BackgroundHelminth infections are proposed to have immunomodulatory activities affecting health outcomes either detrimentally or beneficially. We evaluated the effects of albendazole treatment, every three months for 21 months, on STH, malarial parasitemia and allergy.Methods and FindingsA household-based cluster-randomized, double-blind, placebo-controlled trial was conducted in an area in Indonesia endemic for STH. Using computer-aided block randomization, 481 households (2022 subjects) and 473 households (1982 subjects) were assigned to receive placebo and albendazole, respectively, every three months. The treatment code was concealed from trial investigators and participants. Malarial parasitemia and malaria-like symptoms were assessed in participants older than four years of age while skin prick test (SPT) to allergens as well as reported symptoms of allergy in children aged 5–15 years. The general impact of treatment on STH prevalence and body mass index (BMI) was evaluated. Primary outcomes were prevalence of malarial parasitemia and SPT to any allergen. Analysis was by intention to treat. At 9 and 21 months post-treatment 80.8% and 80.1% of the study subjects were retained, respectively. The intensive treatment regiment resulted in a reduction in the prevalence of STH by 48% in albendazole and 9% in placebo group. Albendazole treatment led to a transient increase in malarial parasitemia at 6 months post treatment (OR 4.16(1.35–12.80)) and no statistically significant increase in SPT reactivity (OR 1.18(0.74–1.86) at 9 months or 1.37 (0.93–2.01) 21 months). No effect of anthelminthic treatment was found on BMI, reported malaria-like- and allergy symptoms. No adverse effects were reported.ConclusionsThe study indicates that intensive community treatment of 3 monthly albendazole administration for 21 months over two years leads to a reduction in STH. This degree of reduction appears safe without any increased risk of malaria or allergies.Trial RegistrationControlled-Trials.com ISRCTN83830814

Chronic helminth infections induce T-cell hyporesponsiveness, which may affect immune responses to other pathogens or to vaccines. This study investigates the influence of Treg activity on proliferation and cytokine responses to BCG and Plasmodium falciparum-parasitized RBC in Indonesian schoolchildren. Geohelminth-infected children's in vitro T-cell proliferation to either BCG or pRBC was reduced compared to that of uninfected children. Although the frequency of CD41 T cells was similar regardless of infection status, the suppressive activity differed between geohelminth-infected and geohelminthuninfected groups: Ag-specific proliferative responses increased upon CD4 1 CD25 hi T-cell depletion in geohelminth-infected subjects only. In addition, IFN-c production in response to both BCG and parasitized RBC was increased after removal of CD4These data demonstrate that geohelminth-associated Treg influence immune responses to bystander Ag of mycobacteria and plasmodia. Geohelminth-induced immune modulation may have important consequences for co-endemic infections and vaccine trials.

IntroductionAlthough highly active antiretroviral therapy (HAART) has a major beneficial effect on HIV-1-infected individuals, 1,2 it is clear that the next major therapeutic breakthrough requires a better definition of strategies for full immune reconstitution. 3 One of the challenges in achieving this goal is our lack of understanding of the precise spectrum or kinetics of the development of immune dysfunction in individual HIV-infected patients and strategies best suited to reconstitute such immune defects. Although virus-specific cytotoxic T lymphocytes (CTLs) clearly play a major role in eliminating virus-infected cells, 4-6 development and maintenance of such CTL pools require CD4 ϩ T helper cell function and an appropriate balance of cytokines. 3,7,8 It is also clear that innate immune mechanisms play a major role particularly during the initial stages of infection, 9,10 influencing the viral load set point, and that virus-neutralizing antibodies contribute to the containment of cell-free virus infection of naive cells. 11,12 Thus, a variety of immune reconstitution strategies need to be explored, some of which may be of benefit to those patients who were initiated on HAART during acute infection, whereas others may be more appropriate to patients with chronic infection. Since the primary target of HIV-1 infection is the CD4 ϩ T cells and the depletion of those cells is one of the major consequences of infection, our laboratory has initially focused on seeking methodologies for the replenishment of this cell lineage.Several studies aimed at immune reconstitution have previously been performed utilizing autologous unfractionated and in vitro expanded CD8 ϩ T cells from HIV-1-infected patients. [13][14][15] Transient decreases in viral load and increases in CD4 ϩ T-cell counts have been achieved utilizing such immune reconstitution therapies. However, these studies used autologous cells collected after HIV infection. Thus, lack of a more profound effect could be due to either an abnormal microenvironment for the adoptively transferred cells to home, survive, and/or execute immune function, or an intrinsic defect in the transferred T cells, as a direct and/or indirect effect of the virus infection. Clearly, a number of defects ranging from loss of lymphocyte specificities and subsets to signaling defects of CD4 ϩ T cells from HIV-1-infected patients have been documented. [16][17][18][19][20] Yet definitive proof for such defects cannot be obtained from the study of humans infected with HIV-1, since it would involve the use of autologous cells obtained prior For personal use only. on May 10, 2018. by guest www.bloodjournal.org From to infection. Hence, such mechanistic questions require the use of an animal model, which provides infection-induced immune dysfunction within an immune system comparable to humans. Simian immunodeficiency virus (SIV)-infected nonhuman primates provide such a model, in which we may attempt to distinguish among the above-mentioned 2 possibilities since the CD4 ϩ T cells can be colle...