Hookworm infections and tuberculosis are co-endemic in many parts of the world. It has been suggested that infection with helminth parasites could suppress the predominant Th1 (IFN-γ-mediated) response needed to control Mycobacterium tuberculosis (Mtb) infection and enhance susceptibility to infection and/or disease. To determine the role of coincident hookworm infection on responses at steady state and on Mtb – specific immune responses in latent tuberculosis (TB), we examined the cellular responses in individuals with latent TB with or without concomitant hookworm infection. By analyzing the expression of Th1, Th2 and Th17 subsets of CD4+ T cells, we were able to demonstrate that the presence of coincident hookworm infection significantly diminished both spontaneously expressed and Mtb – specific mono – and dual – functional Th1 and Th17 cells. Hookworm infection, in contrast, was associated with expanded frequencies of mono – and dual – functional Th2 cells at both steady state and upon antigen – stimulation. This differential induction of CD4+ T cell subsets was abrogated upon mitogen stimulation. In addition, coincident hookworm infection was associated with increased adaptive T regulatory (aTreg) cells but not natural regulatory T cells (nTregs) in latent TB. Finally, the CD4+ T cell cytokine expression pattern was also associated with alterations in the systemic levels of Th1 and Th2 cytokines. Thus, coincident hookworm infection exerts a profound inhibitory effect on protective Th1 and Th17 responses in latent tuberculosis and may predispose toward the development of active tuberculosis in humans.

background Shortening tuberculosis (TB) treatment duration is a research priority. We tested the efficacy and safety of 3-and 4-month regimens containing moxifloxacin in a randomised clinical trial in pulmonary TB (PTB) patients in South India. methods New, sputum-positive, adult, HIV-negative, non-diabetic PTB patients were randomised to 3-or 4-month moxifloxacin regimens [moxifloxacin (M), isoniazid (H), rifampicin (R), pyrazinamide (Z) and ethambutol (E)] or to a control regimen (2H 3 R 3 Z 3 E 3 /4R 3 H 3 ) [C]. The 4 test regimens were 3R 7 H 7 Z 7 E 7 M 7 [M3], 2R 7 H 7 Z 7 E 7 M 7 /2R 7 H 7 M 7 [M4], 2R 7 H 7 Z 7 E 7 M 7 /2R 3 H 3 M 3 [M4-I] or 2R 7 H 7 Z 7 E 7 M 7 /2R 3 H 3 E 3 M 3 [M4-IE]. Treatment was directly observed. Clinical and bacteriological assessments were done monthly during treatment and for 24 months post-treatment. The primary end point was TB recurrence post-treatment.results Of 1371 patients, randomised, modified intention-to-treat (ITT) analysis was done in 1329 and per-protocol (PP) analysis in 1223 patients. Regimen M3 was terminated due to high TB recurrence rates. 'Favourable' response at end of treatment was 96-100% in the moxifloxacin regimens and 93% in the control regimen. Among these, the TB recurrence occurred in 4.1% in the M4 regimen and in 4.5% in the control regimen and demonstrated equivalence within a 5% margin (95% CI À3.68, 4.55). Similar findings were observed in modified ITT analysis. The TB recurrence rates in the M4-I and M4-IE regimens did not show equivalence with the control regimen. Sixteen (1.4%) of 1087 patients in the moxifloxacin regimens required treatment modification.conclusion The 4-month daily moxifloxacin regimen [M4] was found to be equivalent and as safe as the 6-month thrice-weekly control regimen.keywords tuberculosis, chemotherapy of tuberculosis, short course chemotherapy, moxifloxacin, fluoroquinolones Sustainable Development Goals (SDGs): SDG 3 (good health and well-being), SDG 17 (partnerships for the goals)