Strongyloides stercoralis Coinfection Is Associated With Greater Disease Severity, Higher Bacterial Burden, and Elevated Plasma Matrix Metalloproteinases in Pulmonary Tuberculosis

Abstract

Background Helminths and tuberculosis (TB) largely overlap at the population level. Whether helminth infections influence disease severity and bacterial burdens in TB is not well understood. Methods This study was conducted to examine the disease severity in a cohort of pulmonary TB (PTB) individuals with (Ss+) or without (Ss−) seropositivity for Strongyloides stercoralis infection. Results Ss+ was associated with increased risk of cavitation (odds ratio [OR], 4.54; 95% confidence interval [CI], 2.33–9.04; P < .0001) and bilateral lung involvement (OR, 5.97; 95% CI, 3.03–12.09; P < .0001) in PTB individuals. Ss+ was also associated with higher bacterial burdens (OR, 7.57; 95% CI, 4.18–14.05; P < .0001) in PTB individuals. After multivariate analysis adjusting for covariates, Ss+ was still associated with greater risk of cavitation (adjusted OR [aOR], 3.99; 95% CI, 1.73–9.19; P = .0014), bilateral lung involvement (aOR, 4.09; 95% CI, 1.78–9.41; P = .0011), and higher bacterial burden (aOR, 9.32; 95% CI, 6.30–13.96; P < .0001). Finally, Ss+ was also associated with higher plasma levels of matrix metalloproteinases ([MMP]-1, -2, -7, -8, and -9) in PTB individuals. Conclusions Therefore, our data demonstrate that coexistent Ss infection is associated with greater disease severity and higher bacterial burden in PTB. Our data also demonstrate enhanced plasma levels of MMPs in coinfected individuals, suggesting a plausible biological mechanism for these effects.

Helminth Antigen Exposure Enhances Early Immune Control of Mycobacterium tuberculosis in Monocytes and Macrophages

“…Previous studies by our group and others [4, 33, 34] have confirmed a link between chronic helminth infection during TB infection and an increased Th2-type immune response with a concomitant impaired immune control of Mtb. In contrast, the impact of early helminth antigen exposure on host immunity against TB is largely unknown.…”

“…On a similar scale, it has been estimated that up to one-third of the world’s population is infected with helminths and that TB and helminths overlap geographically, with 20–35% of people with TB being infected with helminths [2, 3] (WHO, 2017). Despite multiple studies showing an impact of helminths on cell-mediated immunity, there is yet limited evidence directly linking helminthic infections to the reactivation of latency or the impact on TB disease progression [4]. In fact, recent studies [5, 6] show that helminth exposure may also enhance immunity to mycobacteria and that there is a need to focus on the effects of specific helminth species and at different stages of Mtb infection.…”

Evaluation of some immunological markers related to immune anergy in tuberculosis patients

“…Our main result is that human phagocytes had increased ability to control virulent Mtb during early stages of helminth exposure. Additionally, Ascaris lumbricoides or Schistosoma mansoni antigens showed differential effects on M1/M2 polarization markers of monocyte macrophages and cytokine expression, which indicated a gradual transition into a Th2-type immune response (25).…”

Helminth species dependent effects on Th1 and Th17 cytokines in active tuberculosis patients and healthy community controls

“…Moreover, hookworm infection in TB patients was associated with the therapeutic failure of anti-TB drugs [ 12 ], which could contribute to the increased prevalence of TB. Helminths such as Strongyloides stercoralis [ 13 ] and S . mansoni [ 14 ] infections also increased TB disease severity.…”