Effect of deworming on human T cell responses to mycobacterial antigens in helminth-exposed individuals before and after bacille Calmette-Guérin (BCG) vaccination

Abstract

The protective efficacy of BCG vaccination against pulmonary tuberculosis (TB) is highly variable in different populations. The reason remains to be elucidated. This study aims to investigate the possible effect of intestinal helminths on the immune response to PPD in naturally immunized or BCG-vaccinated humans. The study population was assessed for helminthic infection and those found to be positive were randomly assigned to either an albendazole treatment group or a control group who received a placebo. The immune response to PPD was compared between the two groups. In addition, subjects who were tuberculin skin test-negative in both groups were BCG vaccinated and later on tested for PPD-specific responses. Albendazole induced elimination/or reduction in intestinal worms resulting in a significant improvement in T cell proliferation and in interferon-gamma production by peripheral blood mononuclear cells (PBMC) stimulated with PPD. Moreover, BCG vaccination significantly improved PPD-specific immune responses in the treated group but not in the placebo group. The differences in the in vivo skin test responses were not significant. The data show that cellular immune responses to PPD are reduced in persons with concurrent helminthic infections, perhaps reflecting a lowered resistance to mycobacterial infections. This could explain, at least in part, the reduced efficacy of BCG against TB in helminth-endemic areas of the world.

Figures

Fig. 1

Trial profile.

Fig. 2

Dot plot showing tuberculin skin test reactivity 1·5 and 4·5 months post-BCG vaccination (n = 20). Cut-off values (dashed horizontal lines) for positivity were based on indurations of 5 or 7 mm. *P < 0·001. ○, Individual values; •, mean values.

Fig. 3

Effect of treatment of helminths with albendazole on proliferative responses (a) and IFN-γ secretion (b) to mycobacterial antigen. Peripheral blood mononuclear cells (PBMC) obtained 8 weeks after the first dose of albendazole (□) or placebo (▪) were stimulated without or with phytohaemagglutinin (PHA) or PPD. Proliferative responses are presented as stimulation index (SI (test ct/min/background ct/min)). IFN-γ levels are shown as those in culture supernatants of PHA- or PPD-stimulated PBMC minus those in supernatants of cells cultured with medium alone. The proliferative responses and IFN-γ production in cells cultured with medium alone were

Fig. 4

Cellular immune responses to PPD in the placebo (P) and albendazole (A) groups before and after vaccination with BCG. Ten donors from each group, who were initially tuberculin-negative, were vaccinated with BCG 10 weeks after the first dose of placebo or albendazole. Blood samples were then analysed before and 8 weeks after vaccination. The proliferative responses and IFN-γ production in unstimulated cultures were below 970 ct/min and 366 pg/ml, respectively. Data are presented as dot plots and horizontal lines are mean values.