Anti-IL-9 vaccination prevents worm expulsion and blood eosinophilia in Trichuris muris-infected mice.
Production of neutralizing anti-IL-9 antibodies was induced in mice by immunization with mouse IL-9 coupled to ovalbumin. In the six mouse strains tested, a strong and long-lasting anti-IL-9 response developed with seric inhibitory titers of 10(-3) to 10(-5), as measured in an in vitro IL-9-dependent cell proliferation assay. In vivo, this immunization completely abrogated the increase in mast-cell protease-1 levels as well as the eosinophilia observed in mice after implantation of an IL-9-secreting tumor. We took advantage of this method to assess the role of IL-9 in infections with nematode Trichuris muris, where IL-9 production correlates with the resistant phenotype. C57BL/6 mice, which normally expel the parasite, became susceptible after anti-IL-9 immunization, demonstrating that IL-9 plays a critical role in this model. In addition, neutralization of IL-9 also inhibited parasite-induced blood eosinophilia. Taken together, the present data demonstrate the potency of our strategy to antagonize IL-9 in vivo and shows that this cytokine plays a major role in resistance against T. muris infection. (+info)
The treatment of soil infested with the human whipworm, Trichuris trichiura.
The soil fumigants methyl bromide, chloropircrin and Basamid or mixtures of Basamid and chloropicrin proved to be of no use in filling T. trichiura ova in soil. However, on untreated plots the eggs died at a rate such than only 20% of the ova remained viable after 18 months. (+info)
Peripheral cytokine responses to Trichuris muris reflect those occurring locally at the site of infection.
The study of human cellular immune responses to parasite infection under field conditions is very complex. Often, the only practical site from which to sample the cellular responses is the peripheral blood. Sampling peripheral blood lymphocytes (PBL) relies on the assumption that these peripheral responses accurately reflect the immune responses acting locally at the site of infection. This is a particularly important point for the human intestinal helminth Trichuris trichiura, which solely inhabits the cecum and large intestine and so will stimulate a localized immune response. Using the well-defined model of T. trichiura, T. muris in the mouse, we have demonstrated that the dominant cytokine responses of the mesenteric lymph nodes (MLN) can be detected by sampling PBL. Resistant mice which mount a type 2 cytokine response in their MLN had PBL producing interleukin-4 (IL-4), IL-5, and IL-9, with negligible levels of gamma interferon (IFN-gamma). Conversely, susceptible mice which mount a type 1 cytokine response in their MLN had PBL producing IFN-gamma and negligible levels of type 2 cytokines. We have also shown that the PBL are capable of mounting a functional immune response against T. muris. PBL from immune mice were capable of transferring immunity to T. muris-infected severe combined immunodeficient (C.B-17 scid/scid) mice. Sampling PBL responses is therefore a viable option for monitoring human intestinal immune responses during T. trichiura infection in the field. (+info)
IL-13-mediated worm expulsion is B7 independent and IFN-gamma sensitive.
B7 costimulation is a required component of many type 2 immune responses, including allergy and protective immunity to many nematode parasites. This response includes elevations in Th2 cytokines and associated effector functions including elevations in serum IgG1 and IgE and parasite expulsion. In studies of mice infected with Trichuris muris, blocking B7 ligand interactions inhibited protective immunity, suppressed IL-4 production, and enhanced IFN-gamma production, but unexpectedly did not inhibit production of the Th2 cytokine, IL-13. Blocking both IFN-gamma and B7 restored protective immunity, which was IL-13 dependent, but did not restore IL-4 or associated IgE responses. Although IL-13 was required for worm expulsion in mice in which both IFN-gamma and B7 were blocked, IL-4 could mediate expulsion in the absence of both IL-13 and IFN-gamma. These studies demonstrate that 1) B7 costimulation is required to induce IL-4, but not IL-13 responses; 2) IL-13 is elevated in association with the IFN-gamma response that occurs following inhibition of B7 interactions, but can only mediate IL-4-independent protection when IFN-gamma is also inhibited; and 3) increased IL-13 production, in the absence of increased IL-4 production, is not associated with an IgE response, even in the absence of IFN-gamma. (+info)
Some risk factors of Ascaris and Trichuris infection in Malaysian aborigine (Orang Asli) children.
A study on risk factors of soil-transmitted helminths was conducted in a highly endemic area. In all 205 children (95 boys and 110 girls) participated in this study. The overall prevalences of Ascaris, Trichuris and hookworm infection were 62.5%, 91.7% and 28.8% respectively. Only 22.4% of the children had a single infection either by Ascaris or Trichuris; 69.3% had mixed infection and the most prevalent of mixed infection was a combination of Ascaris and Trichuris. Logistic regression analysis confirmed that low level mother's education was a risk factor for moderate and severe infection of Ascaris and age < or = 6-year-old was a protective factor. In Trichuris infection logistic regression analysis confirmed that usage of well-water and age < or = 6-year-old were the risk factors. Logistic regression analysis on worm scores confirmed that usage of well-water and non-usage of toilets were the risk factors from getting severe worm scores and age < or = 6-year-old was a protective factor. Our finding suggest that socio-behavioural (related to mother's education), demographic (children age) and environmental-factors (usage of well-water and non-usage of toilets) are the elements to be considered in the design of long term soil-transmitted helminths (STH) control in an endemic areas. (+info)
Efficacy of albendazole in the treatment of Trichuris trichuria and Giardia intestinalis infection in rural Malay communities.
A community study was carried out to evaluate the efficacy of a 3-day course of 400 mg albendazole daily in the treatment of Trichuris trichiura and Giardia intestinalis infection. This treatment regimen was effective in the treatment of Trichuris trichiura and Giardia intestinalis infection with cure rates of 91.5% and 96.6% respectively. Uses of a 3-day course of 400 mg albendazole daily should be considered in mass or targeted soil-transmitted helminths chemotherapy particularly in areas where the prevalence of Trichuris trichiura is high and polyparasitism is common. (+info)
Albendazole treatment of children with ascariasis enhances the vibriocidal antibody response to the live attenuated oral cholera vaccine CVD 103-HgR.
Because concurrent infections with geohelminth parasites might impair the immune response to oral vaccines, we studied the vibriocidal antibody response to the oral cholera vaccine CVD 103-HgR in children infected with Ascaris lumbricoides and investigated the effect of albendazole pretreatment on the postvaccination response. Children with ascariasis were randomized to receive either 2 sequential doses of 400 mg of albendazole or placebo. After the second dose, CVD 103-HgR was given, and serum vibriocidal antibody levels were measured before and 10 days after vaccination. Postvaccination rates of seroconversion were greater in the treatment group that received albendazole (P=.06). Significantly greater rates of seroconversion and geometric mean titer were observed in the albendazole group in subjects with non-O ABO blood groups. A significant association was observed between vibriocidal seroconversion rates and treatment group, suggesting that A. lumbricoides infections impair the immune response to oral cholera vaccine, particularly in subjects of non-O blood groups. (+info)
Human infection with Ascaris lumbricoides is associated with a polarized cytokine response.
To define the cytokine response to Ascaris lumbricoides infection, the cellular immune response to adult and larval-stage Ascaris antigens in young adults with moderate infection intensities (n=73) was compared with that of a group of uninfected control subjects (n=40). A. lumbricoides-infected subjects had significantly greater lymphoproliferative responses to adult and larval-stage antigens, compared with uninfected control subjects (P<.01). The frequencies of parasite antigen-stimulated peripheral blood mononuclear cell (PBMC)-expressing interleukin (IL)-4 and IL-5 were significantly greater in the infected group (P<.001), whereas the frequencies of IL-10- and interferon-gamma-expressing PBMC were similar in the 2 groups studied. The ratios of Th2 to Th1 cytokine frequencies were significantly elevated in the infected group, compared with those in uninfected subjects, as was IL-5 protein production by PBMC stimulated with adult (P<.05) and L3/L4 stage (P<.001) antigens. Analysis of these data indicates that A. lumbricoides infections in endemic regions are associated with a highly polarized type 2 cytokine response. (+info)