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

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.

Author Summary

The effects of helminth infection on chronic infectious diseases such as tuberculosis (TB) merit further characterization. There is limited data regarding the impact of helminth co-infection on clinical and immunological outcomes of TB from clinical field studies in high endemic areas. We tried to address some of these issues in a randomized clinical trial in order to investigate the impact of albendazole treatment on helminth co-infected TB patients. In the present study we focused on the clinical and immunological effects of helminth infection on TB. We found that concomitant asymptomatic helminth infection profoundly affects the immune phenotype of TB patients with a strong leaning towards Th2 types of immune response such as increased regulatory T cells as well as IL-5 and IL-10 secreting cells. Furthermore, helminth co-infection was associated with a significantly lower ratio of sputum smear positivity which correlated to the egg load in helminth positive TB patients. Whether the effect of helminth infection may have an impact on the diagnosis and treatment of active TB remains to be further investigated.