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.
To investigate the potential immunomodulatory effects of concurrent ascariasis on the cytokine response to a live oral vaccine, we measured cytokine responses to cholera toxin B subunit (CT-B) following vaccination with the live oral cholera vaccine CVD 103-HgR in Ascaris lumbricoides-infected subjects randomized in a double-blind study to receive two doses of either albendazole or placebo prior to vaccination and in a group of healthy U.S. controls. Postvaccination cytokine responses to CT-B were characterized by transient increases in the production of interleukin-2 (IL-2; P ؍ 0.02) and gamma interferon (IFN-␥; P ؍ 0.001) in the three study groups combined; however, postvaccination increases in IFN-␥ were significant only in the albendazole-treated A. lumbricoides infection group (P ؍ 0.008). Postvaccination levels of IL-2 were significantly greater in the albendazole-treated group compared with the placebo group (P ؍ 0.03). No changes in levels of Th1 and Th2 cytokines in response to control ascaris antigens were observed over the same period. These findings indicate that vaccination with CVD 103-HgR is associated with a Th1 cytokine response (IL-2 and IFN-␥) to CT-B, that infection with A. lumbricoides diminishes the magnitude of this response, and that albendazole treatment prior to vaccination was able to partially reverse the deficit in IL-2. The potential modulation of the immune response to oral vaccines by geohelminth parasites has important implications for the design of vaccination campaigns in geohelminth-endemic areas.
Onchocerca volvulus infection has been associated with impaired cellular responses to parasite antigens, an impairment that may also extend to nonparasite antigens. To investigate the mechanism of this impaired immune response, the effect of concurrent O. volvulus infection on the immune response to tetanus toxoid (TT) following tetanus vaccination was studied. The proliferative, cytokine, and antibody response to TT of O. volvulus-infected subjects (n = 19) and comparable noninfected controls (n = 20) were studied before and 6 months after vaccination with TT. Following vaccination, antibody levels, proliferative responses, and levels of interferon-gamma were significantly greater in noninfected subjects (P < .05, .001, and .05, respectively); however, infected subjects produced interleukin-10, but noninfected controls did not (P < .001). These studies indicate that concurrent infection with O. volvulus can diminish the immune response to an unrelated antigen (TT) by a mechanism that is likely to involve interleukin-10.
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.
The taxonomic attribution of four Leishmania stocks isolated from humans in Ecuador has been explored by both multilocus enzyme electrophoresis and random amplified polymorphic DNA. For three loci, MLEE results showed patterns suggesting a heterozygous state for a diploid organism, while the corresponding homozygous states are characteristic of the Leishmania panamensis/guyanensis complex and Leishmania braziliensis, respectively. Other enzyme loci showed characters attributable to either the L. panamensis/ guyanensis complex or L. braziliensis. RAPD profiles exhibited for several primers a combination of the Leishmania panamensis/ guyanensis complex and L. braziliensis characters. These data hence suggest that the four stocks are the result of hybridization between L. panamensis/guyanensis and L. braziliensis. MLEE data show that the results cannot be attributed to either mixture of stocks, or an F1 in the framework of a simple Mendelian inheritance.
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