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Th1/Th2 polarization by viral and helminth infection in birds.

Mammals developed an immune system able to functionally polarize into so-called type 1 or type 2 immune pathways, to resolve infections with intracellular and extracellular pathogens, respectively. In the well-studied avian immune system of the chicken, however, no evidence for polarized immunity could be found, as yet. To investigate whether these two major arms of mammalian immunity, regulated by a T helper (Th)1/Th2 cytokine balance, evolved similarly in birds, chickens were exposed to a prevalent intracellular (viral) or extracellular (helminth) infection. By using semi-quantitative RT-PCR analysis we provide evidence that polarization of Th1/Th2 type immunity extends beyond mammalian species, and, therefore, has been evolutionary conserved for more than 300 million years, when the lineages of mammalian and avian vertebrates are assumed to have segregated.

Animals↗

Improvements in appetite and growth in helminth-infected schoolboys three and seven weeks after a single dose of pyrantel pamoate.

Appetite and growth were studied in primary schoolboys (6-10 years) infected with Ascaris lumbricoides (86%) and Trichuris trichiura (100%) who received a single dose of pyrantel pamoate (which has little or no effect on Trichuris trichiura) or a placebo. Boys were examined, allocated at random by descending Ascaris egg count to pyrantel (PR, n = 36) or placebo (PL, n = 36) groups, treated, and re-examined 3 and 7 weeks later. The 2 groups did not differ significantly before treatment in helminth infections, appetite, or growth. Three and 7 weeks after treatment, the PR group exhibited significantly greater increases than did the PL group in weight (0.2 kg and 0.4 kg more, respectively) and percentage weight-for-age (0.6% and 1.7% points more, respectively). Appetite increased significantly in the PR group at 3 and 7 weeks (P < 0.0005 and P < 0.01, respectively) but not in the PL group. The prevalence and intensity of A. lumbricoides infection were greatly reduced in the PR group at 3 and 7 weeks (both P < 0.0001) but not in the PL group. We conclude that treatment with pyrantel pamoate may improve appetite and growth in school children in areas where A. lumbricoides infections and poor growth are highly prevalent.

Animals↗

Suppressive antigen-presenting cells in Helminth infection.

Infection with filarial nematodes is commonly associated with a failure of T cells to proliferate in response to parasite antigen. We have investigated the possibility that antigen-presenting cells recruited during filarial infection are responsible for impairment of T cell function. We have found that the human filarial parasite Brugia malayi, when implanted into the peritoneal cavity of mice, recruits a population of adherent cells that actively block the proliferation of T cells. Phenotypic analysis of the recruited cells reveals large numbers of both macrophages and eosinophils and cell sorting experiments demonstrate that these antiproliferative cells are Mac-1-positive. Studies in gene-deficient mice have demonstrated that proliferative suppression is dependent on the in vivo production of IL-4 but not IL-5 or IL-10, while suppression in vitro is not mediated by any known antiproliferative factor. Our results suggest that helminth infection can lead to the development and/or recruitment of an IL-4-dependent macrophage population that mediates suppression via a novel mechanism.

Animals↗

Intestinal helminth infections, anaemia and labour productivity of female tea pluckers in Bangladesh.

We conducted a randomized clinical intervention trial over 24 weeks on a tea estate in north-east Bangladesh to investigate the effect of iron supplementation and anthelmintic treatment on the labour productivity of adult female tea pluckers. A total of 553 full-time tea pluckers, not pregnant and not breastfeeding, were randomly assigned to one of the four intervention groups: group 1 received iron supplementation on a weekly basis, group 2 received anthelmintic treatment at the beginning and half-way through the trial (week 12), group 3 received both iron supplementation as group 1 and anthelmintic treatment as group 2, and group 4 was a control group and received placebos. No significant difference in labour productivity was found between the four intervention groups over the trial period. However, there was a negative association for all three worms (Ascaris lumbricoides, Trichuris trichiura and hookworms) between the intensity of helminth infections (eggs/g faeces) and all measures of labour productivity. Lower haemoglobin values and anaemia (< 120 g/l Hb) were both associated with lower labour productivity and more days sick and absent. Taller women with greater arm circumference were able to pluck more green leaves, earn higher wages and were absent less often.

Adolescent↗

Cytokine-mediated regulation of chronic intestinal helminth infection.

Most inbred strains of mouse infected with the intestinal nematode Trichuris muris are resistant to infection expelling the parasite before adult worms establish. However, a few susceptible strains exist that are incapable of worm expulsion and harbor chronic infections of mature adult worms. Analyses of in vitro cytokine production by cells from the draining lymph node (mesenteric lymph node) have indicated that expulsion phenotype is tightly correlated with the selective expansion of helper T cells (Th) of the Th1 or Th2 cell subset within the mesenteric lymph node, resulting in susceptibility and resistance to T. muris, respectively. We have now confirmed and extended our in vitro observations in a series of experiments involving the in vivo manipulation of host cytokine levels. Depletion of interferon (IFN)-gamma in normally susceptible mice resulted in expulsion of the parasite, representing the first evidence for a role for IFN-gamma in the establishment of chronic helminth infection. Blocking interleukin (IL)-4 function in normally resistant animals prevented the generation of a protective immune response allowing adult stages of the parasite to develop. Conversely the administration of IL-4 to a normally susceptible host facilitated expulsion and indeed enabled established adult worms to be expelled when administered late in infection. In all cases assessment of a variety of in vivo parameters indicative of a Th1- or Th2-type response (parasite-specific immunoglobulin (Ig) G2a and the parasite-specific IgG1, total IgE levels and intestinal mastocytosis, respectively) demonstrated that the in vivo modulation of a Th1- or Th2-specific cytokine allowed the reciprocal Th cell subset to expand and become dominant with dramatic consequences for worm expulsion.

Animals↗

Nonspecific reactions with the intradermal test for hydatidosis in persons with other helminth infections.

A partially purified Echinococcus antigen solution, prepared by boiling hydatid cyst fluid, was used in the intradermal test for hydatid disease in a Peruvian population. An unexpectedly high rate of positive reactions and poor agreement with serological tests suggested the presence of some agent(s) which produced cross-reactions with Echinococcus granulosus antigens in the intradermal test. Testing of hospital patients infected with a variety of helminths demonstrated nonspecific reactions in persons with Hymenolepis nana, Taenia spp., and Fasciola hepatica infections, mixed parasitisms, and several non-helminth pathological conditions. The findings contraindicated the use of the intradermal test for epidemiological surveys of hydatid disease. It is pointed out that intradermal test positivity rates cannot be used as synonymous with infection prevalence and regional differences do not necessarily reflect differences in the prevalence of E. granulosus infection. The greater specificity of some serological tests favor their use for epidemiological purposes.

Antibodies, Heterophile↗

A survey of helminth infection in rats (Rattus spp) from Chiang Mai Moat.

An investigation of helminths in the Norway (brown) rat, Rattus norvegicus, and roof rat, Rattus rattus, from Chiang Mai Moat during May to August 1995, was done. Thirty-three out of thirty-eight trapped rats were infected (86.84%); 16 R. norvegicus (100%) and 17/22 R. rattus (77.27%). The rat was infected with 10 helminth species: 4 trematodes, Centrocestus sp (2.63%), Echinostoma ilocanum (10.52%), Echinostoma malayanum (10.52%) and Quinqueseralis quinqueseralis (39.47%); 2 cestodes, Raillietina sp (36.64%) and Taenia sp (cysticercus) (7.89%); and 4 nematodes, Angiostrongylus cantonensis (42.10%). Nippostrongylus sp (34.21%), Rictularia sp (52.63%) and egg of Capillaria hepatica (7.89%). The helminths were found in the small intestine (84.21%), large intestine (42.10%), lung (36.64%), stomach (28.94%), heart (23.94%), and liver (15.78%). The female Norway rats were infected with 10 species of helminths and the males with 6 species. In the roof rat, 7 species of helminths were found in females and 6 species in males.

Animals↗

Regulation of allergy and autoimmunity in helminth infection.

Parasitic infections are a major theme in the "hygiene hypothesis", as allergies and autoimmune diseases are less prevalent in countries with higher burdens of helminths and other parasitic organisms. Helminths"-the grouping of multicellular worm parasites including nematodes, cestodes and trematodes-tend to establish long-lived, chronic infections indicating successful down-modulation of the host immune system. In this review, we describe the intricate immunology of host-helminth interactions and how parasites manipulate immune responses to enhance their survival. In so doing, they often minimise immunopathology and, it is suggested, reduce host susceptibility to, and severity of allergic and autoimmune diseases. Studies on helminth-infected communities and individuals support the hypothesis that an immuno-regulatory network promoted by parasites extends its influence to limiting allergies. Experimental models are now probing more deeply into the area of immune modulation by helminths, and we discuss the likely mechanisms by which helminths could be establishing a strongly regulatory environment. Understanding and harnessing the modulatory capacity of helminths may uncover novel therapeutic interventions, mimicking and exploiting their evolution for our benefit. Parasitic infections are a major theme in the "hygiene hypothesis", as allergies and autoimmune diseases are less prevalent in countries with higher burdens of helminths and other parasitic organisms. Helminths"-the grouping of multicellular worm parasites including nematodes, cestodes and trematodes-tend to establish long-lived, chronic infections indicating successful down-modulation of the host immune system. In this review, we describe the intricate immunology of host-helminth interactions and how parasites manipulate immune responses to enhance their survival. In so doing, they often minimise immunopathology and, it is suggested, reduce host susceptibility to, and severity of allergic and autoimmune diseases. Studies on helminth-infected communities and individuals support the hypothesis that an immuno-regulatory network promoted by parasites extends its influence to limiting allergies. Experimental models are now probing more deeply into the area of immune modulation by helminths, and we discuss the likely mechanisms by which helminths could be establishing a strongly regulatory environment. Understanding and harnessing the modulatory capacity of helminths may uncover novel therapeutic interventions, mimicking and exploiting their evolution for our benefit.

Animals↗

Contrasting effects of acute and chronic gastro-intestinal helminth infections on a heterologous immune response in a transgenic adoptive transfer model.

We have previously found that co-immunisation with ovalbumin (OVA) and the body fluid of the helminth Ascaris suum inhibited an OVA-specific delayed type hypersensitivity (DTH) response by reducing OVA-specific CD4+ T lymphocyte proliferation via an IL-4 independent mechanism. In the present study, we determined whether parasite infections themselves could induce similar changes to peripheral immunisation by examining the modulation of OVA-specific immune responses during acute and chronic helminth infections. Surprisingly, an acute infection with Trichinella spiralis, but not a chronic infection with Heligmosomoides polygyrus, inhibited the OVA-specific DTH reaction. Correspondingly, the T helper 1 (Th1) OVA-specific response was decreased in mice infected with T. spiralis, but not with H. polygyrus. Inhibition of the Th1 response may be a result of a shift in the Th1/Th2 balance as although both H. polygyrus and T. spiralis infected mice induced a Th2 OVA-specific response, that exhibited by T. spiralis was more potent. Furthermore, although IL-10 secretion upon OVA restimulation was similarly increased by both infections, production of this immunoregulatory cytokine may play a role in the suppression of immune responses observed with T. spiralis infection depending on the context of its release. Interestingly, analysis of the OVA-specific T lymphocyte division by carboxyfluorescein diacetate succinimidyl ester (CFSE) staining revealed that gastro-intestinal infection with the acute helminth T. spiralis, but not with chronic H. polygyrus, inhibited the systemic immune response by significantly inhibiting the antigen-specific T cell proliferation during the primary response, a mechanism similar to that observed when A. suum parasite extracts were directly mixed with the OVA during immunisation in our previous studies.

Acute Disease↗

Age and sex graded helminth infections in a Nigerian village.

Prevalence of helminth parasites was carried out in both male and female villagers graded into three age groups (5-14 years, 15-25 years, 26-55 years). Children between 5 and 14 years of age had the highest prevalence of Ascaris, Schistosoma haematobium and Trichuris while the villagers between 26-55 years of age had lowest prevalence of these parasites. However, hookworms were highly common among the villagers aged between 26 and 55 years and least common among the school children aged between 5 and 14 years. Female children between the ages of 5 and 14 years and males of the same age group were highly infested with Ascaris and Trichuris. This finding in a Nigerian village suggested that helminth infestation is age and sex dependent which is therefore a factor of the frequency in host-parasite contact determined by mode of life of the parasites and the hosts.

Adolescent↗

Co-infection of helminths and malaria: modulation of the immune responses to malaria.

Chronic helminth infections induce strong type 2 and regulatory immune responses and are known to influence immune activity to other antigens such as allergens and vaccines. Since malaria and helminth infections often coincide geographically in the same tropical regions, the question arises whether helminth infections modulate the immune responses towards the malaria parasite and affect its course of disease. Here, we will review studies on co-infections in both animal models and in human populations, and discuss the changes in the immune system seen. Furthermore, the implications of helminth infection for the efficacy of malaria vaccines will be discussed.

Animals↗

Th2 cytokines are associated with reduced worm burdens in a human intestinal helminth infection.

Although T helper 2 (Th2) cytokines are known to be critical in the generation of protective immunity against intestinal helminths in mouse models, it is unclear whether they are important in natural immunity against gut helminthiases in humans. Therefore, we investigated cytokine production in ex vivo whole-blood cultures in response to Ascaris lumbricoides antigen and mitogen in a cross-section of a community where the parasite is hyperendemic. The intensity of A. lumbricoides infection was significantly reduced after age 11 years. Levels of cytokines associated with Th2 lymphocytes (interleukin [IL]-4, IL-9, IL-10, and IL-13) demonstrated an inverse relationship with intensity of A. lumbricoides infection only in individuals aged >11 years. Furthermore, the IL-9, IL-10, and IL-13 produced in response to parasite antigen were of primary importance in this relationship. These findings promote a role for Th2-mediated responses in the age-dependent reduction of intestinal helminth infections in humans.

Adolescent↗