Asymptomatic Helminth Infection in Active Tuberculosis Is Associated with Increased Regulatory and Th-2 Responses and a Lower Sputum Smear Positivity

PLoS Negl Trop Dis. 2015 Aug 6;9(8):e0003994. doi: 10.1371/journal.pntd.0003994. eCollection 2015 Aug.

Abstract

Background: The impact of intestinal helminth infection on the clinical presentation and immune response during active tuberculosis (TB) infection is not well characterized. Our aim was to investigate whether asymptomatic intestinal helminth infection alters the clinical signs and symptoms as well as the cell mediated immune responses in patients with active TB.

Methodology: Consecutive, newly diagnosed TB patients and healthy community controls (CCs) were recruited in North-west Ethiopia. TB-score, body mass index and stool samples were analyzed. Cells from HIV-negative TB patients (HIV-/TB) and from CCs were analyzed for regulatory T-cells (Tregs) and cytokine responses using flow cytometry and ELISPOT, respectively.

Results: A significantly higher ratio of helminth co-infection was observed in TB patients without HIV (Helm+/HIV-/TB) compared to HIV negative CCs, (40% (121/306) versus 28% (85/306), p = 0.003). Helm+/HIV-/TB patients showed significantly increased IL-5 secreting cells compared to Helm-/HIV-/TB (37 SFU (IQR:13-103) versus 2 SFU (1-50); p = 0.02, n = 30). Likewise, levels of absolute Tregs (9.4 (3.2-16.7) cells/μl versus 2.4 (1.1-4.0) cells/μl; p = 0.041) and IL-10 secreting cells (65 SFU (7-196) versus 1 SFU (0-31); p = 0.014) were significantly higher in Helm+/HIV-/TB patients compared to Helm-/HIV-/TB patients. In a multivariate analysis, a lower rate of sputum smear positivity for acid fast bacilli, lower body temperature, and eosinophilia were independently associated with helminth infection in TB patients.

Conclusions: Asymptomatic helminth infection is associated with increased regulatory T-cell and Th2-type responses and a lower rate of sputum smear positivity. Further studies are warranted to investigate the clinical and immunological impact of helminth infection in TB patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Coinfection
  • Feces / parasitology
  • Female
  • Helminthiasis / complications*
  • Humans
  • Intestinal Diseases, Parasitic / complications
  • Intestinal Diseases, Parasitic / parasitology
  • Male
  • Middle Aged
  • Sputum / microbiology*
  • T-Lymphocytes, Regulatory / physiology*
  • Th2 Cells / physiology*
  • Tuberculosis, Pulmonary / complications*
  • Tuberculosis, Pulmonary / diagnosis
  • Tuberculosis, Pulmonary / microbiology
  • Young Adult

Grant support

This study was supported by grant from SAREC/SIDA, EU/EDCTP(JP 10800.006), the Swedish Research Council, the Swedish Heart and Lung Foundation (Oscar II Jubileé Foundation), the Wallenberg Foundation and the Armauer Hansen Research Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.