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

Abstract

BackgroundThe 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.MethodologyConsecutive, 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.ResultsA 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.ConclusionsAsymptomatic 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.

Strongyloides stercoralis infection increases the likelihood to detect Trypanosoma cruzi DNA in peripheral blood in Chagas disease patients

“…Similar results were found in Ethiopia in patients with and without tuberculosis; prevalence of intestinal helminths (being S. stercoralis one of the most frequent one) was 71% in patients with tuberculosis and 36% in healthy household contacts, yielding an odds ratio of 4.7 . A study performed in the same setting showed that patients with tuberculosis and helminth co‐infection had a lower rate of sputum smear positivity than those without helminth co‐infection . More examples of the helminth co‐infection effect have been described in HIV‐infected patients in the tropics, where the presence of intestinal nematodes is associated with decreased CD4+ T‐cell count even under antiretroviral treatment .…”

“…Helminth infections in humans may modify the immune response to other infections or even the antibody production after vaccination . Some examples of how S. stercoralis may modify the immune response against other infections have been described in tuberculosis or malaria . Our group has recently reported how a helminth infection (mostly strongyloidiasis) may modulate the microbiological findings in patients with chronic Chagas disease: S. stercoralis infection was associated with significantly higher proportion of positive T. cruzi DNA detection in peripheral blood .…”

Helminth-Tuberculosis Co-infection: An Immunologic Perspective

“…A more recent study in Ethiopia, however, indicated that, in patients with asymptomatic helminth infection, active TB is associated with lower rates of sputum smear positivity, leading to the conclusion that there was a beneficial effect of helminth infection on bacterial burdens [61]. Moreover, a randomized double blind clinical trial examining the effect of anti-helmintic treatment on clinical improvement of TB after 2 months showed no significant effect of anti-helmintic (albendazole) treatment over placebo [62].…”

“…For example, it has been shown that intestinal helminth co-infection is accompanied by lowered in vitro production of IFNγ and elevated production of IL-10 in individuals with active pulmonary tuberculosis [60]. Similarly, it was also recently shown that helminth infections with coincident active TB have marked decreases in dual-functional Th1 and Th17 cell frequencies [77] which, in one study at least, may be associated with increased Treg and Th2 responses [61]. …”

Friends and foes of tuberculosis: modulation of protective immunity

“…TB patients with concomitant helminth infections present with reduced frequencies of peripheral T cells as well as more severe radiological findings of pulmonary TB disease [173]. Asymptomatic helminth infection was shown to be associated with increased Treg and Th2 responses and a lower rate of sputum smear positivity [174]. Although deworming with albendazole failed to improve clinical symptoms, there was a significant decline in eosinophils and IL-10 production along with weight gain observed in the deworming group compared with placebo 3 months post-treatment [175].…”