Incidence of Active Pulmonary Tuberculosis in Patients with Coincident Filarial and/or Intestinal Helminth Infections Followed Longitudinally in South India

Abstract

BackgroundFilarial (and other helminth) infections are known to modulate mycobacteria-specific pro-inflammatory cytokine responses necessary for maintaining latency in tuberculosis (TB). We sought to address whether helminth co-infection alters progression to active pulmonary TB in a co-endemic area of South India.Methods/Principal FindingsIncidence of active pulmonary TB was assessed in 5096 subjects from five villages among helminth-infected (hel+) and –uninfected (hel−) groups. Baseline stool examinations, circulating filarial antigen, and tuberculin skin testing (PPD) were performed along with chest radiographs, sputum microscopy, and culture. During three follow-up visits each 2.5 years, patients were assessed using PPD tests and questionnaires and—for those with potential symptoms of TB—sputum microscopy and culture. Of the 5096 subjects, 1923 were found to be hel+ and 3173 were hel−. Follow up interval stool examination could not be performed. In each group, 21 developed active TB over the course of the study. After adjusting for sex, age, BCG vaccination status, and PPD positivity, no difference was seen in active TB incidence between hel+ and hel− groups either at baseline (relative risk (RR) 1.60; 95% confidence interval (CI): 0.69, 3.71, P = 0·27), or when followed prospectively (RR 1.24; 95% CI: 0.48, 3.18, P = 0·66).Conclusions/SignificanceOur findings suggest that, despite the immunomodulatory effects of helminth infection, baseline co-morbid infection with these parasites had little effect on the clinical progression from latent to active pulmonary TB.

Neither Primary nor Memory Immunity to Mycobacterium tuberculosis Infection Is Compromised in Mice with Chronic Enteric Helminth Infection

“…In a cross-sectional study in South India, a delayed-type-hypersensitivity response to purified protein derivative (PPD) was not affected by coincident intestinal helminth and/or filarial infections (32). Findings from another large-scale prospective study from the same geographical area demonstrated that there is no difference in the incidences of TB in helminth-infected and uninfected groups (33). Contrasting the above reports, several other studies have demonstrated that helminth coinfection has a negative impact on the outcome of M. tuberculosis infection.…”

Mycobacterium tuberculosis‐specific CD4+ T‐cell response is increased, and Treg cells decreased, in anthelmintic‐treated patients with latent TB

“…Further studies are now needed to investigate the impact on these Treg responses on progression to TB. Although a recent study in India failed to show any effect on the rate of progression to active TB associated with filaria or hookworm infections [48], reinfection with both helminths and M. tuberculosis would be common in this setting [49]. The next question that now needs to be answered is to understand how helminths induce this population of CD4 + FoxP3 + T cells.…”

Anthelmintic Therapy Modifies the Systemic and Mycobacterial Antigen-Stimulated Cytokine Profile in Helminth-Latent Mycobacterium tuberculosis Coinfection

“…Previous studies examining the effect of anthelmintic treatment on clinical outcomes (8,26) as well as on Mycobacterium bovis BCG vaccination (27,28) have yielded conflicting results. However, examination of T cell responses in helminth-infected individuals clearly showed diminished T cell proliferation and IFN-␥ production in response to purified protein derivative (PPD) and partial reversal of the diminished levels following albendazole therapy, although the LTB status of the population was not ascertained (29).…”

“…S. stercoralis infection is often clinically asymptomatic and longstanding due, in large part, to the parasites' autoinfective life cycle and their ability to modulate or evade the host immune system (2,7). Recent epidemiological and experimental data have provided evidence that helminths (both systemic and intestinal) have a negative regulatory role in the immune response to TB infection and disease, although no evidence exists for their having a significant impact on clinical outcomes of TB (1,8,9).…”