more likely to suffer from anemia than women having no or light intensities. These results support routine anthelminthic treatment within prenatal care programs in highly endemic areas.

Adolescent↗

The proportion of helminth infections in a community in western Kenya which would be treated by mass chemotherapy of schoolchildren.

The present study used data from a community-based epidemiological survey of 752 persons in 3 villages in Kisumu District, western Kenya, to examine the proportion of infected persons who would be treated, as well as the effect on helminth egg production, if anthelmintics were provided to schoolchildren. Overall prevalences of hookworm, Ascaris lumbricoides, Trichuris trichiura and Schistosoma mansoni infections were 63%, 16%, 24% and 24% respectively, and intensities were low for all infections. Only 79% of the school-aged children were enrolled. For all 4 infections, a school-based programme would treat between 76% and 86% of infected school-age children and would theoretically eliminate between 83% and 92% of the number of eggs excreted by this age group. Of the total population, school-based programmes would treat only between 31% and 50% of the infected persons and eliminate only 15%, 46%, 29% and 27% of the total number of hookworm, Ascaris, Trichuris and S. mansoni eggs excreted, respectively. Provided that school attendance rates were high in the study area, school-based programmes would be efficient in improving the helminth infection status of school-aged children. On the other hand, adults, non-enrolled school-aged children and preschool children not offered treatment represented more than half of the helminth-infected persons and they excreted between half and 85% of the total burden of helminth eggs in the area. Hence, mass chemotherapy of schoolchildren would be less effective in the control of at least hookworm and S. mansoni infections in this specific community. There should therefore be a community-based approach to helminth control in combination with a school-based programme.

Adolescent↗

[Helminth infections in wild boars in enclosures in southern Germany: species spectrum and infection frequency].

To determine the helminth fauna of wild boars, stomachs and intestines of 124, lungs of 62, and livers of 39 animals from 5 enclosures in Southern Germany were examined. The evaluation of the species composition revealed at least 13 species: Metastrongylus apri, M. salmi, M. pudendotectus, Physocephalus sexalatus, Hyostrongylus rubidus, Globocephalus longemucronatus, Ascaris suum, Trichuris suis, Oesophagostomum dentatum, O. quadrispinulatum, Fasciola hepatica, C. tenuicollis and Capillaria. The most frequently isolated species was M. salmi with 91.9%, followed by G. longemucronatus with 91.1%, M. apri with 88.7%, M. pudendotectus with 87.1%, P. sexalatus with 51.6%, O. dentatum with 46%, T. suis with 30.6%, H. rubidus with 14.5%, A. suum with 12.1% and O. quadrispinulatum with 8.1%. Differences in the prevalence of infection, determined for animals up to 1 year old, 1-2 year-old and adults, were minimal for Metastrongylus spp. and G. longemucronatus. P. sexalatus, T. suis and A. suum, however, occurred more often in 1 year old, whereas H. rubidus, O. dentatum and O. quadrispinulatum were isolated more often from adults. A correlation of the infection rate with the sex of the animals was not found.

Animals↗